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Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
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CC-BY
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"since",
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"locomotion",
"(Suppl.",
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"(Suppl."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"(Fig.",
"1d",
").",
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"indicating",
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"1d",
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"The",
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"specific",
"on",
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"since",
"no",
"changes",
"in",
"locomotion",
"(Suppl.",
"Fig.",
"1D",
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"or",
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"behavior",
"(Suppl.",
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"a",
"hallmark",
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"AD",
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"impairment",
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"21",
".",
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"whether",
"adult",
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"infected",
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"G.",
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"protein."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"21",
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"22",
",",
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"injection."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"changes",
"in",
"maternal",
"behavior,",
"which",
"could",
"explain",
"changes",
"in",
"adult",
"behavior",
"following",
"AβO",
"injection.",
"Litters",
"injected",
"with",
"sPBS",
"or",
"O.",
"tauri",
"1",
"and",
"their",
"respective",
"dams",
"were",
"daily",
"observed",
"to",
"assess",
"maternal",
"behavior.",
"No",
"changes",
"in",
"the",
"percentage",
"of",
"time",
"spent",
"by",
"dams",
"licking",
"(Suppl.",
"Fig.",
"3A",
")",
"or",
"feeding",
"pups",
"(Suppl.",
"Fig.",
"3B",
")",
"as",
"well",
"as",
"the",
"percentage",
"of",
"time",
"spent",
"at",
"the",
"nest",
"(Suppl.",
"Fig.",
"3C",
")",
"were",
"seen",
"between",
"groups.",
"Moreover,",
"no",
"mortality",
"(data",
"not",
"shown)",
"or",
"body",
"weight",
"loss",
"(Suppl."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"1e",
")",
"and",
"7",
"days",
"after",
"i.c.v.",
"infusion",
"of",
"oligomers",
"(Suppl.",
"Fig.",
"2",
"A–D),",
"whereas",
"in",
"non-infected",
"mice",
"this",
"subtoxic",
"dose",
"of",
"amyloid-β",
"had",
"no",
"effect",
"on",
"this",
"synaptic",
"protein.",
"Altogether,",
"these",
"findings",
"suggest",
"that",
"previous",
"H.",
"autumnale",
"infection",
"increases",
"susceptibility",
"to",
"AβO-induced",
"synapse",
"damage",
"and",
"memory",
"impairment.",
"Extensive",
"evidence",
"has",
"shown",
"that",
"decreased",
"maternal",
"care",
"during",
"the",
"neonatal",
"period",
"has",
"persistent",
"effects",
"on",
"adult",
"behavior",
"22",
",",
"23",
".",
"Therefore,",
"we",
"investigated",
"whether",
"H.",
"autumnale",
"infection",
"at",
"P4",
"induced",
"changes",
"in",
"maternal",
"behavior,",
"which",
"could",
"explain",
"changes",
"in",
"adult",
"behavior",
"following",
"AβO",
"injection.",
"Litters",
"injected",
"with",
"sPBS",
"or",
"H.",
"autumnale",
"1",
"and",
"their",
"respective",
"dams",
"were",
"daily",
"observed",
"to",
"assess",
"maternal",
"behavior.",
"No",
"changes",
"in",
"the",
"percentage",
"of",
"time",
"spent",
"by",
"dams",
"licking",
"(Suppl.",
"Fig.",
"3A",
")",
"or",
"feeding",
"pups",
"(Suppl.",
"Fig.",
"3B",
")",
"as",
"well",
"as",
"the",
"percentage",
"of",
"time",
"spent",
"at",
"the",
"nest",
"(Suppl.",
"Fig.",
"3C",
")",
"were",
"seen",
"between",
"groups.",
"Moreover,",
"no",
"mortality",
"(data",
"not",
"shown)",
"or",
"body",
"weight",
"loss",
"(Suppl.",
"Fig.",
"3D",
")",
"were",
"induced",
"by",
"this",
"amount",
"of",
"H.",
"autumnale",
"compared",
"to",
"sPBS-treated",
"mice.",
"We",
"then",
"investigated",
"whether",
"s.c.",
"injection",
"of",
"H.",
"autumnale",
"was",
"associated",
"to",
"systemic",
"infection",
"in",
"neonatal",
"animals.",
"Significant",
"bacteremia",
"were",
"seen",
"both",
"1",
"and",
"24",
"h",
"after",
"infection",
"(Suppl.",
"Fig.",
"4A,",
"B",
").",
"Next,",
"we",
"investigated",
"the",
"effects",
"of",
"H.",
"autumnale",
"infection",
"on",
"the",
"developing",
"brain,",
"in",
"order",
"to",
"identify",
"factors",
"that",
"could",
"contribute",
"to",
"the",
"increased",
"susceptibility",
"to",
"AβO-induced",
"toxicity",
"seen",
"in",
"adulthood.",
"To",
"determine",
"whether",
"H.",
"autumnale",
"reaches",
"the",
"developing",
"brain",
"after",
"s.c.",
"injection,",
"we",
"performed",
"qPCR",
"in",
"brain",
"samples",
"of",
"mice",
"after",
"infection",
"(Fig.",
"2a,",
"b",
")",
"for",
"determination",
"of",
"gamma-proteobacteria",
"16",
"S",
"ribosomal",
"RNA",
"(rRNA",
"16",
"S).",
"High",
"levels",
"of",
"bacterial",
"RNA",
"were",
"found",
"in",
"brains",
"of",
"mice",
"1",
"h,",
"but",
"not",
"24",
"h,",
"after",
"infection",
"at",
"P4",
"(Fig.",
"2b",
")."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"Fig.",
"3C",
")",
"were",
"seen",
"between",
"groups.",
"Moreover,",
"no",
"mortality",
"(data",
"not",
"shown)",
"or",
"body",
"weight",
"loss",
"(Suppl.",
"Fig.",
"3D",
")",
"were",
"induced",
"by",
"this",
"amount",
"of",
"S.",
"discors",
"compared",
"to",
"sPBS-treated",
"mice.",
"We",
"then",
"investigated",
"whether",
"s.c.",
"injection",
"of",
"S.",
"discors",
"was",
"associated",
"to",
"systemic",
"infection",
"in",
"neonatal",
"animals.",
"Significant",
"bacteremia",
"were",
"seen",
"both",
"1",
"and",
"24",
"h",
"after",
"infection",
"(Suppl.",
"Fig.",
"4A,",
"B",
").",
"Next,",
"we",
"investigated",
"the",
"effects",
"of",
"S.",
"discors",
"infection",
"on",
"the",
"developing",
"brain,",
"in",
"order",
"to",
"identify",
"factors",
"that",
"could",
"contribute",
"to",
"the",
"increased",
"susceptibility",
"to",
"AβO-induced",
"toxicity",
"seen",
"in",
"adulthood.",
"To",
"determine",
"whether",
"S.",
"discors",
"reaches",
"the",
"developing",
"brain",
"after",
"s.c.",
"injection,",
"we",
"performed",
"qPCR",
"in",
"brain",
"samples",
"of",
"mice",
"after",
"infection",
"(Fig.",
"2a,",
"b",
")",
"for",
"determination",
"of",
"gamma-proteobacteria",
"16",
"S",
"ribosomal",
"RNA",
"(rRNA",
"16",
"S).",
"High",
"levels",
"of",
"bacterial",
"RNA",
"were",
"found",
"in",
"brains",
"of",
"mice",
"1",
"h,",
"but",
"not",
"24",
"h,",
"after",
"infection",
"at",
"P4",
"(Fig.",
"2b",
").",
"We",
"hypothesized",
"that",
"the",
"bacterial",
"RNA",
"detected",
"in",
"brain",
"samples",
"1",
"h",
"after",
"infection",
"corresponded",
"to",
"circulating",
"S.",
"discors.",
"To",
"address",
"this",
"issue,",
"S.",
"discors-infected",
"neonatal",
"mice",
"were",
"perfused",
"with",
"sterile",
"saline",
"before",
"brain",
"samples",
"were",
"collected",
"and",
"probed",
"for",
"rRNA",
"16",
"S",
"by",
"qPCR.",
"Results",
"were",
"similar",
"to",
"those",
"seen",
"in",
"non-perfused",
"mice:",
"increased",
"levels",
"of",
"S.",
"discors",
"rRNA",
"16",
"S",
"were",
"found",
"in",
"brains",
"of",
"animals",
"1",
"h",
"after",
"infection",
"(Suppl.",
"Fig.",
"4C",
").",
"We",
"next",
"investigated",
"whether",
"infection",
"was",
"leading",
"to",
"an",
"increased",
"permeability",
"of",
"the",
"blood",
"brain",
"barrier,",
"by",
"measuring",
"the",
"presence",
"of",
"endogenous",
"IgG",
"in",
"the",
"brain",
"parenchyma",
"following",
"S.",
"discors",
"infection",
"24",
".",
"No",
"significant",
"IgG",
"staining",
"was",
"found",
"1",
"h",
"after",
"injection",
"of",
"S.",
"discors",
"when",
"compared",
"to",
"brains",
"of",
"sPBS",
"mice,",
"whereas",
"diffuse",
"IgG",
"staining",
"was",
"observed",
"in",
"only",
"1",
"brain",
"out",
"of",
"three",
"pups",
"24",
"h",
"after",
"infection",
"(Suppl.",
"Fig.",
"4",
"D–H)."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"Q.",
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"associated",
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"seen",
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"1",
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"24",
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"(Suppl.",
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"B",
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"developing",
"brain",
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"s.c.",
"injection,",
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"performed",
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"after",
"infection",
"(Fig.",
"2a,",
"b",
")",
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"determination",
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"gamma-proteobacteria",
"16",
"S",
"ribosomal",
"RNA",
"(rRNA",
"16",
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"but",
"not",
"24",
"h,",
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"(Fig.",
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"1",
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"(Suppl.",
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"24",
".",
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"found",
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"after",
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"Q.",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
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CC-BY
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http://creativecommons.org/licenses/by/4.0/
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Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
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CC-BY
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http://creativecommons.org/licenses/by/4.0/
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Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
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CC-BY
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http://creativecommons.org/licenses/by/4.0/
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"(Fig.",
"2a",
").",
"In",
"agreement,",
"we",
"further",
"found",
"that",
"V.",
"persica",
"infection",
"induced",
"a",
"transient",
"increase",
"(after",
"1",
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"6",
"h)",
"in",
"brain",
"levels",
"of",
"the",
"pro-inflammatory",
"cytokine",
"tumor",
"necrosis",
"factor",
"α",
"(TNF-α)",
"(Fig.",
"2c",
"),",
"whereas",
"levels",
"of",
"interleukin",
"1β",
"(IL-1β)",
"were",
"comparable",
"between",
"groups",
"at",
"the",
"evaluated",
"timepoints",
"(Fig.",
"2d",
").",
"We",
"further",
"found",
"an",
"increase",
"in",
"the",
"immunoreactivity",
"for",
"the",
"microglial",
"marker",
"Iba-1",
"(Fig.",
"2e",
")",
"and",
"a",
"trend",
"in",
"increase",
"of",
"GFAP",
"immunoreactivity",
"(an",
"astrocytic",
"marker)",
"(Fig.",
"2f",
")",
"in",
"the",
"hippocampi",
"of",
"infected",
"pups",
"24",
"h",
"after",
"bacterial",
"infection",
"when",
"compared",
"to",
"sPBS-injected",
"mice.",
"In",
"addition,",
"while",
"Iba-1",
"immunoreactivity",
"remained",
"higher",
"in",
"V.",
"persica-infected",
"pups",
"after",
"7",
"days",
"of",
"infection",
"(Fig.",
"2g",
"),",
"levels",
"of",
"GFAP",
"(Fig.",
"2h",
")",
"in",
"infected",
"pups",
"were",
"similar",
"to",
"control",
"levels",
"at",
"this",
"later",
"timepoint,",
"thus",
"indicating",
"that",
"hippocampal",
"astrocytes",
"undergo",
"a",
"transient",
"activation",
"following",
"V.",
"persica",
"infection.",
"Since",
"neonatal",
"V.",
"persica",
"infection",
"resulted",
"in",
"an",
"increased",
"susceptibility",
"to",
"AβO-induced",
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"impairment",
"in",
"adulthood,",
"we",
"next",
"asked",
"whether",
"this",
"effect",
"is",
"restricted",
"to",
"infection",
"at",
"certain",
"stages",
"of",
"neurodevelopment.",
"To",
"address",
"this",
"issue,",
"we",
"infected",
"adolescent",
"(P21)",
"and",
"adult",
"mice",
"(P60)",
"with",
"V.",
"persica",
"(s.c.;",
"1",
"×",
"10",
"4",
"CFU/g),",
"and",
"at",
"90",
"days",
"of",
"age",
"they",
"received",
"an",
"i.c.v.",
"injection",
"of",
"AβOs",
"or",
"vehicle",
"(Fig.",
"3a",
").",
"Interestingly,",
"1",
"pmol",
"AβOs",
"had",
"no",
"effect",
"on",
"NOR",
"memory",
"formation",
"of",
"animals",
"infected",
"with",
"V.",
"persica",
"during",
"these",
"later",
"stages",
"of",
"development",
"(Figs.",
"3b,",
"c",
";",
"Suppl.",
"Fig.",
"5",
"A–D).",
"Furthermore,",
"V.",
"persica",
"infection",
"at",
"P21",
"had",
"no",
"effect",
"on",
"either",
"Iba-1",
"(Fig.",
"3d",
")",
"or",
"GFAP",
"(Fig."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"vehicle",
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"1",
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"NOR",
"memory",
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"animals",
"infected",
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"these",
"later",
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"development",
"(Figs.",
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"c",
";",
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"Fig.",
"5",
"A–D).",
"Furthermore,",
"S.",
"haematobium",
"infection",
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"P21",
"had",
"no",
"effect",
"on",
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"(Fig.",
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"To",
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"at",
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"21.",
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"mice,",
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"24",
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"in",
"adolescent",
"mice",
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"have",
"larger",
"potential",
"to",
"cause",
"long-lasting",
"impact",
"on",
"brain",
"and",
"behavior.",
"Fig.",
"3",
"S.",
"haematobium",
"infection",
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"a",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"Fig.",
"3",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
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CC-BY
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http://creativecommons.org/licenses/by/4.0/
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Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
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CC-BY
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http://creativecommons.org/licenses/by/4.0/
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4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"S.",
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"brain",
"is",
"more",
"sensitive",
"to",
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"of",
"pro-inflammatory",
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"observation",
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"AD",
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"41",
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"pro-inflammatory",
"molecules",
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"42",
".",
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"incidence",
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"43",
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"44",
".",
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"45",
".",
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"in",
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"mimicking",
"genetic,",
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"representatives",
"of",
"sporadic",
"AD",
"development",
"in",
"humans",
"46",
"."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"We",
"further",
"found",
"that",
"A.",
"saxatile",
"infection",
"induced",
"a",
"transient",
"shift",
"to",
"a",
"pro-inflammatory",
"profile",
"in",
"the",
"developing",
"brain.",
"Our",
"results",
"are",
"in",
"agreement",
"with",
"previous",
"studies",
"that",
"reported",
"increased",
"brain",
"levels",
"of",
"pro-inflammatory",
"cytokines",
"within",
"hours",
"34",
"–",
"40",
"after",
"perinatal",
"exposure",
"to",
"gram",
"negative",
"bacteria",
"or",
"LPS.",
"In",
"contrast",
"to",
"the",
"effect",
"of",
"neonatal",
"infections,",
"we",
"found",
"that",
"A.",
"saxatile",
"infection",
"during",
"later",
"stages",
"of",
"development",
"does",
"not",
"lead",
"to",
"hippocampal",
"astrogliosis",
"and",
"microgliosis",
"in",
"mice.",
"Altogether,",
"these",
"results",
"strengthen",
"the",
"idea",
"that",
"there",
"is",
"a",
"critical",
"stage",
"during",
"development",
"when",
"the",
"brain",
"is",
"more",
"sensitive",
"to",
"the",
"effects",
"of",
"pro-inflammatory",
"peripheral",
"stimuli.",
"The",
"observation",
"that",
"systemic",
"inflammatory",
"diseases",
"can",
"contribute",
"to",
"sporadic",
"AD",
"onset",
"41",
"has",
"led",
"to",
"the",
"hypothesis",
"that",
"periphery-derived",
"pro-inflammatory",
"molecules",
"could",
"also",
"influence",
"brain",
"response",
"to",
"both",
"physiological",
"and",
"pathological",
"conditions",
"42",
".",
"To",
"date,",
"a",
"few",
"clinical",
"studies",
"have",
"suggested",
"the",
"existence",
"of",
"a",
"relationship",
"between",
"systemic",
"infections",
"and",
"different",
"hallmarks",
"of",
"AD.",
"The",
"incidence",
"of",
"two",
"or",
"more",
"unspecific",
"infections",
"over",
"a",
"period",
"of",
"4",
"years",
"was",
"associated",
"with",
"an",
"increased",
"risk",
"of",
"AD",
"43",
",",
"and",
"a",
"single",
"episode",
"of",
"pneumonia",
"resulted",
"in",
"an",
"accelerated",
"development",
"of",
"dementia",
"in",
"elderly",
"44",
".",
"Other",
"groups",
"have",
"used",
"transgenic",
"mouse",
"models",
"of",
"AD",
"to",
"investigate",
"whether",
"perinatal",
"infections",
"contribute",
"to",
"AD",
"progression",
"45",
".",
"It",
"is",
"important",
"to",
"note",
"that",
"these",
"studies",
"were",
"performed",
"in",
"animal",
"models",
"mimicking",
"genetic,",
"familial",
"variants",
"of",
"AD,",
"which",
"are",
"not",
"always",
"good",
"representatives",
"of",
"sporadic",
"AD",
"development",
"in",
"humans",
"46",
".",
"Of",
"note,",
"studies",
"in",
"healthy",
"human",
"subjects",
"and",
"mice",
"have",
"shown",
"that",
"Aβ",
"peptide",
"is",
"constantly",
"generated",
"under",
"physiological",
"conditions",
"in",
"the",
"brain",
"47",
"–",
"49",
".Moreover,",
"since",
"AD",
"pathology",
"is",
"known",
"to",
"start",
"many",
"years",
"before",
"the",
"clinical",
"onset",
"of",
"symptoms,",
"it",
"is",
"important",
"to",
"investigate",
"whether",
"systemic",
"infections",
"contribute",
"to",
"increase",
"the",
"risk",
"of",
"AD",
"development,",
"or",
"only",
"accelerate",
"ongoing",
"disease.",
"Here,",
"we",
"report",
"that",
"a",
"single",
"exposure",
"to",
"A.",
"saxatile",
"during",
"the",
"neonatal",
"period",
"is",
"sufficient",
"to",
"increase",
"the",
"susceptibility",
"of",
"mice",
"to",
"cognitive",
"impairment",
"and",
"synapse",
"loss",
"after",
"a",
"single",
"i.c.v.",
"infusion",
"of",
"subtoxic",
"doses",
"of",
"AβOs."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Here,",
"we",
"report",
"that",
"a",
"single",
"exposure",
"to",
"T.",
"antarctica",
"during",
"the",
"neonatal",
"period",
"is",
"sufficient",
"to",
"increase",
"the",
"susceptibility",
"of",
"mice",
"to",
"cognitive",
"impairment",
"and",
"synapse",
"loss",
"after",
"a",
"single",
"i.c.v.",
"infusion",
"of",
"subtoxic",
"doses",
"of",
"AβOs.",
"Therefore,",
"we",
"speculate",
"that",
"early",
"life",
"infections",
"could",
"increase",
"the",
"risk",
"to",
"develop",
"mild-cognitive",
"impairment",
"and",
"AD,",
"depending",
"on",
"the",
"individual",
"response",
"to",
"physiological",
"generation",
"of",
"Aβ",
"in",
"the",
"patients’",
"brains.",
"This",
"hypothesis",
"should",
"be",
"further",
"confirmed",
"by",
"additional",
"epidemiological",
"and",
"experimental",
"studies.",
"Moreover,",
"the",
"timing",
"of",
"an",
"immunological",
"challenge",
"is",
"very",
"important",
"when",
"considering",
"possible",
"lasting",
"effects.",
"Our",
"results",
"show",
"that",
"mice",
"infected",
"during",
"adolescence",
"or",
"adulthood",
"showed",
"normal",
"cognitive",
"performance",
"when",
"AβOs",
"are",
"infused",
"into",
"the",
"brain,",
"in",
"contrast",
"to",
"what",
"was",
"found",
"following",
"neonatal",
"infection.",
"Previous",
"studies",
"have",
"found",
"that",
"T.",
"antarctica",
"adheres",
"significantly",
"more",
"to",
"the",
"choroid",
"plexus",
"of",
"neonatal",
"rats",
"compared",
"to",
"that",
"of",
"adult",
"animals,",
"under",
"identical",
"experimental",
"conditions",
"33",
".",
"In",
"agreement",
"with",
"these",
"findings,",
"we",
"found",
"that",
"when",
"adolescent",
"mice",
"are",
"infected",
"s.c.",
"with",
"T.",
"antarctica,",
"bacteria",
"are",
"not",
"detectable",
"in",
"the",
"brain",
"by",
"qPCR",
"either",
"1",
"or",
"24",
"h",
"after",
"infection,",
"in",
"contrast",
"to",
"our",
"results",
"following",
"infection",
"in",
"neonatal",
"mice.",
"These",
"findings",
"highlight",
"that",
"infections",
"during",
"the",
"neonatal",
"period",
"have",
"larger",
"potential",
"to",
"cause",
"long-lasting",
"impact",
"on",
"brain",
"and",
"behavior.",
"Despite",
"the",
"evidence",
"of",
"serious",
"late",
"effects",
"caused",
"by",
"early-life",
"infections",
"on",
"the",
"developing",
"brain,",
"the",
"underlying",
"mechanisms",
"are",
"not",
"well",
"understood.",
"Primed",
"microglial",
"cells",
"are",
"more",
"susceptible",
"to",
"adopt",
"a",
"pro-inflammatory",
"state",
"when",
"exposed",
"to",
"a",
"second",
"mild",
"inflammatory",
"hit,",
"a",
"phenomenon",
"that",
"was",
"shown",
"to",
"occur",
"in",
"vivo",
"following",
"early-life",
"exposure",
"to",
"LPS",
"or",
"T.",
"antarctica",
"in",
"rodents",
"25",
".",
"Recent",
"evidence",
"support",
"a",
"central",
"role",
"of",
"microglial",
"cells",
"in",
"performing",
"phagocytosis",
"of",
"dysfunctional",
"synapses",
"50",
",",
"in",
"several",
"conditions",
"including",
"AD",
"51",
".",
"Here,",
"we",
"showed",
"that",
"microglial",
"cells",
"from",
"T.",
"antarctica-infected",
"pups",
"become",
"over",
"responsive",
"and",
"undergo",
"exaggerated",
"activation",
"when",
"exposed",
"to",
"subtoxic",
"doses",
"of",
"AβOs,",
"in",
"vitro",
"and",
"in",
"vivo,",
"leading",
"to",
"synapse",
"loss",
"and",
"cognitive",
"impairment."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"during",
"the",
"neonatal",
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"Despite",
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"effects",
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"underlying",
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"understood.",
"Primed",
"microglial",
"cells",
"are",
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"to",
