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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
In the second edition of the Chinese Classification of Mental Disorders (CCMD-2) published by the Chinese Society of Psychiatry the diagnosis of “Qigong Deviation Syndrome” is based upon the following criteria:
- The subject being demonstrably normal before doing qigong exercises
- Psychological and physiological reactions appearing during or after qigong exercises (suggestion and autosuggestion may play an important role in these reactions)
- Complaints of abnormal sensations during or after qigong exercises
- Diagnostic criteria do not meet other mental disorders such as schizophrenia, affective disorder, and neurosis.
While the Chinese Society of Psychiatry prefers the term "qigong deviation", the American Psychiatric Association uses psychosis terminology. Some physicians believe that this disease can be categorized as a culture-bound syndrome, but this point is debated.
Morgellons is poorly understood but the general medical consensus is that it is a form of delusional parasitosis in which individuals have some form of actual skin condition that they believe contains some kind of fibers.
Morgellons (/mɔː(ɹ)ˈdʒɛlənz/) is the informal name of a self-diagnosed skin condition in which individuals have sores that they believe contain some kind of fibers. Morgellons is poorly understood but the general medical consensus is that it is a form of delusional parasitosis; the sores are the result of compulsive scratching, and the fibers, when analysed, turn out to originate from textiles.
The name was coined in 2002 by Mary Leitao, a mother who rejected the medical diagnosis of her son's delusional parasitosis. She revived it from a letter written by a physician in the mid-17th century. Leitao and others involved in her Morgellons Research Foundation successfully lobbied members of the U.S. Congress and the U.S. Centers for Disease Control and Prevention (CDC) to investigate the condition in 2006. CDC researchers issued the results of their multi-year study in January 2012, indicating that there were no disease organisms present in people with Morgellons and that the fibers found were likely cotton, and concluded that the condition was "similar to more commonly recognized conditions such as delusional infestation".
Medical abortions are those induced by abortifacient pharmaceuticals. Medical abortion became an alternative method of abortion with the availability of prostaglandin analogs in the 1970s and the antiprogestogen mifepristone (also known as RU-486) in the 1980s.
The most common early first-trimester medical abortion regimens use mifepristone in combination with a prostaglandin analog (misoprostol or gemeprost) up to 9 weeks gestational age, methotrexate in combination with a prostaglandin analog up to 7 weeks gestation, or a prostaglandin analog alone. Mifepristone–misoprostol combination regimens work faster and are more effective at later gestational ages than methotrexate–misoprostol combination regimens, and combination regimens are more effective than misoprostol alone. This regime is effective in the second trimester. Medical abortion regiments involving mifepristone followed by misoprostol in the cheek between 24 and 48 hours later are effective when performed before 63 days' gestation.
In very early abortions, up to 7 weeks gestation, medical abortion using a mifepristone–misoprostol combination regimen is considered to be more effective than surgical abortion (vacuum aspiration), especially when clinical practice does not include detailed inspection of aspirated tissue. Early medical abortion regimens using mifepristone, followed 24–48 hours later by buccal or vaginal misoprostol are 98% effective up to 9 weeks gestational age. If medical abortion fails, surgical abortion must be used to complete the procedure.
Early medical abortions account for the majority of abortions before 9 weeks gestation in Britain, France, Switzerland, and the Nordic countries. In the United States, the percentage of early medical abortions is far lower.
Medical abortion regimens using mifepristone in combination with a prostaglandin analog are the most common methods used for second-trimester abortions in Canada, most of Europe, China and India, in contrast to the United States where 96% of second-trimester abortions are performed surgically by dilation and evacuation.
Up to 15 weeks' gestation, suction-aspiration or vacuum aspiration are the most common surgical methods of induced abortion. "Manual vacuum aspiration" (MVA) consists of removing the fetus or embryo, placenta, and membranes by suction using a manual syringe, while "electric vacuum aspiration" (EVA) uses an electric pump. These techniques differ in the mechanism used to apply suction, in how early in pregnancy they can be used, and in whether cervical dilation is necessary.
