Military members and female sex workers (FSWs) may be more likely to acquire or transmit HIV. Mapping HIV transmission across these high-risk populations and identifying behaviors associated with sexual network clustering are needed for effective HIV prevention approaches. A cross-sectional study recruited participants newly diagnosed with HIV among militaries, civilians, and FSWs in Zambia, Senegal, and Democratic Republic of the Congo (DRC).
View Article and Find Full Text PDFThe N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.
View Article and Find Full Text PDFPurpose: Postoperative pain is a major concern for patients undergoing ultrasound scalpel-assisted hemorrhoidectomy, potentially exacerbated by delayed wound healing. This study aimed to evaluate the impact of an intimate cleansing gel containing chlorhexidine, hyaluronic acid, and other anti-inflammatory agents (Antroclean Fisioderm) on postoperative pain, itching, and wound healing in patients who had undergone this procedure.
Methods: This multicenter observational case-control study involved a cohort of consecutive adult patients who underwent hemorrhoidectomy using an ultrasound device.
The APOBEC3 family of polynucleotide cytidine deaminases has diverse roles as viral restriction factors and oncogenic mutators. These enzymes convert cytidine to uridine in single-stranded (ss)DNA, inducing genomic mutations that promote drug resistance and tumor heterogeneity. Of the seven human APOBEC3 members, APOBEC3A (A3A) and APOBEC3B (A3B) are most implicated in driving pro-tumorigenic mutations.
View Article and Find Full Text PDFPreclinical methods are needed for screening potential Alzheimer's disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. Long-term potentiation (LTP), which is a correlate of learning and memory, was induced in mature human iPSC-derived cortical neurons cultured on microelectrode arrays utilizing circuit patterns connecting two adjacent electrodes.
View Article and Find Full Text PDFACS Biomater Sci Eng
November 2024
Myelination and the formation of nodes of Ranvier are essential for the rapid conduction of nerve impulses along axons in the peripheral nervous system (PNS). While many animal-based and serum-containing models of peripheral myelination have been developed, these have limited ability when it comes to studying genetic disorders affecting peripheral myelination. We report a fully induced pluripotent stem cell (iPSC)-derived human model of peripheral myelination using Schwann cells (SCs) and motoneurons, cultured in a serum-free medium on patterned and nonpatterned surfaces.
View Article and Find Full Text PDFLegumes are notorious for coevolutionary arms races where chemical defenses are employed to ward off herbivores-particularly insect seed predators. Locoweeds are legumes containing the toxic alkaloid swainsonine which can poison livestock, but its role as a deterrent for insects is unknown. Swainsonine is produced by the fungal endophyte Alternaria section Undifilum, and the chemical composition of the toxin has been well characterized.
View Article and Find Full Text PDFThe aim of these evidence-based guidelines is to present a consensus position from members of the Italian Unitary Society of Colon-Proctology (Società Italiana Unitaria di Colon-Proctologia, SIUCP) on the diagnosis and management of hemorrhoidal disease, with the goal of guiding physicians in the choice of the best treatment option. A panel of experts was charged by the Board of the SIUCP to develop key questions on the main topics related to the management of hemorrhoidal disease and to perform an accurate and comprehensive literature search on each topic, in order to provide evidence-based answers to the questions and to summarize them in statements. All the clinical questions were discussed by the expert panel in multiple rounds through the Delphi approach and, for each statement, a consensus among the experts was reached.
View Article and Find Full Text PDFPenile cancer, while rare, is a critical public health issue due to its profound impact on patients and the complexities of its management. The disease's multifactorial etiology includes risk factors such as HPV infection, poor hygiene, smoking, genetic predispositions, and socioeconomic determinants. This article provides a comprehensive review and analysis of these diverse risk factors, aiming to enhance understanding of the disease's underlying causes.
View Article and Find Full Text PDFAficamten, a small molecule selective inhibitor of cardiac myosin, was characterised in preclinical and studies.Protein binding in human plasma was 10.4% unbound and ranged from 1.
View Article and Find Full Text PDFMultiplexed spatial profiling of mRNAs has recently gained traction as a tool to explore the cellular diversity and the architecture of tissues. We propose a sensitive, open-source, simple and flexible method for the generation of in situ expression maps of hundreds of genes. We use direct ligation of padlock probes on mRNAs, coupled with rolling circle amplification and hybridization-based in situ combinatorial barcoding, to achieve high detection efficiency, high-throughput and large multiplexing.
View Article and Find Full Text PDFBackground: The order Isopoda Latreille, 1816 consists of species occurring in terrestrial, marine and freshwater environments. In the Southern Ocean (SO), this group is amongst the most speciose and occur at all depths. Isopoda biogeography, despite being studied since the first Antarctic expeditions, is still poorly known from a geographical point of view and shows large occurrence gaps for some groups in specific sectors of the SO.
