<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 Placental abruption and can you explain it in depth? [/INST] Placental abruption is when the placenta separates early from the uterus, in other words separates before childbirth. It occurs most commonly around 25 weeks of pregnancy. Symptoms may include vaginal bleeding, lower abdominal pain, and dangerously low blood pressure. Complications for the mother can include disseminated intravascular coagulopathy and kidney failure. Complications for the baby can include fetal distress, low birthweight, preterm delivery, and stillbirth.The cause of placental abruption is not entirely clear. Risk factors include smoking, pre-eclampsia, prior abruption (most important and predictive risk factor), trauma during pregnancy, cocaine use, and previous cesarean section. Diagnosis is based on symptoms and supported by ultrasound. It is classified as a complication of pregnancy.For small abruption, bed rest may be recommended, while for more significant abruptions or those that occur near term, delivery may be recommended. If everything is stable, vaginal delivery may be tried, otherwise cesarean section is recommended. In those less than 36 weeks pregnant, corticosteroids may be given to speed development of the babys lungs. Treatment may require blood transfusion or emergency hysterectomy.Placental abruption occurs in about 1 in 200 pregnancies. Along with placenta previa and uterine rupture it is one of the most common causes of vaginal bleeding in the later part of pregnancy. Placental abruption is the reason for about 15% of infant deaths around the time of birth. The condition was described at least as early as 1664.

Signs and symptoms
In the early stages of placental abruption, there may be no symptoms. When symptoms develop, they tend to develop suddenly. Common symptoms include:

sudden-onset abdominal pain
contractions that seem continuous and do not stop
vaginal bleeding
enlarged uterus (disproportionate to the gestational age of the fetus)
decreased fetal movement
decreased fetal heart rate.Vaginal bleeding, if it occurs, may be bright red or dark.A placental abruption caused by arterial bleeding at the center of the placenta leads to sudden development of severe symptoms and life-threatening conditions including fetal heart rate abnormalities, severe maternal hemorrhage, and disseminated intravascular coagulation (DIC). Those abruptions caused by venous bleeding at the periphery of the placenta develop more slowly and cause small amounts of bleeding, intrauterine growth restriction, and oligohydramnios (low levels of amniotic fluid).

Risk factors
Pre-eclampsia
Chronic hypertension
Short umbilical cord
Premature rupture of membranes
Prolonged rupture of membranes (>24 hours).
Thrombophilia
Polyhydramnios
Multiparity
Multiple pregnancy
Maternal age: pregnant women who are younger than 20 or older than 35 are at greater riskRisk factors for placental abruption include disease, trauma, history, anatomy, and exposure to substances. The risk of placental abruption increases sixfold after severe maternal trauma. Anatomical risk factors include uncommon uterine anatomy (e.g. bicornuate uterus), uterine synechiae, and leiomyoma. Substances that increase risk of placental abruption include cocaine and tobacco when consumed during pregnancy, especially the third trimester. History of placental abruption or previous Caesarian section increases the risk by a factor of 2.3.

Pathophysiology
In the vast majority of cases, placental abruption is caused by the maternal vessels tearing away from the decidua basalis, not the fetal vessels. The underlying cause is often unknown. A small number of abruptions are caused by trauma that stretches the uterus. Because the placenta is less elastic than the uterus, it tears away when the uterine tissue stretches suddenly. When anatomical risk factors are present, the placenta does not attach in a place that provides adequate support, and it may not develop appropriately or be separated as it grows. Cocaine use during the third trimester has a 10% chance of causing abruption. Though the exact mechanism is not known, cocaine and tobacco cause systemic vasoconstriction, which can severely restrict the placental blood supply (hypoperfusion and ischemia), or otherwise disrupt the vasculature of the placenta, causing tissue necrosis, bleeding, and therefore abruption.In most cases, placental disease and abnormalities of the spiral arteries develop throughout the pregnancy and lead to necrosis, inflammation, vascular problems, and ultimately, abruption. Because of this, most abruptions are caused by bleeding from the arterial supply, not the venous supply. Production of thrombin via massive bleeding causes the uterus to contract and leads to DIC.The accumulating blood pushes between the layers of the decidua, pushing the uterine wall and placenta apart. When the placenta is separated, it is unable to exchange waste, nutrients, and oxygen, a necessary function for the fetuss survival. The fetus dies when it no longer receives enough oxygen and nutrients to survive.

Diagnosis
Placental abruption is suspected when a pregnant mother has sudden localized abdominal pain with or without bleeding. The fundus may be monitored because a rising fundus can indicate bleeding. An ultrasound may be used to rule out placenta praevia but is not diagnostic for abruption. The diagnosis is one of exclusion, meaning other possible sources of vaginal bleeding or abdominal pain have to be ruled out in order to diagnose placental abruption. Of note, use of magnetic resonance imaging has been found to be highly sensitive in depicting placental abruption, and may be considered if no ultrasound evidence of placental abruption is present, especially if the diagnosis of placental abruption would change management.

Classification
Based on severity:

Class 0: Asymptomatic. Diagnosis is made retrospectively by finding an organized blood clot or a depressed area on a delivered placenta.
Class 1: Mild and represents approximately 48% of all cases. Characteristics include the following:
No vaginal bleeding to mild vaginal bleeding
Slightly tender uterus
Normal maternal blood pressure and heart rate
No coagulopathy
No fetal distress
Class 2: Moderate and represents approximately 27% of all cases. Characteristics include the following:
No vaginal bleeding to moderate vaginal bleeding
Moderate-to-severe uterine tenderness with possible tetanic contractions
Maternal tachycardia with orthostatic changes in blood pressure and heart rate
Fetal distress
Hypofibrinogenemia (i.e., 50–250 mg/dL)
Class 3: Severe and represents approximately 24% of all cases. Characteristics include the following:
No vaginal bleeding to heavy vaginal bleeding
Very painful tetanic uterus
Maternal shock
Hypofibrinogenemia (i.e., <150 mg/dL)
Coagulopathy
Fetal death

Prevention
Although the risk of placental abruption cannot be eliminated, it can be reduced. Avoiding tobacco, alcohol and cocaine during pregnancy decreases the risk. Staying away from activities which have a high risk of physical trauma is also important. Women who have high blood pressure or who have had a previous placental abruption and want to conceive must be closely supervised by a doctor.The risk of placental abruption can be reduced by maintaining a good diet including taking folate, regular sleep patterns and correction of pregnancy-induced hypertension.Use of aspirin before 16 weeks of pregnancy to prevent pre-eclampsia also appears effective at preventing placental abruption.

Management
Treatment depends on the amount of blood loss and the status of the fetus. If the fetus is less than 36 weeks, and neither mother or fetus are in any distress, then they may simply be monitored in hospital until a change in condition or fetal maturity whichever comes first.
Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother is in distress. Blood volume replacement to maintain blood pressure and blood plasma replacement to maintain fibrinogen levels may be needed </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 Fasciculation and can you explain it in depth? [/INST] A fasciculation, or muscle twitch, is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as many as 70% of people experiencing them. They can be benign, or associated with more serious conditions.  When no cause or pathology is identified, they are diagnosed as benign fasciculation syndrome.

