vania-janet/multiturn-rag-retrieval-data huggingface dataset:
Cavalier King Charles Spaniel
Syringomyelia ( SM ) is a condition affecting the brain and spine , causing symptoms ranging from mild discomfort to severe pain and partial paralysis . It is caused by a malformation , commonly known as Chiari Malformation , in the lower back of the skull which reduces the space available to the brain , compressing it and often forcing it out ( herniating it ) through the opening into the spinal cord . This blocks the flow of cerebral spinal fluid ( CSF ) around the brain and spine and increases the fluid 's pressure , creating turbulence which in turn is believed to create fluid pockets , or syrinxes ( hence the term syringomyelia ) , in the spinal cord . Syringomyelia is rare in most breeds but has become widespread in the Cavalier King Charles Spaniel , with international research samples in the past few years consistently showing over 90 % of Cavaliers have the malformation , and that between 30 -- 70 % have syrinxes . However , most dogs with syrinxes are not symptomatic . Although symptoms of syringomyelia can present at any age , they typically appear between six months and four years of age in 85 % of symptomatic dogs , according to Clare Rusbridge , a research scientist . Symptoms include sensitivity around the head , neck , or shoulders , often indicated by a dog whimpering or frequently scratching at the area of his neck or shoulder . Scratching is often unilateral -- restricted to one side of the body . Scratching motions are frequently performed without actually making physical contact with the body ( `` air scratching '' ) . The scratching behavior appears involuntary and the dog frequently scratches while walking -- without stopping -- in a way that is very atypical of normal scratching ( `` bunny hopping '' ) . Scratching typical of SM is usually worse when the dog is wearing a collar , is being walked on leash , or is excited , and first thing in the morning or at night .
Endoplasmic reticulum
Abnormalities in XBP1 lead to a heightened endoplasmic reticulum stress response and subsequently causes a higher susceptibility for inflammatory processes that may even contribute to Alzheimer 's disease . In the colon , XBP1 anomalies have been linked to the inflammatory bowel diseases including Crohn 's disease .
Autophagy
Cells that undergo an extreme amount of stress experience cell death either through apoptosis or necrosis . Prolonged autophagy activation leads to a high turnover rate of proteins and organelles . A high rate above the survival threshold may kill cancer cells with a high apoptotic threshold . This technique can be utilized as a therapeutic cancer treatment .
Flint water crisis
Childhood lead exposure causes a reduction in intellectual functioning and IQ , academic performance , and problem - solving skills , and an increased risk of attention deficit disorder , aggression , and hyperactivity . According to studies , children with elevated levels of lead in the blood are more likely as adults to commit crimes , be imprisoned , be unemployed or underemployed , or be dependent on government services . In addition , early - life exposure to lead may increase risk of later - life neurological disorders such as Alzheimer 's disease , and this risk is likely to persist into late life long after lead has been removed from the body . A 2014 study by researchers at Risk Science Center at the University of Michigan , completed before the Flint water crisis came to light , estimated the annual cost of childhood lead exposure in Michigan at $330 million ( $205 million in decreases in lifetime earnings , $105 million in additional criminal justice system expenditures , $18 million in health expenditures to diagnose lead positioning and lead - linked attention deficit disorder ) , and $2.5 million in additional special education expenditures .
Apoptosis
The caspase proteins are integral parts of the apoptosis pathway , so it follows that knock - outs made have varying damaging results . A caspase 9 knock - out leads to a severe brain malformation . A caspase 8 knock - out leads to cardiac failure and thus embryonic lethality . However , with the use of cre - lox technology , a caspase 8 knock - out has been created that exhibits an increase in peripheral T cells , an impaired T cell response , and a defect in neural tube closure . These mice were found to be resistant to apoptosis mediated by CD95 , TNFR , etc. but not resistant to apoptosis caused by UV irradiation , chemotherapeutic drugs , and other stimuli . Finally , a caspase 3 knock - out was characterized by ectopic cell masses in the brain and abnormal apoptotic features such as membrane blebbing or nuclear fragmentation . A remarkable feature of these KO mice is that they have a very restricted phenotype : Casp3 , 9 , APAF - 1 KO mice have deformations of neural tissue and FADD and Casp 8 KO showed defective heart development , however in both types of KO other organs developed normally and some cell types were still sensitive to apoptotic stimuli suggesting that unknown proapoptotic pathways exist .
