<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 Postpartum infections and can you explain it in depth? [/INST] Postpartum infections, also known as childbed fever and puerperal fever, are any bacterial infections of the female reproductive tract following childbirth or miscarriage. Signs and symptoms usually include a fever greater than 38.0 °C (100.4 °F), chills, lower abdominal pain, and possibly bad-smelling vaginal discharge. It usually occurs after the first 24 hours and within the first ten days following delivery.The most common infection is that of the uterus and surrounding tissues known as puerperal sepsis, postpartum metritis, or postpartum endometritis. Risk factors include Caesarean section (C-section), the presence of certain bacteria such as group B streptococcus in the vagina, premature rupture of membranes, multiple vaginal exams, manual removal of the placenta, and prolonged labour among others. Most infections involve a number of types of bacteria. Diagnosis is rarely helped by culturing of the vagina or blood. In those who do not improve, medical imaging may be required. Other causes of fever following delivery include breast engorgement, urinary tract infections, infections of an abdominal incision or an episiotomy, and atelectasis.Due to the risks following Caesarean section, it is recommended that all women receive a preventive dose of antibiotics such as ampicillin around the time of surgery. Treatment of established infections is with antibiotics, with most people improving in two to three days. In those with mild disease, oral antibiotics may be used; otherwise intravenous antibiotics are recommended. Common antibiotics include a combination of ampicillin and gentamicin following vaginal delivery or clindamycin and gentamicin in those who have had a C-section. In those who are not improving with appropriate treatment, other complications such as an abscess should be considered.In 2015, about 11.8 million maternal infections occurred. In the developed world about 1% to 2% develop uterine infections following vaginal delivery. This increases to 5% to 13% among those who have more difficult deliveries and 50% with C-sections before the use of preventive antibiotics. In 2015, these infections resulted in 17,900 deaths down from 34,000 deaths in 1990. They are the cause of about 10% of deaths around the time of pregnancy. The first known descriptions of the condition date back to at least the 5th century BCE in the writings of Hippocrates. These infections were a very common cause of death around the time of childbirth starting in at least the 18th century until the 1930s when antibiotics were introduced. In 1847, Hungarian physician Ignaz Semmelweiss decreased death from the disease in the First Obstetrical Clinic of Vienna from nearly 20% to 2% through the use of handwashing with calcium hypochlorite.

Signs and symptoms
Signs and symptoms usually include a fever greater than 38.0 °C (100.4 °F), chills, low abdominal pain, and possibly bad-smelling vaginal discharge. It usually occurs after the first 24 hours and within the first ten days following delivery.

Causes
After childbirth, a womans genital tract has a large bare surface, which is prone to infection. Infection may be limited to the cavity and wall of her uterus, or it may spread beyond to cause septicaemia (blood poisoning) or other illnesses, especially when her resistance has been lowered by long labour or severe bleeding. Puerperal infection is most common on the raw surface of the interior of the uterus after separation of the placenta (afterbirth), but pathogenic organisms may also affect lacerations of any part of the genital tract. By whatever portal, they can invade the bloodstream and lymph system to cause sepsis, cellulitis (inflammation of connective tissue), and pelvic or generalized peritonitis (inflammation of the abdominal lining). The severity of the illness depends on the virulence of the infecting organism, the resistance of the invaded tissues, and the general health of the woman. Organisms commonly producing this infection are Streptococcus pyogenes; staphylococci (inhabitants of the skin and of pimples, carbuncles, and many other pustular eruptions); the anaerobic streptococci, which flourish in devitalized tissues such as may be present after long and injurious labour and unskilled instrumental delivery; Escherichia coli and Clostridium perfringens (inhabitants of the lower bowel); and Clostridium tetani.

Risk factors
Causes (listed in order of decreasing frequency) include endometritis, urinary tract infection, pneumonia/atelectasis, wound infection, and septic pelvic thrombophlebitis. Septic risk factors for each condition are listed in order of the postpartum day (PPD) on which the condition generally occurs.

PPD 0: atelectasis risk factors include general anesthesia, cigarette smoking, and obstructive lung disease.
PPD 1–2: urinary tract infections risk factors include multiple catheterization during labor, multiple vaginal examinations during labor, and untreated bacteriuria.
PPD 2–3: endometritis ( the most common cause ) risk factors include emergency cesarean section, prolonged membrane rupture, prolonged labor, and multiple vaginal examinations during labor.
PPD 4–5: wound infection risk factors include emergency cesarean section, prolonged membrane rupture, prolonged labor, and multiple vaginal examinations during labor.
PPD 5–6: septic pelvic thrombophlebitis risk factors include emergency cesarean section, prolonged membrane rupture, prolonged labor, and diffuse difficult vaginal childbirth.
PPD 7–21: mastitis risk factors include nipple trauma from breastfeeding.

Diagnosis
Puerperal fever is diagnosed with:

A temperature rise above 38 °C (100.4 °F) maintained over 24 hours or recurring during the period from the end of the first to the end of the 10th day after childbirth or abortion. (ICD-10)
Oral temperature of 38 °C (100.4 °F) or more on any two of the first ten days postpartum. (USJCMW)Puerperal fever  (from the Latin puer, male child (boy)), is no longer favored as a diagnostic category. Instead, contemporary terminology specifies:
the specific target of infection: endometritis (inflammation of the inner lining of the uterus), metrophlebitis (inflammation of the veins of the uterus), and peritonitis (inflammation of the membrane lining of the abdomen).
the severity of the infection: less serious infection (contained multiplication of microbes) or possibly life-threatening sepsis (uncontrolled and uncontained multiplication of microbes throughout the blood stream).Endometritis is a polymicrobial infection.  It frequently includes organisms such as Ureaplasma, Streptococcus, Mycoplasma, and Bacteroides, and may also include organisms such as Gardnerella, Chlamydia, Lactobacillus, Escherichia, and Staphylococcus.

Differential diagnosis
A number of other conditions can cause fevers following delivery including: urinary tract infections, breast engorgement, atelectasis and surgical incisions, among others.

Management
Antibiotics have been used to prevent and treat these infections—however, the misuse of antibiotics is a serious problem for global health. It is recommended that guidelines be followed that outline when it is appropriate to give antibiotics and which antibiotics are most effective.Atelectasis: mild to moderate fever, no changes or mild rales on chest auscultation.Management: pulmonary exercises, ambulation (deep breathing and walking).
Urinary tract infection: high fever, malaise, costovertebral tenderness, positive urine culture.Management: antibiotics as per culture sensitivity (cephalosporine).
Endometritis: moderate fever, exquisite uterine tenderness, minimal abdominal findings.Management: multiple agent IV antibiotics to cover polymicrobial organisms: clindamycin, gentamicin, addition of ampicillin if no response, no cultures are necessary.
Wound infection: persistent spiking fever despite antibiotics, wound erythema or fluctuance, wound drainage.Management: antibiotics for cellulitis, open and drain wound, saline-soaked packing twice a day, secondary closure.
Septic pelvic thrombophlebitis: persistent wide fever swings despite antibiotics, usually normal abdominal or pelvic exams.Management: IV heparin for 7–10 days at rates sufficient to prolong the PTT to double the baseline values.
Mastitis: unilateral, localized erythema, edema, tenderness.Management: antibiotics for cellulitis, open and drain abscess if present.

