<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 Intrahepatic cholestasis of pregnancy and can you explain it in depth? [/INST] Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, cholestasis of pregnancy, jaundice of pregnancy, and prurigo gravidarum, is a medical condition in which cholestasis occurs during pregnancy. It typically presents with itching and can lead to complications for both mother and baby.
Pruritus (itching) is a common symptom of pregnancy, affecting around 23% of women. The majority of times, itching is a minor annoyance caused by changes to the skin, especially that of the abdomen. However, there are instances when itching may be a symptom of ICP. Although typically noticed on the palms of the hands and the soles of the feet, the itching can occur anywhere on the body.
ICP occurs most commonly in the third trimester, but can begin at any time during the pregnancy.

Signs and symptoms
Most women with this condition present in the third trimester (although it can present as early as seven weeks) with itching without a rash. Typically, the itching is localized to the palms of the hands and soles of the feet, but can be anywhere on the body.
Hallmarks of ICP include the following symptoms:Most common:

Itching, in particular but not limited to that of the palms of the hands and soles of the feet, without presence of a rash
Itching that is more noticeable in the evening
Darker urineLess common:

Lighter stools
Increased clotting time (due to possibly associated vitamin K deficiency)
Fatigue
Increased nausea
Decrease in appetite
Jaundice (less than 10% of women)
Upper right quadrant painNot all ICP sufferers have all of the above symptoms.

Mechanism
The causes of intrahepatic cholestasis of pregnancy are still not fully understood, but are thought to be caused through a combination of genetics, hormones and environment. Hormones, environmental and genetic factors are all thought to contribute to the condition.
ICP commonly occurs in the third trimester at the time when hormone levels are at their highest.
Twin and triplet pregnancies, which are associated with higher hormone levels, show a higher incidence of ICP.
ICP resolves quickly after delivery, when placental hormone production ceases.
Older high-dose estrogen oral contraceptive pills could cause features of ICP.

Estrogens
Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes.

Progesterone
Treatment with progesterone in the third trimester of pregnancy has been shown to be associated with the development of ICP, and levels of metabolites of progesterone, particularly sulfated progesterone, are higher in patients with ICP than unaffected women, suggesting that progesterone may have a bigger role than estrogen in ICP.

Genetic factors
Clustering of cases of ICP in families, geographic variation in rates of ICP, and recurrence of ICP in 45-70% of subsequent pregnancies all suggest a genetic component to the disease. Genetic mutations in the hepatocellular transport protein ABCB4 (MDR3), which controls secretion of phosphatidylcholine into bile, have been found in cases of ICP.Genetic mutations affecting hepatic bile salt transport molecules have also been found in patients with progressive familial intrahepatic cholestasis. It has been found that mothers of patients with this disease have a higher incidence of ICP, suggesting that heterozygote carriers of these mutations are also predisposed to ICP.In addition to genetic changes to bile salt transport molecules, high levels of estrogen glucuronides have been shown to inhibit the bile salt export pump (BSEP) ABCB11, and high levels of progesterone to inhibit the ABCB4 (MDR3) phospholipid transporter.Consequently, both genetic mutations in hepatocyte proteins involved in bile secretion together with inhibition of those proteins by high levels of hormone metabolites in pregnancy may have roles in the pathogenesis of ICP.

Environmental factors
A number of features of ICP suggest that environmental factors also have a role in the disease:

It has been reported that the incidence of ICP is higher in winter than summer.
The incidence of ICP in Chile has dropped from 14% of pregnancies before 1975 to 4% in 2016.
ICP recurs in between 60% and 90% of subsequent pregnancies.
Low serum selenium levels have been linked to ICP, although the role of selenium in bile secretion is not known.

Diagnosis
ICP is diagnosed by blood tests including a serum bile acid test and liver function test. While most pregnant women experience some itch from time to time, itching without a visible rash, or persistent or extensive itch symptoms should be reported to the midwife or obstetrician. It is important to note that as the level of itch does not correlate with bile acid levels (shown to be the most likely cause of stillbirth in ICP), the itch in ICP can range from being mild to severe.To obtain a diagnosis of ICP, a liver function test and a serum bile acid test should be requested. Although the ALT level may be raised, 20% of women with ICP will always have a normal LFT test result </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 Intrauterine hypoxia and can you explain it in depth? [/INST] Intrauterine hypoxia (also known as fetal hypoxia) occurs when the fetus is deprived of an adequate supply of oxygen.  It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction, maternal diabetes (prepregnancy or gestational diabetes) and maternal smoking. Intrauterine growth restriction may cause or be the result of hypoxia.  Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system (the brain and spinal cord). This results in an increased mortality rate, including an increased risk of sudden infant death syndrome (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as epilepsy, attention deficit hyperactivity disorder, eating disorders and cerebral palsy.

Presentation
Maternal Consequences
Complications arising from intrauterine hypoxia are some of the leading causes of preeclampsia.  Preeclampsia is a hypertensive disorder that occurs during the second trimester (after the 20th week of pregnancy) resulting from a poorly perfused placenta. Studies from the World Health Organization show that globally, about 14% (50,000- 750000 women) of maternal deaths annually are caused by preeclampsia and eclampsia.During pregnancy, women with preeclampsia faces serious risk of damage to vital organs such as the kidneys, liver, brain, and the blood system. This hypertensive disorder may also cause damage to the placenta leading to issues such as premature births, miscarriages, placental abruption, or even stillbirths. In some cases, preeclampsia can eventually lead to stroke and organ failure.  Untreated, preeclampsia can progress and turn into eclampsia which is much more severe with the addition of seizures. Eclampsia seizures could lead to uncontrollable twitching and a loss of consciousness, which could potentially lead to the death of the mother and or the baby.

Cause
Intrauterine hypoxia can be attributed to maternal, placental, or fetal conditions. Kingdom and Kaufmann classifies three categories for the origin of fetal hypoxia: 1) pre-placental (both mother and fetus are hypoxic), 2) utero-placental (mother is normal but placenta and fetus is hypoxic), 3) post-placental (only fetus is hypoxic).Pre-placental hypoxia is most commonly caused by external hypoxic environments (such as high altitude). It can also be caused by maternal respiratory conditions (such as asthma), cardiovascular conditions (such as heart failure, pulmonary hypertension, and cyanotic heart disease), and hematological conditions (such as anemia). Conditions such as obesity, nutritional deficiencies, infections, chronic inflammations, and stress can also affect the maternal oxygen supply and fetal uptake.The most preventable cause is maternal smoking. Cigarette smoking by expectant mothers has been shown to have a wide variety of deleterious effects on the developing fetus. Among the negative effects are carbon monoxide induced tissue hypoxia and placental insufficiency which causes a reduction in blood flow from the uterus to the placenta thereby reducing the availability of oxygenated blood to the fetus. Placental insufficiency as a result of smoking has been shown to have a causal effect in the development of pre-eclampsia. While some previous studies have suggested that carbon monoxide from cigarette smoke may have a protective effect against preeclampsia, a recent study conducted by the Genetics of Pre-Eclampsia Consortium in the United Kingdom found that smokers were five times more likely to develop pre-eclampsia.Nicotine alone has been shown to be a teratogen which affects the autonomic nervous system, leading to increased susceptibility to hypoxia-induced brain damage.
Maternal anemia in which smoking has also been implicated is another factor associated with IH/BA. Smoking by expectant mothers causes a decrease in maternal nucleated red blood cells, thereby reducing the amount of red blood cells available for oxygen transport.Utero-placental hypoxia is associated with abnormal placental implantation, impaired vascular remodeling and vascular diseases. It is also associated with pregnancies complicated by gestational hypertension, intrauterine growth restriction, and pre-eclampsia.Post-placental hypoxia is associated with mechanical obstructions of the umbilical cords, reduced uterine artery flow, progressive fetal cardiac failure, and genetic anomalies.The perinatal brain injury occurring as a result of birth asphyxia, manifesting within 48 hours of birth, is a form of hypoxic ischemic encephalopathy.

Diagnosis
Treatment
Treatment of infants with birth asphyxia by lowering the core body temperature is now known to be an effective therapy to reduce mortality and improve neurological outcome in survivors, and hypothermia therapy for neonatal encephalopathy begun within 6 hours of birth significantly increases the chance of normal survival in affected infants.There has long been a debate over whether newborn infants with birth asphyxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen. Increasing the oxygen concentration to the mother has shown little effect on the fetus as hyperoxygenated blood does not perfuse the placental exchange site well.Underlying etiology of intrauterine hypoxia serves as a potential therapeutic target </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 Injury and can you explain it in depth? [/INST] An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, or overexertion. Injuries can occur in any part of the body, and different symptoms are associated with different injuries.
Treatment of a major injury is typically carried out by a health professional and varies greatly depending on the nature of the injury. Traffic collisions are the most common cause of accidental injury and injury-related death among humans. Injuries are distinct from chronic conditions, psychological trauma, infections, or medical procedures, though injury can be a contributing factor to any of these.
Several major health organizations have established systems for the classification and description of human injuries.