Cavalier King Charles Spaniel
Nearly all Cavaliers eventually have mitral valve disease , with heart murmurs which may progressively worsen , leading to heart failure . This condition is polygenic ( affected by multiple genes ) , and therefore all lines of Cavaliers worldwide are susceptible . It is the leading cause of death in the breed . A survey by The Kennel Club of the United Kingdom showed that 42.8 % of Cavalier deaths are cardiac related . The next most common causes are cancer ( 12.3 % ) and old age ( 12.2 % ) . The condition can begin to emerge at an early age and statistically may be expected to be present in more than half of all Cavalier King Charles Spaniels by age 5 . It is rare for a 10 - year - old Cavalier not to have a heart murmur . While heart disease is common in dogs generally -- one in 10 of all dogs will eventually have heart problems -- mitral valve disease is generally ( as in humans ) a disease of old age . The `` hinge '' on the heart 's mitral valve loosens and can gradually deteriorate , along with the valve 's flaps , causing a heart murmur ( as blood seeps through the valve between heartbeats ) then congestive heart failure . The Cavalier is particularly susceptible to early - onset heart disease , which may be evident in dogs as young as one or two years of age .
T cell
T - cell exhaustion is the progressive loss of T - cell function . It can occur during sepsis and after other acute or chronic infections .
Collagen
Vitamin C deficiency causes scurvy , a serious and painful disease in which defective collagen prevents the formation of strong connective tissue . Gums deteriorate and bleed , with loss of teeth ; skin discolors , and wounds do not heal . Prior to the 18th century , this condition was notorious among long - duration military , particularly naval , expeditions during which participants were deprived of foods containing vitamin C .
Sickle cell disease
Sickle cell disease occurs when a person inherits two abnormal copies of the haemoglobin gene , one from each parent . This gene occurs in chromosome 11 . Several subtypes exist , depending on the exact mutation in each haemoglobin gene . An attack can be set off by temperature changes , stress , dehydration and high altitude . A person with a single abnormal copy does not usually have symptoms and is said to have sickle cell trait . Such people are also referred to as carriers . Diagnosis is by a blood test , and some countries test all babies at birth for the disease . Diagnosis is also possible during pregnancy .
Carbon monoxide poisoning
Another mechanism involves effects on the mitochondrial respiratory enzyme chain that is responsible for effective tissue utilization of oxygen . Carbon monoxide binds to cytochrome oxidase with less affinity than oxygen , so it is possible that it requires significant intracellular hypoxia before binding . This binding interferes with aerobic metabolism and efficient adenosine triphosphate synthesis . Cells respond by switching to anaerobic metabolism , causing anoxia , lactic acidosis , and eventual cell death . The rate of dissociation between carbon monoxide and cytochrome oxidase is slow , causing a relatively prolonged impairment of oxidative metabolism .
Sickle cell disease
From birth to five years of age , penicillin daily , due to the immature immune system that makes them more prone to early childhood illnesses is recommended . Dietary supplementation of folic acid had been previously recommended by the WHO . A 2016 Cochrane review of its use found `` the effect of supplementation on anaemia and any symptoms of anaemia remains unclear '' due to a lack of medical evidence .