Epidemiology
The number of cases of puerperal sepsis per year shows wide variations among published literature—this may be related to different definitions, recordings etc. Globally, bacterial infections are the cause of 10% of maternal deaths—this is more common in low income countries but is also a direct cause of maternal deaths in high-income countries.In the United States, puerperal infections are believed to occur in between 1% and 8% of all births. About three die from puerperal sepsis for every 100,000 births. The single most important risk factor is Caesarean section. The number of maternal deaths in the United States is about 13 in 100,000. They make up about 11% of pregnancy-related deaths in the United States.In the United Kingdom from 1985–2005, the number of direct deaths associated with genital tract sepsis per 100,000 pregnancies was 0.40–0.85. In 2003–2005, genital tract sepsis accounted for 14% of direct causes of maternal death.Puerperal infections in the 18th and 19th centuries affected, on average, 6 to 9 women in every 1,000 births, killing two to three of them with peritonitis or sepsis. It was the single most common cause of maternal mortality, accounting for about half of all deaths related to childbirth, and was second only to tuberculosis in killing women of childbearing age. A rough estimate is that about 250,000–500,000 died from puerperal fever in the 18th and 19th centuries in England and Wales alone.

History
Although it had been recognized from as early as the time of the Hippocratic corpus that women in childbed were prone to fevers, the distinct name, "puerperal fever" appears in historical records only from the early 18th century.The death rate for women giving birth decreased in the 20th century in developed countries. The decline may be partly attributed to improved environmental conditions, better obstetrical care, and the use of antibiotics. Another reason appears to be a lessening of the virulence or invasiveness of Streptococcus pyogenes. This organism is also the cause of scarlet fever, which over the same period had declined but has seen a rise in last decade worldwide especially in Asia with smaller outbreaks in US and Canada. UK had reported 12,906 cases between September 2015 and April 2016 which is the largest outbreak since 1969.

"The Doctors Plague"
From the 1600s through the mid-to-late 1800s, the majority of childbed fever cases were caused by the doctors themselves. With no knowledge of germs, doctors did not believe hand washing was needed.
Hospitals for childbirth became common in the 17th century in many European cities. These "lying-in" hospitals were established at a time when there was no knowledge of antisepsis or epidemiology, and women were subjected to crowding, frequent vaginal examinations, and the use of contaminated instruments, dressings, and bedding. It was common for a doctor to deliver one baby after another, without washing his hands or changing clothes between patients.
The first recorded epidemic of puerperal fever occurred at the Hôtel-Dieu de Paris in 1646. Hospitals throughout Europe and America consistently reported death rates between 20% to 25% of all women giving birth, punctuated by intermittent epidemics with up to 100% fatalities of women giving birth in childbirth wards.In the 1800s Ignaz Semmelweis noticed that women giving birth at home had a much lower incidence of childbed fever than those giving birth in the doctors maternity ward.  His investigation discovered that washing hands with an antiseptic, in this case a calcium hypochlorite solution, before a delivery reduced childbed fever fatalities by 90%. Publication of his findings was not well received by the medical profession. The idea conflicted both with the existing medical concepts and with the image doctors had of themselves. The scorn and ridicule of doctors was so extreme that Semmelweis moved from Vienna and, following a breakdown, was eventually committed to a mental asylum, where he died.Semmelweis was not the only doctor ignored after sounding a warning about this issue: in Treatise on the Epidemic of Puerperal Fever (1795), ex-naval surgeon and Aberdonian obstetrician Alexander Gordon (1752–1799) warned that the disease was transmitted from one case to another by midwives and doctors.  Gordon wrote, "It is a disagreeable declaration for me to mention, that I myself was the means of carrying the infection to a great number of women."Thomas Watson (1792–1882), Professor of Medicine at Kings College Hospital, London, wrote in 1842: "Wherever puerperal fever is rife, or when a practitioner has attended any one instance of it, he should use most diligent ablution." Watson recommended handwashing with chlorine solution and changes of clothing for obstetric attendants "to prevent the practitioner becoming a vehicle of contagion and death between one patient and another."

Hygienic measures
In 1843, Oliver Wendell Holmes Sr. published The Contagiousness of Puerperal Fever and controversially concluded that puerperal fever was frequently carried from patient to patient by physicians and nurses; he suggested that clean clothing and avoidance of autopsies by those aiding birth would prevent the spread of puerperal fever. Holmes quoted Dr. James Blundell as stating, "... in my own family, I had rather that those I esteemed the most should be delivered unaided, in a stable, by the mangerside, than that they should receive the best help, in the fairest apartment, but exposed to the vapors of this pitiless disease."Holmes conclusions were ridiculed by many contemporaries, including Charles Delucena Meigs, a well-known obstetrician, who stated, "Doctors are gentlemen, and gentlemens hands are clean." Richard Gordon states that Holmes exhortations "outraged obstetricians, particularly in Philadelphia". In those days, "surgeons operated in blood-stiffened frock coats—the stiffer the coat, the prouder the busy surgeon", "pus was as inseparable from surgery as blood", and "Cleanliness was next to prudishness". He quotes Sir Frederick Treves on that era: "There was no object in being clean.  Indeed, cleanliness was out of place.  It was considered to be finicking and affected.  An executioner might as well manicure his nails before chopping off a head".In 1844, Ignaz Semmelweis was appointed assistant lecturer in the First Obstetric Division of the Vienna General Hospital (Allgemeines Krankenhaus), where medical students received their training. Working without knowledge of Holmes essay, Semmelweis noticed his wards 16% mortality rate from fever was substantially higher than the 2% mortality rate in the Second Division, where midwifery students were trained. Semmelweis also noticed that puerperal fever was rare in women who gave birth before arriving at the hospital. Semmelweis noted that doctors in First Division performed autopsies each morning on women who had died the previous day, but the midwives were not required or allowed to perform such autopsies. He made the connection between autopsies and puerperal fever after a colleague, Jakob Kolletschka, died of sepsis after accidentally cutting his hand while performing an autopsy.
Semmelweis began experimenting with various cleansing agents and, from May 1847, ordered all doctors and students working in the First Division wash their hands in chlorinated lime solution before starting ward work, and later before each vaginal examination. The mortality rate from puerperal fever in the division fell from 18% in May 1847 to less than 3% in June–November of the same year.  While his results were extraordinary, he was treated with skepticism and ridicule (see Response to Semmelweis).
He did the same work in St. Rochus hospital in Pest, Hungary, and published his findings in 1860, but his discovery was again ignored.In 1935, Leonard Colebrook showed Prontosil was effective against haemolytic streptococcus and hence a cure for puerperal fever.

Notable cases
Elite status was no protection against postpartum infections, as the deaths of several English queens attest. Elizabeth of York, queen consort of Henry VII, died of puerperal fever one week after giving birth to a daughter, who also died. Her son Henry VIII had two wives who died this way, Jane Seymour and Catherine Parr.
Suzanne Barnard, mother of philosopher Jean-Jacques Rousseau, contracted childbed fever after giving birth to him and died nine days later. Her infant son was also in perilous health following the birth; the adult Rousseau later wrote that "I came into the world with so few signs of life that little hope was entertained of preserving me". He was nursed back to health by an aunt. French natural philosopher Émilie du Châtelet died in 1749. Mary Wollstonecraft, author of Vindication of the Rights of Woman, died ten days after giving birth to her second daughter, who grew up to write Frankenstein. Other notables include African-American poet Phillis Wheatley (1784), British housekeeping authority Isabella Beeton, and American author Jean Webster in 1916 died of puerperal fever.In Charles Dickens novel A Christmas Carol, it is implied that both Scrooges mother and younger sister perished from this condition, explaining the characters animosity towards his nephew Fred and also his poor relationship with his own father.

See also
Postpartum confinement, a traditional practice after childbirth

References
Further reading
Chaim W, Burstein E (August 2003). "Postpartum infection treatments: a review". Expert Opinion on Pharmacotherapy (review). 4 (8): 1297–313. doi:10.1517/14656566.4.8.1297. PMID 12877638 </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 Bifascicular block 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 Akinetopsia and can you explain it in depth? [/INST] Akinetopsia (Greek: a for "without", kine for "to move" and opsia for "seeing"), also known as cerebral akinetopsia or motion blindness, is a term introduced by Semir Zeki to describe an extremely rare neuropsychological disorder, having only been documented in a handful of medical cases, in which a patient cannot perceive motion in their visual field, despite being able to see stationary objects without issue. There are varying degrees of akinetopsia: from seeing motion as frames of a cinema reel to an inability to discriminate any motion. There is currently no effective treatment or cure for akinetopsia.

