<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 Rectal prolapse and can you explain it in depth? [/INST] A rectal prolapse occurs when walls of the rectum have prolapsed to such a degree that they protrude out of the anus and are visible outside the body. However, most researchers agree that there are 3 to 5 different types of rectal prolapse, depending on whether the prolapsed section is visible externally, and whether the full or only partial thickness of the rectal wall is involved.Rectal prolapse may occur without any symptoms, but depending upon the nature of the prolapse there may be mucous discharge (mucus coming from the anus), rectal bleeding, degrees of fecal incontinence and obstructed defecation symptoms.Rectal prolapse is generally more common in elderly women, although it may occur at any age and in either sex. It is very rarely life-threatening, but the symptoms can be debilitating if left untreated. Most external prolapse cases can be treated successfully, often with a surgical procedure. Internal prolapses are traditionally harder to treat and surgery may not be suitable for many patients.

Classification
The different kinds of rectal prolapse can be difficult to grasp, as different definitions are used and some recognize some subtypes and others do not. Essentially, rectal prolapses may be:
full thickness (complete), where all the layers of the rectal wall prolapse, or involve the mucosal layer only (partial)
external  if they protrude from the anus and are visible externally, or internal if they do not
circumferential, where the whole circumference of the rectal wall prolapse, or segmental if only parts of the circumference of the rectal wall prolapse
present at rest, or occurring during straining.External (complete) rectal prolapse (rectal procidentia, full thickness rectal prolapse, external rectal prolapse) is
a full thickness, circumferential, true intussusception of the rectal wall which protrudes from the anus and is visible externally.Internal rectal intussusception (occult rectal prolapse, internal procidentia) can be defined as a funnel shaped infolding of the upper rectal (or lower sigmoid) wall that can occur during defecation. This infolding is perhaps best visualised as folding a sock inside out, creating "a tube within a tube". Another definition is "where the rectum collapses but does not exit the anus". Many sources differentiate between internal rectal intussusception and mucosal prolapse, implying that the former is a full thickness prolapse of rectal wall. However, a publication by the American Society of Colon and Rectal Surgeons stated that internal rectal intussusception involved the mucosal and submucosal layers separating from the underlying muscularis mucosa layer attachments, resulting in the separated portion of rectal lining "sliding" down. This may signify that authors use the terms internal rectal prolapse and internal mucosal prolapse to describe the same phenomena.
Mucosal prolapse (partial rectal mucosal prolapse) refers to prolapse of the loosening of the submucosal attachments to the muscularis propria of the distal rectummucosal layer of the rectal wall. Most sources define mucosal prolapse as an external, segmental prolapse which is easily confused with prolapsed (3rd or 4th degree) hemorrhoids (piles). However, both internal mucosal prolapse (see below) and circumferential mucosal prolapse are described by some. Others do not consider mucosal prolapse a true form of rectal prolapse.Internal mucosal prolapse (rectal internal mucosal prolapse, RIMP) refers to prolapse of the mucosal layer of the rectal wall which does not protrude externally. There is some controversy surrounding this condition as to its relationship with hemorrhoidal disease, or whether it is a separate entity. The term "mucosal hemorrhoidal prolapse" is also used.Solitary rectal ulcer syndrome (SRUS, solitary rectal ulcer, SRU) occurs with internal rectal intussusception and is part of the spectrum of rectal prolapse conditions. It describes ulceration of the rectal lining caused by repeated frictional damage as the internal intussusception is forced into the anal canal during straining. SRUS can be considered a consequence of internal intussusception, which can be demonstrated in 94% of cases.
Mucosal prolapse syndrome (MPS) is recognized by some. It includes solitary rectal ulcer syndrome, rectal prolapse, proctitis cystica profunda, and inflammatory polyps. It is classified as a chronic benign inflammatory disorder.
Rectal prolapse and internal rectal intussusception has been classified according to the size of the prolapsed section of rectum, a function of rectal mobility from the sacrum and infolding of the rectum. This classification also takes into account sphincter relaxation:
Grade I: nonrelaxation of the sphincter mechanism (anismus)
Grade II: mild intussusception
Grade III: moderate intussusception
Grade IV: severe intussusception
Grade V: rectal prolapseRectal internal mucosal prolapse has been graded according to the level of descent of the intussusceptum, which was predictive of symptom severity:
first degree prolapse is detectable below the anorectal ring on straining
second degree when it reached the dentate line
third degree when it reached the anal verge
The most widely used classification of internal rectal prolapse is according to the height on the rectal/sigmoid wall from which they originate and by whether the intussusceptum remains within the rectum or extends into the anal canal. The height of intussusception from the anal canal is usually estimated by defecography.Recto-rectal (high) intussusception (intra-rectal intussusception) is where the intussusception starts in the rectum, does not protrude into the anal canal, but stays within the rectum. (i.e. the intussusceptum originates in the rectum and does not extend into the anal canal. The intussuscipiens includes rectal lumen distal to the intussusceptum only). These are usually intussusceptions that originate in the upper rectum or lower sigmoid.Recto-anal (low) intussusception (intra-anal intussusception) is where the intussusception starts in the rectum and protrudes into the anal canal (i.e. the intussusceptum originates in the rectum, and the intussuscipiens includes part of the anal canal)
An Anatomico-Functional Classification of internal rectal intussusception has been described, with the argument that other factors apart from the height of intussusception above the anal canal appear to be important to predict symptomology. The parameters of this classification are anatomic descent, diameter of intussuscepted bowel, associated rectal hyposensitivity and associated delayed colonic transit:

Type 1: Internal recto-rectal intussusception
Type 1W Wide lumen
Type 1N Narrowed lumen
Type 2: Internal recto-anal intussusception
Type 2W Wide Lumen
Type 2N Narrowed lumen
Type 2M Narrowed internal lumen with associated rectal hyposensitivity or early megarectum
Type 3: Internal-external recto-anal intussusception

Diagnosis
History
Patients may have associated gynecological conditions which may require multidisciplinary management. History of constipation is important because some of the operations may worsen constipation. Fecal incontinence may also influence the choice of management.

Physical examination
Rectal prolapse may be confused easily with prolapsing hemorrhoids. Mucosal prolapse also differs from prolapsing (3rd or 4th degree) hemorrhoids, where there is a segmental prolapse of the hemorrhoidal tissues at the 3, 7 and 11 oclock positions. Mucosal prolapse can be differentiated from a full thickness external rectal prolapse (a complete rectal prolapse) by the orientation of the folds (furrows) in the prolapsed section. In full thickness rectal prolapse, these folds run circumferential.  In mucosal prolapse, these folds are radially. The folds in mucosal prolapse are usually associated with internal hemorrhoids. Furthermore, in rectal prolapse, there is a sulcus present between the prolapsed bowel and the anal verge, whereas in hemorrhoidal disease there is no sulcus. Prolapsed, incarcerated hemorrhoids are extremely painful, whereas as long as a rectal prolapse is not strangulated, it gives little pain and is easy to reduce.The prolapse may be obvious, or it may require straining and squatting to produce it. The anus is usually patulous, (loose, open) and has reduced resting and squeeze pressures. Sometimes it is necessary to observe the patient while they strain on a toilet to see the prolapse happen (the perineum can be seen with a mirror or by placing an endoscope in the bowl of the toilet). A phosphate enema may need to be used to induce straining.The perianal skin may be macerated (softening and whitening of skin that is kept constantly wet) and show excoriation.

Proctoscopy/sigmoidoscopy/colonoscopy
These may reveal congestion and edema (swelling) of the distal rectal mucosa, and in 10-15% of cases there may be a solitary rectal ulcer on the anterior rectal wall. Localized inflammation or ulceration can be biopsied and may lead to a diagnosis of SRUS or colitis cystica profunda. Rarely, a neoplasm (tumour) may form on the leading edge of the intussusceptum. In addition, patients are frequently elderly and therefore have increased incidence of colorectal cancer. Full length colonoscopy is usually carried out in adults prior to any surgical intervention. These investigations may be used with contrast media (barium enema) which may show the associated mucosal abnormalities.

Videodefecography
This investigation is used to diagnose internal intussusception, or demonstrate a suspected external prolapse that could not be produced during the examination. It is usually not necessary with obvious external rectal prolapse. Defecography may demonstrate associated conditions like cystocele, vaginal vault prolapse or enterocele.

Colonic transit studies
Colonic transit studies may be used to rule out colonic inertia if there is a history of severe constipation. Continent prolapse patients with slow transit constipation, and who are fit for surgery may benefit from subtotal colectomy with rectopexy.

Anorectal manometry
This investigation objectively documents the functional status of the sphincters. However, the clinical significance of the findings are disputed by some. It may be used to assess for pelvic floor dyssenergia, (anismus is a contraindication for certain surgeries, e.g. STARR), and these patients may benefit from post-operative biofeedback therapy. Decreased squeeze and resting pressures are usually the findings, and this may predate the development of the prolapse. Resting tone is usually preserved in patients with mucosal prolapse. In patients with reduced resting pressure, levatorplasty may be combined with prolapse repair to further improve continence.