Sickle cell disease
The gene defect is a known mutation of a single nucleotide ( see single - nucleotide polymorphism -- SNP ) ( GAG codon changing to GTG ) of the β - globin gene , which results in glutamic acid ( E / Glu ) being substituted by valine ( V / Val ) at position 6 . Haemoglobin S with this mutation is referred to as HbS , as opposed to the normal adult HbA . This is normally a benign mutation , causing no apparent effects on the secondary , tertiary , or quaternary structures of haemoglobin in conditions of normal oxygen concentration . What it does allow for , under conditions of low oxygen concentration , is the polymerization of the HbS itself . The deoxy form of haemoglobin exposes a hydrophobic patch on the protein between the E and F helices ( Phe 85 , Leu 88 ) . The hydrophobic side chain of the valine residue at position 6 of the beta chain in haemoglobin is able to associate with the hydrophobic patch , causing HbS molecules to aggregate and form fibrous precipitates .
Nutrition and cognition
Insufficient intake of selected vitamins , or certain metabolic disorders , may affect cognitive processes by disrupting the nutrient - dependent processes within the body that are associated with the management of energy in neurons , which can subsequently affect synaptic plasticity , or the ability to encode new memories .
Luteinizing hormone
Diminished secretion of LH can result in failure of gonadal function ( hypogonadism ) . This condition is typically manifest in males as failure in production of normal numbers of sperm . In females , amenorrhea is commonly observed . Conditions with very low LH secretions include :
Taxation in the United States
Certain civil penalties apply for failures to follow CBP rules and pay duty . Goods of persons subject to such penalties may be seized and sold by CBP . In addition , criminal penalties may apply for certain offenses . Criminal penalties may be as high as twice the value of the goods plus twenty years in jail .
Autophagy
Another study demonstrated that skeletal muscle fibres of collagen VI knockout mice showed signs of degeneration due to an insufficiency of autophagy which led to an accumulation of damaged mitochondria and excessive cell death . Exercise - induced autophagy was unsuccessful however ; but when autophagy was induced artificially post-exercise , the accumulation of damaged organelles in collagen VI deficient muscle fibres was prevented and cellular homeostasis was maintained . Both studies demonstrate that autophagy induction may contribute to the beneficial metabolic effects of exercise and that it is essential in the maintaining of muscle homeostasis during exercise , particularly in collagen VI fibres .
Nutrition and cognition
Patients deficient in B despite normal absorption functionality may be treated through oral administration of at least 6 μg / day of the vitamin in pill form . Patients who suffer from irreversible causes of deficiency , such as pernicious anemia or old age , will need lifelong treatment with pharmacological doses of B. Strategy for treatment is dependent on the patient 's level of deficiency as well as their level of cognitive functioning . Treatment for those with severe deficiency involves 1000 μg of B administered intramuscularly daily for one week , weekly for one month , then monthly for the rest of the patients life . The progression of neurological manifestations of cobalamin deficiency is generally gradual . As a result , early diagnosis is important or else irreversible damage may occur . Patients who become demented usually show little to no cognitive improvement with the administration of B. There is risk that folic acid administered to those with B deficiency may mask anemic symptoms without solving the issue at hand . In this case , patients would still be at risk for neurological deficits associated with B deficiency - related anemia , which are not associated with anemia related to folate deficiency .
Non-communicable disease
Cystic fibrosis is an example of an inherited disease that is caused by a mutation on a gene . The faulty gene impairs the normal movement of sodium chloride in and out of cells , which causes the mucus - secreting organs to produce abnormally thick mucus . The gene is recessive , meaning that a person must have two copies of the faulty gene for them to develop the disease . Cystic fibrosis affects the respiratory , digestive and reproductive systems , as well as the sweat glands . The mucus secreted is very thick and blocks passageways in the lungs and digestive tracts . This mucus causes problems with breathing and with the digestion and absorption of nutrients .
