<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Spinal muscular atrophy and can you explain it in depth? [/INST] Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death. It may also appear later in life and then have a milder course of the disease. The common feature is progressive weakness of voluntary muscles, with arm, leg and respiratory muscles being affected first. Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures.The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into a number of types.Spinal muscular atrophy is due to an abnormality (mutation) in the SMN1 gene which encodes SMN, a protein necessary for survival of motor neurons. Loss of these neurons in the spinal cord prevents signalling between the brain and skeletal muscles. Another gene, SMN2, is considered a disease modifying gene, since usually the more the SMN2 copies, the milder is the disease course. The diagnosis of SMA is based on symptoms and confirmed by genetic testing.Usually, the mutation in the SMN1 gene is inherited from both parents in an autosomal recessive manner, although in around 2% of cases it occurs during early development (de novo). The incidence of spinal muscular atrophy worldwide varies from about 1 in 4,000 births to around 1 in 16,000 births, with 1 in 7,000 and 1 in 10,000 commonly quoted for Europe and the US respectively.Outcomes in the natural course of the disease vary from death within a few weeks after birth in the most acute cases to normal life expectancy in the protracted SMA forms. The introduction of causative treatments in 2016 has significantly improved the outcomes. Medications that target the genetic cause of the disease include nusinersen, risdiplam, and the gene therapy medication onasemnogene abeparvovec. Supportive care includes physical therapy, occupational therapy, respiratory support, nutritional support, orthopaedic interventions, and mobility support.

Classification
5q SMA is a single disease that manifests over a wide range of severity, affecting infants through adults. Before its genetics was understood, its varying manifestations were thought to be different diseases – Werdnig–Hoffmann disease when young children were affected and Kugelberg–Welander disease for late-onset cases.In 1990, it was realised that these separate diseases formed a spectrum of the same disorder. Spinal muscular atrophy was then classified into 3–5 clinical types based either on the age of symptom onset or on the maximum motor function achieved. Currently, the consensus is that the phenotype of spinal muscular atrophy spans a continuum of symptoms without clear delineation of subtypes. However, the traditional classification, outlined in the table below, is still used today both in clinical research and sometimes, controversially, as a criterion of access to therapies.

For convenience, care-focused publications classify patients into "non-sitters", "sitters" and "walkers" based on their actual functional status.
Motor development and disease progression in people with SMA is usually assessed using validated functional scales – CHOP-INTEND (The Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders) or HINE (Hammersmith Infant Neurological Examination) in infants; and either the MFM (Motor Function Measure) or one of several variants of the HFMS (Hammersmith Functional Motor Scale) in older patients.
The eponymous label Werdnig–Hoffmann disease (sometimes misspelled with a single n) refers to the earliest clinical descriptions of childhood SMA by Johann Hoffmann and Guido Werdnig. The eponymous term Kugelberg–Welander disease named after Erik Klas Hendrik Kugelberg (1913–1983) and Lisa Welander (1909–2001), who first documented the late-onset form and distinguished it from muscular dystrophy. Very rarely used Dubowitz disease (not to be confused with Dubowitz syndrome) is named after Victor Dubowitz, an English neurologist who authored several studies on the intermediate SMA phenotype.

Signs and symptoms
The symptoms vary depending on the SMA type, the stage of the disease as well as individual factors. Signs and symptoms below are most common in the severe SMA type 0/I:
Areflexia, particularly in extremities
Overall muscle weakness, poor muscle tone, limpness or a tendency to flop
Difficulty achieving developmental milestones, difficulty sitting/standing/walking
In small children: adopting of a frog-leg position when sitting (hips abducted and knees flexed)
Loss of strength of the respiratory muscles: weak cough, weak cry (infants), accumulation of secretions in the lungs or throat, respiratory distress
Bell-shaped torso (caused by using only abdominal muscles for respiration) in severe SMA type
Fasciculations (twitching) of the tongue
Difficulty sucking or swallowing, poor feeding

Causes
Spinal muscular atrophy is caused by a genetic mutation in the SMN1 gene.Human chromosome 5 contains two nearly identical genes at location 5q13: a telomeric copy SMN1 and a centromeric copy SMN2. In healthy individuals, the SMN1 gene codes the survival of motor neuron protein (SMN) which, as its name says, plays a crucial role in survival of motor neurons. The SMN2 gene, on the other hand – due to a variation in a single nucleotide (840.C→T) – undergoes alternative splicing at the junction of intron 6 to exon 8, with only 10–20% of SMN2 transcripts coding a fully functional survival of motor neuron protein (SMN-fl) and 80–90% of transcripts resulting in a truncated protein compound (SMNΔ7) which is rapidly degraded in the cell.In individuals affected by SMA, the SMN1 gene is mutated in such a way that it is unable to correctly code the SMN protein – due to either a deletion occurring at exon 7 or to other point mutations (frequently resulting in the functional conversion of the SMN1 sequence into SMN2). Almost all people, however, have at least one functional copy of the SMN2 gene (with most having 2–4 of them) which still codes 10–20% of the usual level of the SMN protein, allowing some neurons to survive. In the long run, however, the reduced availability of the SMN protein results in gradual death of motor neuron cells in the anterior horn of spinal cord and the brain. Skeletal muscles, which all depend on these motor neurons for neural input, now have decreased innervation (also called denervation), and therefore have decreased input from the central nervous system (CNS). Decreased impulse transmission through the motor neurons leads to decreased contractile activity of the denervated muscle. Consequently, denervated muscles undergo progressive atrophy (waste away).Muscles of lower extremities are usually affected first, followed by muscles of upper extremities, spine and neck and, in more severe cases, pulmonary and mastication muscles. Proximal muscles are always affected earlier and to a greater degree than distal muscles.The severity of SMA symptoms is broadly related to how well the remaining SMN2 genes can make up for the loss of function of SMN1. This partly depends on the number of copies of the SMN2 gene present on the chromosome. Whilst healthy individuals usually carry two SMN2 gene copies, people with SMA can have anything between 1 and 5 (or more) of them; the greater the number of SMN2 copies, the milder the disease severity. Thus, most SMA type I babies have one or two SMN2 copies; people with SMA II and III usually have at least three SMN2 copies; and people with SMA IV normally have at least four of them. However, the correlation between symptom severity and SMN2 copy number is not absolute and there seem to exist other factors affecting the disease phenotype.Spinal muscular atrophy is inherited in an autosomal recessive pattern, which means that the defective gene is located on an autosome. Two copies of the defective gene – one from each parent – are required to inherit the disorder: the parents may be carriers and not personally affected. SMA seems to appear de novo (i.e., without any hereditary causes) in around 2–4% of cases.Spinal muscular atrophy affects individuals of all ethnic groups, unlike other well known autosomal recessive disorders, such as sickle cell disease and cystic fibrosis, which have significant differences in occurrence rate among ethnic groups. The overall prevalence of SMA, of all types and across all ethnic groups, is in the range of 1 per 10,000 individuals; the gene frequency is around 1:100, therefore, approximately one in 50 persons are carriers. There are no known health consequences of being a carrier. A person may learn carrier status only if ones child is affected by SMA or by having the SMN1 gene sequenced.Affected siblings usually have a very similar form of SMA. However, occurrences of different SMA types among siblings do exist – while rare, these cases might be due to additional de novo deletions of the SMN gene, not involving the NAIP gene, or the differences in SMN2 copy numbers.

Diagnosis
SMA is diagnosed using genetic testing that detects homozygous deletion of the SMN1 gene in over 95% of cases, and a compound SMN1 mutation in the remaining patients. Genetic testing is usually carried out using a blood sample, and MLPA is one of more frequently used genetic testing techniques, as it also allows establishing the number of SMN2 gene copies, which has clinical importance.Symptomatically, SMA can be diagnosed with a degree of certainty only in children with the acute form who manifest a progressive illness with paradoxical breathing, bilateral low muscle tone and absent tendon reflexes.

Early diagnosis
Early diagnosis of SMA, at the asymptomatic stage of the disease, allows for

Preimplantation testing
Preimplantation genetic diagnosis can be used to screen for SMA-affected embryos during in-vitro fertilisation.

Prenatal testing
Prenatal testing for SMA is possible through chorionic villus sampling, cell-free fetal DNA analysis and other methods.

Newborn screening
Routine newborn screening for SMA is becoming increasingly commonplace in developed countries, given the availability of causative treatments that are most effective at the asymptomatic stage of the disease. In 2018, newborn screening for SMA was added to the US list of recommended newborn screening tests and as of April 2020 it has been adopted in 39 US states. As of May 2021, SMA newborn screening has been implemented in Taiwan and is in the course of implementation in Australia, Belgium, Canada, France, Germany, Netherlands, Poland, Serbia and Slovenia. Additionally, pilot projects are being conducted in Australia, China, Italy, and Japan.

Carrier testing
Those at risk of being carriers of SMN1 deletion, and thus at risk of having offspring affected by SMA, can undergo carrier analysis using a blood or saliva sample. The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they are a carrier. The carrier frequency of SMA is comparable to other disorders like thalassemia and in a north Indian cohort has been found to be 1 in 38. However, genetic testing will not be able to identify all individuals at risk since about 2% of cases are caused by de novo mutations and 5% of the normal population have two copies of SMN1 on the same chromosome, which makes it possible to be a carrier by having one chromosome with two copies and a second chromosome with zero copies. This situation will lead to a false negative result, as the carrier status will not be correctly detected by a traditional genetic test.

