Desialylation and Apoptosis in Immune Thrombocytopenia: Implications for Pathogenesis and Treatment.

Immune thrombocytopenia (ITP) is an autoimmune disease in which platelet autoantibodies play a significant role in its pathogenesis. Regulatory T cell dysfunction and T cell-mediated cytotoxicity also contribute to thrombocytopenia. Current therapies are directed towards immune suppression and modulation as well as stimulation of platelet production with thrombopoietin receptor agonists.

Antithrombotic efficacy and bleeding risks of vaccine-induced immune thrombotic thrombocytopenia treatments.

Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend nonheparin anticoagulants and IV immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (eg, concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies because of their ability to disrupt VITT IgG-platelet factor 4 (PF4) binding.

LongReadSum: A fast and flexible quality control and signal summarization tool for long-read sequencing data.

While several well-established quality control (QC) tools are available for short reads sequencing data, there is a general paucity of computational tools that provide long read metrics in a fast and comprehensive manner across all major sequencing platforms (such as PacBio, Oxford Nanopore, Illumina Complete Long Read) and data formats (such as ONT POD5, FAST5, basecall summary files and PacBio unaligned BAM). Additionally, none of the current tools provide support for summarizing Oxford Nanopore basecall signal or comprehensive base modification (methylation) information from genomic data. Furthermore, nowadays a single PromethION flowcell on the Oxford Nanopore platform can generate terabytes of signal data, which cannot be handled by existing tools designed for small-scale flowcells.

Can primary health care mitigate the effects of economic crises on child health in Latin America? An integrated multicountry evaluation and forecasting analysis.

Background: Latin American and Caribbean countries are dealing with the combined challenges of pandemic-induced socicoeconomic stress and increasing public debt, potentially leading to reductions in welfare and health-care services, including primary care. We aimed to evaluate the impact of primary health-care coverage on child mortality in Latin America over the past two decades and to forecast the potential effects of primary health-care mitigation during the current economic crisis.

Methods: This multicountry study integrated retrospective impact evaluations in Brazil, Colombia, Ecuador, and Mexico from 2000 to 2019 with forecasting models covering up to 2030.

Down-regulation of wheat Rubisco activase isoforms expression by virus-induced gene silencing.

Rubisco activase (Rca) is an essential photosynthetic enzyme that removes inhibitors from the catalytic sites of the carboxylating enzyme Rubisco. In wheat, Rca is composed of one longer 46 kDa α-isoform and two shorter 42 kDa β-isoforms encoded by the genes and . produces a single transcript from which a short 1β-isoform is expressed, whereas two alternative transcripts are generated from directing expression of either a long 2α-isoform or a short 2β-isoform.

Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze.

GPIbα-filamin A interaction regulates megakaryocyte localization and budding during platelet biogenesis.

Glycoprotein Ibα (GPIbα) is expressed on the surface of platelets and megakaryocytes (MKs) and anchored to the membrane skeleton by filamin A (flnA). Although GPIb and flnA have fundamental roles in platelet biogenesis, the nature of this interaction in megakaryocyte biology remains ill-defined. We generated a mouse model expressing either human wild-type (WT) GPIbα (hGPIbαWT) or a flnA-binding mutant (hGPIbαFW) and lacking endogenous mouse GPIbα.

Immune Thrombosis: Exploring the Significance of Immune Complexes and NETosis.

Neutrophil extracellular traps (NETs) are major contributors to inflammation and autoimmunity, playing a key role in the development of thrombotic disorders. NETs, composed of DNA, histones, and numerous other proteins serve as scaffolds for thrombus formation and promote platelet activation, coagulation, and endothelial dysfunction. Accumulating evidence indicates that NETs mediate thrombosis in autoimmune diseases, viral and bacterial infections, cancer, and cardiovascular disease.

Determination of Antibody Activity by Platelet Aggregation.