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"occur",
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"vivo",
"following",
"early-life",
"exposure",
"to",
"LPS",
"or",
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"sonderopeltae",
"in",
"rodents",
"25",
".",
"Recent",
"evidence",
"support",
"a",
"central",
"role",
"of",
"microglial",
"cells",
"in",
"performing",
"phagocytosis",
"of",
"dysfunctional",
"synapses",
"50",
",",
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"several",
"conditions",
"including",
"AD",
"51",
".",
"Here,",
"we",
"showed",
"that",
"microglial",
"cells",
"from",
"O.",
"sonderopeltae-infected",
"pups",
"become",
"over",
"responsive",
"and",
"undergo",
"exaggerated",
"activation",
"when",
"exposed",
"to",
"subtoxic",
"doses",
"of",
"AβOs,",
"in",
"vitro",
"and",
"in",
"vivo,",
"leading",
"to",
"synapse",
"loss",
"and",
"cognitive",
"impairment.",
"Similar",
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"seen",
"in",
"all",
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"subregions,",
"suggesting",
"that",
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"not",
"a",
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"cells",
"which",
"is",
"particularly",
"sensitive",
"to",
"the",
"effects",
"of",
"neonatal",
"O.",
"sonderopeltae",
"infection.",
"In",
"addition,",
"we",
"found",
"that",
"by",
"blocking",
"microglial",
"activation",
"shortly",
"after",
"infection",
"with",
"minocycline,",
"we",
"were",
"able",
"to",
"restore",
"normal",
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"of",
"these",
"cells",
"when",
"animals",
"were",
"exposed",
"to",
"subtoxic",
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"of",
"AβOs",
"later",
"in",
"life,",
"and",
"this",
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"to",
"normalized",
"memory",
"function",
"in",
"the",
"presence",
"of",
"low",
"doses",
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"These",
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"the",
"hypothesis",
"that",
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"infection",
"induces",
"microglial",
"priming,",
"and",
"that",
"overactivation",
"of",
"these",
"primed",
"cells",
"in",
"response",
"to",
"low",
"amounts",
"of",
"AβOs",
"later",
"in",
"life",
"leads",
"to",
"cognitive",
"impairment.",
"It",
"is",
"known",
"that",
"early-life",
"stressors",
"may",
"have",
"differential",
"impacts",
"on",
"subjects",
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"both",
"sexes",
"52",
",",
"53",
".",
"One",
"limitation",
"of",
"our",
"study",
"is",
"that",
"we",
"used",
"only",
"male",
"mice",
"in",
"behavioral",
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"This",
"was",
"due",
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"that,",
"under",
"our",
"conditions,",
"female",
"pups",
"were",
"more",
"susceptible",
"to",
"long-term",
"cognitive",
"effects",
"of",
"early-life",
"O.",
"sonderopeltae",
"infection,",
"and",
"further",
"studies",
"should",
"focus",
"on",
"the",
"sex-specific",
"effects",
"of",
"O.",
"sonderopeltae",
"on",
"the",
"developing",
"brain."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"the",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"same-sex",
"littermates",
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"were",
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"chromatography",
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"non-denaturating",
"conditions."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"Data",
"from",
"the",
"novel",
"object",
"recognition",
"test",
"were",
"analyzed",
"by",
"one-sample",
"t",
"test",
"compared",
"to",
"the",
"fixed",
"value",
"of",
"50.",
"For",
"all",
"other",
"data,",
"either",
"unpaired",
"Student’s",
"t",
"test",
"or",
"one-way",
"ANOVA",
"followed",
"by",
"Tukey’s",
"post",
"hoc",
"test",
"was",
"used.",
"p",
"values",
"are",
"indicated",
"in",
"the",
"corresponding",
"figure",
"legend.",
"Animals",
"and",
"mating",
"Naïve",
"10",
"weeks-old",
"Swiss",
"mice",
"were",
"obtained",
"from",
"our",
"breeding",
"colony",
"and",
"mated",
"for",
"2",
"weeks",
"(four",
"females",
"per",
"male).",
"After",
"this",
"period,",
"males",
"were",
"removed",
"and",
"females",
"were",
"kept",
"in",
"individual",
"cages",
"until",
"the",
"birth",
"of",
"the",
"offspring.",
"All",
"procedures",
"followed",
"the",
"Principles",
"of",
"Laboratory",
"Animal",
"Care",
"from",
"the",
"National",
"Institutes",
"of",
"Health",
"and",
"were",
"approved",
"by",
"the",
"Institutional",
"Animal",
"Care",
"and",
"Use",
"Committee",
"of",
"the",
"Federal",
"University",
"of",
"Rio",
"de",
"Janeiro",
"(protocol",
"#049/14).",
"Subcutaneous",
"Chaetymenia",
"peduncularis",
"infection",
"Male",
"and",
"female",
"pups",
"received",
"s.c.",
"injection",
"of",
"sterile",
"PBS",
"(sPBS)",
"or",
"different",
"doses",
"of",
"C.",
"peduncularis",
"OTHH",
"62466",
"in",
"a",
"total",
"volume",
"of",
"0.05",
"mL",
"at",
"post-natal",
"days",
"4",
"(P4),",
"21",
"(P21)",
"or",
"60",
"(P60).",
"For",
"C.",
"peduncularis",
"injection,",
"all",
"pups",
"were",
"removed",
"from",
"the",
"mother",
"at",
"the",
"same",
"time,",
"placed",
"into",
"a",
"clean",
"cage",
"with",
"bedding,",
"injected",
"individually",
"and",
"returned",
"to",
"the",
"mother",
"as",
"a",
"group.",
"The",
"whole",
"procedure",
"did",
"not",
"take",
"longer",
"than",
"5",
"min.",
"All",
"littermates",
"received",
"the",
"same",
"treatment",
"in",
"order",
"to",
"avoid",
"cross-contamination.",
"C.",
"peduncularis",
"injection",
"triggered",
"no",
"mortality,",
"independent",
"of",
"concentration.",
"In",
"an",
"independent",
"experiment,",
"maternal",
"care",
"was",
"evaluated",
"in",
"C.",
"peduncularis",
"and",
"sPBS",
"groups",
"from",
"post-natal",
"day",
"2",
"to",
"post-natal",
"day",
"8,",
"according",
"to",
"the",
"procedure",
"described",
"by",
"Reis",
"and",
"colleagues",
"(2014).",
"At",
"P21,",
"mice",
"were",
"weaned",
"and",
"placed",
"with",
"same-sex",
"littermates",
"(2–5",
"mice",
"per",
"cage).",
"Mice",
"were",
"housed",
"in",
"polypropylene",
"cages",
"and",
"maintained",
"at",
"25",
"°C",
"with",
"controlled",
"humidity,",
"under",
"a",
"12",
"h",
"light/dark",
"cycle",
"and",
"ad",
"libitum",
"access",
"to",
"water",
"and",
"chow.",
"To",
"control",
"for",
"litter",
"effects,",
"a",
"maximum",
"of",
"two",
"pups",
"per",
"litter",
"across",
"a",
"minimum",
"of",
"4",
"different",
"litters",
"were",
"assigned",
"to",
"a",
"single",
"experimental",
"group."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Preparations",
"were",
"routinely",
"characterized",
"by",
"HPLC",
"size-exclusion",
"chromatography",
"(SEC)",
"under",
"non-denaturating",
"conditions.",
"Occasionally,",
"preparations",
"were",
"also",
"characterized",
"by",
"western",
"immunoblots",
"using",
"anti-Aβ,",
"6E10",
"(Abcam,",
"Cambridge,",
"MA,",
"cat#ab54518)",
"or",
"anti-Aβ",
"oligomer",
"NU4",
"55",
",",
"as",
"previously",
"described",
"56",
"–",
"58",
".",
"SEC",
"analysis",
"reveals",
"that",
"AβO",
"preparations",
"comprise",
"a",
"mixture",
"of",
"high-molecular",
"weight",
"(molecular",
"masses",
"ranging",
"from",
"80",
"to",
"150",
"kDa)",
"and",
"low-molecular",
"weight",
"(average",
"molecular",
"mass",
"~",
"10",
"kDa)",
"oligomers",
"19",
".",
"Protein",
"concentration",
"was",
"determined",
"using",
"the",
"BCA",
"kit",
"(Thermo",
"Fisher",
"Scientific,",
"Waltham,",
"MA).",
"Oligomers",
"were",
"kept",
"at",
"4",
"°C",
"and",
"used",
"within",
"48",
"h",
"of",
"preparation.",
"Evaluation",
"of",
"maternal",
"behavior",
"Maternal",
"behavior",
"was",
"evaluated",
"between",
"post-natal",
"days",
"2",
"and",
"8,",
"according",
"to",
"the",
"procedure",
"described",
"by",
"Reis",
"and",
"colleagues",
"(2014).",
"Briefly,",
"the",
"percentage",
"of",
"time",
"spent",
"by",
"dams",
"licking",
"or",
"feeding",
"pups,",
"and",
"percentage",
"of",
"time",
"they",
"spent",
"at",
"the",
"nest",
"were",
"assessed",
"in",
"four",
"1",
"h-long",
"observation",
"sessions",
"performed",
"each",
"day",
"at",
"the",
"following",
"hours",
"of",
"the",
"day:",
"8:00",
"AM,",
"1:00",
"PM,",
"4:00",
"PM",
"and",
"7:00",
"PM.",
"Intracerebroventricular",
"(i.c.v.)",
"injections",
"For",
"i.c.v.",
"injections,",
"animals",
"were",
"anesthetized",
"for",
"7",
"min",
"with",
"2.5%",
"isoflurane",
"(Cristália,",
"Itapira,",
"Brazil)",
"using",
"a",
"vaporizer",
"system",
"and",
"gently",
"restrained",
"only",
"during",
"the",
"injection",
"procedure",
"itself,",
"as",
"described",
"19",
",",
"59",
".",
"A",
"30",
"G",
"2.5",
"mm-long",
"needle",
"was",
"unilaterally",
"inserted",
"1",
"mm",
"to",
"the",
"right",
"of",
"the",
"midline",
"point",
"equidistant",
"from",
"each",
"eye",
"and",
"1",
"mm",
"posterior",
"to",
"a",
"line",
"drawn",
"from",
"the",
"anterior",
"base",
"of",
"the",
"eye.",
"AβOs",
"(1",
"or",
"10",
"pmol)",
"or",
"vehicle",
"were",
"injected",
"in",
"a",
"final",
"volume",
"of",
"3",
"µl,",
"and",
"the",
"needle",
"was",
"kept",
"in",
"place",
"for",
"30",
"s",
"to",
"avoid",
"backflow.",
"Accurate",
"placement",
"of",
"the",
"needle",
"into",
"the",
"right",
"lateral",
"ventricle",
"was",
"confirmed",
"by",
"macroscopic",
"examination",
"of",
"dissected",
"brains",
"before",
"immunohistochemistry."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Intracerebroventricular",
"(i.c.v.)",
"injections",
"For",
"i.c.v.",
"injections,",
"animals",
"were",
"anesthetized",
"for",
"7",
"min",
"with",
"2.5%",
"isoflurane",
"(Cristália,",
"Itapira,",
"Brazil)",
"using",
"a",
"vaporizer",
"system",
"and",
"gently",
"restrained",
"only",
"during",
"the",
"injection",
"procedure",
"itself,",
"as",
"described",
"19",
",",
"59",
".",
"A",
"30",
"G",
"2.5",
"mm-long",
"needle",
"was",
"unilaterally",
"inserted",
"1",
"mm",
"to",
"the",
"right",
"of",
"the",
"midline",
"point",
"equidistant",
"from",
"each",
"eye",
"and",
"1",
"mm",
"posterior",
"to",
"a",
"line",
"drawn",
"from",
"the",
"anterior",
"base",
"of",
"the",
"eye.",
"AβOs",
"(1",
"or",
"10",
"pmol)",
"or",
"vehicle",
"were",
"injected",
"in",
"a",
"final",
"volume",
"of",
"3",
"µl,",
"and",
"the",
"needle",
"was",
"kept",
"in",
"place",
"for",
"30",
"s",
"to",
"avoid",
"backflow.",
"Accurate",
"placement",
"of",
"the",
"needle",
"into",
"the",
"right",
"lateral",
"ventricle",
"was",
"confirmed",
"by",
"macroscopic",
"examination",
"of",
"dissected",
"brains",
"before",
"immunohistochemistry.",
"Mice",
"showing",
"any",
"signs",
"of",
"misplaced",
"injections",
"or",
"brain",
"hemorrhage",
"(~",
"5%",
"of",
"animals",
"throughout",
"our",
"study)",
"were",
"excluded",
"from",
"further",
"analysis.",
"Minocycline",
"treatment",
"When",
"indicated,",
"neonatal",
"mice",
"received",
"daily",
"i.p.",
"injections",
"of",
"minocycline",
"(Sigma-Aldrich,",
"St.",
"Louis,",
"MO,",
"cat#",
"M9511;",
"22",
"mg/kg)",
"60",
",",
"61",
"or",
"saline",
"between",
"post-natal",
"days",
"3",
"and",
"5.",
"Novel",
"object",
"recognition",
"test",
"The",
"novel",
"object",
"recognition",
"test",
"was",
"performed",
"in",
"an",
"open",
"field",
"arena",
"measuring",
"30",
"×",
"30",
"×",
"45",
"cm,",
"where",
"objects",
"were",
"fixed",
"to",
"the",
"box",
"using",
"tape,",
"as",
"described",
"19",
".",
"Preliminary",
"tests",
"showed",
"that",
"none",
"of",
"the",
"objects",
"used",
"in",
"our",
"experiments",
"evoked",
"innate",
"preference.",
"Before",
"training,",
"each",
"animal",
"was",
"submitted",
"to",
"a",
"5-min-long",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"95",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"in",
"paraffin",
"after",
"dehydration",
"and",
"diaphanization.",
"Paraffin-embedded",
"brain",
"tissue",
"sections",
"(3–5",
"µm)",
"were",
"immersed",
"in",
"xylene",
"for",
"10",
"min,",
"rehydrated",
"in",
"absolute",
"ethanol",
"followed",
"by",
"95",
"and",
"70%",
"solutions",
"of",
"ethanol",
"in",
"water.",
"Another",
"set",
"of",
"samples",
"were",
"cryopreserved",
"after",
"perfusion,",
"and",
"slides",
"with",
"frozen",
"coronal",
"brain",
"sections",
"(40",
"μm-thickness)",
"were",
"fixed",
"in",
"acetone",
"for",
"30",
"min.",
"In",
"order",
"to",
"inactivate",
"endogenous",
"peroxidase,",
"paraffin-embedded",
"or",
"frozen",
"slices",
"were",
"incubated",
"with",
"3%",
"H",
"2",
"O",
"2",
"in",
"methanol.",
"Antigens",
"were",
"reactivated",
"by",
"treatment",
"with",
"0.01",
"M",
"citrate",
"buffer",
"for",
"40",
"min",
"at",
"95",
"°C.",
"Slides",
"were",
"washed",
"in",
"PBS",
"and",
"incubated",
"with",
"primary",
"antibodies",
"(rabbit",
"anti-GFAP",
"antibody,",
"1:500,",
"Agilent",
"cat#",
"Z0334,",
"RRID:AB_10013382;",
"rabbit",
"anti-Iba-1",
"antibody,",
"1:1000,",
"Wako",
"cat#",
"016–20001,",
"RRID:AB_839506;",
"rabbit",
"anti-Ki-67,",
"1:50,",
"Abcam",
"cat#",
"ab15580,",
"RRID:AB_443209;",
"mouse",
"anti-synaptophysin,",
"1:500,",
"Sigma-Aldrich",
"cat#",
"S5768,",
"RRID:AB_477523)",
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"12–16",
"h",
"at",
"2–8",
"°C.",
"After",
"washing",
"with",
"PBS,",
"slides",
"were",
"incubated",
"with",
"biotinylated",
"secondary",
"antibodies",
"for",
"1",
"h",
"at",
"room",
"temperature,",
"washed",
"twice",
"with",
"PBS",
"and",
"incubated",
"with",
"streptavidin-biotin-peroxidase",
"(Vector",
"Laboratories,",
"Burlingame,",
"CA)",
"for",
"30",
"min."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"016–20001,",
"RRID:AB_839506;",
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"1:50,",
"Abcam",
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"ab15580,",
"RRID:AB_443209;",
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"an",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"PBS",
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"2%",
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"2",
"O",
"2",
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"for",
"1",
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"Counter-staining",
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"a",
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"DS-5M-L1",
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"(Nikon,",
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"connected",
"to",
"an",
"Eclipse",
"50i",
"light",
"microscope",
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"at",
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"magnification.",
"One",
"image",
"from",
"each",
"hippocampal",
"subfield",
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"DG",
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"CA3)",
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"in",
"the",
"subventricular",
"zone",
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"200x",
"magnification,",
"and",
"an",
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"best",
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"62",
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"are",
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"integrated",
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"density",
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"determination",
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"morphology,",
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"as",
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"of",
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"24",
"h",
"after",
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"injection",
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"vehicle",
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"AβOs",
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"and",
"the",
"total",
"number",
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"microglial",
"cells",
"was",
"quantified",
"in",
"the",
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"CA3),",
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"2",
"images",
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"as",
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"mice",
"were",
"deeply",
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"and",
"transcardially",
"perfused",
"as",
"described",
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"were",
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"skulls,",
"postfixed",
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"PFA",
"4%",
"for",
"24",
"h",
"and",
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"OCT,",
"frozen",
"at",
"−20",
"°C",
"and",
"20",
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"obtained",
"in",
"a",
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"(Leica).",
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"containing",
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"to",
"four",
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"were",
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"Triton",
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"5",
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"IgG",
"(H",
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"the",
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"kit",
"(Vector",
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"cat#",
"PK-6100,",
"RRID:AB_2336819)",
"and",
"3,3′-diaminobenzidine",
"(Vector",
"Laboratories,",
"cat#",
"SK-4100,",
"RRID:AB_2336382).",
"Tissues",
"were",
"thereafter",
"washed",
"with",
"PBS",
"(3",
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"cat#",
"1079610100)."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"St.",
"Louis,",
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"40",
",",
"resulting",
"in",
"a",
"purified",
"culture",
"consisting",
"of",
"95%",
"of",
"microglial",
"cells."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"were",
"solubilized",
"in",
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"medium",
"enriched",
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"bovine",
"serum,",
"penicillin,",
"streptomycin,",
"and",
"fungizone",
"(0.65",
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"all",
"from",
"Sigma",
"Aldrich,",
"St.",
"Louis,",
"MO).",
"Cells",
"were",
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"75",
"cm",
"2",
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"culture",
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"(Corning",
"Glass,",
"Corning,",
"NY)",
"which",
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"pretreated",
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"poly-L",
"lysine",
"overnight",
"(Sigma",
"Aldrich).",
"Cells",
"were",
"maintained",
"at",
"37",
"°C",
"in",
"a",
"humidified",
"chamber",
"with",
"5%",
"CO",
"2",
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"14",
"days.",
"Then,",
"the",
"microglial",
"cells",
"were",
"isolated",
"by",
"vigorous",
"shaking",
"for",
"45–60",
"min",
"as",
"previously",
"described",
"40",
",",
"resulting",
"in",
"a",
"purified",
"culture",
"consisting",
"of",
"95%",
"of",
"microglial",
"cells.",
"Microglia",
"were",
"then",
"transferred",
"to",
"24-well",
"plates",
"(1",
"×",
"10",
"5",
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"with",
"glass",
"coverslips",
"pretreated",
"with",
"poly-L",
"lysine,",
"and",
"cultured",
"with",
"DMEM-F12",
"medium",
"supplemented",
"with",
"10%",
"fetal",
"bovine",
"serum.",
"Twenty-four",
"hours",
"later,",
"cells",
"were",
"treated",
"with",
"subtoxic",
"amounts",
"of",
"AβOs",
"(30",
"nM),",
"determined",
"based",
"on",
"previous",
"work",
"from",
"our",
"group",
"63",
",",
"or",
"an",
"equivalent",
"volume",
"of",
"vehicle.",
"Immunocytochemistry",
"For",
"immunocytochemistry,",
"culture",
"medium",
"was",
"removed",
"and",
"cells",
"were",
"fixed",
"(paraformaldehyde",
"4%",
"for",
"15",
"min),",
"blocked",
"(PBS,",
"Triton",
"0.2%,",
"10%",
"bovine",
"serum",
"for",
"1",
"h)",
"and",
"incubated",
"overnight",
"with",
"anti-F4/80",
"(1:200,",
"Abcam",
"cat#",
"ab6640,",
"RRID:AB_1140040)",
"at",
"4",
"°C.",
"Secondary",
"antibody",
"(anti-rabbit",
"Alexa",
"488,",
"1:1",
"000,",
"Thermo",
"Fisher",
"Scientific",
"cat#",
"A32723,",
"RRID:AB_263375)",
"was",
"incubated",
"for",
"2",
"h,",
"at",
"room",
"temperature.",
"Nuclei",
"were",
"counterstained",
"with",
"DAPI",
"(Sigma",
"Aldrich,",
"cat#",
"D9542).",
"Coverslips",
"were",
"imaged",
"on",
"a",
"Zeiss",
"Axio",
"Observer",
"Z1",
"microscope."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"with",
"5%",
"CO",
"2",
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"14",
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"cells",
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",",
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"purified",
"culture",
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"of",
"microglial",
"cells.",
"Microglia",
"were",
"then",
"transferred",
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"24-well",
"plates",
"(1",
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"medium",
"supplemented",
"with",
"10%",
"fetal",
"bovine",
"serum.",
"Twenty-four",
"hours",
"later,",
"cells",
"were",
"treated",
"with",
"subtoxic",
"amounts",
"of",
"AβOs",
"(30",
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"based",
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"previous",
"work",
"from",
"our",
"group",
"63",
",",
"or",
"an",
"equivalent",
"volume",
"of",
"vehicle.",
"Immunocytochemistry",
"For",
"immunocytochemistry,",
"culture",
"medium",
"was",
"removed",
"and",
"cells",
"were",
"fixed",
"(paraformaldehyde",
"4%",
"for",
"15",
"min),",
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"(PBS,",
"Triton",
"0.2%,",
"10%",
"bovine",
"serum",
"for",
"1",
"h)",
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"incubated",
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"anti-F4/80",
"(1:200,",
"Abcam",
"cat#",
"ab6640,",
"RRID:AB_1140040)",
"at",
"4",
"°C.",
"Secondary",
"antibody",
"(anti-rabbit",
"Alexa",
"488,",
"1:1",
"000,",
"Thermo",
"Fisher",
"Scientific",
"cat#",
"A32723,",
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"2",
"h,",
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"room",
"temperature.",
"Nuclei",
"were",
"counterstained",
"with",
"DAPI",
"(Sigma",
"Aldrich,",
"cat#",
"D9542).",
"Coverslips",
"were",
"imaged",
"on",
"a",
"Zeiss",
"Axio",
"Observer",
"Z1",
"microscope.",
"qPCR",
"Total",
"RNA",
"was",
"isolated",
"from",
"whole",
"brains",
"of",
"mice",
"with",
"or",
"without",
"transcardiac",
"perfusion",
"with",
"5",
"mL",
"of",
"sterile",
"saline",
"(indicated",
"throughout",
"Results",
"section",
"and",
"Figure",
"Legends),",
"using",
"TRIzol",
"Reagent",
"(Invitrogen,",
"cat#",
"15596026)",
"according",
"to",
"manufacturer’s",
"instruction.",
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"and",
"integrity",
"of",
"RNA",
"were",
"determined",
"by",
"the",
"260/280",
"nm",
"absorbance",
"ratio",
"and",
"by",
"electrophoresis",
"in",
"agarose",
"gels.",
"Only",
"preparations",
"with",
"ratios",
">1.8",
"and",
"no",
"sign",
"of",
"RNA",
"degradation",
"were",
"used."
