Insights into VTE risk in trauma patients: an observational study in an Irish trauma patient population.

Background: The rate of VTE in trauma patients varies significantly in the reported literature. We aimed to determine the incidence of VTE in trauma patients in a trauma-receiving hospital over a 7-year period. We sought to evaluate the timing and nature of VTE events and explore the patterns of co-occurrence between PE and DVT, while factoring in clinical care and death outcome.

Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

The differential impacts of equivalent gating-charge mutations in voltage-gated sodium channels.

Voltage-gated sodium (Nav) channels are pivotal for cellular signaling, and mutations in Nav channels can lead to excitability disorders in cardiac, muscular, and neural tissues. A major cluster of pathological mutations localizes in the voltage-sensing domains (VSDs), resulting in either gain-of-function, loss-of-function effects, or both. However, the mechanism behind this functional diversity of mutations at equivalent positions remains elusive.

Prevalence, predisposing factors, and turnover intention related to low back pain among health workers in Accra, Ghana.

Background: Globally, low back pain (LBP) is responsible for disability among 60.1 million people. Health workers face a higher likelihood of being exposed to LBP compared to employees in the construction and manufacturing sectors.

Novel T Cell reactivities to Hybrid Insulin Peptides in Islet Autoantibody-Positive At-Risk Subjects.

Type 1 Diabetes (T1D) is an autoimmune disease mediated by autoreactive T cells. Our studies indicate that CD4 T cells reactive to Hybrid Insulin Peptides (HIPs) play a critical role in T cell-mediated beta-cell destruction. We have shown that HIPs form in human islets between fragments of the C-peptide and cleavage products of secretory granule proteins.

An update on selective estrogen receptor modulator: repurposing and formulations.

The selective estrogen receptor modulator (SERM) raloxifene hydrochloride (RLH) is used extensively in the management and prevention of breast cancer and osteoporosis. Recent clinical studies show the repurposing of RLH in various diseases based on its structure and some clinical trials studies. Optimizing the clinical effectiveness of this important drug requires a thorough review of the formulation techniques, patent environment, and analytical procedures.

Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Hypoxia-triggered ERRα acetylation enhanced its oncogenic role and promoted progression of renal cell carcinoma by coordinating autophagosome-lysosome fusion.

Estrogen-related receptor α (ERRα) is dysregulated in many types of cancer and exhibits oncogenic activity by promoting tumorigenesis and metastasis of cancer cells. However, its defined role in renal cell carcinoma (RCC) has not been fully elucidated. To reveal the biological function of ERRα and determine the underlying regulatory mechanism in RCC, the quantitative proteomics analysis and mechanism investigation were conducted.

A macro-transection model of brain trauma for neuromaterial testing with functional electrophysiological readouts.

Functional recovery in penetrating neurological injury is hampered by a lack of clinical regenerative therapies. Biomaterial therapies show promise as medical materials for neural repair through immunomodulation, structural support, and delivery of therapeutic biomolecules. However, a lack of facile and pathology-mimetic models for therapeutic testing is a bottleneck in neural tissue engineering research.

First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer.

Colorectal cancer (CRC) constitutes the second leading cause of cancer-related death worldwide and advanced CRCs are resistant to targeted therapies, chemotherapies and immunotherapies. p38α (Mapk14) has been suggested as a therapeutic target in CRC; however, available p38α inhibitors only allow for insufficient target inhibition. Here we describe a unique class of p38α inhibitors with ultralong target residence times (designated ULTR-p38i) that robustly inhibit p38α downstream signaling and induce distinct biological phenotypes.

Psychological distress in adolescence and later economic and health outcomes in the United States population: A retrospective and modeling study.

Background: Federal policy impact analyses in the United States do not incorporate the potential economic benefits of adolescent mental health policies. Understanding the extent to which economic benefits may offset policy costs would support more effective policymaking. This study estimates the relationship between adolescent psychological distress and later health and economic outcomes and uses these estimates to determine the potential economic effects of a hypothetical policy.

Economic burden of musculoskeletal disorders in Tanzania: results from a community-based survey.

Objectives: To identify, measure and value the economic burden of musculoskeletal (MSK) disorders in the Kilimanjaro region, Tanzania.

Design: Community-based cross-sectional survey (undertaken between January and September 2021).

Setting: Hai district, Kilimanjaro, Tanzania.

Anti-proteolytic regulation of KRAS by USP9X/NDRG3 in KRAS-driven cancer development.

Cancers with activating mutations of KRAS show a high prevalence but remain intractable, requiring innovative strategies to overcome the poor targetability of KRAS. Here, we report that KRAS expression is post-translationally up-regulated through deubiquitination when the scaffolding function of NDRG3 (N-Myc downstream-regulated gene 3) promotes specific interaction between KRAS and a deubiquitinating enzyme, USP9X. In KRAS-mutant cancer cells KRAS protein expression, downstream signaling, and cell growth are highly dependent on NDRG3.

Epilepsy therapy beyond neurons: unveiling astrocytes as cellular targets.

Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies.

Lebanese Cannabis sativa L. extract protects from cisplatin-induced nephrotoxicity in mice by inhibiting podocytes apoptosis.

Background: Cisplatin is an anti-cancer drug used to treat a plethora of solid tumors. However, it is associated with dose dependent nephrotoxicity limiting its use as anticancer agent.

Objective: The current study aimed to investigate the nephroprotective effect of native Lebanese Cannabis sativa in both in vitro and in vivo mice model of cisplatin-induced nephrotoxicity.

Assessing the Current Limitations of Large Language Models in Advancing Health Care Education.