MVA, also known as "mini-suction" and "menstrual extraction", can be used in very early pregnancy, and does not require cervical dilation. Dilation and curettage (D&C), the second most common method of surgical abortion, is a standard gynecological procedure performed for a variety of reasons, including examination of the uterine lining for possible malignancy, investigation of abnormal bleeding, and abortion. Curettage refers to cleaning the walls of the uterus with a curette. The World Health Organization recommends this procedure, also called "sharp curettage," only when MVA is unavailable.
From the 15th week of gestation until approximately the 26th, other techniques must be used. Dilation and evacuation (D&E) consists of opening the cervix of the uterus and emptying it using surgical instruments and suction. After the 16th week of gestation, abortions can also be induced by intact dilation and extraction (IDX) (also called intrauterine cranial decompression), which requires surgical decompression of the fetus's head before evacuation. IDX is sometimes called "partial-birth abortion", which has been federally banned in the United States.
In the third trimester of pregnancy, induced abortion may be performed surgically by intact dilation and extraction or by hysterotomy. Hysterotomy abortion is a procedure similar to a caesarean section and is performed under general anesthesia. It requires a smaller incision than a caesarean section and is used during later stages of pregnancy.
First-trimester procedures can generally be performed using local anesthesia, while second-trimester methods may require deep sedation or general anesthesia.
Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) is a sporadic prion protein disease identified in 2008 and first described in 2010 by Zou W.Q. and coworkers from the United States National Prion Disease Pathology Surveillance Center.
VPSPr is very rare, occurring in just 2 or 3 out of every 100 million people. (Nine cases had been identified in the UK by 2013.) It has similarities to Creutzfeldt–Jakob disease, but clinical manifestations differ somewhat, and the abnormal prion protein (PrP) is less resistant to digestion by proteases; some variants are more sensitve to proteases than others, hence the name: variably protease-sensitive.
Patients present with psychiatric symptoms, speech deficits (aphasia and/or dysarthria), and cognitive impairment. Ataxia and parkinsonism can develop. Average age at onset is 70 years, and duration of survival is 24 months. About 40% of patients have a family history of dementia.
Diagnosis is difficult. MRI, EEG, and tests for 14-3-3 protein and tau protein are usually not helpful, and no mutations have been observed in the coding region of the PrP gene.
If diagnosed in time, the various forms of plague are usually highly responsive to antibiotic therapy. The antibiotics often used are streptomycin, chloramphenicol and tetracycline. Amongst the newer generation of antibiotics, gentamicin and doxycycline have proven effective in monotherapeutic treatment of plague.
The plague bacterium could develop drug-resistance and again become a major health threat. One case of a drug-resistant form of the bacterium was found in Madagascar in 1995. Further outbreaks in Madagascar were reported in November 2014 and October 2017.
Since human plague is rare in most parts of the world, routine vaccination is not needed other than for those at particularly high risk of exposure, nor for people living in areas with enzootic plague, meaning it occurs at regular, predictable rates in populations and specific areas, such as the western United States. It is not even indicated for most travellers to countries with known recent reported cases, particularly if their travel is limited to urban areas with modern hotels. The CDC thus only recommends vaccination for: (1) all laboratory and field personnel who are working with "Y. pestis" organisms resistant to antimicrobials; (2) people engaged in aerosol experiments with "Y. pestis"; and (3) people engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas).
A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine.
Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy (AD-RVCL) (previously known also as Cerebroretinal Vasculopathy, CRV, or Hereditary Vascular Retinopathy, HVR or Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke, HERNS) is an inherited condition resulting from a frameshift mutation to the TREX1 gene. This genetically inherited condition affects the retina and the white matter of the central nervous system, resulting in vision loss, lacunar strokes and ultimately dementia. Symptoms commonly begin in the early to mid-forties, and treatments currently aim to manage or alleviate the symptoms rather than treating the underlying cause. The overall prognosis is poor, and death can sometimes occur within 10 years of the first symptoms appearing.
AD-RVCL (CRV) Acronym
Autosomal Dominance (genetics) means only one copy of the gene is necessary for the symptoms to manifest themselves.
Retinal Vasculopathy means a disorder that is associated with a disease of the blood vessels in the retina.