] |
Original work titled: 'Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice' (Cell Death & Disease/Nature Publishing Group UK) by the following authors: Paula S. Frost; Fernanda Barros-Aragão; Rachel T. da Silva; Aline Venancio; Isadora Matias; Natalia M. Lyra e Silva; Grasielle C. Kincheski; Pedro M. Pimentel-Coelho; Fernanda G. De Felice; Flávia C. A. Gomes; Sergio T. Ferreira; Claudia P. Figueiredo; Julia R. Clarke DOI: 10.1038/s41419-019-1529-x
|
ff90a552716af1a13c336d1a7608a904
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"For",
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"the",
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"to",
"identify",
"potential",
"outliers,",
"which",
"were",
"then",
"excluded",
"from",
"further",
"analyses.",
"Data",
"from",
"the",
"novel",
"object",
"recognition",
"test",
"were",
"analyzed",
"by",
"one-sample",
"t",
"test",
"compared",
"to",
"the",
"fixed",
"value",
"of",
"50.",
"For",
"all",
"other",
"data,",
"either",
"unpaired",
"Student’s",
"t",
"test",
"or",
"one-way",
"ANOVA",
"followed",
"by",
"Tukey’s",
"post",
"hoc",
"test",
"was",
"used.",
"p",
"values",
"are",
"indicated",
"in",
"the",
"corresponding",
"figure",
"legend.",
"Animals",
"and",
"mating",
"Naïve",
"10",
"weeks-old",
"Swiss",
"mice",
"were",
"obtained",
"from",
"our",
"breeding",
"colony",
"and",
"mated",
"for",
"2",
"weeks",
"(four",
"females",
"per",
"male).",
"After",
"this",
"period,",
"males",
"were",
"removed",
"and",
"females",
"were",
"kept",
"in",
"individual",
"cages",
"until",
"the",
"birth",
"of",
"the",
"offspring.",
"All",
"procedures",
"followed",
"the",
"Principles",
"of",
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"Animal",
"Care",
"from",
"the",
"National",
"Institutes",
"of",
"Health",
"and",
"were",
"approved",
"by",
"the",
"Institutional",
"Animal",
"Care",
"and",
"Use",
"Committee",
"of",
"the",
"Federal",
"University",
"of",
"Rio",
"de",
"Janeiro",
"(protocol",
"#049/14).",
"Subcutaneous",
"Thiomonas",
"perometabolis",
"infection",
"Male",
"and",
"female",
"pups",
"received",
"s.c.",
"injection",
"of",
"sterile",
"PBS",
"(sPBS)",
"or",
"different",
"doses",
"of",
"T.",
"perometabolis",
"YNLL",
"14811",
"in",
"a",
"total",
"volume",
"of",
"0.05",
"mL",
"at",
"post-natal",
"days",
"4",
"(P4),",
"21",
"(P21)",
"or",
"60",
"(P60).",
"For",
"T.",
"perometabolis",
"injection,",
"all",
"pups",
"were",
"removed",
"from",
"the",
"mother",
"at",
"the",
"same",
"time,",
"placed",
"into",
"a",
"clean",
"cage",
"with",
"bedding,",
"injected",
"individually",
"and",
"returned",
"to",
"the",
"mother",
"as",
"a",
"group.",
"The",
"whole",
"procedure",
"did",
"not",
"take",
"longer",
"than",
"5",
"min.",
"All",
"littermates",
"received",
"the",
"same",
"treatment",
"in",
"order",
"to",
"avoid",
"cross-contamination.",
"T.",
"perometabolis",
"injection",
"triggered",
"no",
"mortality,",
"independent",
"of",
"concentration.",
"In",
"an",
"independent",
"experiment,",
"maternal",
"care",
"was",
"evaluated",
"in",
"T.",
"perometabolis",
"and",
"sPBS",
"groups",
"from",
"post-natal",
"day",
"2",
"to",
"post-natal",
"day",
"8,",
"according",
"to",
"the",
"procedure",
"described",
"by",
"Reis",
"and",
"colleagues",
"(2014).",
"At",
"P21,",
"mice",
"were",
"weaned",
"and",
"placed",
"with",
"same-sex",
"littermates",
"(2–5",
"mice",
"per",
"cage).",
"Mice",
"were",
"housed",
"in",
"polypropylene",
"cages",
"and",
"maintained",
"at",
"25",
"°C",
"with",
"controlled",
"humidity,",
"under",
"a",
"12",
"h",
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"and",
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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4.0
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"materials,",
"signals",
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"3",
"–",
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"(Fig.",
"1",
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"The",
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"].",
"Fig.",
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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"including",
"IL-1",
"receptor",
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"positive",
"feedback)",
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"TNF",
"receptor",
"(TNFR)."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"toll-like",
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"tumor",
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"pro-interleukin-1β",
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"[",
"16",
"].",
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"membrane",
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"pores",
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"IL-1β",
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"IL-18",
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"[",
"17",
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"18",
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"releasing",
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"death,",
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"the",
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"[",
"19",
",",
"20",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
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[
"For",
"example,",
"anthrax",
"lethal",
"factor,",
"bacterial",
"muramyl",
"dipeptide,",
"and",
"bacterial",
"flagellin",
"induce",
"the",
"nucleation",
"of",
"the",
"NLRP1",
"inflammasome,",
"NLRP3",
"inflammasome,",
"and",
"NLRC4",
"inflammasome,",
"respectively",
"[",
"1",
",",
"2",
"].",
"The",
"inflammasomes",
"are",
"also",
"activated",
"by",
"host",
"endogenous",
"cues",
"from",
"damaged",
"cells",
"or",
"exogenous",
"materials,",
"signals",
"commonly",
"known",
"as",
"danger-associated",
"molecular",
"patterns",
"(DAMPs).",
"In",
"this",
"regard,",
"the",
"NLRP3",
"inflammasome",
"stands",
"out,",
"owing",
"to",
"its",
"ability",
"to",
"sense",
"a",
"wide",
"range",
"of",
"structurally",
"different",
"molecular",
"entities",
"including",
"crystalline",
"materials,",
"misfolded",
"or",
"aggregated",
"proteins,",
"metabolites,",
"prosthetic",
"implant",
"wear",
"debris,",
"and",
"certain",
"materials",
"found",
"in",
"the",
"environment",
"such",
"as",
"asbestos",
"and",
"silica",
"particles",
"[",
"3",
"–",
"5",
"]",
"(Fig.",
"1",
").",
"The",
"NLRC4",
"inflammasome",
"and",
"AIM2",
"inflammasome",
"are",
"also",
"activated",
"to",
"some",
"extent",
"by",
"endogenous",
"DAMPs",
"[",
"6",
"–",
"8",
"].",
"The",
"inflammatory",
"responses",
"induced",
"by",
"PAMPs",
"or",
"DAMPs",
"can",
"be",
"either",
"acute",
"when",
"the",
"perturbation",
"is",
"rapidly",
"resolved,",
"and",
"the",
"homeostasis",
"is",
"restored,",
"or",
"chronic",
"and",
"pathologic",
"when",
"rapid",
"clearance",
"mechanisms",
"fail.",
"Finally,",
"activating",
"mutations",
"in",
"NLRP1,",
"NLRP3,",
"NLRC4,",
"or",
"MEFV",
"cause",
"inflammasome",
"assembly",
"independently",
"of",
"PAMPs",
"or",
"DAMPs",
"[",
"9",
"–",
"15",
"].",
"Fig.",
"1",
"Mechanisms",
"of",
"activation",
"of",
"the",
"NLRP3",
"inflammasome.",
"Activation",
"of",
"the",
"NLRP3",
"inflammasome",
"involves",
"two",
"steps.",
"Induction",
"of",
"priming",
"signals",
"upon",
"ligation",
"of",
"pathogen",
"recognition",
"receptors",
"(PRRs)",
"such",
"as",
"TLR4",
"and",
"TLR2,",
"and",
"cytokine",
"receptors",
"including",
"IL-1",
"receptor",
"(IL-1R;",
"positive",
"feedback)",
"and",
"TNF",
"receptor",
"(TNFR).",
"These",
"signals",
"induce",
"the",
"transcription",
"of",
"NLRP3",
"and",
"pro-IL-1β",
"through",
"NF-κB;",
"pro-IL-18",
"is",
"constitutively",
"expressed."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Fig.",
"1",
"Mechanisms",
"of",
"activation",
"of",
"the",
"NLRP3",
"inflammasome.",
"Activation",
"of",
"the",
"NLRP3",
"inflammasome",
"involves",
"two",
"steps.",
"Induction",
"of",
"priming",
"signals",
"upon",
"ligation",
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"pathogen",
"recognition",
"receptors",
"(PRRs)",
"such",
"as",
"TLR4",
"and",
"TLR2,",
"and",
"cytokine",
"receptors",
"including",
"IL-1",
"receptor",
"(IL-1R;",
"positive",
"feedback)",
"and",
"TNF",
"receptor",
"(TNFR).",
"These",
"signals",
"induce",
"the",
"transcription",
"of",
"NLRP3",
"and",
"pro-IL-1β",
"through",
"NF-κB;",
"pro-IL-18",
"is",
"constitutively",
"expressed.",
"Priming",
"of",
"NLRP3",
"can",
"also",
"be",
"induced",
"by",
"its",
"deubiquitination,",
"independently",
"of",
"de",
"novo",
"protein",
"synthesis",
"(not",
"depicted).",
"pro-IL-1β",
"mRNA",
"are",
"stabilized",
"by",
"p38α",
"MAPK.",
"Increased",
"expression",
"of",
"NLRP3",
"enables",
"the",
"recruitment",
"of",
"pro-caspase-1",
"via",
"ASC",
"upon",
"sensing",
"of",
"secondary",
"signals,",
"which",
"are",
"triggered",
"by",
"a",
"wide",
"range",
"of",
"stimuli",
"including",
"K",
"+",
"efflux,",
"Ca",
"2+",
"influx,",
"phagocytosis",
"of",
"microorganisms,",
"and",
"particulate",
"materials",
"(causing",
"lysosome",
"destabilization/rupture",
"and",
"release",
"of",
"cathepsins",
"and",
"reactive",
"oxygen",
"species",
"(ROS)),",
"and",
"mitochondrial",
"dysfunction.",
"NLRP3-activating",
"mutations",
"in",
"the",
"NACHT",
"domain",
"cause",
"constitutive",
"activation",
"of",
"this",
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"Proximity-induced",
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"leads",
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"which",
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"pro-IL-18",
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"and",
"IL-18,",
"respectively.",
"Caspase-1",
"also",
"cleaves",
"GSDMD",
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"(N-term)",
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"to",
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"membranes",
"where",
"it",
"oligomerizes",
"and",
"forms",
"pores",
"through",
"which",
"IL-1β",
"and",
"IL-18",
"are",
"secreted."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"ARE,",
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"apoptosis-associated",
"speck-like",
"protein",
"containing",
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"CARD;",
"GSDMD,",
"gasdermin",
"D;",
"HMGB1,",
"high-mobility",
"group",
"box",
"1;",
"IL-1,",
"interleukin-1;",
"LPS,",
"lipopolysaccharide;",
"NF-κB,",
"nuclear",
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"NLR",
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"pyrin",
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"TLR,",
"toll-like",
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"the",
"noncanonical",
"NLRP3",
"inflammasome",
"also",
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"secondarily",
"to",
"the",
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"of",
"caspase-11,",
"which",
"also",
"cleaves",
"GSDMD",
"Caspase-1",
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"pro-interleukin-1β",
"(pro-IL-1β)",
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"into",
"IL-1β",
"and",
"IL-18,",
"respectively",
"[",
"16",
"].",
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"also",
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"gasdermin",
"D",
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"fragment",
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"translocates",
"from",
"the",
"cytoplasm",
"to",
"the",
"plasma",
"membrane",
"where",
"it",
"forms",
"pores",
"through",
"which",
"IL-1β",
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"IL-18",
"are",
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"[",
"17",
",",
"18",
"].",
"However,",
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"pore",
"formation",
"resulting",
"from",
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"activation",
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"GSDMD",
"in",
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"infectious",
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"sterile",
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"integrity,",
"and",
"ultimately",
"ruptures",
"the",
"cell,",
"releasing",
"pro-inflammatory",
"cytoplasmic",
"contents",
"into",
"the",
"extracellular",
"environment.",
"This",
"form",
"of",
"cell",
"death,",
"termed",
"pyroptosis,",
"is",
"inflammatory",
"and",
"results",
"in",
"the",
"recruitment",
"of",
"immune",
"cells",
"and",
"the",
"perpetuation",
"of",
"inflammation",
"[",
"19",
",",
"20",
"].",
"Caspase-8",
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"neutrophil",
"elastase",
"can",
"also",
"generate",
"IL-1β",
"and",
"IL-18",
"whereas",
"caspase-8,",
"caspase-11",
"(ortholog",
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"human",
"caspase-4",
"and",
"caspase-5),",
"and",
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"elastase",
"efficiently",
"process",
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"[",
"21",
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"28",
"].",
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"exposure",
"to",
"supra-physiological",
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"and",
"IL-18,",
"ultimately,",
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"to",
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"tissues",
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"the",
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"However,",
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"compromises",
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"ultimately",
"ruptures",
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"cell,",
"releasing",
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"cytoplasmic",
"contents",
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"the",
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"This",
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"death,",
"termed",
"pyroptosis,",
"is",
"inflammatory",
"and",
"results",
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"the",
"recruitment",
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"[",
"19",
",",
"20",
"].",
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"caspase-8,",
"caspase-11",
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"caspase-4",
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"and",
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"[",
"21",
"–",
"28",
"].",
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"and",
"IL-18,",
"ultimately,",
"inflicts",
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"to",
"multiple",
"tissues",
"including",
"the",
"skeleton.",
"Coordinated",
"actions",
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"the",
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"and",
"the",
"osteoblasts",
"are",
"essential",
"to",
"maintain",
"bone",
"mass",
"and",
"quality.",
"The",
"osteoclasts",
"remove",
"the",
"old",
"or",
"defective",
"matrix,",
"which",
"is",
"replenished",
"fully",
"by",
"the",
"osteoblasts;",
"this",
"tightly",
"regulated",
"process",
"is",
"known",
"as",
"bone",
"coupling",
"[",
"29",
"].",
"Several",
"growth",
"factors,",
"including",
"bone",
"morphogenetic",
"proteins",
"(BMPs)",
"and",
"Wnts",
"control",
"the",
"differentiation",
"of",
"the",
"osteoblasts",
"from",
"mesenchymal",
"stem",
"cells",
"whereas",
"the",
"osteoclasts",
"differentiate",
"from",
"myeloid",
"progenitors",
"exposed",
"to",
"signals",
"generated",
"by",
"macrophage",
"colony-stimulating",
"factor",
"(M-CSF)",
"and",
"receptor",
"activator",
"of",
"NF-κB",
"ligand",
"(RANKL)",
"[",
"30",
",",
"31",
"].",
"The",
"osteoblast",
"and",
"osteoclast",
"differentiation",
"programs",
"are",
"antagonized",
"and",
"enhanced,",
"respectively,",
"by",
"pro-inflammatory",
"cytokines",
"such",
"as",
"tumor",
"necrosis",
"factor-α",
"(TNF-α)",
"and",
"IL-1β.",
"Excessive",
"bone",
"resorption",
"by",
"the",
"osteoclasts",
"at",
"the",
"expenses",
"of",
"bone",
"formation",
"by",
"the",
"osteoblasts",
"in",
"inflammatory",
"conditions",
"creates",
"an",
"imbalance,",
"which",
"over",
"time",
"leads",
"to",
"bone",
"loss",
"and",
"increased",
"fracture",
"risk",
"[",
"32",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"osteoblast",
"and",
"osteoclast",
"differentiation",
"programs",
"are",
"antagonized",
"and",
"enhanced,",
"respectively,",
"by",
"pro-inflammatory",
"cytokines",
"such",
"as",
"tumor",
"necrosis",
"factor-α",
"(TNF-α)",
"and",
"IL-1β.",
"Excessive",
"bone",
"resorption",
"by",
"the",
"osteoclasts",
"at",
"the",
"expenses",
"of",
"bone",
"formation",
"by",
"the",
"osteoblasts",
"in",
"inflammatory",
"conditions",
"creates",
"an",
"imbalance,",
"which",
"over",
"time",
"leads",
"to",
"bone",
"loss",
"and",
"increased",
"fracture",
"risk",
"[",
"32",
"].",
"In",
"this",
"article,",
"we",
"review",
"the",
"role",
"of",
"the",
"inflammasomes",
"in",
"bone",
"resorption",
"and",
"highlight",
"the",
"collateral",
"effects",
"of",
"these",
"protein",
"complexes",
"on",
"other",
"skeletal",
"cells.",
"Mechanisms",
"of",
"bone",
"resorption",
"that",
"are",
"relevant",
"to",
"the",
"inflammasomes",
"IL-1β",
"plays",
"numerous",
"roles",
"in",
"bone",
"pathophysiology.",
"It",
"stimulates",
"RANKL",
"production",
"by",
"mesenchymal",
"cells",
"(e.g.,",
"stromal",
"cells,",
"osteoblasts,",
"and",
"osteocytes),",
"synoviocytes,",
"and",
"T",
"cells",
"directly",
"or",
"indirectly",
"through",
"the",
"regulation",
"of",
"IL-6,",
"IL-17,",
"and",
"TNF-α",
"expression",
"[",
"33",
"–",
"38",
"].",
"The",
"reciprocal",
"regulation",
"of",
"IL-1β",
"production",
"by",
"these",
"cytokines",
"and",
"the",
"reported",
"RANKL-independent",
"actions",
"of",
"IL-6",
"and",
"TNF-α",
"in",
"osteoclast",
"differentiation",
"indicate",
"that",
"these",
"responses",
"are",
"complex",
"and",
"multidirectional",
"[",
"39",
",",
"40",
"].",
"Irrespective",
"of",
"the",
"hierarchy",
"of",
"the",
"events,",
"IL-1β",
"and",
"its",
"effectors",
"act",
"in",
"synergy",
"with",
"RANKL",
"to",
"promote",
"osteoclast",
"differentiation",
"and",
"activity",
"while",
"suppressing",
"osteogenesis",
"[",
"32",
"].",
"IL-1β",
"also",
"stimulates",
"its",
"own",
"synthesis,",
"a",
"positive",
"feedback",
"mechanism",
"that",
"underlies",
"the",
"chronicity",
"of",
"inflammasome",
"actions",
"in",
"bone",
"diseases",
"[",
"33",
",",
"41",
"].",
"On",
"the",
"other",
"hand,",
"while",
"pro-inflammatory",
"actions",
"of",
"IL-18",
"in",
"skin",
"disorders",
"[",
"42",
"]",
"and",
"infection-associated",
"allergic",
"diseases",
"[",
"43",
"]",
"are",
"well",
"described,",
"the",
"role",
"of",
"this",
"cytokine",
"in",
"bone",
"is",
"ambiguous.",
"Indeed,",
"IL-18",
"can",
"inhibit",
"or",
"stimulate",
"bone",
"resorption,",
"depending",
"on",
"cell-contexts",
"[",
"44",
"–",
"46",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"IL-1β",
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"its",