Occurrence
Injuries may be intentional or unintentional. Intentional injuries may be acts of violence against others or self-harm against ones own person. Accidental injuries may be unforeseeable or they may be caused by negligence The most common types of unintentional injuries in order are traffic accidents, falls, drowning, burns, and accidental poisoning. Certain types of injuries are more common in developed countries or developing countries. Traffic injuries are more likely to kill pedestrians than drivers in developing countries. Scalding burns are more common in developed countries, while open-flame injuries are more common in developing countries.As of 2021, approximately 4.4 million people are killed due to injuries each year worldwide, constituting nearly 8% of all deaths. 3.16 million of these injuries are unintentional and 1.25 million are intentional. Traffic accidents are the most common form of deadly injury, causing about one-third of injury-related deaths. One-sixth are caused by suicide, and one-tenth are caused by homicide. Tens of millions of individuals require medical treatment for nonfatal injuries each year, and injuries are responsible for about 10% of all years lived with disability. Men are twice as likely to be killed through injury than women. In 2013, 367,000 children under the age of five died from injuries, down from 766,000 in 1990.

Classification systems
The World Health Organization (WHO) developed the International Classification of External Causes of Injury (ICECI). Under this system, injuries are classified by mechanism of injury, objects/substances producing injury, place of occurrence, activity when injured, the role of human intent, and additional modules. These codes allow the identification of distributions of injuries in specific populations and case identification for more detailed research on causes and preventive efforts.The United States Bureau of Labor Statistics developed the Occupational Injury and Illness Classification System (OIICS). Under this system injuries are classified by nature, part of body affected, source and secondary source, and event or exposure. The OIICS was first published in 1992 and has been updated several times since. The Orchard Sports Injury and Illness Classification System (OSIICS), previously OSICS, is used to classify injuries to enable research into specific sports injuries.The injury severity score (ISS) is a medical score to assess trauma severity. It correlates with mortality, morbidity, and hospitalization time after trauma. It is used to define the term major trauma (polytrauma), recognized when the ISS is greater than 15. The AIS Committee of the Association for the Advancement of Automotive Medicine designed and updates the scale.

Mechanisms
Trauma
Traumatic injury is caused by an external object making forceful contact with the body, resulting in a wound. Major trauma is a severe traumatic injury that has the potential to cause disability or death. Serious traumatic injury most often occurs as a result of traffic collisions. Traumatic injury is the leading cause of death in people under the age of 45.Blunt trauma injuries are caused by the forceful impact of an external object. Injuries from blunt trauma may cause internal bleeding and bruising from ruptured capillaries beneath the skin, abrasion from scraping against the superficial epidermis, lacerated tears on the skin or internal organs, or bone fractures. Crush injuries are a severe form of blunt trauma damage that apply large force to a large area over a longer period of time. Penetrating trauma injuries are caused by external objects entering the tissue of the body through the skin. Low-velocity penetration injuries are caused by sharp objects, such as stab wounds, while high-velocity penetration injuries are caused by ballistic projectiles, such as gunshot wounds or injuries caused by shell fragments. Perforated injuries result in an entry wound and an exit wound, while puncture wounds result only in an entry wound. Puncture injuries result in a cavity in the tissue.

Burns
Burn injury is caused by contact with extreme temperature, chemicals, or radiation. The effects of burns vary depending on the depth and size. Superficial or first-degree burns only affect the epidermis, causing pain for a short period of time. Superficial partial-thickness burns cause weeping blisters and require dressing. Deep partial-thickness burns are dry and less painful due to the burning away of the skin and require surgery. Full-thickness or third-degree burns affect the entire dermis and is susceptible to infection. Fourth-degree burns reach deep tissues such as muscles and bones, causing loss of the affected area.Thermal burns are the most common type of burn, caused by contact with excessive heat, including contact with flame, contact with hot surfaces, or scalding burns caused by contact with hot water or steam. Frostbite is a type of burn caused by contact with excessive cold, causing cellular injury and deep tissue damage through the crystallization of water in the tissue. Friction burns are caused by friction with external objects, resulting in a burn and abrasion. Radiation burns are caused by exposure to ionizing radiation. Most radiation burns are sunburns caused by ultraviolet radiation or high exposure to radiation through medical treatments such as repeated radiography or radiation therapy.Electrical burns are caused by contact with electricity as it enters and passes through the body. They are often deeper than other burns, affecting lower tissues as electricity penetrates the skin, and the full extent of electrical burns are often obscured. They will also cause extensive destruction of tissue at the entry and exit points. Electrical injuries in the home are often minor, while high tension power cables cause serious electrical injuries in the workplace. Lightning strikes can also cause severe electrical injuries. Fatal electrical injuries are often caused by tetanic spasm inducing respiratory arrest or interference with the heart causing cardiac arrest.Chemical burns are caused by contact with corrosive substances such as acid or alkali. Chemical burns are rarer than most other burns, though there are many chemicals that can damage tissue. The most common chemical-related injuries are those caused by carbon monoxide, ammonia, chlorine, hydrochloric acid, and sulfuric acid. Some chemical weapons induce chemical burns, such as white phosphorus. Most chemical burns are treated with extensive application of water to remove the chemical contaminant, though some burn-inducing chemicals react with water to create more severe injuries. The ingestion of corrosive substances can cause chemical burns to the larynx and stomach.

Other mechanisms
Toxic injury is caused by the ingestion, inhalation, injection, or absorption of a toxin. This may occur through an interaction caused by a drug or the ingestion of a poison. Different toxins may cause different types of injuries, and many will cause injury to specific organs. Toxins in gases, dusts, aerosols, and smoke can be inhaled, potentially causing respiratory failure. Respiratory toxins can be released by structural fires, industrial accidents, domestic mishaps, or through chemical weapons. Some toxicants may affect other parts of the body after inhalation, such as carbon monoxide.Asphyxia causes injury to the body from a lack of oxygen. It can be caused by drowning, inhalation of certain substances, strangulation, blockage of the airway, traumatic injury to the airway, apnea, and other means. The most immediate injury caused by asphyxia is hypoxia, which can in turn cause acute lung injury or acute respiratory distress syndrome as well as damage to the circulatory system. The most severe injury associated with asphyxiation is cerebral hypoxia and ischemia, in which the brain receives insufficient oxygen or blood, resulting in neurological damage or death. Specific injuries are associated with water inhalation, including alveolar collapse, atelectasis, intrapulmonary shunting, and ventilation perfusion mismatch. Simple asphyxia is caused by a lack of external oxygen supply. Systemic asphyxia is caused by exposure to a compound that prevents oxygen from being transported or used by the body. This can be caused by azides, carbon monoxide, cyanide, smoke inhalation, hydrogen sulfide, methemoglobinemia-inducing substances, opioids, or other systemic asphyxiants. Ventilation and oxygenation are necessary for treatment of asphyxiation, and some asphyxiants can be treated with antidotes.Injuries of overuse or overexertion can occur when the body is strained through use, affecting the bones, muscles, ligaments, or tendons. Sports injuries are often overuse injuries such as tendinopathy. Over-extension of the ligaments and tendons can result in sprains and strains, respectively. Repetitive sedentary behaviors such as extended use of a computer or a physically repetitive occupation may cause a repetitive strain injury. Extended use of brightly lit screens may also cause eye strain.

Locations
Abdomen
Abdominal trauma includes injuries to the stomach, intestines, liver, pancreas, kidneys, gallbladder, and spleen. Abdominal injuries are typically caused by traffic accidents, assaults, falls, and work-related injuries, and physical examination is often unreliable in diagnosing blunt abdominal trauma. Splenic injury can cause low blood volume or blood in the peritoneal cavity. The treatment and prognosis of splenic injuries are dependent on cardiovascular stability. The gallbladder is rarely injured in blunt trauma, occurring in about 2% of blunt abdominal trauma cases. Injuries to the gallbladder are typically associated with injuries to other abdominal organs. The intestines are susceptible to injury following blunt abdominal trauma. The kidneys are protected by other structures in the abdomen, and most injuries to the kidney are a result of blunt trauma. Kidney injuries typically cause blood in the urine.Due to its location in the body, pancreatic injury is relatively uncommon but more difficult to diagnose. Most injuries to the pancreas are caused by penetrative trauma, such as gunshot wounds and stab wounds. Pancreatic injuries occur in under 5% of blunt abdominal trauma cases. The severity of pancreatic injury depends primarily on the amount of harm caused to the pancreatic duct. The stomach is also well protected from injury due to its heavy layering, its extensive blood supply, and its position relative to the rib cage. As with pancreatic injuries, most traumatic stomach injuries are caused by penetrative trauma, and most civilian weapons do not cause long-term tissue damage to the stomach. Blunt trauma injuries to the stomach are typically caused by traffic accidents. Ingestion of corrosive substances can cause chemical burns to the stomach. Liver injury is the most common type of organ damage in cases of abdominal trauma. The livers size and location in the body makes injury relatively common compared to other abdominal organs, and blunt trauma injury to the liver is typically treated with nonoperative management. Liver injuries are rarely serious, though most injuries to the liver are concomitant with other injuries, particularly to the spleen, ribs, pelvis, or spinal cord. The liver is also susceptible to toxic injury, with overdose of paracetamol being a common cause of liver failure.