Anal electromyography/pudendal nerve testing
It may be used to evaluate incontinence, but there is disagreement about what relevance the results may show, as rarely do they mandate a change of surgical plan. There may be denervation of striated musculature on the electromyogram. Increased nerve conduction periods (nerve damage), this may be significant in predicting post-operative incontinence.

Complete rectal prolapse
Rectal prolapse is a "falling down" of the rectum so that it is visible externally. The appearance is of a reddened, proboscis-like object through the anal sphincters. Patients find the condition embarrassing. The symptoms can be socially debilitating without treatment, but it is rarely life-threatening.The true incidence of rectal prolapse is unknown, but it is thought to be uncommon. As most affected people are elderly, the condition is generally under-reported. It may occur at any age, even in children, but there is peak onset in the fourth and seventh decades. Women over 50 are six times more likely to develop rectal prolapse than men. It is rare in men over 45 and in women under 20. When males are affected, they tend to be young and report significant bowel function symptoms, especially obstructed defecation, or have a predisposing disorder (e.g., congenital anal atresia). When children are affected, they are usually under the age of 3.
35% of women with rectal prolapse have never had children, suggesting that pregnancy and labour are not significant factors. Anatomical differences such as the wider pelvic outlet in females may explain the skewed gender distribution.Associated conditions, especially in younger patients include autism, developmental delay syndromes and psychiatric conditions requiring several medications.

Signs and symptoms
Signs and symptoms include:

history of a protruding mass.
degrees of fecal incontinence, (50-80% of patients) which may simply present as a mucous discharge.
constipation (20-50% of patients) also described as tenesmus (a sensation of incomplete evacuation of stool) and obstructed defecation.
a feeling of bearing down.
rectal bleeding
diarrhea and erratic bowel habits.Initially, the mass may protrude through the anal canal only during defecation and straining, and spontaneously return afterwards. Later, the mass may have to be pushed back in following defecation. This may progress to a chronically prolapsed and severe condition, defined as spontaneous prolapse that is difficult to keep inside, and occurs with walking, prolonged standing, coughing or sneezing (Valsalva maneuvers). A chronically prolapsed rectal tissue may undergo pathological changes such as thickening, ulceration and bleeding.If the prolapse becomes trapped externally outside the anal sphincters, it may become strangulated and there is a risk of perforation.  This may require an urgent surgical operation if the prolapse cannot be manually reduced. Applying granulated sugar on the exposed rectal tissue can reduce the edema (swelling) and facilitate this.

Cause
The precise cause is unknown, and has been much debated. In 1912 Moschcowitz proposed that rectal prolapse was a sliding hernia through a pelvic fascial defect.This theory was based on the observation that rectal prolapse patients have a mobile and unsupported pelvic floor, and a hernia sac of peritoneum from the Pouch of Douglas and rectal wall can be seen.  Other adjacent structures can sometimes be seen in addition to the rectal prolapse. Although a pouch of Douglas hernia, originating in the cul de sac of Douglas, may protrude from the anus (via the anterior rectal wall), this is a different situation from rectal prolapse.
Shortly after the invention of defecography, In 1968 Broden and Snellman used cinedefecography to show that rectal prolapse begins as a circumferential intussusception of the rectum, which slowly increases over time. The leading edge of the intussusceptum may be located at 6–8 cm or at 15–18 cm from the anal verge. This proved an older theory from the 18th century by John Hunter and Albrecht von Haller that this condition is essentially a full-thickness rectal intussusception, beginning about 3 inches above the dentate line and protruding externally.Since most patients with rectal prolapse have a long history of constipation, it is thought that prolonged, excessive and repetitive straining during defecation may predispose to rectal prolapse. Since rectal prolapse itself causes functional obstruction, more straining may result from a small prolapse, with increasing damage to the anatomy. This excessive straining may be due to predisposing pelvic floor dysfunction (e.g. obstructed defecation) and anatomical factors:
Abnormally low descent of the peritoneum covering the anterior rectal wall
poor posterior rectal fixation, resulting in loss of posterior fixation of the rectum to the sacral curve
loss of the normal horizontal position of the rectum with lengthening (redundant rectosigmoid) and downward displacement of the sigmoid and rectum
long rectal mesentery
a deep cul-de-sac
levator diastasis
a patulous, weak anal sphincterSome authors question whether these abnormalities are the cause, or secondary to the prolapse. Other predisposing factors/associated conditions include:

pregnancy (although 35% of women who develop rectal prolapse are nulliparous) (have never given birth)
previous surgery (30-50% of females with the condition underwent previous gynecological surgery)
pelvic neuropathies and neurological disease
high gastrointestinal helminth loads (e.g. Whipworm)
COPD
cystic fibrosis The association with uterine prolapse (10-25%) and cystocele (35%) may suggest that there is some underlying abnormality of the pelvic floor that affects multiple pelvic organs. Proximal bilateral pudendal neuropathy has been demonstrated in patients with rectal prolapse who have fecal incontinence. This finding was shown to be absent in healthy subjects, and may be the cause of denervation-related atrophy of the external anal sphincter. Some authors suggest that pudendal nerve damage is the cause for pelvic floor and anal sphincter weakening, and may be the underlying cause of a spectrum of pelvic floor disorders.Sphincter function in rectal prolapse is almost always reduced. This may be the result of direct sphincter injury by chronic stretching of the prolapsing rectum. Alternatively, the intussuscepting rectum may lead to chronic stimulation of the rectoanal inhibitory reflex (RAIR - contraction of the external anal sphincter in response to stool in the rectum). The RAIR was shown to be absent or blunted. Squeeze (maximum voluntary contraction) pressures may be affected as well as the resting tone. This is most likely a denervation injury to the external anal sphincter.The assumed mechanism of fecal incontinence in rectal prolapse is by the chronic stretch and trauma to the anal sphincters and the presence of a direct conduit (the intussusceptum) connecting rectum to the external environment which is not guarded by the sphincters.The assumed mechanism of obstructed defecation is by disruption to the rectum and anal canals ability to contract and fully evacuate rectal contents. The intussusceptum itself may mechanically obstruct the rectoanal lumen, creating a blockage that straining, anismus and colonic dysmotility exacerbate.Some believe that internal rectal intussusception represents the initial form of a progressive spectrum of disorders the extreme of which is external rectal prolapse. The intermediary stages would be gradually increasing sizes of intussusception. However, internal intussusception rarely progresses to external rectal prolapse. The factors that result in a patient progressing from internal intussusception to a full thickness rectal prolapse remain unknown. Defecography studies demonstrated that degrees of internal intussusception are present in 40% of asymptomatic subjects, raising the possibility that it represents a normal variant in some, and may predispose patients to develop symptoms, or exacerbate other problems.

Treatment
Conservative
Surgery is thought to be the only option to potentially cure a complete rectal prolapse. For people with medical problems that make them unfit for surgery, and those who have minimal symptoms, conservative measures may be beneficial. Dietary adjustments, including increasing dietary fiber may be beneficial to reduce constipation, and thereby reduce straining. A bulk forming agent (e.g. psyllium) or stool softener can also reduce constipation.

Surgical
Surgery is often required to prevent further damage to the anal sphincters. The goals of surgery are to restore the normal anatomy and to minimize symptoms. There is no globally agreed consensus as to which procedures are more effective, and there have been over 50 different operations described.Surgical approaches in rectal prolapse can be either perineal or abdominal. A perineal approach (or trans-perineal) refers to surgical access to the rectum and sigmoid colon via an incision around the anus and perineum (the area between the genitals and the anus). Abdominal approach (trans-abdominal approach) involves the surgeon cutting into the abdomen and gaining surgical access to the pelvic cavity. Procedures for rectal prolapse may involve fixation of the bowel (rectopexy), or resection (a portion removed), or both. Trans-anal (endo-anal) procedures are also described where access to the internal rectum is gained through the anus itself.
Abdominal procedures are associated with lower risk of postoperative recurrence of the prolapse, compared with perineal procedures (6.1% vs 16.3% in patients who are younger than 65 years of age at the time of surgery).

Abdominal procedures
The abdominal approach carries a small risk of impotence in males (e.g. 1-2% in abdominal rectopexy). Abdominal operations may be open or laparoscopic (keyhole surgery).Laparoscopic procedures
Recovery time following laparoscopic surgery is shorter and less painful than following traditional abdominal surgery. Instead of opening the pelvic cavity with a wide incision (laparotomy), a laparoscope (a thin, lighted tube) and surgical instruments are inserted into the pelvic cavity via small incisions. Rectopexy and anterior resection have been performed laparoscopically with good results.