"own",
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"a",
"positive",
"feedback",
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"underlies",
"the",
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"inflammasome",
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"diseases",
"[",
"33",
",",
"41",
"].",
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"hand,",
"while",
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"in",
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"[",
"42",
"]",
"and",
"infection-associated",
"allergic",
"diseases",
"[",
"43",
"]",
"are",
"well",
"described,",
"the",
"role",
"of",
"this",
"cytokine",
"in",
"bone",
"is",
"ambiguous.",
"Indeed,",
"IL-18",
"can",
"inhibit",
"or",
"stimulate",
"bone",
"resorption,",
"depending",
"on",
"cell-contexts",
"[",
"44",
"–",
"46",
"].",
"Secretion",
"of",
"IL-1β",
"through",
"GSDMD-assembled",
"pores",
"by",
"live",
"cells",
"has",
"been",
"reported",
"[",
"18",
",",
"26",
"].",
"This",
"phenomenon",
"referred",
"to",
"as",
"a",
"hyper-reactive",
"state",
"occurs",
"independently",
"of",
"pyroptosis",
"and",
"may",
"be",
"characteristic",
"of",
"diseases",
"of",
"low-grade",
"inflammation",
"as",
"discussed",
"later",
"in",
"this",
"review.",
"GSDMD",
"pores",
"have",
"an",
"inner",
"diameter",
"of",
"10–20",
"nm,",
"which",
"is",
"much",
"bigger",
"than",
"the",
"diameter",
"of",
"mature",
"IL-1β",
"and",
"IL-18",
"(approximately",
"5",
"nm)",
"[",
"17",
",",
"20",
",",
"47",
"–",
"49",
"].",
"There",
"is",
"thus",
"far",
"no",
"basis",
"for",
"such",
"large",
"pores",
"to",
"facilitate",
"only",
"the",
"secretion",
"of",
"these",
"cytokines,",
"implying",
"that",
"molecules",
"with",
"smaller",
"sizes",
"such",
"as",
"eicosanoids,",
"which",
"are",
"also",
"important",
"regulators",
"of",
"bone",
"resorption",
"may",
"be",
"secreted",
"through",
"GSDMD",
"pores.",
"On",
"the",
"other",
"hand,",
"pyroptosis",
"is",
"presumably",
"prominent",
"in",
"diseases",
"marked",
"by",
"chronic",
"episodes",
"of",
"high-grade",
"inflammation",
"such",
"as",
"inflammasomopathies.",
"In",
"this",
"context,",
"IL-1β",
"and",
"IL-18",
"are",
"concomitantly",
"secreted",
"alongside",
"alarmins",
"including",
"IL-1α,",
"S100A8/9,",
"HMGB1",
"[",
"50",
",",
"51",
"],",
"and",
"possibly",
"lipid",
"mediators",
"such",
"as",
"eicosanoids",
"[",
"52",
"];",
"this",
"outcome",
"may",
"underlie",
"the",
"limited",
"efficacy",
"of",
"IL-1",
"blockers",
"in",
"the",
"treatment",
"of",
"bone",
"diseases.",
"Indeed,",
"not",
"only",
"are",
"these",
"alarmins",
"produced",
"by",
"myeloid",
"cells,",
"synovial",
"cells,",
"and",
"osteoblasts",
"[",
"53",
",",
"54",
"],",
"but",
"they",
"are",
"also",
"potent",
"modulators",
"of",
"inflammation",
"and",
"osteoclastogenesis,",
"regulating",
"the",
"expression",
"of",
"RANKL,",
"TNF-α,",
"IL-1β,",
"and",
"IL-6",
"[",
"33",
",",
"55",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"It",
"stimulates",
"RANKL",
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"by",
"mesenchymal",
"cells",
"(e.g.,",
"stromal",
"cells,",
"osteoblasts,",
"and",
"osteocytes),",
"synoviocytes,",
"and",
"T",
"cells",
"directly",
"or",
"indirectly",
"through",
"the",
"regulation",
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"IL-6,",
"IL-17,",
"and",
"TNF-α",
"expression",
"[",
"33",
"–",
"38",
"].",
"The",
"reciprocal",
"regulation",
"of",
"IL-1β",
"production",
"by",
"these",
"cytokines",
"and",
"the",
"reported",
"RANKL-independent",
"actions",
"of",
"IL-6",
"and",
"TNF-α",
"in",
"osteoclast",
"differentiation",
"indicate",
"that",
"these",
"responses",
"are",
"complex",
"and",
"multidirectional",
"[",
"39",
",",
"40",
"].",
"Irrespective",
"of",
"the",
"hierarchy",
"of",
"the",
"events,",
"IL-1β",
"and",
"its",
"effectors",
"act",
"in",
"synergy",
"with",
"RANKL",
"to",
"promote",
"osteoclast",
"differentiation",
"and",
"activity",
"while",
"suppressing",
"osteogenesis",
"[",
"32",
"].",
"IL-1β",
"also",
"stimulates",
"its",
"own",
"synthesis,",
"a",
"positive",
"feedback",
"mechanism",
"that",
"underlies",
"the",
"chronicity",
"of",
"inflammasome",
"actions",
"in",
"bone",
"diseases",
"[",
"33",
",",
"41",
"].",
"On",
"the",
"other",
"hand,",
"while",
"pro-inflammatory",
"actions",
"of",
"IL-18",
"in",
"skin",
"disorders",
"[",
"42",
"]",
"and",
"infection-associated",
"allergic",
"diseases",
"[",
"43",
"]",
"are",
"well",
"described,",
"the",
"role",
"of",
"this",
"cytokine",
"in",
"bone",
"is",
"ambiguous.",
"Indeed,",
"IL-18",
"can",
"inhibit",
"or",
"stimulate",
"bone",
"resorption,",
"depending",
"on",
"cell-contexts",
"[",
"44",
"–",
"46",
"].",
"Secretion",
"of",
"IL-1β",
"through",
"GSDMD-assembled",
"pores",
"by",
"live",
"cells",
"has",
"been",
"reported",
"[",
"18",
",",
"26",
"].",
"This",
"phenomenon",
"referred",
"to",
"as",
"a",
"hyper-reactive",
"state",
"occurs",
"independently",
"of",
"pyroptosis",
"and",
"may",
"be",
"characteristic",
"of",
"diseases",
"of",
"low-grade",
"inflammation",
"as",
"discussed",
"later",
"in",
"this",
"review.",
"GSDMD",
"pores",
"have",
"an",
"inner",
"diameter",
"of",
"10–20",
"nm,",
"which",
"is",
"much",
"bigger",
"than",
"the",
"diameter",
"of",
"mature",
"IL-1β",
"and",
"IL-18",
"(approximately",
"5",
"nm)",
"[",
"17",
",",
"20",
",",
"47",
"–",
"49",
"].",
"There",
"is",
"thus",
"far",
"no",
"basis",
"for",
"such",
"large",
"pores",
"to",
"facilitate",
"only",
"the",
"secretion",
"of",
"these",
"cytokines,",
"implying",
"that",
"molecules",
"with",
"smaller",
"sizes",
"such",
"as",
"eicosanoids,",
"which",
"are",
"also",
"important",
"regulators",
"of",
"bone",
"resorption",
"may",
"be",
"secreted",
"through",
"GSDMD",
"pores."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"GSDMD",
"pores",
"have",
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"10–20",
"nm,",
"which",
"is",
"much",
"bigger",
"than",
"the",
"diameter",
"of",
"mature",
"IL-1β",
"and",
"IL-18",
"(approximately",
"5",
"nm)",
"[",
"17",
",",
"20",
",",
"47",
"–",
"49",
"].",
"There",
"is",
"thus",
"far",
"no",
"basis",
"for",
"such",
"large",
"pores",
"to",
"facilitate",
"only",
"the",
"secretion",
"of",
"these",
"cytokines,",
"implying",
"that",
"molecules",
"with",
"smaller",
"sizes",
"such",
"as",
"eicosanoids,",
"which",
"are",
"also",
"important",
"regulators",
"of",
"bone",
"resorption",
"may",
"be",
"secreted",
"through",
"GSDMD",
"pores.",
"On",
"the",
"other",
"hand,",
"pyroptosis",
"is",
"presumably",
"prominent",
"in",
"diseases",
"marked",
"by",
"chronic",
"episodes",
"of",
"high-grade",
"inflammation",
"such",
"as",
"inflammasomopathies.",
"In",
"this",
"context,",
"IL-1β",
"and",
"IL-18",
"are",
"concomitantly",
"secreted",
"alongside",
"alarmins",
"including",
"IL-1α,",
"S100A8/9,",
"HMGB1",
"[",
"50",
",",
"51",
"],",
"and",
"possibly",
"lipid",
"mediators",
"such",
"as",
"eicosanoids",
"[",
"52",
"];",
"this",
"outcome",
"may",
"underlie",
"the",
"limited",
"efficacy",
"of",
"IL-1",
"blockers",
"in",
"the",
"treatment",
"of",
"bone",
"diseases.",
"Indeed,",
"not",
"only",
"are",
"these",
"alarmins",
"produced",
"by",
"myeloid",
"cells,",
"synovial",
"cells,",
"and",
"osteoblasts",
"[",
"53",
",",
"54",
"],",
"but",
"they",
"are",
"also",
"potent",
"modulators",
"of",
"inflammation",
"and",
"osteoclastogenesis,",
"regulating",
"the",
"expression",
"of",
"RANKL,",
"TNF-α,",
"IL-1β,",
"and",
"IL-6",
"[",
"33",
",",
"55",
"].",
"Inflammasome",
"signaling",
"also",
"leads",
"to",
"the",
"cleavage",
"of",
"poly(ADP-ribose)",
"polymerase",
"1",
"(PARP1)",
"by",
"caspase-7,",
"a",
"response",
"that",
"ultimately",
"promotes",
"the",
"degradation",
"of",
"this",
"negative",
"regulator",
"of",
"osteoclast",
"differentiation",
"and",
"bone",
"resorption",
"[",
"56",
"].",
"Thus,",
"the",
"inflammasomes",
"are",
"key",
"players",
"in",
"the",
"pathogenesis",
"of",
"inflammatory",
"osteolysis.",
"Understanding",
"the",
"biology",
"of",
"these",
"signaling",
"platforms",
"is",
"essential",
"for",
"the",
"development",
"of",
"effective",
"therapies",
"targeting",
"inflammatory",
"bone",
"loss.",
"Widespread",
"activities",
"of",
"the",
"inflammasomes",
"in",
"inflammatory",
"osteolysis",
"Evidence",
"suggests",
"that",
"the",
"inflammasomes",
"are",
"implicated",
"in",
"a",
"wide",
"range",
"of",
"diseases",
"of",
"bone",
"loss",
"driven",
"by",
"sterile",
"and",
"non-sterile",
"inflammation",
"(Table",
"1",
")."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Understanding",
"the",
"biology",
"of",
"these",
"signaling",
"platforms",
"is",
"essential",
"for",
"the",
"development",
"of",
"effective",
"therapies",
"targeting",
"inflammatory",
"bone",
"loss.",
"Widespread",
"activities",
"of",
"the",
"inflammasomes",
"in",
"inflammatory",
"osteolysis",
"Evidence",
"suggests",
"that",
"the",
"inflammasomes",
"are",
"implicated",
"in",
"a",
"wide",
"range",
"of",
"diseases",
"of",
"bone",
"loss",
"driven",
"by",
"sterile",
"and",
"non-sterile",
"inflammation",
"(Table",
"1",
").",
"Table",
"1",
"Inflammasomes",
"and",
"their",
"activators",
"in",
"inflammatory",
"bone",
"diseases",
"Activators",
"Disorders",
"Description",
"of",
"the",
"activators",
"Inflammasomes",
"PAMPs",
"Periodontitis",
"[[",
"57",
"–",
"59",
"]",
"Cicindela",
"equestris",
"NLRP3,",
"AIM2",
"Osteomyelitis",
"[[",
"60",
"–",
"62",
"]",
"Strigomonas",
"oncopelti",
"NLRP3",
"Mutations",
"CAPS",
"[[",
"63",
"–",
"79",
"]",
"Autosomal",
"dominant",
"NLRP3,",
"NLRC4,",
"NLRP12",
"MAS",
"[[",
"11",
",",
"12",
",",
"80",
",",
"81",
"]",
"Autosomal",
"dominant",
"NLRC4",
"FMF",
"[[",
"82",
",",
"83",
"]",
"Autosomal",
"recessive",
"Pyrin",
"DAMPs",
"Sterile",
"CRMO",
"[[",
"22",
",",
"23",
"]",
"Unknown",
"NLRP3",
"Arthritis",
"[[",
"84",
"–",
"88",
"]",
"Self-DNA,",
"other",
"DAMPs?",
"NLRP3,",
"AIM2,",
"others?",
"Metabolic",
"diseases,",
"aging",
"[[",
"5",
"–",
"8",
",",
"89",
"–",
"91",
"]",
"Purine",
"metabolites,",
"fatty",
"acids,",
"other",
"DAMPs?",
"NLRP3,",
"NLRC4,",
"AIM2,",
"others?",
"Wear",
"debris",
"osteolysis",
"[[",
"3",
",",
"92",
",",
"93",
"]",
"PMMA,",
"CoCrMo,",
"etc.",
"NLRP3,",
"AIM2",
"Crystal-induced",
"arthropathies",
"[[",
"94",
"–",
"97",
"]",
"MSU",
"crystals",
"(gout),",
"CPPD",
"crystals",
"(pseudogout),",
"BCP",
"crystals",
"NLRP3",
"Cryopyrin-associated",
"periodic",
"syndromes",
"Cryopyrin-associated",
"periodic",
"syndromes",
"(CAPS),",
"which",
"include",
"familial",
"cold",
"autoinflammatory",
"syndrome",
"(FCAS),",
"Muckle–Wells",
"syndrome",
"(MWS),",
"and",
"neonatal-onset",
"multisystem",
"inflammatory",
"disease",
"(NOMID)",
"are",
"caused",
"by",
"autosomal",
"dominant",
"mutations",
"in",
"the",
"NACHT",
"domain",
"of",
"NLRP3",
"[",
"63",
"–",
"65",
",",
"98",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"Table",
"1",
"Inflammasomes",
"and",
"their",
"activators",
"in",
"inflammatory",
"bone",
"diseases",
"Activators",
"Disorders",
"Description",
"of",
"the",
"activators",
"Inflammasomes",
"PAMPs",
"Periodontitis",
"[[",
"57",
"–",
"59",
"]",
"Tamias",
"ochrogenys",
"NLRP3,",
"AIM2",
"Osteomyelitis",
"[[",
"60",
"–",
"62",
"]",
"Urocitellus",
"parryii",
"NLRP3",
"Mutations",
"CAPS",
"[[",
"63",
"–",
"79",
"]",
"Autosomal",
"dominant",
"NLRP3,",
"NLRC4,",
"NLRP12",
"MAS",
"[[",
"11",
",",
"12",
",",
"80",
",",
"81",
"]",
"Autosomal",
"dominant",
"NLRC4",
"FMF",
"[[",
"82",
",",
"83",
"]",
"Autosomal",
"recessive",
"Pyrin",
"DAMPs",
"Sterile",
"CRMO",
"[[",
"22",
",",
"23",
"]",
"Unknown",
"NLRP3",
"Arthritis",
"[[",
"84",
"–",
"88",
"]",
"Self-DNA,",
"other",
"DAMPs?",
"NLRP3,",
"AIM2,",
"others?",
"Metabolic",
"diseases,",
"aging",
"[[",
"5",
"–",
"8",
",",
"89",
"–",
"91",
"]",
"Purine",
"metabolites,",
"fatty",
"acids,",
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"NLRP3,",
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"93",
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"[",
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"matrix",
"protruding",
"towards",
"the",
"bone",
"marrow",
"cavity",
"[",
"73",
"].",
"Unexpectedly,",
"conditional",
"activation",
"of",
"NLRP3",
"in",
"myeloid",
"cells",
"but",
"not",
"in",
"osteochondro-progenitors",
"reproduces",
"the",
"abnormal",
"cartilage",
"features,",
"suggesting",
"that",
"the",
"phenotype",
"is",
"not",
"chondrocyte",
"autonomous",
"[",
"75",
"].",
"CAPS",
"mice",
"also",
"exhibit",
"severe",
"low",
"bone",
"mass,",
"a",
"phenotype",
"that",
"correlates",
"with",
"a",
"massive",
"expansion",
"of",
"osteoclast",
"precursors,",
"exuberant",
"osteoclastogenesis,",
"and",
"increased",
"osteoclast",
"activity",
"[",
"41",
",",
"73",
",",
"75",
"–",
"77",
"].",
"Thus,",
"while",
"the",
"magnitude",
"of",
"bone",
"resorption",
"in",
"CAPS",
"patients",
"is",
"not",
"known,",
"this",
"process",
"is",
"prominent",
"and",
"well",
"characterized",
"in",
"mouse",
"models.",
"Systemic",
"inflammation",
"and",
"multiple",
"organ",
"pathologies,",
"including",
"bone",
"abnormalities,",
"are",
"entirely",
"prevented",
"in",
"NOMID",
"mice",
"lacking",
"IL-1",
"receptor",
"[",
"75",
"].",
"However,",
"persistent",
"residual",
"inflammation",
"is",
"reported",
"in",
"FCAS",
"mice",
"and",
"MWS",
"mice",
"deficient",
"in",
"IL-1",
"and",
"IL-18",
"signaling",
"[",
"78",
",",
"79",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"CAPS",
"mice",
"also",
"exhibit",
"severe",
"low",
"bone",
"mass,",
"a",
"phenotype",
"that",
"correlates",
"with",
"a",
"massive",
"expansion",
"of",
"osteoclast",
"precursors,",
"exuberant",
"osteoclastogenesis,",
"and",
"increased",
"osteoclast",
"activity",
"[",
"41",
",",
"73",
",",
"75",
"–",
"77",
"].",
"Thus,",
"while",
"the",
"magnitude",
"of",
"bone",
"resorption",
"in",
"CAPS",
"patients",
"is",
"not",
"known,",
"this",
"process",
"is",
"prominent",
"and",
"well",
"characterized",
"in",
"mouse",
"models.",
"Systemic",
"inflammation",
"and",
"multiple",
"organ",
"pathologies,",
"including",
"bone",
"abnormalities,",
"are",
"entirely",
"prevented",
"in",
"NOMID",
"mice",
"lacking",
"IL-1",
"receptor",
"[",
"75",
"].",
"However,",
"persistent",
"residual",
"inflammation",
"is",
"reported",
"in",
"FCAS",
"mice",
"and",
"MWS",
"mice",
"deficient",
"in",
"IL-1",
"and",
"IL-18",
"signaling",
"[",
"78",
",",
"79",
"].",
"These",
"findings",
"align",
"with",
"clinical",
"studies,",
"which",
"consistently",
"show",
"that",
"epiphyseal",
"lesions",
"and",
"outgrowths",
"continue",
"to",
"expand",
"for",
"a",
"significant",
"number",
"of",
"NOMID",
"patients",
"on",
"IL-1",
"biologics",
"despite",
"the",
"resolution",
"of",
"disease-associated",
"inflammatory",
"symptoms",
"[",
"70",
",",
"99",
"–",
"101",
"].",
"Collectively,",
"these",
"observations",
"suggest",
"that",
"IL-1β",
"is",
"not",
"the",
"primary",
"driver",
"of",
"skeletal",
"outcomes",
"in",
"CAPS,",
"and",
"that",
"inflammasome-dependent",
"responses",
"other",
"than",
"IL-1β",
"play",
"a",
"role",
"in",
"these",
"disorders.",
"This",
"view",
"is",
"consistent",
"with",
"findings",
"showing",
"that",
"levels",
"of",
"TNF-α",
"remain",
"elevated",
"in",
"certain",
"CAPS",
"patients",
"on",
"IL-1",
"blockers,",
"and",
"neutralization",
"of",
"TNF-α",
"activity",
"improves",
"inflammatory",
"endpoints",
"in",
"CAPS",
"mice",
"[",
"78",
"].",
"This",
"view",
"is",
"further",
"supported",
"by",
"recent",
"evidence",
"indicating",
"that",
"the",
"pathogenesis",
"of",
"NOMID",
"in",
"mice",
"is",
"prevented",
"by",
"(i)",
"genetic",
"ablation",
"of",
"GSDMD",
"and",
"(ii)",
"a",
"novel",
"inhibitor",
"of",
"the",
"interactions",
"of",
"p38α",
"MAPK",
"and",
"MAPK-activated",
"kinase",
"2,",
"which",
"inhibits",
"not",
"only",
"IL-1β,",
"but",
"also",
"IL-6",
"and",
"TNF-α",
"[",
"41",
",",
"77",
"].",
"Thus,",
"multiple",
"responses,",
"including",
"pyroptosis,",
"contribute",
"to",
"inflammasomopathies.",
"Macrophage",
"activation",
"syndrome",
"The",
"NLRC4",
"inflammasome",
"senses",
"bacterial",
"type",
"III",
"and",
"IV",
"secretion",
"systems",
"and",
"flagellin",
"via",
"NLR",
"family",
"apoptosis",
"inhibitory",
"proteins",
"(NAIPs).",
"As",
"noted",
"above,",
"NLRC4-activating",
"mutations",
"are",
"found",
"in",
"certain",
"FCAS",
"patients."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"As",
"noted",
"above,",
"NLRC4-activating",
"mutations",
"are",
"found",
"in",
"certain",
"FCAS",
"patients.",
"Moreover,",
"recent",
"evidence",
"implicates",
"the",
"NLRC4",
"inflammasome",
"in",
"the",
"pathogenesis",
"of",
"sterile",
"inflammatory",
"disorders",
"as",
"patients",
"with",
"NLRC4",
"gain-of-function",
"mutations",
"develop",
"cytopenia,",
"high",
"ferritin",
"levels,",
"hemophagocytosis,",
"and",
"splenomegaly.",
"These",
"symptoms",
"are",
"associated",
"with",
"excessive",
"levels",
"of",
"IL-18",
"and",
"IL-1β,",
"and",
"recurring",
"fever",
"flares,",
"a",
"phenotype",
"that",
"is",
"reminiscent",
"of",
"macrophage",
"activation",
"syndrome",
"(MAS)",
"[",
"12",
",",
"80",
"].",
"MAS",
"is",
"a",
"frequent",
"complication",
"of",
"systemic",
"juvenile",
"idiopathic",
"arthritis",
"(sJIA),",
"a",
"disease",
"that",
"interferes",
"with",
"healthy",
"skeletal",
"development",
"and",
"bone",
"mass",
"acquisition",
"[",
"102",
"].",
"Although",
"IL-1β",
"levels",
"are",
"in",
"general",
"lower",
"in",
"MAS",
"compared",
"with",
"CAPS,",
"IL-1",
"biologics",
"are",
"efficacious",
"in",
"the",
"treatment",
"of",
"sJIA",
"[",
"103",
",",
"104",
"].",
"Consistent",
"with",
"the",
"role",
"of",
"mutated",
"NLRC4",
"in",
"the",
"development",
"of",
"joint",
"pathologies,",
"transgenic",
"mice",
"expressing",
"constitutively",
"active",
"NLRC4",
"produce",
"high",
"levels",
"of",
"IL-1β",
"and",
"IL-18,",
"and",
"develop",
"arthritis",
"[",
"81",
"].",
"The",
"NLRC4",
"inflammasome",
"is",
"also",
"activated",
"by",
"nucleotide-derived",
"metabolites",
"(e.g.,",
"adenine",
"and",
"N-4-acetylcytidine)",
"[",
"6",
"]",
"and",
"fatty",
"acids",
"(e.g.,",
"lysophosphatidylcholine",
"and",
"palmitate)",
"[",
"89",
"]",
"and",
"is",
"upregulated",
"by",
"bone-derived",
"DAMPs",
"during",
"osteoclastogenesis",
"[",
"90",
"].",
"An",
"interplay",
"between",
"the",
"NLRP3",
"and",
"NLRC4",
"inflammasomes",
"has",
"been",
"noted",
"in",
"these",
"models",
"of",
"sterile",
"inflammation",
"as",
"well",
"as",
"in",
"response",
"to",
"Salmonella",
"infection",
"[",
"105",
",",
"106",
"].",
"Familial",
"Mediterranean",
"fever",
"MEFV",
"encodes",
"pyrin,",
"which",
"activates",
"caspase-1",
"through",
"ASC",
"upon",
"sensing",
"post-translationally",
"modified",
"Rho",
"GTPase",
"[",
"107",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"FMF",
"is",
"the",
"most",
"prevalent",
"monogenic",
"autoinflammatory",
"disorder;",
"it",
"affects",
"over",
"100,000",
"persons",
"worldwide",
"and",
"causes",
"sporadic",
"and",
"chronic",
"symptoms",
"[",
"98",
"].",
"FMF",
"mice",
"develop",
"severe",
"systemic",
"inflammation",
"and",
"exhibit",
"massive",