Management
The management of SMA varies based upon the severity and type. In the most severe forms (types 0/1), individuals have the greatest muscle weakness requiring prompt intervention. Whereas the least severe form (type 4/adult onset), individuals may not seek the certain aspects of care until later (decades) in life. While types of SMA and individuals among each type may differ, therefore specific aspects of an individuals care can differ.

Medication
Nusinersen (marketed as Spinraza) is used to treat spinal muscular atrophy. It is an antisense nucleotide that modifies the alternative splicing of the SMN2 gene. It is given directly to the central nervous system using an intrathecal injection. Nusinersen prolongs survival and improves motor function in infants with SMA. It was approved for use in the US in 2016, and for use in the EU in 2017.Onasemnogene abeparvovec (marketed as Zolgensma) is a gene therapy treatment which uses self-complementary adeno-associated virus type 9 (scAAV-9) as a vector to deliver the SMN1 transgene. The therapy was first approved in the US in May 2019 as an intravenous formulation for children below 24 months of age. Approval in the European Union, Japan and other countries followed, albeit often with different approval scopes.Risdiplam (marketed as Evrysdi) is a medication taken by mouth in liquid form. It is a pyridazine derivative that works by increasing the amount of functional survivor motor neuron protein produced by the SMN2 gene through modifying its splicing pattern. Risdiplam was first approved for medical use in the United States in August 2020 and has since been approved in over 30 countries.

Breathing
The respiratory system is the most common system to be affected and the complications are the leading cause of death in SMA types 0/1 and 2. SMA type 3 can have similar respiratory problems, but it is more rare. The complications that arise due to weakened intercostal muscles because of the lack of stimulation from the nerve. The diaphragm is less affected than the intercostal muscles. Once weakened, the muscles never fully recover the same functional capacity to help in breathing and coughing as well as other functions. Therefore, breathing is more difficult and pose a risk of not getting enough oxygen/shallow breathing and insufficient clearance of airway secretions. These issues more commonly occurs while asleep, when muscles are more relaxed. Swallowing muscles in the pharynx can be affected, leading to aspiration coupled with a poor coughing mechanism increases the likelihood of infection/pneumonia. Mobilizing and clearing secretions involve manual or mechanical chest physiotherapy with postural drainage, and manual or mechanical cough assistance device. To assist in breathing, Non-invasive ventilation (BiPAP) is frequently used and tracheostomy may be sometimes performed in more severe cases; both methods of ventilation prolong survival to a comparable degree, although tracheostomy prevents speech development.

Nutrition
The more severe the type of SMA, the more likely to have nutrition related health issues. Health issues can include difficulty in feeding, jaw opening, chewing and swallowing. Individuals with such difficulties can be at increase risk of over or undernutrition, failure to thrive and aspiration. Other nutritional issues, especially in individuals that are non-ambulatory (more severe types of SMA), include food not passing through the stomach quickly enough, gastric reflux, constipation, vomiting and bloating. Therein, it could be necessary in SMA type I and people with more severe type II to have a feeding tube or gastrostomy. Additionally, metabolic abnormalities resulting from SMA impair β-oxidation of fatty acids in muscles and can lead to organic acidemia and consequent muscle damage, especially when fasting. It is suggested that people with SMA, especially those with more severe forms of the disease, reduce intake of fat and avoid prolonged fasting (i.e., eat more frequently than healthy people) as well as choosing softer foods to avoid aspiration. During an acute illness, especially in children, nutritional problems may first present or can exacerbate an existing problem (example: aspiration) as well as cause other health issues such as electrolyte and blood sugar disturbances.

Orthopaedics
Skeletal problems associated with weak muscles in SMA include tight joints with limited range of movement, hip dislocations, spinal deformity, osteopenia, an increase risk of fractures and pain. Weak muscles that normally stabilize joints such as the vertebral column lead to development of kyphosis and/or scoliosis and joint contracture. Spine fusion is sometimes performed in people with SMA I/II once they reach the age of 8–10 to relieve the pressure of a deformed spine on the lungs. Furthermore, immobile individuals, posture and position on mobility devices as well as range of motion exercises, and bone strengthening can be important to prevent complications. People with SMA might also benefit greatly from various forms of physiotherapy, occupational therapy and physical therapy.Orthotic devices can be used to support the body and to aid walking. For example, orthotics such as AFOs (ankle foot orthoses) are used to stabilise the foot and to aid gait, TLSOs (thoracic lumbar sacral orthoses) are used to stabilise the torso. Assistive technologies may help in managing movement and daily activity and greatly increase the quality of life.

Other
Although the heart is not a matter of routine concern, a link between SMA and certain heart conditions has been suggested.Children with SMA do not differ from the general population in their behaviour; their cognitive development can be slightly faster, and certain aspects of their intelligence are above the average. Despite their disability, SMA-affected people report high degree of satisfaction from life.Palliative care in SMA has been standardised in the Consensus Statement for Standard of Care in Spinal Muscular Atrophy which has been recommended for standard adoption worldwide.

Prognosis
In the absence of pharmacological treatment, people with SMA tend to deteriorate over time. Recently, survival has increased in severe SMA patients with aggressive and proactive supportive respiratory and nutritional support.If left untreated, the majority of children diagnosed with SMA type 0 and 1 do not reach the age of 4, recurrent respiratory problems being the primary cause of death. With proper care, milder SMA type I cases (which account for approx. 10% of all SMA1 cases) live into adulthood. Long-term survival in SMA type I is not sufficiently evidenced; however, as of 2007 advances in respiratory support seem to have brought down mortality.In untreated SMA type II, the course of the disease is slower to progress and life expectancy is less than the healthy population. Death before the age of 20 is frequent, although many people with SMA live to become parents and grandparents. SMA type III has normal or near-normal life expectancy if standards of care are followed. Type IV, adult-onset SMA usually means only mobility impairment and does not affect life expectancy.

Research directions
Since the underlying genetic cause of SMA was identified in 1995, several therapeutic approaches have been proposed and investigated that primarily focus on increasing the availability of SMN protein in motor neurons. The main research directions have been as follows:

SMN1 gene replacement
Gene therapy in SMA aims at restoring the SMN1 gene function through inserting specially crafted nucleotide sequence (a SMN1 transgene) into the cell nucleus using a viral vector. This approach has been exploited by the first approved gene therapy for SMA, scAAV-9 based treatment onasemnogene abeparvovec.

SMN2 alternative splicing modulation
This approach aims at modifying the alternative splicing of the SMN2 gene to force it to code for higher percentage of full-length SMN protein. Sometimes it is also called gene conversion, because it attempts to convert the SMN2 gene functionally into SMN1 gene. It is the therapeutic mechanism of the approved medications nusinersen and risdiplam.
Branaplam is another SMN2 splicing modulator that has reached the clinical stage of development.Historically, this research direction investigated also other molecules. RG3039, also known as Quinazoline495, was a proprietary quinazoline derivative developed by Repligen and licensed to Pfizer in March 2014 which was discontinued shortly after, having only completed phase I trials. PTK-SMA1 was a proprietary small-molecule splicing modulator of the tetracyclines group developed by Paratek Pharmaceuticals and about to enter clinical development in 2013 which however never happened due to Paratek downsizing at that time. RG7800, developed by Hoffmann-La Roche, was a molecule akin to risdiplam that has undergone phase I testing but was discontinued due to animal toxicity. Early leads also included sodium orthovanadate and aclarubicin.Morpholino-type antisense oligonucleotides, with the same cellular target as nusinersen, remain a subject of research in treating SMA and other single-gene diseases, including at the University College London and at the University of Oxford.

SMN2 gene activation
This approach aims at increasing expression (activity) of the SMN2 gene, thus increasing the amount of full-length SMN protein available.

Oral salbutamol (albuterol), a popular asthma medicine, showed therapeutic potential in SMA both in vitro and in three small-scale clinical trials involving patients with SMA types 2 and 3, besides offering respiratory benefits.A few compounds initially showed promise but failed to demonstrate efficacy in clinical trials. Butyrates (sodium butyrate and sodium phenylbutyrate) held some promise in in vitro studies but a clinical trial in symptomatic people did not confirm their efficacy. Another clinical trial in pre-symptomatic types 1–2 infants was completed in 2015 but no results have been published.
Valproic acid (VPA) was used in SMA on an experimental basis in the 1990s and 2000s because in vitro research suggested its moderate effectiveness. However, it demonstrated no efficacy in achievable concentrations when subjected to a large clinical trial. It has also been proposed that it may be effective in a subset of people with SMA but its action may be suppressed by fatty acid translocase in others. Others argue it may actually aggravate SMA symptoms. It is currently not used due to the risk of severe side effects related to long-term use. A 2019 meta-analysis suggested that VPA may offer benefits, even without improving functional score.
Hydroxycarbamide (hydroxyurea) was shown effective in mouse models and subsequently commercially researched by Novo Nordisk, Denmark, but demonstrated no effect on people with SMA in subsequent clinical trials.Compounds which increased SMN2 activity in vitro but did not make it to the clinical stage include growth hormone, various histone deacetylase inhibitors, benzamide M344, hydroxamic acids (CBHA, SBHA, entinostat, panobinostat, trichostatin A, vorinostat), prolactin as well as natural polyphenol compounds like resveratrol and curcumin. Celecoxib, a p38 pathway activator, is sometimes used off-label by people with SMA based on a single animal study but such use is not backed by clinical-stage research.

