Cardio-Obstetrics Practice in Latin America: A Regional Survey of General Cardiologists.

Background: Cardiovascular (CV) disease is a leading cause of death in pregnant women globally, especially in low- and middle-income countries including Latin America (LATAM), where there is lack of data on how cardiologists are trained in cardio-obstetrics (CO) and the practice patterns in the care of pregnant patients.

Objectives: The authors aimed to identify CO competency and practice patterns among LATAM general cardiologists.

Methods: An anonymous cross-sectional Google-based electronic survey was sent via email to clinical cardiologists through local American College of Cardiology chapters and CV societies.

Optimal chemokine receptors for enhancing immune cell trafficking in adoptive cell therapy.

Recently, a strategy involving the engineering of chemokine receptors on immune cells was developed to optimize adoptive cell therapy (ACT) for solid tumors. Given the variability in chemokine secretion among different tumor types, identifying and modulating the appropriate chemokine receptors is crucial. In this study, we utilized extensive RNA sequencing data from both tumor tissues from The Cancer Genome Atlas and normal tissues from Genotype-Tissue Expression to investigate the expression profiles of chemokines.

Super-photostable organic dye for long-term live-cell single-protein imaging.

Organic dyes play a crucial role in live-cell imaging because of their advantageous properties, such as photostability and high brightness. Here we introduce a super-photostable and bright organic dye, Phoenix Fluor 555 (PF555), which exhibits an order-of-magnitude longer photobleaching lifetime than conventional organic dyes without the requirement of any anti-photobleaching additives. PF555 is an asymmetric cyanine structure in which, on one side, the indole in the conventional Cyanine-3 is substituted with 3-oxo-quinoline.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Challenges and insights of transferring animal maze studies principles to human spatial learning research.

Maze tasks, originally developed in animal research, have become a popular method for studying human cognition, particularly with the advent of virtual reality. However, these experiments frequently rely on simplified environments and tasks, which may not accurately reflect the complexity of real-world situations. Our pilot study aims to transfer a multi-alternative maze with a complex task structure, previously demonstrated to be useful in studying animal cognition, to studying human spatial cognition.

Intracellular protein-lipid interactions drive presynaptic assembly prior to neurexin recruitment.

Neurexin cell-adhesion molecules regulate synapse development and function by recruiting synaptic components. Here, we uncover a mechanism for presynaptic assembly that precedes neurexin recruitment, mediated by interactions between cytosolic proteins and membrane phospholipids. Developmental imaging in C.

Quantitative Lipidomics of Biological Samples Using Supercritical Fluid Chromatography Mass Spectrometry.

Lipidomics has attracted attention in the discovery of unknown biomolecules and for capturing the changes in metabolism caused by genetic and environmental factors in an unbiased manner. However, obtaining reliable lipidomics data, including structural diversity and quantification data, is still challenging. Supercritical fluid chromatography (SFC) is a suitable technique for separating lipid molecules with high throughput and separation efficiency.

Glia: The Cellular Glue that binds Circadian Rhythms and Sleep.

Glia are increasingly appreciated as serving an important function in the control of sleep and circadian rhythms. Glial cells in Drosophila and mammals regulate daily rhythms of locomotor activity and sleep as well as homeostatic rebound following sleep deprivation. In addition, they contribute to proposed functions of sleep, with different functions mapping to varied glial subtypes.

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Gynecological complications and treatment strategies in patients after hematopoietic stem cell transplantation.

In women after hematopoietic stem cell transplantation (HSCT), complications associated with the original disease and therapies used both before and after transplantation often occur, which significantly affects their quality of life. The most common gynaecological complications include secondary cancers, premature ovarian insufficiency (POI), infertility and chronic graft-versus-host disease (cGVHD). Cervical cancer is the most common secondary genital cancer in patients after HSCT.

Prevalence of pathogenic variants of inborn errors of immunity in critically ill children admitted to the pediatric intensive care unit for sepsis: A Moroccan cohort study.

Introduction: Pediatric sepsis remains a leading cause of morbidity and mortality in Africa. Nearly half of pediatric sepsis deaths occur in previously healthy children. The role of inborn errors of immunity (IEI) in susceptibility to sepsis is yet to be identified and their prevalence amongst previously healthy children admitted to the pediatric intensive care unit (PICU) is unclear.