Signs and symptoms
Akinetopsia can be separated into two categories, "inconspicuous akinetopsia" or "gross akinetopsia", based on symptom severity and the amount the akinetopsia affects the patients quality of life.

Inconspicuous akinetopsia
Inconspicuous akinetopsia is often described by seeing motion as a cinema reel or a multiple exposure photograph. This is the most common kind of akinetopsia and many patients consider the stroboscopic vision as a nuisance. The akinetopsia often occurs with visual trailing (palinopsia), with afterimages being left at each frame of the motion. It is caused by prescription drugs, hallucinogen persisting perception disorder (HPPD), and persistent aura without infarction. The pathophysiology of akinetopsia palinopsia is not known, but it has been hypothesized to be due to inappropriate activation of physiological motion suppression mechanisms which are normally used to maintain visual stability during eye movements (e.g. saccadic suppression).

Gross akinetopsia
Gross akinetopsia is an extremely rare condition. Patients have profound motion blindness and struggle in performing the activities of daily living. Instead of seeing vision as a cinema reel, these patients have trouble perceiving gross motion. Most of what is known about this extremely rare condition was learned through the case study of one patient, LM. LM described pouring a cup of tea or coffee difficult "because the fluid appeared to be frozen, like a glacier". She did not know when to stop pouring, because she could not perceive the movement of the fluid rising. LM and other patients have also complained of having trouble following conversations, because lip movements and changing facial expressions were missed. LM stated she felt insecure when more than two people were walking around in a room: "people were suddenly here or there but I have not seen them moving". Movement is inferred by comparing the change in position of an object or person. LM and others have described crossing the street and driving cars to also be of great difficulty. LM started to train her hearing to estimate distance.A change in brain structure (typically lesions) disturbs the psychological process of understanding sensory information, in this case visual information. Disturbance of only visual motion is possible due to the anatomical separation of visual motion processing from other functions. Like akinetopsia, perception of color can also be selectively disturbed as in achromatopsia. There is an inability to see motion despite normal spatial acuity, flicker detection, stereo and color vision. Other intact functions include visual space perception and visual identification of shapes, objects, and faces. Besides simple perception, akinetopsia also disturbs visuomotor tasks, such as reaching for objects and catching objects. When doing tasks, feedback of ones own motion appears to be important.

Causes
Brain lesions
Akinetopsia may be an acquired deficit from lesions in the posterior side of the visual cortex. Lesions more often cause gross akinetopsia. The neurons of the middle temporal cortex respond to moving stimuli and hence the middle temporal cortex is the motion-processing area of the cerebral cortex. In the case of LM, the brain lesion was bilateral and symmetrical, and at the same time small enough not to affect other visual functions. Some unilateral lesions have been reported to impair motion perception as well. Akinetopsia through lesions is rare, because damage to the occipital lobe usually disturbs more than one visual function. Akinetopsia has also been reported as a result of traumatic brain injury.

Transcranial magnetic stimulation
Inconspicuous akinetopsia can be selectively and temporarily induced using transcranial magnetic stimulation (TMS) of area V5 of the visual cortex in healthy subjects. It is performed on a 1 cm² surface of the head, corresponding in position to area V5. With an 800-microsecond TMS pulse and a 28 ms stimulus at 11 degrees per second, V5 is incapacitated for about 20–30 ms. It is effective between −20 ms and +10 ms before and after onset of a moving visual stimulus. Inactivating V1 with TMS could induce some degree of akinetopsia 60–70 ms after the onset of the visual stimulus. TMS of V1 is not nearly as effective in inducing akinetopsia as TMS of V5.

Alzheimers disease
Besides memory problems, Alzheimers patients may have varying degrees of akinetopsia. This could contribute to their marked disorientation. While Pelak and Hoyt have recorded an Alzheimers case study, there has not been much research done on the subject yet.

Antidepressants
Inconspicuous akinetopsia can be triggered by high doses of certain antidepressants with vision returning to normal once the dosage is reduced.

Areas of visual perception
Two relevant visual areas for motion processing are V5 and V1. These areas are separated by their function in vision. A functional area is a set of neurons with common selectivity and stimulation of this area, specifically behavioral influences. There have been over 30 specialized processing areas found in the visual cortex.

V5
V5, also known as visual area MT (middle temporal), is located laterally and ventrally in the temporal lobe, near the intersection of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus. All of the neurons in V5 are motion selective, and most are directionally selective. Evidence of functional specialization of V5 was first found in primates. Patients with akinetopsia tend to have unilateral or bi-lateral damage to the V5.

V1
V1, also known as the primary visual cortex, is located in Brodmann area 17. V1 is known for its pre-processing capabilities of visual information; however, it is no longer considered the only perceptually effective gateway to the cortex. Motion information can reach V5 without passing through V1 and a return input from V5 to V1 is not required for seeing simple visual motion. Motion-related signals arrive at V1 (60–70 ms) and V5 (< 30 ms) at different times, with V5 acting independently of V1. Patients with blindsight have damage to V1, but because V5 is intact, they can still sense motion. Inactivating V1 limits motion vision, but does not stop it completely.

Ventral and dorsal streams
Another thought on visual brain organization is the theory of streams for spatial vision, the ventral stream for perception and the dorsal stream for action. Since LM has impairment in both perception and action (such as grasping and catching actions), it has been suggested that V5 provides input to both perception and action processing streams.

Case studies
Potzl and Redlichs patient
In 1911, Potzl and Redlich reported a 58-year-old female patient with bilateral damage to her posterior brain. She described motion as if the object remained stationary but appeared at different successive positions. Additionally, she also lost a significant amount of her visual field and had anomic aphasia.

Goldstein and Gelbs patient
In 1918, Goldstein and Gelb reported a 24-year-old male who suffered a gunshot wound in the posterior brain. The patient reported no impression of movement. He could state the new position of the object (left, right, up, down), but saw "nothing in between". While Goldestein and Gelb believed the patient had damaged the lateral and medial parts of the left occipital lobe, it was later indicated that both occipital lobes were probably affected, due to the bilateral, concentric loss of his visual field. He lost his visual field beyond a 30-degree eccentricity and could not identify visual objects by their proper names.

"LM"
Most of what is known about akinetopsia was learned from LM, a 43-year-old female admitted into the hospital October 1978 complaining of headache and vertigo. LM was diagnosed with thrombosis of the superior sagittal sinus which resulted in bilateral, symmetrical lesions posterior of the visual cortex. These lesions were verified by PET and MRI in 1994. LM had minimal motion perception that was preserved as perhaps a function of V1, as a function of a "higher" order visual cortical area, or some functional sparing of V5.LM found no effective treatment, so she learned to avoid conditions with multiple visual motion stimuli, i.e. by not looking at or fixating them. She developed very efficient coping strategies to do this and nevertheless lived her life. In addition, she estimated the distance of moving vehicles by means of sound detection in order to continue to cross the street.LM was tested in three areas against a 24-year-old female subject with normal vision:

Visual functions other than movement vision
LM had no evidence of a color discrimination deficit in either center or periphery of visual fields. Her recognition time for visual objects and words was slightly higher than the control, but not statistically significant. There was no restriction in her visual field and no scotoma.