SMN stabilisation
SMN stabilisation aims at stabilising the SMNΔ7 protein, the short-lived defective protein coded by the SMN2 gene, so that it is able to sustain neuronal cells.No compounds have been taken forward to the clinical stage. Aminoglycosides showed capability to increase SMN protein availability in two studies. Indoprofen offered some promise in vitro.

Neuroprotection
Neuroprotective drugs aim at enabling the survival of motor neurons even with low levels of SMN protein.

Olesoxime was a proprietary neuroprotective compound developed by the French company Trophos, later acquired by Hoffmann-La Roche, which showed stabilising effect in a phase-II clinical trial involving people with SMA types 2 and 3. Its development was discontinued in 2018 in view of competition from nusinersen and underwhelming data from an open-label extension trial.Of clinically studied compounds which did not show efficacy, thyrotropin-releasing hormone (TRH) held some promise in an open-label uncontrolled clinical trial but did not prove effective in a subsequent double-blind placebo-controlled trial </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Vasculitic neuropathy and can you explain it in depth? [/INST] Vasculitic neuropathy is a peripheral neuropathic disease. In a vasculitic neuropathy  there is damage to the vessels that supply blood to the nerves. It can be as part of a systemic problem or can exist as a single-organ issue only affecting the peripheral nervous system (PNS). It is diagnosed with the use of electrophysiological testing, blood tests, nerve biopsy and clinical examination. It is a serious medical condition that can cause prolonged morbidity and disability and generally requires treatment. Treatment depends on the type but it is mostly with corticosteroids or immunomodulating therapies.

Types
There are three main categories of vasculitic neuropathies: primary, secondary and non-systemic.

Primary systemic vasculitic neuropathy
Some patients with systemic vasculitis will have their multi-organ disease spread to the peripheral nervous system; this is primary vasculitic neuropathy. Some examples of systemic vasculitic disease are: IgA vasculitis, Hypocomplementemic urticarial vasculitis, polyarteritis nodosa (PAN) and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides such as granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA).

Vasculitic neuropathy secondary to other disease
Some patients with a non-vasculitic systemic disease or another illness such as infection or malignancy can subsequently develop vasculitic neuropathy as a direct consequence of the former illness; this is secondary vasculitic neuropathy. Some examples of such illness which can cause vasculitic neuropathy are:
Connective tissue diseases: rheumatoid arthritis, systemic lupus erythematosus, primary sjögrens, dermatomyositis.
Infectious diseases: hepatitis B, hepatitis C, human immunodeficiency virus (HIV), cytomegalovirus, lyme disease, human T-cell-lymphotrophic virus-I, parvovirus B19.
Malignancy.
Drugs (amphetamines, sympathomimetics, cocaine, etc.)
Vaccinations.

Non-systemic vasculitic neuropathy
Non-systemic vasculitic neuropathy (NSVN) is a diagnosis of elimination </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Lenz microphthalmia syndrome and can you explain it in depth? [/INST] Lenz microphthalmia syndrome is a very rare inherited disorder characterized by abnormal smallness of one or both eyes (microphthalmos) sometimes with droopy eyelids (blepharoptosis), resulting in visual impairment or blindness. Eye problems may include coloboma, microcornea, and glaucoma </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Oophoritis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Odontogenic cyst and can you explain it in depth? [/INST] Odontogenic cyst are a group of jaw cysts that are formed from tissues involved in odontogenesis (tooth development). Odontogenic cysts are closed sacs, and have a distinct membrane derived from rests of odontogenic epithelium. It may contain air, fluids, or semi-solid material. Intra-bony cysts are most common in the jaws, because the mandible and maxilla are the only bones with epithelial components. That odontogenic epithelium is critical in normal tooth development. However, epithelial rests may be the origin for the cyst lining later.
Not all oral cysts are odontogenic cyst. For example, mucous cyst of the oral mucosa and nasolabial duct cyst are not of odontogenic origin.
In addition, there are several conditions with so-called (radiographic) pseudocystic appearance in jaws; ranging from anatomic variants such as Stafne static bone cyst, to the aggressive aneurysmal bone cyst.

Classification
I. Cysts of the jaws
A. Epithelial-lined cysts
1. Developmental origin
(a) Odontogenic
i. Gingival cyst of infants
ii. Odontogenic keratocyst
iii. Dentigerous cyst
iv. Eruption cyst
v. Gingival cyst of adults
vi. Developmental lateral periodontal cyst
vii. Botryoid odontogenic cyst
viii. Glandular odontogenic cyst
ix. Calcifying odontogenic cyst
(b) Non-odontogenic
i. Midpalatal raphé cyst of infants
ii. Nasopalatine duct cyst
iii. Nasolabial cyst
2. Inflammatory origin
i. Radicular cyst, apical and lateral
ii. Residual cyst
iii. Paradental cyst and juvenile paradental cyst
iv. Inflammatory collateral cyst
B. Non-epithelial-lined cysts
1. Solitary bone cyst
2. Aneurysmal bone cyst
II. Cysts associated with the maxillary antrum
1. Mucocele
2. Retention cyst
3. Pseudocyst
4. Postoperative maxillary cyst
III. Cysts of the soft tissues of the mouth, face and neck
1. Dermoid and epidermoid cysts
2. Lymphoepithelial (branchial) cyst
3. Thyroglossal duct cyst
4. Anterior median lingual cyst (intralingual cyst of foregut origin)
5. Oral cysts with gastric or intestinal epithelium (oral alimentary tract cyst)
6. Cystic hygroma
7. Nasopharyngeal cyst
8 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Late congenital syphilitic oculopathy and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Parathyroid hormone and can you explain it in depth? [/INST] Parathyroid hormone (PTH), also called parathormone or parathyrin,  is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.PTH influences bone remodeling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time.  PTH is secreted in response to low blood serum calcium (Ca2+) levels.  PTH indirectly stimulates osteoclast activity within the bone matrix (osteon), in an effort to release more ionic calcium (Ca2+) into the blood to elevate a low serum calcium level.  The bones act as a (metaphorical) "bank of calcium" from which the body can make "withdrawals" as needed to keep the amount of calcium in the blood at appropriate levels despite the ever-present challenges of metabolism, stress, and nutritional variations. PTH is "a key that unlocks the bank vault" to remove the calcium.
PTH is secreted primarily by the chief cells of the parathyroid glands. The gene for PTH is located on chromosome 11. It is a polypeptide containing 84 amino acids, which is a prohormone. It has a molecular mass around 9500 Da. Its action is opposed by the hormone calcitonin.
There are two types of PTH receptors. Parathyroid hormone 1 receptors, activated by the 34 N-terminal amino acids of PTH, are present at high levels on the cells of bone and kidney. Parathyroid hormone 2 receptors are present at high levels on the cells of central nervous system, pancreas, testes, and placenta. The half-life of PTH is about 4 minutes.Disorders that yield too little or too much PTH, such as hypoparathyroidism, hyperparathyroidism, and paraneoplastic syndromes can cause bone disease, hypocalcemia, and hypercalcemia.

Structure
hPTH-(1-84) crystallizes as a slightly bent, long, helical dimer. The extended helical conformation of hPTH-(1-84) is the likely bioactive conformation. The N-terminal fragment 1-34 of parathyroid hormone (PTH) has been crystallized and the structure has been refined to 0.9 Å resolution.

Function
Regulation of serum calcium
Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine:In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of osteoprotegerin (OPG). Free OPG competitively binds to RANKL as a decoy receptor, preventing RANKL from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates osteoclast precursors, which are of a monocyte lineage, to fuse. The resulting multinucleated cells are osteoclasts, which ultimately mediate bone resorption. Estrogen also regulates this pathway through its effects on PTH. Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity in the bone marrow, thymus, and peripheral lymphoid organs. In the bone marrow, estrogen downregulates the proliferation of hematopoietic stem cells through an IL-7 dependent mechanism.In the kidney, around 250 mmol of calcium ions are filtered into the glomerular filtrate per day. Most of this (245 mmol/d) is reabsorbed from the tubular fluid, leaving about 5 mmol/d to be excreted in the urine. This reabsorption occurs throughout the tubule (most, 60-70%, of it in the proximal tubule), except in the thin segment of the loop of Henle. Circulating parathyroid hormone only influences the reabsorption that occurs in the distal tubules and the renal collecting ducts (but see Footnote). A more important effect of PTH on the kidney is, however, its inhibition of the reabsorption of phosphate (HPO42−) from the tubular fluid, resulting in a decrease in the plasma phosphate concentration.  Phosphate ions form water-insoluble salts with calcium. Thus, a decrease in the phosphate concentration of the  blood plasma (for a given total calcium concentration) increases the amount of calcium that is ionized. A third important effect of PTH on the kidney is its stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine.Via the kidney, PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin.
PTH was one of the first hormones to be shown to use the G-protein adenylyl cyclase second messenger system.