Face
Facial trauma may affect the eyes, nose, ears, or mouth. Nasal trauma is a common injury and the most common type of facial injury. Oral injuries are typically caused by traffic accidents or alcohol-related violence, though falls are a more common cause in young children. The primary concerns regarding oral injuries are that the airway is clear and that there are no concurrent injuries to other parts of the head or neck. Oral injuries may occur in the soft tissue of the face, the hard tissue of the mandible, or as dental trauma.The ear is susceptible to trauma in head injuries due to its prominent location and exposed structure. Ear injuries may be internal or external. Injuries of the external ear are typically lacerations of the cartilage or the formation of a hematoma. Injuries of the middle and internal ear may include a perforated eardrum or trauma caused by extreme pressure changes. The ear is also highly sensitive to blast injury. The bones of the ear are connected to facial nerves, and ear injuries can cause paralysis of the face. Trauma to the ear can cause hearing loss.Eye injuries often take place in the cornea, and they have the potential to permanently damage vision. Corneal abrasions are a common injury caused by contact with foreign objects. The eye can also be injured by a foreign object remaining in the cornea. Radiation damage can be caused by exposure to excessive light, often caused by welding without eye protection or being exposed to excessive ultraviolet radiation, such as sunlight. Exposure to corrosive chemicals can permanently damage the eyes, causing blindness if not sufficiently irrigated. The eye is protected from most blunt injuries by the infraorbital margin, but in some cases blunt force may cause an eye to hemorrhage or tear. Overuse of the eyes can cause eye strain, particularly when looking at brightly lit screens for an extended period.

Heart
Cardiac injuries affect the heart and blood vessels. Blunt cardiac injury in a common injury caused by blunt trauma to the heart. It can be difficult to diagnose, and it can have many effects on the heart, including contusions, ruptures, acute valvular disorders, arrhythmia, or heart failure. Penetrative trauma to the heart is typically caused by stab wounds or gunshot wounds. Accidental cardiac penetration can also occur in rare cases from a fractured sternum or rib. Stab wounds to the heart are typically survivable with medical attention, though gunshot wounds to the heart are not. The right ventricle is most susceptible to injury due to its prominent location. The two primary consequences of traumatic injury to the heart are severe hemorrhaging and fluid buildup around the heart.

Musculoskeletal
Musculoskeletal injuries affect the skeleton and the muscular system. Soft tissue injuries affect the skeletal muscles, ligaments, and tendons. Ligament and tendon injuries account for half of all musculoskeletal injuries. Ligament sprains and tendon strains are common injuries that do not require intervention, but the healing process is slow. Physical therapy can be used to assist reconstruction and use of injured ligaments and tendons. Torn ligaments or tendons typically require surgery. Skeletal muscles are abundant in the body and commonly injured when engaging in athletic activity. Muscle injuries trigger an inflammatory response to facilitate healing. Blunt trauma to the muscles can cause contusions and hematomas. Excessive tensile strength can overstretch a muscle, causing a strain. Strains may present with torn muscle fibers, hemorrhaging, or fluid in the muscles. Severe muscle injuries in which a tear extends across the muscle can cause total loss of function. Penetrative trauma can cause laceration to muscles, which may take an extended time to heal. Unlike contusions and strains, lacerations are uncommon in sports injuries.Traumatic injury may cause various bone fractures depending on the amount of force, direction of the force, and width of the area affected. Pathologic fractures occur when a previous condition weakens the bone until it can be easily fractured. Stress fractures occur when the bone is overused or suffers under excessive or traumatic pressure, often during athletic activity. Hematomas occur immediately following a bone fracture, and the healing process often takes from six weeks to three months to complete, though continued use of the fractured bone will prevent healing. Articular cartilage damage may also affect function of the skeletal system, and it can cause posttraumatic osteoarthritis. Unlike most bodily structures, cartilage cannot be healed once it is damaged.

Nervous system
Injuries to the nervous system include brain injury, spinal cord injury, and nerve injury. Trauma to the brain causes traumatic brain injury (TBI), causing "long-term physical, emotional, behavioral, and cognitive consequences". Mild TBI, including concussion, often occurs during athletic activity, military service, or as a result of untreated epilepsy, and its effects are typically short-term. More severe injuries to the brain cause moderate TBI, which may cause confusion or lethargy, or severe TBI, which may result in a coma or a secondary brain injury. TBI is a leading cause of mortality. Approximately half of all trauma-related deaths involve TBI. Non-traumatic injuries to the brain causeacquired brain injury (ABI). This can be caused by stroke, a brain tumor, poison, infection, cerebral hypoxia, drug use, or the secondary effect of a TBI.Injury to the spinal cord is not immediately terminal, but it is associated with concomitant injuries, lifelong medical complications, and reduction in life expectancy. It may result in complications in several major organ systems and a significant reduction in mobility or paralysis. Spinal shock causes temporary paralysis and loss of reflexes. Unlike most other injuries, damage to the peripheral nerves is not healed through cellular proliferation. Following nerve injury, the nerves undergo degeneration before regenerating, and other pathways can be strengthened or reprogrammed to make up for lost function. The most common form of peripheral nerve injury is stretching, due to their inherent elasticity. Nerve injuries may also be caused by laceration or compression.

Pelvis
Injuries to the pelvic area include injuries to the bladder, rectum, colon, and reproductive organs. Traumatic injury to the bladder is rare and often occurs with other injuries to the abdomen and pelvis. The bladder is protected by the peritoneum, and most cases of bladder injury are concurrent with a fracture of the pelvis. Bladder trauma typically causes hematuria, or blood in the urine. Ingestion of alcohol may cause distension of the bladder, increasing the risk of injury. A catheter may be used to extract blood from the bladder in the case of hemorrhaging, though injuries that break the peritoneum typically require surgery. The colon is rarely injured by blunt trauma, with most cases occurring from penetrative trauma through the abdomen. Rectal injury is less common than injury to the colon, though the rectum is more susceptible to injury following blunt force trauma to the pelvis.Injuries to the male reproductive system are rarely fatal and typically treatable through grafts and reconstruction. The elastic nature of the scrotum makes it resistant to injury, accounting for 1% of traumatic injuries. Trauma to the scrotum may cause damage to the testis or the spermatic cord. Trauma to the penis can cause penile fracture, typically as a result of vigorous intercourse. Injuries to the female reproductive system are often a result of pregnancy and childbirth or sexual activity. They are rarely fatal, but they can produce a variety of complications, such as chronic discomfort, dyspareunia, infertility, or the formation of fistulas. Age can greatly affect the nature of genital injuries in women due to changes in hormone composition. Childbirth is the most common cause of genital injury to women of reproductive age. Many cultures practice female genital mutilation, which is estimated to affect over 125 million women and girls worldwide as of 2018. Tears and abrasions to the vagina are common during sexual intercourse, and these may be exacerbated in instances of non-consensual sexual activity.

Respiratory tract
Injuries to the respiratory tract affect the lungs, diaphragm, trachea, bronchus, pharynx, or larynx. Tracheobronchial injuries are rare and often associated with other injuries. Bronchoscopy is necessary for an accurate diagnosis of tracheobronchial injury. The neck, including the pharynx and larynx, is highly vulnerable to injury due to its complex, compacted anatomy. Injuries to this area can cause airway obstruction. Ingestion of corrosive chemicals can cause chemical burns to the larynx. Inhalation of toxic materials can also cause serious injury to the respiratory tract.Severe trauma to the chest can cause damage to the lungs, including pulmonary contusions, accumulation of blood, or a collapsed lung. The inflammation response to a lung injury can cause acute respiratory distress syndrome. Injuries to the lungs may cause symptoms ranging from shortness of breath to terminal respiratory failure. Injuries to the lungs are often fatal, and survivors often have a reduced quality of life. Injuries to the diaphragm are uncommon and rarely serious, but blunt trauma to the diaphragm can result in the formation of a hernia over time. Injuries to the diaphragm may present in many ways, including abnormal blood pressure, cardiac arrest, gastroinetestinal obstruction, and respiratory insufficiency. Injuries to the diaphragm are often associated with other injuries in the chest or abdomen, and its position between two major cavities of the human body may complicate diagnosis.