Bacterial Isolates and Their Antimicrobial Susceptibility Patterns Among Pediatric Patients with Urinary Tract Infections: A Retrospective Cross-Sectional Study at Tertiary Level in Afghanistan.

Introduction: The widespread use of antibiotics is a serious and alarming situation in terms of the development of antimicrobial resistance. The current study was conducted to demonstrate the types of organism isolated from the urine of patients presenting with UTI symptoms as well as their antimicrobial sensitivity spectrum.

Methodology: A descriptive cross-sectional study was conducted, and 272 positive urine cultures from children under 5 years of age with signs and symptoms of a UTI were included in the study.

Ligand Design with Accelerated Disulfide Formation with Serum Albumin to Extend Blood Retention.

We proposed a novel ligand for the interaction with human serum albumin (HSA) to extend the blood half-life of small molecular weight therapeutics. The ligand features an alkyl chain and an activated disulfide to allow binding to the hydrophobic pockets of HSA and the formation of disulfide to Cys34 of HSA, thereby minimizing the initial renal clearance. The dual nature of the ligand-HSA bonding was expected to give the ligand long blood retention.

Ophthalmological manifestations in inflammatory bowel disease under the watchful eye of a gastroenterologist from a tertiary centre.

Introduction: Ophthalmological manifestations (O-EIM) are one of the extraintestinal manifestations (EIM) of inflammatory bowel disease (IBD), although their frequency and potential relationship with disease activity and treatment remain underestimated.

Aim: The aim of this screening questionnaire was to assess the number of EIM, including O-EIM, among patients with IBD.

Material And Methods: 436 patients with IBD and 102 patients without IBD were included in this single-centre retrospective study.

Dense-core vesicles contain exosomes in secretory cells.

Dense-core vesicles (DCVs) are found in various types of cells, such as neurons, pancreatic β-cells, and chromaffin cells. These vesicles release transmitters, peptides, and hormones to regulate diverse functions, such as the stress response, immune response, behavior, and blood glucose levels. In traditional electron microscopy after chemical fixation, it is often reported that the dense cores occupy a portion of the vesicle towards the center and are surrounded by a clear halo.

In vivo base editing extends lifespan of a humanized mouse model of prion disease.

Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.

Stable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain.

Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

A nationwide provider survey of neuro-oncology tumor boards in a lower-middle-income country: Comparing centers with and without tumor boards.

Objectives: To provide information about implementation, resources, practice patterns and prevalent perceptions regarding neuro-oncology tumor boards (NOTBs) in a lower middle income country.

Methods: A nationwide survey was designed to include licensed neurosurgeons involving data on practice, structure, and perceptions of NOTBs with non-probability sampling, a pre-validated proforma, data analysis using SPSS v27, and geospatial mapping using Quantum GIS.

Results: 139 neurosurgeons were surveyed from 63 neurosurgical centers of a lower middle income country.

In Silico design and molecular dynamics analysis of imidazole derivatives as selective cyclooxygenase-2 inhibitors.

Cyclooxygenase-2 (COX-2), a key enzyme in the inflammatory pathway, is the target for various nonsteroidal anti-inflammatory drugs (NSAIDs) and selective inhibitors known as coxibs. This study focuses on the development of novel imidazole derivatives as COX-2 inhibitors, utilizing a Structure-Activity Relationship (SAR) approach to enhance binding affinity and selectivity. Molecular docking was performed using Autodock Vina, revealing binding energies of -6.

Anti-inflammatory effects of moxifloxacin and levofloxacin on cadmium-activated human astrocytes: Inhibition of proinflammatory cytokine release, TLR4/STAT3, and ERK/NF-κB signaling pathway.

Cadmium is a non-essential element and neurotoxin that causes neuroinflammation, which leads to neurodegenerative diseases and brain cancer. To date, there are no specific or effective therapeutic agents to control inflammation and alleviate cadmium-induced progressive destruction of brain cells. Fluoroquinolones (FQs), widely used antimicrobials with effective blood-brain barrier penetration, show promise in being repurposed as anti-inflammatory drugs.