The integration of large language models (LLMs), as seen with the generative pretrained transformers series, into health care education and clinical management represents a transformative potential. The practical use of current LLMs in health care sparks great anticipation for new avenues, yet its embracement also elicits considerable concerns that necessitate careful deliberation. This study aims to evaluate the application of state-of-the-art LLMs in health care education, highlighting the following shortcomings as areas requiring significant and urgent improvements: (1) threats to academic integrity, (2) dissemination of misinformation and risks of automation bias, (3) challenges with information completeness and consistency, (4) inequity of access, (5) risks of algorithmic bias, (6) exhibition of moral instability, (7) technological limitations in plugin tools, and (8) lack of regulatory oversight in addressing legal and ethical challenges.

Advanced Targeted Therapy for Colorectal Cancer with Lipid Nanoparticles.

Targeted therapy for colorectal cancer (CRC) appears to have great potential with lipid nanoparticles (LNPs). The advances in LNP-based techniques, such as liposomes, exosomes, micelles, solid lipid nanoparticles (SLNs), nano-cubosomes, and plant- derived LNPs (PDLNPs), are explored in detail in this thorough review. Every platform provides distinct advantages: liposomes enable precise drug release and improved delivery; exosomes function as organic nanocarriers for focused treatment; SLNs offer greater stability; micelles enhance drug solubility and resistance; nano-cubosomes tackle low bioavailability; and PDLNPs offer biocompatible substitutes.

Elevating Therapeutic Penetration: Innovations in Drug Delivery for Enhanced Permeation and Skin Cancer Management.

Skin cancer stands as a challenging global health concern, necessitating innovative approaches to cure deficiencies within traditional therapeutic modalities. While conventional drug delivery methods through injection or oral administration have long prevailed, the emergence of topical drug administration presents a compelling alternative. The skin, aside from offering a swift and painless procedure, serves as a reservoir, maintaining drug efficacy over extended durations.

Comparative effects of biocontrol agent and pathogen on : insights into fungal-plant interactions.

Tobacco () black shank disease, caused by , is a significant threat to tobacco crops, leading to severe economic losses. Prolonged use of agrochemicals to control this disease has prompted the exploration of eco-friendly biological control strategies. This study investigated the effects of , a biocontrol agent, on in comparison to , focusing on growth, biomass, root morphology and anatomy, hormonal changes, and osmotic regulation.

Aloperine Alleviates Atherosclerosis by Inhibiting NLRP3 Inflammasome Activation in Macrophages and ApoE Mice.

Background And Aims: Atherosclerosis is a chronic cardiovascular disease which is regarded as one of the most common causes of death in the elderly. Recent evidence has shown that atherosclerotic patients can benefit by targeting interleukin-1 beta (IL-1β). Aloperine (ALO) is an alkaloid which is mainly isolated from L.

One size does not fit all: revising traditional paradigms for assessing accuracy of QSAR models used for virtual screening.

Traditional best practices for quantitative structure activity relationship (QSAR) modeling recommend dataset balancing and balanced accuracy (BA) as the key desired objective of model development. This study explores the value of the conventional norms in the context of using QSAR models for virtual screening of modern large and ultra-large chemical libraries. For this increasingly common task, we now recommend the use of models with the highest positive predictive value (PPV) built on imbalanced training sets as preferred virtual screening tools.

Nootkatone inhibits the progression of glioblastoma by activating the ATF4-CHOP-CHAC1 pathway.

Glioblastoma multiforme (GBM) represents a primary brain tumor that is widely prevalent, and clinical drugs available for its treatment exhibit varying degrees of resistance. Nootkatone (NKT) is a functional sesquiterpene sourced from traditional Chinese medicine --Alpinia Oxyphylla Miq and has been reported to have a diverse range of pharmacological properties. However, it remains unknown whether there are effects of NKT on GBM.

Utility of ursodiol prophylaxis against sinusoidal obstruction syndrome (SOS)/ veno-occlusive disease (VOD) in acute leukemia patients receiving gemtuzumab-ozogamicin (GO) or inotuzumab-ozogamicin (InO).

Purpose: Sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) is a serious complication in hematopoietic stem-cell transplant (HSCT) patients. Gemtuzumab-ozogamicin (GO) and InO are known to cause SOS/VOD in leukemic and transplant populations. Due to limited data on ursodiol prophylaxis in non-HSCT patients, we aimed to assess hepatotoxicity, SOS/VOD incidences, time to hepatotoxicity, and confirmed SOS/VOD in adults receiving GO or InO ± ursodiol.

Fungus Promotes CD8 T Cell-Mediated Anti-Tumor Immunity by Affecting Tumor-Associated Macrophages-Derived CCRL2.

Introduction: fungus (HSF)is an artificial substitute for and has shown promising therapeutic effects in various diseases including cancer. Previous studies have demonstrated that HSF can affect macrophage polarization and activate systemic immune response. In our preliminary experiments, we validated that HSF inhibited the proliferation of lung cancer (LC) cells, but the underlying mechanism is elusive.

The impact of borneolum on Citalopram hydrobromide pharmacokinetics and serotonin levels in the hypothalamus of conscious rats.

Borneolum (BO) is an effectiveness adjuvant in facilitating the transportation of central nervous system drugs to the brain by opening the blood-brain barrier (BBB). Citalopram hydrobromide (CIT-HBr), a widely prescribed serotonin (5-HT) reuptake inhibitor, restricts the efficacy due to the BBB, resulting in slow onset and systemic side effects. Enhancing CIT-HBr's efficacy through BO appears to be a promising approach.