Diagnosis
The most effective way to detect fasciculations may be surface electromyography (EMG). Surface EMG is more sensitive than needle electromyography and clinical observation in the detection of fasciculation in people with amyotrophic lateral sclerosis.Deeper areas of contraction can be detected by electromyography (EMG) testing, though they can happen in any skeletal muscle in the body. Fasciculations arise as a result of spontaneous depolarization of a lower motor neuron leading to the synchronous contraction of all the skeletal muscle fibers within a single motor unit. An example of normal spontaneous depolarization is the constant contractions of cardiac muscle, causing the heart to beat. Usually, intentional movement of the involved muscle causes fasciculations to cease immediately, but they may return once the muscle is at rest again.
Tics must also be distinguished from fasciculations. Small twitches of the upper or lower eyelid, for example, are not tics, because they do not involve a whole muscle, rather are twitches of a few muscle fibre bundles, that are not suppressible.

Causes
Fasciculations have a variety of causes, the majority of which are benign, but can also be due to disease of the motor neurons. They are encountered by up to 70% of all healthy people, though for most, it is quite infrequent. In some cases, the presence of fasciculations can be annoying and interfere with quality of life. If a neurological examination is otherwise normal and EMG testing does not indicate any additional pathology, a diagnosis of  benign fasciculation syndrome is usually made.

Risk factors
Risk factors for benign fasciculations are age, stress, fatigue, and strenuous exercise. Fasciculations can be caused by anxiety, caffeine or alcohol and thyroid disease </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 Uterus and can you explain it in depth? [/INST] The uterus (from Latin "uterus", plural uteri) or womb () is the main hormone-responsive, secondary sex organ of the female reproductive system in humans, and most other mammals. Events occurring within the uterus are described with the term in utero. In the human, the lower end of the uterus, the cervix, opens into the vagina, while the upper end, the fundus, is connected to the fallopian tubes. It is within the uterus that the embryo and later fetus develops during gestation. In the human embryo, the uterus develops from the paramesonephric ducts which fuse into the single organ known as a simplex uterus. The uterus has different forms in many other animals and in some it exists as two separate uteri known as a duplex uterus.
In medicine, and related professions the term uterus is consistently used, while the Germanic-derived term womb is commonly used in everyday contexts.

Structure in humans
The human uterus is located within the pelvic region immediately behind and almost overlying the bladder, and in front of the sigmoid colon. The human uterus is pear-shaped and about 7.6 cm (3.0 in) long, 4.5 cm (1.8 in) broad (side to side), and 3.0 cm (1.2 in) thick. A typical adult uterus weighs about 60 grams. The uterus can be divided anatomically into four regions: the fundus – the uppermost rounded portion of the uterus, the corpus (body), the cervix, and the cervical canal. The cervix protrudes into the vagina. The uterus is held in position within the pelvis by ligaments, which are part of the endopelvic fascia. These ligaments include the pubocervical ligaments, the cardinal ligaments, and the uterosacral ligaments. It is covered by a sheet-like fold of peritoneum, the broad ligament.

From outside to inside, regions of the uterus include:

Cervix uteri – "neck of uterus"
External orifice of the uterus
Cervical canal
Internal orifice of the uterus
Body (Latin: Corpus)
Uterine cavity
Fundus

Layers
The uterus has three layers, which together form the uterine wall. From innermost to outermost, these layers are the endometrium, myometrium, and perimetrium.The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer; the functional layer thickens and then is sloughed during the menstrual cycle or estrous cycle. During pregnancy, the uterine glands and blood vessels in the endometrium further increase in size and number and form the decidua. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus.The myometrium of the uterus mostly consists of smooth muscle. The innermost layer of myometrium is known as the junctional zone, which becomes thickened in adenomyosis.The perimetrium is a serous layer of visceral peritoneum. It covers the outer surface of the uterus.Surrounding the uterus is a layer or band of fibrous and fatty connective tissue called the parametrium that connects the uterus to other tissues of the pelvis.
Commensal organisms are present in the uterus and form the uterine microbiome.

Support
The uterus is primarily supported by the pelvic diaphragm, perineal body, and urogenital diaphragm. Secondarily, it is supported by ligaments, including the peritoneal ligament and the broad ligament of uterus.

Major ligaments
It is held in place by several peritoneal ligaments, of which the following are the most important (there are two of each):

Axis
Normally, the human uterus lies in anteversion and anteflexion. In most women, the long axis of the uterus is bent forward on the long axis of the vagina, against the urinary bladder. This position is referred to as anteversion of the uterus. Furthermore, the long axis of the body of the uterus is bent forward at the level of the internal os with the long axis of the cervix. This position is termed anteflexion of the uterus. The uterus assumes an anteverted position in 50% of women, a retroverted position in 25% of women, and a midposed position in the remaining 25% of women.

Position
The uterus is located in the middle of the pelvic cavity, in the frontal plane (due to the broad ligament of the uterus). The fundus does not extend above the linea terminalis, while the vaginal part of the cervix does not extend below the interspinal line. The uterus is mobile and moves posteriorly under the pressure of a full bladder, or anteriorly under the pressure of a full rectum. If both are full, it moves upwards. Increased intra-abdominal pressure pushes it downwards. The mobility is conferred to it by a musculo-fibrous apparatus that consists of suspensory and sustentacular parts. Under normal circumstances, the suspensory part keeps the uterus in anteflexion and anteversion (in 90% of women) and keeps it "floating" in the pelvis. The meanings of these terms are described below:

The sustentacular part supports the pelvic organs and comprises the larger pelvic diaphragm in the back and the smaller urogenital diaphragm in the front.
The pathological changes of the position of the uterus are:

retroversion/retroflexion, if it is fixed
hyperanteflexion – tipped too forward; most commonly congenital, but may be caused by tumors
anteposition, retroposition, lateroposition – the whole uterus is moved; caused by parametritis or tumors
elevation, descensus, prolapse
rotation (the whole uterus rotates around its longitudinal axis), torsion (only the body of the uterus rotates around)
inversionIn cases where the uterus is "tipped", also known as retroverted uterus, the woman may have symptoms of pain during sexual intercourse, pelvic pain during menstruation, minor incontinence, urinary tract infections, fertility difficulties, and difficulty using tampons.  A pelvic examination by a doctor can determine if a uterus is tipped.

Blood supply
The human uterus is supplied by arterial blood both from the uterine artery and the ovarian artery. Another anastomotic branch may also supply the uterus from anastomosis of these two arteries.

Nerve supply
Afferent nerves supplying the uterus are T11 and T12. Sympathetic supply is from the hypogastric plexus and the ovarian plexus. Parasympathetic supply is from the S2, S3 and S4 nerves.

Development
Bilateral Müllerian ducts form during early human fetal life. In males, anti-müllerian hormone (AMH) secreted from the testes leads to the ducts regression. In females, these ducts give rise to the Fallopian tubes and the uterus. In humans, the lower segments of the two ducts fuse to form a single uterus; in cases of uterine malformations this fusion may be disturbed. The different uterine morphologies among the mammals are due to varying degrees of fusion of the Müllerian ducts.
Various congenital conditions of the uterus can develop in utero. Though uncommon, some of these are didelphic uterus, bicornate uterus and others.

Function
The reproductive function of the human uterus is to accept a fertilized ovum, which passes through the utero-tubal junction from the fallopian tube. The fertilized ovum divides mitotically to become a blastocyst, which implants into the endometrium and derives nourishment from blood vessels which develop exclusively for this purpose. The fertilized ovum becomes an embryo, attaches to the wall of the uterus, creates a placenta, and develops into a fetus (gestates) until childbirth occurs. Due to anatomical barriers such as the pelvis, the uterus is pushed partially into the abdomen due to its expansion during pregnancy. Even during pregnancy, the mass of a human uterus amounts to only about a kilogram (2.2 pounds).
The uterus also plays a role in sexual response, by directing blood flow to the pelvis and ovaries, and to the external genitalia
There is also some evidence from rat studies that the uterus plays a role in cognition in a similar way to the ovaries. A study on rat models found that when the uterus was removed, the rats performed more poorly on spatial memory tasks. Prof. Bimonte-Nelson, the co-author of the study, explained: "the bodys autonomic nervous system, which regulates automated metabolic processes, such as heart rate, breathing, digestion, and sexual arousal, also has links to the uterus and brain." No similar studies have yet been conducted on humans.