Regulation of serum phosphate
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine.
However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. The absorption of phosphate is not as dependent on vitamin D as is that of calcium. The end result of PTH release is a small net drop in the serum concentration of phosphate.

Vitamin D synthesis
PTH upregulates the activity of 1-α-hydroxylase enzyme, which converts 25-hydroxycholecalciferol, the major circulating form of inactive vitamin D, into 1,25-dihydroxycholecalciferol, the active form of vitamin D, in the kidney.

Interactive pathway map
Regulation of PTH secretion
Secretion of parathyroid hormone is determined chiefly by serum ionized calcium concentration through negative feedback. Parathyroid cells express calcium-sensing receptors on the cell surface. PTH is secreted when [Ca2+] is decreased (calcitonin is secreted when serum calcium levels are elevated). The G-protein-coupled calcium receptors bind extracellular calcium and may be found on the surface on a wide variety of cells distributed in the brain, heart, skin, stomach, C cells, and other tissues.  In the parathyroid gland, high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C.  This hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to liberate intracellular messengers IP3 and diacylglycerol (DAG).  Ultimately, these two messengers result in a release of calcium from intracellular stores into the cytoplasmic space.  Hence a high extracellular calcium concentration leads to an increase in the cytoplasmic calcium concentration.  In contrast to the mechanism that most secretory cells use, this high cytoplasmic calcium concentration inhibits the fusion of vesicles containing granules of preformed PTH with the membrane of the parathyroid cell, and thus inhibits release of PTH.
In the parathyroids, magnesium serves this role in stimulus-secretion coupling. A mild decrease in serum magnesium levels stimulates the reabsorptive activity PTH has on the kidneys. Severe hypomagnesemia inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.

Stimulators
Decreased serum [Ca2+].
Mild decreases in serum [Mg2+].
An increase in serum phosphate (increased phosphate causes it to complex with serum calcium,  forming calcium phosphate, which reduces stimulation of Ca-sensitive receptors (CaSr) that do not sense calcium phosphate, triggering an increase in PTH).
Adrenaline
Histamine

Inhibitors
Increased serum [Ca2+].
Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia).
Calcitriol
Increase in serum phosphate. Fibroblast growth factor-23 (FGF23) is produced in osteoblasts (from bone) in response to increases in serum phosphate (Pi). It binds to the fibroblast growth factor receptor of the parathyroid and suppresses PTH release. This may seem contradictory because PTH actually helps rid the blood of phosphates but it is also causes release of phosphate into the blood from bone resorption. FGF23 inhibits PTH and then takes its place helping inhibit re-absorption of phosphate in the kidney without the phosphate releasing effect on bones.

Disorders
Hyperparathyroidism, the presence of excessive amounts of parathyroid hormone in the blood, occurs in two very distinct sets of circumstances </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Perinephritis and can you explain it in depth? [/INST]  </s>


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Flail chest and can you explain it in depth? [/INST] Flail chest is a life-threatening medical condition that occurs when a segment of the rib cage breaks due to trauma and becomes detached from the rest of the chest wall. Two of the symptoms of flail chest are chest pain and shortness of breath.It occurs when multiple adjacent ribs are broken in multiple places, separating a segment, so a part of the chest wall moves independently. The number of ribs that must be broken varies by differing definitions: some sources say at least two adjacent ribs are broken in at least two places, some require three or more ribs in two or more places. The flail segment moves in the opposite direction to the rest of the chest wall: because of the ambient pressure in comparison to the pressure inside the lungs, it goes in while the rest of the chest is moving out, and vice versa. This so-called "paradoxical breathing" is painful and increases the work involved in breathing.
Flail chest is usually accompanied by a pulmonary contusion, a bruise of the lung tissue that can interfere with blood oxygenation. Often, it is the contusion, not the flail segment, that is the main cause of respiratory problems in people with both injuries.Surgery to fix the fractures appears to result in better outcomes.

Signs and symptoms
Two of the symptoms of flail chest are chest pain and shortness of breath.The characteristic paradoxical motion of the flail segment occurs due to pressure changes associated with respiration that the rib cage normally resists:

During normal inspiration, the diaphragm contracts and intercostal muscles pull the rib cage out. Pressure in the thorax decreases below atmospheric pressure, and air rushes in through the trachea. The flail segment will be pulled in with the decrease in pressure while the rest of the rib cage expands.
During normal expiration, the diaphragm and intercostal muscles relax increasing internal pressure, allowing the abdominal organs to push air upwards and out of the thorax. However, a flail segment will also be pushed out while the rest of the rib cage contracts.Paradoxical motion is a late sign of flail segment; therefore, an absence of paradoxical motion does not mean the patient does not have a flail segment.
The constant motion of the ribs in the flail segment at the site of the fracture is extremely painful, and, untreated, the sharp broken edges of the ribs are likely to eventually puncture the pleural sac and lung, possibly causing a pneumothorax. The concern about "mediastinal flutter" (the shift of the mediastinum with paradoxical diaphragm movement) does not appear to be merited. Pulmonary contusions are commonly associated with flail chest and that can lead to respiratory failure. This is due to the paradoxical motions of the chest wall from the fragments interrupting normal breathing and chest movement. Typical paradoxical motion is associated with stiff lungs, which requires extra work for normal breathing, and increased lung resistance, which makes air flow difficult. The respiratory failure from the flail chest requires mechanical ventilation and a longer stay in an intensive care unit. It is the damage to the lungs from the flail segment that is life-threatening.

Causes
The most common causes of flail chest injuries are vehicle collisions, which account for 76% of flail chest injuries. Another main cause of flail chest injuries is falling.  This mainly occurs in the elderly, who are more impacted by the falls as a result of their weak and frail bones, unlike their younger counterparts who can fall without being impacted as severely. Falls account for 14% of flail chest injuries.Flail chest typically occurs when three or more adjacent ribs are fractured in two or more places, allowing that segment of the thoracic wall to displace and move independently of the rest of the chest wall. Flail chest can also occur when ribs are fractured proximally in conjunction with disarticulation of costal cartilages distally. For the condition to occur, generally there must be a significant force applied over a large surface of the thorax to create the multiple anterior and posterior rib fractures. Rollover and crushing injuries most commonly break ribs at only one point, whereas for flail chest to occur a significant impact is required, breaking the ribs in two or more places. This can be caused by forceful accidents such as the aforementioned vehicle collisions or significant falls. In the elderly, it can be caused by deterioration of bone, although rare. In children, the majority of flail chest injuries result from common blunt force traumas or metabolic bone diseases, including a group of genetic disorders known as osteogenesis imperfecta.

Diagnosis
Diagnosis is by physical examination performed by a physician. The diagnosis may be assisted or confirmed by use of medical imaging with either plain X ray or CT scan.

Treatment
Treatment of the flail chest initially follows the principles of advanced trauma life support. Further treatment includes:

Good pain management includes early regional anesthesia (e.g. intercostal blocks or erector spinae plane blocks) and avoiding opioid pain medication as much as possible. This allows much better ventilation, with improved tidal volume, and increased blood oxygenation.
Positive pressure ventilation, meticulously adjusting the ventilator settings to avoid pulmonary barotrauma.
Chest tubes as required.
Adjustment of position to make the person most comfortable and provide relief of pain.
Aggressive pulmonary toiletA person may be intubated with a double lumen tracheal tube. In a double lumen endotracheal tube, each lumen may be connected to a different ventilator. Usually one side of the chest is affected more than the other, so each lung may require drastically different pressures and flows to adequately ventilate.
Surgical fixation can help in significantly reducing the duration of ventilatory support and in conserving the pulmonary function.
Surgical intervention has also been shown to reduce the need for tracheostomy, reduces the time spent in the intensive care unit following a traumatic flail chest injury and could reduce the risk of acquiring pneumonia after such an event.

