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Topic Review
Use of Glucagon-Like Peptide-1
Glucagon-like peptide-1 (GLP-1) is a human incretin hormone derived from the proglucagon molecule. GLP-1 receptor agonists are frequently used to treat type 2 diabetes mellitus and obesity. However, the hormone affects the liver, pancreas, brain, fat cells, heart, and gastrointestinal tract. The results showed that GLP-1 agonists can benefit defined off-medication motor scores in Parkinson’s Disease and improve emotional well-being. In Alzheimer’s disease, GLP-1 analogs can improve the brain’s glucose metabolism by improving glucose transport across the blood–brain barrier. In depression, the analogs can improve quality of life and depression scales. GLP-1 analogs can also have a role in treating chemical dependency, inhibiting dopaminergic release in the brain’s reward centers, decreasing withdrawal effects and relapses. These medications can also improve lipotoxicity by reducing visceral adiposity and decreasing liver fat deposition, reducing insulin resistance and the development of non-alcoholic fatty liver diseases. The adverse effects are primarily gastrointestinal. Therefore, GLP-1 analogs can benefit other conditions besides traditional diabetes and obesity uses.
  • 965
  • 10 Jul 2022
Topic Review
Molecular Mechanisms of Resistance to PARP Inhibitors
PARP1 enzyme plays an important role in DNA damage recognition and signalling. PARP inhibitors are approved in breast, ovarian, pancreatic, and prostate cancers harbouring a pathogenic variant in BRCA1 or BRCA2, where PARP1 inhibition results mainly in synthetic lethality in cells with impaired homologous recombination. However, the increasingly wide use of PARP inhibitors in clinical practice has highlighted the problem of resistance to therapy. Several different mechanisms of resistance have been proposed, although only the acquisition of secondary mutations in BRCA1/2 has been clinically proved.
  • 965
  • 07 Jun 2022
Topic Review
Invasive Saprochaete Infections
Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life-threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia.
  • 964
  • 08 Dec 2020
Topic Review
Fluoxetine-Mediated CYP2D6 Inhibition
Fluoxetine is still one of the most widely used antidepressants in the world. The drug is extensively metabolized by several cytochrome P450 (CYP450) enzymes and subjected to a myriad of CYP450-mediated drug interactions. In a multidrug regimen, preemptive mitigation of drug–drug interactions requires knowledge of fluoxetine actions on these CYP450 enzymes. The major metabolic pathway of fluoxetine leading to the formation of its active metabolite, norfluoxetine, is mediated by CYP2D6. Fluoxetine and norfluoxetine are strong affinity substrates of CYP2D6 and can inhibit, potentially through various mechanisms, the metabolism of other sensitive CYP2D6 substrates. Remarkably, fluoxetine-mediated CYP2D6 inhibition subsides long after fluoxetine first passes through the liver and even remains long after the discontinuation of the drug. The long-term inhibition of CYP2D6 is likely a result of competitive inhibition due to 1) the strong affinity binding of fluoxetine and norfluoxetine to the enzyme and 2) unbound fluoxetine and norfluoxetine levels circulating in the blood for a long period of time because of their long elimination half-life.
  • 964
  • 04 Feb 2021
Topic Review
MRNA Splicing Machinery
Dysregulation of messenger RNA (mRNA) processing—in particular mRNA splicing—is a hallmark of cancer. Compared to normal cells, cancer cells frequently present aberrant mRNA splicing, which promotes cancer progression and treatment resistance. This hallmark provides opportunities for developing new targeted cancer treatments. Splicing of precursor mRNA into mature mRNA is executed by a dynamic complex of proteins and small RNAs called the spliceosome. Spliceosomes are part of the supraspliceosome, a macromolecular structure where all co-transcriptional mRNA processing activities in the cell nucleus are coordinated. Here we review the biology of the mRNA splicing machinery in the context of other mRNA processing activities in the supraspliceosome. 
  • 964
  • 23 Jun 2021
Topic Review
Pseudobulbar Affect
Pseudobulbar affect (PBA), or emotional incontinence, is a type of emotional disturbance characterized by uncontrollable episodes of crying, laughing, anger or other emotional displays. PBA occurs secondary to a neurologic disorder or brain injury. Patients may find themselves crying uncontrollably at something that is only moderately sad, being unable to stop themselves for several minutes. Episodes may also be mood-incongruent: a patient may laugh uncontrollably when angry or frustrated, for example. Sometimes, the episodes may switch between emotional states, resulting in the patient crying uncontrollably before dissolving into fits of laughter. The pseudobulbar affect, also referred to as emotional lability, should not be confused with labile mood or labile emotions that stem from emotional instability – affective dysregulation – commonly seen in personality disorders.