Perineal procedures
The perineal approach generally results in less post-operative pain and complications, and a reduced length of hospital stay. These procedures generally carry a higher recurrence rate and poorer functional outcome. The perineal procedures include perineal rectosigmoidectomy and Delorme repair. Elderly, or other medically high-risk patients are usually treated by perineal procedures,  as they can be performed under a regional anesthetic, or even local anesthetic with intravenous sedation, thus avoid the risks of a general anesthetic. Alternatively, perineal procedures may be selected to reduce risk of nerve damage, for example in young male patients for whom sexual dysfunction may be a major concern.Perineal rectosigmoidectomy
The goal of Perineal rectosigmoidectomy is to resect or remove the redundant bowel. This is done through the perineum. The lower rectum is anchored to the sacrum through fibrosis in order to prevent future prolapse. The full thickness of the rectal wall is incised at a level just above the dentate line. Redundant rectal and sigmoid wall is removed and the new edge of colon is reconnected (anastomosed) with the anal canal with stitches or staples. This procedure may be combined with levatorplasty, to tighten the pelvic muscles. A combined a perineal proctosigmoidectomy with anterior levatorplasty is also called an Altemeier procedure. Levatorplasty is performed to correct levator diastasis which is commonly associated with rectal prolapse. Perineal rectosigmoidectomy was first introduced by Mikulicz in 1899, and it remained the preferred treatment in Europe for many years. It was Popularized by Altemeier. The procedure is simple, safe and effective. Continence levatorplasty may enhance restoration of continence (2/3 of patients). Complications occur in less than 10% of cases, and include pelvic bleeding, pelvic abscess and anastomotic dehiscence (splitting apart of the stitches inside), bleeding or leak at a dehiscence Mortality is low. Recurrence rates are higher than for abdominal repair, 16-30%, but more recent studies give lower recurrence rates. Additional levatorplasty can reduce recurrence rates to 7%.Delorme Procedure
This is a modification of the perineal rectosigmoidectomy, differing in that only the mucosa and submucosa are excised from the prolapsed segment, rather than full thickness resection. The prolapse is exposed if it is not already present, and the mucosal and submucosal layers are stripped from the redundant length of bowel. The muscle layer that is left is plicated (folded) and placed as a buttress above the pelvic floor. The edges of the mucosal are then stitched back together. "Mucosal proctectomy" was first discussed by Delorme in 1900, now it is becoming more popular again as it has low morbidity and avoids an abdominal incision, while effectively repairing the prolapse. The procedure is ideally suited to those patients with full-thickness prolapse limited to partial circumference (e.g., anterior wall) or less-extensive prolapse (perineal rectosigmoidectomy may be difficult in this situation). Fecal incontinence is improved following surgery (40%–75% of patients). Post operatively, both mean resting and squeeze pressures were increased. Constipation is improved in 50% of cases, but often urgency and tenesmus are created. Complications, including infection, urinary retention, bleeding, anastomotic dehiscence (opening of the stitched edges inside), stricture (narrowing of the gut lumen), diarrhea, and fecal impaction occur in 6-32% of cases. Mortality occurs in 0–2.5% cases. There is a higher recurrence rate than abdominal approaches (7-26% cases).Anal encirclement (Thirsch procedure)
This procedure can be carried out under local anaesthetic. After reduction of the prolapse, a subcutaneous suture (a stich under the skin) or other material is placed encircling the anus, which is then made taut to prevent further prolapse. Placing silver wire around the anus first described by Thiersch in 1891. Materials used include nylon, silk, silastic rods, silicone, Marlex mesh, Mersilene mesh, fascia, tendon, and Dacron. This operation does not correct the prolapse itself, it merely supplements the anal sphincter, narrowing the anal canal with the aim of preventing the prolapse from becoming external, meaning it remains in the rectum. This goal is achieved in 54-100% cases. Complications include breakage of the encirclement material, fecal impaction, sepsis, and erosion into the skin or anal canal. Recurrence rates are higher than the other perineal procedures. This procedure is most often used for people who have a severe condition or who have a high risk of adverse effects from general anesthetic, and who may not tolerate other perineal procedures.

Internal rectal intussusception
Internal rectal intussusception (rectal intussusception, internal intussusception, internal rectal prolapse, occult rectal prolapse, internal rectal procidentia and rectal invagination) is a medical condition defined as a funnel shaped infolding of the rectal wall that can occur during defecation.This phenomenon was first described in the late 1960s when defecography was first developed and became widespread. Degrees of internal intussusception have been demonstrated in 40% of asymptomatic subjects, raising the possibility that it represents a normal variant in some, and may predispose patients to develop symptoms, or exacerbate other problems.

Symptoms
Internal intussusception may be asymptomatic, but common symptoms include:
Fecal leakage
Sensation of obstructed defecation (tenesmus).
Pelvic pain.
Rectal bleeding.Recto-rectal intussusceptions may be asymptomatic, apart from mild obstructed defecation. "interrupted defaecation" in the morning is thought by some to be characteristic.Recto-anal intussusceptions commonly give more severe symptoms of straining, incomplete evacuation, need for digital evacuation of stool, need for support of the perineum during defecation, urgency, frequency or intermittent fecal incontinence.It has been observed that intussusceptions of thickness ≥3 mm, and those that appear to cause obstruction to rectal evacuation may give clinical symptoms.

Cause
There are two schools of thought regarding the nature of internal intussusception, viz: whether it is a primary phenomenon, or secondary to (a consequence of) another condition.
Some believe that it represents the initial form of a progressive spectrum of disorders the extreme of which is external rectal prolapse. The intermediary stages would be gradually increasing sizes of intussusception. The folding section of rectum can cause repeated trauma to the mucosa, and can cause solitary rectal ulcer syndrome. However, internal intussusception rarely progress to external rectal prolapse.Others argue that the majority of patients appear to have rectal intussusception as a consequence of obstructed defecation rather than a cause, possibly related to excessive straining in patients with obstructed defecation. Patients with other causes of obstructed defecation (outlet obstruction) like anismus also tend to have higher incidence of internal intussusception. Enteroceles are coexistent in 11% of patients with internal intussusception. Symptoms of internal intussusception overlap with those of rectocele, indeed the 2 conditions can occur together.Patients with solitary rectal ulcer syndrome combined with internal intussusception (as 94% of SRUS patients have) were shown to have altered rectal wall biomechanics compared to patients with internal intussusception alone. The presumed mechanism of the obstructed defecation is by telescoping of the intussusceptum, occluding the rectal lumen during attempted defecation. One study analysed resected rectal wall specimens in patients with obstructed defecation associated with rectal intussusception undergoing stapled trans-anal rectal resection. They reported abnormalities of the enteric nervous system and estrogen receptors. One study concluded that intussusception of the anterior rectal wall shares the same cause as rectocele, namely deficient recto-vaginal ligamentous support.

Comorbidities and complications
The following conditions occur more commonly in patients with internal rectal intussusception than in the general population:

Rectocele
Solitary rectal ulcer syndrome.

Diagnosis
Unlike external rectal prolapse, internal rectal intussusception is not visible externally, but it may still be diagnosed by digital rectal examination, while the patient strains as if to defecate. Imaging such as a defecating proctogram or dynamic MRI defecography can demonstrate the abnormal folding of the rectal wall. Some have advocated the use of anorectal physiology testing (anorectal manometry).

Treatment
Non surgical measures to treat internal intussusception include pelvic floor retraining, a bulking agent (e.g. psyllium), suppositories or enemas to relieve constipation and straining. If there is incontinence (fecal leakage or more severe FI), or paradoxical contraction of the pelvic floor (anismus), then biofeedback retraining is indicated. Some researchers advise that internal intussusception be managed conservatively, compared to external rectal prolapse which usually requires surgery.As with external rectal prolapse, there are a great many different surgical interventions described. Generally, a section of rectal wall can be resected (removed), or the rectum can be fixed (rectopexy) to its original position against the sacral vertebrae, or a combination of both methods. Surgery for internal rectal prolapse can be via the abdominal approach or the transanal approach.It is clear that there is a wide spectrum of symptom severity, meaning that some patients may benefit from surgery and others may not. Many procedures receive conflicting reports of success, leading to a lack of any consensus about the best way to manage this problem. Relapse of the intussusception after treatment is a problem. Two of the most commonly employed procedures are discussed below.

laparoscopic ventral (mesh) rectopexy (LVR)
This procedure aims to "[correct] the descent of the posterior and middle pelvic compartments combined with reinforcement of the rectovaginal septum".Rectopexy has been shown to improve anal incontinence (fecal leakage) in patients with rectal intussusception. The operation has been shown to have low recurrence rate (around 5%). It also improves obstructed defecation symptoms.Complications include constipation, which is reduced if the technique does not use posterior rectal mobilization (freeing the rectum from its attached back surface).The advantage of the laparoscopic approach is decreased healing time and less complications.