Disturbance of movement vision
LMs impression of movement depended on the direction of the movement (horizontal vs vertical), the velocity, and whether she fixated in the center of the motion path or tracked the object with her eyes. Circular light targets were used as stimuli.In studies, LM reported some impression of horizontal movement at a speed of 14 degrees of her predetermined visual field per second (deg/s) while fixating in the middle of the motion path, with difficulty seeing motion both below and above this velocity. When allowed to track the moving spot, she had some horizontal movement vision up to 18 deg/s. For vertical movement, the patient could only see motion below 10 deg/s fixated or 13 deg/s when tracking the target. The patient described her perceptual experience for stimulus velocities higher than 18 and 13 deg/s, respectively as "one light spot left or right" or "one light spot up or down" and "sometimes at successive positions in between", but never as motion.

Motion in depth
To determine perception of motion in depth, studies were done in which the experimenter moved a black painted wooden cube on a tabletop either towards the patient or away in line of sight. After 20 trials at 3 or 6 deg/s, the patient had no clear impression of movement. However she knew the object had changed in position, she knew the size of the cube, and she could correctly judge the distance of the cube in relation to other nearby objects.

Inner and outer visual fields
Detection of movement in the inner and outer visual fields was tested. Within her inner visual field, LM could detect some motion, with horizontal motion more easily distinguished than vertical motion. In her peripheral visual field, the patient was never able to detect any direction of movement. LMs ability to judge velocities was also tested. LM underestimated velocities over 12 deg/s.

Motion aftereffect and Phi phenomenon
Motion aftereffect of vertical stripes moving in a horizontal direction and a rotating spiral were tested. She was able to detect motion in both patterns, but reported motion aftereffect in only 3 of the 10 trials for the stripes, and no effect for the rotating spiral. She also never reported any impression of motion in depth of the spiral. In Phi phenomenon two circular spots of light appear alternating. It appears that the spot moves from one location to the other. Under no combination of conditions did the patient report any apparent movement. She always reported two independent light spots.

Visually guided pursuit eye and finger movements
LM was to follow the path of a wire mounted onto a board with her right index finger. The test was performed under purely tactile (blindfolded), purely visual (glass over the board), or tactile-visual condition. The patient performed best in the purely tactile condition and very poorly in the visual condition. She did not benefit from the visual information in the tactile-visual condition either. The patient reported that the difficulty was between her finger and her eyes. She could not follow her finger with her eyes if she moved her finger too fast.

Additional experiments
In 1994, several other observations of LMs capabilities were made using a stimulus with a random distribution of light squares on a dark background that moved coherently. With this stimulus, LM could always determine the axis of motion (vertical, horizontal), but not always the direction. If a few static squares were added to the moving display, identification of direction fell to chance, but identification of the axis of motion was still accurate. If a few squares were moving opposite and orthogonal to the predominant direction, her performance on both direction and axis fell to chance. She was also unable to identify motion in oblique directions, such as 45, 135, 225, and 315 degrees, and always gave answers in cardinal directions, 0, 90, 180, and 270 degrees.

"TD"
In 2019, Heutink and colleagues described a 37-year old female patient (TD) with akinetopsia, who was admitted to Royal Dutch Visio, Centre of Expertise for blind and partially sighted people. TD suffered an ischaemic infarction of the occipitotemporal region in the right hemisphere and a smaller infarction in the left occipital hemisphere. MRI confirmed that the damaged brain areas contained area V5 in both hemispheres. TD experienced problems with perceiving visual motion and also reported that bright colours and sharp contrasts made her feel sick. TD also had problems perceiving objects that were more than ± 5 meters away from her. Although TD had some impairments of lower visual functions, these could not explain the problems she experienced with regard to motion perception. Neuropsychological assessment revealed no evidence of Balints Syndrome, hemispatial neglect or visual extinction, prosopagnosia or object agnosia. There was some evidence for impaired spatial processing. On several behavioural tests, TD showed a specific and selective impairment of motion perception that was comparable to LMs performance.TDs ability to determine the direction of movement was tested using a task in which small grey blocks all moved in the same direction with the same speed against a black background. The blocks could move in four directions: right to left, left to right, upward and downward. Speed of movement was varied from 2, 4.5, 9, 15 and 24 degrees per second. Speed and direction were varied randomly across trials. TD had perfect perception of motion direction at speed up to 9 degrees per second. When speed of targets was above 9 degrees per second, TDs performance dropped dramatically to 50% correct at a speed of 15 degrees per second and 0% correct at 24 degrees per second. When the blocks moved at 24 degrees per second, TD consistently reported the exact opposite direction of the actual movement.

Pelak and Hoyts Alzheimers patient
In 2000, a 70-year-old man presented with akinetopsia. He had stopped driving two years prior because he could no longer "see movement while driving". His wife noted that he could not judge the speed of another car or how far away it was </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 Biotin deficiency and can you explain it in depth? [/INST] Biotin deficiency is a nutritional disorder which can become serious, even fatal, if allowed to progress untreated. It can occur in people of any age, ancestry, or of either gender. Biotin is part of the B vitamin family. Biotin deficiency rarely occurs among healthy people because the daily requirement of biotin is low, many foods provide adequate amounts of it, intestinal bacteria synthesize small amounts of it, and the body effectively scavenges and recycles it in the kidneys during production of urine. However, deficiencies can be caused by consuming raw egg whites over a period of weeks to months. Egg whites contain high levels of avidin, a protein that binds biotin strongly. When cooked, avidin is partially denatured and binding to biotin is reduced. However one study showed that 30-40% of the avidin activity was still present in the white after frying or boiling.  Genetic disorders such as biotinidase deficiency, multiple carboxylase deficiency, and holocarboxylase synthetase deficiency can also lead to inborn or late-onset forms of biotin deficiency. In all cases – dietary, genetic, or otherwise – supplementation with biotin is the primary method of treatment.

Signs and symptoms
Rashes including red, patchy ones near the mouth (erythematous periorofacial macular rash)
Fine and brittle hair

Psychological
Hallucinations
Lethargy
Mild depression, which may progress to profound fatigue and, eventually, to somnolence
Generalized muscular pains (myalgia)
Paresthesias

Causes
Total parenteral nutrition without biotin supplementation: Several cases of biotin deficiency in patients receiving prolonged total parenteral nutrition (TPN) therapy without added biotin have been reported. Therefore, all patients receiving TPN must also receive biotin at the recommended daily dose, especially if TPN therapy is expected to last more than 1 week. All hospital pharmacies currently include biotin in TPN preparations.
Protein deficiency: A shortage of proteins involved in biotin homeostasis can cause biotin deficiency. The main problems involved in biotin homeostasis are HCS, BTD (biotinidase deficiency) and SMVT
Anticonvulsant therapy: Prolonged use of certain drugs (especially highly common prescription anti-seizure medications such as phenytoin, primidone, and carbamazepine), may lead to biotin deficiency; however, valproic acid therapy is less likely to cause this condition. Some anticonvulsants (antiepileptic drugs) inhibit biotin transport across the intestinal mucosa. Evidence suggests that these anticonvulsants accelerate biotin catabolism, which means that its necessary for people to take supplemental biotin, in addition to the usual minimum daily requirements, if theyre treated with anticonvulsant medication(s) that have been linked to biotin deficiency.
Severe malnourishment
Prolonged oral antibiotic therapy: Prolonged use of oral antibiotics has been associated with biotin deficiency. Alterations in the intestinal flora caused by the prolonged administration of antibiotics are presumed to be the basis for biotin deficiency.
Genetic mutation: Mikati et al. (2006) reported a case of partial biotinidase deficiency (plasma biotinidase level of 1.3 nm/min/mL) in a 7-month-old boy. The boy presented with perinatal distress followed by developmental delay, hypotonia, seizures, and infantile spasms without alopecia or dermatitis. The childs neurologic symptoms abated following biotin supplementation and antiepileptic drug therapy. DNA mutational analysis revealed that the child was homozygous for a novel E64K mutation and that his mother and father were heterozygous for the novel E64K mutation.