Benzo(a)pyrene
BaP has an effect on the number of white blood cells , inhibiting some of them from differentiating into macrophages , the body 's first line of defense to fight infections . In 2016 , the molecular mechanism was uncovered as damage to the macrophage membrane 's lipid raft integrity by decreasing membrane cholesterol at 25 % . This means less immunoreceptors CD32 ( a member of the Fc family of immunoreceptors ) could bind to IgG and turn the white blood cell into a macrophage . Therefore , macrophage membranes become susceptibile to bacterial infections .
Lead poisoning
In acute poisoning , typical neurological signs are pain , muscle weakness , numbness and tingling , and , rarely , symptoms associated with inflammation of the brain . Abdominal pain , nausea , vomiting , diarrhea , and constipation are other acute symptoms . Lead 's effects on the mouth include astringency and a metallic taste . Gastrointestinal problems , such as constipation , diarrhea , poor appetite , or weight loss , are common in acute poisoning . Absorption of large amounts of lead over a short time can cause shock ( insufficient fluid in the circulatory system ) due to loss of water from the gastrointestinal tract . Hemolysis ( the rupture of red blood cells ) due to acute poisoning can cause anemia and hemoglobin in the urine . Damage to kidneys can cause changes in urination such as decreased urine output . People who survive acute poisoning often go on to display symptoms of chronic poisoning .
Huntington's disease
Mutant Huntingtin is expressed throughout the body and associated with abnormalities in peripheral tissues that are directly caused by such expression outside the brain . These abnormalities include muscle atrophy , cardiac failure , impaired glucose tolerance , weight loss , osteoporosis , and testicular atrophy .
Protein folding
A protein is considered to be misfolded if it can not achieve its normal native state . This can be due to mutations in the amino acid sequence or a disruption of the normal folding process by external factors . The misfolded protein typically contains β - sheets that are organized in a supramolecular arrangement known as a cross-β structure . These β - sheet - rich assemblies are very stable , very insoluble , and generally resistant to proteolysis . The structural stability of these fibrillar assemblies is caused by extensive interactions between the protein monomers , formed by backbone hydrogen bonds between their β - strands . The misfolding of proteins can trigger the further misfolding and accumulation of other proteins into aggregates or oligomers . The increased levels of aggregated proteins in the cell leads to formation of amyloid - like structures which can cause degenerative disorders and cell death . The amyloids are fibrillary structure that contain intermolecular hydrogen bonds , which are highly insoluble , and made from converted protein aggregates . Therefore , the proteasome pathway may not be efficient enough to degrade the misfolded proteins prior to aggregation . Misfolded proteins can interact with one another and form structured aggregates and gain toxicity through intermolecular interactions .
Mechanism of action of aspirin
A side - effect of aspirin mechanism is that the ability of the blood in general to clot is reduced , and excessive bleeding may result from the use of aspirin .
Tooth decay
Dental caries can also cause bad breath and foul tastes . In highly progressed cases , an infection can spread from the tooth to the surrounding soft tissues . Complications such as cavernous sinus thrombosis and Ludwig angina can be life - threatening .
Insulin
If beta cells are destroyed by an autoimmune reaction , insulin can no longer be synthesized or be secreted into the blood . This results in type 1 diabetes mellitus , which is characterized by abnormally high blood glucose concentrations , and generalized body wasting . In type 2 diabetes mellitus the destruction of beta cells is less pronounced than in type 1 diabetes , and is not due to an autoimmune process . Instead there is an accumulation of amyloid in the pancreatic islets , which likely disrupts their anatomy and physiology . The pathogenesis of type 2 diabetes is not well understood but patients exhibit a reduced population of islet beta - cells , reduced secretory function of islet beta - cells that survive , and peripheral tissue insulin resistance . Type 2 diabetes is characterized by high rates of glucagon secretion into the blood which are unaffected by , and unresponsive to the concentration of glucose in the blood . Insulin is still secreted into the blood in response to the blood glucose . As a result , the insulin levels , even when the blood sugar level is normal , are much higher than they are in healthy persons . There are a variety of treatment regimens , none of which is entirely satisfactory . When the pancreas 's capacity to secrete insulin can no longer keep the blood sugar level within normal bounds , insulin injections are given .
