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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Most patients with "ETV6-ACSL6"-related disease present with findings similar to eosinophilia, hypereosinophila, or chronic eosinophilic leukemia; at least 4 cases presented with eosinophilia plus findings of the red blood cell neoplasm, polycythemia vera; three cases resembled acute myelogenous leukemia; and one case presented with findings of a combined Myelodysplastic syndrome/myeloproliferative neoplasm. Best treatments for "ETV6-ACSL6"-related disease are unclear. Patients with the polycythemia vera form of the disease have been treated by reducing the circulating red blood cell load by phlebotomy or suppressing red blood cell formation using hydroxyurea. Individual case studies report that "ETV6-ACSL6"-associated disease is insensitive to tyrosine kinase inhibitors. Best treatment currently available, therefore, may involve chemotherapy and bone marrow transplantion.
Patients with hematological disease related to the cited "FLT3" fusion genes present with either a myeloid or lymphoid neoplasm plus eosinophilia. Four of 6 patients with "ETV6-FLT3"-related disease, a patient with "GOLGB1-FLT3"-related disease, and a patient with "TRIP11-FLT3"-related disease presented with findings similar to T-cell lymphoma while a patient with "SPTBN1-FLT3"-related disease had findings of chronic myelogenous leukemia. Two patients with "ETV6-FLT3"-related disease experienced complete hematologic remissions when treated with a multi-kinase inhibitor, sunitinib, that has inhibitory activity against FLT3 protein. However, these remissions were short-lived. A third patient with "ETV6-FLT3"-related disease was treated with a similarly active kinase inhibitor, sorafenib. This patient achieved a complete hematological response and was then given a hematopoietic stem cell transplantation. The latter treatment regimen, FLT3 inhibitor followed by hematopoietic stem cell transplantation, may be the best approach currently available for treating "FLT3"-releated hematological disease.
Treatment largely depends upon individual disease progression and the nature of presenting symptoms. Antimalarials, corticosteroids, and other drugs may be prescribed, if deemed appropriate by the treating physician.
Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed in order to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications such as prednisone, mycophenolic acid and tacrolimus have been used in the past.
Disease-modifying antirheumatic drugs (DMARDs) are used preventively to reduce the incidence of flares, the progress of the disease, and the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are antimalarials such as hydroxychloroquine and immunosuppressants (e.g. methotrexate and azathioprine). Hydroxychloroquine is an FDA-approved antimalarial used for constitutional, cutaneous, and articular manifestations. Hydroxychloroquine has relatively few side effects, and there is evidence that it improves survival among people who have SLE.
Cyclophosphamide is used for severe glomerulonephritis or other organ-damaging complications. Mycophenolic acid is also used for treatment of lupus nephritis, but it is not FDA-approved for this indication, and FDA is investigating reports that it may be associated with birth defects when used by pregnant women.
Most patients will maintain a diagnosis of undifferentiated connective tissue disease. However, about one third of UCTD patients will differentiate to a specific autoimmune disease, like rheumatoid arthritis or systemic sclerosis. About 12 percent of patients will go into remission.
Severe vitamin D deficiency has been associated with the progression of UCTD into defined connective tissue diseases. The presence of the autoantibodies anti-dsDNA, anti-Sm, and anti-cardiolipin has been shown to correlate with the development of systemic lupus erythematosus, specifically.
Since the conversion of dihydroxyphenylserine (Droxidopa; trade name: Northera; also known as L-DOPS, L-threo-dihydroxyphenylserine, L-threo-DOPS and SM-5688), to norepinephrine bypasses the dopamine beta-hydroxylation step of catecholamine synthesis, L-Threo-DOPS is the ideal therapeutic agent. In humans with DβH deficiency, L-Threo-DOPS, a synthetic precursor of noradrenaline, administration has proven effective in dramatic increase of blood pressure and subsequent relief of postural symptoms.
L-DOPS continues to be studied pharmacologically and pharmacokinetically and shows an ability to increase the levels of central nervous system norepinephrine by a significant amount. This is despite the fact that L-DOPS has a relative difficulty crossing the blood-brain barrier when compared to other medications such as L-DOPA. When used concurrently, there is evidence to show that there is increased efficacy as they are both intimately involved and connected to the pathway in becoming norepinephrine.
