SciCombinator

Discover the most talked about and latest scientific content & concepts.

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Transcatheter aortic valve replacement (TAVR) is well established for treating patients with severe aortic stenosis considered at intermediate to high surgical risk. Blood disorders such as anemia, thrombocytopenia, and acquired type 2A von Willebrand disease are relatively frequent in TAVR candidates, and multiple studies to date have highlighted their potential clinical association with mortality and/or bleeding complications post-TAVR. The present review provides an overview of various blood disorders observed pre- and post-TAVR, with special focus on their incidence, etiology, clinical association, and management.

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Endoscopic transpapillary or transanastomotic pancreatic duct drainage (PD) is the mainstay of drainage in symptomatic pancreatic duct obstruction or leakage. However, transpapillary or transanastomotic PD can be technically difficult due to the tight stricture or surgically altered anatomy (SAA), and endoscopic ultrasound (EUS)-guided PD (EUS-PD) is now increasingly used as an alternative technique. There are two approaches in EUS-PD: EUS-guided rendezvous (EUS-RV) and EUS-guided transmural drainage (EUS-TMD). In cases with normal anatomy, EUS-RV should be the first approach, whereas EUS-TMD can be selected in cases with SAA or duodenal obstruction. In our literature review, technical success and adverse event rates were 78.7% and 21.8%, respectively. The technical success rate of EUS-RV appeared lower than EUS-TMD due to the difficulty in guidewire passage. In future, development of dedicated devices and standardization of EUS-PD procedure are necessary.

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Background/Study context: Posture and gait are complex sensorimotor functions affected by age. These difficulties are particularly apparent when performing cognitively demanding tasks. Characterizing the functional organization of brain networks involved in these associations remains a challenge because of the incompatibility of brain imagery techniques with gross body movements. The present study aimed at testing whether resting-state functional connectivity of sensorimotor networks is associated with posture and gait performance recorded offline, in young and older adults.

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To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy.

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To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.

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To compare re-rupture rate, complication rate, and functional outcome after operative versus nonoperative treatment of Achilles tendon ruptures; to compare re-rupture rate after early and late full weight bearing; to evaluate re-rupture rate after functional rehabilitation with early range of motion; and to compare effect estimates from randomised controlled trials and observational studies.

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The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 Å resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257’s unexpected opposing functional profile of CB2 antagonism versus CB1 agonism. Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system.

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Background: Mosquito-borne flaviviruses, such as dengue and Japanese encephalitis virus (JEV), cause life-threatening diseases, particularly in the tropics. Methods: Here we performed unbiased metagenomic sequencing of RNA extracted from the serum of four patients and the plasma of one patient, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illness, together with the serum from one healthy control, in 2014. Results: We identified and assembled a complete dengue virus type 3 sequence from a case of severe dengue fever. We also identified a small number of JEV sequences in the serum of two adults with febrile illness, including one with severe dengue. Phylogenetic analysis revealed that the dengue sequence belonged to genotype III. It has an estimated divergence time of 13.86 years from the most highly related Indian strains. In total, 11 amino acid substitutions were predicted for this strain in the antigenic envelope protein, when compared to the parent strain used for development of the first commercial dengue vaccine.  Conclusions: We demonstrate that both genome assembly and detection of a low number of viral sequences are possible through the unbiased sequencing of clinical material. These methods may help ascertain causal agents for febrile illnesses with no known cause.

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Simultaneous detection of correlated multi-biomarkers on a single low-cost platform in ultra-low fluid volumes with robustness is in growing demand for the development of wearable diagnostics. A non-faradaic biosensor for the simultaneous detection of alcohol, glucose, and lactate utilizing low volumes (1⁻5 μL) of sweat is demonstrated. Biosensing is implemented using nanotextured ZnO films integrated on a flexible porous membrane to achieve enhanced sensor performance. The ZnO sensing region is functionalized with enzymes specific for the detection of alcohol, glucose, and lactate in the ranges encompassing their physiologically relevant levels. A non-faradaic chronoamperometry technique is used to measure the current changes associated with interactions of the target biomarkers with their specific enzyme. The specificity performance of the biosensing platform was established in the presence of cortisol as the non-specific molecule. Biosensing performance of the platform in a continuous mode performed over a 1.5-h duration showed a stable current response to cumulative lifestyle biomarker concentrations with capability to distinguish reliably between low, mid, and high concentration ranges of alcohol (0.1, 25, 100 mg/dL), glucose (0.1, 10, 50 mg/dL), and lactate (1, 50, 100 mM). The low detection limits and a broader dynamic range for the lifestyle biomarker detection are quantified in this research demonstrating its suitability for translation into a wearable device.

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Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial mucosal layers, which have to be crossed by drug molecules in order to exert a therapeutic effect. Another barrier is the pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes. Although the nasal, buccal and pulmonary routes of administration avoid the first-pass effect, they are still dependent on absorption of drug molecules across the mucosal surfaces to achieve systemic drug delivery. Bioenhancers (drug absorption enhancers of natural origin) have been identified that can increase the quantity of unchanged drug that appears in the systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism. The aim of this paper is to provide an overview of natural bioenhancers and their main mechanisms of action for the nasal, buccal, pulmonary and oral routes of drug administration. Poorly bioavailable drugs such as large, hydrophilic therapeutics are often administered by injections. Bioenhancers may potentially be used to benefit patients by making systemic delivery of these poorly bioavailable drugs possible via alternative routes of administration (i.e., oral, nasal, buccal or pulmonary routes of administration) and may also reduce dosages of small molecular drugs and thereby reduce treatment costs.