Skin
Most injuries to the skin are minor and do not require specialist treatment. Lacerations of the skin are typically repaired with sutures, staples, or adhesives. The skin is susceptible to burns, and burns to the skin often cause blistering. Abrasive trauma scrapes or rubs off the skin, and severe abrasions require skin grafting to repair. Skin tears involve the removal of the epidermis or dermis through friction or shearing forces, often in vulnerable populations such as the elderly. Skin injuries are potentially complicated by foreign bodies such as glass, metal, or dirt that entered the wound, and skin wounds often require cleaning.

Treatment
Much of medical practice is dedicated to the treatment of injuries. Traumatology is the study of traumatic injuries and injury repair. Certain injuries may be treated by specialists. Serious injuries sometimes require trauma surgery. Following serious injuries, physical therapy and occupational therapy are sometimes used for rehabilitation. Medication is commonly used to treat injuries.
Emergency medicine during major trauma prioritizes the immediate consideration of life-threatening injuries that can be quickly addressed. The airway is evaluated, clearing bodily fluids with suctioning or creating an artificial airway if necessary. Breathing is evaluated by evaluating motion of the chest wall and checking for blood or air in the pleural cavity. Circulation is evaluated to resuscitate the patient, including the application of intravenous therapy. Disability is evaluated by checking for responsiveness and reflexes. Exposure is then used to examine the patient for external injury. Following immediate life-saving procedures, a CT scan is used for a more thorough diagnosis. Further resuscitation may be required, including ongoing blood transfusion, mechanical ventilation and nutritional support.Pain management is another aspect of injury treatment. Pain serves as an indicator to determine the nature and severity of an injury, but it can also worsen an injury, reduce mobility, and affect quality of life. Analgesic drugs are used to reduce the pain associated with injuries, depending on the persons age, the severity of the injury, and previous medical conditions that may affect pain relief. NSAIDs such as aspirin and ibuprofen are commonly used for acute pain. Opioid medications such as fentanyl, methadone, and morphine are used to treat severe pain in major trauma, but their use is limited due to associated long-term risks such as addiction.

Complications
Complications may arise as a result of certain injuries, increasing the recovery time, further exasperating the symptoms, or potentially causing death. The extent of the injury and the age of the injured person may contribute to the likelihood of complications. Infection of wounds is a common complication in traumatic injury, resulting in diagnoses such as pneumonia or sepsis. Wound infection prevents the healing process from taking place and can cause further damage to the body. A majority of wounds are contaminated with microbes from other parts of the body, and infection takes place when the immune system is unable to address this contamination. The surgical removing of devitalized tissue and the use of topical antimicrobial agents can prevent infection.Hemorrhaging of blood is a common result of injuries, and it can cause several complications. Pooling of blood under the skin can cause a hematoma, particularly after blunt trauma or the suture of a laceration. Hematomas are susceptible to infection and are typically treated compression, though surgery is necessary in severe cases. Excessive blood loss can cause hypovolemic shock in which cellular oxygenation can no longer take place. This can cause tachycardia, hypotension, coma, or organ failure. Fluid replacement is often necessary to treat blood loss. Other complications of injuries include cavitation, development of fistulas, and organ failure.

Social and psychological aspects
Injuries often cause psychological harm in addition to physical harm. Traumatic injuries are associated with psychological trauma and distress, and some victims of traumatic injuries will display symptoms of post-traumatic stress disorder during and after the recovery of the injury. The specific symptoms and their triggers vary depending on the nature of the injury. Body image and self-esteem can also be affected by injury </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 Cutaneous leishmaniasis and can you explain it in depth? [/INST] Cutaneous leishmaniasis is the most common form of leishmaniasis affecting humans. It is a skin infection caused by a single-celled parasite that is transmitted by the bite of a phlebotomine sand fly. There are about thirty species of Leishmania that may cause cutaneous leishmaniasis.
This disease is considered to be a zoonosis (an infectious disease that is naturally transmissible from animals to humans), with the exception of Leishmania tropica — which is often an anthroponotic disease (an infectious disease that is naturally transmissible from humans to vertebrate animals).

Signs and symptoms
Post kala-azar dermal leishmaniasis
Post-kala-azar dermal leishmaniasis (PKDL) is a recurrence of kala-azar that may appear on the skin of affected individuals months and up to 20 years after being partially treated, untreated or even in those considered adequately treated. In Sudan, they can be demonstrated in up to 60% of treated cases. They manifest as hypopigmented skin lesions (such as macules, papules, nodules), or facial redness. Though any organism causing kala-azar can lead to PKDL, it is commonly associated with Leishmania donovani which gives different disease patterns in India and Sudan. In the Indian variant, nodules enlarge with time and form plaques but rarely ulcerate, but nodules from the African variety often ulcerate as they progress. Nerve involvement is common in African variety but rare in Indian subcontinent. Histology demonstrates a mixture of chronic inflammatory cells; there can be macrophage or epitheloid granuloma. Parasite concentration is not consistent among studies, perhaps reflecting low sensitivity of diagnostic methods used in earlier entries.Current approach to diagnosis involves

demonstration of parasite by microscopy, in vitro culture or animal inoculation;
immunodiagnosis of parasite antigen;
detection of parasite DNA in tissue.Newer polymerase chain reaction (PCR) based tools have higher sensitivity and specificity. Emergence of PKDL has been reported in HIV affected individuals and may become a problem in the future.
Sodium stibogluconate alone or in combination with rifampicin is used for the treatment of PKDL for a long course of up to 4 months. Compliance can be an issue for such a long course.

Mucocutaneous leishmaniasis
Mucocutaneous leishmaniasis is an especially disturbing form of cutaneous leishmaniasis, because it produces destructive and disfiguring lesions of the face. It is most often caused by Leishmania braziliensis, but cases caused by L. aethiopica have also been described.Mucocutaneous leishmaniasis is very difficult to treat. Treatment involves the use of pentavalent antimonial compounds, which are highly toxic (common side effects include thrombophlebitis, pancreatitis, cardiotoxicity and hepatotoxicity) and not very effective. For example, in one study, despite treatment with high doses of sodium stibogluconate for 28 days, only 30% of patients remained disease-free at 12 months follow-up. Even in those patients who achieve an apparent cure, as many as 19% will relapse. Several drug combinations with immunomodulators have been tested, for example, a combination of pentoxifylline (inhibitor of TNF-α) and a pentavalent antimonial at a high dose for 30 days in a small-scale (23 patients) randomised placebo-controlled study from Brazil achieved cure rates of 90% and reduced time to cure, a result that should be interpreted cautiously in light of inherent limitations of small-scale studies. In an earlier small-scale (12 patients) study, addition of imiquimod showed promising results which need yet to be confirmed in larger trials.

Pathophysiology
Promastigotes of Leishmania are transmitted to human skin by the bite of a sandfly. Leishmania then invades human macrophages and replicates intracellularly. A raised, red lesion develops at the site of the bite (often weeks or sometimes years afterwards). The lesion then ulcerates and may become secondarily infected with bacteria. In many species (for example, L. major) the lesion often spontaneously heals with atrophic scarring. In some species (for example, L. braziliensis) the lesion may spontaneously heal with scarring, but then reappear elsewhere (especially as destructive mucocutaneous lesions). Lesions of other Leishmania species may spontaneously heal and then reappear as satellite lesions around the site of the original lesion, or along the route of lymphatic drainage.Some species tend to cause cutaneous leishmaniasis (e.g., L. major and L.tropica), whereas some species tend to cause visceral leishmaniasis (e.g., L. infantum and L. donovani), though emerging research (due to high deployment rates of western countries to indigenous areas) is showing these species specific presentation lines are blurring.

Diagnosis
Diagnosis is based on the characteristic appearance of non-healing raised, scaling lesions that may ulcerate and become secondarily infected with organisms such as Staphylococcus aureus, in someone who has returned from an endemic area.In resource limited settings, fine-needle aspiration of the lesion  is confirmatory with identification of amastigote form of Leishmania. The gold standard for diagnosis is a PCR test.

Treatment
American cutaneous and mucocutaneous leishmaniasis
The best treatment for American cutaneous and mucocutaneous leishmaniasis (ACML) is not known. Pentavalent antimonial drugs (sodium stibogluconate (SSG) and meglumine antimonate (Glucantime, MA)) have been used since the 1940s, but they are expensive, toxic, and painful. Treatments that work for one species of Leishmania may not work for another; therefore, it is recommended that the exact species be identified prior to initiating treatment. Unfortunately, leishmaniasis is an orphan disease in developed nations, and almost all the current treatment options are toxic with significant side effects.The best-studied treatments for ACML caused by two Leishmania species are listed below. However, one should note that most of the studies examining treatments of ACML were poorly designed. Therefore, no definitive treatment guidelines or recommendations are currently available, as large-scale and well-conducted studies are necessary to evaluate the long-term effects of current treatments.
Leishmania braziliensis and Leishmania panamensis: There is good evidence that oral allopurinol plus intramuscular MA is superior to either medication alone. In addition, a 20-day course of intravenous MA was better than a 7-day course as well as a 3- or 7-day course of intravenous MA with paromomycin + 12% methylbenzethonium chloride.
For L. braziliensis, oral pentoxifylline plus intravenous SSG seems to be more efficacious than intravenous SSG alone, and intravenous MA was superior to intramuscular paromomycin sulfate and IV pentamidine. Likewise, intramuscular MA was shown to be better than the Bacillus Calmette-Guerin vaccine.
For L. panamensis, oral ketoconazole, oral miltefosine, and topical paromomycin + 12% methylbenzethonium chloride were shown to be superior to placebo.There is no strong evidence for the efficacy of surgery, oral itraconazole and fluconazole, oral antibiotics (rifampicin, metronidazole, cotrimoxazole), intravenous or topical amphotericin B, oral dapsone, photodynamic therapy, promoting healing therapies, laser, or cryotherapy treatments.