Stapled trans-anal rectal resection (STARR)
This operation aims to "remove the anorectal mucosa circumferential and reinforce the anterior anorectal junction wall with the use of a circular stapler". In contrast to other methods, STARR does not correct the descent of the rectum, it removes the redundant tissue. The technique was developed from a similar stapling procedure for prolapsing hemorrhoids. Since, specialized circular staplers have been developed for use in external rectal prolapse and internal rectal intussusception.Complications, sometimes serious, have been reported following STARR,  but the procedure is now considered safe and effective. STARR is  contraindicated in patients with weak sphincters (fecal incontinence and urgency are a possible complication) and with anismus (paradoxical contraction of the pelvic floor during attempted defecation). The operation has been shown to improve rectal sensitivity and decrease rectal volume, the reason thought to create urgency. 90% of patients do not report urgency 12 months after the operation. The anal sphincter may also be stretched during the operation. STARR was compared with biofeedback and found to be more effective at reducing symptoms and improving quality of life.

Mucosal prolapse
Rectal mucosal prolapse (mucosal prolapse, anal mucosal prolapse) is a sub-type of rectal prolapse, and refers to abnormal descent of the rectal mucosa through the anus. It is different to an internal intussusception (occult prolapse) or a complete rectal prolapse (external prolapse, procidentia) because these conditions involve the full thickness of the rectal wall, rather than only the mucosa (lining).Mucosal prolapse is a different condition to prolapsing (3rd or 4th degree) hemorrhoids, although they may look similar.
Rectal mucosal prolapse can be a cause of obstructed defecation (outlet obstruction). and rectal malodor.

Symptoms
Symptom severity increases with the size of the prolapse, and whether it spontaneously reduces after defecation, requires manual reduction by the patient, or becomes irreducible. The symptoms are identical to advanced hemorrhoidal disease, and include:

Fecal leakage causing staining of undergarments
Rectal bleeding
Mucous rectal discharge
Rectal pain
Pruritus ani

Cause
The condition, along with complete rectal prolapse and internal rectal intussusception, is thought to be related to chronic straining during defecation and constipation.
Mucosal prolapse occurs when the results from loosening of the submucosal attachments (between the mucosal layer and the muscularis propria) of the distal rectum. The section of prolapsed rectal mucosa can become ulcerated, leading to bleeding.

Diagnosis
Mucosal prolapse can be differentiated from a full thickness external rectal prolapse (a complete rectal prolapse) by the orientation of the folds (furrows) in the prolapsed section. In full thickness rectal prolapse, these folds run circumferential. In mucosal prolapse, these folds are radially. The folds in mucosal prolapse are usually associated with internal hemorrhoids.

Treatment
EUA (examination under anesthesia) of anorectum and banding of the mucosa with rubber bands.

Solitary rectal ulcer syndrome and colitis cystica profunda
Solitary rectal ulcer syndrome (SRUS, SRU), is a disorder of the rectum and anal canal, caused by straining and increased pressure during defecation. This increased pressure causes the anterior portion of the rectal lining to be forced into the anal canal (an internal rectal intussusception). The lining of the rectum is repeatedly damaged by this friction, resulting in ulceration. SRUS can therefore be considered to be a consequence of internal intussusception (a sub type of rectal prolapse), which can be demonstrated in 94% of cases. It may be asymptomatic, but it can cause rectal pain, rectal bleeding, rectal malodor, incomplete evacuation and obstructed defecation (rectal outlet obstruction).

Symptoms
Symptoms include:
Straining during defecation
Mucous rectal discharge
Rectal bleeding
Sensation of incomplete evacuation (tenesmus)
constipation, or more rarely diarrhea
fecal incontinence (rarely)

Prevalence
The condition is thought to be uncommon. It usually occurs in young adults, but children can be affected too.

Cause
The essential cause of SRUS is thought to be related to too much straining during defecation.
Overactivity of the anal sphincter during defecation causes the patient to require more effort to expel stool. This pressure is produced by the modified valsalva manovoure (attempted forced exhalation against a closed glottis, resulting in increased abdominal and intra-rectal pressure). Patiest with SRUS were shown to have higher intra-rectal pressures when straining than healthy controls. SRUS is also associated with prolonged and incomplete evacuation of stool.More effort is required because of concomitant anismus, or non-relaxation/paradoxical contraction of puborectalis (which should normally relax during defecation). The increased pressure forces the anterior rectal lining against the contracted puborectalis and frequently the lining prolapses into the anal canal during straining and then returns to its normal position afterwards.
The repeated trapping of the lining can cause the tissue to become swollen and congested. Ulceration is thought to be caused by resulting poor blood supply (ischemia), combined with repeated frictional trauma from the prolapsing lining, and exposure to increased pressure are thought to cause ulceration. Trauma from hard stools may also contribute.
The site of the ulcer is typically on the anterior wall of the rectal ampulla, about 7–10 cm from the anus. However, the area may of ulceration may be closer to the anus, deeper inside, or on the lateral or posterior rectal walls. The name "solitary" can be misleading since there may be more than one ulcer present. Furthermore, there is a "preulcerative phase" where there is no ulcer at all.Pathological specimens of sections of rectal wall taken from SRUS patients show thickening and replacement of muscle with fibrous tissue and excess collagen. Rarely, SRUS can present as polyps in the rectum.SRUS is therefore associated and with internal, and more rarely, external rectal prolapse. Some believe that SRUS represents a spectrum of different diseases with different causes.Another condition associated with internal intussusception is colitis cystica profunda (also known as CCP, or proctitis cystica profunda), which is cystica profunda in the rectum. Cystica profunda is characterized by formation of mucin cysts in the muscle layers of the gut lining, and it can occur anywhere along the gastrointestinal tract. When it occurs in the rectum, some believe to be an interchangeable diagnosis with SRUS since the histologic features of the conditions overlap. Indeed, CCP is managed identically to SRUS.Electromyography may show pudendal nerve motor latency.

Complications
Complications are uncommon, but include massive rectal bleeding, ulceration into the prostate gland or formation of a stricture. Very rarely, cancer can arise on the section of prolapsed rectal lining.

Diagnosis and investigations
SRUS is commonly misdiagnosed, and the diagnosis is not made for 5–7 years. Clinicians may not be familiar with the condition, and treat for Inflammatory bowel disease, or simple constipation.The thickened lining or ulceration can also be mistaken for types of cancer.The differential diagnosis of SRUS (and CCP) includes:
polyps
endometriosis
inflammatory granulomas
infectious disorders
drug-induced colitis
mucus-producing adenocarcinomaDefecography, sigmoidoscopy,  transrectal ultrasound, mucosal biopsy, anorectal manometry and electromyography have all been used to diagnose and study SRUS. Some recommend biopsy as essential for diagnosis since ulcerations may not always be present, and others state defecography as the investigation of choice to diagnose SRUS.

Treatment
Although SRUS is not a medically serious disease, it can be the cause of significantly reduced quality of life for patients. It is difficult to treat, and treatment is aimed at minimizing symptoms.
Stopping straining during bowel movements, by use of correct posture, dietary fiber intake (possibly included bulk forming laxatives such as psyllium), stool softeners (e.g. polyethylene glycol, and biofeedback retraining to coordinate pelvic floor during defecation.Surgery may be considered, but only if non surgical treatment has failed and the symptoms are severe enough to warrant the intervention. Improvement with surgery is about 55-60%.Ulceration may persist even when symptoms resolve.

Mucosal prolapse syndrome
A group of conditions known as Mucosal prolapse syndrome (MPS) has now been recognized. It includes SRUS, rectal prolapse, proctitis cystica profunda, and inflammatory polyps. It is classified as a chronic benign inflammatory disorder. The unifying feature is varying degrees of rectal prolapse, whether internal intussusception (occult prolapse) or external prolapse.

Epidemiology
Rectal prolapse affects less than 0.5% of the general population. It affects women more commonly, with a female to male ratio of 9:1.

Pornography
Rosebud pornography and Prolapse pornography (or rosebudding or rectal prolapse pornography) is an anal sex practice that occurs in some extreme anal pornography wherein a pornographic actor or actress performs a rectal prolapse wherein the walls of the rectum slip out of the anus. Rectal prolapse is a serious medical condition that requires the attention of a medical professional. However, in rosebud pornography, it is performed deliberately. Michelle Lhooq, writing for VICE, argues that rosebudding is an example of producers making extreme content due to the easy availability of free pornography on the internet. She also argues that rosebudding is a way for pornographic actors and actresses to distinguish themselves. Repeated rectal prolapses can cause bowel problems and anal leakage and therefore risk the health of pornographic actors or actresses who participate in them. Lhooq also argues that some who participate in this form of pornography are unaware of the consequences.

Terminology
Prolapse refers to "the falling down or slipping of a body part from its usual position or relations". It is derived from the Latin pro- - "forward" + labi - "to slide". "Prolapse". Merriam-Webster Dictionary </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 Renal medullary carcinoma and can you explain it in depth? [/INST] Renal medullary carcinoma is a rare type of cancer that affects the kidney.  It tends to be aggressive, difficult to treat, and is often metastatic at the time of diagnosis.  Most individuals with this type of cancer have sickle cell trait or rarely sickle cell disease, suggesting that the sickle cell trait may be a risk factor for this type of cancer.