View Article and Find Full Text PDFThe pharmacokinetics, metabolism, excretion, mass balance, and tissue distribution of [C]aficamten were evaluated following oral administration of an 8 mg/kg dose in Sprague Dawley rats and in a quantitative whole-body autoradiography study in Long Evans rats.[C]Aficamten accounted for ∼80% and a hydroxylated metabolite (M1) accounted for ∼12% of total radioactivity in plasma over 48-h (AUC). Plasma was 4-h and the of total plasma radioactivity was 5.
View Article and Find Full Text PDFIntroduction: Drought is one of the biggest problems for crop production and also affects the survival and persistence of soil rhizobia, which limits the establishment of efficient symbiosis and endangers the productivity of legumes, the main source of plant protein worldwide.
Aim: Since the biodiversity can be altered by several factors including abiotic stresses or cultural practices, the objective of this research was to evaluate the effect of water availability, plant genotype and agricultural management on the presence, nodulation capacity and genotypic diversity of rhizobia.
Method: A field experiment was conducted with twelve common bean genotypes under irrigation and rain-fed conditions, both in conventional and organic management.
Embryonic development is a complex and dynamic process that unfolds over time and involves the production and diversification of increasing numbers of cells. The impact of developmental time on the formation of the central nervous system is well documented, with evidence showing that time plays a crucial role in establishing the identity of neuronal subtypes. However, the study of how time translates into genetic instructions driving cell fate is limited by the scarcity of suitable experimental tools.
View Article and Find Full Text PDFPreclinical methods are needed for screening potential Alzheimer's disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. A potential functional parameter to be monitored is long-term potentiation (LTP), which is a correlate of learning and memory, that would be one of the first functions effected by AD onset.
View Article and Find Full Text PDFSmall ruminants affected by brucellosis, caused mainly by Brucella melitensis and B. ovis, suffer reproductive disorders, leading to significant economic losses worldwide. Vaccination is an essential tool to prevent the disease in ovine and caprine livestock, but the only vaccine recommended to date is B.
View Article and Find Full Text PDFSalmonella enterica subsp. enterica serovar Typhimurium variant 4,[5],12:i:- (so called S. 4,[5],12:i:-) has rapidly become one of the most prevalent serovars in humans in Europe, with clinical cases associated with foodborne from pork products.
View Article and Find Full Text PDFOne of the main causes of human brucellosis is Brucella melitensis infecting small ruminants. To date, Rev1 is the only vaccine successfully used to control ovine and caprine brucellosis. However, it is pathogenic for pregnant animals, resulting in abortions and vaginal and milk shedding, as well as being infectious for humans.
View Article and Find Full Text PDFAPOBEC3B cytosine deaminase contributes to the mutational burdens of tumors, resulting in tumor progression and therapy resistance. Small molecule APOBEC3B inhibitors have potential to slow or mitigate these detrimental outcomes. Through molecular dynamics (MD) simulations and computational solvent mapping analysis, we identified a novel putative allosteric pocket on the C-terminal domain of APOBEC3B (A3Bctd), and virtually screened the ChemBridge Diversity Set (N~110,000) against both the active and potential allosteric sites.
View Article and Find Full Text PDFThe emergence of foodborne strains carrying antimicrobial resistance (AMR) in mobile genetic elements (MGE) is a significant public health threat in a One Health context requiring continuous surveillance. Resistance to ciprofloxacin and cephalosporins is of particular concern. Since pigs are a relevant source of foodborne for human beings, we studied transmissible AMR genes and MGE in a collection of 83 strains showing 9 different serovars and 15 patterns of multidrug resistant (MDR) previously isolated from pigs raised in the conventional breeding system of Northern Spain.
View Article and Find Full Text PDFIn vitro culture longevity has long been a concern for disease modeling and drug testing when using contractable cells. The dynamic nature of certain cells, such as skeletal muscle, contributes to cell surface release, which limits the system's ability to conduct long-term studies. This study hypothesized that regulating the extracellular matrix (ECM) dynamics should be able to prolong cell attachment on a culture surface.
View Article and Find Full Text PDFBackground: Distributional data on planktonic, benthic and sympagic copepods collected in the framework of the XXXIV Expeditions of the Italian National Antarctic Programme (PNRA) to the Ross Sea sector from 2018-2019 are here provided. These occurrences correspond to specimens collected from the 25 μm filters used in the desalination plant of the Italian research station "Mario Zucchelli" (MZS), located in the Terra Nova Bay area (TNB; Ross Sea, Antarctica). This dataset is a contribution to the Antarctic Biodiversity Portal, the thematic Antarctic node for both the Ocean Biogeographic Information System (AntOBIS) and the Global Biodiversity Information Facility Antarctic Biodiversity Information Facility (ANTABIF).
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