Old World cutaneous leishmaniasis
Similar to ACML, the treatment recommendations for Old World cutaneous leishmaniasis (OWCL) are uncertain due to the variability of and inconsistencies within the research.Most studies done to assess treatments of OWCL included two species of parasites, Leishmania major and Leishmania tropica. The most well-studied treatments for OWCL are oral itraconazole and topical paromomycin.Patients treated with oral itraconazole for an average of 2.5 months had a higher cure rate compared to placebo, but they also had a higher rate of side effects, including gastrointestinal complaints, abnormal liver function, headaches, and dizziness.Patients treated with topical paromomycin showed no difference in cure rate compared to placebo, but patients treated with paromomycin had a higher rate of adverse skin reactions.The treatments for other Leishmania species responsible for OWCL, such as L. infantum, L. aethiopica, and L. donovani, have not been thoroughly studied. In addition, the effects of leishmaniasis treatment in children, women of childbearing age, patients with comorbidities, and immunocompromised patients have not been well established.

Epidemiology
Cutaneous leishmaniasis is endemic in all tropical and subtropical areas of the world. The distribution of this disease is very tightly linked to geography, and villages even 15 miles apart can have very different rates of cutaneous leishmaniasis.Most species of Leishmania are capable of infecting humans and causing cutaneous leishmaniasis. In the New World, these organisms include L. amazonensis, L. braziliensis, L. guyanensis, L. lainsoni, L. lindenbergi, L. mexicana, L. naiffi, L. panamensis, L. peruviana, L. shawi, and L. venezuelensis. Old World species that cause cutaneous leishmaniasis include L. aethiopica, L. infantum, L. major, and L. tropica. With the exception of L. tropica — which is commonly associated with human settlements and therefore considered to be an anthroponotic species — all of these organisms are zoonotic. As demographic changes occur in developing nations, some species that have traditionally been considered to be zoonotic (e.g., L. panamensis) are becoming primarily human pathogens.Dogs and rodents serve as the primary animal reservoir hosts in the sylvatic cycle, but people with chronic PKDL can also serve as important reservoir hosts for cutaneous leishmaniasis. The most common vectors for cutaneous leishmaniasis in the Old World are sandflies of the genus Phlebotomus, while Lutzomyia and those within the family Psychodidae (especially the genus Psychodopygus) are the most common vectors in the New World </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 Nicotine dependence and can you explain it in depth? [/INST] Nicotine dependence is a state of dependence upon nicotine. Nicotine dependence is a chronic, relapsing disease defined as a compulsive craving to use the drug, despite social consequences, loss of control over drug intake,  and emergence of withdrawal symptoms. Tolerance is another component of drug dependence. Nicotine dependence develops over time as a person continues to use nicotine. The most commonly used tobacco product is cigarettes, but all forms of tobacco use and e-cigarette use can cause dependence. Nicotine dependence is a serious public health problem because it leads to continued tobacco use, which is one of the leading preventable causes of death worldwide, causing more than 8 million deaths per year.According to the World Health Organization, "Greater nicotine dependence has been shown to be associated with lower motivation to quit, difficulty in trying to quit, and failure to quit, as well as with smoking the first cigarette earlier in the day and smoking more cigarettes per day." The WHO estimates that there are 1.1 billion smokers globally. Of the 34 million smokers in the US in 2018, 74.6% smoked every day, indicating the potential for some level of nicotine dependence. There is an increased frequency of nicotine dependence in people with anxiety disorders.There are different ways of measuring nicotine dependence. Common dependence assessment scales for cigarette smokers are the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual of Mental Disorders, the Cigarette Dependence Scale, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives (WISDM).Nicotine is a parasympathomimetic stimulant that attaches to nicotinic acetylcholine receptors in the brain. Neuroplasticity within the brains reward system, including an increase in the number of nicotine receptors, occurs as a result of long-term nicotine use, leading to nicotine dependence. There are genetic risk factors for developing dependence. For instance, genetic markers for a specific type of nicotinic receptor (the α5-α3-β4 nicotine receptors) have been linked to increased risk for dependence. Evidence-based treatments, including medications (nicotine replacement therapy, bupropion, varenicline, or cytisine) and behavioral counseling, can double or triple a smokers chances of quitting successfully.

Definition
Nicotine dependence is defined as a neurobiological adaptation to repeated drug exposure that is manifested by highly controlled or compulsive use, the development of tolerance, experiencing withdrawal symptoms upon cessation including cravings, and an inability to quit despite harmful effects. Nicotine dependence has also been conceptualized as a chronic, relapsing disease. A 1988 Surgeon General report states, "Tolerance" is another aspect of drug addiction [dependence] whereby a given dose of a drug produces less effect or increasing doses are required to achieve a specified intensity of response. Physical dependence on the drug can also occur, and is characterized by a withdrawal syndrome that usually accompanies drug abstinence. After cessation of drug use, there is a strong tendency to relapse."Nicotine dependence leads to heavy smoking and causes severe withdrawal symptoms and relapse back to smoking. Nicotine dependence develops over time as a person continues to use nicotine. Teenagers do not have to be daily or long-term smokers to show withdrawal symptoms. Relapse should not frustrate the nicotine user from trying to quit again. A 2015 review found "Avoiding withdrawal symptoms is one of the causes of continued smoking or relapses during attempts at cessation, and the severity and duration of nicotine withdrawal symptoms predict relapse." Symptoms of nicotine dependence include irritability, anger, impatience, and problems in concentrating.

Diagnosis
There are different ways of measuring nicotine dependence. The five common dependence assessment scales are the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual of Mental Disorders, the Cigarette Dependence Scale, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives.The Fagerström Test for Nicotine Dependence focuses on measuring physical dependence which is defined "as a state produced by chronic drug administration, which is revealed by the occurrence of signs of physiological dysfunction when the drug is withdrawn; further, this dysfunction can be reversed by the administration of drug". The long use of Fagerström Test for Nicotine Dependence is supported by the existence of significant preexisting research, and its conciseness.The 4th edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) had a nicotine dependence diagnosis which was defines as "...a cluster of cognitive, behavioral, and physiological symptoms..." In the updated DSM-5 there is no nicotine dependence diagnosis, but rather Tobacco Use Disorder, which is defined as, "A problematic pattern of tobacco use leading to clinically significant impairment or distress, as manifested by at least 2 of the following [11 symptoms], occurring within a 12-month period."The Cigarette Dependence Scale was developed "to index dependence outcomes and not dependence mechanisms". The Nicotine Dependence Syndrome Scale, "a 19-item self-report measure, was developed as a multidimensional scale to assess nicotine dependence". The Wisconsin Inventory of Smoking Dependence Motives "is a 68-item measure developed to assess dependence as a motivational state".

Mechanisms
Traditional cigarettes are the most common delivery device for nicotine. However, electronic cigarettes are becoming more popular. Nicotine can also be delivered via other tobacco products such as chewing tobacco, snus, pipe tobacco, hookah, all of which can produce nicotine dependence.