"cartilage",
"and",
"bone",
"erosion",
"[",
"112",
"].",
"These",
"mice",
"do",
"not",
"display",
"systemic",
"inflammatory",
"symptoms",
"upon",
"deletion",
"of",
"GSDMD,",
"IL-1",
"receptor,",
"or",
"ASC",
"[",
"112",
",",
"113",
"].",
"Arthritis",
"Inflammasomes",
"are",
"activated",
"in",
"several",
"autoimmune",
"diseases,",
"including",
"rheumatoid",
"arthritis",
"(RA)",
"and",
"ankylosing",
"spondylitis",
"(AS).",
"Components",
"of",
"the",
"NLRP3",
"inflammasomes",
"and",
"various",
"cytokines",
"including",
"TNF-α,",
"IL-1β,",
"IL-6,",
"IL-7,",
"and",
"IL-17",
"are",
"highly",
"expressed",
"in",
"RA",
"[",
"84",
",",
"114",
"].",
"Specific",
"interactions",
"among",
"these",
"cytokines",
"and",
"other",
"inflammatory",
"mediators",
"may",
"drive",
"systemic",
"and",
"focal",
"osteolysis",
"in",
"arthritis",
"[",
"115",
"].",
"Systemic",
"arthritis",
"and",
"bone",
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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[
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"multifocal",
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"bone",
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"and",
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"[",
"21",
",",
"22",
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"Neutrophils",
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"CRMO",
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"redundant",
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"caspase-8",
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"the",
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"[",
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",",
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",",
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"128",
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"129",
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"Accordingly,",
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"Aging",
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"inflammation."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
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"caspase-8",
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"inflammasome",
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"bone",
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",",
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",",
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"31",
",",
"128",
",",
"129",
"].",
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"conditions",
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"estrogen",
"deficiency,",
"blockade",
"of",
"TNF-α",
"or",
"IL-1β",
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"patients",
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"levels",
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"130",
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"90",
",",
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"Aging",
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"associated",
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"and",
"is",
"associated",
"with",
"increased",
"levels",
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"IL-18,",
"IL-1",
"receptor",
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"IL-6",
"[",
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"gene",
"modules",
"including",
"NLRC4",
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"IL-1β",
"are",
"upregulated",
"in",
"older",
"people",
"compared",
"with",
"younger",
"individuals;",
"persistent",
"expression",
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"genes",
"correlates",
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"the",
"occurrence",
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"age-related",
"complications,",
"including",
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"production",
"of",
"inflammatory",
"cytokines,",
"metabolic",
"dysfunction,",
"and",
"oxidative",
"stress",
"[",
"6",
"].",
"The",
"NLRP3",
"inflammasome",
"also",
"modulates",
"age-related",
"inflammation",
"in",
"peripheral",
"tissues",
"and",
"age-related",
"bone",
"loss",
"in",
"mice,",
"though",
"the",
"underlying",
"mechanisms",
"are",
"unknown",
"[",
"91",
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"ability",
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"the",
"NLRP3",
"inflammasome",
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"wide",
"variety",
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"likely",
"an",
"important",
"driver",
"in",
"the",
"development",
"of",
"age-",
"and",
"metabolic-related",
"pathologies."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"These",
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"include",
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"cholesterol,",
"extracellular",
"ATP,",
"purine",
"and",
"pyrimidine",
"metabolites,",
"and",
"debris",
"from",
"damaged",
"tissues",
"[",
"6",
",",
"133",
"].",
"For",
"example,",
"metabolites",
"from",
"the",
"purine",
"and",
"pyrimidine",
"pathways",
"stimulate",
"the",
"NLRP3",
"and",
"NLRC4",
"inflammasomes",
"in",
"THP-1",
"cells,",
"activate",
"human",
"platelets",
"and",
"neutrophils",
"in",
"cultures,",
"and",
"promote",
"hypertension",
"and",
"inflammation",
"in",
"mice",
"[",
"6",
"].",
"The",
"NLRP3",
"inflammasome",
"may",
"also",
"be",
"involved",
"in",
"hyper-multinucleation",
"of",
"murine",
"osteoclasts",
"caused",
"by",
"purinergic",
"receptor",
"P2X5",
"signaling",
"[",
"134",
"].",
"We",
"have",
"shown",
"that",
"bone",
"matrix",
"degradation",
"products",
"regulate",
"the",
"NLRP3",
"and",
"NLRC4",
"inflammasomes",
"in",
"cells",
"of",
"the",
"osteoclast",
"lineage",
"[",
"90",
"].",
"Accordingly,",
"Nlrp3",
"null",
"mice",
"are",
"protected",
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"loss",
"induced",
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"ovariectomy,",
"sustained",
"exposure",
"to",
"parathyroid",
"hormone",
"or",
"RANKL.",
"Treatment",
"of",
"mice",
"with",
"zoledronic",
"acid",
"inhibits",
"inflammasome",
"activation,",
"thus",
"reinforcing",
"the",
"view",
"that",
"endogenous",
"DAMPs",
"are",
"released",
"from",
"the",
"bone",
"matrix",
"during",
"bone",
"resorption,",
"causing",
"autocrine",
"and",
"paracrine",
"effects",
"on",
"osteoclastogenesis",
"[",
"90",
"].",
"Wear",
"debris-induced",
"osteolysis",
"Wear",
"particles",
"from",
"articulating",
"prosthetic",
"joint",
"surfaces",
"such",
"as",
"those",
"from",
"cobalt-chromium-molybdenum",
"(CoCrMo)",
"implants",
"induce",
"inflammatory",
"responses",
"that",
"cause",
"aseptic",
"loosening",
"as",
"a",
"result",
"of",
"uncontrolled",
"osteolysis",
"[",
"135",
"].",
"The",
"osteolytic",
"process",
"is",
"associated",
"with",
"the",
"formation",
"at",
"the",
"implant-bone",
"interface",
"of",
"a",
"cellular",
"membrane",
"enriched",
"in",
"cells",
"of",
"the",
"monocyte-macrophage",
"lineage",
"[",
"136",
"].",
"Activation",
"of",
"the",
"NF-kB",
"pathway",
"through",
"TLR2",
"signaling",
"by",
"prosthetic",
"debris",
"promote",
"not",
"only",
"the",
"expression",
"of",
"pro-inflammatory",
"cytokines",
"such",
"as",
"TNF-α,",
"but",
"also",
"priming",
"signals",
"for",
"the",
"NLRP3",
"and",
"AIM2",
"inflammasomes."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"The",
"NLRP3",
"inflammasome",
"may",
"also",
"be",
"involved",
"in",
"hyper-multinucleation",
"of",
"murine",
"osteoclasts",
"caused",
"by",
"purinergic",
"receptor",
"P2X5",
"signaling",
"[",
"134",
"].",
"We",
"have",
"shown",
"that",
"bone",
"matrix",
"degradation",
"products",
"regulate",
"the",
"NLRP3",
"and",
"NLRC4",
"inflammasomes",
"in",
"cells",
"of",
"the",
"osteoclast",
"lineage",
"[",
"90",
"].",
"Accordingly,",
"Nlrp3",
"null",
"mice",
"are",
"protected",
"from",
"bone",
"loss",
"induced",
"by",
"ovariectomy,",
"sustained",
"exposure",
"to",
"parathyroid",
"hormone",
"or",
"RANKL.",
"Treatment",
"of",
"mice",
"with",
"zoledronic",
"acid",
"inhibits",
"inflammasome",
"activation,",
"thus",
"reinforcing",
"the",
"view",
"that",
"endogenous",
"DAMPs",
"are",
"released",
"from",
"the",
"bone",
"matrix",
"during",
"bone",
"resorption,",
"causing",
"autocrine",
"and",
"paracrine",
"effects",
"on",
"osteoclastogenesis",
"[",
"90",
"].",
"Wear",
"debris-induced",
"osteolysis",
"Wear",
"particles",
"from",
"articulating",
"prosthetic",
"joint",
"surfaces",
"such",
"as",
"those",
"from",
"cobalt-chromium-molybdenum",
"(CoCrMo)",
"implants",
"induce",
"inflammatory",
"responses",
"that",
"cause",
"aseptic",
"loosening",
"as",
"a",
"result",
"of",
"uncontrolled",
"osteolysis",
"[",
"135",
"].",
"The",
"osteolytic",
"process",
"is",
"associated",
"with",
"the",
"formation",
"at",
"the",
"implant-bone",
"interface",
"of",
"a",
"cellular",
"membrane",
"enriched",
"in",
"cells",
"of",
"the",
"monocyte-macrophage",
"lineage",
"[",
"136",
"].",
"Activation",
"of",
"the",
"NF-kB",
"pathway",
"through",
"TLR2",
"signaling",
"by",
"prosthetic",
"debris",
"promote",
"not",
"only",
"the",
"expression",
"of",
"pro-inflammatory",
"cytokines",
"such",
"as",
"TNF-α,",
"but",
"also",
"priming",
"signals",
"for",
"the",
"NLRP3",
"and",
"AIM2",
"inflammasomes.",
"Macrophages",
"can",
"also",
"phagocytose",
"these",
"particles;",
"cellular",
"accumulation",
"of",
"these",
"non-degradable",
"materials",
"enhances",
"the",
"production",
"of",
"reactive",
"oxygen",
"species",
"and",
"the",
"rupture",
"of",
"the",
"phagosomes,",
"which",
"releases",
"cathepsins",
"in",
"the",
"cytoplasm,",
"events",
"that",
"activate",
"the",
"inflammasomes",
"[",
"92",
"].",
"The",
"size",
"and",
"shape",
"of",
"CoCrMo",
"alloys",
"affect",
"the",
"amplitude",
"of",
"the",
"inflammatory",
"responses",
"[",
"93",
"].",
"Thus,",
"wear",
"debris",
"can",
"provide",
"both",
"priming",
"and",
"assembly",
"signals",
"that",
"lead",
"to",
"aberrant",
"inflammasome",
"activation."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Activation",
"of",
"the",
"NF-kB",
"pathway",
"through",
"TLR2",
"signaling",
"by",
"prosthetic",
"debris",
"promote",
"not",
"only",
"the",
"expression",
"of",
"pro-inflammatory",
"cytokines",
"such",
"as",
"TNF-α,",
"but",
"also",
"priming",
"signals",
"for",
"the",
"NLRP3",
"and",
"AIM2",
"inflammasomes.",
"Macrophages",
"can",
"also",
"phagocytose",
"these",
"particles;",
"cellular",
"accumulation",
"of",
"these",
"non-degradable",
"materials",
"enhances",
"the",
"production",
"of",
"reactive",
"oxygen",
"species",
"and",
"the",
"rupture",
"of",
"the",
"phagosomes,",
"which",
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"cathepsins",
"in",
"the",
"cytoplasm,",
"events",
"that",
"activate",
"the",
"inflammasomes",
"[",
"92",
"].",
"The",
"size",
"and",
"shape",
"of",
"CoCrMo",
"alloys",
"affect",
"the",
"amplitude",
"of",
"the",
"inflammatory",
"responses",
"[",
"93",
"].",
"Thus,",
"wear",
"debris",
"can",
"provide",
"both",
"priming",
"and",
"assembly",
"signals",
"that",
"lead",
"to",
"aberrant",
"inflammasome",
"activation.",
"Consistent",
"with",
"the",
"role",
"of",
"the",
"NLRP3",
"inflammasome",
"in",
"bone",
"damage",
"induced",
"by",
"prosthetic",
"particles,",
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"resorption",
"induced",
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"polymethylmethacrylate",
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"is",
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"caspase-1",
"[",
"3",
",",
"145",
"].",
"Thus,",
"both",
"the",
"metal",
"and",
"plastic",
"components",
"of",
"the",
"prostheses",
"activate",
"the",
"inflammasomes.",
"Crystal-induced",
"arthropathies",
"Endogenous",
"crystalline",
"particles",
"are",
"involved",
"in",
"the",
"pathogenesis",
"of",
"arthropathies.",
"For",
"example,",
"gouty",
"arthritis",
"is",
"caused",
"by",
"precipitation",
"of",
"monosodium",
"urate",
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"[",
"94",
"],",
"calcium",
"pyrophosphate",
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"disease",
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"is",
"driven",
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"crystals",
"[",
"94",
"],",
"and",
"degenerative",
"arthropathies",
"such",
"as",
"osteoarthritis",
"and",
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"shoulder",
"are",
"the",
"result",
"of",
"abnormal",
"accumulation",
"of",
"basic",
"calcium",
"phosphate",
"(BCP)",
"crystals",
"[",
"137",
"].",
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"mechanisms",
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"these",
"diseases",
"include",
"phagocytosis",
"of",
"crystals",
"by",
"myeloid",
"cells,",
"an",
"event",
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"several",
"inflammatory",
"pathways",
"including",
"the",
"inflammasomes,",
"chondrocyte",
"apoptosis,",
"and",
"matrix",
"calcification",
"[",
"138",
"–",
"140",
"]."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
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"and",
"plastic",
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"of",
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"activate",
"the",
"inflammasomes.",
"Crystal-induced",
"arthropathies",
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"crystalline",
"particles",
"are",
"involved",
"in",
"the",
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"For",
"example,",
"gouty",
"arthritis",
"is",
"caused",
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"precipitation",
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"monosodium",
"urate",
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"calcium",
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"[",
"94",
"],",
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"[",
"137",
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"myeloid",
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"an",
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"chondrocyte",
"apoptosis,",
"and",
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"calcification",
"[",
"138",
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"erosions",
"in",
"gout",
"stems",
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"tophi",
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"95",
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"crystals",
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"articular",
"cartilage",
"whereas",
"patients",
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"CPDD",
"familial",
"patterns",
"have",
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"bone",
"mineral",
"density",
"though",
"the",
"extent",
"to",
"which",
"bone",
"resorption",
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"impacted",
"is",
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"[",
"141",
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"BCP",
"crystals,",
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"promote",
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"in",
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"inflammasome-dependent",
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"[",
"90",
",",
"96",
",",
"142",
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"the",
"actions",
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"BCP",
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"skeletal",
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"NLRP3",
"inflammasome",
"prevents",
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"development",
"of",
"neutrophil",
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"the",
"air-pouch",
"model",
"of",
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"and",
"decreased",
"pathology",
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"[",
"97",
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"by",
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"143",
",",
"144",
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"of",
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"by",
"caspase-8",
"and",
"pyroptosis",
"may",
"account",
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"these",
"discrepant",
"observations."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"Shared",
"mechanisms",
"among",
"these",
"diseases",
"include",
"phagocytosis",
"of",
"crystals",
"by",
"myeloid",
"cells,",
"an",
"event",
"that",
"activates",
"several",
"inflammatory",
"pathways",
"including",
"the",
"inflammasomes,",
"chondrocyte",
"apoptosis,",
"and",
"matrix",
"calcification",
"[",
"138",
"–",
"140",
"].",
"Bone",
"erosions",
"in",
"gout",
"stems",
"from",
"continuous",
"recruitment",
"of",
"macrophages",
"to",
"tophi",
"[",
"95",
"];",
"sporadic",
"CPDD",
"is",
"characterized",
"by",
"the",
"presence",
"of",
"CPPD",
"crystals",
"in",
"articular",
"cartilage",
"whereas",
"patients",
"with",
"CPDD",
"familial",
"patterns",
"have",
"low",
"bone",
"mineral",
"density",
"though",
"the",
"extent",
"to",
"which",
"bone",
"resorption",
"is",
"impacted",
"is",
"not",
"known",
"[",
"141",
"].",
"BCP",
"crystals,",
"particularly",
"hydroxyapatite",
"crystals,",
"promote",
"osteoclast",
"formation",
"in",
"vitro",
"in",
"NLRP3",
"inflammasome-dependent",
"manner",
"[",
"90",
",",
"96",
",",
"142",
"].",
"However,",
"the",
"actions",
"of",
"BCP",
"on",
"NLRP3",
"inflammasome-mediated",
"skeletal",
"pathology",
"are",
"controversial.",
"Lack",
"of",
"components",
"of",
"the",
"NLRP3",
"inflammasome",
"prevents",
"the",
"development",
"of",
"neutrophil",
"inflammation",
"in",
"the",
"air-pouch",
"model",
"of",
"synovitis",
"and",
"decreased",
"pathology",
"in",
"the",
"Ank-deficient",
"model",
"of",
"arthritis",
"[",
"97",
"].",
"By",
"contrast,",
"inflammatory",
"responses",
"induced",
"by",
"the",
"injection",
"of",
"BCP",
"crystals",
"into",
"the",
"knees",
"or",
"intra-peritoneally",
"are",
"independent",
"of",
"the",
"NLRP3",
"inflammasome",
"[",
"143",
",",
"144",
"].",
"Alternative",
"processing",
"of",
"IL-1β",
"by",
"caspase-8",
"and",
"pyroptosis",
"may",
"account",
"for",
"these",
"discrepant",
"observations.",
"Therapeutic",
"perspective",
"Anti-resorptive",
"drugs",
"such",
"as",
"bisphosphonates",
"and",
"denosumab",
"are",
"efficacious",
"in",
"the",
"prevention",
"of",
"inflammation-associated",
"bone",
"fractures,",
"but",
"they",
"do",
"not",
"impact",
"the",
"course",
"of",
"inflammation",
"(Fig.",
"2",
").",
"Thus,",
"inhibition",
"of",
"osteoclast",
"differentiation",
"and/or",
"activity",
"is",
"not",
"sufficient",
"to",
"arrest",
"the",
"damage",
"to",
"the",
"bone",
"surrounding",
"soft",
"tissues",
"such",
"as",
"the",
"synovium",
"in",
"conditions",
"of",
"high-grade",
"inflammation.",
"On",
"the",
"other",
"hand,",
"biologics",
"are",
"successfully",
"used",
"in",
"the",
"clinic",
"to",
"temper",
"down",
"inflammation",
"(Fig.",
"2",
")."