Platelets play an important role in hemostasis by forming clots and stopping bleeding. In immune thrombotic conditions, platelets and leukocytes are aberrantly activated by pathogenic antibodies resulting in platelet aggregates and NETosis, leading to thrombosis and thrombocytopenia. A simple assay that assesses platelet function and antibody activity is light transmission aggregometry.

High density SNP array and reanalysis of genome sequencing uncovers CNVs associated with neurodevelopmental disorders in KOLF2.1J iPSCs.

The KOLF2.1J iPSC line was recently proposed as a reference iPSC to promote the standardization of research studies in the stem cell field. Due to overall good performance differentiating to neural cell lineages, high gene editing efficiency, and absence of genetic variants associated to neurological disorders KOLF2.

A survey of algorithms for the detection of genomic structural variants from long-read sequencing data.

As long-read sequencing technologies are becoming increasingly popular, a number of methods have been developed for the discovery and analysis of structural variants (SVs) from long reads. Long reads enable detection of SVs that could not be previously detected from short-read sequencing, but computational methods must adapt to the unique challenges and opportunities presented by long-read sequencing. Here, we summarize over 50 long-read-based methods for SV detection, genotyping and visualization, and discuss how new telomere-to-telomere genome assemblies and pangenome efforts can improve the accuracy and drive the development of SV callers in the future.

Construction and Evaluation of a Realistic Low-Cost Model for Training in Chest-Tube Insertion.

Introduction: Emergency thoracostomy is applied in life-threatening situations. Simulation plays a pivotal role in training in invasive techniques used mainly in stressful situations. Currently available commercial simulation models for thoracostomy have various drawbacks.

Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done.

Removal of redox-sensitive Rubisco Activase does not alter Rubisco regulation in soybean.

Rubisco activase (Rca) facilitates the catalytic repair of Rubisco, the CO-fixing enzyme of photosynthesis, following periods of darkness, low to high light transitions or stress. Removal of the redox-regulated isoform of Rubisco activase, Rca-α, enhances photosynthetic induction in Arabidopsis and has been suggested as a strategy for the improvement of crops, which may experience frequent light transitions in the field; however, this has never been tested in a crop species. Therefore, we used RNAi to reduce the Rca-α content of soybean (Glycine max cv.

NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet serious adverse effect of the adenoviral vector vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen) against COVID-19.

Feasibility of a Multimodal Prehabilitation Programme in Patients Undergoing Cytoreductive Surgery for Advanced Ovarian Cancer: A Pilot Study.

Introduction: Treatment for advanced ovarian cancer (AOC) comprises cytoreductive surgery combined with chemotherapy. Multimodal prehabilitation programmes before surgery have demonstrated efficacy in postoperative outcomes in non-gynaecological surgeries. However, the viability and effects of these programmes on patients with AOC are unknown.

Antiplatelet antibody predicts platelet desialylation and apoptosis in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a bleeding disorder caused by dysregulated B- and T- cell functions, which lead to platelet destruction. A well-recognized mechanism of ITP pathogenesis involves anti-platelet and anti-megakaryocyte antibodies recognizing membrane glycoprotein (GP) complexes, mainly GPIb/IX and GPIIb/IIIa. In addition to the current view of phagocytosis of the opsonised platelets by splenic and hepatic macrophages via their Fc γ receptors, antibodyinduced platelet desialylation and apoptosis have also been reported to contribute to ITP pathogenesis.

Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells.

The World Health Organization reported that approximately 324,000 new cases of melanoma skin cancer were diagnosed worldwide in 2020. The incidence of melanoma has been increasing over the past decades. Targeting apoptotic pathways is a potential therapeutic strategy in the transition to preclinical models and clinical trials.

Second victim phenomenon in a surgical area: Online survey.

Background And Aim Of Study: An effective and accessible first source of support for second victims (SV) is usually the colleagues themselves, who should have tools to help emotionally and detect the unusual course of a SV. The aim of this work is to assess health professionals' perception of the phenomenon, as well as their capability to apply psychological first aid.

Material And Methods: Observational descriptive study through online surveys answered anonymously.