Signs and symptoms
In a case series of 34 patients, Davis and colleagues reported the following signs and symptoms:
macroscopically visible (gross) hematuria (60%)
abdominal or back/flank pain (50%)
significant weight loss (25%)Other researchers have reported a palpable renal mass or enlarged lymph nodes.

Causes
The etiology of renal medullary carcinoma is still not completely understood.  However, the majority of individuals diagnosed with this type of cancer have had sickle cell trait, in which the person carries one normal copy of the hemoglobin A gene (HbA) and one copy of the hemoglobin A gene harboring the genetic mutation found in sickle cell disease (HbS).  These individuals do not have sickle cell disease but can manifest symptoms such as kidney damage over the course of their lives.  The other genetic or environmental factors that contribute to the risk of renal medullary carcinoma are unknown.

Mechanism
The finding that virtually all people affected by renal medullary carcinoma carry at least one copy of the HbS mutation suggests that sickle cell trait somehow predisposes to this type of cancer. The precise mechanism is unknown, but red blood cells with a sickle cell configuration have been identified in pathology specimens.

Diagnosis
The diagnosis of renal medullary carcinoma is typically made after individuals with sickle cell trait present with the typical signs and symptoms outlined above, in combination with radiographic imaging (usually abdominal/pelvic CT scan) studies and ultimately surgical biopsy and pathological examination of the tumor.  Findings on radiographic examination are non-specific and can reveal a mass deep within the kidney. Histopathology studies show a distinctive pattern that can be distinguished from other renal tumors.

Classification
Renal medullary carcinoma has been termed "the seventh sickle cell nephropathy" because it is found almost exclusively in individuals with sickle cell trait or occasionally in those with sickle cell disease.

Prevention
Renal medullary carcinoma is extremely rare and it is not currently possible to predict those individuals with sickle cell trait who will eventually develop this cancer </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 Mees lines 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 Problem gambling and can you explain it in depth? [/INST] Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to DSM-5 if certain diagnostic criteria are met. Pathological gambling is a common disorder that is associated with both social and family costs.
The DSM-5 has re-classified the condition as an addictive disorder, with those affected exhibiting many similarities to those who have substance addictions.
The term gambling addiction has long been used in the recovery movement. Pathological gambling was long considered by the American Psychiatric Association to be an impulse-control disorder rather than an addiction. However, data suggest a closer relationship between pathological gambling and substance use disorders than exists between PG and obsessive-compulsive disorder, largely because the behaviors in problem gambling and most primary substance use disorders (i.e. those not resulting from a desire to "self-medicate" for another condition such as depression) seek to activate the brains reward mechanisms while the behaviors characterizing obsessive-compulsive disorder are prompted by overactive and misplaced signals from the brains fear mechanisms.Problem gambling is an addictive behavior with a high comorbidity with alcohol problems. A common tendency shared by people who have a gambling addiction is impulsivity.

Signs and symptoms
Research by governments in Australia led to a universal definition for that country which appears to be the only research-based definition not to use diagnostic criteria: "Problem gambling is characterized by many difficulties in limiting money and/or time spent on gambling which leads to adverse consequences for the gambler, others, or for the community." The University of Maryland Medical Center defines pathological gambling as "being unable to resist impulses to gamble, which can lead to severe personal or social consequences".Most other definitions of problem gambling can usually be simplified to any gambling that causes harm to the gambler or someone else in any way; however, these definitions are usually coupled with descriptions of the type of harm or the use of diagnostic criteria. The DSM-V has since reclassified pathological gambling as "gambling disorder" and has listed the disorder under substance-related and addictive disorders rather than impulse-control disorders. This is due to the symptomatology of the disorder resembling an addiction not dissimilar to that of a substance use disorder. In order to be diagnosed, an individual must have at least four of the following symptoms in a 12-month period:
Needs to gamble with increasing amounts of money in order to achieve the desired excitement
Is restless or irritable when attempting to cut down or stop gambling
Has made repeated unsuccessful efforts to control, cut back, or stop gambling
Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past gambling experiences, handicapping or planning the next venture, thinking of ways to get money with which to gamble)
Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed)
After losing money gambling, often returns another day to get even ("chasing" ones losses)
Lies to conceal the extent of involvement with gambling
Has jeopardized or lost a significant relationship, job, education, or career opportunity because of gambling
Relies on others to provide money to relieve desperate financial situations caused by gambling

Factors that lead to gambling addiction
Mayo Clinic specialists state that compulsive gambling may be result from biological, genetic, and environmental factors, such as:
mental health disorders (the presence of substance use disorders, personality disorders, emotional states)
age and sex (usually found in youth or middle-aged people, and more common to men than women)
impact on family or friends
personality traits
drugs with rare side-effects (for example, antipsychotic medications or dopamine agonists).Other studies add the following triggers to the mentioned above:
traumatic conditions
job-related stress
solitude
other addictionsIf not treated, problem gambling may cause very serious and lasting effects on an individuals life:
relationship related issues
problems with money, bankruptcy
legal problems, imprisonment
health problems
suicide, including suicidal thoughts and attempts

Suicide rates
A gambler who does not receive treatment for pathological gambling when in a desperation phase may contemplate suicide. Problem gambling is often associated with increased suicidal ideation and attempts compared to the general population.Early onset of problem gambling may increase lifetime risk of suicide. Both comorbid substance use and comorbid mental disorders increase the risk of suicide in people with problem gambling. A 2010 Australian hospital study found that 17% of suicidal patients admitted to the Alfred Hospitals emergency department were problem gamblers.

Mechanisms
Biology
According to the Illinois Institute for Addiction Recovery, evidence indicates that pathological gambling is an addiction similar to chemical addiction. It has been observed that some pathological gamblers have lower levels of norepinephrine than normal gamblers. According to a study conducted by Alec Roy, formerly at the National Institute on Alcohol Abuse and Alcoholism, norepinephrine is secreted under stress, arousal, or thrill, so pathological gamblers gamble to make up for their under-dosage.Studies have compared pathological gamblers to substance addicts, concluding that addicted gamblers display more physical symptoms during withdrawal.Deficiencies in serotonin might also contribute to compulsive behavior, including a gambling addiction. There are three important points discovered after these antidepressant studies:
Antidepressants can reduce pathological gambling in case when there is an effect on serotonergic reuptake inhibitors and 5-HT1/5-HT2 receptor antagonists.
Pathological gambling, as the part of obsessive-compulsive disorder, requires the higher doses of antidepressants as is usually required for depressive disorders.
In cases where participants do not have or have minimal symptoms of anxiety or depression, antidepressants still have those effect.A limited study was presented at a conference in Berlin, suggesting opioid release differs in problem gamblers from the general population, but in a very different way from people who have a substance use disorder.The findings in one review indicated the sensitization theory is responsible. Dopamine dysregulation syndrome has been observed in the aforementioned theory in people with regard to such activities as gambling.Some medical authors suggest that the biomedical model of problem gambling may be unhelpful because it focuses only on individuals. These authors point out that social factors may be a far more important determinant of gambling behavior than brain chemicals and they suggest that a social model may be more useful in understanding the issue. For example, an apparent increase in problem gambling in the UK may be better understood as a consequence of changes in legislation which came into force in 2007 and enabled casinos, bookmakers, and online betting sites to advertise on TV and radio for the first time and which eased restrictions on the opening of betting shops and online gambling sites.Pathological gambling is similar to many other impulse-control disorders such as kleptomania. According to evidence from both community- and clinic-based studies, individuals who are pathological gamblers are highly likely to exhibit other psychiatric problems concurrently, including substance use disorders, mood and anxiety disorders, or personality disorders.Pathological gambling shows several similarities with substance use disorders. There is a partial overlap in diagnostic criteria; pathological gamblers are also likely to have a substance use disorder. The "telescoping phenomenon" reflects the rapid development from initial to problematic behavior in women compared with men. This phenomenon was initially described for alcoholism, but it has also been applied to pathological gambling. Also biological data provide a support for a relationship between pathological gambling and substance use disorder. A comprehensive UK Gambling Commission study from 2018 has also hinted at the link between gambling addiction and a reduction in physical activity, poor diet and overall well-being. The study links problem gambling to a myriad of issues affecting relationships, and social stability.

Psychological
Several psychological mechanisms are thought to be implicated in the development and maintenance of problem gambling. First, reward processing seems to be less sensitive with problem gamblers. Second, some individuals use problem gambling as an escape from the problems in their lives (an example of negative reinforcement). Third, personality factors play a role, such as narcissism, risk-seeking, sensation-seeking, and impulsivity. Fourth, problem gamblers have a number of cognitive biases, including the illusion of control, unrealistic optimism, overconfidence and the gamblers fallacy (the incorrect belief that a series of random events tends to self-correct so that the absolute frequencies of each of various outcomes balance each other out). Fifth, problem gamblers represent a chronic state of a behavioral spin process, a gambling spin, as described by the criminal spin theory.Spains gambling watchdog has made an update to its 2019–2020 Responsible Gaming Program, classifying problem gambling as a mental disorder.