Physiotherapy
In order to begin a rehabilitation program for a flail chest it is important to treat the persons pain so they are able to perform the proper exercises. Due to the underlying conditions that the flail segment has caused onto the respiratory system, chest physiotherapy is important to reduce further complications.  Proper positioning of the body is key, including postural alignment for proper drainage of mucous secretions.  The therapy will consist of a variety of postural positioning and changes in order to increase normal breathing.  Along with postural repositioning, a variety of breathing exercises are also very important in order to allow the chest wall to reposition itself back to normal conditions.  Breathing exercises will also include coughing procedures.  Furthermore, range of motion exercises are given to reduce the atrophy of the musculature </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Obesity and can you explain it in depth? [/INST] Obesity is a medical condition, sometimes considered a disease, in which abnormal or excess body fat has accumulated to such an extent that it may have a negative effect on health. People are classified as obese when their body mass index (BMI)—a measurement obtained by dividing a persons weight by the square of the persons height (despite known allometric inaccuracies)—is over 30 kg/m2; the range 25–30 kg/m2 is defined as overweight. Some East Asian countries use lower values to calculate obesity.Obesity is a major cause of disability and is correlated with various diseases and conditions, particularly cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. High BMI is a marker of risk for, but not a direct cause of, diseases caused by diet and physical activity. A reciprocal link has been found between obesity and depression, with obesity increasing the risk of clinical depression, and also depression leading to a higher chance of developing obesity.Obesity has individual, socioeconomic, and environmental causes. Some of the known causes are diet, physical activity, automation, urbanization, genetic susceptibility, medications, mental disorders, economic policies, endocrine disorders, and exposure to endocrine-disrupting chemicals.
Epidemiologic studies of overweight and obesity in children and adults covering 195 countries have shown that the prevalence of obesity has steadily increased in most countries, doubling in 73 countries between the years 1980 and 2015. As of 2015, the United States and China had the largest numbers of obese adults, and China and India had the largest numbers of obese children. By 2018, 42% of Americans were obese.While a majority of obese individuals at any given time are attempting to lose weight and are often successful, research shows that maintaining that weight loss over the long term proves to be rare. The reasons for weight cycling are not fully understood but may include decreased energy expenditure combined with an increased biological urge to eat during and after caloric restriction. More studies are needed to determine if weight cycling and yo-yo dieting contribute to inflammation and disease risk in obese individuals.Although there is no effective, well-defined, evidence-based intervention for preventing obesity, obesity prevention will require a complex approach, including interventions at community, family, and individual levels. Changes to diet and exercising are the main treatments recommended by health professionals. Diet quality can be improved by reducing the consumption of energy-dense foods, such as those high in fat or sugars, and by increasing the intake of dietary fiber. However, large-scale analyses have found an inverse relationship between energy density and energy cost of foods in developed nations. Medications can be used, along with a suitable diet, to reduce appetite or decrease fat absorption. If diet, exercise, and medication are not effective, a gastric balloon or surgery may be performed to reduce stomach volume or length of the intestines, leading to feeling full earlier, or a reduced ability to absorb nutrients from food.Obesity is a leading preventable cause of death worldwide, with increasing rates in adults and children. In 2015, 600 million adults (12%) and 100 million children were obese in 195 countries. Obesity is more common in women than in men. Public health officials view it as one of the most serious public health problems of the 21st century. Today, obesity is stigmatized in most of the world. Conversely, some cultures, past and present, have a favorable view of obesity, seeing it as a symbol of wealth and fertility. Nevertheless, in 2013, several medical societies, including the American Medical Association and the American Heart Association, classified obesity as a disease.

Classification
Obesity is typically defined as a substantial accumulation of body fat that could impact health. Medical organizations tend to classify people as obese based on body mass index (BMI) – a ratio of a persons weight in kilograms to the square of their height in meters. For adults, the World Health Organization (WHO) defines overweight as a BMI 25 or higher, and obese as a BMI 30 or higher. For children, obesity measures take age into consideration along with height and weight. For children aged 5–19, the WHO defines obesity as a BMI two standard deviations above the median for their age (a BMI around 18 for a five-year old; around 30 for a 19-year old). For children under five, the WHO defines obesity as a weight three standard deviations above the median for their height. The U.S. Centers for Disease Control and Prevention (CDC) further subdivides obesity based on BMI, with a BMI 30 to 35 called class 1 obesity; 35 to 40, class 2 obesity; and 40+, class 3 obesity.It further evaluated in terms of fat distribution via the waist–hip ratio and total cardiovascular risk factors. BMI is closely related to both percentage body fat and total body fat.In children, a healthy weight varies with age and sex. Obesity in children and adolescents is defined not as an absolute number but in relation to a historical normal group, such that obesity is a BMI greater than the 95th percentile. The reference data on which these percentiles were based date from 1963 to 1994, and thus have not been affected by the recent increases in weight.Some modifications to the WHO definitions have been made by particular organizations. The surgical literature breaks down class II and III or only class III obesity into further categories whose exact values are still disputed.
Any BMI ≥ 35 or 40 kg/m2 is severe obesity.
A BMI of ≥ 35 kg/m2 and experiencing obesity-related health conditions or ≥ 40 or 45 kg/m2 is morbid obesity.
A BMI of ≥ 45 or 50 kg/m2 is super obesity.As Asian populations develop negative health consequences at a lower BMI than Caucasians, some nations have redefined obesity; Japan has defined obesity as any BMI greater than 25 kg/m2 while China uses a BMI of greater than 28 kg/m2.

Effects on health
Excessive body weight has a strong link to many diseases and conditions, particularly cardiovascular diseases, diabetes mellitus type 2, obstructive sleep apnea, certain types of cancer, osteoarthritis, and asthma. As a result, obesity has been found to reduce life expectancy.

Mortality
Obesity is one of the leading preventable causes of death worldwide. A number of reviews have found that mortality risk is lowest at a BMI of 20–25 kg/m2 in non-smokers and at 24–27 kg/m2 in current smokers, with risk increasing along with changes in either direction. This appears to apply in at least four continents. Other evidence suggests that the association of BMI and waist circumference with mortality is U- or J-shaped, while the association between waist-to-hip ratio and waist-to-height ratio with mortality is more positive. In Asians the risk of negative health effects begins to increase between 22 and 25 kg/m2. In 2021, the World Health Organization estimated that obesity caused at least 2.8 million deaths annually. On average, obesity reduces life expectancy by six to seven years, a BMI of 30–35 kg/m2 reduces life expectancy by two to four years, while severe obesity (BMI ≥ 40 kg/m2) reduces life expectancy by ten years.

Morbidity
Obesity increases the risk of many physical and mental conditions. These comorbidities are most commonly shown in metabolic syndrome, a combination of medical disorders which includes: diabetes mellitus type 2, high blood pressure, high blood cholesterol, and high triglyceride levels. A study from the RAK Hospital found that obese people are at a greater risk of developing long COVID. The CDC has found that obesity is the single strongest risk factor for severe COVID-19 illness.Complications are either directly caused by obesity or indirectly related through mechanisms sharing a common cause such as a poor diet or a sedentary lifestyle. The strength of the link between obesity and specific conditions varies. One of the strongest is the link with type 2 diabetes. Excess body fat underlies 64% of cases of diabetes in men and 77% of cases in women.Health consequences fall into two broad categories: those attributable to the effects of increased fat mass (such as osteoarthritis, obstructive sleep apnea, social stigmatization) and those due to the increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease). Increases in body fat alter the bodys response to insulin, potentially leading to insulin resistance. Increased fat also creates a proinflammatory state, and a prothrombotic state.

Metrics of health
Newer research has focused on methods of identifying healthier obese people by clinicians, and not treating obese people as a monolithic group. Obese people who do not experience medical complications from their obesity are sometimes called (metabolically) healthy obese, but the extent to which this group exists (especially among older people) is in dispute. The number of people considered metabolically healthy depends on the definition used, and there is no universally accepted definition. There are numerous obese people who have relatively few metabolic abnormalities, and a minority of obese people have no medical complications. The guidelines of the American Association of Clinical Endocrinologists call for physicians to use risk stratification with obese patients when considering how to assess their risk of developing type 2 diabetes.: 59–60 In 2014, the BioSHaRE–EU Healthy Obese Project (sponsored by Maelstrom Research, a team under the Research Institute of the McGill University Health Centre) came up with two definitions for healthy obesity, one more strict and one less so:
To come up with these criteria, BioSHaRE controlled for age and tobacco use, researching how both may effect the metabolic syndrome associated with obesity, but not found to exist in the metabolically healthy obese. Other definitions of metabolically healthy obesity exist, including ones based on waist circumference rather than BMI, which is unreliable in certain individuals.Another identification metric for health in obese people is calf strength, which is positively correlated with physical fitness in obese people. Body composition in general is hypothesized to help explain the existence of metabolically healthy obesity—the metabolically healthy obese are often found to have low amounts of ectopic fat (fat stored in tissues other than adipose tissue) despite having overall fat mass equivalent in weight to obese people with metabolic syndrome.: 1282

Survival paradox
Although the negative health consequences of obesity in the general population are well supported by the available evidence, health outcomes in certain subgroups seem to be improved at an increased BMI, a phenomenon known as the obesity survival paradox. The paradox was first described in 1999 in overweight and obese people undergoing hemodialysis, and has subsequently been found in those with heart failure and peripheral artery disease (PAD).In people with heart failure, those with a BMI between 30.0 and 34.9 had lower mortality than those with a normal weight. This has been attributed to the fact that people often lose weight as they become progressively more ill. Similar findings have been made in other types of heart disease. People with class I obesity and heart disease do not have greater rates of further heart problems than people of normal weight who also have heart disease. In people with greater degrees of obesity, however, the risk of further cardiovascular events is increased. Even after cardiac bypass surgery, no increase in mortality is seen in the overweight and obese. One study found that the improved survival could be explained by the more aggressive treatment obese people receive after a cardiac event. Another study found that if one takes into account chronic obstructive pulmonary disease (COPD) in those with PAD, the benefit of obesity no longer exists.