Potential causes
Smoking: Recent studies suggest that smoking can lead to marginal biotin deficiency because it speeds up biotin catabolism (especially in women).
Excessive alcohol consumption
Excessive consumption of antidiuretics or inadequate levels of antidiuretic hormone
Intestinal malabsorption caused by short bowel syndrome

Biochemistry
Biotin is a coenzyme for five carboxylases in the human body (propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and 2 forms of acetyl-CoA carboxylase.) Therefore, biotin is essential for amino acid catabolism, gluconeogenesis, and fatty acid metabolism. Biotin is also necessary for gene stability because it is covalently attached to histones. Biotinylated histones play a role in repression of transposable elements and some genes. Normally, the amount of biotin in the body is regulated by dietary intake, biotin transporters (monocarboxylate transporter 1 and sodium-dependent multivitamin transporter), peptidyl hydrolase biotinidase (BTD), and the protein ligase holocarboxylase synthetase. When any of these regulatory factors are inhibited, biotin deficiency could occur.

Diagnosis
The most reliable and commonly used methods for determining biotin status in the body are:

excretion of 3-hydroxyisovaleric acid and biotin in urine
activity of propionyl-CoA carboxylase in lymphocytes

Treatment
In the United States, biotin supplements are readily available without a prescription in amounts ranging from 300 to 10,000 micrograms (30 micrograms is identified as Adequate Intake).

Epidemiology
Since biotin is present in many foods at low concentrations, deficiency is rare except in locations where malnourishment is very common. Pregnancy, however, alters biotin catabolism and despite a regular biotin intake, half of the pregnant women in the U.S. are marginally biotin deficient.

See also
Biotinidase deficiency
Holocarboxylase synthetase deficiency
Multiple carboxylase deficiency

References
Possible references
Adhisivam B, Mahto D, Mahadevan S (March 2007). "Biotin responsive limb weakness". Indian Pediatr. 44 (3): 228–30. PMID 17413203.
Baykal T, Gokcay G, Gokdemir Y, Demir F, Seckin Y, Demirkol M, Jensen K, Wolf B (2005). "Asymptomatic adults and older siblings with biotinidase deficiency ascertained by family studies of index cases". J. Inherit. Metab. Dis. 28 (6): 903–12. doi:10.1007/s10545-005-0161-3. PMID 16435182. S2CID 22277450.
Boas MA (1927). "The Effect of Desiccation upon the Nutritive Properties of Egg-white". Biochem. J. 21 (3): 712–724.1. doi:10.1042/bj0210712. PMC 1251968. PMID 16743887.
Dobrowolski SF, Angeletti J, Banas RA, Naylor EW (February 2003). "Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency". Mol. Genet. Metab. 78 (2): 100–7. doi:10.1016/S1096-7192(02)00231-7. PMID 12618081.
Forbes GM, Forbes A (1997). "Micronutrient status in patients receiving home parenteral nutrition". Nutrition. 13 (11–12): 941–4. doi:10.1016/S0899-9007(97)00334-1. PMID 9433708.
Genc GA, Sivri-Kalkanoğlu HS, Dursun A, Aydin HI, Tokatli A, Sennaroglu L, Belgin E, Wolf B, Coşkun T (February 2007). "Audiologic findings in children with biotinidase deficiency in Turkey". Int. J. Pediatr. Otorhinolaryngol. 71 (2): 333–9. doi:10.1016/j.ijporl.2006.11.001. PMID 17161472.
González EC, Marrero N, Frómeta A, Herrera D, Castells E, Pérez PL (July 2006). "Qualitative colorimetric ultramicroassay for the detection of biotinidase deficiency in newborns". Clin. Chim. Acta. 369 (1): 35–9. doi:10.1016/j.cca.2006.01.009. PMID 16480705.
Hassan YI, Zempleni J (July 2006). "Epigenetic regulation of chromatin structure and gene function by biotin". J. Nutr. 136 (7): 1763–5. doi:10.1093/jn/136.7.1763. PMC 1479604. PMID 16772434.
Higuchi R, Mizukoshi M, Koyama H, Kitano N, Koike M (February 1998). "Intractable diaper dermatitis as an early sign of biotin deficiency". Acta Paediatr. 87 (2): 228–9. doi:10.1080/08035259850157732. PMID 9512215.
László A, Schuler EA, Sallay E, Endreffy E, Somogyi C, Várkonyi A, Havass Z, Jansen KP, Wolf B (2003). "Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies". J. Inherit. Metab. Dis. 26 (7): 693–8. doi:10.1023/B:BOLI.0000005622.89660.59. PMID 14707518. S2CID 12601233.
Mock DM (February 1999). "Biotin status: which are valid indicators and how do we know?". J. Nutr. 129 (2S Suppl): 498S–503S. doi:10.1093/jn/129.2.498S. PMID 10064317.
Mock DM (December 1991). "Skin manifestations of biotin deficiency". Semin Dermatol. 10 (4): 296–302. PMID 1764357.
Möslinger D, Mühl A, Suormala T, Baumgartner R, Stöckler-Ipsiroglu S (December 2003). "Molecular characterisation and neuropsychological outcome of 21 patients with profound biotinidase deficiency detected by newborn screening and family studies". Eur. J. Pediatr. 162 (Suppl 1): S46–9. doi:10.1007/s00431-003-1351-3. PMID 14628140. S2CID 6490712.
Neto EC, Schulte J, Rubim R, Lewis E, DeMari J, Castilhos C, Brites A, Giugliani R, Jensen KP, Wolf B (March 2004). "Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations". Braz. J. Med. Biol. Res. 37 (3): 295–9. doi:10.1590/S0100-879X2004000300001. PMID 15060693.
Schulpis KH, Gavrili S, Tjamouranis J, Karikas GA, Kapiki A, Costalos C (May 2003). "The effect of neonatal jaundice on biotinidase activity". Early Hum. Dev. 72 (1): 15–24. doi:10.1016/S0378-3782(02)00097-X. PMID 12706308.
Thompson, J, Manore M, Sheeshka J (2010). "Nutrients involved in energy metabolism and blood health".  In Bennett G, Swieg C,  et al. (eds.). Nutrition: A functional Approach. Toronto: Pearson Canada. p. 353. ISBN 9780321740212.
Velázquez A (1997). "Biotin deficiency in protein-energy malnutrition: implications for nutritional homeostasis and individuality". Nutrition. 13 (11–12): 991–2. doi:10.1016/S0899-9007(97)00345-6. PMID 9433719.
Weber P, Scholl S, Baumgartner ER (July 2004). "Outcome in patients with profound biotinidase deficiency: relevance of newborn screening". Dev Med Child Neurol. 46 (7): 481–4. doi:10.1111/j.1469-8749.2004.tb00509.x. PMID 15230462.
Welling DB (August 2007). "Long-term follow-up of hearing loss in biotinidase deficiency". J. Child Neurol. 22 (8): 1055. doi:10.1177/0883073807305789. PMID 17761663. S2CID 39911504.
Wiznitzer M, Bangert BA (July 2003). "Biotinidase deficiency: clinical and MRI findings consistent with myelopathy". Pediatr. Neurol. 29 (1): 56–8 </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 Systematized epidermal nevus 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 Pallister–Killian syndrome and can you explain it in depth? [/INST] The Pallister–Killian syndrome (PKS), also termed tetrasomy 12p mosaicism or the Pallister mosaic aneuploidy syndrome, is an extremely rare and severe genetic disorder. PKS is due to the presence of an extra and abnormal chromosome termed a small supernumerary marker chromosome (sSMC). sSMCs contain copies of genetic material from parts of virtually any other chromosome and, depending on the genetic material they carry, can cause various genetic disorders and neoplasms. The sSMC in PKS consists of multiple copies of the short (i.e. "p") arm of chromosome 12. Consequently, the multiple copies of the genetic material in the sSMC plus the two copies of this genetic material in the two normal chromosome 12s are overexpressed and thereby cause the syndrome. Due to a form of genetic mosaicism, however, individuals with PKS differ in the tissue distributions of their sSMC and therefore show different syndrome-related birth defects and disease severities. For example, individuals with the sSMC in their heart tissue are likely to have cardiac structural abnormalities while those without this sSMC localization have a structurally normal heart.PKS was first described by Philip Pallister in 1977 and further researched by Maria Teschler-Nicola and Wolfgang Killian in 1981.