Diagnosis
The most common instrument used to screen for "probable pathological gambling" behavior is the South Oaks Gambling Screen (SOGS) developed by Lesieur and Blume (1987) at the South Oaks Hospital in New York City. In recent years the use of SOGS has declined due to a number of criticisms, including that it overestimates false positives (Battersby, Tolchard, Thomas & Esterman, 2002).
The DSM-IV diagnostic criteria presented as a checklist is an alternative to SOGS, it focuses on the psychological motivations underpinning problem gambling and was developed by the American Psychiatric Association. It consists of ten diagnostic criteria. One frequently used screening measure based upon the DSM-IV criteria is the National Opinion Research Center DSM Screen for Gambling Problems (NODS). The Canadian Problem Gambling Inventory (CPGI) and the Victorian Gambling Screen (VGS) are newer assessment measures. The Problem Gambling Severity Index, which focuses on the harms associated with problem gambling, is composed of nine items from the longer CPGI. The VGS is also harm based and includes 15 items. The VGS has proven validity and reliability in population studies as well as Adolescents and clinic gamblers.

Treatment
Most treatment for problem gambling involves counseling, step-based programs, self-help, peer-support, medication, or a combination of these. However, no one treatment is considered to be most efficacious and, in the United States, no medications have been approved for the treatment of pathological gambling by the U.S. Food and Drug Administration (FDA).
Gamblers Anonymous (GA) is a commonly used treatment for gambling problems. Modeled after Alcoholics Anonymous, GA is a twelve-step program that emphasizes a mutual-support approach. There are three in-patient treatment centers in North America. One form of counseling, cognitive behavioral therapy (CBT) has been shown to reduce symptoms and gambling-related urges. This type of therapy focuses on the identification of gambling-related thought processes, mood and cognitive distortions that increase ones vulnerability to out-of-control gambling. Additionally, CBT approaches frequently utilize skill-building techniques geared toward relapse prevention, assertiveness and gambling refusal, problem solving and reinforcement of gambling-inconsistent activities and interests.As to behavioral treatment, some recent research supports the use of both activity scheduling and desensitization in the treatment of gambling problems. In general, behavior analytic research in this area is growing There is evidence that the SSRI paroxetine is efficacious in the treatment of pathological gambling. Additionally, for patients with both pathological gambling and a comorbid bipolar spectrum condition, sustained-release lithium has shown efficacy in a preliminary trial. The opioid antagonist drug nalmefene has also been trialled quite successfully for the treatment of compulsive gambling. Group concepts based on CBT, such as the metacognitive training for problem gambling have also proven effective.

Step-based programs
12 Step-based programs such as Gamblers Anonymous are specific to gambling and generic to healing addiction, creating financial health, and improving mental wellness. Commercial alternatives that are designed for clinical intervention, using the best of health science and applied education practices, have been used as patient-centered tools for intervention since 2007. They include measured efficacy and resulting recovery metrics.

Motivational interviewing
Motivational interviewing is one of the treatments of compulsive gambling. The motivational interviewers basic goal is promoting readiness to change through thinking and resolving mixed feelings. Avoiding aggressive confrontation, argument, labeling, blaming, and direct persuasion, the interviewer supplies empathy and advice to compulsive gamblers who define their own goal. The focus is on promoting freedom of choice and encouraging confidence in the ability to change.

Peer support
A growing method of treatment is peer support. With the advancement of online gambling, many gamblers experiencing issues use various online peer-support groups to aid their recovery. This protects their anonymity while allowing them to attempt recovery on their own, often without having to disclose their issues to loved ones.

Self-help
Research into self-help for problem gamblers has shown benefits. A study by Wendy Slutske of the University of Missouri concluded one-third of pathological gamblers overcome it by natural recovery.

Anti-addiction drugs
Self-exclusion
Gambling self-exclusion (voluntary exclusion) programs are available in the US, the UK, Canada, Australia, South Africa, France, and other countries. They seem to help some (but not all) problem gamblers to gamble less often.Some experts maintain that casinos in general arrange for self-exclusion programs as a public relations measure without actually helping many of those with problem gambling issues. A campaign of this type merely "deflects attention away from problematic products and industries", according to Natasha Dow Schull, a cultural anthropologist at New York University and author of the book Addiction by Design.There is also a question as to the effectiveness of such programs, which can be difficult to enforce. In the province of Ontario, Canada, for example, the Self-Exclusion program operated by the governments Ontario Lottery and Gaming Corporation (OLG) is not effective, according to investigation conducted by the television series, revealed in late 2017. |"Gambling addicts ... said that while on the ... self-exclusion list, they entered OLG properties on a regular basis" in spite of the facial recognition technology in place at the casinos, according to the Canadian Broadcasting Corporation. As well, a CBC journalist who tested the system found that he was able to enter Ontario casinos and gamble on four distinct occasions, in spite of having been registered and photographed for the self-exclusion program. An OLG spokesman provided this response when questioned by the CBC: "We provide supports to self-excluders by training our staff, by providing disincentives, by providing facial recognition, by providing our security officers to look for players. No one element is going to be foolproof because it is not designed to be foolproof".

Impact (Australia)
According to the Productivity Commissions 2010 final report into gambling, the social cost of problem gambling is close to 4.7 billion dollars a year. Some of the harms resulting from problem gambling include depression, suicide, lower work productivity, job loss, relationship breakdown, crime and bankruptcy. A survey conducted in 2008 found that the most common motivation for fraud was problem gambling, with each incident averaging a loss of $1.1 million. According to Darren R. Christensen. Nicki A. Dowling, Alun C. Jackson and Shane A.Thomas a survey done from 1994 to 2008 in Tasmania gave results that gambling participation rates have risen rather than fallen over this period.

Prevalence
Europe
In Europe, the rate of problem gambling is typically 0.5 to 3 percent. The "British Gambling Prevalence Survey 2007", conducted by the United Kingdom Gambling Commission, found approximately 0.6 percent of the adult population had problem gambling issues—the same percentage as in 1999. The highest prevalence of problem gambling was found among those who participated in spread betting (14.7%), fixed odds betting terminals (11.2%), and betting exchanges (9.8%). In Norway, a December 2007 study showed the amount of current problem gamblers was 0.7 percent.With gambling addiction on the rise worldwide and across Europe in particular, those calling gambling a disease have been gaining grounds. The UK Gambling Commission announced a significant shift in their approach to gambling through their reclassification of gambling as a disease, and therefore, it should be addressed adequately by the NHS.
The World Health Organization has also classified gambling a disease. In its 72nd World Health Assembly held on Saturday, May 25, 2019, ‘gaming disorder’ was recognized as an official illness. The 194-member meet added excessive gaming to a classified list of diseases as it revised its International Statistical Classification of Diseases and Related Health Problems (ICD-11).

North America
In the United States, the percentage of pathological gamblers was 0.6 percent, and the percentage of problem gamblers was 2.3 percent in 2008. Studies commissioned by the National Gambling Impact Study Commission Act has shown the prevalence rate ranges from 0.1 percent to 0.6 percent. Nevada has the highest percentage of pathological gambling; a 2002 report estimated 2.2 to 3.6 percent of Nevada residents over the age of 18 could be called problem gamblers. Also, 2.7 to 4.3 percent could be called probable pathological gamblers.According to a 1997 meta-analysis by Harvard Medical Schools division on addictions, 1.1 percent of the adult population of the United States and Canada could be called pathological gamblers </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 Naxos syndrome 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 Amish lethal microcephaly 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 Webbed neck 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 Fibrocystic breast changes and can you explain it in depth? [/INST] Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle due to hormonal stimulation. These are normal breast changes, not associated with cancer.Risk factors include an early age at first menstrual period and either having children at a late age or not at all. It is not a disease but represents normal breast changes. Diagnosis involves ruling out breast cancer. Fibrocystic changes include fibroadenomas, fibrosis, and papillomas of the breast.Management may involve education about the condition, using a well fitting bra, and pain medication, if needed. Occasionally danazol or tamoxifen may be used for pain. It is estimated that up to 60% of women are affected. Most commonly between the ages of 30 and 50 years.

Signs and symptoms
The changes in fibrocystic breast disease are characterised by the appearance of fibrous tissue and a lumpy, cobblestone texture in the breasts. These lumps are smooth with well defined edges, and free-moving regarding adjacent structures. These lumps can sometimes be obscured by irregularities in the breast associated with the condition. Theyre often found in the upper, outer sections of the breast (nearest to the armpit), but can be found throughout the breast. Women with fibrocystic changes may experience a persistent or intermittent aching or breast tenderness related to periodic swelling. Breasts and nipples may also be tender or itchy.
Symptoms follow a periodic trend closely tied to the menstrual cycle. Symptoms tend to peak in the days to weeks before each period and decrease afterwards. At peak, breasts may feel full, heavy, swollen, and tender to the touch. No complications related to breastfeeding have been found.