Causes
The "a calorie is a calorie" model of obesity posits a combination of excessive food energy intake and a lack of physical activity as the cause of most cases of obesity. A limited number of cases are due primarily to genetics, medical reasons, or psychiatric illness. In contrast, increasing rates of obesity at a societal level are felt to be due to an easily accessible and palatable diet, increased reliance on cars, and mechanized manufacturing.A 2006 review identified ten other possible contributors to the recent increase of obesity: (1) insufficient sleep, (2) endocrine disruptors (environmental pollutants that interfere with lipid metabolism), (3) decreased variability in ambient temperature, (4) decreased rates of smoking, because smoking suppresses appetite, (5) increased use of medications that can cause weight gain (e.g., atypical antipsychotics), (6) proportional increases in ethnic and age groups that tend to be heavier, (7) pregnancy at a later age (which may cause susceptibility to obesity in children), (8) epigenetic risk factors passed on generationally, (9) natural selection for higher BMI, and (10) assortative mating leading to increased concentration of obesity risk factors (this would increase the number of obese people by increasing population variance in weight). According to the Endocrine Society, there is "growing evidence suggesting that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight".

Diet
A 2016 review supported excess appetite for palatable, high-calorie food (especially fat, sugar, and certain animal proteins) as the primary factor driving obesity worldwide, likely because of imbalances in neurotransmitters affecting the drive to eat. Dietary energy supply per capita varies markedly between different regions and countries. It has also changed significantly over time. From the early 1970s to the late 1990s the average food energy available per person per day (the amount of food bought) increased in all parts of the world except Eastern Europe. The United States had the highest availability with 3,654 calories (15,290 kJ) per person in 1996. This increased further in 2003 to 3,754 calories (15,710 kJ). During the late 1990s, Europeans had 3,394 calories (14,200 kJ) per person, in the developing areas of Asia there were 2,648 calories (11,080 kJ) per person, and in sub-Saharan Africa people had 2,176 calories (9,100 kJ) per person. Total food energy consumption has been found to be related to obesity.The widespread availability of dietary guidelines has done little to address the problems of overeating and poor dietary choice. From 1971 to 2000, obesity rates in the United States increased from 14.5% to 30.9%. During the same period, an increase occurred in the average amount of food energy consumed. For women, the average increase was 335 calories (1,400 kJ) per day (1,542 calories (6,450 kJ) in 1971 and 1,877 calories (7,850 kJ) in 2004), while for men the average increase was 168 calories (700 kJ) per day (2,450 calories (10,300 kJ) in 1971 and 2,618 calories (10,950 kJ) in 2004). Most of this extra food energy came from an increase in carbohydrate consumption rather than fat consumption. The primary sources of these extra carbohydrates are sweetened beverages, which now account for almost 25 percent of daily food energy in young adults in America, and potato chips. Consumption of sweetened beverages such as soft drinks, fruit drinks, and iced tea is believed to be contributing to the rising rates of obesity and to an increased risk of metabolic syndrome and type 2 diabetes. Vitamin D deficiency is related to diseases associated with obesity.As societies become increasingly reliant on energy-dense, big-portions, and fast-food meals, the association between fast-food consumption and obesity becomes more concerning. In the United States, consumption of fast-food meals tripled and food energy intake from these meals quadrupled between 1977 and 1995.Agricultural policy and techniques in the United States and Europe have led to lower food prices. In the United States, subsidization of corn, soy, wheat, and rice through the U.S. farm bill has made the main sources of processed food cheap compared to fruits and vegetables. Calorie count laws and nutrition facts labels attempt to steer people toward making healthier food choices, including awareness of how much food energy is being consumed.
Obese people consistently under-report their food consumption as compared to people of normal weight. This is supported both by tests of people carried out in a calorimeter room and by direct observation.

Sedentary lifestyle
A sedentary lifestyle plays a significant role in obesity. Worldwide there has been a large shift towards less physically demanding work, and currently at least 30% of the worlds population gets insufficient exercise. This is primarily due to increasing use of mechanized transportation and a greater prevalence of labor-saving technology in the home. In children, there appear to be declines in levels of physical activity (with particularly strong declines in the amount of walking and physical education), likely due to safety concerns, changes in social interaction (such as fewer relationships with neighborhood children), and inadequate urban design (such as too few public spaces for safe physical activity). World trends in active leisure time physical activity are less clear. The World Health Organization indicates people worldwide are taking up less active recreational pursuits, while a study from Finland found an increase and a study from the United States found leisure-time physical activity has not changed significantly. A 2011 review of physical activity in children found that it may not be a significant contributor.In both children and adults, there is an association between television viewing time and the risk of obesity. A review found 63 of 73 studies (86%) showed an increased rate of childhood obesity with increased media exposure, with rates increasing proportionally to time spent watching television.

Genetics
Like many other medical conditions, obesity is the result of an interplay between genetic and environmental factors. Polymorphisms in various genes controlling appetite and metabolism predispose to obesity when sufficient food energy is present. As of 2006, more than 41 of these sites on the human genome have been linked to the development of obesity when a favorable environment is present. People with two copies of the FTO gene (fat mass and obesity associated gene) have been found on average to weigh 3–4 kg more and have a 1.67-fold greater risk of obesity compared with those without the risk allele. The differences in BMI between people that are due to genetics varies depending on the population examined from 6% to 85%.Obesity is a major feature in several syndromes, such as Prader–Willi syndrome, Bardet–Biedl syndrome, Cohen syndrome, and MOMO syndrome. (The term "non-syndromic obesity" is sometimes used to exclude these conditions.) In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single point DNA mutation.Studies that have focused on inheritance patterns rather than on specific genes have found that 80% of the offspring of two obese parents were also obese, in contrast to less than 10% of the offspring of two parents who were of normal weight. Different people exposed to the same environment have different risks of obesity due to their underlying genetics.The thrifty gene hypothesis postulates that, due to dietary scarcity during human evolution, people are prone to obesity. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would be more likely to survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This theory has received various criticisms, and other evolutionarily-based theories such as the drifty gene hypothesis and the thrifty phenotype hypothesis have also been proposed.

Other illnesses
Certain physical and mental illnesses and the pharmaceutical substances used to treat them can increase risk of obesity. Medical illnesses that increase obesity risk include several rare genetic syndromes (listed above) as well as some congenital or acquired conditions: hypothyroidism, Cushings syndrome, growth hormone deficiency, and some eating disorders such as binge eating disorder and night eating syndrome. However, obesity is not regarded as a psychiatric disorder, and therefore is not listed in the DSM-IVR as a psychiatric illness. The risk of overweight and obesity is higher in patients with psychiatric disorders than in persons without psychiatric disorders.Certain medications may cause weight gain or changes in body composition; these include insulin, sulfonylureas, thiazolidinediones, atypical antipsychotics, antidepressants, steroids, certain anticonvulsants (phenytoin and valproate), pizotifen, and some forms of hormonal contraception.

Social determinants
While genetic influences are important to understanding obesity, they cannot explain the current dramatic increase seen within specific countries or globally. Though it is accepted that energy consumption in excess of energy expenditure leads to increases in body weight on an individual basis, the cause of the shifts in these two factors on the societal scale is much debated. There are a number of theories as to the cause but most believe it is a combination of various factors.
The correlation between social class and BMI varies globally. A review in 1989 found that in developed countries women of a high social class were less likely to be obese. No significant differences were seen among men of different social classes. In the developing world, women, men, and children from high social classes had greater rates of obesity. An update of this review carried out in 2007 found the same relationships, but they were weaker. The decrease in strength of correlation was felt to be due to the effects of globalization. Among developed countries, levels of adult obesity, and percentage of teenage children who are overweight, are correlated with income inequality. A similar relationship is seen among US states: more adults, even in higher social classes, are obese in more unequal states.Many explanations have been put forth for associations between BMI and social class. It is thought that in developed countries, the wealthy are able to afford more nutritious food, they are under greater social pressure to remain slim, and have more opportunities along with greater expectations for physical fitness. In undeveloped countries the ability to afford food, high energy expenditure with physical labor, and cultural values favoring a larger body size are believed to contribute to the observed patterns. Attitudes toward body weight held by people in ones life may also play a role in obesity. A correlation in BMI changes over time has been found among friends, siblings, and spouses. Stress and perceived low social status appear to increase risk of obesity.Smoking has a significant effect on an individuals weight. Those who quit smoking gain an average of 4.4 kilograms (9.7 lb) for men and 5.0 kilograms (11.0 lb) for women over ten years. However, changing rates of smoking have had little effect on the overall rates of obesity.In the United States, the number of children a person has is related to their risk of obesity. A womans risk increases by 7% per child, while a mans risk increases by 4% per child. This could be partly explained by the fact that having dependent children decreases physical activity in Western parents.In the developing world urbanization is playing a role in increasing rate of obesity. In China overall rates of obesity are below 5%; however, in some cities rates of obesity are greater than 20%. In part, this may be because of urban design issues (such as inadequate public spaces for physical activity). Time spent in motor vehicles, as opposed to active transportation options such as cycling or walking, is correlated with increased risk of obesity.Malnutrition in early life is believed to play a role in the rising rates of obesity in the developing world. Endocrine changes that occur during periods of malnutrition may promote the storage of fat once more food energy becomes available.