Presentation
Individuals with PKS present prenatally or at birth with multiple birth defects. These defects include: brain atrophy, agenesis of the corpus callosum, polymicrogyria of the brain, and/or spot calcifications in the brains lateral sulcus; deafness and/or blindness; autonomic nervous system dysfunctions such as anhidrosis, hypohidrosis, and/or episodic spells of hyperventilation interspersed with breath-holding; symptoms of spinal cord malformations; profound or less commonly mild to severe intellectual disability; epileptic seizures; heart and/or anal defects; diaphragmatic hernias; marked muscle weakness; supernumerary nipples; abnormal facial features such as frontal bossing, high frontal hairline, balding around the temple and frontal areas, sparse eyebrows and lashes, hypertelorism, small and flat nose, full cheeks, long philtrum, large mouth with downturned corners, thin cupids bow-shaped upper lip, micrognathia (i.e. undersized jaw), disformed ears that are low-set, thick eyebrows, and/or prominent lips and chin; abnormal oral/dental features such as enlarged tongue, overgrowth of the alveolar ridge and/or gums, delayed teeth eruption, and/or missing or double teeth; patchy skin depigmentations; skeletal anomalies such as limb shortening, lymphedema, increased soft tissues in the extremities, short/broad palms and/or fingers, and/or clinodactyly of the fifth fingers or toes; excessive prenatal and birth weights followed by postnatal declines in growth rates; delayed closure of the anterior fontanel; and/or delayed puberty in males but not females.

Causes
PKS is caused by an sSMC that consists of two copies or, less commonly, four copies of the genetic material in the p arm of chromosome 12. Recent studies in two individuals with PKS found their sSMCs consisted specifically of genetic material located in a stretch of chromosome 12 s p arm starting at its band 11 and running to its end. This area, called the PKS critical region, contains three genes, ING4, CHD4, and MFAP5 (also termed the MAGP2 gene), which are candidates for contributing to the development of the syndrome.One suggested mechanism for the development of the sSMC in PKS involves three sequential events: 1) chromosome 12 suffers a nondisjunction, i.e. a failure of its homologous chromosomes or sister chromatids to separate properly during the second meiosis cell division that forms maternal eggs; 2) while most of the eggs with this nondisjunction die, a rare egg with the nondisjunction acquires a second structural aberration, isochromosome formation, that results in the creation of an extra chromosome consisting of copies of two or four p arms but no q arms of chromosome 12, i.e. the sSMC; and 3) the sSMC-containing egg, after being fertilized by a genetically normal sperm, develops into an offspring containing copies of this sSMC in some but not all cells, tissues, and/or organs consequently have some but not all of the defects associated with PKS. This mechanism applies only to female parents who are by far the most common originators of the sSMC in PKS. The mechanism explaining the few cases in which male parents form a sperm containing this sSMC has not yet been clearly formulated.

Diagnosis
Prenatal diagnosis
PKS is commonly diagnosed by detecting its causative sSMC as defined by identifying the overexpression of its genetic material. This method has detected the sSMC and therefore diagnosed a fetus as having PKS based on genomic analyses of fetal skin fibroblasts, placenta chorionic villi, cells isolated from the amniotic fluid, fibroblasts isolated from the fetuss umbilical cord, and cells isolated from the fetuss umbilical cord blood. PKS can also be diagnose using fetal ultasound imaging methods. Ultrasound imaging in PKS commonly find fetuses that are too large for their gestational age, contain polyhydramnios (excess amniotic fluid in their amniotic sacs), and have rhizomelic limbs (shortening of the proximal part of the limbs). Less commonly, the imaging evidences diaphragmatic hernias and/or various other major PKS structural malformations. In most cases, however, the ultrasound findings are not diagnostic of PKS. Furthermore, ultrasound diagnoses is best applied in the second or third pregnancy trimester when structural anomalies are more clearly defined and detectable.Because the prenatal diagnosis of PKS using the methods just cited is difficult, often indecisive, and/or best employed later in a womans pregnancy, prenatal cell-free DNA screening (cfDNA screening), also known as noninvasive prenatal screening, has been used to diagnose PKS. This method can diagnose PKS in 10 week and older fetuses. In cfDNA screening, DNA from a mothers blood is extracted and screened for the presence of specific chromosome abnormalities such as those associated with the Down syndrome, Patau syndrome (also termed trisomy 13), and Edwards syndrome (also termed trisomy 18). (Small amounts of a fetuss DNA escapes through the placenta to circulate in the mothers blood.) A genome-wide association study done in China used genome-wide cfDNA analyses to diagnose various chromosome-related disorders including PKS. The study scanned the DNA in the blood of 29,007 pregnant women and found three cases with abnormal amount of DNA originating from the entire p-arm of chromosome 12. All three cases were confirmed to have a fetus with PKS. Two of these cases were missed by chromosomal microarray analysis of the placenta and chorionic villi. However, the study did not define the rate of false negative cases, i.e. negative results in women actually carrying a fetus with PKS </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 Oculodentodigital dysplasia 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 Trench fever and can you explain it in depth? [/INST] Trench fever (also known as "five-day fever", "quintan fever" (Latin: febris quintana), and "urban trench fever") is a moderately serious disease transmitted by body lice. It infected armies in Flanders, France, Poland, Galicia, Italy, Salonika, Macedonia, Mesopotamia, Russia and Egypt in World War I. Three noted cases during WWI were the authors J. R. R. Tolkien, A. A. Milne, and C. S. Lewis. From 1915 to 1918 between one-fifth and one-third of all British troops reported ill had trench fever while about one-fifth of ill German and Austrian troops had the disease. The disease persists among the homeless. Outbreaks have been documented, for example, in Seattle and Baltimore in the United States among injection drug users and in Marseille, France, and Burundi.Trench fever is also called Wolhynia fever, shin bone fever, Meuse fever, His disease and His–Werner disease or Werner-His disease (after Wilhelm His Jr. and Heinrich Werner).
The disease is caused by the bacterium Bartonella quintana (older names: Rochalimea quintana, Rickettsia quintana), found in the stomach walls of the body louse. Bartonella quintana is closely related to Bartonella henselae, the agent of cat scratch fever and bacillary angiomatosis.

Signs and symptoms
The disease is classically a five-day fever of the relapsing type, rarely exhibiting a continuous course. The incubation period is relatively long, at about two weeks. The onset of symptoms is usually sudden, with high fever, severe headache, pain on moving the eyeballs, soreness of the muscles of the legs and back, and frequently hyperaesthesia of the shins. The initial fever is usually followed in a few days by a single, short rise but there may be many relapses between periods without fever. The most constant symptom is pain in the legs. Recovery takes a month or more. Lethal cases are rare, but in a few cases "the persistent fever might lead to heart failure". Aftereffects may include neurasthenia, cardiac disturbances and myalgia.

Pathophysiology
Bartonella quintana is transmitted by contamination of a skin abrasion or louse-bite wound with the faeces of an infected body louse (Pediculus humanus corporis). There have also been reports of an infected louse bite passing on the infection.

Diagnosis
Serological testing is typically used to obtain a definitive diagnosis. Most serological tests would succeed only after a certain period of time past the symptom onset (usually a week). The differential diagnosis list includes typhus, ehrlichiosis, leptospirosis, Lyme disease, and virus-caused exanthema (measles or rubella).