Biomolecular
Pre-existing cognitive and mood disorders may influence the development and maintenance of nicotine dependence. Nicotine is a parasympathomimetic stimulant that binds to and activates nicotinic acetylcholine receptors in the brain, which subsequently causes the release of dopamine and other neurotransmitters, such as norepinephrine, acetylcholine, serotonin, gamma-aminobutyric acid, glutamate, endorphins, and several neuropeptides. Repeated exposure to nicotine can cause an increase in the number of nicotinic receptors, which is believed to be a result of receptor desensitization and subsequent receptor upregulation. This upregulation or increase in the number of nicotinic receptors significantly alters the functioning of the brain reward system. With constant use of nicotine, tolerance occurs at least partially as a result of the development of new nicotinic acetylcholine receptors in the brain. After several months of nicotine abstinence, the number of receptors go back to normal. Nicotine also stimulates nicotinic acetylcholine receptors in the adrenal medulla, resulting in increased levels of adrenaline and beta-endorphin. Its physiological effects stem from the stimulation of nicotinic acetylcholine receptors, which are located throughout the central and peripheral nervous systems. Chronic nicotinic acetylcholine receptor activation from repeated nicotine exposure can induce strong effects on the brain, including changes in the brains physiology, that result from the stimulation of regions of the brain associated with reward, pleasure, and anxiety. These complex effects of nicotine on the brain are still not well understood.When these receptors are not occupied by nicotine, they are believed to produce withdrawal symptoms. These symptoms can include cravings for nicotine, anger, irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger, weight gain, and difficulty concentrating.Neuroplasticity within the brains reward system occurs as a result of long-term nicotine use, leading to nicotine dependence. There are genetic risk factors for developing dependence. For instance, genetic markers for a specific type of nicotinic receptor (the α5-α3-β4 nicotine receptors) have been linked to increased risk for dependence. The most well-known hereditary influence related to nicotine dependence is a mutation at rs16969968 in the nicotinic acetylcholine receptor CHRNA5, resulting in an amino acid alteration from aspartic acid to asparagine. The single-nucleotide polymorphisms (SNPs) rs6474413 and rs10958726 in CHRNB3 are highly correlated with nicotine dependence. Many other known variants within the CHRNB3–CHRNA6 nicotinic acetylcholine receptors are also correlated with nicotine dependence in certain ethnic groups. There is a relationship between CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptors and complete smoking cessation. Increasing evidence indicates that the genetic variant CHRNA5 predicts the response to smoking cessation medicine.

Psychosocial
In addition to the specific neurological changes in nicotinic receptors, there are other changes that occur as dependence develops. Through various conditioning mechanisms (operant and cue/classical), smoking comes to be associated with different mood and cognitive states as well as external contexts and cues.

Treatment
There are treatments for nicotine dependence, although the majority of the evidence focuses on treatments for cigarette smokers rather than people who use other forms of tobacco (e.g., chew, snus, pipes, hookah, e-cigarettes). Evidence-based medicine can double or triple a smokers chances of quitting successfully.

Medication
There are eight major evidence-based medications for treating nicotine dependence: bupropion, cytisine (not approved for use in some countries, including the US), nicotine gum, nicotine inhaler, nicotine lozenge/mini-lozenge, nicotine nasal spray, nicotine patch, and varenicline. These medications have been shown to significantly improve long-term (i.e., 6-months post-quit day) abstinence rates, especially when used in combination with psychosocial treatment. The nicotine replacement treatments (i.e., patch, lozenge, gum) are dosed based on how dependent a smoker is—people who smoke more cigarettes or who smoke earlier in the morning use higher doses of nicotine replacement treatments. There is no consensus for remedies for tobacco use disorder among pregnant smokers who also use alcohol and stimulants.

Vaccine
TA-NIC is a proprietary vaccine in development similar to TA-CD but being used to create human anti-nicotine antibodies in a person to destroy nicotine in the human body so that it is no longer effective.

Psychosocial
Psychosocial interventions delivered in-person (individually or in a group) or over the phone (including mobile phone interventions) have been shown to effectively treat nicotine dependence. These interventions focus on providing support for quitting and helping with smokers with problem-solving and developing healthy responses for coping with cravings, negative moods, and other situations that typically lead to relapse. The combination of pharmacotherapy and psychosocial interventions has been shown to be especially effective.

Epidemiology
First-time nicotine users develop a dependence about 32% of the time. There are approximately 976 million smokers in the world. Estimates are that half of smokers (and one-third of former smokers) are dependent based on DSM criteria, regardless of age, gender or country of origin, but this could be higher if different definitions of dependence were used. Recent data suggest that, in the United States, the rates of daily smoking and the number of cigarettes smoked per day are declining, suggesting a reduction in population-wide dependence among current smokers. However, there are different groups of people who are more likely to smoke than the average population, such as those with low education or low socio-economic status and those with mental illness. There is also evidence that among smokers, some subgroups may be more dependent than other groups. Men smoke at higher rates than do women and score higher on dependence indices; however, women may be less likely to be successful in quitting, suggesting that women may be more dependent by that criterion. There is an increased frequency of nicotine dependence in people with anxiety disorders. 6% of smokers who want to quit smoking each year are successful at quitting. Nicotine withdrawal is the main factor hindering smoking cessation. A 2010 World Health Organization report states, "Greater nicotine dependence has been shown to be associated with lower motivation to quit, difficulty in trying to quit, and failure to quit, as well as with smoking the first cigarette earlier in the day and smoking more cigarettes per day." E-cigarettes may result in starting nicotine dependence again. Greater nicotine dependence may result from dual use of traditional cigarettes and e-cigarettes. Like tobacco companies did in the last century, there is a possibility that e-cigarettes could result in a new form of dependency on nicotine across the world.

Concerns
Nicotine dependence results in substantial mortality, morbidity, and socio-economic impacts. Nicotine dependence is a serious public health concern due to it being one of the leading causes of avoidable deaths worldwide. The medical community is concerned that e-cigarettes may escalate global nicotine dependence, particularly among adolescents who are attracted to many of the flavored e-cigarettes. There is strong evidence that vaping induces symptoms of dependence in users </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 Cat anatomy and can you explain it in depth? [/INST] The anatomy of the domestic cat is similar to that of other members of the genus Felis.

Mouth
Permanent dentition teeth
Cats are carnivores that have highly specialized teeth. There are four types of permanent dentition teeth that structure the mouth: twelve incisors, four canines, ten premolars and four molars. The premolar and first molar are located on each side of the mouth that together are called the carnassial pair. The carnassial pair specialize in cutting food and are parallel to the jaw. The incisors located in the front section of the lower and upper mouth are small, narrow, and have a single root. They are used for grasping and biting food.

Deciduous dentition teeth
A cat also has a deciduous dentition prior to the formation of the permanent one. This dentition emerges seven days after birth and it is composed of 26 teeth with slight differences. The mouth will have smaller incisors, slender and strongly curved upper canines, vertical lower canines, and even smaller upper and lower molars. Although the upper and lower molars are smaller than the ones that arise during permanent dentition, the similarities are striking.

Tongue
The cats tongue is covered in a mucous membrane and the dorsal aspect has 5 types of sharp spines, or papillae. The 5 papillae are filiform, fungiform, foliate, vallate, and conical.  A cats sense of smell and taste work closely together, having a vomeronasal organ that allows them to use their tongue as scent tasters, while its longitudinal, transverse, and vertical intrinsic muscles aid in movement.

Ears
Similar to dogs, cats have sensitive ears that allow them to move each ear independently of one another. Because of this mobility, a cat can move its body in one direction and point its ears in another direction. The rostral, caudal, dorsal, and ventral auricular muscle groups of each ear comprise fifteen muscles that are responsible for this ability. Most cats have straight ears pointing upward. Unlike with dogs, flap-eared breeds are extremely rare (Scottish Folds have one such exceptional mutation). When angry or frightened, a cat will lay back its ears to accompany the growling or hissing sounds it makes. Cats also turn their ears back when they are playing or to listen to a sound coming from behind them. The fold of skin forming a pouch on the lower posterior part of the ear, known as Henrys pocket, is usually prominent in a cats ear. Its function is unknown, though it may assist in filtering sounds.

Nose
Cats are highly territorial, and secretion of odors plays a major role in cat communication. The nose helps cats to identify territories, other cats and mates, to locate food, and has various other uses. A cats sense of smell is believed to be about fourteen times more sensitive than that of humans. The rhinarium (the leathery part of the nose we see) is quite tough, to allow it to absorb rather rough treatment sometimes. The color varies according to the genotype (genetic makeup) of the cat. A cats skin has the same color as the fur, but the color of the nose leather is probably dictated by a dedicated gene. Cats with white fur have skin susceptible to damage by ultraviolet light, which may cause cancer. Extra care is required when outside in the hot sun.

Legs
Cats are digitigrades, which means that they walk on their toes just like dogs. The advantage of this is that cats (including other digitigrades) are more agile than other animals. This is because all animals usually have ground reaction forces (GRFs) at around two to three times their body weight per limb. Digitigrades have a higher GRF compared to other animals due to the increased weight on a smaller surface area, which would be about six times their body weight per limb.Toe tufts are commonly found on cats with medium to long coats. Clumps of fur that stick out at least 1–2 cm (0.39–0.79 in) beyond the paw pad can be considered tufts. In addition to soft paw pads, toe tufts help a cat to silently stalk its prey by muffling excess noise. However, outdoor cats tend to lose their toe tufts due to excessive abrasion on the rougher outdoor surfaces. This is in distinct contrast to indoor cats who spend most of their time walking on carpet or smooth floors.
Cats are also able to walk very precisely. Adult cats walk with a "four-beat gait" meaning that each foot does not step on the same spot as each other. Whether they walk fast or slow, a cats walk is considered symmetric because the right limbs imitate the position of the left limbs as they walk. This type of locomotion provides sense of touch on all four paws that are necessary for precise coordination.The Cats vertebrae are held by muscles rather than ligaments like humans. This contributes to the cats elasticity and ability to elongate and contract their back by curving it upwards or oscillating it along their vertebral line.

