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Topic Review
Proteopathy
In medicine, proteopathy (/proʊtiːˈɒpəθiː/; from proteo- [pref. protein]; -pathy [suff. disease]; proteopathies pl.; proteopathic adj) refers to a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a toxic gain-of-function) or they can lose their normal function. The proteopathies (also known as proteinopathies, protein conformational disorders, or protein misfolding diseases) include such diseases as Creutzfeldt–Jakob disease and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, and a wide range of other disorders. The term proteopathy was first proposed in 2000 by Lary Walker and Harry LeVine. The concept of proteopathy can trace its origins to the mid-19th century, when, in 1854, Rudolf Virchow coined the term amyloid ("starch-like") to describe a substance in cerebral corpora amylacea that exhibited a chemical reaction resembling that of cellulose. In 1859, Friedreich and Kekulé demonstrated that, rather than consisting of cellulose, "amyloid" actually is rich in protein. Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross-polarized light after staining with the dye Congo red, as well as a fibrillar ultrastructure when viewed with an electron microscope. However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign.
  • 988
  • 24 Nov 2022
Topic Review
Genetic Landscape of Common Epilepsies
Genetics play a substantial role in epilepsy. This study presents a panoramic view of genetics known so far that contributes to common epilepsies and how the use of genetics has evolved in clinical implications of the field for disease prognosis, diagnosis as well as in treatment management.  Discussing the risk factors – both genetic and non- genetic, or a combination of both, and how it can be a vital tool for prognosis or diagnosis of different endo-phenotypes of common epilepsies. Such markers hold the potential for genetic diagnosis. So, here we discussed how far are we from achieving this goal of precision medicine and clinical utility in real-time settings. 
  • 987
  • 26 Feb 2021
Topic Review
Acute Kidney Injury (AKI)
Acute kidney injury (AKI) is characterized by an acute loss of renal function. In clinical practice, AKI is defined by an elevation of creatinine plasma concentration above ≥0.3 mg/dL in the first 48 h, an urine volume below 0.5 mL/kg/h for 6 h, or an 1.5 fold increase in serum creatinine as compared with the baseline values.
  • 986
  • 01 Feb 2021
Topic Review
Thoracic Aortic Aneurysms
Thoracic aortic aneurysms (TAA) are permanent and localized dilations of the aorta that predispose patients to a life-threatening risk of aortic dissection or rupture. The identification of pathogenic variants that cause hereditary forms of TAA has delineated fundamental molecular processes required to maintain aortic homeostasis. Vascular smooth muscle cells (VSMCs) elaborate and remodel the extracellular matrix (ECM) in response to mechanical and biochemical cues from their environment. Causal variants for hereditary forms of aneurysm compromise the function of gene products involved in the transmission or interpretation of these signals, initiating processes that eventually lead to degeneration and mechanical failure of the vessel. These include mutations that interfere with transduction of stimuli from the matrix to the actin–myosin cytoskeleton through integrins, and those that impair signaling pathways activated by transforming growth factor-β (TGF-β).
  • 983
  • 16 Feb 2021
Topic Review
Microbiota-Mitochondria Inter-Talk
The rising prevalence of obesity and type 2 diabetes (T2D) is a growing concern worldwide. New discoveries in the field of metagenomics and clinical research have revealed that the gut microbiota plays a key role in these metabolic disorders. The mechanisms regulating microbiota composition are multifactorial and include resistance to stress, presence of pathogens, diet, cultural habits and general health conditions. Recent evidence has shed light on the influence of microbiota quality and diversity on mitochondrial functions. Of note, the gut microbiota has been shown to regulate crucial transcription factors, coactivators, as well as enzymes implicated in mitochondrial biogenesis and metabolism. Moreover, microbiota metabolites seem to interfere with mitochondrial oxidative/nitrosative stress and autophagosome formation, thus regulating the activation of the inflammasome and the production of inflammatory cytokines, key players in chronic metabolic disorders. This review focuses on the association between intestinal microbiota and mitochondrial function and examines the mechanisms that may be the key to their use as potential therapeutic strategies in obesity and T2D management.
  • 982
  • 21 Oct 2020
Topic Review
Obesity and Mood Disorders
Obesity and mood disorders are considered as the most prevalent morbidities in many countries. We suppose that epigenetic mechanisms may induce higher rates of obesity in subjects who suffer from mood disorders. In this study, we focused on the potential roles of DNA methylation on mood disorders and obesity development.