Cerebral means having to do with the brain.
Leukodystrophy means a degeneration of the white matter of the brain.
Pathogenesis
The main pathologic process centers on small blood vessels that prematurely “drop out” and disappear. The retina of the eye and white matter of the brain are the most sensitive to this pathologic process. Over a five to ten-year period, this vasculopathy (blood vessel pathology) results in vision loss and destructive brain lesions with neurologic deficits and death.
Most recently, AD-RVCL (CRV) has been renamed. The new name is CHARIOT which stands for Cerebral Hereditary Angiopathy with vascular Retinopathy and Impaired Organ function caused by TREX1 mutations.
Treatment
Currently, there is no therapy to prevent the blood vessel deterioration.
About TREX1
The official name of the TREX1 gene is “three prime repair exonuclease 1.” The normal function of the TREX1 gene is to provide instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during genetic material in preparation for cell division, DNA repair, cell death, and other processes.
Changes (mutations) to the TREX1 gene can result in a range of conditions one of which is AD-RVCL. The mutations to the TREX1 gene are believed to prevent the production of the 3-prime repair exonuclease 1 enzyme. Researchers suggest that the absence of this enzyme may result in an accumulation of unneeded DNA and RNA in cells. These DNA and RNA molecules may be mistaken by cells for those of viral invaders, triggering immune system reactions that result in the symptoms of AD-RVCL.
Mutations in the TREX1 gene have also been identified in people with other disorders involving the immune system. These disorders include a chronic inflammatory disease called systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin.
The TREX1 gene is located on chromosome 3: base pairs 48,465,519 to 48,467,644
The immune system.
- The immune system is composed of white blood cells or leukocytes.
- There are 5 different types of leukocytes.
- Combined, the 5 different leukocytes represent the 2 types of immune systems (The general or innate immune system and the adaptive or acquired immune system).
- The adaptive immune system is composed of two types of cells (B-cells which release antibodies and T-cells which destroy abnormal and cancerous cells).
How the immune system becomes part of the condition.
During mitosis, tiny fragments of “scrap” single strand DNA naturally occur inside the cell. Enzymes find and destroy the “scrap” DNA. The TREX1 gene provides the information necessary to create the enzyme that destroys this single strand “scrap” DNA. A mutation in the TREX1 gene causes the enzyme that would destroy the single strand DNA to be less than completely effective. The less than completely effective nature of the enzyme allows “scrap” single strand DNA to build up in the cell. The buildup of “scrap” single strand DNA alerts the immune system that the cell is abnormal.
The abnormality of the cells with the high concentration of “scrap” DNA triggers a T-cell response and the abnormal cells are destroyed. Because the TREX1 gene is identical in all of the cells in the body the ineffective enzyme allows the accumulation of “scrap” single strand DNA in all of the cells in the body. Eventually, the immune system has destroyed enough of the cells in the walls of the blood vessels that the capillaries burst open. The capillary bursting happens throughout the body but is most recognizable when it happens in the eyes and brain because these are the two places where capillary bursting has the most pronounced effect.
Characteristics of AD-RVCL
- No recognizable symptoms until after age 40.
- No environmental toxins have been found to be attributable to the condition.
- The condition is primarily localized to the brain and eyes.
- Optically correctable, but continuous, deterioration of visual acuity due to extensive multifocal microvascular abnormalities and retinal neovascularization leading, ultimately, to a loss of vision.
- Elevated levels of alkaline phosphatase.
- Subtle vascular changes in the retina resembling telangiectasia (spider veins) in the parafovea circulation.
- Bilateral capillary occlusions involving the perifovea vessels as well as other isolated foci of occlusion in the posterior pole of the retina.
- Headaches due to papilledema.
- Mental confusion, loss of cognitive function, loss of memory, slowing of speech and hemiparesis due to “firm masses” and white, granular, firm lesions in the brain.
- Jacksonian seizures and grand mal seizure disorder.
- Progressive neurologic deterioration unresponsive to systemic corticosteroid therapy.
- Discrete, often confluent, foci of coagulation necrosis in the cerebral white matter with intermittent findings of fine calcium deposition within the necrotic foci.