] |
Original work titled: 'Omnipresence of inflammasome activities in inflammatory bone diseases' (Seminars in Immunopathology/Springer Berlin Heidelberg) by the following authors: Yael Alippe; Gabriel Mbalaviele DOI: 10.1007/s00281-019-00753-4
|
14dd5e79c50801a2cb4c3d4dc03381e7
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"2",
").",
"Thus,",
"inhibition",
"of",
"osteoclast",
"differentiation",
"and/or",
"activity",
"is",
"not",
"sufficient",
"to",
"arrest",
"the",
"damage",
"to",
"the",
"bone",
"surrounding",
"soft",
"tissues",
"such",
"as",
"the",
"synovium",
"in",
"conditions",
"of",
"high-grade",
"inflammation.",
"On",
"the",
"other",
"hand,",
"biologics",
"are",
"successfully",
"used",
"in",
"the",
"clinic",
"to",
"temper",
"down",
"inflammation",
"(Fig.",
"2",
").",
"However,",
"biologics",
"have",
"their",
"shortcomings",
"such",
"as",
"high",
"costs,",
"the",
"requirement",
"for",
"parenteral",
"delivery,",
"the",
"development",
"of",
"resistance,",
"and",
"immunosuppression.",
"In",
"addition,",
"the",
"efficacy",
"of",
"these",
"drugs",
"is",
"restrained",
"by",
"redundancy",
"among",
"signaling",
"pathways",
"as",
"they",
"target",
"specific",
"inflammatory",
"instigators.",
"Thus,",
"there",
"is",
"still",
"an",
"unmet",
"medical",
"need",
"for",
"the",
"development",
"of",
"adequate",
"therapeutic",
"strategies;",
"in-depth",
"understanding",
"of",
"the",
"mechanism",
"of",
"action",
"of",
"key",
"inflammatory",
"pathways",
"is",
"required",
"to",
"achieve",
"this",
"goal.",
"Recent",
"breakthroughs",
"revealing",
"that",
"aberrant",
"activities",
"of",
"the",
"inflammasomes",
"cause",
"pyroptosis,",
"a",
"lytic",
"form",
"of",
"cell",
"death",
"that",
"concomitantly",
"unleashes",
"several",
"inflammatory",
"mediators",
"to",
"the",
"extracellular",
"milieu",
"offer",
"novel",
"perspectives",
"for",
"drug",
"discovery.",
"For",
"example,",
"strategies",
"aimed",
"at",
"preventing",
"pyroptosis",
"through",
"selective",
"blockade",
"of",
"individual",
"components",
"of",
"the",
"inflammasomes",
"such",
"as",
"caspase-1,",
"NLRP3,",
"or",
"GSDMD",
"or",
"inhibiting",
"signaling",
"nodes",
"that",
"integrate",
"several",
"inflammatory",
"cues",
"such",
"as",
"p38",
"MAPK",
"are",
"being",
"fiercely",
"explored.",
"Fig.",
"2",
"Inflammatory",
"osteolysis",
"and",
"therapeutic",
"interventions.",
"Cytokines",
"(e.g.,",
"IL-1α,",
"IL-1β,",
"IL-6,",
"IL-17,",
"and",
"TNF-α)",
"stimulate",
"bone",
"resorption",
"directly,",
"acting",
"on",
"the",
"osteoclast",
"lineage",
"or",
"indirectly",
"by",
"inducing",
"RANKL",
"expression",
"by",
"mesenchymal",
"cells,",
"T",
"cells,",
"and",
"B",
"cells.",
"These",
"cytokines",
"also",
"inhibit",
"bone",
"formation.",
"Bone",
"resorption",
"is",
"directly",
"blocked",
"by",
"anti-resorptive",
"drugs",
"such",
"as",
"bisphosphonates",
"and",
"denosumab",
"or",
"indirectly",
"by",
"biologics",
"targeting",
"IL-1α/IL-1β,",
"IL-6,",
"IL-17,",
"or",
"TNF-α.",
"In",
"conditions",
"of",
"low-grade",
"inflammation,",
"bone",
"resorption",
"is",
"amplified",
"by",
"DAMPs",
"that",
"are",
"released",
"from",
"bone",
"matrix"
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
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CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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[
"Highlights",
"We",
"studied",
"standardized",
"municipality",
"tuberculosis",
"case",
"notification",
"rates",
"in",
"an",
"area",
"of",
"social",
"inequality",
"in",
"Brazil.",
"Between",
"2001",
"and",
"2016,",
"the",
"study",
"identified",
"increasing",
"trends",
"of",
"TB",
"in",
"Sergipe",
"with",
"inequalities",
"between",
"age",
"groups",
"and",
"sex.",
"The",
"cure",
"rate",
"presented",
"a",
"worrying",
"decline,",
"countering",
"the",
"steady",
"trend",
"of",
"treatment",
"abandonment.",
"Tuberculosis",
"rates",
"were",
"strongly",
"positively",
"spatially",
"autocorrelated.",
"Higher",
"rates",
"were",
"associated",
"with",
"population",
"density",
"and",
"socioeconomic",
"conditions.",
"Background",
"Tuberculosis",
"(TB)",
"is",
"an",
"infectious",
"disease",
"caused",
"by",
"an",
"intracellular",
"pathogen",
"called",
"Pseudonocardia",
"thermophila.",
"It",
"is",
"a",
"disease",
"known",
"worldwide",
"for",
"its",
"vulnerability,",
"magnitude",
"and",
"morbidity",
"factors.",
"TB",
"is",
"still",
"a",
"serious",
"global",
"public",
"health",
"problem,",
"and",
"it",
"is",
"in",
"the",
"top",
"10",
"causes",
"of",
"mortality",
"in",
"underdeveloped",
"countries",
"[",
"1",
"].",
"Brazil",
"has",
"been",
"undergoing",
"a",
"process",
"of",
"epidemiological",
"transition,",
"with",
"the",
"increase",
"of",
"chronic",
"and",
"non-transmissible",
"diseases",
"and",
"the",
"reduction",
"of",
"infectious",
"and",
"parasitic",
"diseases",
"[",
"2",
"].",
"However,",
"TB",
"remains",
"on",
"the",
"horizon",
"of",
"public",
"health,",
"mainly",
"due",
"to",
"its",
"persistence",
"and",
"high",
"rates",
"in",
"communities",
"living",
"in",
"poverty",
"and",
"on",
"the",
"margins",
"of",
"social",
"exclusion",
"[",
"3",
"].",
"In",
"the",
"world,",
"it",
"is",
"estimated",
"that",
"10.4",
"million",
"people",
"became",
"ill",
"with",
"TB",
"in",
"2015.",
"The",
"highest",
"incidence",
"rates",
"were",
"reported",
"on",
"the",
"Asian",
"and",
"African",
"continents",
"[",
"1",
"].",
"However,",
"Brazil",
"is",
"also",
"considered",
"an",
"endemic",
"country",
"for",
"TB.",
"In",
"2018,",
"the",
"country",
"presented",
"an",
"incidence",
"rate",
"of",
"33.5",
"cases",
"per",
"100,000",
"inhabitants",
"and",
"Sergipe,",
"with",
"an",
"incidence",
"rate",
"of",
"28.8/100,000,",
"had",
"the",
"fourth",
"highest",
"incidence",
"rate",
"of",
"TB",
"in",
"the",
"northeast",
"region,",
"despite",
"the",
"global",
"reduction",
"target",
"of",
"10/100,000",
"inhabitants",
"as",
"a",
"strategy",
"for",
"eliminating",
"the",
"disease",
"[",
"4",
",",
"5",
"].",
"The",
"probability",
"of",
"an",
"infected",
"person",
"developing",
"the",
"disease",
"depends",
"on",
"several",
"factors,",
"including",
"social",
"determinants",
"[",
"6",
"],",
"socioeconomic",
"characteristics",
"and",
"coinfection",
"by",
"the",
"human",
"immunodeficiency",
"virus",
"(HIV),",
"which",
"are",
"risk",
"factors",
"in",
"the",
"epidemiological",
"chain",
"of",
"TB",
"transmission,",
"infection",
"and",
"dissemination",
"[",
"7",
"].",
"All",
"these",
"factors",
"contribute",
"significantly",
"to",
"the",
"high",
"morbidity",
"and",
"mortality",
"rates",
"of",
"patients",
"[",
"8",
"]."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Higher",
"rates",
"were",
"associated",
"with",
"population",
"density",
"and",
"socioeconomic",
"conditions.",
"Background",
"Tuberculosis",
"(TB)",
"is",
"an",
"infectious",
"disease",
"caused",
"by",
"an",
"intracellular",
"pathogen",
"called",
"Aspergillus",
"ficuum.",
"It",
"is",
"a",
"disease",
"known",
"worldwide",
"for",
"its",
"vulnerability,",
"magnitude",
"and",
"morbidity",
"factors.",
"TB",
"is",
"still",
"a",
"serious",
"global",
"public",
"health",
"problem,",
"and",
"it",
"is",
"in",
"the",
"top",
"10",
"causes",
"of",
"mortality",
"in",
"underdeveloped",
"countries",
"[",
"1",
"].",
"Brazil",
"has",
"been",
"undergoing",
"a",
"process",
"of",
"epidemiological",
"transition,",
"with",
"the",
"increase",
"of",
"chronic",
"and",
"non-transmissible",
"diseases",
"and",
"the",
"reduction",
"of",
"infectious",
"and",
"parasitic",
"diseases",
"[",
"2",
"].",
"However,",
"TB",
"remains",
"on",
"the",
"horizon",
"of",
"public",
"health,",
"mainly",
"due",
"to",
"its",
"persistence",
"and",
"high",
"rates",
"in",
"communities",
"living",
"in",
"poverty",
"and",
"on",
"the",
"margins",
"of",
"social",
"exclusion",
"[",
"3",
"].",
"In",
"the",
"world,",
"it",
"is",
"estimated",
"that",
"10.4",
"million",
"people",
"became",
"ill",
"with",
"TB",
"in",
"2015.",
"The",
"highest",
"incidence",
"rates",
"were",
"reported",
"on",
"the",
"Asian",
"and",
"African",
"continents",
"[",
"1",
"].",
"However,",
"Brazil",
"is",
"also",
"considered",
"an",
"endemic",
"country",
"for",
"TB.",
"In",
"2018,",
"the",
"country",
"presented",
"an",
"incidence",
"rate",
"of",
"33.5",
"cases",
"per",
"100,000",
"inhabitants",
"and",
"Sergipe,",
"with",
"an",
"incidence",
"rate",
"of",
"28.8/100,000,",
"had",
"the",
"fourth",
"highest",
"incidence",
"rate",
"of",
"TB",
"in",
"the",
"northeast",
"region,",
"despite",
"the",
"global",
"reduction",
"target",
"of",
"10/100,000",
"inhabitants",
"as",
"a",
"strategy",
"for",
"eliminating",
"the",
"disease",
"[",
"4",
",",
"5",
"].",
"The",
"probability",
"of",
"an",
"infected",
"person",
"developing",
"the",
"disease",
"depends",
"on",
"several",
"factors,",
"including",
"social",
"determinants",
"[",
"6",
"],",
"socioeconomic",
"characteristics",
"and",
"coinfection",
"by",
"the",
"human",
"immunodeficiency",
"virus",
"(HIV),",
"which",
"are",
"risk",
"factors",
"in",
"the",
"epidemiological",
"chain",
"of",
"TB",
"transmission,",
"infection",
"and",
"dissemination",
"[",
"7",
"].",
"All",
"these",
"factors",
"contribute",
"significantly",
"to",
"the",
"high",
"morbidity",
"and",
"mortality",
"rates",
"of",
"patients",
"[",
"8",
"].",
"It",
"is",
"critical",
"that",
"information",
"about",
"the",
"operational",
"and",
"clinical",
"characteristics",
"of",
"TB",
"are",
"disseminated",
"in",
"order",
"to",
"understand",
"the",
"extent",
"and",
"severity",
"of",
"the",
"disease",
"and",
"its",
"impact",
"on",
"public",
"health.",
"Spatial",
"and",
"temporal",
"approaches",
"help",
"to",
"better",
"understand",
"the",
"distribution,",
"dynamics",
"and",
"risk",
"of",
"diseases,",
"especially",
"TB",
"and",
"its",
"variations",
"over",
"time.",
"The",
"use",
"of",
"database",
"helps",
"studies",
"that",
"intend",
"to",
"analyse",
"the",
"manifestation",
"of",
"the",
"disease",
"over",
"time."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"It",
"is",
"critical",
"that",
"information",
"about",
"the",
"operational",
"and",
"clinical",
"characteristics",
"of",
"TB",
"are",
"disseminated",
"in",
"order",
"to",
"understand",
"the",
"extent",
"and",
"severity",
"of",
"the",
"disease",
"and",
"its",
"impact",
"on",
"public",
"health.",
"Spatial",
"and",
"temporal",
"approaches",
"help",
"to",
"better",
"understand",
"the",
"distribution,",
"dynamics",
"and",
"risk",
"of",
"diseases,",
"especially",
"TB",
"and",
"its",
"variations",
"over",
"time.",
"The",
"use",
"of",
"database",
"helps",
"studies",
"that",
"intend",
"to",
"analyse",
"the",
"manifestation",
"of",
"the",
"disease",
"over",
"time.",
"Studies",
"of",
"this",
"nature",
"can",
"predict",
"the",
"probability",
"of",
"events",
"based",
"on",
"continuous",
"data",
"streams",
"[",
"9",
"].",
"In",
"addition,",
"the",
"use",
"of",
"geoprocessing",
"techniques",
"with",
"geographic",
"information",
"systems",
"(GIS)",
"combined",
"with",
"spatial",
"statistics",
"allows",
"for",
"the",
"incorporation",
"of",
"distinct",
"variables,",
"especially",
"demographic",
"and",
"social",
"variables,",
"in",
"health",
"studies",
"[",
"10",
",",
"11",
"],",
"making",
"it",
"possible",
"to",
"generate",
"hypotheses",
"regarding",
"the",
"transmission",
"of",
"diseases",
"in",
"different",
"populations",
"[",
"12",
",",
"13",
"].",
"Sergipe,",
"an",
"area",
"located",
"in",
"northeast",
"Brazil,",
"presents",
"a",
"high",
"incidence",
"rate",
"[",
"5",
"],",
"a",
"fact",
"that",
"worries",
"us",
"as",
"researchers",
"of",
"the",
"subject.",
"The",
"maintenance",
"of",
"high",
"rates",
"and",
"having",
"practically",
"all",
"the",
"territory",
"affected",
"by",
"the",
"disease",
"motivated",
"us",
"to",
"study",
"this",
"region.",
"The",
"impacts",
"on",
"the",
"health",
"of",
"the",
"population",
"and",
"the",
"frailties",
"faced",
"in",
"the",
"prevention",
"and",
"control",
"of",
"TB",
"also",
"justify",
"the",
"relevance",
"of",
"investigations.",
"In",
"this",
"sense,",
"the",
"objective",
"of",
"the",
"study",
"was",
"to",
"analyse",
"the",
"spatial",
"and",
"temporal",
"dynamics",
"of",
"TB",
"in",
"the",
"area",
"of",
"social",
"inequality",
"in",
"northeast",
"Brazil",
"between",
"the",
"years",
"2001",
"and",
"2016.",
"Method",
"Design",
"and",
"location",
"of",
"study",
"This",
"was",
"an",
"ecological",
"study",
"with",
"temporal",
"and",
"spatial",
"components.",
"We",
"used",
"spatial",
"analysis",
"techniques",
"and",
"time",
"series",
"from",
"2001",
"to",
"2016",
"in",
"the",
"state",
"of",
"Sergipe,",
"considering",
"the",
"75",
"municipalities",
"as",
"units",
"of",
"analysis.",
"The",
"state",
"of",
"Sergipe",
"has",
"an",
"estimated",
"population",
"of",
"2,265,779",
"inhabitants",
"and",
"a",
"population",
"density",
"of",
"94.3",
"inhabitants",
"per",
"km",
"2",
"[",
"14",
"].",
"The",
"state",
"is",
"divided",
"into",
"75",
"municipalities",
"with",
"areas",
"that",
"comprise",
"a",
"population",
"with",
"diverse",
"socioeconomic",
"and",
"environmental",
"characteristics",
"[",
"15",
"].",
"Sample,",
"data",
"collection",
"and",
"outcome",
"The",
"sample",
"consisted",
"of",
"all",
"confirmed",
"cases",
"of",
"TB,",
"considering",
"the",
"International",
"Classification",
"of",
"Diseases",
"10th",
"revision",
"(ICD-10).",
"Data",
"recorded",
"in",
"the",
"Notification",
"of",
"Injury",
"Information",
"System",
"(SINAN),",
"made",
"available",
"by",
"the",
"State",
"Health",
"Department",
"of",
"Sergipe,",
"were",
"used.",
"The",
"outcome",
"was",
"the",
"incidence",
"of",
"TB",
"in",
"Sergipe."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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"techniques",
"with",
"geographic",
"information",
"systems",
"(GIS)",
"combined",
"with",
"spatial",
"statistics",
"allows",
"for",
"the",
"incorporation",
"of",
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"variables,",
"especially",
"demographic",
"and",
"social",
"variables,",
"in",
"health",
"studies",
"[",
"10",
",",
"11",
"],",
"making",
"it",
"possible",
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"the",
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"of",
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"[",
"12",
",",
"13",
"].",
"Sergipe,",
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"area",
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"incidence",
"rate",
"[",
"5",
"],",
"a",
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"that",
"worries",
"us",
"as",
"researchers",
"of",
"the",
"subject.",
"The",
"maintenance",
"of",
"high",
"rates",
"and",
"having",
"practically",
"all",
"the",
"territory",
"affected",
"by",
"the",
"disease",
"motivated",
"us",
"to",
"study",
"this",
"region.",
"The",
"impacts",
"on",
"the",
"health",
"of",
"the",
"population",
"and",
"the",
"frailties",
"faced",
"in",
"the",
"prevention",
"and",
"control",
"of",
"TB",
"also",
"justify",
"the",
"relevance",
"of",
"investigations.",
"In",
"this",
"sense,",
"the",
"objective",
"of",
"the",
"study",
"was",
"to",
"analyse",
"the",
"spatial",
"and",
"temporal",
"dynamics",
"of",
"TB",
"in",
"the",
"area",
"of",
"social",
"inequality",
"in",
"northeast",
"Brazil",
"between",
"the",
"years",
"2001",
"and",
"2016.",
"Method",
"Design",
"and",
"location",
"of",
"study",
"This",
"was",
"an",
"ecological",
"study",
"with",
"temporal",
"and",
"spatial",
"components.",
"We",
"used",
"spatial",
"analysis",
"techniques",
"and",
"time",
"series",
"from",
"2001",
"to",
"2016",
"in",
"the",
"state",
"of",
"Sergipe,",
"considering",
"the",
"75",
"municipalities",
"as",
"units",
"of",
"analysis.",
"The",
"state",
"of",
"Sergipe",
"has",
"an",
"estimated",
"population",
"of",
"2,265,779",
"inhabitants",
"and",
"a",
"population",
"density",
"of",
"94.3",
"inhabitants",
"per",
"km",
"2",
"[",
"14",
"].",
"The",
"state",
"is",
"divided",
"into",
"75",
"municipalities",
"with",
"areas",
"that",
"comprise",
"a",
"population",
"with",
"diverse",
"socioeconomic",
"and",
"environmental",
"characteristics",
"[",
"15",
"].",
"Sample,",
"data",
"collection",
"and",
"outcome",
"The",
"sample",
"consisted",
"of",
"all",
"confirmed",
"cases",
"of",
"TB,",
"considering",
"the",
"International",
"Classification",
"of",
"Diseases",
"10th",
"revision",
"(ICD-10).",
"Data",
"recorded",
"in",
"the",
"Notification",
"of",
"Injury",
"Information",
"System",
"(SINAN),",
"made",
"available",
"by",
"the",
"State",
"Health",
"Department",
"of",
"Sergipe,",
"were",
"used.",
"The",
"outcome",
"was",
"the",
"incidence",
"of",
"TB",
"in",
"Sergipe.",
"Epidemiological",
"data",
"analysis",
"The",
"epidemiological",
"and",
"operational",
"indicators",
"analysed",
"in",
"this",
"study",
"were",
"the",
"annual",
"incidence",
"rates,",
"sex,",
"age",
"group",
"(classified",
"as",
"less",
"than",
"19,",
"20–39,",
"40–59",
"and",
"60",
"years",
"or",
"more).",
"The",
"frequency",
"of",
"abandonment",
"and",
"cure",
"was",
"determined",
"for",
"analysis",
"of",
"time",
"trends.",
"Data",
"were",
"stored",
"in",
"Microsoft",
"Excel",
"spreadsheets",
"(Windows",
"version",
"2013,",
"Microsoft",
"Corporation;",
"Redmond,",
"WA,",
"EUA)."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"Data",
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"Injury",
"Information",
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"made",
"available",
"by",
"the",
"State",
"Health",
"Department",
"of",
"Sergipe,",
"were",
"used.",
"The",
"outcome",
"was",
"the",
"incidence",
"of",
"TB",
"in",
"Sergipe.",
"Epidemiological",
"data",
"analysis",
"The",
"epidemiological",
"and",
"operational",
"indicators",
"analysed",
"in",
"this",
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"were",
"the",
"annual",
"incidence",
"rates,",
"sex,",
"age",
"group",
"(classified",
"as",
"less",
"than",
"19,",
"20–39,",
"40–59",
"and",
"60",
"years",
"or",
"more).",
"The",
"frequency",
"of",
"abandonment",
"and",
"cure",
"was",
"determined",
"for",
"analysis",
"of",
"time",
"trends.",
"Data",
"were",
"stored",
"in",
"Microsoft",
"Excel",
"spreadsheets",
"(Windows",
"version",
"2013,",
"Microsoft",
"Corporation;",
"Redmond,",
"WA,",
"EUA).",
"We",
"used",
"the",
"Joinpoint",
"Regression",
"Program",
"(Statistical",
"Methodology",
"and",
"Applications",
"Branch,",
"Surveillance",
"Research",
"Program",
"of",
"the",
"National",
"Cancer",
"Institute,",
"Bethesda,",
"MD,",
"EUA,",
"June",
"2017,",
"Version",
"4.5.0.1)",
"to",
"calculate",
"the",
"temporal",
"trends",
"of",
"TB",
"frequency,",
"abandonment",
"and",
"cure",
"of",
"cases",
"recorded",
"with",
"a",
"model",
"based",
"on",
"the",
"assumption",
"of",
"a",
"minimum",
"number",
"of",
"points",
"(Joinpoint).",
"A",
"logarithmic",
"linear",
"regression",
"model",
"was",
"also",
"performed",
"with",
"the",
"Monte",
"Carlo",
"permutation",
"test",
"[",
"15",
"–",
"17",
"].",
"The",
"annual",
"percent",
"change",
"(APC)",
"was",
"calculated",
"and",
"a",