There is hope and evidence that L-DOPS can be used much more widely to help other conditions or symptoms such as pain, chronic stroke symptoms, and progressive supranuclear palsy, amongst others. Clinically, L-DOPS has been already shown to be helpful in treating a variety of other conditions related to hypotension including the following:
- Diabetes induced orthostatic hypotension
- Dialysis-induced hypotension
- Orthostatic intolerance
- Familial amyloidotic polyneuropathy
- Spinal Cord Injury related hypotension
Empirical evidence of mild effectiveness has been reported using mineralocorticoids or adrenergic receptor agonists as therapies.
Other medications that can bring relief to symptoms include:
- phenylpropanolamine- due to pressor response to vascular α-adrenoceptors
- indomethacin
Vitamin C (ascorbic acid) is also a required cofactor for the Dopamine beta hydroxylase enzyme. Recent research has shown that vitamin C rapidly catalyzes the conversion of dopamine to norepinephrine through stimulation of the dopamine beta hydroxylase enzyme.
Untreated individuals with DβH deficiency should avoid hot environments, strenuous exercise, standing still, and dehydration.
The type of treatment needed for dogs diagnosed with CM/SM depends on the severity of the condition and the age of the dog. Young dogs with clinical signs should be considered for surgical removal to minimize the progression of the disease as the dog ages. Older dogs with little or no clinical signs may be treated medically, rather than surgically. However, severe cases of CM/SM may require surgery regardless of age. The goal of surgery is syrynx decompression through restoration of normal cerebrospinal fluid circulation.
The surgical treatment of CM in dogs is described as "foramen magnum decompression FMD". Despite an approximately 80% success rate with this surgical technique, there is a 25% to 50% relapse, primarily due to excessive scar tissue formation at the decompression site. A cranioplasty may be performed instead, in which a plate, constructed using titanium mesh and bone cement, is fixed to the back of the skull following a standard FMD procedure. The procedure had been effective in humans. The postoperative relapse rate associated with the titanium cranioplasty procedure is less than 7%.
Some practitioners believe there would be evidence indicating anxiolytics to be helpful in treating children and adults with selective mutism, to decrease anxiety levels and thereby speed the process of therapy. Use of medication may end after nine to twelve months, once the person has learned skills to cope with anxiety and has become more comfortable in social situations. Medication is more often used for older children, teenagers, and adults whose anxiety has led to depression and other problems.
Medication, when used, should never be considered the entire treatment for a person with selective mutism. While on medication, the person should be in therapy to help them learn how to handle anxiety and prepare them for life without medication.
Antidepressants have been used in addition to self-modeling and mystery motivation to aid in the learning process.
Spacing is important to integrate, especially with self-modeling. Repeated and spaced out use of interventions is shown to be the most helpful long-term for learning. Viewing videotapes of self-modeling should be shown over a spaced out period of time of approximately 6 weeks.
Both therapy and a number of medications have been found to be useful for treating childhood anxiety disorders. Therapy is generally preferred to medication.
Cognitive behavioral therapy (CBT) is a good first therapy approach. Studies have gathered substantial evidence for treatments that are not CBT based as being effective forms of treatment, expanding treatment options for those who do not respond to CBT. Like adults, children may undergo psychotherapy, cognitive-behavioral therapy, or counseling. Family therapy is a form of treatment in which the child meets with a therapist together with the primary guardians and siblings. Each family member may attend individual therapy, but family therapy is typically a form of group therapy. Art and play therapy are also used. Art therapy is most commonly used when the child will not or cannot verbally communicate, due to trauma or a disability in which they are nonverbal. Participating in art activities allows the child to express what they otherwise may not be able to communicate to others. In play therapy, the child is allowed to play however they please as a therapist observes them. The therapist may intercede from time to time with a question, comment, or suggestion. This is often most effective when the family of the child plays a role in the treatment.
If a medication option is warranted, antidepressants such as SSRIs and SNRIs can be effective. Minor side effects with medications, however, are common.
Many other remedies have been used for anxiety disorder. These include kava, where the potential for benefit seems greater than that for harm with short-term use in those with mild to moderate anxiety. The American Academy of Family Physicians (AAFP) recommends use of kava for those with mild to moderate anxiety disorders who are not using alcohol or taking other medicines metabolized by the liver, and who wish to use "natural" remedies. Side effects of kava in the clinical trials were rare and mild.