Clinical significance
A hysterectomy is the surgical removal of the uterus which may be carried out for a number of reasons including the ridding of tumours both benign and malignant. A complete hysterectomy involves the removal of the body, fundus, and cervix of the uterus. A partial hysterectomy may just involve the removal of the uterine body while leaving the cervix intact. It is the most commonly performed gynecological surgical procedure.
During pregnancy the growth rate of the fetus can be assessed by measuring the fundal height.
Some pathological states include:

Prolapse of the uterus
Carcinoma of the cervix – malignant neoplasm
Carcinoma of the uterus – malignant neoplasm
Fibroids – benign neoplasms
Adenomyosis – ectopic growth of endometrial tissue within the myometrium
Endometritis, infection at the uterine cavity
Pyometra – infection of the uterus, most commonly seen in dogs
Uterine malformations mainly congenital malformations including Uterine Didelphys, bicornuate uterus and septate uterus. It also includes congenital absence of the uterus Rokitansky syndrome
Ashermans syndrome, also known as intrauterine adhesions, occurs when the basal layer of the endometrium is damaged by instrumentation (e.g., D&C) or infection (e.g., endometrial tuberculosis) resulting in endometrial scarring followed by adhesion formation that partially or completely obliterates the uterine cavity
Hematometra, which is accumulation of blood within the uterus.
Accumulation of fluids other than blood or of unknown constitution. One study came to the conclusion that postmenopausal women with endometrial fluid collection on gynecologic ultrasonography should undergo endometrial biopsy if the endometrial lining is thicker than 3 mm or if the endometrial fluid is echogenic. In cases of a lining 3 mm or less and clear endometrial fluid, endometrial biopsy was not regarded to be necessary, but endocervical curettage to rule out endocervical cancer was recommended.
Myometritis – inflammation of the muscular uterine wall.

Other animals
Most animals that lay eggs, such as birds and reptiles, including most ovoviviparous species, have an oviduct instead of a uterus. However,  recent research into the biology of the viviparous (not merely ovoviviparous) skink Trachylepis ivensi has revealed development of a very close analogue to eutherian mammalian placental development.In monotremes, mammals which lay eggs, namely the platypus and the echidnas, either the term uterus or oviduct is used to describe the same organ, but the egg does not develop a placenta within the mother and thus does not receive further nourishment after formation and fertilization.
Marsupials have two uteri, each of which connect to a lateral vagina and which both use a third, middle "vagina" which functions as the birth canal. Marsupial embryos form a choriovitelline placenta (which can be thought of as something between a monotreme egg and a "true" placenta), in which the eggs yolk sac supplies a large part of the embryos nutrition but also attaches to the uterine wall and takes nutrients from the mothers bloodstream. However, bandicoots also have a rudimentary chorioallantoic placenta, similar to those of placental mammals.

The fetus usually develops fully in placental mammals and only partially in marsupials including kangaroos and opossums </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 Stenosis 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 Opioid use disorder and can you explain it in depth? [/INST] Opioid use disorder (OUD) is a substance use disorder relating to the use of an opioid. Any such disorder causes significant impairment or distress. Signs of the disorder include a strong desire to use opioids, increased tolerance to opioids, difficulty fulfilling obligations, trouble reducing use, and withdrawal symptoms with discontinuation. Opioid withdrawal symptoms may include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood. Addiction and dependence are components of a substance use disorder. Complications may include opioid overdose, suicide, HIV/AIDS, hepatitis C, and problems at school, work, or home.An article in The Lancet compared the harm and dependence liability of 20 drugs, using a scale from zero to three for physical dependence, psychological dependence, and pleasure to create a mean score for dependence. The 20 drugs were several opioids (morphine, heroin, methadone, hydromorphone, oxycodone), barbiturates (pentobarbital, secobarbital, amobarbital, phenobarbital), benzodiazepines (diazepam, temazepam, nitrazepam, lorazepam, triazolam), nicotine, cocaine, amphetamine, MDMA (ecstasy), alcohol, and cannabis. Selected results can be seen in the chart below. Diacetylmorphine and morphine both scored a 3.0 and ranked highest. Hydromorphone followed with a mean of 2.76, cocaine scoring 2.4, oxycodone 2.31, and methadone at 1.75. The mean benzodiazepine score was elevated to due to high scores exhibited by triazolam and temazepam for pleasure and psychological dependence.
Opioids include substances such as heroin, morphine, fentanyl, codeine, dihydrocodeine, oxycodone, and hydrocodone. In the United States, a majority of heroin users begin by using prescription opioids that may also be bought illegally. Risk factors for misuse include a history of substance use, substance use among family and friends, mental illness, low socioeconomic status, and race. Diagnosis may be based on criteria by the American Psychiatric Association in the DSM-5. If more than two of eleven criteria are present during a year, the diagnosis is said to be present.Individuals with an opioid use disorder are often treated with opioid replacement therapy using methadone or buprenorphine. Being on such treatment reduces the risk of death. Additionally, individuals may benefit from cognitive behavioral therapy, other forms of support from mental health professionals such as individual or group therapy, twelve-step programs, and other peer support programs. The medication naltrexone may also be useful to prevent relapse. Naloxone is useful for treating an opioid overdose and giving those at risk naloxone to take home is beneficial.In 2013, opioid use disorders affected about 0.4% of people. As of 2016, about 27 million people are affected. Long term opioid use occurs in about 4% of people following their use for trauma or surgery-related pain. Onset is often in young adulthood. Males are affected more often than females. It resulted in 122,000 deaths worldwide in 2015, up from 18,000 deaths in 1990. In the United States during 2020 alone, there were more than 65,000 deaths due to opioid overdose, of which more than 15,000 were the result of heroin use.

Signs and symptoms
Signs and symptoms include:
Drug seeking behavior
Increased use over time
Legal or social ramifications secondary to drug use
Multiple prescriptions from different providers
Multiple medical complications from drug use (HIV/AIDS, hospitalizations, abscesses)
Opioid cravings
Withdrawal symptomsAddiction and dependence are components of a substance use disorder and addiction represents the more severe form. Opioid dependence can occur as physical dependence, psychological dependence, or both.

Withdrawal
Opioid withdrawal can occur with a sudden decrease in, or the cessation of, opioids after prolonged use. Onset of withdrawal depends on which opioid was used last. With heroin this typically occurs five hours after use, while with methadone it might not occur until two days later. The length of time that major symptoms occur also depends on the opioid used. For heroin withdrawal, symptoms are typically greatest at two to four days, and can last for up to two weeks. Less significant symptoms may remain for an even longer period, in which case the withdrawal is known as post-acute-withdrawal syndrome.

Treatment of withdrawal may include methadone and buprenorphine. Medications for nausea or diarrhea may also be used.