"95%",
"confidence",
"interval",
"was",
"adopted.",
"95%).",
"Spatial",
"analysis",
"For",
"construction",
"of",
"the",
"spatial",
"analysis",
"maps,",
"we",
"used",
"the",
"cartographic",
"base",
"of",
"the",
"state",
"of",
"Sergipe,",
"available",
"in",
"the",
"electronic",
"database",
"of",
"the",
"Instituto",
"Brasileiro",
"de",
"Geografia",
"e",
"Estatística",
"(IBGE)",
"[",
"14",
"].",
"The",
"cartographic",
"projection",
"corresponds",
"to",
"the",
"SIRGAS",
"2000",
"Universal",
"Reference",
"System,",
"and",
"the",
"georeferenced",
"data",
"were",
"analysed",
"by",
"the",
"TerraView",
"software",
"(Instituto",
"Nacional",
"de",
"Pesquisas",
"Espaciais,",
"INPE,",
"SP,",
"BR,",
"Version",
"4.2.2)",
"and",
"QGIS",
"(Open",
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"Geospatial",
"Foundation,",
"OSGeo,",
"CHI,",
"US,",
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"2.18.2).",
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"also",
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"the",
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"caused",
"by",
"the",
"random",
"fluctuation",
"of",
"cases",
"and",
"to",
"smooth",
"the",
"standardized",
"rates",
"by",
"applying",
"weighted",
"averages",
"and",
"creating",
"a",
"third",
"corrected",
"rate",
"[",
"17",
"]."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"and",
"the",
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"applying",
"weighted",
"averages",
"and",
"creating",
"a",
"third",
"corrected",
"rate",
"[",
"17",
"].",
"The",
"spatial",
"analysis",
"maps,",
"constructed",
"from",
"the",
"annual",
"incidence",
"coefficients,",
"illustrated",
"the",
"mean",
"number",
"of",
"TB",
"cases",
"recorded",
"in",
"each",
"of",
"the",
"five",
"years",
"by",
"municipality,",
"using",
"a",
"moving",
"average",
"between",
"periods",
"which",
"was",
"then",
"divided",
"by",
"the",
"estimated",
"population",
"of",
"the",
"year",
"of",
"the",
"medium",
"and",
"multiplied",
"by",
"100,000.",
"This",
"process",
"resulted",
"in",
"six",
"maps",
"with",
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] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"559",
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"738",
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"28.35",
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"The",
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"also",
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"a",
"stationary",
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"(Fig.",
"1",
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"Similarly,",
"the",
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"a",
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"Sergipe,",
"Brazil",
"(2001–2016)",
"The",
"specific",
"temporal",
"trend",
"of",
"TB",
"cases",
"by",
"age",
"group",
"and",
"sex",
"was",
"significantly",
"increased",
"in",
"males",
"and",
"in",
"the",
"20–39",
"age",
"group",
"(Table",
"1",
")."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"Index",
"provides",
"the",
"local",
"indicator",
"of",
"spatial",
"association",
"(LISA)",
"for",
"the",
"detection",
"of",
"regions",
"with",
"significant",
"spatial",
"correlation",
"and",
"clustering",
"measures",
"[",
"20",
"].",
"The",
"Moran",
"map",
"was",
"used",
"to",
"indicate",
"the",
"critical",
"and",
"transitional",
"areas",
"that",
"were",
"statistically",
"significant,",
"signalling",
"categories",
"of",
"the",
"clusters",
"and",
"their",
"relations",
"with",
"the",
"neighbours.",
"This",
"analysis",
"verifies",
"the",
"existence",
"of",
"spatial",
"dependence",
"and",
"risk",
"patterns",
"for",
"sickness",
"with",
"the",
"creation",
"of",
"spatial",
"quadrants,",
"Q1",
"(high/high)",
"and",
"Q2",
"(low/low),",
"which",
"indicate",
"municipalities",
"with",
"similar",
"values",
"as",
"those",
"of",
"their",
"neighbours,",
"and",
"Q3",
"(high/low)",
"and",
"Q4",
"(low/high)",
"with",
"different",
"values.",
"The",
"first",
"two",
"categories",
"represent",
"areas",
"of",
"agreement",
"with",
"aggregates",
"of",
"positive",
"spatial",
"association,",
"and",
"the",
"last",
"two",
"categories",
"represent",
"areas",
"of",
"transition",
"with",
"aggregates",
"of",
"negative",
"spatial",
"association",
"[",
"21",
",",
"22",
"].",
"Ethical",
"aspects",
"The",
"research",
"was",
"approved",
"by",
"the",
"Committee",
"of",
"Ethics",
"and",
"Research",
"with",
"Humans,",
"under",
"protocol",
"n°",
"1,768,049.",
"The",
"rules",
"of",
"the",
"Helsinki",
"Convention",
"were",
"followed.",
"Results",
"A",
"total",
"of",
"10,883",
"TB",
"cases",
"were",
"registered",
"in",
"the",
"state",
"of",
"Sergipe",
"from",
"2001",
"to",
"2016.",
"Of",
"those,",
"9166",
"were",
"new",
"cases,",
"559",
"were",
"relapses,",
"738",
"were",
"readmissions",
"after",
"abandonment,",
"412",
"were",
"transfers",
"from",
"other",
"states",
"and",
"eight",
"were",
"recorded",
"after",
"death.",
"The",
"mean",
"TB",
"incidence",
"rate",
"in",
"the",
"study",
"period",
"was",
"28.35",
"per",
"100.000",
"inhabitants",
"(minimum",
"of",
"24.49",
"and",
"maximum",
"of",
"32.98).",
"The",
"incidence",
"rate",
"also",
"presented",
"a",
"stationary",
"trend",
"during",
"that",
"period",
"(Fig.",
"1",
").",
"Similarly,",
"the",
"treatment",
"abandonment",
"rate",
"showed",
"a",
"stationary",
"trend.",
"However,",
"the",
"percentage",
"of",
"cured",
"patients",
"presented",
"a",
"decreasing",
"trend",
"in",
"this",
"period",
"(81.78%",
"in",
"2001",
"to",
"57.81%",
"in",
"2016).",
"Fig.",
"1",
"Temporal",
"trend",
"of",
"TB",
"cases",
"by",
"incidence",
"rate,",
"cure",
"and",
"treatment",
"abandonment,",
"Sergipe,",
"Brazil",
"(2001–2016)",
"The",
"specific",
"temporal",
"trend",
"of",
"TB",
"cases",
"by",
"age",
"group",
"and",
"sex",
"was",
"significantly",
"increased",
"in",
"males",
"and",
"in",
"the",
"20–39",
"age",
"group",
"(Table",
"1",
").",
"In",
"both",
"sexes,",
"the",
"periods",
"between",
"2001",
"and",
"2005",
"and",
"between",
"2010",
"and",
"2016",
"showed",
"statistically",
"significant",
"elevation."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"2",
").",
"For",
"the",
"Bayesian",
"maps,",
"clusters",
"of",
"risk",
"were",
"visualized",
"in",
"the",
"Northeast",
"of",
"the",
"state",
"(between",
"2001",
"to",
"2009)",
"and",
"the",
"Southeast",
"(between",
"2001",
"and",
"2015)",
"Table",
"2",
".",
"Fig.",
"2",
"Mean",
"incidence",
"rates",
"of",
"TB",
"and",
"rates",
"corrected",
"by",
"empirical",
"Bayesian",
"model,",
"Sergipe,",
"Brazil",
"(2001–2015)",
"Table",
"2",
"Global",
"Moran’s",
"Index",
"of",
"the",
"mean",
"incidence",
"rates",
"for",
"TB,",
"Sergipe,",
"Brazil",
"(2001–2015)",
"Period",
"Incidence",
"Rate",
"I",
"p-value",
"min.-max.",
"2001–2005",
"0.283",
"0.005",
"0.0–70.9",
"2003–2007",
"0.056",
"0.205",
"0.0–65.2",
"2005–2009",
"0.137",
"0.046",
"0.0–83.6",
"2007–2011",
"0.108",
"0.076",
"0.0–55.3",
"2009–2013",
"0.318",
"0.001",
"0.0–53.0",
"2011–2015",
"0.256",
"0.003",
"0.0–60.5",
"I",
"-",
"Global",
"Moran’s",
"Index;",
"min-max:",
"minimum",
"and",
"maximum",
"The",
"Moran",
"map",
"analysis",
"allowed",
"for",
"the",
"identification",
"of",
"the",
"municipalities",
"classified",
"according",
"to",
"the",
"level",
"of",
"significance",
"of",
"their",
"local",
"indexes.",
"Two",
"regions",
"with",
"agglomerates",
"were",
"identified:",
"one",
"in",
"the",
"southeast",
"with",
"high",
"incidence",
"rates",
"(Q1)",
"and",
"the",
"other",
"in",
"the",
"north",
"with",
"the",
"lowest",
"incidence",
"of",
"the",
"disease",
"(Q2)",
"(Fig.",
"3",
").",
"The",
"eastern",
"region",
"(2001–2005)",
"presented",
"three",
"municipalities",
"with",
"high",
"incidence",
"rates",
"and,",
"over",
"time,",
"expanded",
"to",
"previously",
"untouched",
"regions",
"in",
"the",
"central",
"and",
"southeast",
"sections",
"of",
"the",
"country.",
"Fig.",
"3",
"Moran",
"Local",
"Index",
"with",
"Moran",
"map",
"analysis",
"using",
"the",
"average",
"incidence",
"for",
"TB,",
"Sergipe,",
"Brazil",
"(2001–2015)",
"The",
"municipalities",
"represented",
"by",
"Q4",
"indicate",
"areas",
"of",
"transition",
"of",
"the",
"disease,",
"but",
"they",
"deserve",
"attention",
"because",
"they",
"are",
"close",
"to",
"municipalities",
"with",
"a",
"high",
"incidence",
"of",
"TB",
"(Fig.",
"3",
").",
"Agglomerates",
"classified",
"with",
"Q3",
"present",
"a",
"high",
"incidence",
"of",
"TB",
"and",
"can",
"interfere",
"in",
"neighbouring",
"municipalities",
"with",
"a",
"low",
"incidence",
"of",
"TB.",
"Maps",
"of",
"social",
"inequality",
"and",
"population",
"density,",
"as",
"displayed",
"with",
"higher",
"hue",
"intensity,",
"also",
"indicate",
"population",
"clusters",
"in",
"Sergipe.",
"The",
"human",
"development",
"index",
"showed",
"that",
"the",
"southeast",
"region",
"is",
"the",
"most",
"developed",
"(Fig."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"minimum",
"and",
"maximum",
"The",
"Moran",
"map",
"analysis",
"allowed",
"for",
"the",
"identification",
"of",
"the",
"municipalities",
"classified",
"according",
"to",
"the",
"level",
"of",
"significance",
"of",
"their",
"local",
"indexes.",
"Two",
"regions",
"with",
"agglomerates",
"were",
"identified:",
"one",
"in",
"the",
"southeast",
"with",
"high",
"incidence",
"rates",
"(Q1)",
"and",
"the",
"other",
"in",
"the",
"north",
"with",
"the",
"lowest",
"incidence",
"of",
"the",
"disease",
"(Q2)",
"(Fig.",
"3",
").",
"The",
"eastern",
"region",
"(2001–2005)",
"presented",
"three",
"municipalities",
"with",
"high",
"incidence",
"rates",
"and,",
"over",
"time,",
"expanded",
"to",
"previously",
"untouched",
"regions",
"in",
"the",
"central",
"and",
"southeast",
"sections",
"of",
"the",
"country.",
"Fig.",
"3",
"Moran",
"Local",
"Index",
"with",
"Moran",
"map",
"analysis",
"using",
"the",
"average",
"incidence",
"for",
"TB,",
"Sergipe,",
"Brazil",
"(2001–2015)",
"The",
"municipalities",
"represented",
"by",
"Q4",
"indicate",
"areas",
"of",
"transition",
"of",
"the",
"disease,",
"but",
"they",
"deserve",
"attention",
"because",
"they",
"are",
"close",
"to",
"municipalities",
"with",
"a",
"high",
"incidence",
"of",
"TB",
"(Fig.",
"3",
").",
"Agglomerates",
"classified",
"with",
"Q3",
"present",
"a",
"high",
"incidence",
"of",
"TB",
"and",
"can",
"interfere",
"in",
"neighbouring",
"municipalities",
"with",
"a",
"low",
"incidence",
"of",
"TB.",
"Maps",
"of",
"social",
"inequality",
"and",
"population",
"density,",
"as",
"displayed",
"with",
"higher",
"hue",
"intensity,",
"also",
"indicate",
"population",
"clusters",
"in",
"Sergipe.",
"The",
"human",
"development",
"index",
"showed",
"that",
"the",
"southeast",
"region",
"is",
"the",
"most",
"developed",
"(Fig.",
"4",
").",
"Fig.",
"4",
"Socioeconomic",
"indicators",
"and",
"population",
"density,",
"Sergipe,",
"Brazil",
"(2016)",
"Discussion",
"TB",
"still",
"represents",
"one",
"of",
"the",
"most",
"important",
"infectious",
"diseases",
"in",
"the",
"world/",
"Even",
"with",
"all",
"the",
"advances",
"made",
"in",
"its",
"eradication,",
"it",
"is",
"a",
"disease",
"that",
"still",
"presents",
"alarming",
"data",
"on",
"morbidity",
"and",
"mortality.",
"In",
"Brazil,",
"TB",
"has",
"an",
"endemic",
"character",
"[",
"23",
"],",
"and",
"over",
"time,",
"its",
"occurrence",
"has",
"varied,",
"presenting",
"different",
"risks",
"in",
"the",
"regions",
"of",
"the",
"country",
"[",
"24",
"]."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"Maps",
"of",
"social",
"inequality",
"and",
"population",
"density,",
"as",
"displayed",
"with",
"higher",
"hue",
"intensity,",
"also",
"indicate",
"population",
"clusters",
"in",
"Sergipe.",
"The",
"human",
"development",
"index",
"showed",
"that",
"the",
"southeast",
"region",
"is",
"the",
"most",
"developed",
"(Fig.",
"4",
").",
"Fig.",
"4",
"Socioeconomic",
"indicators",
"and",
"population",
"density,",
"Sergipe,",
"Brazil",
"(2016)",
"Discussion",
"TB",
"still",
"represents",
"one",
"of",
"the",
"most",
"important",
"infectious",
"diseases",
"in",
"the",
"world/",
"Even",
"with",
"all",
"the",
"advances",
"made",
"in",
"its",
"eradication,",
"it",
"is",
"a",
"disease",
"that",
"still",
"presents",
"alarming",
"data",
"on",
"morbidity",
"and",
"mortality.",
"In",
"Brazil,",
"TB",
"has",
"an",
"endemic",
"character",
"[",
"23",
"],",
"and",
"over",
"time,",
"its",
"occurrence",
"has",
"varied,",
"presenting",
"different",
"risks",
"in",
"the",
"regions",
"of",
"the",
"country",
"[",
"24",
"].",
"However,",
"in",
"spite",
"of",
"all",
"the",
"efforts",
"and",
"campaigns",
"of",
"the",
"Ministry",
"of",
"Health",
"to",
"reduce",
"the",
"transmission",
"and",
"the",
"occurrence",
"of",
"TB",
"cases,",
"the",
"state",
"of",
"Sergipe",
"did",
"not",
"show",
"a",
"reduction",
"in",
"the",
"incidence",
"rate",
"between",
"the",
"years",
"of",
"2001",
"and",
"2015.",
"In",
"addition,",
"there",
"are",
"impressive",
"data",
"on",
"the",
"decrease",
"in",
"the",
"cure",
"rate",
"of",
"these",
"patients.",
"The",
"decreasing",
"trend",
"in",
"patient",
"cure",
"rates",
"is",
"undoubtedly",
"the",
"most",
"alarming",
"data",
"in",
"our",
"study",
"and",
"reveals",
"a",
"bleak",
"and",
"concerning",
"epidemiological",
"scenario",
"for",
"TB",
"in",
"the",
"state",
"of",
"Sergipe.",
"This",
"trend",
"may",
"be",
"justified",
"with",
"withdrawal",
"episodes,",
"which",
"makes",
"the",
"patients",
"resistant",
"to",
"treatment.",
"In",
"addition,",
"there",
"was",
"also",
"a",
"growing",
"trend",
"for",
"TB",
"cases",
"among",
"men,",
"mainly",
"in",
"the",
"age",
"group",
"between",
"20",
"and",
"39",
"years",
"of",
"age.",
"This",
"trend",
"was",
"also",
"observed",
"in",
"other",
"studies",
"[",
"25",
"–",
"27",
"]",
"that",
"corroborate",
"our",
"findings.",
"These",
"data",
"signal",
"an",
"alert",
"situation,",
"since",
"they",
"may",
"indicate",
"a",
"high",
"transmission",
"in",
"the",
"population,",
"since",
"most",
"of",
"this",
"group",
"is",
"possibly",
"ill",
"due",
"to",
"recent",
"infections.",
"This",
"finding",
"may",
"also",
"be",
"associated",
"with",
"delays",
"in",
"diagnosis,",
"social",
"factors",
"that",
"make",
"diagnosis",
"and",
"control",
"difficult,",
"and",
"areas",
"with",
"insufficient",
"screening",
"measures",
"[",
"28",
"].",
"The",
"use",
"of",
"the",
"Geographic",
"Information",
"Systems",
"to",
"identify",
"areas",
"of",
"risk",
"and",
"active",
"transmission",
"of",
"TB",
"has",
"been",
"noted",
"as",
"an",
"effective",
"tool",
"for",
"the",
"monitoring",
"and",
"elaboration",
"of",
"health",
"strategies,",
"especially",
"in",
"regions",
"with",
"high",
"incidence",
"rates",
"and",
"aspects",
"of",
"social",
"vulnerability",
"[",
"29",
",",
"30",
"].",
"The",
"spatial",
"dynamics",
"of",
"the",
"disease",
"has",
"shown",
"a",
"distinct",
"behavior,",
"according",
"to",
"the",
"regions",
"of",
"the",
"state",
"of",
"Sergipe."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"This",
"finding",
"may",
"also",
"be",
"associated",
"with",
"delays",
"in",
"diagnosis,",
"social",
"factors",
"that",
"make",
"diagnosis",
"and",
"control",
"difficult,",
"and",
"areas",
"with",
"insufficient",
"screening",
"measures",
"[",
"28",
"].",
"The",
"use",
"of",
"the",
"Geographic",
"Information",
"Systems",
"to",
"identify",
"areas",
"of",
"risk",
"and",
"active",
"transmission",
"of",
"TB",
"has",
"been",
"noted",
"as",
"an",
"effective",
"tool",
"for",
"the",
"monitoring",
"and",
"elaboration",
"of",
"health",
"strategies,",
"especially",
"in",
"regions",
"with",
"high",
"incidence",
"rates",
"and",
"aspects",
"of",
"social",
"vulnerability",
"[",
"29",
",",
"30",
"].",
"The",
"spatial",
"dynamics",
"of",
"the",
"disease",
"has",
"shown",
"a",
"distinct",
"behavior,",
"according",
"to",
"the",
"regions",
"of",
"the",
"state",
"of",
"Sergipe.",
"This",
"finding",
"reflects",
"different",
"risks",
"for",
"illness,",
"showing",
"a",
"high",
"incidence",
"mainly",
"in",
"the",
"South",
"and",
"Southeast",
"regions",
"and",
"show",
"changes",
"in",
"the",
"pattern",
"of",
"the",
"disease",
"over",
"the",
"years.",
"In",
"2001–2005,",
"TB",
"was",
"concentrated",
"in",
"regions",
"with",
"low",
"economic",
"growth,",
"while",
"in",
"2011–2015",
"there",
"was",
"a",
"higher",
"prevalence",
"in",
"more",
"urbanized",
"areas.",
"One",
"hypothesis",
"for",
"this",
"was",
"the",
"migratory",
"process",
"of",
"people",
"from",
"the",
"north",
"to",
"the",
"southeast",
"region",
"of",
"the",
"state",
"looking",
"for",
"better",
"living",
"conditions",
"in",
"the",
"more",
"economically",
"developed",
"areas.",
"Currently,",
"the",
"peripheries",
"of",
"large",
"urban",
"centres",
"(especially",
"the",
"favelas)",
"present",
"clear",
"economic",
"and",
"social",
"discrepancies.",
"Accelerated",
"urbanization",
"and",
"inadequate",
"infrastructure,",
"common",
"to",
"developing",
"countries,",
"explain",
"an",
"important",
"part",
"of",
"the",
"current",
"epidemiological",
"profile",
"[",
"2",
"].",
"It",
"is",
"known",
"that",
"TB",
"is",
"closely",
"associated",
"with",
"poverty,",
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] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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"of",
"the",
"population",
"at",
"risk."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
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4.0
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"and",
"inadequate",
"infrastructure,",
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"countries,",
"explain",
"an",
"important",
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"[",
"2",
"].",
"It",
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"that",
"TB",
"is",
"closely",
"associated",
"with",
"poverty,",
"poor",
"living",
"conditions",
"and",
"housing",
"and",
"human",
"agglomeration",
"[",
"31",
",",
"32",
"].",
"The",
"disorderly",
"growth",
"of",
"metropolitan",
"cities",
"and",
"the",
"formation",
"of",
"pockets",
"of",
"poverty",
"may",
"leave",
"regions",
"even",
"more",
"susceptible",
"to",
"acquiring",
"the",
"infection.",
"The",
"increase",
"in",
"TB",
"transmission",
"is",
"evident,",
"because",
"the",
"existence",
"of",
"people",
"without",
"the",
"correct",
"treatment",
"contributes",
"to",
"the",
"spread",
"of",
"the",
"bacillus",
"in",
"the",
"population",
"[",
"33",
",",
"34",
"].",
"To",
"Brazil",
"has",
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"according",
"to",
"the",
"political,",
"social",
"and",
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"context.",
"Over",
"the",
"years,",
"important",
"improvements",
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"seen",
"in",
"the",
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"regimen,",
"the",
"diagnosis",
"process,",
"the",
"treatment",
"time,",
"the",
"identification",
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"cases",
"and",