- Vasculopathic changes involving both arteries and veins of medium and small caliber present in the cerebral white matter.
- Fibroid necrosis of vessel walls with extravasation of fibrinoid material into adjacent parenchyma present in both necrotic and non-necrotic tissue.
- Obliterative fibrosis in all the layers of many vessel walls.
- Parivascular, adventitial fibrosis with limited intimal thickening.
Conditions with similar symptoms that AD-RVCL can be misdiagnosed as:
- Brain tumors
- Diabetes
- Macular degeneration
- Telangiectasia (Spider veins)
- Hemiparesis (Stroke)
- Glaucoma
- Hypertension (high blood pressure)
- Systemic Lupus Erythematosus (SLE (same original pathogenic gene, but definitely a different disease because of a different mutation in TREX1))
- Polyarteritis nodosa
- Granulomatosis with polyangiitis
- Behçet's disease
- Lymphomatoid granulomatosis
- Vasculitis
Clinical Associations
- Raynaud's phenomenon
- Anemia
- Hypertension
- Normocytic anemia
- Normochromic anemia
- Gastrointestinal bleeding or telangiectasias
- Elevated alkaline phosphatase
Definitions
- Coagulation necrosis
- Endothelium
- Fibrinoid
- Fibrinoid necrosis
- Frameshift mutation
- Hemiparesis
- Jacksonian seizure
- Necrotic
- Necrosis
- Papilledema
- Perivascular
- Retinopathy
- Telangiectasia
- Vasculopathy
- Vascular
What AD-RVCL is not:
- Infection
- Cancer
- Diabetes
- Glaucoma
- Hypertension
- A neurological disorder
- Muscular dystrophy
- Systemic Lupus Erythematosis (SLE)
- Vasculitis
Things that have been tried but turned out to be ineffective or even make things worse:
- Antibiotics
- Steroids
- X-Ray therapy
- Immunosuppression
History of AD-RVCL (CRV)
- 1985 – 1988: CRV (Cerebral Retinal Vasculopathy) was discovered by John P. Atkinson, MD at Washington University School of Medicine in St. Louis, MO
- 1988: 10 families worldwide were identified as having CRV
- 1991: Related disease reported, HERNS (Hereditary Endiotheliopathy with Retinopathy, Nephropathy and Stroke – UCLA
- 1998: Related disease reported, HRV (Hereditary Retinal Vasculopathy) – Leiden University, Netherlands
- 2001: Localized to Chromosome 3.
- 2007: The specific genetic defect in all of these families was discovered in a single gene called TREX1
- 2008: Name changed to AD-RVCL Autosomal Dominant-Retinal Vasculopathy with Cerebral Leukodystrophy
- 2009: Testing for the disease available to persons 21 and older
- 2011: 20 families worldwide were identified as having CRV
- 2012: Obtained mouse models for further research and to test therapeutic agents
Osteochondromas are often asymptomatic and may not cause any kind of discomfort. They are often found accidentally when an X-ray is done for an unrelated reason.
- X-rays are the first tests performed that characterize a lesion. They show a clear picture of dense structures of bones, and will also indicate bone growth pertaining to osteochondroma.
- Computed Tomography (CT) scan can identify the bony lesion in great details and show the presence of calcification. These tests also provide great details, especially in soft tissues with the aide of cross-sectional images.
- Magnetic Resonance Imaging (MRI) is the most accurate method for detecting bone masses in symptomatic cases to depict precise morphology of a tumor. It is used to verify if the palpable mass is continuous with the cortex of the affected bone and to differentiate an osteochondroma from other lesions on the surface of the bone. MRI can also be used to look for cartilage on the surface of tumor and can depict any vascular complications caused by the tumor. An MRI can identify tumors of the spinal column and is often used to diagnose low grade osteosarcoma.
- Ultrasound is done if aneurysms or pseudoaneurysms and venous or arterial thrombosis is suspected. Ultrasound is an accurate method for examining the cartilaginous cap of the osteochondroma. It is also a way of pinpointing bursitis. However, it cannot be used to predict if the growth of tumor is inward in regards to the cap.