Inositol has been found to have modest effects in people with panic disorder or obsessive-compulsive disorder. There is insufficient evidence to support the use of St. John's wort, valerian or passionflower.
Aromatherapy has shown some tentative benefits for anxiety reduction in people with cancer when done with massages, although it not clear whether it could just enhance the effect of massage itself.
Treatment depends on the location and size of the AVM and whether there is bleeding or not.
The treatment in the case of sudden bleeding is focused on restoration of vital function. Anticonvulsant medications such as phenytoin are often used to control seizure; medications or procedures may be employed to relieve intracranial pressure. Eventually, curative treatment may be required to prevent recurrent hemorrhage. However, any type of intervention may also carry a risk of creating a neurological deficit.
Preventive treatment of as yet unruptured brain AVMs has been controversial, as several studies suggested favorable long-term outcome for unruptured AVM patients not undergoing intervention. The NIH-funded longitudinal ARUBA study ("A Randomized trial of Unruptured Brain AVMs) compares the risk of stroke and death in patients with preventive AVM eradication versus those followed without intervention. Interim results suggest that fewer strokes occur as long as patients with unruptured AVM do not undergo intervention. Because of the higher than expected event rate in the interventional arm of the ARUBA study, NIH/NINDS stopped patient enrollment in April 2013, while continuing to follow all participants to determine whether the difference in stroke and death in the two arms changes over time.
Surgical elimination of the blood vessels involved is the preferred curative treatment for many types of AVM. Surgery is performed by a neurosurgeon who temporarily removes part of the skull (craniotomy), separates the AVM from surrounding brain tissue, and resects the abnormal vessels. While surgery can result in an immediate, complete removal of the AVM, risks exist depending on the size and the location of the malformation. The AVM must be resected en bloc, for partial resection will likely cause severe hemorrhage. The preferred treatment of Spetzler-Martin grade 1 and 2 AVMs in young, healthy patients is surgical resection due to the relatively small risk of neurological damage compared to the high lifetime risk of hemorrhage. Grade 3 AVMs may or may not be amenable to surgery. Grade 4 and 5 AVMs are not usually surgically treated.
Radiosurgery has been widely used on small AVMs with considerable success. The Gamma Knife is an apparatus used to precisely apply a controlled radiation dosage to the volume of the brain occupied by the AVM. While this treatment does not require an incision and craniotomy (with their own inherent risks), three or more years may pass before the complete effects are known, during which time patients are at risk of bleeding. Complete obliteration of the AVM may or may not occur after several years, and repeat treatment may be needed. Radiosurgery is itself not without risk. In one large study, nine percent of patients had transient neurological symptoms, including headache, after radiosurgery for AVM. However, most symptoms resolved, and the long-term rate of neurological symptoms was 3.8%.
Embolization is performed by interventional neuroradiologists and the occlusion of blood vessels most commonly is obtained with Ethylene-vinyl alcohol copolymer (Onyx) or N-butyl cyanoacrylate (NBCA). These substances are introduced by a radiographically guided catheter, and block vessels responsible for blood flow into the AVM. Embolization is frequently used as an adjunct to either surgery or radiation treatment. Embolization reduces the size of the AVM and during surgery it reduces the risk of bleeding. However, embolization alone may completely obliterate some AVMs. In high flow intranidal fistulas balloons can also be used to reduce the flow so that embolization can be done safely.
Iodine deficiency is treated by ingestion of iodine salts, such as found in food supplements. Mild cases may be treated by using iodized salt in daily food consumption, or drinking more milk, or eating egg yolks, and saltwater fish. For a salt and/or animal product restricted diet, sea vegetables (kelp, hijiki, dulse, nori (found in sushi)) may be incorporated regularly into a diet as a good source of iodine.
The recommended daily intake of iodine for adult women is 150–300 µg for maintenance of normal thyroid function; for men it is somewhat less at 150 µg.