  • 964
  • 30 Sep 2022
Topic Review
Diagnosing Primary Ciliary Dyskinesia
Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts collaborated with the American Thoracic Society (ATS) to create a clinical diagnostic guideline for patients across North America, specifically considering the local resources and limitations for PCD diagnosis in the United States and Canada. Nasal nitric oxide (nNO) testing is recommended for first-line testing in patients ≥5 years old with a compatible clinical phenotype; however, all low nNO values require confirmation with genetic testing or ciliary electron micrograph (EM) analysis. Furthermore, these guidelines recognize that not all North American patients have access to nNO testing and isolated genetic testing is appropriate in cases with strong clinical PCD phenotypes. For unresolved diagnostic cases, referral to a PCD Foundation accredited center is recommended.
  • 964
  • 26 Jul 2021
Topic Review
School Design on Users’ Responses
This systematic review focused on the effect of the educational environment design on students’ and teachers’ performance, satisfaction, and wellbeing. Starting from a bulk of 1307 articles, a set of N = 68 empirical papers was selected and organized on the basis of four different content clusters, i.e., architectural building design and aesthetic features, indoor environmental features, classroom design, and school green spaces/outdoor spaces. From the analysis of research findings, the key role of pleasant, warm, and flexible learning environments emerged, for promoting both wellbeing and performance of users. More specifically, the presence of charming colors and pictures, ergonomic furniture, and adequate acoustic, thermal comfort, ventilation, and natural lighting have emerged as important features that school designers should care for. Furthermore, an integration of both indoor and outdoor learning situations showed to be effective for improving students’ learning and wellbeing.
  • 963
  • 29 Oct 2020
Topic Review
SARS-CoV-2 Vaccination-Associated Coagulopathy
Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.
  • 963
  • 21 Mar 2022
Topic Review
Metabolic Equivalent
The Metabolic Equivalent of Task (MET), or simply metabolic equivalent, is a physiological measure expressing the energy cost of physical activities and is defined as the ratio of metabolic rate (and therefore the rate of energy consumption) during a specific physical activity to a reference metabolic rate, set by convention to 3.5 ml O2·kg−1·min−1 or approximately: [math]\displaystyle{ \text{1 MET}\ = 1 \dfrac{\text{kcal}}{\text{kg}*\text{h}}\ = 4.184 \dfrac{\text{kJ}}{\text{kg}*\text{h}} = 1.1622222... \dfrac{\text{W}}{\text{kg}} }[/math] Still another definition of 1 MET is 58.2 W/m2 (18.4 Btu/h·ft2), which is equal to the rate of energy produced per unit surface area of an average person seated at rest. The surface area of an average person is 1.8 m2 (19 ft2). Metabolic rate is usually expressed in terms of unit area of the total body surface (ANSI/ASHRAE Standard 55). Originally, 1 MET was considered as the Resting Metabolic Rate (RMR) obtained during quiet sitting. MET values of activities range from 0.9 (sleeping) to 23 (running at 22.5 km/h or a 4:17 mile pace). Although the RMR of any person may deviate from the reference value, MET can be thought of as an index of the intensity of activities: for example, an activity with a MET value of 2, such as walking at a slow pace (e.g., 3 km/h) would require twice the energy that an average person consumes at rest (e.g., sitting quietly). MET is used as a means of expressing the intensity and energy expenditure of activities in a way comparable among persons of different weight. Actual energy expenditure (e.g., in calories or joules) during an activity depends on the person's body mass; therefore, the energy cost of the same activity will be different for persons of different weight. However, since the RMR is also dependent on body mass in a similar way, it is assumed that the ratio of this energy cost to the RMR of each person will remain more or less stable for the specific activity and thus independent of each person's weight. The 1 MET reference value of 1 kcal·kg−1·h−1, is used by convention and refers to a typical metabolism at rest of an "average" individual. It is not an approximation of Basal Metabolic Rate (BMR), which is the minimum metabolic rate obtained under specified conditions. This is illustrated by sleeping having a MET of 0.9, while an individual's normal sleeping metabolism may be greater than the BMR.
  • 964
  • 14 Oct 2022
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