Cats are also able to jump from larger heights without serious injury due to the efficient performance in their limbs and ability to control impact forces. In this case, hindlimbs are able to absorb more shock and energy in comparison to the forelimbs, when jumping from surface to surface, as well as steer the cat for weight bearing and breaking.

Claws
Like nearly all members of the family Felidae, cats have protractable claws. In their normal, relaxed position, the claws are sheathed with the skin and fur around the toe pads. This keeps the claws sharp by preventing wear from contact with the ground and allows the silent stalking of prey. The claws on the forefeet are typically sharper than those on the hind feet. Cats can voluntarily extend their claws on one or more paws. They may extend their claws in hunting or self-defense, climbing, "kneading", or for extra traction on soft surfaces (bedspreads, thick rugs, skin, etc.). It is also possible to make a cooperative cat extend its claws by carefully pressing both the top and bottom of the paw. The curved claws can become entangled in carpet or thick fabric, which can cause injury if the cat is unable to free itself.
Most cats have a total of 18 digits and claws. 5 on each forefoot, the 5th digit being the dewclaw; and 4 on each hind foot. The dewclaw is located high on the foreleg, is not in contact with the ground and is non-weight bearing.Some cats can have more than 18 digits, due to a common mutation called polydactyly or polydactylism, which can result in five to seven toes per paw.

Temperature and heart rate
The normal body temperature of a cat is between 38.3 and 39.0 °C (100.9 and 102.2 °F). A cat is considered febrile (hyperthermic) if it has a temperature of 39.5 °C (103.1 °F) or greater, or hypothermic if less than 37.5 °C (99.5 °F). For comparison, humans have an average body temperature of about 37.0 °C (98.6 °F). A domestic cats normal heart rate ranges from 140 to 220 beats per minute (bpm), and is largely dependent on how excited the cat is. For a cat at rest, the average heart rate usually is between 150 and 180 bpm, more than twice that of a human, which averages 70 bpm.

Skin
Cats possess rather loose skin, which allows them to turn and confront a predator or another cat in a fight, even when it has a grip on them. This is also an advantage for veterinary purposes, as it simplifies injections. In fact, the lives of cats with chronic kidney disease can sometimes be extended for years by the regular injection of large volumes of fluid subcutaneously.

Scruff
The particularly loose skin at the back of the neck is known as the scruff, and is the area by which a mother cat grips her kittens to carry them. As a result, cats tend to become quiet and passive when gripped there. This behavior also extends into adulthood, when a male will grab the female by the scruff to immobilize her while he mounts, and to prevent her from running away as the mating process takes place.This technique can be useful when attempting to treat or move an uncooperative cat; however, since an adult cat is heavier than a kitten, a pet cat should never be carried by the scruff, but should instead have its weight supported at the rump and hind legs, and at the chest and front paws.

Primordial pouches
Some cats share common traits due to heredity. One of those is the primordial pouch, sometimes referred to as "spay sway" by owners who notice it once the cat has been spayed or neutered. It is located on a cats belly. Its appearance is similar to a loose flap of skin that might occur if the cat had been overweight and had then lost weight. It provides a little extra protection against kicks, which are common during cat fights as a cat will try to rake with its rear claws. In wild cats, the ancestors of domesticated felines, this pouch appears to be present to provide extra room in case the animal has the opportunity to eat a large meal and the stomach needs to expand. This stomach pouch also allows the cat to bend and expand, allowing for faster running and higher jumping.

Skeleton
Cats have seven cervical vertebrae like almost all mammals, thirteen thoracic vertebrae (humans have twelve), seven lumbar vertebrae (humans have five), three sacral vertebrae (humans have five because of their bipedal posture), and, except for Manx cats and other shorter tailed cats, twenty-two or twenty-three caudal vertebrae (humans have three to five, fused into an internal coccyx). The extra lumbar and thoracic vertebrae account for the cats enhanced spinal mobility and flexibility, compared to humans. The caudal vertebrae form the tail, used by the cat as a counterbalance to the body during quick movements.  Between their vertebrae, they have elastic discs, useful for cushioning the jump landings.
Unlike human arms, cat forelimbs are attached to the shoulder by free-floating clavicle bones, which allows them to pass their body through any space into which they can fit their heads.

Skull
The cat skull is unusual among mammals in having very large eye sockets and a powerful and specialized jaw.: 35  Compared to other felines, domestic cats have narrowly spaced canine teeth, adapted to their preferred prey of small rodents.

Muscles
Internal abdominal oblique
This muscles origin is the lumbodorsal fascia and ribs. Its insertion is at the pubis and linea alba (via aponeurosis), and its action is the compression of abdominal contents. It also laterally flexes and rotates the vertebral column.

Transversus abdominis
This muscle is the innermost abdominal muscle. Its origin is the second sheet of the lumbodorsal fascia and the pelvic girdle and its insertion is the linea alba. Its action is the compression of the abdomen.

Rectus abdominis
This muscle is under the extensive aponeurosis situated on the ventral surface of the cat. Its fibers are extremely longitudinal, on each side of the linea alba. It is also traversed by the inscriptiones tendinae, or what others called myosepta.

Deltoid
The deltoid muscles lie just lateral to the trapezius muscles, originating from several fibers spanning the clavicle and scapula, converging to insert at the humerus. Anatomically, there are only two deltoids in the cat, the acromiodeltoid and the spinodeltoid. However, to conform to human anatomy standards, the clavobrachialis is now also considered a deltoid and is commonly referred to as the clavodeltoid.

Acromiodeltoid
The acromiodeltoid is the shortest of the deltoid muscles. It lies lateral to (to the side of) the clavodeltoid, and in a more husky cat it can only be seen by lifting or reflecting the clavodeltoid. It originates at the acromion process and inserts at the deltoid ridge. When contracted, it raises and rotates the humerus outward.

Spinodeltoid
A stout and short muscle lying posterior to the acromiodeltoid. It lies along the lower border of the scapula, and it passes through the upper forelimb, across the upper end of muscles of the upper forelimb. It originates at the spine of the scapula and inserts at the deltoid ridge. Its action is to raise and rotate the humerus outward.

Head
Masseter
The Masseter is a great, powerful, and very thick muscle covered by a tough, shining fascia lying ventral to the zygomatic arch, which is its origin. It inserts into the posterior half of the lateral surface of the mandible. Its action is the elevation of the mandible (closing of the jaw).

Temporalis
The temporalis is a great mass of mandibular muscle, and is also covered by a tough and shiny fascia. It lies dorsal to the zygomatic arch and fills the temporal fossa of the skull. It arises from the side of the skull and inserts into the coronoid process of the mandible. It too, elevates the jaw.

Ocular
Cats have three eyelids. The cats third eyelid is known as the nictitating membrane. It is located in the inner corner of the eye, which is also covered by conjunctiva. In healthy cats, the conjunctiva of the eyelids is not readily visible and has a pale, pink color.

Integumental
The two main integumental muscles of a cat are the platysma and the cutaneous maximus. The cutaneous maximus covers the dorsal region of the cat and allows it to shake its skin. The platysma covers the neck and allows the cat to stretch the skin over the pectoralis major and deltoid muscles.

Neck and back
Rhomboideus
The rhomboideus is a thick, large muscle below the trapezius muscles. It extends from the vertebral border of the scapula to the mid-dorsal line. Its origin is from the neural spines of the first four thoracic vertebrae, and its insertion is at the vertebral border of the scapula. Its action is to draw the scapula to the dorsal.

Rhomboideus capitis
The Rhomboideus capitis is the most cranial of the deeper muscles. It is underneath the clavotrapezius. Its origin is the superior nuchal line, and its insertion is at the scapula. Action draws scapula cranially.

Splenius
The Splenius is the most superficial of all the deep muscles. It is a thin, broad sheet of muscle underneath the clavotrapezius and deflecting it. It is crossed also by the rhomboideus capitis. Its origin is the mid-dorsal line of the neck and fascia. The insertion is the superior nuchal line and atlas. It raises or turns the head.

Serratus ventralis
The serratus ventralis is exposed by cutting the wing-like latissimus dorsi. The said muscle is covered entirely by adipose tissue. The origin is from the first nine or ten ribs and from part of the cervical vertebrae.

Serratus Dorsalis
The serratus dorsalis is medial to both the scapula and the serratus ventralis. Its origin is via apoeurosis following the length of the mid-dorsal line, and its insertion is the dorsal portion of the last ribs. Its action is to depress and retracts the ribs during breathing.

Intercostals
The intercostals are a set of muscles sandwiched among the ribs. They interconnect ribs, and are therefore the primary respiratory skeletal muscles. They are divided into the external and the internal subscapularis. The origin and insertion are in the ribs. The intercostals pull the ribs backwards or forwards.