However, too high iodine intake, for example due to overdosage of iodine supplements, can have toxic side effects. It can lead to hyperthyroidism and consequently high blood levels of thyroid hormones (hyperthyroxinemia). In case of extremely high single-dose iodine intake, typically a short-term suppression of thyroid function (Wolff–Chaikoff effect) occurs. Persons with pre-existing thyroid disease, elderly persons, fetuses and neonates, and patients with other risk factors are at a higher risk of experiencing iodine-induced thyroid abnormalities. In particular, in persons with goiter due to iodine deficiency or with altered thyroid function, a form of hyperthyroidism called Jod-Basedow phenomenon can be triggered even at small or single iodine dosages, for example as a side effect of administration of iodine-containing contrast agents. In some cases, excessive iodine contributes to a risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease).
The application of MRI plays a significant role in the early diagnosis and treatment of SCIWORA in children and adults. Recently, systematic reviews on SCIWORA described the clinical and radiological patterns and correlations with neurological outcome.C.K. Boese und P. Lechler: "Spinal cord injury without radiologic abnormalities in adults: a systematic review." In: "Journal of Trauma and Acute Care Surgery." 78, 2015, S. 320-330 .Boese CK, Oppermann J, Siewe J, Eysel P, Scheyerer MJ, Lechler P.: "Spinal cord injury without radiologic abnormality in children: a systematic review and meta-analysis." In: "Journal of Trauma and Acute Care Surgery." 75, 2013. Boese and Lechler proposed a MRI-based classification for SCIWORA which correlated with the neurological outcome:
Chiari-like malformation (CM) is the most common cause of foramen magnum obstruction and syringomyelia in dogs. Syringomyelia (SM) is a disease of the spinal cord typified by fluid filled cavities, or syrinxes, within the spinal cord substance. The disease is caused by the obstruction of cerebrospinal fluid (CSF), in the nervous system. A situation of high pressure in the spinal cord compared to low pressure outside, leads to fluid accumulation, which eventually forms cavities. CM is a condition characterized by the mismatch of size between the brain and the skull. The skull is too small causing part of the brain to descend out of the skull through the opening at its base, crowding the spinal cord. The cause of CM is not yet fully understood. CM is rare in most breeds but reportedly has become very widespread in the Cavalier King Charles Spaniel and the Griffon Bruxellois (Brussels Griffon). As many as 95% of Cavalier King Charles Spaniels may have CM. It is worldwide in scope and not limited to any country, breeding line, or kennel, and experts report that it is believed to be inherited in the Cavalier King Charles Spaniel. CM is so widespread in the Cavalier that it may be an inherent part of the CKCS's breed standard. This disease not only affects thousands of dogs, but a similar condition affects over three hundred thousand children yearly. Therefore, canines are an appropriate model for the treatment of the human condition.
The Cleveland steamer is a colloquial term for a form of coprophilia, where someone defecates on their partner's chest.
The term received news attention through its use in a U.S. Congress staff hoax email and being addressed by the United States Federal Communications Commission.
No randomized, controlled clinical trial has established a survival benefit for treating patients (either with open surgery or radiosurgery) with AVMs that have not yet bled.
Coprophilia (from Greek "κόπρος, kópros—excrement" and "φιλία, philía—liking, fondness"), also called scatophilia or scat (Greek: "σκατά, skatá-feces"), is the paraphilia involving sexual arousal and pleasure from feces. In the "Diagnostic and Statistical Manual of Mental Disorders" (DSM), published by the American Psychiatric Association, it is classified under 302.89 – Paraphilia NOS (Not Otherwise Specified) and has no diagnostic criteria other than a general statement about paraphilias that says "the diagnosis is made if the behavior, sexual urges, or fantasies cause clinically significant distress or impairment in social, occupational, or other important areas of functioning". Furthermore, the DSM-IV-TR notes, "Fantasies, behaviors, or objects are paraphilic only when they lead to clinically significant distress or impairment (e.g. are obligatory, result in sexual dysfunction, require participation of nonconsenting individuals, lead to legal complications, interfere with social relationships)".
Although there may be no connection between coprophilia and sadomasochism (SM), the limited data on the former comes from studies of the latter. A study of 164 males in Finland from two SM clubs found that 18.2% had engaged in coprophilia; 3% as a sadist, 6.1% as a masochist, and 9.1% as both. 18% of heterosexuals and 17% of homosexuals in the study pool had tried coprophilia, showing no statistically significant difference between heterosexuals and homosexuals. In a separate article analyzing 12 men who engaged in bestiality, an additional analysis of an 11-man subgroup revealed that 6 had engaged in coprophilic behavior, compared with only 1 in the matched control group consisting of 12 SM-oriented males who did not engage in bestiality.
