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Topic Review
Atypical Chronic Myeloid Leukemia
Atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML) is a rare myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with a high rate of transformation to acute myeloid leukemia, and poor survival. Until now, the diagnosis has been based on morphological grounds only, possibly making the real frequency of the disease underestimated. Only recently, new insights in the molecular biology of MDS/MPN syndromes have deepened our knowledge of aCML, enabling us to have a better molecular profile of the disease. The knowledge gleaned from next generation sequencing has complemented morphologic and laboratory WHO criteria for myeloid neoplasms and can provide greater specificity in distinguishing aCML from alternative MDS/MPN or MPNs. The most commonly mutated genes (> 20%) in aCML are SETBP1, ASXL1, N/K-RAS, SRSF2, and TET2, and less frequently (< 10%) CBL, CSFR3, JAK2, EZH2, and ETNK1. Several of these mutations affect the JAK-STAT, MAPK, and ROCK signaling pathways, which are targetable by inhibitors that are already in clinical use and may lead to a personalized treatment of aCML patients unfit for allogeneic transplant, which is currently the only curative option for fit patients. 
  • 1.5K
  • 27 Oct 2020
Topic Review
Atypical Depression
Atypical depression as it has been known in the DSM IV, is depression that shares many of the typical symptoms of the psychiatric syndromes of major depression or dysthymia but is characterized by improved mood in response to positive events. In contrast to atypical depression, people with melancholic depression generally do not experience an improved mood in response to normally pleasurable events. Atypical depression also features significant weight gain or an increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment. Despite its name, "atypical" depression does not mean it is uncommon or unusual. The reason for its name is twofold: it was identified with its "unique" symptoms subsequent to the identification of melancholic depression and its responses to the two different classes of antidepressants that were available at the time were different from melancholic depression (i.e., MAOIs had clinically significant benefits for atypical depression, while tricyclics did not). Atypical depression is four times more common in females than in males. Individuals with atypical features tend to report an earlier age of onset (e.g. while in high school) of their depressive episodes, which also tend to be more chronic and only have partial remission between episodes. Younger individuals may be more likely to have atypical features, whereas older individuals may more often have episodes with melancholic features. Atypical depression has high comorbidity of anxiety disorders, carries more risk of suicidal behavior, and has distinct personality psychopathology and biological traits. Atypical depression is more common in individuals with bipolar I, bipolar II, cyclothymia and seasonal affective disorder. Depressive episodes in bipolar disorder tend to have atypical features, as does depression with seasonal patterns.
  • 595
  • 02 Nov 2022
Topic Review
Atypical Endometriosis-Associated Biomarkers
Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. Atypical endometriosis can be a transitioning entity from endometriosis to endometriosis-associated ovarian cancers. 39 studies assessing numerous molecular targets of AE, such as immunohistochemical expression of BAF250, PIK3CA, PTEN, HNF-1beta, ER, and PR. Unfortunately, these molecular biomarkers of AE require expensive molecular analysis, histological examination is always needed, and none of them has such strong evidence to justify their systematic use in the management of the neoplastic risk of endometriosis. Further studies are needed to validate evidence on available biomarkers for the presence of AE, which is a high oncologic risk condition. Moreover, the introduction of novel serum biomarkers could be useful for the non-invasive diagnosis of AE.
  • 678
  • 05 May 2022
Topic Review
Atypical Femoral Fractures Related to Bisphosphonate Treatment
Atypical femoral fractures (AFF) are rare fragility fractures in the subtrocantheric or diaphysis femoral region associated with long-term bisphosphonate (BP) treatment. The etiology of AFF is still unclear even though a genetic basis is suggested. 
  • 393
  • 07 Feb 2022
Topic Review
Atypical Positional Vertigo
Benign paroxysmal positional vertigo is the most frequent cause of vertigo. As its name indicates, it is characterized by vertigo episodes of sudden onset and end, triggered by changes in head’s position with regard to gravity. It is located in the labyrinth, and its cause is mechanical. However, this is an etiologic diagnosis, reached after questioning and examining the patient. Based on what patients report, the duration of symptoms lasts seconds; however, many overestimate the duration of the vertiginous sensation. The trigger effect of positional changes is a key issue to be addressed. A great variability of autonomic symptoms, including nausea and vomiting, can accompany BPPV. Gait instability, headache, and additional neurologic complaints are potential red flags in the differential diagnosis. With a defined position trigger effect, it is the neurologist’s job to perform an examination to confirm the diagnosis of paroxysmal positional vertigo (PPV), and by virtue of the vertigo duration and nystagmus characteristics, to determine lesion localization (peripheral versus central) and to design a management plan.