Pathophysiology
The exact mechanism of the condition is not fully understood, though it is known to be tied to hormone level fluctuation, the condition usually subsides after menopause and is closely related to the menstrual cycle. Post-menopausal under hormone replacement therapy have also reported symptoms of fibrocystic breast changes indicating hormones may play a major role.
This condition is an accumulative process, partly caused by the normal hormonal variation during a womans monthly cycle. The most important of these hormones include: estrogen, progesterone and prolactin.
These hormones directly affect the breast tissue by causing cells to grow and multiply. Other hormones such as TSH, insulin, growth hormone and growth factors such as TGF-beta exert both direct and indirect effects by amplifying or regulating cell growth. Chronic hormonal fluctuations eventually produce small cysts and/or areas of dense or fibrotic tissue over the years. By the age of 30, multiple small cysts and breast pain may arise. Larger cysts usually do not occur until after the age of 35. Over time, presumably driven by aberrant growth signals, such lesions may accumulate epigenetic, genetic and karyotypic changes such as modified expression of hormone receptors and loss of heterozygosity.
Several variants of fibrocystic breast changes may be distinguished and may vary in cause and genetic predisposition. Adenosis involves an abnormal count and density of lobular units, while other lesions appear to mainly arise from ductal epithelial origins.
Theres evidence that iodine deficiency contributes to fibrocystic breast changes by enhancing breast tissue sensitivity to estrogen.

Diagnosis
This is an exclusion diagnosis, mostly done based on the clinical presentation after ruling out breast cancer. Nipple fluid aspiration can be used as a classification cyst type method (and to some extent improve breast cancer risk prediction) but its rarely used in practice. Biopsy or fine needle aspiration are rarely warranted.Fibrocystic breast disease is primarily diagnosed based on the symptoms, clinical breast exam and physical exam. During this examination, the doctor looks for unusual breast areas, both visually and manually. Also, the lymph nodes located in the axilla and lower neck are examined. A complete and accurate medical history is also helpful in the diagnosing process. If the patients medical history and physical exam findings are consistent with normal breast changes, no additional tests are needed; otherwise the patient will be asked to return a few weeks later for reassessment. Women may detect lumps in their breasts during self-examination, if this happens its strongly advised to visit a health professional right away.

Imaging
In order to establish whether the lump is a cyst or not, several imaging tests may be performed, these may include: mammography, X-rays, MRIs and ultrasound studies. Mammography is usually the first imaging test to be ordered when unusual breast changes are found during a clinical breast examination. A diagnostic mammography consists of X-ray series that provide clear and specific visualization areas in the breast.
Ultrasounds and MRIs are commonly performed in conjunction with mammographies as they produce clear images of the breast that clearly distinguish between solid masses and fluid-filled breast cysts. These can better evaluate dense breast tissue; specially in young patients, under 30 years.

Biopsy
Breast biopsy is a test used to confirm the suspected diagnosis, only after imaging tests have already been performed and revealed unusual looking areas. The procedure consists in removing a sample of breast tissue which is then studied by a pathologist under a microscope. The specialist analyzing the tissue sample will be able to conclude if the breast changes are benign or malignant.
There are four main types of procedures for breast biopsy that may be performed, these include: fine-needle, core-needle, stereotactic biopsy and surgical approach. A fine-needle aspiration biopsy is usually ordered when the doctor is almost certain that the lump is a cyst. This test is generally performed in conjunction with an ultrasound which is helpful in guiding the needle into a small or hard to find lump. The procedure consists in inserting a thin needle into the breast tissue while the lump is palpated and seen live under sonographic ultrasound waves.
The core-needle biopsy is normally performed under local anesthesia and in a physicians office. The needle used in this procedure is slightly larger than the one used in a fine-needle biopsy because the procedure is intended to remove a small cylinder of tissue that will be sent to the laboratory for further examination.
A newer type of breast biopsy technique is the stereotactic biopsy which relies on a three-dimensional X-ray to guide the needle of non-palpable mass. The biopsy is performed in a similar manner, by using a needle to remove tissue sample but locating the specific area of the breast is done by X-raying the breast in two different angles. Surgical biopsy is performed to remove the entire lump or a part of it. It may be painful and is done under local anesthesia.

Treatment
Most women with fibrocystic changes who are asymptomatic do not need treatment, only a closer follow-up may be advised. Theres no widely accepted treatment or prevention strategy for this condition. When the patient is symptomatic treatment may be necessary, same guidelines as treatment for cyclical breast pain are followed. Theres still controversy whether benign breast conditions improve or worsen with the use of oral contraceptives or hormone replacement therapy.Small-scale studies have indicated that fibrocystic breast changes may improve by making dietary changes (especially by reducing caffeine intake and related methylxanthines found in chocolate or tea) and usage of vitamin supplements. Tentative evidence has shown beneficial effects of iodine supplementation in women with fibrocystic breast changes.

Prognosis
There are usually no adverse side effects associated with this condition. In almost all cases it subsides after menopause. A possible complication arises through the fact that cancerous tumors may be more difficult to detect in women with fibrocystic changes.

Breast cancer risk
Breast cancer risk is elevated in a defined fraction of the lesions. Except for people with a strong family history of breast cancer, where the risk is two-fold, nonproliferative lesions have no increased risk. Proliferative lesions also have approximately a two-fold risk. In particular, atypical hyperplasia which is associated with an increased risk of developing breast cancer. Theres two types of atypical hyperplasia: lobular and ductal; the lobular type is associated a greater cancer risk of approximately 5-fold and especially high relative risk in premenopausal women. Atypical ductal hyperplasia is associated with 2.4-fold risk. In contrast, a New England Journal of Medicine article  states that for women with a strong familial history of breast cancer, the risk of future breast cancer is roughly doubled, independent of histological status </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 Familial cutaneous collagenoma 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 Breast engorgement and can you explain it in depth? [/INST] Breast engorgement occurs in the mammary glands due to expansion and pressure exerted by the synthesis and storage of breast milk. It is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and curvature of the nipple region by making the breast inflexible, flat, hard, and swollen. The nipples on an engorged breast are flat or inverted. Sometimes it may lead to striae on nipples, mainly a preceding symptom of septation mastitis.Engorgement usually happens when the breasts switch from colostrum to mature milk (often referred to as when the milk "comes in"). However, engorgement can also happen later if lactating women miss several nursings and not enough milk is expressed from the breasts. It can be exacerbated by insufficient breastfeeding and/or blocked milk ducts.  When engorged the breasts may swell, throb, and cause mild to extreme pain.
Engorgement may lead to mastitis (inflammation of the breast) and untreated engorgement puts pressure on the milk ducts, often causing a plugged duct.  The woman will often feel a lump in one part of the breast, and the skin in that area may be red and/or warm.  If it continues unchecked, the plugged duct can become a breast infection, at which point she may have a fever or flu-like symptoms.

Signs and symptoms
Symptoms include the breasts being swollen and oedematous, and the skin appearing shiny and diffusely red. Usually the whole of both breasts are affected, and they are painful. The woman may have a fever that usually subsides in 24 hours </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 Homocystinuria and can you explain it in depth? [/INST] Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate.

Signs and symptoms
This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague.Signs and symptoms of homocystinuria that may be seen include the following:

Cause
It is usually caused by the deficiency of the enzyme cystathionine beta synthase, mutations of other related enzymes such as methionine synthase, or the deficiency of folic acid, vitamin B12 and/or pyridoxine (vitamin B6).

Diagnosis
The term homocystinuria describes an increased excretion of the thiol amino acid homocysteine in urine (and incidentally, also an increased concentration in plasma). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects (cobalamin defects, methionine synthase deficiency, MTHFR) and vitamin deficiencies including riboflavin (vitamin B2), pyridoxal phosphate (vitamin B6), folate (vitamin B9), and cobalamin (vitamin B12). In light of this, a combined approach to laboratory diagnosis is required to reach a differential diagnosis.CBS deficiency may be diagnosed by routine metabolic biochemistry. Genetic testing may be used to screen for known SNPs (mutations). In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency, or the cobalamin defects) in lieu of the elevated methionine concentration. Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of disulphides (e.g., cysteine in cystine-homocysteine, homocysteine in homocysteine-homocysteine) via disulfide bonds. Since as an equilibrium process the proportion of free homocystene is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.

Treatment
No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as pyridoxine) </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 Pterygium inversum unguis 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 Flashback 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 Muenke syndrome and can you explain it in depth? [/INST] Muenke syndrome, also known as FGFR3-related craniosynostosis, is a human specific condition characterized by the premature closure of certain bones of the skull during development, which affects the shape of the head and face. First described by Maximilian Muenke, the syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 8 percent of all cases of craniosynostosis.