There is preliminary evidence that iodine deficiency enhances the sensitivity of breast tissue to estrogen. In rats treated with estradiol, iodine deficiency has been shown to lead to changes similar to benign breast changes that are reversible by increased iodine in the diet. In a few studies, iodine supplementation had beneficial effects (such as reducing the presence of breast cyst, fibrous tissue plaques and breast pain) in women with fibrocystic breast changes.
Protective effects of iodine on breast cancer have been postulated from epidemiologic evidence and described in animal models. In view of the antiproliferative properties of iodine in breast tissue, molecular iodine supplementation has been suggested as an adjuvant in breast cancer therapy.
Some types of BDSM play include, but are not limited to:
- Animal roleplay
- Bondage
- Breast torture
- Cock and ball torture (CBT)
- Erotic electrostimulation
- Edgeplay
- Flogging
- Golden showers (urinating)
- Human furniture
- Japanese bondage
- Medical play
- Paraphilic infantilism
- Predicament bondage
- Pussy torture
- Sexual roleplay
- Spanking
- Suspension
- Torture
- Tickle torture
- Wax play
Nichols (2006) compiled some common clinical issues: countertransference, non-disclosure, coming-out, partner/families, and bleed-through.
Countertransference is a common problem in clinical settings. Despite having no evidence, therapists may find themselves believing that their client’s pathology is "self-evident". Therapists may feel intense disgust and aversive reactions. Feelings of countertransference can interfere with therapy. Another common problem is when clients conceal their sexual preferences from their therapists. This can compromise any therapy. To avoid non-disclosure, therapists are encouraged to communicate their openness in indirect ways with literatures and artworks in the waiting room. Therapists can also deliberately bring up BDSM topics during the course of therapy. With less informed therapists, sometimes they over-focus on clients’ sexuality which detracts from original issues such as family relationships, depression, etc. A special subgroup that needs counselling is the "newbie". Individuals just coming out might have internalized shame, fear, and self-hatred about their sexual preferences. Therapists need to provide acceptance, care, and model positive attitude; providing reassurance, psychoeducation, and bibliotherapy for these clients is crucial. The average age when BDSM individuals realize their sexual preference is around 26 years. Many people hide their sexuality until they can no longer contain their desires. However, they may have married or had children by this point. Therefore, therapists need to facilitate couple's counselling and disclosure. It is important for therapists to consider fairness to partner and family of clients. In situations when boundaries between roles in the bedroom and roles in the rest of the relationship blurs, a "bleed-through" problem has occurred. Therapists need to help clients resolve distress and deal with any underlying problems that led to the initial bleed-through.
SCIWORA may present as a complete spinal cord injury (total loss of sensation and function below the lesion) or incomplete spinal cord injury (some sensation and/or function is preserved). It is present in a significant number of children with SCI. Notably, the clinical symptoms can present with a delay of hours to days after the trauma. This phenomenon was primarily seen in children but was reported in adults as well. The duration of symptoms varies widely. A full recovery can be achieved without treatment within minutes to hours and permanent injuries might prevail. Overall, there seems to be a relation between extent of damage to the spinal cord and the clinical prognosis. The prognostic value of intra- and extra-medullary MRI findings is subject of ongoing research in the field of SCIWORA.
Sadomasochism is the giving or receiving pleasure from acts involving the receipt or infliction of pain or humiliation. Practitioners of sadomasochism may seek sexual gratification from their acts. While the terms sadist and masochist refer respectively to one who enjoys giving or receiving pain, practitioners of sadomasochism may switch between activity and passivity.
The abbreviation S&M is often used for sadomasochism, although practitioners themselves normally remove the ampersand and use the acronym S-M or SM or S/M when written throughout the literature. Sadomasochism is not considered a clinical paraphilia unless such practices lead to clinically significant distress or impairment for a diagnosis. Similarly, sexual sadism within the context of mutual consent, generally known under the heading BDSM, is distinguished from non-consensual acts of sexual violence or aggression.