Caudofemoralis
The caudofemoralis is a muscle found in the pelvic limb. The Caudofemoralis acts to flex the tail laterally to its respective side when the pelvic limb is bearing weight. When the pelvic limb is lifted off the ground, contraction of the caudofemoralis causes the limb to abduct and the shank to extend by extending the hip joint.

Pectoral
Pectoantebrachialis
Pectoantebrachialis muscle is just one-half-inch wide and is the most superficial in the pectoral muscles. Its origin is the manubrium of the sternum, and its insertion is in a flat tendon on the fascia of the proximal end of the ulna. Its action is to draw the forelimb towards the chest. There is no human equivalent.

Pectoralis major
The pectoralis major, also called pectoralis superficialis, is a broad triangular portion of the pectoralis muscle which is immediately below the pectoantebrachialis. It is smaller than the pectoralis minor muscle. Its origin is the sternum and median ventral raphe, and its insertion is at the humerus. Its action is to draw the forelimb towards the chest.

Pectoralis minor
The pectoralis minor muscle is larger than the pectoralis major. However, most of its anterior border is covered by the pectoralis major. Its origins are ribs three–five, and its insertion is the coracoid process of the scapula. Its actions are the tipping of the scapula and the elevation of ribs three–five.

Xiphihumeralis
The most posterior, flat, thin, and long strip of pectoral muscle is the xiphihumeralis. It is a band of parallel fibers that is found in felines but not in humans. Its origin is the xiphoid process of the sternum. The insertion is the humerus.

Trapezius
In the cat there are three thin flat muscles that cover the back, and to a lesser extent, the neck. They pull the scapula toward the mid-dorsal line, anteriorly, and posteriorly.

Clavotrapezius
The most anterior of the trapezius muscles, it is also the largest. Its fibers run obliquely to the ventral surface. Its origin is the superior nuchal line and median dorsal line and its insertion is the clavicle. Its action is to draw the clavicle dorsally and towards the head.

Acromiotrapezius
Acromiotrapezius is the middle trapezius muscle. It covers the dorsal and lateral surfaces of the scapula. Its origin is the neural spines of the cervical vertebrae and its insertion is in the metacromion process and fascia of the clavotrapezius. Its action is to draw the scapula to the dorsal, and hold the two scapula together.

Spinotrapezius
Spinotrapezius, also called thoracic trapezius, is the most posterior of the three. It is triangular shaped. Posterior to the acromiotrapezius and overlaps latissimus dorsi on the front. Its origin is the neural spines of the thoracic vertebrae and its insertion is the scapular fascia. Its action is to draw the scapula to the dorsal and caudal region.

Digestive system
The digestion system of cats begins with their sharp teeth and abrasive tongue papillae, which help them tear meat, which is most, if not all, of their diet. Cats naturally do not have a diet high in carbohydrates, and therefore, their saliva doesnt contain the enzyme amylase. Food moves from the mouth through the esophagus and into the stomach. The gastrointestinal tract of domestic cats contains a small cecum and unsacculated colon. The cecum while similar to dogs, doesnt have a coiled cecum.
The stomach of the cat can be divided into distinct regions of motor activity. The proximal end of the stomach relaxes when food is digested. While food is being digested this portion of the stomach either has rapid stationary contractions or a sustained tonic contraction of muscle. These different actions result in either the food being moved around or the food moving towards the distal portion of the stomach. The distal portion of the stomach undergoes rhythmic cycles of partial depolarization. This depolarization sensitizes muscle cells so they are more likely to contract. The stomach is not only a muscular structure, it also serves a chemical function by releasing hydrochloric acid and other digestive enzymes to break down food.
Food moves from the stomach into the small intestine. The first part of the small intestine is the duodenum. As food moves through the duodenum, it mixes with bile, a fluid that neutralizes stomach acid and emulsifies fat. The pancreas releases enzymes that aid in digestion so that nutrients can be broken down and pass through the intestinal mucosa into the blood and travel to the rest of the body. The pancreas doesnt produce starch processing enzymes because cats dont eat a diet high in carbohydrates. Since the cat digests low amounts of glucose, the pancreas uses amino acids to trigger insulin release instead.
Food then moves on to the jejunum. This is the most nutrient absorptive section of the small intestine. The liver regulates the level of nutrients absorbed into the blood system from the small intestine. From the jejunum, whatever food that has not been absorbed is sent to the ileum which connects to the large intestine. The first part of the large intestine is the cecum and the second portion is the colon. The large intestine reabsorbs water and forms fecal matter.
There are some things that the cats are not able to digest. For example, cats clean themselves by licking their fur with their tongue, which causes them to swallow a lot of fur. This causes a build-up of fur in a cats stomach and creates a mass of fur. This is often thrown up and is better known as a hairball.The short length of the digestive tract of the cat causes cats digestive system to weigh less than other species of animals, which allows cats to be active predators. While cats are well adapted to be predators they have a limited ability to regulate catabolic enzymes of amino acids meaning amino acids are constantly being destroyed and not absorbed </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 Oculopharyngeal muscular dystrophy and can you explain it in depth? [/INST] Oculopharyngeal muscular dystrophy (OPMD) is a rare form of muscular dystrophy with symptoms generally starting when an individual is 40 to 50 years old. It can be autosomal dominant neuromuscular disease or autosomal recessive. The most common inheritance of OPMD is autosomal dominant, which means only one copy of the mutated gene needs to be present in each cell. Children of an affected parent have a 50% chance of inheriting the mutant gene.Autosomal dominant inheritance is the most common form of inheritance. Less commonly, OPMD can be inherited in an autosomal recessive pattern, which means that two copies of the mutated gene need to be present in each cell, both parents need to be carriers of the mutated gene, and usually show no signs or symptoms.  The PABPN1 mutation contains a GCG trinucleotide repeat  at the 5 end of the coding region, and expansion of this repeat which then leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease.

Signs and symptoms
In terms of the signs (and symptoms) of oculopharyngeal muscular dystrophy would be consistent with the following:
PtosisWeakness of the extraocular musclesDysphagiaAspiration pneumonia (complication)Proximal limb weaknessThough the aforementioned signs/symptoms are the most common, there have been cases though rare, where the peripheral nervous system has had involvement with significant reduction of myelinated fibers In homozygous cases, this muscular dystrophy is severe and starts earlier in the affected individuals life.

Genetics
The genetics of this type of muscular dystrophy revolve around the PABPN1 gene. This gene suffers mutations that cause the PABPN1 protein to have extra alanine (amino acids), this manifests itself physically in the symptoms of this MD.The expansion caused by the mutations on the PABPN1 gene ultimately interrupts the cellular mechanics of poly(A) RNA. In most cases oculopharyngeal muscular dystrophy is inherited via autosomal dominance.The alleles, which are a variant form of a gene involved in this form of MD are:  PABPN1, (GCG)n EXPANSION, (GCG)8-13, PABPN1, (GCG)n EXPANSION, (GCG)7 and PABPN1, GLY12ALA.

Diagnosis
The diagnosis of oculopharyngeal muscular dystrophy can be done via two methods, a muscle biopsy or a blood draw with genetic testing for GCG trinucleotide expansions in the PABPN1 gene. The genetic blood testing is more common. Additionally, a distinction between OPMD and myasthenia gravis or mitochondrial myopathy must be made, in regards to the differential diagnosis of this condition.

Treatment
Currently no cure or specific treatment exists to eliminate the symptoms or stop the disease progression. A consistent diet planned with the help of a dietitian along with exercises taught by a speech therapist can assist with mild symptoms of dysphagia. Surgical intervention can also help temporarily manage symptoms related to the ptosis and dysphagia. Cutting one of the throat muscles internally, an operation called cricopharyngeal myotomy, can be one way to ease symptoms in more severe cases. However, for a majority of people, the benefits from such treatments are only temporary. There is currently no treatment available to address the proximal limb weakness. Many of those affected with the proximal limb weakness will eventually require assistive devices such as canes, braces or a wheelchair. As with all surgical procedures, they come with many risk factors. As the dysphagia becomes more severe, patients become malnourished, lose significant weight, become dehydrated and suffer from repeated incidents of aspiration pneumonia. These last two are often the cause of death.

Epidemiology
The disease is found across 5 continents (30 countries) and is frequently seen in French Canadians, with a prevalence 1:1000. OPMD affects males and females equally, and affected individuals have been found in Europe (France), Jewish Ashkenazi, and Spanish Americans.

See also
Muscular dystrophy
PABPN1

References
Further reading
Raz, Yotam; Raz, Vered (2014-01-01). "Oculopharyngeal muscular dystrophy as a paradigm for muscle aging". Frontiers in Aging Neuroscience. 6: 317. doi:10.3389/fnagi.2014.00317. PMC 4226162. PMID 25426070.
Hill, M. E.; Creed, G. A.; McMullan, T. F. W.; Tyers, A. G.; Hilton-Jones, D.; Robinson, D. O.; Hammans, S. R. (1 March 2001). "Oculopharyngeal muscular dystrophy". Brain </s>