Signs and symptoms
Many people with this disorder have a premature fusion of skull bones along the coronal suture. Not every case has had craniosynostosis however. Other parts of the skull may be malformed as well. This will usually cause an abnormally shaped head, wide-set eyes, low set ears and flattened cheekbones in these patients. About 5 percent of affected individuals have an enlarged head (macrocephaly). There may also be associated hearing loss in 10–33% of cases and it is important for affected individuals to have hearing tests to check on the possibility of a problem. They can lose about 33-100% of hearing.Most people with this condition have normal intellect, but developmental delay and learning disabilities are possible. The signs and symptoms of Muenke syndrome vary among affected people, and some findings overlap with those seen in other craniosynostosis syndromes. Between 6 percent and 7 percent of people with the gene mutation associated with Muenke syndrome do not have any of the characteristic features of the disorder.

Other Implications of Muenke Syndrome
Apart from craniosynostosis, it has been suggested that hearing loss, and learning difficulties are common in Muenke syndrome.  According to Ulster Medical Journal, most individuals with Muenke syndrome may have limb findings.  The most common ocular finding in Muenke syndrome is strabismus as studied by Dr. Agochukwu-Nwubah and her researching team.
Approximately 20% of people with Muenke Syndrome will also be affected by epilepsy.

Causes
Muenke syndrome is caused by a specific gene mutation in the FGFR3 gene. The mutation arises randomly; there is no full understanding for what causes this mutation.  This mutation causes the FGFR3 protein to be overly active; it interferes with normal bone growth, and allows skull bones to fuse prematurely. There is no connection between anything mother did (or did not do) to activate the syndrome. If neither of the parents have Muenke syndrome, chances of having another child with the syndrome are minimal.
This condition is inherited in an autosomal dominant pattern. This means if a parent has Muenke syndrome, every newborn has a 50% chance of inheriting the syndrome.

Genetics
Muenke syndrome is inherited in an autosomal dominant pattern. In some cases, an affected person inherits the mutation from one affected parent. If a patient is shown to have Muenke, they have a 50/50 chance of passing it on to their children. Not all cases of Muenke however is obvious. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
A single mutation in the FGFR3 gene cause this syndrome. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. This mutation causes the FGFR3 protein to be overly active, which interferes with normal bone growth and allows the bones of the skull to fuse before they should.As stated by researchers at the University of Washington, Muenke syndrome is inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity.”  Prenatal diagnosis for pregnancies at increased risk is possible if the defining mutation has been identified in the family (Agochukwu et.al. 2006).  According to the article Craniosynostosis: Molecular Genetics, penetrance is higher in females (87%) than in males (76%).  Muenke syndrome is estimated to account for 25%-30% of all genetic causes of craniosynostosis according to the Journal of Anatomy.

Diagnosis
The diagnosis of Muenke syndrome is suspected bases on abnormal skull shape and a diagnosis of coronal craniosynostosis.  In 2006, Agochukwu and her colleagues concluded that “A distinct Muenke syndrome phenotype includes: uni or bilateral coronal synostosis, midface hypoplasia, broad toes, and brachydactyly.”  Due to phenotypic overlap and/or mild phenotypes, clinical differentiation of this syndrome may be difficult.  The suspected diagnosis is confirmed by a blood test to check for gene mutation.  To establish the extent of disease in an individual diagnosed with Muenke syndrome, various evaluations are recommended.

Treatment
The treatment of Muenke syndrome is focused on the correction of the abnormal skull shape and mirrors the treatment of coronal craniosynostosis.  The abnormal growth patterns continue throughout the growing years; therefore, intervention, accurate diagnosis, and a customized, expertly carried-out treatment plan should be a primary concern.  Although the timing of surgery can be highly individualized, surgical correction of the bicoronal craniosynostosis is most often done between 6 and 12 months of age.  Surgery is usually performed through a scalp incision that lies concealed within the hair of the head.  Your craniofacial surgeon will work in concert with a pediatric neurosurgeon in order to safely remove the bones of the skull.  Then, the craniofacial surgeon reshapes and repositions those bones to give a more normal skull shape.

References
Rannan-Eliya SV, Taylor IB, De Heer IM, Van Den Ouweland AM, Wall SA, Wilkie AO (August 2004). "Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis". Hum. Genet. 115 (3): 200–7. doi:10.1007/s00439-004-1151-5. PMID 15241680. S2CID 24791706.
Agochukwu NB, Doherty ES, Muenke M (December 7, 2010). "Muenke Syndrome". Gene Reviews. PMID 20301588.
Hughes J, Nevin NC, Morrison PJ (2001). "Familial craniosynostosis due to Pro250Arg mutation in the fibroblast growth factor receptor 3 gene". Ulster Med J. 70 (70): 47–50. PMC 2449219 </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 Linear gingival erythema 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 Herpetic whitlow and can you explain it in depth? [/INST] A herpetic whitlow is a lesion (whitlow) on a finger or thumb caused by the herpes simplex virus.  It is a painful infection that typically affects the fingers or thumbs.  Occasionally infection occurs on the toes or on the nail cuticle.  Herpes whitlow can be caused by infection by HSV-1 or HSV-2. HSV-1 whitlow is often contracted by health care workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions. It is also often observed in thumb-sucking children with primary HSV-1 oral infection (autoinoculation) prior to seroconversion, and in adults aged 20 to 30 following contact with HSV-2-infected genitals.

Symptoms and signs
Symptoms of herpetic whitlow include swelling, reddening and tenderness of the skin of infected finger. This may be accompanied by fever and swollen lymph nodes. Small, clear vesicles initially form individually, then merge and become cloudy, unlike in bacterial whitlow when there is pus. Associated pain often seems largely relative to the physical symptoms. The herpes whitlow lesion usually heals in two to three weeks. It may reside in axillary sensory ganglia to cause recurrent herpetic lesions on that arm or digits. Blistering can occur in severe cases.

Causes
In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the cutting, chewing or sucking of fingernail or thumbnail.In adults, it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because of increased exposure to the herpes virus.Contact sports are also a potential source of infection with herpetic whitlows.

Treatment
Although it is a self-limited illness, oral or intravenous antiviral treatments, particularly acyclovir, have been used in the management of immunocompromised or severely infected patients. It is usually given when the condition fails to improve on its own. Topical acyclovir has not been shown to be effective in management of herpetic whitlow. Famciclovir has been demonstrated to effectively treat and prevent recurrent episodes.  Lancing or surgically debriding the lesion may make it worse by causing a superinfection or encephalitis.

Prognosis
Even though the disease is self-limiting, as with many herpes infections, the virus lies dormant in the peripheral nervous system. The disease recurs in about 20-50% of people. The most severe infection is usually the first one, with recurrences subsequently getting milder. The lesions the disease makes will either dry out, or burst, followed by healing </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 Fibrochondrogenesis and can you explain it in depth? [/INST] Fibrochondrogenesis is a rare autosomal recessive form of osteochondrodysplasia, causing abnormal fibrous development of cartilage and related tissues.It is a lethal rhizomelic (malformations which result in short, underdeveloped limbs) form of dwarfism, exhibiting both skeletal dysplasia (malformations of bone) and fibroblastic dysplasia (abnormal development of fibroblasts, specialized cells that make up fibrous connective tissue, which plays a role in the formation of cellular structure and promotes healing of damaged tissues) </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 Galactocele 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 Quadricuspid aortic valve and can you explain it in depth? [/INST] A quadricuspid aortic valve (QAV) is a rare congenital heart defect characterized by the presence of four cusps, instead of the usual three found normally in the aortic valve. It is a defect that occurs during embryological development of the aortic trunk during gestation. There is an increased risk of developing post-natal aortic regurgitations and other heart-related diseases; therefore patients with the condition should be carefully monitored.

Signs and symptoms
Complications
The most common complications of QAV are aortic regurgitations. This is caused by the inadequate closing of the four cusps at the end of systole </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 Neutrophil-specific granule deficiency and can you explain it in depth? [/INST] Neutrophil-specific granule deficiency ( previously known as lactoferrin deficiency) is a rare congenital immunodeficiency characterized  by an increased risk for pyogenic infections due to defective production of specific granules and gelatinase granules in patient neutrophils.

Symptoms and signs
Atypical infections are the key clinical manifestation of SGD. Within the first few years of life, patients will experience repeated pyogenic infections by species such as Staphylococcus aureus, Pseudomonas aeruginosa or other Enterobacteriaceae, and Candida albicans. Cutaneous ulcers or abscesses and pneumonia and chronic lung disease are common. Patients may also develop sepsis, mastoiditis, otitis media, and lymphadenopathy. Infants may present with vomiting, diarrhea, and failure to thrive.Diagnosis can be made based upon CEBPE gene mutation or a pathognomonic finding of a blood smear showing lack of specific granules </s>