- Angiography is used to detect vascular lesions caused by osteochondroma due to ossified cartilaginous cap. It is also used to characterize malignant transformation lesions through neovascularity.
- Clinical testing such as sequence analysis can be done of the entire coding regions of both "EXT1" and "EXT2" to detect mutations.
- A biopsy of the tissue sample of the tumor can also be taken to check for cancer.
Tests for osteochondroma can also identify diseases such as secondary peripheral chondrosarcoma and Multiple osteochondromatosis. In large, secondary chondrosarcoma arises at the site of osteochondroma due to increased thickness of the cartilage cap indicating potential malignant transformation. The symptoms of multiple osteochondromatosis are similar to solitary osteochondroma, but they are often more severe. Painless bumps can arise at the site of tumor and pain and other discomforts can also take place if pressure is put on the soft tissues, nerves, or blood vessels. Dysplasia Epiphysealis Hemimelica (DEH) or Trevor's disease and metachondromatosis (MC) are considered differential diagnosis of both solitary and hereditary osteochondromas. DEH is described as a type of over growth at one or more epiphyses. Similar to osteochondroma, DEH is diagnosed prior to 15 years of age and the growth of lesions end at puberty, when the growth plates close. Metachondromatosis is a rare disorder that exhibit symptoms of both multiple osteochondromas and enchondromas in children and is also inherited in autosomal dominant mode.
Osteochondromas are benign lesions and do not affect life expectancy. Complete excision of osteochondroma is curative and the reoccurrences take place when the removal of tumor is incomplete. Multiple reoccurrences in a well-excised lesion indicate that it may be malignant. The risk of malignant transformation takes place in 1–5% of individuals. If any symptoms of cancerous tumor takes place, then the patient should be evaluated by a bone specialist. No treatment is necessary for Solitary osteochondromas that are asymptomatic. Treatments for solitary osteochondroma are careful observation over time and taking regular x-rays to monitor any changes in the tumor. If the lesion is causing pain with activity, nerve or vessel impingement, or if the bone growth has fully matured and the presence of a large cartilage cap is prominent, then it is advised that the tumor be surgically removed.
Osteochondromas have a low rate of malignancy (<1%) and resection of the tumor is suggested if symptoms such as pain, limitation of movement, or impingement on nerves or vessels occur. Resection of the tumor also takes place when the tumor increases in size and progresses towards malignancy. During surgical resection, the entire lesion along with the cartilaginous cap should be removed to minimize any chances of reoccurrences. Surgical treatment becomes the sole treatment of choice if common complications such as fractures, symptoms of peripheral nerves such as paresthesia, paraplegia, peroneal neuropathy, and upper limb neuropathy take place. A prophylactic resection is suggested if the lesion lies next to a vessel.
Depending on the size and location of the tumor, the time it takes to return to normal daily activities varies between individuals. Limitation on some activities is advised if pain or discomfort persists after surgical excision.
Tissue biopsy is the diagnostic modality of choice. Due to a high incidence of lymph node involvement, a sentinel lymph node biopsy is often performed. A common characteristic of epithelioid sarcoma (observed in 80% of all cases) is the loss of function of the SMARCB1 gene (also termed BAF47, INI1, or hSNF5). Immunohistochemical staining of INI1 is available and can be used for the diagnosis of epithelioid sarcoma. MRI is the diagnostic modality of choice for imaging prior to biopsy and pathologic diagnosis, with the primary role being the determination of anatomic boundaries.
The staging for epithelioid sarcoma takes into account size and location of the primary tumor, lymph node involvement, presence and location of metastasis, and histologic grade (a measure of disease aggressiveness)
Dendritic cells (DCs) are antigen-presenting cells (also known as "accessory cells") of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.
Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the "dendrites" that give the cell its name (δένδρον or déndron being Greek for "tree"). While similar in appearance, these are structures distinct from the dendrites of neurons. Immature dendritic cells are also called veiled cells, as they possess large cytoplasmic 'veils' rather than dendrites.
The morphology of dendritic cells results in a very large surface-to-volume ratio. That is, the dendritic cell has a very large surface area compared to the overall cell volume.