Treatment
The treatment of trench fever can vary from case to case, as the human body has the ability to rid itself of the disease without medical intervention. Some patients will require treatment, and others will not. For those who do require treatment, the best treatment comes by way of doxycycline in combination with gentamicin.  Chloramphenicol is an alternative medication recommended under circumstances that render use of tetracycline derivates undesirable, such as severe liver disease, kidney dysfunction, in children under nine years and in pregnant women. The medication is administered for seven to ten days.

Epidemiology
Trench fever is a vector borne disease in which humans are primarily the main hosts. The vector through which the disease is typically transmitted is referred to as the human body louse "Pediculus humanus humanus", which is better known as lice. The British Expeditionary Force Pyrexia of Unknown Origin Enquiry Sub-Committee concluded that the specific means by which the vector infected the host was louse waste entering the body through abraded skin. Although the disease is typically found in humans, the gram negative bacterium which induce the disease have been seen in mammals such as dogs, cats, and macaques in small numbers.Being that the vector of the disease is human body louse, it can be determined that the main risk factors for infection are mostly in relation to contracting body louse. Specifically, some risk factors include: body louse infestation, overcrowded and unhygienic conditions, body hygiene, war, famine, malnutrition, alcoholism, homelessness, and intravenous drug abuse.The identified risk factors directly correlate with the subpopulations of identified infected persons throughout the duration of the known disease. Historically, trench fever was found in young male soldiers of World War I, whereas in the 21st century the disease mostly has a prevalence in middle aged homeless men. This can be seen when looking at a 21st-century outbreak of the disease in Denver, Colorado, where researcher David McCormick and his colleagues came across the gram negative bacterium in 15% of the 241 homeless persons who were tested. Another study done in Marseille, France found the bacterium in 5.4% of the 930 homeless individuals they tested.

History
Trench fever was first described and reported by British major John Graham in June 1915. He reported symptoms such as dizziness, headaches, and pain in the shins and back </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 Pachygyria and can you explain it in depth? [/INST] Pachygyria (from the Greek "pachy" meaning "thick" or "fat" gyri) is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, the onset and severity depending on the severity of the cortical malformation. Infantile spasms are common in affected children, as is intractable epilepsy.

Presentation
The term pachygyria does not directly relate to a specific malformation but rather is used to generally describe physical characteristics of the brain in association with several neuronal migration disorders; most commonly disorders relating to varied degrees of lissencephaly.  Lissencephaly is present in 1 of 85,470 births and the life span of those affected is short as only a few survive past the age of 20.
Pachygyria is a condition identified by a type of cortical genetic malformation. Clinicians will subjectively determine the malformation based on the degree of malposition and the extent of thickened abnormal grey differentiation present.

Connections to epilepsy, lissencephaly, and subcortical band heterotopia
Various degrees of intensity and locations of epilepsy are associated with malformations of cortical development. Researchers suggest that approximately 40% of children diagnosed with drug-resistant epilepsy have some degree of cortical malformation.Lissencephaly (to which pachygyria is most closely linked) is associated with severe mental retardation, epilepsy, and motor disability. Two characteristics of lissencephaly include its absence of convolutions (agyria) and decreased presence of convolutions (pachygyria).   The types of seizures associated with lissencephaly include:

persisting spasms
focal seizures
tonic seizures
atypical seizures
atonic seizures Other possible symptoms of lissencephaly include telecanthus, estropia, hypertelorism, varying levels of mental retardation, cerebellar hypoplasia, corpus callosum aplasia, and decreased muscle tone and tendon reflexes.  Over 90% of children affected with lissencephaly have seizures.Patients with subcortical band heterotopia (another disorder associated with pachygyria) typically have milder symptoms and their cognitive function is closely linked to the thickness of the subcortical band and the degree of pachygyria present.

Causes
Pachygyria is caused by a breakdown in the fetal neuronal migration process due to genetic or possibly environmental influences.  The affected cerebral cortex will typically have only four developed layers instead of the normal six.
One of the best known and most common types of neuronal migration disorders is lissencephaly, a diffuse cortical malformation relating directly to agyria and pachygyria. Incomplete neuronal migration during the early fetal brain development is the precursor to lissencephaly.
Should neurons follow an abnormal migration during development possible cortical malformations include classical lissencephaly (as stated above) and subcortical band heterotopia with an agyria-pachygyria band spectrum.

Normal neuronal migration
Normal neuronal migration involves the development of six cortical layers, each one performing distinct functions.Normal cerebral development occurs in three dynamic and overlapping stages:
first stage: stem cells proliferate and differentiate into neurons or glial cells within the forebrain and the ventricular and subventricular zones lining the cerebral cavity;
in humans this stage lasts from gestational weeks 5-6 to 16-20;
second stage: migration away from the origin in a radial fashion along the glial fibers from the periventricular region of the ganglionic eminences towards the pial surface;
the generations settle into a pattern within the cortical plate during this stage;
in humans this stage lasts from gestational weeks 6-7 to 20-24;
third stage: apoptosis and synaptogenesis within the six cortical layers to develop correct cortical organization;
in humans this stage lasts from gestational week 16 until long after birth.Most types of incomplete neuronal migration to the cortex occur during the third and fourth gestational months. The abnormal migration of the neurons causes them to not reach their proper final destinations, which results in failure of the sulci and gyri to form.The stage of cortical development at which migration is arrested is directly related to the level of structural malposition.One of the most critical stages in brain development is when the post-mitotic neurons migrate from the ventricular zone to form the cortical plate. Migration arrested toward the latter part of development usually restricts the abnormal cell position to the cortex level.

Neuronal migration disorder caused by genetic mutations
Several genetic mutations have been isolated and linked to specific malformations of the cerebral cortex.  Genes shown to cause lissencephaly include both autosomal and X-linked genes.  Below, the mutations of LIS1 or DCX genes are discussed as they are most commonly linked to neuronal migration disorders including lissencephaly-pachygyria and subcortical band heterotopia.

LIS1
LIS1 is responsible for the autosomal form of lissencephaly.  Mutations of the LIS1 gene are associated with about 80% of those affected with lissencephaly.
LIS1 was the first human neuronal migration gene to be cloned.  It is responsible for encoding the alpha subunit of the intracellular Ib isoform of platelet-activating factor acetylhydrolase.  It is located on chromosome 17p13.3 and has 11 exons with a coding region of 1233bp.  LIS1 protein appears to interact with tubulin to suppress microtubule dynamics.  The protein is highly conserved and studies have shown that it participates in cytoplasmic dynein-mediated nucleokinesis, somal translocation, cell motility, mitosis, and chromosome segregation.  LIS1 encodes for a 45kDa protein called PAFAH1B1 that contains seven WD40 repeats required for proper neuronal migration.  The LIS1 gene encodes for a protein similar to the β subunit of G proteins responsible for degrading bioactive lipid platelet-activating factor (PAF).  This leads to theories that LIS1 might exert its effect on migration through microtubules.  Specific concentrations of PAF may be necessary for optimal neuronal migration by influencing cell morphology adhesion properties.  Studies have shown that addition of PAF or inhibition of platelet-activating factor acetylhydrolase (PAF-AH) decreases cerebellar granule cell migration in vitro.  Addition of PAF to hippocampal cells have shown growth cone collapse and neurite retraction.  LIS1 knockout homozygous null mice die during embryogenesis and heterozygous mice survive with delayed neuronal migration confirmed by in vitro and in vivo cell migration assays.
Most lissencephaly cases are associated with deletions of mutations of the LIS1 gene and the results are usually more severe in the posterior brain regions.One study showed that of an isolated group of patients with lissencephaly, 40% resulted from an LIS1 deletion and another 25% resulted from an intragenic mutation of the gene.  Patients with missense mutations tend to have less severe symptoms, pachygyria, and rare cases of subcortical band heterotopia.  Truncated (shortened) mutations of LIS1 tend to cause severe lissencephaly.