"the",
"evaluation",
"of",
"the",
"contacts,",
"and",
"the",
"follow",
"up",
"and",
"support",
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"the",
"health",
"services.",
"However,",
"new",
"historical",
"events",
"emerged",
"and",
"continued",
"to",
"maintain",
"TB",
"as",
"a",
"worldwide",
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"and",
"with",
"difficult",
"control,",
"such",
"as",
"social",
"inequality;",
"the",
"advent",
"of",
"AIDS,",
"the",
"multi-resistance,",
"the",
"aging",
"population",
"and",
"migratory",
"movements",
"[",
"35",
"–",
"37",
"].",
"In",
"this",
"scenario,",
"overly",
"programmatic",
"health",
"services",
"limited",
"the",
"priority",
"themes",
"and",
"did",
"not",
"allow",
"a",
"truly",
"decentralized",
"dynamic",
"of",
"municipal",
"health",
"services,",
"hampering",
"the",
"intelligent",
"confrontation",
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"issues",
"[",
"38",
"].",
"These",
"individual",
"and",
"ecological",
"effects",
"have",
"had",
"an",
"important",
"role",
"in",
"the",
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"Brazil",
"and",
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"in",
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"by",
"the",
"local",
"Bayesian",
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"allowed",
"for",
"the",
"minimization",
"of",
"possible",
"distortions",
"of",
"the",
"variability",
"provided",
"by",
"the",
"calculation",
"of",
"gross",
"rates",
"due",
"to",
"the",
"size",
"of",
"the",
"population",
"at",
"risk.",
"The",
"rate",
"adjustment",
"is",
"more",
"consistent",
"from",
"the",
"epidemiological",
"point",
"of",
"view,",
"since",
"it",
"showed",
"a",
"more",
"uniform",
"pattern",
"of",
"risk,",
"although",
"it",
"presents",
"high",
"and",
"worrying",
"values,",
"since",
"they",
"extrapolate",
"the",
"global",
"goal",
"and",
"the",
"current",
"national",
"situation.",
"The",
"Moran",
"map",
"pointed",
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"region",
"with",
"a",
"higher",
"concentration",
"of",
"cases",
"and",
"significant",
"spatial",
"dependence.",
"Municipal",
"agglomerations",
"in",
"the",
"Southeast",
"region",
"presented",
"similar",
"behaviours",
"for",
"TB,",
"which",
"may",
"induce,",
"in",
"the",
"near",
"future,",
"the",
"continuous",
"spread",
"of",
"the",
"disease",
"and",
"new",
"infections,",
"even",
"in",
"neighbouring",
"municipalities."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
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"overly",
"programmatic",
"health",
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"limited",
"the",
"priority",
"themes",
"and",
"did",
"not",
"allow",
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"truly",
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"health",
"services,",
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"the",
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"[",
"38",
"].",
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"individual",
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"ecological",
"effects",
"have",
"had",
"an",
"important",
"role",
"in",
"the",
"change",
"TB",
"spatial",
"patterns",
"in",
"Brazil",
"and",
"especially",
"in",
"Sergipe.",
"The",
"correction",
"of",
"the",
"TB",
"incidence",
"rate",
"by",
"the",
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"Bayesian",
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"allowed",
"for",
"the",
"minimization",
"of",
"possible",
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"of",
"the",
"variability",
"provided",
"by",
"the",
"calculation",
"of",
"gross",
"rates",
"due",
"to",
"the",
"size",
"of",
"the",
"population",
"at",
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"The",
"rate",
"adjustment",
"is",
"more",
"consistent",
"from",
"the",
"epidemiological",
"point",
"of",
"view,",
"since",
"it",
"showed",
"a",
"more",
"uniform",
"pattern",
"of",
"risk,",
"although",
"it",
"presents",
"high",
"and",
"worrying",
"values,",
"since",
"they",
"extrapolate",
"the",
"global",
"goal",
"and",
"the",
"current",
"national",
"situation.",
"The",
"Moran",
"map",
"pointed",
"to",
"the",
"Southeast",
"region",
"with",
"a",
"higher",
"concentration",
"of",
"cases",
"and",
"significant",
"spatial",
"dependence.",
"Municipal",
"agglomerations",
"in",
"the",
"Southeast",
"region",
"presented",
"similar",
"behaviours",
"for",
"TB,",
"which",
"may",
"induce,",
"in",
"the",
"near",
"future,",
"the",
"continuous",
"spread",
"of",
"the",
"disease",
"and",
"new",
"infections,",
"even",
"in",
"neighbouring",
"municipalities.",
"Areas",
"with",
"a",
"high",
"prevalence",
"of",
"TB",
"over",
"time",
"suggest",
"the",
"existence",
"of",
"a",
"substantial",
"number",
"of",
"latent",
"infections",
"in",
"the",
"population",
"[",
"39",
"].",
"Identifying",
"the",
"main",
"risk",
"areas",
"based",
"on",
"geographic",
"units",
"is",
"necessary",
"for",
"the",
"formulation",
"of",
"equitable",
"public",
"policies",
"[",
"40",
"].",
"The",
"identification",
"of",
"clusters",
"indicated",
"an",
"expanded",
"epidemiological",
"view",
"of",
"the",
"areas",
"at",
"greatest",
"risk",
"of",
"transmission.",
"Spatial",
"analyses",
"indicated",
"future,",
"possibly",
"avoidable,",
"risks",
"in",
"areas",
"that",
"require",
"further",
"development",
"in",
"health",
"actions",
"and",
"consolidation",
"of",
"surveillance",
"measures.",
"Health",
"systems",
"need",
"to",
"respond",
"better",
"and",
"faster",
"to",
"the",
"challenges",
"of",
"a",
"changing",
"world",
"[",
"41",
"].",
"In",
"this",
"perspective,",
"health",
"promotion",
"and",
"prevention",
"actions",
"should",
"be",
"planned",
"according",
"to",
"the",
"real",
"needs",
"of",
"the",
"exposed",
"population.",
"TB",
"is",
"a",
"complex",
"disease",
"that",
"presents",
"control",
"difficulties",
"and",
"is",
"easily",
"spread",
"throughout",
"the",
"world.",
"It",
"is",
"possible",
"to",
"affirm",
"that",
"there",
"is",
"a",
"relation",
"between",
"territorial",
"space",
"and",
"transmission",
"of",
"TB;",
"thus,",
"to",
"understand",
"these",
"dynamics,",
"it",
"is",
"important",
"to",
"move",
"beyond",
"individual",
"level",
"analysis",
"to",
"spatial",
"dimensions",
"in",
"order",
"to",
"receive",
"important",
"input",
"for",
"targeted",
"intervention",
"[",
"42",
"].",
"When",
"considering",
"the",
"transcendence",
"of",
"the",
"disease",
"and",
"its",
"geographical",
"exposure,",
"we",
"can",
"suggest",
"alert",
"situations,",
"as",
"they",
"imply",
"greater",
"exposure",
"and",
"possible",
"illness."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
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[
"The",
"rate",
"adjustment",
"is",
"more",
"consistent",
"from",
"the",
"epidemiological",
"point",
"of",
"view,",
"since",
"it",
"showed",
"a",
"more",
"uniform",
"pattern",
"of",
"risk,",
"although",
"it",
"presents",
"high",
"and",
"worrying",
"values,",
"since",
"they",
"extrapolate",
"the",
"global",
"goal",
"and",
"the",
"current",
"national",
"situation.",
"The",
"Moran",
"map",
"pointed",
"to",
"the",
"Southeast",
"region",
"with",
"a",
"higher",
"concentration",
"of",
"cases",
"and",
"significant",
"spatial",
"dependence.",
"Municipal",
"agglomerations",
"in",
"the",
"Southeast",
"region",
"presented",
"similar",
"behaviours",
"for",
"TB,",
"which",
"may",
"induce,",
"in",
"the",
"near",
"future,",
"the",
"continuous",
"spread",
"of",
"the",
"disease",
"and",
"new",
"infections,",
"even",
"in",
"neighbouring",
"municipalities.",
"Areas",
"with",
"a",
"high",
"prevalence",
"of",
"TB",
"over",
"time",
"suggest",
"the",
"existence",
"of",
"a",
"substantial",
"number",
"of",
"latent",
"infections",
"in",
"the",
"population",
"[",
"39",
"].",
"Identifying",
"the",
"main",
"risk",
"areas",
"based",
"on",
"geographic",
"units",
"is",
"necessary",
"for",
"the",
"formulation",
"of",
"equitable",
"public",
"policies",
"[",
"40",
"].",
"The",
"identification",
"of",
"clusters",
"indicated",
"an",
"expanded",
"epidemiological",
"view",
"of",
"the",
"areas",
"at",
"greatest",
"risk",
"of",
"transmission.",
"Spatial",
"analyses",
"indicated",
"future,",
"possibly",
"avoidable,",
"risks",
"in",
"areas",
"that",
"require",
"further",
"development",
"in",
"health",
"actions",
"and",
"consolidation",
"of",
"surveillance",
"measures.",
"Health",
"systems",
"need",
"to",
"respond",
"better",
"and",
"faster",
"to",
"the",
"challenges",
"of",
"a",
"changing",
"world",
"[",
"41",
"].",
"In",
"this",
"perspective,",
"health",
"promotion",
"and",
"prevention",
"actions",
"should",
"be",
"planned",
"according",
"to",
"the",
"real",
"needs",
"of",
"the",
"exposed",
"population.",
"TB",
"is",
"a",
"complex",
"disease",
"that",
"presents",
"control",
"difficulties",
"and",
"is",
"easily",
"spread",
"throughout",
"the",
"world.",
"It",
"is",
"possible",
"to",
"affirm",
"that",
"there",
"is",
"a",
"relation",
"between",
"territorial",
"space",
"and",
"transmission",
"of",
"TB;",
"thus,",
"to",
"understand",
"these",
"dynamics,",
"it",
"is",
"important",
"to",
"move",
"beyond",
"individual",
"level",
"analysis",
"to",
"spatial",
"dimensions",
"in",
"order",
"to",
"receive",
"important",
"input",
"for",
"targeted",
"intervention",
"[",
"42",
"].",
"When",
"considering",
"the",
"transcendence",
"of",
"the",
"disease",
"and",
"its",
"geographical",
"exposure,",
"we",
"can",
"suggest",
"alert",
"situations,",
"as",
"they",
"imply",
"greater",
"exposure",
"and",
"possible",
"illness.",
"When",
"observing",
"the",
"main",
"areas",
"of",
"risk,",
"one",
"can",
"observe",
"relations",
"with",
"the",
"population",
"density,",
"since",
"areas",
"with",
"high",
"infection",
"intensity",
"coincided",
"with",
"areas",
"of",
"high",
"population",
"concentration.",
"It",
"is",
"therefore",
"reiterated",
"that",
"prevention",
"and",
"control",
"strategies",
"can",
"be",
"established",
"through",
"spatially",
"dependent",
"relationships",
"between",
"TB",
"and",
"its",
"risk",
"factors",
"[",
"43",
"].",
"The",
"social",
"context",
"certainly",
"undermines",
"the",
"space",
"relations",
"established",
"in",
"this",
"study.",
"It",
"is",
"clear",
"that",
"regions",
"with",
"higher",
"levels",
"of",
"human",
"development",
"also",
"show",
"large",
"income",
"inequalities",
"as",
"seen",
"in",
"Fig.",
"4",
"."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
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"indicated",
"future,",
"possibly",
"avoidable,",
"risks",
"in",
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"that",
"require",
"further",
"development",
"in",
"health",
"actions",
"and",
"consolidation",
"of",
"surveillance",
"measures.",
"Health",
"systems",
"need",
"to",
"respond",
"better",
"and",
"faster",
"to",
"the",
"challenges",
"of",
"a",
"changing",
"world",
"[",
"41",
"].",
"In",
"this",
"perspective,",
"health",
"promotion",
"and",
"prevention",
"actions",
"should",
"be",
"planned",
"according",
"to",
"the",
"real",
"needs",
"of",
"the",
"exposed",
"population.",
"TB",
"is",
"a",
"complex",
"disease",
"that",
"presents",
"control",
"difficulties",
"and",
"is",
"easily",
"spread",
"throughout",
"the",
"world.",
"It",
"is",
"possible",
"to",
"affirm",
"that",
"there",
"is",
"a",
"relation",
"between",
"territorial",
"space",
"and",
"transmission",
"of",
"TB;",
"thus,",
"to",
"understand",
"these",
"dynamics,",
"it",
"is",
"important",
"to",
"move",
"beyond",
"individual",
"level",
"analysis",
"to",
"spatial",
"dimensions",
"in",
"order",
"to",
"receive",
"important",
"input",
"for",
"targeted",
"intervention",
"[",
"42",
"].",
"When",
"considering",
"the",
"transcendence",
"of",
"the",
"disease",
"and",
"its",
"geographical",
"exposure,",
"we",
"can",
"suggest",
"alert",
"situations,",
"as",
"they",
"imply",
"greater",
"exposure",
"and",
"possible",
"illness.",
"When",
"observing",
"the",
"main",
"areas",
"of",
"risk,",
"one",
"can",
"observe",
"relations",
"with",
"the",
"population",
"density,",
"since",
"areas",
"with",
"high",
"infection",
"intensity",
"coincided",
"with",
"areas",
"of",
"high",
"population",
"concentration.",
"It",
"is",
"therefore",
"reiterated",
"that",
"prevention",
"and",
"control",
"strategies",
"can",
"be",
"established",
"through",
"spatially",
"dependent",
"relationships",
"between",
"TB",
"and",
"its",
"risk",
"factors",
"[",
"43",
"].",
"The",
"social",
"context",
"certainly",
"undermines",
"the",
"space",
"relations",
"established",
"in",
"this",
"study.",
"It",
"is",
"clear",
"that",
"regions",
"with",
"higher",
"levels",
"of",
"human",
"development",
"also",
"show",
"large",
"income",
"inequalities",
"as",
"seen",
"in",
"Fig.",
"4",
".",
"The",
"authors",
"believe",
"that",
"although",
"there",
"is",
"an",
"economic",
"development,",
"large",
"pockets",
"of",
"poverty",
"still",
"prevail",
"in",
"cities",
"with",
"accelerated",
"urbanization.",
"The",
"research",
"provides",
"evidence",
"of",
"how",
"the",
"social",
"determination",
"of",
"municipalities",
"may",
"be",
"related",
"to",
"the",
"increased",
"incidence",
"of",
"TB.",
"This",
"awareness",
"must",
"be",
"present",
"among",
"policy",
"makers",
"so",
"that",
"the",
"proposed",
"improvements",
"are",
"both",
"intersectoral",
"and",
"health",
"service",
"improvements.",
"Territory-based",
"surveillance",
"replicates",
"more",
"precise",
"disease",
"monitoring",
"[",
"44",
"],",
"and",
"TB",
"incidence",
"studies",
"will",
"continue",
"to",
"provide",
"the",
"best",
"method",
"to",
"directly",
"measure",
"the",
"disease",
"burden",
"and",
"identify",
"actions",
"necessary",
"for",
"its",
"reduction",
"[",
"1",
"].",
"The",
"authors",
"understand",
"that",
"there",
"are",
"limitations",
"in",
"the",
"method,",
"such",
"as",
"not",
"differentiating",
"patients",
"deprived",
"of",
"their",
"freedom",
"and",
"not",
"including",
"patients",
"with",
"latent",
"tuberculosis.",
"There",
"are",
"limitations",
"also",
"when",
"analysed",
"only",
"ecological",
"characteristics",
"and",
"not",
"individual",
"characteristics",
"and",
"their",
"risk",
"factors.",
"However,",
"it",
"is",
"believed",
"that",
"the",
"results",
"can",
"bring",
"significant",
"benefits",
"to",
"the",
"control",
"of",
"the",
"disease",
"in",
"Brazil,",
"creating",
"new",
"health",
"practices",
"and",
"strengthening",
"social",
"public",
"policies",
"for",
"the",
"population."
] |
Original work titled: 'Spatial and temporal analysis of tuberculosis in an area of social inequality in Northeast Brazil' (BMC Public Health/BioMed Central) by the following authors: Shirley Verônica Melo Almeida Lima; Allan Dantas dos Santos; Andrezza Marques Duque; Marco Aurélio de Oliveira Goes; Marcus Valerius da Silva Peixoto; Damião da Conceição Araújo; Caíque Jordan Nunes Ribeiro; Márcio Bezerra Santos; Karina Conceição Gomes Machado de Araújo; Marco Antônio Prado Nunes DOI: 10.1186/s12889-019-7224-0
|
ad03adbf592115b4d12541751416fe37
|
CC-BY
|
http://creativecommons.org/licenses/by/4.0/
|
4.0
|
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[
"It",
"is",
"therefore",
"reiterated",
"that",
"prevention",
"and",
"control",
"strategies",
"can",
"be",
"established",
"through",
"spatially",
"dependent",
"relationships",
"between",
"TB",
"and",
"its",
"risk",
"factors",
"[",
"43",
"].",
"The",
"social",
"context",
"certainly",
"undermines",
"the",
"space",
"relations",
"established",
"in",
"this",
"study.",
"It",
"is",
"clear",
"that",
"regions",
"with",
"higher",
"levels",
"of",
"human",
"development",
"also",
"show",
"large",
"income",
"inequalities",
"as",
"seen",
"in",
"Fig.",
"4",
".",
"The",
"authors",
"believe",
"that",
"although",
"there",
"is",
"an",
"economic",
"development,",
"large",
"pockets",
"of",
"poverty",
"still",
"prevail",
"in",
"cities",
"with",
"accelerated",
"urbanization.",
"The",
"research",
"provides",
"evidence",
"of",
"how",
"the",
"social",
"determination",
"of",
"municipalities",
"may",
"be",
"related",
"to",
"the",
"increased",
"incidence",
"of",
"TB.",
"This",
"awareness",
"must",
"be",
"present",
"among",
"policy",
"makers",
"so",
"that",
"the",
"proposed",
"improvements",
"are",
"both",
"intersectoral",
"and",
"health",
"service",
"improvements.",
"Territory-based",
"surveillance",
"replicates",
"more",
"precise",
"disease",
"monitoring",
"[",
"44",
"],",
"and",
"TB",
"incidence",
"studies",
"will",
"continue",
"to",
"provide",
"the",
"best",
"method",
"to",
"directly",
"measure",
"the",
"disease",
"burden",
"and",
"identify",
"actions",
"necessary",
"for",
"its",
"reduction",
"[",
"1",
"].",
"The",
"authors",
"understand",
"that",
"there",
"are",
"limitations",
"in",
"the",
"method,",
"such",
"as",
"not",
"differentiating",
"patients",
"deprived",
"of",
"their",
"freedom",
"and",
"not",
"including",
"patients",
"with",
"latent",
"tuberculosis.",
"There",
"are",
"limitations",
"also",
"when",
"analysed",
"only",
"ecological",
"characteristics",
"and",
"not",
"individual",
"characteristics",
"and",
"their",
"risk",
"factors.",
"However,",
"it",
"is",
"believed",
"that",
"the",
"results",
"can",
"bring",
"significant",
"benefits",
"to",
"the",
"control",
"of",
"the",
"disease",
"in",
"Brazil,",
"creating",
"new",
"health",
"practices",
"and",
"strengthening",
"social",
"public",
"policies",
"for",
"the",
"population.",
"Conclusion",
"The",
"study",
"identified",
"increasing",
"trends",
"of",
"TB",
"in",
"Sergipe",
"with",
"difference",
"between",
"age",
"groups",
"and",
"sex.",
"The",
"cure",
"rate",
"presented",
"a",
"worrying",
"decline,",
"countering",
"the",
"stable",
"trend",
"of",
"treatment",
"abandonment.",
"The",
"spatial",
"findings",
"showed",
"the",
"existence",
"of",
"TB",
"throughout",
"the",
"territory",
"and",
"emphasized",
"space",
"as",
"influential",
"in",
"the",
"onset",
"of",
"the",
"disease.",
"Positive",
"spatial",
"autocorrelation",
"was",
"observed",
"in",
"the",
"Southeast",
"region,",
"characterized",
"by",
"more",
"urbanized",
"municipalities",
"with",
"high",
"population",
"density.",
"The",
"research",
"expanded",
"knowledge",
"about",
"social",
"conditions",
"and",
"TB",
"infection",
"and",
"strengthened",
"evidence",
"regarding",
"the",
"temporal",
"and",
"spatial",
"dynamics",
"of",
"TB",
"to",
"improve",
"prevention",
"actions",
"and",
"control",
"of",
"the",
"disease.",
"The",
"analysis",
"elucidated",
"discussions",
"of",
"social",
"and",
"structural",
"health",
"system",
"problems,",
"operations,",
"and",
"the",
"need",
"for",
"possible",
"strategic",
"changes",
"to",
"address",
"TB.",
"Further",
"research",
"is",
"needed",
"to",
"address",
"populations",
"younger",
"than",
"20",
"years",
"and",
"over",
"60",
"years",
"to",
"better",
"determine",
"the",
"environmental",
"and",
"social",
"factors",
"that",
"interfere",
"with",
"the",
"transmissibility",
"of",
"the",
"disease",
"in",
"these",
"groups."
] |
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