  • 980
  • 05 Jan 2021
Topic Review
Diabetes Mellitus and COVID-19
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a global pandemic. The hyperglycemia in patients with diabetes mellitus (DM) substantially compromises their innate immune system. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) receptors to enter the affected cell. Uncontrolled hyperglycemia-induced glycosylation of ACE2 and the S protein of SARS-CoV-2 could facilitate the binding of S protein to ACE2, enabling viral entry. Downregulation of ACE2 activity secondary to SARS-CoV-2 infection, with consequent accumulation of angiotensin II and metabolites, eventually leads to poor outcomes. The altered binding of ACE2 with SARS-CoV-2 and the compromised innate immunity of patients with DM increase their susceptibility to COVID-19; COVID-19 induces pancreatic β-cell injury and poor glycemic control, which further compromises the immune response and aggravates hyperglycemia and COVID-19 progression, forming a vicious cycle. Sequential cleavage of viral S protein by furin and transmembrane serine protease 2 (TMPRSS2) triggers viral entry to release the viral genome into the target cell. Hence, TMPRSS2 and furin are possible drug targets. As type 1 DM exhibits a Th1-driven autoimmune process, the relatively lower mortality of COVID-19 in type 1 DM compared to type 2 DM might be attributed to an imbalance between Th1 and Th2 immunity. The anti-inflammatory effects of dipeptidyl peptidase-4 inhibitor may benefit patients with DM and COVID-19. The potential protective effects of sodium–glucose cotransporter-2 inhibitor (SGLT2i), including reduction in lactate level, prevention of lowering of cytosolic pH and reduction in pro-inflammatory cytokine levels may justify the provision of SGLT2i to patients with DM and mild or asymptomatic COVID-19. For patients with DM and COVID-19 who require hospitalization, insulin-based treatment is recommended with cessation of metformin and SGLT2i. Further evidence from randomized or case–control clinical trials is necessary to elucidate the effectiveness and pitfalls of different types of medication for DM.
  • 980
  • 22 Dec 2020
Topic Review
GABAB Receptor
The γ-aminobutyric acid (GABA) type B receptor (GABAB-R) belongs to class C of the G-protein coupled receptors (GPCRs). Together with the GABAA receptor, the receptor mediates the neurotransmission of GABA, the main inhibitory neurotransmitter in the central nervous system (CNS).
  • 980
  • 01 Dec 2021
Topic Review
Mucoadhesive Chitosan Nanoparticles
Chitosan is a polysaccharide polymer produced by alkaline deacetylation of chitin. It has a positive charge that may interact with negatively charged mucosal surfaces.
  • 977
  • 18 Mar 2021
Topic Review
Enteric Fever Progression
In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This entry attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of Salmonella typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular Salmonella typhoidal species.
  • 976
  • 23 Feb 2021
Topic Review
Melanoma Single-Cell Biology
Cellular heterogeneity is regarded as a major factor for treatment response and resistance in a variety of malignant tumors, including malignant melanoma. More recent developments of single-cell sequencing technology provided deeper insights into this phenomenon. Single-cell data were used to identify prognostic subtypes of melanoma tumors, with a special emphasis on immune cells and fibroblasts in the tumor microenvironment. Moreover, treatment resistance to checkpoint inhibitor therapy has been shown to be associated with a set of differentially expressed immune cell signatures unraveling new targetable intracellular signaling pathways. Characterization of T cell states under checkpoint inhibitor treatment showed that exhausted CD8+ T cell types in melanoma lesions still have a high proliferative index. Other studies identified treatment resistance mechanisms to targeted treatment against the mutated BRAF serine/threonine protein kinase including repression of the melanoma differentiation gene microphthalmia-associated transcription factor (MITF) and induction of AXL receptor tyrosine kinase. Interestingly, treatment resistance mechanisms not only included selection processes of pre-existing subclones but also transition between different states of gene expression. Taken together, single-cell technology has provided deeper insights into melanoma biology and has put forward our understanding of the role of tumor heterogeneity and transcriptional plasticity, which may impact on innovative clinical trial designs and experimental approaches.
  • 975
  • 25 Feb 2021
Topic Review
Serology in SARS-CoV-2 Infection
SARS-CoV-2/Coronavirus 2019 (COVID-19) is responsible for the pandemic, which started in December 2019. In addition to the typical respiratory symptoms, this virus also causes other severe complications, including neurological ones. In diagnostics, serological and polymerase chain reaction tests are useful not only in detecting past infections but can also predict the response to vaccination. It is now believed that an immune mechanism rather than direct viral neuroinvasion is responsible for neurological symptoms. For this reason, it is important to assess the presence of antibodies not only in the serum but also in the cerebrospinal fluid (CSF), especially in the case of neuro-COVID. A particular group of patients are people with multiple sclerosis (MS) whose disease-modifying drugs weaken the immune system and lead to an unpredictable serological response to SARS-CoV-2 infection. Based on available data, the article summarizes the current serological information concerning COVID-19 in CSF in patients with severe neurological complications and in those with MS. 
  • 972
  • 06 Feb 2022
Topic Review
Zebrafish Models for Skeletal Muscle Senescence
Aging and sarcopenic changes in skeletal muscles not only reduce locomotor activities in elderly people but also increase the chance of trauma, such as bone fractures, and the incidence of other diseases, such as metabolic syndrome, due to reduced physical activity.