Doublecortin
Doublecortin (DCX or XLIS) mutations are responsible for X-linked disorders. While LIS1 mutations tend to cause severe malformations in the posterior brain, DCX mutations focus much of their destruction on anterior malformations and are linked to lissencephaly in males and subcortical band heterotopias in females.  Women with DCX mutations tend to have an anteriorly-predominant subcortical band heterotopia and pachygyria.  DCX was the first known gene causing X-linked lissencephaly and subcortical band heterotopia.  It is found on chromosome Xq22.3-q23 and has nine exons that code for 360 proteins.  DCX is expressed exclusively in the fetal brain.Spastic cerebral palsy is by far the most common type, occurring in 70% to 80% of all cases. Moreover, spastic CP accompanies one of the other types in 30% of all cases. People with this type are hypertonic and have a neuromuscular condition stemming from damage to the corticospinal tract or the motor cortex that affects the nervous systems ability to receive gamma amino butyric acid in the area(s) affected by the disability.Spastic CP is further classified by topography dependent on the region of the body affected; these include:
Spastic hemiplegia (one side being affected). Generally, injury to muscle-nerves controlled by the brains left side will cause a right body deficit, and vice versa. Typically, people that have spastic hemiplegia are the most ambulatory, although they generally have dynamic equinus on the affected side and are primarily prescribed ankle-foot orthoses to prevent said equinus.[11]
Spastic diplegia (the lower extremities are affected with little to no upper-body spasticity). The most common form of the spastic forms. Most people with spastic diplegia are fully ambulatory and have a scissors gait. Flexed knees and hips to varying degrees are common. Hip problems, dislocations, and in three-quarters of spastic diplegics, also strabismus (crossed eyes), can be present as well. In addition, these individuals are often nearsighted. The intelligence of a person with spastic diplegia is unaffected by the condition.
Spastic tetraplegia (all four limbs affected equally). People with spastic quadriplegia are the least likely to be able to walk, or if they can, to want to walk, because their muscles are too tight and it is too much effort to do so. Some children with quadriplegia also have hemiparetic tremors, an uncontrollable shaking that affects the limbs on one side of the body and impairs normal movement.
Occasionally, terms such as monoplegia, paraplegia, triplegia, and pentaplegia may also be used to refer to specific manifestations of the spasticity.

Pathogenesis
Pachygyria, lissencephaly (smooth brain), and polymicrogyria (multiple small gyri) are all the results of abnormal cell migration. The abnormal migration is typically associated with a disorganized cellular architecture, failure to form six layers of cortical neurons (a four-layer cortex is common), and functional problems. The abnormal formation of the brain may be associated with seizures, developmental delay, and mental dysfunctions.Normally, the brain cells begin to develop in the periventricular region (germinal matrix) and then migrate from medial to lateral, to form the cerebral cortex.

Diagnosis
Different imaging modalities are commonly used for diagnosis. While computed tomography (CT) provides higher spatial resolution imaging of the brain, cerebral cortex malformations are more easily visualized in vivo and classified using magnetic resonance imaging (MRI) which provides higher contrast imaging and better delineation of white and gray matter.Diffuse pachygyria (a mild form of lissencephaly) can be seen on an MRI as thickened cerebral cortices with few and large gyri and incomplete development of the Sylvian fissures.
severe epilepsy
reduced longevity
varying degrees of mental retardation
intractable epilepsy
spasticityCognitive ability correlates with the thickness of any subcortical band present and the degree of pachygyria.

Classifications
The degree of cerebral cortex malformation caused by genetic mutations is classified by the degree of malposition and the extent of faulty grey matter differentiation.Neuronal migration disorders are generally classified into three groups:

lissencephaly/subcortical band heterotopia
cobblestone
‘other’ heterotopias The ‘other’ types are associated with corpus callosum agenesis or cerebellar hypoplasia while the cobblestone lissencephalies are associated with eye and muscle disorders.Classical lissencephaly, also known as type I or generalized agyria-pachygyria, is a severe brain malformation of a smooth cerebral surface, abnormally thick (10-20mm) cortex with four layers, widespread neuronal heterotopia, enlarged ventricles, and agenesis or malformation of the corpus callosum. Classical lissencephaly can range from agyria to regional pachygyria and is usually present along with subcortical band heterotopia (known as ‘double cortex’ to describe the circumferential bands of heterotopic neurons located beneath the cortex). Subcortical band heterotopia is a malformation slightly different from lissencephaly that is now classified under the agyria-pachygyria-band spectrum because it consists of a gyral pattern consistent with broad convolutions and an increased cortical thickness.
The established classification scheme for lissencephaly is based on the severity (grades 1-6) and the gradient.
Grade 1: generalized agyria
Grade 2: variable degree of agyria
Grade 3: variable degree of pachygyria
Grade 4: generalized pachygyria
Grade 5: mixed pachygyria and subcortical band heterotopia
Grade 6: subcortical band heterotopia alone
Gradient ‘a’: from posterior to anterior gradient
Gradient ‘b’: from anterior to posterior gradient Grade 1 and Grade 4 are very rare </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 Ileus and can you explain it in depth? [/INST] Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction.
The word ileus is from Ancient Greek eileós (εἰλεός, "intestinal obstruction"). The term subileus refers to a partial obstruction.

Signs and symptoms
Symptoms of ileus include, but are not limited to:
moderate to severe, diffuse abdominal pain
constipation
abdominal distension
nausea/vomiting, especially after meals
vomiting of  bilious fluid
lack of bowel movement and/or flatulence
excessive belching

Cause
Decreased propulsive ability may be broadly classified as caused either by bowel obstruction or intestinal atony or paralysis. However, instances with symptoms and signs of a bowel obstruction occur, but with the absence of a mechanical obstruction, mainly in acute colonic pseudo-obstruction, Ogilvies syndrome.

Bowel obstruction
A bowel obstruction is generally a mechanical obstruction of the gastrointestinal tract.

Intestinal paralysis
Paralysis of the intestine is often termed paralytic ileus, in which the intestinal paralysis need not be complete, but it must be sufficient to prohibit the passage of food through the intestine and lead to intestinal blockage.  Paralytic ileus is a common side effect of some types of surgery, commonly called postsurgical ileus. It can also result from certain drugs and from various injuries and illnesses, such as acute pancreatitis. Paralytic ileus causes constipation and bloating. On listening to the abdomen with a stethoscope, no bowel sounds are heard because the bowel is inactive.A temporary paralysis of a portion of the intestines occurs typically after abdominal surgery. Since the intestinal content of this portion is unable to move forward, food or drink should be avoided until peristaltic sound is heard, by auscultation (use of a stethoscope) of the area where this portion lies. Intestinal atony or paralysis may be caused by inhibitory neural reflexes, inflammation or other implication of neurohumoral peptides.

Risk factors
gastrointestinal surgery or other GI procedures
electrolyte imbalance (Namely hypokalemia and hypercalcemia)
diabetic ketoacidosis (DKA), and other causes of metabolic acidosis
hypothyroidism
diabetes
medications (e.g. opioids or antimuscarinics)
severe illness (Inflammation with peritonitis)
spinal cord injury, those with injury above thoracic vertebrae 5 (T5) will have hypomotility problems within the bowel
acute intermittent porphyria

Treatment
Traditionally, nothing by mouth was considered to be mandatory in all cases, but gentle feeding by enteral feeding tube may help to restore motility by triggering the guts normal feedback signals, so this is the recommended management initially. When the patient has severe, persistent signs that motility is completely disrupted, nasogastric suction and parenteral nutrition may be required until passage is restored. In such cases, continuing aggressive enteral feeding causes a risk of perforating the gut.
Several options are available in the case of paralytic ileus </s>