Opioid intoxication
Signs and symptoms of opioid intoxication include:

Opioid overdose
Signs and symptoms of opioid overdose include, but are not limited to:
Pin-point pupils may occur. Patient presenting with dilated pupils may still be experiencing an opioid overdose.
Decreased heart rate
Decreased body temperature
Decreased breathing
Altered level of consciousness. People may be unresponsive or unconscious.
Pulmonary edema (fluid accumulation in the lungs)
Shock
Death

Cause
Opioid use disorder can develop as a result of self-medication. Scoring systems have been derived to assess the likelihood of opiate addiction in chronic pain patients. Prescription opioids are the source of nearly half of misused opioids and the majority of these are initiated for trauma or surgery pain management. Further to this, healthcare practitioners have long been aware that despite the effective use of opioids for managing pain, the empirical evidence that supports the use of opioids long term is minimal. In addition to this, many studies that involved patients with chronic pain have failed to show any sustained improvement in their pain or ability to function with long term opioid use.According to position papers on the treatment of opioid dependence published by the United Nations Office on Drugs and Crime and the World Health Organization, care providers should not treat opioid use disorder as the result of a weak moral character or will but as a medical condition. Some evidence suggests the possibility that opioid use disorders occur due to genetic or other chemical mechanisms which may be difficult to identify or change, such as dysregulation of brain circuitry involving reward and volition. However, the exact mechanisms involved are unclear, leading to debate regarding the influence of biology and free will.

Mechanism
Addiction
Addiction is a brain disorder characterized by compulsive drug use despite adverse consequences. Addiction is a component of a substance use disorder and represents the most severe form of the disorder.Overexpression of the gene transcription factor ΔFosB in the nucleus accumbens plays a crucial role in the development of an addiction to opioids and other addictive drugs by sensitizing drug reward and amplifying compulsive drug-seeking behavior. Like other addictive drugs, overuse of opioids leads to increased ΔFosB expression in the nucleus accumbens. Opioids affect dopamine neurotransmission in the nucleus accumbens via the disinhibition of dopaminergic pathways as a result of inhibiting the GABA-based projections to the ventral tegmental area (VTA) from the rostromedial tegmental nucleus (RMTg), which negatively modulate dopamine neurotransmission. In other words, opioids inhibit the projections from the RMTg to the VTA, which in turn disinhibits the dopaminergic pathways that project from the VTA to the nucleus accumbens and elsewhere in the brain.The differences in the genetic regions encoding the dopamine receptors for each individual may help to elucidate part of the risk for opioid addiction and general substance abuse. Studies of the D2 Dopamine Receptor, in particular, have shown some promising results. One specific SNP is at the TaqI RFLP (rs1800497). In a study of 530 Han Chinese heroin-addicted individuals from a Methadone Maintenance Treatment Program, those with the specific genetic variation showed higher mean heroin consumption by around double those without the SNP. This study showed a p-value of .003 and along with several other works, this helps to show the contribution of dopamine receptors to substance addiction and more specifically, to opioid abuse.
Neuroimaging has shown functional and structural alterations in the brain. A 2017 study showed that chronic intake of opioids, such as heroin, may cause long-term effects in the orbitofrontal area (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Moreover, neuroimaging and neuropsychological studies demonstrated dysregulation of circuits associated with emotion, stress and high impulsivity.

Dependence
Drug dependence is an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake). Dependence is a component of a substance use disorder. Opioid dependence can manifest as physical dependence, psychological dependence, or both.Increased brain-derived neurotrophic factor (BDNF) signaling in the ventral tegmental area (VTA) has been shown to mediate opioid-induced withdrawal symptoms via downregulation of insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and mechanistic target of rapamycin complex 2 (mTORC2). As a result of downregulated signaling through these proteins, opiates cause VTA neuronal hyperexcitability and shrinkage (specifically, the size of the neuronal soma is reduced). It has been shown that when an opiate-naive person begins using opiates in concentrations that induce euphoria, BDNF signaling increases in the VTA.Upregulation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway by cAMP response element binding protein (CREB), a gene transcription factor, in the nucleus accumbens is a common mechanism of psychological dependence among several classes of drugs of abuse. Upregulation of the same pathway in the locus coeruleus is also a mechanism responsible for certain aspects of opioid-induced physical dependence.

Opioid receptors
A genetic basis for the efficacy of opioids in the treatment of pain has been demonstrated for several specific variations; however, the evidence for clinical differences in opioid effects is ambiguous. The pharmacogenomics of the opioid receptors and their endogenous ligands have been the subject of intensive activity in association studies. These studies test broadly for a number of phenotypes, including opioid dependence, cocaine dependence, alcohol dependence, methamphetamine dependence/psychosis, response to naltrexone treatment, personality traits, and others. Major and minor variants have been reported for every receptor and ligand coding gene in both coding sequences, as well as regulatory regions.
Newer approaches shift away from analysis of specific genes and regions, and are based on an unbiased screen of genes across the entire genome, which have no apparent relationship to the phenotype in question. These GWAS studies yield a number of implicated genes, although many of them code for seemingly unrelated proteins in processes such as cell adhesion, transcriptional regulation, cell structure determination, and RNA, DNA, and protein handling/modifying.

118A>G variant
While over 100 variants have been identified for the opioid mu-receptor, the most studied mu-receptor variant is the non-synonymous 118A>G variant, which results in functional changes to the receptor, including lower binding site availability, reduced mRNA levels, altered signal transduction, and increased affinity for beta-endorphin. In theory, all of these functional changes would reduce the impact of exogenous opioids, requiring a higher dose to achieve the same therapeutic effect. This points to a potential for greater addictive capacity in these individuals who require higher dosages to achieve pain control. However, evidence linking the 118A>G variant to opioid dependence is mixed, with associations shown in a number of study groups, but negative results in other groups. One explanation for the mixed results is the possibility of other variants which are in linkage disequilibrium with the 118A>G variant and thus contribute to different haplotype patterns that more specifically associated with opioid dependence.

Non-opioid receptor genes
The preproenkephalin gene, PENK, encodes for the endogenous opiates that modulate pain perception, and are implicated in reward and addiction. (CA) repeats in the 3 flanking sequence of the PENK gene was associated with greater likelihood of opiate dependence in repeated studies. Variability in the MCR2 gene, encoding melanocortin receptor type 2 has been associated with both protective effects and increased susceptibility to heroin addiction. The CYP2B6 gene of the cytochrome P450 family also mediates breakdown of opioids and thus may play a role in dependence and overdose.

Diagnosis
The DSM-5 guidelines for the diagnosis of opioid use disorder require that the individual has a significant impairment or distress related to opioid uses. To make the diagnosis two or more of eleven criteria must be present in a given year:
More opioids are taken than intended
The individual is unable to decrease the number of opioids used
Large amounts of time are spent trying to obtain opioids, use opioids, or recover from taking them
The individual has cravings for opioids
Difficulty fulfilling professional duties at work or school
Continued use of opioids leading to social and interpersonal consequences
Decreased social or recreational activities
Using opioids despite being in physically dangerous settings
Continued use despite opioids worsening physical or psychological health (i.e. depression, constipation)
Tolerance
WithdrawalThe severity can be classified as mild, moderate, or severe based on the number of criteria present.

Prevention
The CDC gives specific recommendations for prescribers regarding initiation of opioids, clinically appropriate use of opioids, and assessing possible risks associated with opioid therapy. Large retail pharmacy chains in the US are implementing protocols, guidelines, and initiatives to take back unused opioids, providing naloxone kits, and being vigilant for suspicious prescriptions. Insurance programs can help limit opioid use by setting quantity limits on prescriptions or requiring prior authorizations for certain medications.