  • 971
  • 22 Dec 2022
Topic Review
Integrated Diagnostics of Thyroid Nodules
Thyroid nodules are commonly detected in daily clinical practice, and their diagnosis and therapy usually involve different specialists and various diagnostic and therapeutic methods. Thyroid nodule management requires the integration of laboratory, imaging, and pathology examinations to achieve a proper diagnosis. It enables the elimination of unnecessary therapeutic procedures in many individuals and the timely identification of patients who require specific therapies. Furthermore, bioinformatics may change the current management of clinical data, enabling more personalized diagnostic approaches for patients with thyroid nodules.
  • 970
  • 16 Jan 2024
Topic Review
Probiotics and Vacccines
It has been recognized that microbiota plays a key role in shaping immune system maturation and activity. Since probiotic administration influences the microbiota composition and acts as a biological response modifier, the efficacy of an adjuvant for boosting vaccine-specific immunity is investigated.
  • 967
  • 10 Aug 2021
Topic Review
Long-term Complications of Standing
The long-term complications of standing are the conditions that may arise after prolonged time in a standing or upright position including standing, walking or running. Many of the complications come from prolonged standing (more the 60% of a work day) that is repeated several times a week. There are many different jobs that require prolonged standing. These included: "retail staff, Baristas, bartenders, assembly line workers, security staff, engineers, catering staff, library assistants, hair stylists and laboratory technicians." Cornell university has calculated that "Standing requires ~20% more energy than sitting".
  • 967
  • 14 Oct 2022
Topic Review
Acute Biphenotypic Leukaemia
Acute biphenotypic leukaemia is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability to differentiate into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage". The direct reasons leading to BAL are still not clear. BAL can be de novo or secondary to previous cytotoxic therapy. Many factors, such viruses, hereditary factors, and radiation, might have a relationship with BAL. BAL is hard to treat. Usually the chemotherapy is chosen according to the morphology of the blast (ALL or AML). A blood-forming stem-cell transplantation is highly recommended. About 5% of acute leukaemia cases are BAL. BAL can occur in all ages of people but occurs more in adults than in children.
  • 967
  • 11 Nov 2022
Topic Review
Hyperuricemia and Gout
Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of individuals with hyperuricemia have never had a gout flare(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout flares. As the molecule of uric acid has its dual effects in vivo with antioxidant properties as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or monosodium urate (MSU) crystals. 
  • 965
  • 22 Mar 2021
Topic Review
Mind-Body Interventions for Psoriasis
Psoriasis is a chronic inflammatory disorder involving but not limited to the skin, with decisive immunological and genetic elements, upon which environmental factors may act. Conventional therapies include topical, systemic, and biologic agents. However, some of these therapies may trigger adverse effects of varying severity, at times may not be effective, or simply involve too high costs. For this reason, many patients resort to complementary and alternative medicine (CAM) to treat this pathology, with acupuncture, cupping, psychotherapy, and climatotherapy to name the most common procedures. In the following paragraphs, the CAM methods used for psoriasis are evaluated with respect to their efficacy, as shown in the English literature.
  • 965
  • 07 May 2021
Topic Review
Heart Arrhythmia
Heart arrhythmia (also known as arrhythmia, dysrhythmia, or irregular heartbeat) is a group of conditions in which the heartbeat is irregular, too fast, or too slow. A heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia and a heart rate that is too slow – below 60 beats per minute – is called bradycardia. Many types of arrhythmia have no symptoms. When symptoms are present these may include palpitations or feeling a pause between heartbeats. In more serious cases there may be lightheadedness, passing out, shortness of breath, or chest pain. While most types of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in cardiac arrest. There are four main types of arrhythmia: extra beats, supraventricular tachycardias, ventricular arrhythmias, and bradyarrhythmias. Extra beats include premature atrial contractions, premature ventricular contractions, and premature junctional contractions. Supraventricular tachycardias include atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Ventricular arrhythmias include ventricular fibrillation and ventricular tachycardia. Arrhythmias are due to problems with the electrical conduction system of the heart. Arrhythmias may occur in children; however, the normal range for the heart rate is different and depends on age. A number of tests can help with diagnosis including an electrocardiogram (ECG) and Holter monitor. Most arrhythmias can be effectively treated. Treatments may include medications, medical procedures such as inserting a pacemaker, and surgery. Medications for a fast heart rate may include beta blockers or agents that attempt to restore a normal heart rhythm such as procainamide. This latter group may have more significant side effects especially if taken for a long period of time. Pacemakers are often used for slow heart rates. Those with an irregular heartbeat are often treated with blood thinners to reduce the risk of complications. Those who have severe symptoms from an arrhythmia may receive urgent treatment with a controlled electric shock in the form of cardioversion or defibrillation. Arrhythmia affects millions of people. In Europe and North America, as of 2014, atrial fibrillation affects about 2% to 3% of the population. Atrial fibrillation and atrial flutter resulted in 112,000 deaths in 2013, up from 29,000 in 1990. Sudden cardiac death is the cause of about half of deaths due to cardiovascular disease or about 15% of all deaths globally. About 80% of sudden cardiac death is the result of ventricular arrhythmias. Arrhythmias may occur at any age but are more common among older people.
  • 965
  • 08 Oct 2022
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