Gut bacteria
The study of the effect of infectious agents on metabolism is still in its early stages. Gut flora has been shown to differ between lean and obese people. There is an indication that gut flora can affect the metabolic potential. This apparent alteration is believed to confer a greater capacity to harvest energy contributing to obesity. Whether these differences are the direct cause or the result of obesity has yet to be determined unequivocally. The use of antibiotics among children has also been associated with obesity later in life.An association between viruses and obesity has been found in humans and several different animal species. The amount that these associations may have contributed to the rising rate of obesity is yet to be determined.

Other factors
A number of reviews have found an association between short duration of sleep and obesity. Whether one causes the other is unclear. Even if short sleep does increase weight gain it is unclear if this is to a meaningful degree or if increasing sleep would be of benefit.Certain aspects of personality are associated with being obese. Loneliness, neuroticism, impulsivity, and sensitivity to reward are more common in people who are obese while conscientiousness and self-control are less common in people who are obese. Because most of the studies on this topic are questionnaire-based, it is possible that these findings overestimate the relationships between personality and obesity: people who are obese might be aware of the social stigma of obesity and their questionnaire responses might be biased accordingly. Similarly, the personalities of people who are obese as children might be influenced by obesity stigma, rather than these personality factors acting as risk factors for obesity.

Pathophysiology
Two distinct but related processes are considered to be involved in the development of obesity: sustained positive energy balance (energy intake exceeding energy expenditure) and the resetting of the body weight "set point" at an increased value. The second process explains why finding effective obesity treatments has been difficult. While the underlying biology of this process still remains uncertain, research is beginning to clarify the mechanisms.At a biological level, there are many possible pathophysiological mechanisms involved in the development and maintenance of obesity. This field of research had been almost unapproached until the leptin gene was discovered in 1994 by J. M. Friedmans laboratory. While leptin and ghrelin are produced peripherally, they control appetite through their actions on the central nervous system. In particular, they and other appetite-related hormones act on the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the melanocortin pathway being the most well understood. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brains feeding and satiety centers, respectively.The arcuate nucleus contains two distinct groups of neurons. The first group coexpresses neuropeptide Y (NPY) and agouti-related peptide (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH. The second group coexpresses pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and has stimulatory inputs to the VMH and inhibitory inputs to the LH. Consequently, NPY/AgRP neurons stimulate feeding and inhibit satiety, while POMC/CART neurons stimulate satiety and inhibit feeding. Both groups of arcuate nucleus neurons are regulated in part by leptin. Leptin inhibits the NPY/AgRP group while stimulating the POMC/CART group. Thus a deficiency in leptin signaling, either via leptin deficiency or leptin resistance, leads to overfeeding and may account for some genetic and acquired forms of obesity.

Public health
The World Health Organization (WHO) predicts that overweight and obesity may soon replace more traditional public health concerns such as undernutrition and infectious diseases as the most significant cause of poor health. Obesity is a public health and policy problem because of its prevalence, costs, and health effects. The United States Preventive Services Task Force recommends screening for all adults followed by behavioral interventions in those who are obese. Public health efforts seek to understand and correct the environmental factors responsible for the increasing prevalence of obesity in the population. Solutions look at changing the factors that cause excess food energy consumption and inhibit physical activity. Efforts include federally reimbursed meal programs in schools, limiting direct junk food marketing to children, and decreasing access to sugar-sweetened beverages in schools. The World Health Organization recommends the taxing of sugary drinks. When constructing urban environments, efforts have been made to increase access to parks and to develop pedestrian routes. There is low quality evidence that nutritional labelling with energy information on menus can help to reduce energy intake while dining in restaurants.

Reports
Many organizations have published reports pertaining to obesity. In 1998, the first US Federal guidelines were published, titled "Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report". In 2006, the Canadian Obesity Network, now known as Obesity Canada published the "Canadian Clinical Practice Guidelines (CPG) on the Management and Prevention of Obesity in Adults and Children". This is a comprehensive evidence-based guideline to address the management and prevention of overweight and obesity in adults and children.In 2004, the United Kingdom Royal College of Physicians, the Faculty of Public Health and the Royal College of Paediatrics and Child Health released the report "Storing up Problems", which highlighted the growing problem of obesity in the UK. The same year, the House of Commons Health Select Committee published its "most comprehensive inquiry [...] ever undertaken" into the impact of obesity on health and society in the UK and possible approaches to the problem. In 2006, the National Institute for Health and Clinical Excellence (NICE) issued a guideline on the diagnosis and management of obesity, as well as policy implications for non-healthcare organizations such as local councils. A 2007 report produced by Derek Wanless for the Kings Fund warned that unless further action was taken, obesity had the capacity to debilitate the National Health Service financially. In 2022 the National Institute for Health and Care Research (NIHR) published a comprehensive review of research on what local authorities can do to reduce obesity.The Obesity Policy Action (OPA) framework divides measure into upstream policies, midstream policies, and downstream policies. Upstream policies have to do with changing society, while midstream policies try to alter behaviors believed to contribute to obesity at the individual level, while downstream policies treat currently obese people.

Management
The main treatment for obesity consists of weight loss via lifestyle interventions, including prescribed diets and physical exercise. Although it is unclear what diets might support long-term weight loss, and although the effectiveness of low-calorie diets is debated, lifestyle changes that reduce calorie consumption or increase physical exercise over the long term also tend to produce some sustained weight loss, despite slow weight regain over time. Although 87% of participants in the National Weight Control Registry were able to maintain 10% body weight loss for 10 years, the most appropriate dietary approach for long term weight loss maintenance is still unknown. In the US, intensive behavioral interventions combining both dietary changes and exercise are recommended. Intermittent fasting has no additional benefit of weight loss compared to continuous energy restriction. Adherence is a more important factor in weight loss success than whatever kind of diet an individual undertakes.Several hypo-caloric diets are effective. In the short-term low carbohydrate diets appear better than low fat diets for weight loss. In the long term, however, all types of low-carbohydrate and low-fat diets appear equally beneficial. A 2014 review found that the heart disease and diabetes risks associated with different diets appear to be similar. Promotion of the Mediterranean diets among the obese may lower the risk of heart disease. Decreased intake of sweet drinks is also related to weight-loss. Success rates of long-term weight loss maintenance with lifestyle changes are low, ranging from 2–20%. Dietary and lifestyle changes are effective in limiting excessive weight gain in pregnancy and improve outcomes for both the mother and the child. Intensive behavioral counseling is recommended in those who are both obese and have other risk factors for heart disease.

Medical interventions
Five medications have evidence for long-term use orlistat, lorcaserin, liraglutide, phentermine–topiramate, and naltrexone–bupropion. They result in weight loss after one year ranged from 3.0 to 6.7 kg (6.6-14.8 lbs) over placebo. Orlistat, liraglutide, and naltrexone–bupropion are available in both the United States and Europe, phentermine–topiramate is available only in the United States. European regulatory authorities rejected lorcaserin and phentermine-topiramate, in part because of associations of heart valve problems with lorcaserin and more general heart and blood vessel problems with phentermine–topiramate. Lorcaserin was available in the United States and then removed from the market in 2020 due to its association with cancer. Orlistat use is associated with high rates of gastrointestinal side effects and concerns have been raised about negative effects on the kidneys. There is no information on how these drugs affect longer-term complications of obesity such as cardiovascular disease or death, however, liraglutide, when used for type 2 diabetes, does reduce cardiovascular events.The most effective treatment for obesity is bariatric surgery. The types of procedures include laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, vertical-sleeve gastrectomy, and biliopancreatic diversion. Surgery for severe obesity is associated with long-term weight loss, improvement in obesity-related conditions, and decreased overall mortality, however, improved metabolic health results from the weight loss, not the surgery. One study found a weight loss of between 14% and 25% (depending on the type of procedure performed) at 10 years, and a 29% reduction in all cause mortality when compared to standard weight loss measures. Complications occur in about 17% of cases and reoperation is needed in 7% of cases.

Epidemiology
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In earlier historical periods obesity was rare, and achievable only by a small elite, although already recognised as a problem for health. But as prosperity increased in the Early Modern period, it affected increasingly larger groups of the population. Prior to the 1970s, obesity was a relatively rare condition even in the wealthiest of nations, and when it did exist it tended to occur among the wealthy. Then, a confluence of events started to change the human condition. The average BMI of populations in first-world countries started to increase and, consequently, there was a rapid increase in the proportion of people overweight and obese.In 1997, the WHO formally recognized obesity as a global epidemic. As of 2008, the WHO estimates that at least 500 million adults (greater than 10%) are obese, with higher rates among women than men. The global prevalence of obesity more than doubled between 1980 and 2014. In 2014, more than 600 million adults were obese, equal to about 13 percent of the worlds adult population. The percentage of adults affected in the United States as of 2015–2016 is about 39.6% overall (37.9% of males and 41.1% of females).The rate of obesity also increases with age at least up to 50 or 60 years old and severe obesity in the United States, Australia, and Canada is increasing faster than the overall rate of obesity. The OECD has projected an increase in obesity rates until at least 2030, especially in the United States, Mexico and England with rates reaching 47%, 39% and 35%, respectively.Once considered a problem only of high-income countries, obesity rates are rising worldwide and affecting both the developed and developing world. These increases have been felt most dramatically in urban settings. The only remaining region of the world where obesity is not common is sub-Saharan Africa.