Opioid related deaths
Naloxone is used for the emergency treatment of an overdose. It can be given by many routes (e.g., intramuscular, intravenous, subcutaneous, intranasal, and inhalation) and acts quickly by displacing opioids from opioid receptors and preventing activation of these receptors by opioids. Naloxone kits are recommended for laypersons who may witness an opioid overdose, for individuals with large prescriptions for opioids, those in substance use treatment programs, or who have been recently released from incarceration. Since this is a life-saving medication, many areas of the United States have implemented standing orders for law enforcement to carry and give naloxone as needed. In addition, naloxone could be used to challenge a persons opioid abstinence status prior to starting a medication such as naltrexone, which is used in the management of opioid addiction.Good Samaritan laws typically protect bystanders that administer naloxone. In the United States, at least 40 states have Good Samaritan laws to encourage bystanders to take action without fear of prosecution. As of 2019, 48 states allow for a pharmacist to have the authority to distribute naloxone without an individual prescription.Homicide, suicide, accidents and liver disease are also opioid related causes of death for those with OUD. Many of these opioid related causes of death are unnoticed due to the often limited information provided on death certificates.

Management
Opioid use disorders typically require long-term treatment and care with the goal of reducing risks for the individual, reducing criminal behaviour, and improving the long-term physical and psychological condition of the person. Some strategies aim to reduce drug use and lead to abstinence from opioids, while others attempt to stabilize on prescribed methadone or buprenorphine with continued replacement therapy indefinitely. No single treatment works for everyone, so several strategies have been developed including therapy and drugs.
As of 2013 in the US, there was a significant increase of prescription opioid abuse compared to illegal opiates like heroin. This development has also implications for the prevention, treatment and therapy of opioid dependence. Though treatment reduces mortality rates, the period during the first four weeks after treatment begins and the four weeks after treatment ceases are the times that carry the highest risk for drug-related deaths. These periods of increased vulnerability are significant because many of those in treatment leave programs during these critical periods.

Medications
Opioid replacement therapy (ORT) involves replacing an opioid, such as heroin, with a longer acting but less euphoric opioid. Commonly used drugs for ORT are methadone or buprenorphine which are taken under medical supervision. As of 2018, buprenorphine/naloxone is preferentially recommended, as the addition of the opioid antagonist naloxone is believed to reduce the risk of abuse via injection or insufflation without causing impairment.The driving principle behind ORT is the programs capacity to facilitate a resumption of stability in the users life, while the patient experiences reduced symptoms of drug withdrawal and less intense drug cravings; a strong euphoric effect is not experienced as a result of the treatment drug. In some countries (not the US, or Australia), regulations enforce a limited time for people on ORT programs that conclude when a stable economic and psychosocial situation is achieved. (People with HIV/AIDS or hepatitis C are usually excluded from this requirement.) In practice, 40–65% of patients maintain abstinence from additional opioids while receiving opioid replacement therapy and 70–95% can reduce their use significantly. Along with this is a concurrent elimination or reduction in medical (improper diluents, non-sterile injecting equipment), psychosocial (mental health, relationships), and legal (arrest and imprisonment) issues that can arise from the use of illegal opioids. Clonidine or lofexidine can help treat the symptoms of withdrawal.Participation in methadone and buprenorphine treatment reduces the risk of mortality due to overdose. The starting of methadone and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies. ORT has proven to be the most effective treatment for improving the health and living condition of people experiencing illegal opiate use or dependence, including mortality reduction and overall societal costs, such as the economic loss from drug-related crime and healthcare expenditure. ORT is endorsed by the World Health Organization, United Nations Office on Drugs and Crime and UNAIDS as being effective at reducing injection, lowering risk for HIV/AIDS, and promoting adherence to antiretroviral therapy.Buprenorphine and methadone work by reducing opioid cravings, easing withdrawal symptoms, and blocking the euphoric effects of opioids via cross-tolerance, and in the case of buprenorphine, a high-affinity partial agonist, also due to opioid receptor saturation. It is this property of buprenorphine that can induce acute withdrawal when administered before other opioids have left the body. Naltrexone, a μ-opioid receptor antagonist, also blocks the euphoric effects of opioids by occupying the opioid receptor, but it does not activate it, so it does not produce sedation, analgesia, or euphoria, and thus it has no potential for abuse or diversion.In the United States, since March 2020 as a result of the COVID-19 pandemic, buprenorphine may be dispensed via telemedicine.The ultimate aim of methadone maintenance is for the individual to return to a more normal life. They could be eligible for drug dependency care, career counseling, and educational assistance once they start taking methadone under medical supervision. They can self-refer to social service providers as they continue to feel better and want to get back on their feet.
Methadone may even be able to assist these individuals in avoiding relapse. Methadone is a long-acting drug, which means it sticks to the same opioid receptors in the brain as opium and prescription painkillers. As a result, patients who are taking methadone as part of an overdose treatment procedure will not feel opioid cravings or the severe withdrawal effects that come with it. This will encourage people in rehab to concentrate more on medication, laying a solid foundation for healing, rather than constantly fighting cravings and relapse impulses.
Methadone is a long-acting drug that can last up to 56 hours in the body. This means it fits better as a preventive drug so it doesnt require regular dosing during the day. Methadone users in detox also find more luck in therapy because they dont have to deal with constant opioid cravings or the severity of acute withdrawal symptoms. Advantages of methadone include:

Reduction in infectious disease due to the cessation of opiate misuse, especially injection drug abuse
Reduction in illegal crime due to the cessation in illicit drug usage
Overall increase in quality of life
Improved social functioning
More attendance in alcohol therapy since withdrawal symptoms arent a diversionMethadone replacement therapy will also help people achieve stabilization early on in their rehabilitation. People should devote 100% of their time to recovery, helping them to solve the underlying problems that lead to their opiate addiction. They will get a career and start to find a better balance in their lives. It also enables parents to continue raising their children in a safe home environment.
When their conditions improve and they want to refrain from taking methadone, they must be properly weaned off the medication, which must be done under medical observation.
Although other medication-assisted therapies for opiate addiction, such as buprenorphine, are available, methadone is often seen as the most promising alternative for people who are heavily addicted to opiates. Methadone has a number of serious side effects, including:

Slowed breathing
Sexual dysfunction
Nausea
Vomiting
Restlessness
Itchy eyesDosages can be adjusted after 1–2 days, or another medication may be recommended for your situation if you experience side effects.
Lung and breathing complications are possible long-term side effects of methadone use. Methadone, as an opiate, has the potential to be addictive. Many opponents believe that replacement drugs only substitute one addiction with another, and that methadone can be manipulated and exploited in some cases. Long-term usage has the ability to cause brain changes. Methadone causes changes in thought, cognitive performance, and memory by influencing nerve cells in the brain. An initial review is performed during alcohol therapy. The person will be evaluated and interviewed during this evaluation, and then the treatment team will then devise the optimal treatment plan for that individual.
Methadone
Methadone is a drug used for both opioid overuse treatment and for chronic pain, it is known as a full opioid agonist. Methadone is the most common prescribed out of all the medications used for addiction; this is due to the fact that it has more advantages and less disadvantages than the other medications. Due to methadones longer half life, it is much more challenging to prescribe dosage amounts compared to others. The long half life has good benefits, one of these benefits being the fact that if a dose is missed in the 24 hours of the last, the patient will not typically struggle with withdrawal symptoms quite yet. Methadone can be found in a couple different forms: tablet, oral solution, or an injection. The first time this medication was put to use was during World War II, it was a safer alternative to morphine.