Insulin
When the glucose level comes down to the usual physiologic value , insulin release from the β - cells slows or stops . If the blood glucose level drops lower than this , especially to dangerously low levels , release of hyperglycemic hormones ( most prominently glucagon from islet of Langerhans alpha cells ) forces release of glucose into the blood from the liver glycogen stores , supplemented by gluconeogenesis if the glycogen stores become depleted . By increasing blood glucose , the hyperglycemic hormones prevent or correct life - threatening hypoglycemia .
Eating disorder
Bulimia nervosa symptoms include heart problems like an irregular heartbeat that can lead to heart failure and death may occur . This occurs because of the electrolyte imbalance that is a result of the constant binge and purge process . The probability of a gastric rupture increases . A gastric rupture is when there is a sudden rupture of the stomach lining that can be fatal. The acids that are contained in the vomit can cause a rupture in the esophagus as well as tooth decay . As a result , to laxative abuse , irregular bowel movements may occur along with constipation . Sores along the lining of the stomach called peptic ulcers begin to appear and the chance of developing pancreatitis increases .
White blood cell
Defined as total lymphocyte count below 1.0 x10 / L , the cells most commonly affected are CD4+ T cells . Like neutropenia , lymphocytopenia may be acquired or intrinsic and there are many causes . This is not a complete list .
Sickle cell disease
Phase 1 clinical trials of gene therapy for sickle cell disease in humans were started in 2014 . The clinical trials will assess the safety and initial evidence for efficacy of an autologous transplant of lentiviral vector - modified bone marrow for adults with severe sickle cell disease . As of 2016 , however , no randomized controlled trials have been reported . A case report for the first person treated was published in March 2017 .
Mechanism of action of aspirin
The disease causes fatty liver with minimal inflammation and severe encephalopathy ( with swelling of the brain ) . The liver may become slightly enlarged and firm , and there is a change in the appearance of the kidneys . Jaundice is not usually present .
Oncogene
A mutation within a proto - oncogene , or within a regulatory region ( for example the promoter region ) , can cause a change in the protein structure , causing an increase in protein ( enzyme ) activity a loss of regulation An increase in the amount of a certain protein ( protein concentration ) , caused by an increase of protein expression ( through misregulation ) an increase of protein ( mRNA ) stability , prolonging its existence and thus its activity in the cell gene duplication ( one type of chromosome abnormality ) , resulting in an increased amount of protein in the cell A chromosomal translocation ( another type of chromosome abnormality ) There are 2 different types of chromosomal translocations that can occur : translocation events which relocate a proto - oncogene to a new chromosomal site that leads to higher expression translocation events that lead to a fusion between a proto - oncogene and a 2nd gene ( this creates a fusion protein with increased cancerous / oncogenic activity ) the expression of a constitutively active hybrid protein . This type of mutation in a dividing stem cell in the bone marrow leads to adult leukemia Philadelphia Chromosome is an example of this type of translocation event . This chromosome was discovered in 1960 by Peter Nowell and David Hungerford , and it is a fusion of parts of DNA from chromosome 22 and chromosome 9 . The broken end of chromosome 22 contains the `` BCR '' gene , which fuses with a fragment of chromosome 9 that contains the `` ABL1 '' gene . When these two chromosome fragments fuse the genes also fuse creating a new gene : `` BCR - ABL '' . This fused gene encodes for a protein that displays high protein tyrosine kinase activity ( this activity is due to the `` ABL1 '' half of the protein ) . The unregulated expression of this protein activates other proteins that are involved in cell cycle and cell division which can cause a cell to grow and divide uncontrollably ( the cell becomes cancerous ) . As a result , the Philadelphia Chromosome is associated with Chronic Myelogenous Leukemia ( as mentioned before ) as well as other forms of Leukemia .