  • 784
  • 26 May 2022
Topic Review
Atypical Skull-Base Osteomyelitis
Atypical skull-base osteomyelitis is a rare but fatal disease that usually involves infection of the ethmoid, sphenoid, occipital, or temporal bones that form the skull base. Unlike typical (so-called otogenic), atypical skull-base osteomyelitis has no otogenic cause. Instead, some authors call atypical skull-base osteomyelitis sinonasal, since the infection most often originates from the nose and paranasal sinuses. 
  • 445
  • 09 May 2023
Topic Review
Atypical Teratoid/Rhabdoid Tumor in Taiwan
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal brain tumor most commonly presenting in young children. Older age, supratentorial site, and treatment with radiotherapy, chemotherapy, or both were significantly associated with better survival of patients with AT/RT in Taiwan. 
  • 572
  • 08 Feb 2022
Topic Review
Atypical Ubiquitination and Parkinson’s Disease
Ubiquitination (the covalent attachment of ubiquitin molecules to target proteins) is one of the main post-translational modifications of proteins. Historically, the type of polyubiquitination, which involves K48 lysine residues of the monomeric ubiquitin, was the first studied type of ubiquitination. It usually targets proteins for their subsequent proteasomal degradation. All the other types of ubiquitination, including monoubiquitination; multi-monoubiquitination; and polyubiquitination involving lysine residues K6, K11, K27, K29, K33, and K63 and N-terminal methionine, were defined as atypical ubiquitination (AU). Good evidence now exists that AUs, participating in the regulation of various cellular processes, are crucial for the development of Parkinson’s disease (PD). These AUs target various proteins involved in PD pathogenesis. The K6-, K27-, K29-, and K33-linked polyubiquitination of alpha-synuclein, the main component of Lewy bodies, and DJ-1 (another PD-associated protein) is involved in the formation of insoluble aggregates. Multifunctional protein kinase LRRK2 essential for PD is subjected to K63- and K27-linked ubiquitination. Mitophagy mediated by the ubiquitin ligase parkin is accompanied by K63-linked autoubiquitination of parkin itself and monoubiquitination and polyubiquitination of mitochondrial proteins with the formation of both classical K48-linked ubiquitin chains and atypical K6-, K11-, K27-, and K63-linked polyubiquitin chains. The ubiquitin-specific proteases USP30, USP33, USP8, and USP15, removing predominantly K6-, K11-, and K63-linked ubiquitin conjugates, antagonize parkin-mediated mitophagy. 
  • 443
  • 13 May 2022
Topic Review
Audiovestibular Disorders after COVID-19 Vaccine
The SARS-CoV-2 vaccination campaign is probably one of the most historic public hygiene measures in modern medicine. The drama of the pandemic has forced the scientific community to accelerate the development and commercialization of vaccines, thereby enhancing the phases of active surveillance. Among the adverse events following immunization (AEFI) reported, those of an audiovestibular interest, such as sudden sensorineural hearing loss (SSNHL), tinnitus, dizziness, and vertigo, constitute a very small percentage.
  • 976
  • 05 May 2022
Topic Review
Auditory Mismatch Responses and Speech Perception Development
Auditory Mismatch Responses (MMR), as the Mismatch Negativity (MMN) and Late Discriminative Negativity (LDN), change from birth to adulthood, reflecting auditory and brain maturation and language experience. Throughout development, the MMR can present a different polarity, latency, amplitude, and scalp distribution than the adult MMN/LDN. In addition, conventional ERP analysis can be complemented with time–frequency analysis (TF) to preserver non-stimulus locked neural activity, which is abundant in paediatric EEG. Although TF analysis is less popular in the MMN research field, it may help further our understanding of how speech perception develops in early childhood and in clinical populations in particular, as children with Developmental Language Disorder (DLD).
  • 157
  • 12 Jan 2024
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