Buprenorphine
Buprenorphine is a partial opioid receptor agonist. Unlike methadone and other full opioid receptor agonists, buprenorphine is less likely to cause respiratory depression due to its ceiling effect. Buprenorphine is known to be more at a risk of misuse or overdose compared to buprenorphine-naloxone and methadone, but treatment with buprenorphine may be associated with reduced mortality. Buprenorphine under the tongue is often used to manage opioid dependence. Preparations were approved for this use in the United States in 2002. Some formulations of buprenorphine incorporate the opiate antagonist naloxone during the production of the pill form to prevent people from crushing the tablets and injecting them, instead of using the sublingual (under the tongue) route of administration.

Other opioids
Evidence of effects of heroin maintenance compared to methadone are unclear as of 2010. A Cochrane review found some evidence in opioid users who had not improved with other treatments. In Switzerland, Germany, the Netherlands, and the United Kingdom, long-term injecting drug users who do not benefit from methadone and other medication options may be treated with injectable heroin that is administered under the supervision of medical staff. Other countries where it is available include Spain, Denmark, Belgium, Canada, and Luxembourg.Dihydrocodeine in both extended-release and immediate-release form are also sometimes used for maintenance treatment as an alternative to methadone or buprenorphine in some European countries. Dihydrocodeine is an opioid agonist. It may be used as a second line treatment. A 2020 systematic review found low quality evidence that dihydrocodeine may be no more effective than other routinely used medication interventions in reducing illicit opiate use.An extended-release morphine confers a possible reduction of opioid use and with fewer depressive symptoms but overall more adverse effects when compared to other forms of long-acting opioids. Retention in treatment was not found to be significantly different. It is used in Switzerland and more recently in Canada.

Naltrexone
Naltrexone is an opioid receptor antagonist used for the treatment of opioid addiction. Naltrexone is not as widely used as buprenorphine or methadone for OUD due to low rates of patient acceptance, non-adherence due to daily dosing, and difficulty achieving abstinence from opioids before beginning treatment. Additionally, dosing naltrexone after recent opioid use could lead to precipitated withdrawal. Conversely, naltrexone antagonism at the opioid receptor can be overcome with higher doses of opioids. Naltrexone monthly IM injections received FDA approval in 2010, for the treatment of opioid dependence in abstinent opioid users.

Behavioral therapy
Cognitive behavioral therapy
Cognitive behavioral therapy (CBT), a form of psychosocial intervention that is used to improve mental health, may not be as effective as other forms of treatment. CBT primarily focuses on an individuals coping strategies to help change their cognition, behaviors and emotions about the problem. This intervention has demonstrated success in many psychiatric conditions (e.g., depression) and substance use disorders (e.g., tobacco). However, the use of CBT alone in opioid dependence has declined due to the lack of efficacy, and many are relying on medication therapy or medication therapy with CBT, since both were found to be more efficacious than CBT alone. A form of CBT therapy known as motivational interviewing (MI) is often used opioid use disorder. MI leverages a person intrinsic motivation to recover through education, formulation of relapse prevention strategies, reward for adherence to treatment guidelines, and positive thinking to keep motivation high—which are based on a persons socioeconomic status, gender, race, ethnicity, sexual orientation, and their readiness to recover.

Twelve-step programs
While medical treatment may help with the initial symptoms of opioid withdrawal, once the first stages of withdrawal are through, a method for long-term preventative care is attendance at 12-step groups such as Narcotics Anonymous. Narcotics Anonymous is a global service that provides multilingual recovery information and public meetings free of charge. Some evidence supports the use of these programs in adolescents as well.The 12-step program is an adapted form of the Alcoholics Anonymous program. The program strives to help create behavioural change by fostering peer-support and self-help programs. The model helps assert the gravity of addiction by enforcing the idea that addicts must surrender to the fact that they are addicted and be able to recognize the problem. It also helps maintain self-control and restraint to help promote ones capabilities.

Digital care programs
Digital care programs (see telehealth or digital health) have increased in number since the Coronavirus pandemic mandated the increased usage of remote healthcare options. These programs offer treatment and continuing care remotely, via smartphone and desktop applications. This often includes remote substance testing, access to peer support meetings, recovery coaching or therapy, and self-guided learning modules. Examples of digital care programs for opioid use disorder include: Chess, Pear Therapeutics, DynamiCare Health, Kaden Health and WeConnect.

Epidemiology
Globally, the number of people with opioid dependence increased from 10.4 million in 1990 to 15.5 million in 2010. In 2016, the numbers rose to 27 million people who experienced this disorder. Opioid use disorders resulted in 122,000 deaths worldwide in 2015, up from 18,000 deaths in 1990. Deaths from all causes rose from 47.5 million in 1990 to 55.8 million in 2013.

United States
The current epidemic of opioid abuse is the most lethal drug epidemic in American history. In 2008, there were four times as many deaths due to overdose than there were in 1999. In 2017, in the US, "the age-adjusted drug poisoning death rate involving opioid analgesics increased from 1.4 to 5.4 deaths per 100,000 population between 1999 and 2010, decreased to 5.1 in 2012 and 2013, then increased to 5.9 in 2014, and to 7.0 in 2015. The age-adjusted drug poisoning death rate involving heroin doubled from 0.7 to 1.4 deaths per 100,000 resident population between 1999 and 2011 and then continued to increase to 4.1 in 2015."In 2017, the U.S. Department of Health and Human Services (HHS) announced a public health emergency due to an increase in the misuse of opioids. The administration introduced a strategic framework called the Five-Point Opioid Strategy, which includes providing access recovery services, increasing the availability of reversing agents for overdose, funding opioid misuse and pain research, changing treatments of people managing pain, and updating public health reports related to combating opioid drug misuse.The US epidemic in the 2000s is related to a number of factors. Rates of opioid use and dependency vary by age, sex, race, and socioeconomic status. With respect to race the discrepancy in deaths is thought to be due to an interplay between physician prescribing and lack of access to healthcare and certain prescription drugs. Men are at higher risk for opioid use and dependency than women, and men also account for more opioid overdoses than women, although this gap is closing. Women are more likely to be prescribed pain relievers, be given higher doses, use them for longer durations, and may become dependent upon them faster.Deaths due to opioid use also tend to skew at older ages than deaths from use of other illicit drugs. This does not reflect opioid use as a whole, which includes individuals in younger age demographics. Overdoses from opioids are highest among individuals who are between the ages of 40 and 50, in contrast to heroin overdoses, which are highest among individuals who are between the ages of 20 and 30. 21- to 35-year-olds represent 77% of individuals who enter treatment for opioid use disorder, however, the average age of first-time use of prescription painkillers was 21.2 years of age in 2013. Among the middle class means of acquiring funds have included Elder financial abuse through a vulnerability of financial transactions of selling items and international dealers noticing a lack of enforcement in their transaction scams throughout the Caribbean.In 2018, the Massachusetts Supreme Judicial Court found that a probationer with opioid use disorder could be detained for a parole violation after she tested positive for fentanyl.In October 2021, New York Governor Kathy Hochul signed legislation to combat the opioid crisis. This included establishing a program for the use of medication-assisted substance use disorder treatment for incarcerated individuals in state and local correctional facilities, decriminalizing the possession and sale of hypodermic needles and syringes, establishing an online directory for distributors of opioid antagonists, and expanding the number of eligible crimes committed by individuals with a substance use disorder that may be considered for diversion to a substance use treatment program. Until these laws were signed, incarcerated New Yorkers did not reliably have access to medication-assisted treatment and syringe possession was still a class A misdemeanor despite New York authorizing and funding syringe exchange and access programs </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 Testicular pain and can you explain it in depth? [/INST] Testicular pain, also known as scrotal pain, occurs when part or all of either one or both testicles hurt. Pain in the scrotum is also often included. Testicular pain may be of sudden onset or of long duration.Causes range from non serious muscular skeletal problems to emergency conditions such as Fournier gangrene and testicular torsion. The diagnostic approach involves making sure no serious conditions are present. Diagnosis may be supported by ultrasound, urine tests, and blood tests.Pain management is typically given with definitive management depending on the underlying cause.