History
Etymology
Obesity is from the Latin obesitas, which means "stout, fat, or plump". Ēsus is the past participle of edere (to eat), with ob (over) added to it. The Oxford English Dictionary documents its first usage in 1611 by Randle Cotgrave.

Historical attitudes
Ancient Greek medicine recognizes obesity as a medical disorder, and records that the Ancient Egyptians saw it in the same way. Hippocrates wrote that "Corpulence is not only a disease itself, but the harbinger of others". The Indian surgeon Sushruta (6th century BCE) related obesity to diabetes and heart disorders. He recommended physical work to help cure it and its side effects. For most of human history mankind struggled with food scarcity. Obesity has thus historically been viewed as a sign of wealth and prosperity. It was common among high officials in Europe in the Middle Ages and the Renaissance as well as in Ancient East Asian civilizations. In the 17th century, English medical author Tobias Venner is credited with being one of the first to refer to the term as a societal disease in a published English language book.With the onset of the Industrial Revolution it was realized that the military and economic might of nations were dependent on both the body size and strength of their soldiers and workers. Increasing the average body mass index from what is now considered underweight to what is now the normal range played a significant role in the development of industrialized societies. Height and weight thus both increased through the 19th century in the developed world. During the 20th century, as populations reached their genetic potential for height, weight began increasing much more than height, resulting in obesity. In the 1950s increasing wealth in the developed world decreased child mortality, but as body weight increased heart and kidney disease became more common.
During this time period, insurance companies realized the connection between weight and life expectancy and increased premiums for the obese.Many cultures throughout history have viewed obesity as the result of a character flaw. The obesus or fat character in Ancient Greek comedy was a glutton and figure of mockery. During Christian times the food was viewed as a gateway to the sins of sloth and lust. In modern Western culture, excess weight is often regarded as unattractive, and obesity is commonly associated with various negative stereotypes. People of all ages can face social stigmatization, and may be targeted by bullies or shunned by their peers.Public perceptions in Western society regarding healthy body weight differ from those regarding the weight that is considered ideal  – and both have changed since the beginning of the 20th century. The weight that is viewed as an ideal has become lower since the 1920s. This is illustrated by the fact that the average height of Miss America pageant winners increased by 2% from 1922 to 1999, while their average weight decreased by 12%. On the other hand, peoples views concerning healthy weight have changed in the opposite direction. In Britain, the weight at which people considered themselves to be overweight was significantly higher in 2007 than in 1999. These changes are believed to be due to increasing rates of adiposity leading to increased acceptance of extra body fat as being normal.Obesity is still seen as a sign of wealth and well-being in many parts of Africa. This has become particularly common since the HIV epidemic began.

The arts
The first sculptural representations of the human body 20,000–35,000 years ago depict obese females. Some attribute the Venus figurines to the tendency to emphasize fertility while others feel they represent "fatness" in the people of the time. Corpulence is, however, absent in both Greek and Roman art, probably in keeping with their ideals regarding moderation. This continued through much of Christian European history, with only those of low socioeconomic status being depicted as obese.During the Renaissance some of the upper class began flaunting their large size, as can be seen in portraits of Henry VIII of England and Alessandro dal Borro. Rubens (1577–1640) regularly depicted heavyset women in his pictures, from which derives the term Rubenesque. These women, however, still maintained the "hourglass" shape with its relationship to fertility. During the 19th century, views on obesity changed in the Western world. After centuries of obesity being synonymous with wealth and social status, slimness began to be seen as the desirable standard. In his 1819 print, The Belle Alliance, or the Female Reformers of Blackburn!!!, artist George Cruikshank criticised the work of female reformers in Blackburn and used fatness as a means to portray them as unfeminine.

Society and culture
Economic impact
In addition to its health impacts, obesity leads to many problems including disadvantages in employment and increased business costs. These effects are felt by all levels of society from individuals, to corporations, to governments.
In 2005, the medical costs attributable to obesity in the US were an estimated $190.2 billion or 20.6% of all medical expenditures, while the cost of obesity in Canada was estimated at CA$2 billion in 1997 (2.4% of total health costs). The total annual direct cost of overweight and obesity in Australia in 2005 was A$21 billion. Overweight and obese Australians also received A$35.6 billion in government subsidies. The estimate range for annual expenditures on diet products is $40 billion to $100 billion in the US alone.The Lancet Commission on Obesity in 2019 called for a global treaty—modelled on the WHO Framework Convention on Tobacco Control—committing countries to address obesity and undernutrition, explicitly excluding the food industry from policy development. They estimate the global cost of obesity  $2 trillion a year, about or 2.8% of world GDP.Obesity prevention programs have been found to reduce the cost of treating obesity-related disease. However, the longer people live, the more medical costs they incur. Researchers, therefore, conclude that reducing obesity may improve the publics health, but it is unlikely to reduce overall health spending.

Obesity can lead to social stigmatization and disadvantages in employment. When compared to their normal weight counterparts, obese workers on average have higher rates of absenteeism from work and take more disability leave, thus increasing costs for employers and decreasing productivity. A study examining Duke University employees found that people with a BMI over 40 kg/m2 filed twice as many workers compensation claims as those whose BMI was 18.5–24.9 kg/m2. They also had more than 12 times as many lost work days. The most common injuries in this group were due to falls and lifting, thus affecting the lower extremities, wrists or hands, and backs. The Alabama State Employees Insurance Board approved a controversial plan to charge obese workers $25 a month for health insurance that would otherwise be free unless they take steps to lose weight and improve their health. These measures started in January 2010 and apply to those state workers whose BMI exceeds 35 kg/m2 and who fail to make improvements in their health after one year.Some research shows that obese people are less likely to be hired for a job and are less likely to be promoted. Obese people are also paid less than their non-obese counterparts for an equivalent job; obese women on average make 6% less and obese men make 3% less.Specific industries, such as the airline, healthcare and food industries, have special concerns. Due to rising rates of obesity, airlines face higher fuel costs and pressures to increase seating width. In 2000, the extra weight of obese passengers cost airlines US$275 million. The healthcare industry has had to invest in special facilities for handling severely obese patients, including special lifting equipment and bariatric ambulances. Costs for restaurants are increased by litigation accusing them of causing obesity. In 2005 the US Congress discussed legislation to prevent civil lawsuits against the food industry in relation to obesity; however, it did not become law.With the American Medical Associations 2013 classification of obesity as a chronic disease, it is thought that health insurance companies will more likely pay for obesity treatment, counseling and surgery, and the cost of research and development of fat treatment pills or gene therapy treatments should be more affordable if insurers help to subsidize their cost. The AMA classification is not legally binding, however, so health insurers still have the right to reject coverage for a treatment or procedure.In 2014, The European Court of Justice ruled that morbid obesity is a disability. The Court said that if an employees obesity prevents them from "full and effective participation of that person in professional life on an equal basis with other workers", then it shall be considered a disability and that firing someone on such grounds is discriminatory.

Size acceptance
The principal goal of the fat acceptance movement is to decrease discrimination against people who are overweight and obese. However, some in the movement are also attempting to challenge the established relationship between obesity and negative health outcomes.A number of organizations exist that promote the acceptance of obesity. They have increased in prominence in the latter half of the 20th century. The US-based National Association to Advance Fat Acceptance (NAAFA) was formed in 1969 and describes itself as a civil rights organization dedicated to ending size discrimination.The International Size Acceptance Association (ISAA) is a non-governmental organization (NGO) which was founded in 1997. It has more of a global orientation and describes its mission as promoting size acceptance and helping to end weight-based discrimination. These groups often argue for the recognition of obesity as a disability under the US Americans With Disabilities Act (ADA). The American legal system, however, has decided that the potential public health costs exceed the benefits of extending this anti-discrimination law to cover obesity.

Industry influence on research
In 2015, the New York Times published an article on the Global Energy Balance Network, a nonprofit founded in 2014 that advocated for people to focus on increasing exercise rather than reducing calorie intake to avoid obesity and to be healthy. The organization was founded with at least $1.5M in funding from the Coca-Cola Company, and the company has provided $4M in research funding to the two founding scientists Gregory A. Hand and Steven N. Blair since 2008.

Childhood obesity
The healthy BMI range varies with the age and sex of the child. Obesity in children and adolescents is defined as a BMI greater than the 95th percentile. The reference data that these percentiles are based on is from 1963 to 1994 and thus has not been affected by the recent increases in rates of obesity. Childhood obesity has reached epidemic proportions in the 21st century, with rising rates in both the developed and the developing world. Rates of obesity in Canadian boys have increased from 11% in the 1980s to over 30% in the 1990s, while during this same time period rates increased from 4 to 14% in Brazilian children. In the UK, there were 60% more obese children in 2005 compared to 1989. In the US, the percentage of overweight and obese children increased to 16% in 2008, a 300% increase over the prior 30 years.As with obesity in adults, many factors contribute to the rising rates of childhood obesity </s>