Definition
Testicular pain is when part or all of either one or both testicles hurt. Pain of the scrotum is often included. It may be either acute, subacute or chronic depending on its duration.

Chronic scrotal pain
Chronic scrotal pain (pain for greater than 3 months) may occur due to a number of underlying conditions. It occurs in 15-19% of men post vasectomy, due to infections such as epididymitis, prostatitis, and orchitis, as well as varicocele, hydrocele, spermatocele, polyarteritis nodosa, testicular torsion, previous surgery and trauma.  In 25% of cases the cause is never determined. The pain can persist for a long and indefinite period of time following the vasectomy, in which case it is termed post-vasectomy pain syndrome (PVPS).

Differential diagnosis
The differential diagnosis of testicular pain is broad and involves conditions from benign to life-threatening. The most common causes of pain in children presenting to the emergency room are testicular torsion (16%), torsion of a testicular appendage (46%), and epididymitis (35%).  In adults, the most common cause is epididymitis.

Testicular torsion
Testicular torsion usually presents with an acute onset of diffuse testicular pain and tenderness  of less than 6 hrs of duration. There is often an absent or decreased cremasteric reflex, the testicle is elevated, and often is horizontal. It occurs annually in about 1 in 4,000 males before 25 years of age, is most frequent among adolescents (65% of cases presenting between 12 – 18 years of age), and is rare after 35 years of age. Because it can lead to necrosis within a few hours, it is considered a surgical emergency. Another version of this condition is a chronic illness called intermittent testicular torsion (ITT) which is characterized by recurrent rapid acute onset of pain in one testis which will temporarily assume a horizontal or elevated position in the scrotum similar to that of a full torsion followed by eventual spontaneous detortion and rapid solution of pain.  Nausea or vomiting may also occur.

Epididymitis and orchitis
Epididymitis occurs when there is inflammation of the epididymis (a curved structure at the back of the testicle).  This condition usually presents with gradual onset of varying degrees of pain, and the scrotum may be red, warm and swollen.  It is often accompanied by symptoms of a urinary tract infection, fever, and in over half of cases it presents in combination with orchitis.  In those between the ages of 14 to 35 it is usually caused by either gonorrhea or chlamydia.  In people either older or younger E </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 Telangiectasia and can you explain it in depth? [/INST] Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on the body, but are commonly seen on the face around the nose, cheeks and chin. Dilated blood vessels can also develop on the legs, although when they occur on the legs, they often have underlying venous reflux or "hidden varicose veins" (see Venous hypertension section below). When found on the legs, they are found specifically on the upper thigh, below the knee joint and around the ankles.
Many patients with spider veins seek the assistance of physicians who specialize in vein care or peripheral vascular disease. These physicians are called vascular surgeons or phlebologists. More recently, interventional radiologists have started treating venous problems.
Some telangiectasias are due to developmental abnormalities that can closely mimic the behaviour of benign vascular neoplasms. They may be composed of abnormal aggregations of arterioles, capillaries or venules. Because telangiectasias are vascular lesions, they blanch when tested with diascopy.
Telangiectasias, aside from presenting in many other conditions, are one of the features of the acronymically named CREST syndrome, a form of systemic scleroderma. The syndrome recognises the significantly co-presenting symptoms of calcinosis, Raynauds phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia.

Causes
The causes of telangiectasia can be divided into congenital and acquired factors.

Genetic
Goldman states that "numerous inherited or congenital conditions display cutaneous telangiectasia". These include:

Bloom syndrome (homozygous null mutation in BLM DNA repair enzyme. similar mechanism and etiology to ataxia telangiectasia)
Naevus flammeus (port-wine stain)
Klippel–Trenaunay syndrome
Maffucci syndrome (multiple enchondromas and hemangiomas)
Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu syndrome)
Ataxia–telangiectasia
Sturge–Weber syndrome, a nevus formation in the skin supplied by the trigeminal nerve and associated with facial port-wine stains, glaucoma, meningeal angiomas and intellectual disabilities
Hypotrichosis–lymphedema–telangiectasia syndrome, caused by mutation in transcription factor SOX18

Venous hypertension
In the past, it was believed that leg varicose veins or telangectasia were caused by high venous pressure or "venous hypertension". However it is now understood that venous reflux disease is usually the cause of these problems.Telangiectasia in the legs is often related to the presence of venous reflux within underlying varicose veins. Flow abnormalities within the medium-sized veins of the leg (reticular veins) can also lead to the development of telangiectasia.
Factors that predispose to the development of varicose and telangiectatic leg veins include

Age
Sex: It used to be thought that females were affected far more than males. However, research has shown 79% of adult males and 88% of adult females have leg telangectasia (spider veins).
Pregnancy: Pregnancy is a key factor contributing to the formation of varicose and spider veins. Changes in hormone levels are one of the most important reasons women are more likely to develop varicose veins during pregnancy. There is an increase in progesterone, which causes the veins to relax and potentially swell more easily. Theres also a significant increase in the blood volume during pregnancy, which tends to distend veins, causing valve dysfunction which leads to blood pooling in the veins. Moreover, later in pregnancy, the enlarged uterus can compress veins, causing higher vein pressure leading to dilated veins. Varicose veins that form during pregnancy may spontaneously improve or even disappear a few months after delivery.
Life-style/occupation: Those who are involved with prolonged sitting or standing in their daily activities have an increased risk of developing varicose veins. The weight of the blood continuously pressing against the closed valves causes them to fail, leading to vein distention.

Other acquired causes
Acquired telangiectasia, not related to other venous abnormalities, for example on the face and trunk, can be caused by factors such as

Cushings syndrome
Rosacea
Blepharitis
Environmental damage such as that caused by sun or cold exposure
Age
Trauma to skin such as contusions or surgical incisions.
Radiation exposure such as that experienced during radiotherapy for the treatment of cancer, e.g., radiation proctitis
Chemotherapy
Carcinoid syndrome
Limited systemic sclerosis/scleroderma (a scleroderma sub-type)
Chronic treatment with topical corticosteroids may lead to telangiectasia.
Spider angiomas are a radial array of tiny arterioles that commonly occur in pregnant women and in patients with hepatic cirrhosis and are associated with palmar erythema.  In men, they are related to high estrogen levels secondary to liver disease.
Tempi syndrome
Tobacco smoking
Cutaneous collagenous vasculopathy

Treatment
Before any treatment of leg telangectasia (spider veins) is considered, it is essential to have duplex ultrasonography, the test that has replaced Doppler ultrasound. The reason for this is that there is a clear association between leg telangectasia (spider veins) and underlying venous reflux. Research has shown that 88% to 89% of women with telangectasia (spider veins) have refluxing reticular veins close, and 15% have incompetent perforator veins nearby. As such, it is essential to both find and treat underlying venous reflux before considering any treatment at all.
Sclerotherapy is the "gold standard" and is preferred over laser for eliminating telangiectasiae and smaller varicose leg veins </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 Ophthalmoparesis 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 Body odor and can you explain it in depth? [/INST] Body odor or body odour (BO) is present in all animals and its intensity can be influenced by many factors (behavioral patterns, survival strategies). Body odor has a strong genetic basis, but can also be strongly influenced by various diseases and physiological conditions. Though body odor has played an important role (and continues to do so in many life forms) in early humankind, it is generally considered to be an unpleasant odor amongst many human cultures.

Causes
In humans, the formation of body odors is caused by factors such as diet, sex, health, and medication, but the major contribution comes from bacterial activity on skin gland secretions. Humans have three types of sweat glands: eccrine sweat glands, apocrine sweat glands and sebaceous glands. Eccrine sweat glands are present from birth, while the latter two become activated during puberty. Among the different types of human skin glands, body odor is primarily the result of the apocrine sweat glands, which secrete the majority of chemical compounds that the skin flora metabolize into odorant substances. This happens mostly in the axillary (armpit) region, although the gland can also be found in the areola, anogenital region, and around the navel. In humans, the armpit regions seem more important than the genital region for body odor, which may be related to human bipedalism. The genital and armpit regions also contain springy hairs which help diffuse body odors.The main components of human axillary odor are unsaturated or hydroxylated branched fatty acids with E-3M2H (E-3-methylhex-2-enoic acid) and HMHA (3-hydroxy-3-methylhexanoic acid), sulfanylalkanols and particularly 3M3SH (3-methyl-3-sulfanylhexan-1-ol), and the odoriferous steroids androstenone (5α-androst-16-en-3-one) and androstenol (5α-androst-16-en-3α-ol). E-3M2H is bound and carried by two apocrine secretion odor-binding proteins, ASOB1 and ASOB2, to the skin surface.Body odor is influenced by the actions of the skin flora, including members of Corynebacterium, which manufacture enzymes called lipases that break down the lipids in sweat to create smaller molecules like butyric acid. Greater bacteria populations of Corynebacterium jeikeium are found more in the armpits of men, whereas greater population numbers of Staphylococcus haemolyticus are found in the armpits of women. This causes male armpits to give off a rancid/cheese-like smell, whereas female armpits give off a more fruity/onion-like smell. Staphylococcus hominis is also known for producing thioalcohol compounds that contribute to odors. These smaller molecules smell, and give body odor its characteristic aroma. Propionic acid (propanoic acid) is present in many sweat samples. This acid is a breakdown product of some amino acids by propionibacteria, which thrive in the ducts of adolescent and adult sebaceous glands. Because propionic acid is chemically similar to acetic acid, with similar characteristics including odor, body odors may be identified as having a vinegar-like smell by certain people. Isovaleric acid (3-methyl butanoic acid) is the other source of body odor as a result of actions of the bacteria Staphylococcus epidermidis, which is also present in several types of strong cheese.
Factors such as food, drink, and diseases can affect body odor, as can lifestyle and genetics.

Function
Animals
In many animals, body odor plays an important survival function. Strong body odor can be a warning signal for predators to stay away (such as porcupine stink), or it can also be a signal that the prey animal is unpalatable. For example, some animals species, who feign death to survive (like opossums), in this state produce a strong body odor to deceive a predator that the prey animal has been dead for a long time and is already in the advanced stage of decomposing. Some animals with strong body odor are rarely attacked by most predators, although they can still be killed and eaten by birds of prey, which are tolerant of carrion odors.Body odor is an important feature of animal physiology. It plays a different role in different animal species. For example, in some predator species that hunt by stalking (such as big and small cats), the absence of body odor is important, and they spend plenty of time and energy to keep their body free of odor. For other predators, such as those that hunt by visually locating prey and running for long distances after it (such as dogs and wolves), the absence of body odor is not critical. In most animals, body odor intensifies in moments of stress and danger.

Humans
Sebaceous and apocrine glands become active at puberty. This, as well as many apocrine glands being close to the sex organs, points to a role related to mating. Compared to other primates, humans have extensive axillary hair and have many odor producing sources, in particular many apocrine glands. In women, the sense of olfaction is strongest around the time of ovulation, significantly stronger than during other phases of the menstrual cycle and also stronger than the sense in males.Humans can olfactorily detect blood-related kin. Mothers can identify by body odor their biological children, but not their stepchildren. Preadolescent children can olfactorily detect their full siblings, but not half-siblings or step-siblings, and this might explain incest avoidance and the Westermarck effect. Babies can recognize their mothers by smell while mothers, fathers, and other relatives can identify a baby by smell.Humans have few olfactory receptor cells compared to dogs and few functional olfactory receptor genes compared to rats. This is in part due to a reduction of the size of the snout in order to achieve depth perception as well as other changes related to bipedalism. However, it has been argued that humans may have larger brain areas associated with olfactory perception compared to other species.Studies have suggested that people might be using odor cues associated with the immune system to select mates. Using a brain-imaging technique, Swedish researchers have shown that homosexual and heterosexual males brains respond in different ways to two odors that may be involved in sexual arousal, and that homosexual men respond in the same way as heterosexual women, though it could not be determined whether this was cause or effect. When the study was expanded to include lesbian women, the results were consistent with previous findings – meaning that lesbian women were not as responsive to male-identified odors, while responding to female odors in a similar way as heterosexual males. According to the researchers, this research suggests a possible role for human pheromones in the biological basis of sexual orientation.

Genes affecting body odor
MHC
Body odor is largely influenced by major histocompatibility complex (MHC) molecules. These are genetically determined and play an important role in immunity of the organism. The vomeronasal organ contains cells sensitive to MHC molecules in a genotype-specific way.Experiments on animals and volunteers have shown that potential sexual partners tend to be perceived more attractive if their MHC composition is substantially different. Married couples are more different regarding MHC genes than would be expected by chance. This behavior pattern promotes variability of the immune system of individuals in the population, thus making the population more robust against new diseases. Another reason may be to prevent inbreeding.

ABCC11
The ABCC11 gene determines axillary body odor and the type of earwax. The loss of a functional ABCC11 gene is caused by a 538G>A single-nucleotide polymorphism, resulting in a loss of body odor in people who are specifically homozygous for it. Firstly, it affects apocrine sweat glands by reducing secretion of odorous molecules and its precursors. The lack of ABCC11 function results in a decrease of the odorant compounds 3M2H, HMHA, and 3M3SH via a strongly reduced secretion of the precursor amino-acid conjugates 3M2H–Gln, HMHA–Gln, and Cys–Gly–(S) 3M3SH; and a decrease of the odoriferous steroids androstenone and androstenol, possibly due to the reduced levels and secretion of DHEAS and DHEA (possibly bacterial substrates for odoriferous steroids). Secondly, it is also associated with a strongly reduced/atrophic size of apocrine sweat glands and a decreased protein (such as ASOB2) concentration in axillary sweat.The non-functional ABCC11 allele is predominant among East Asians (80–95%), but very low in other ancestral groups (0–3%). Most of the worlds population has the gene that codes for the wet-type earwax and average body odor; however, East Asians are more likely to inherit the allele associated with the dry-type earwax and a reduction in body odor. The hypothesized reduction in body odor may be due to adaptation to colder climates by their ancient Northeast Asian ancestors.However, research has observed that this allele is not solely responsible for ethnic differences in scent. A 2016 study analyzed differences across ethnicities in volatile organic compounds (VOCs), across racial groups and found that while they largely did not differ significantly qualitatively, they did differ quantitatively. Of the observed differences, they were found to vary with ethnic origin, but not entirely with ABCC11 genotype.It has been noted that there is currently no evidence that sweat secretion glands nor sweat production varies across ethnicities. One large study failed to find any significant differences across ethnicity in residual compounds on the skin, including those located in sweat </s>