Personalised estimates of dosage within a population-based cohort suggest limited evidence that drinking water chemistry modulates health outcomes.

Access to clean drinking water is crucial for human health, but there are concerns that consumption levels of particular solutes may be linked to negative health outcomes. Many studies use data aggregated to area-level to assess consumption-health associations, but these do not account for differences in behaviour between individuals. Therefore, we combined publicly reported tap water chemistry from compliance data with estimated drinking water consumption within the home calculated from a water habits survey for 1970 UK adults from the TwinsUK cohort.

Beta-blockers after myocardial infarction: effects according to sex in the REBOOT trial.

Background And Aims: Recent trials have challenged the guideline recommendation of beta-blockers for post-myocardial infarction (MI) patients without reduced left ventricular ejection fraction (LVEF). Whether these recent findings apply equally to women and men remains unknown.

Methods: Using data from REBOOT (tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion), the largest randomized trial evaluating the effect of beta-blockers after acute MI with LVEF > 40%, a pre-specified sex-specific subgroup analysis was performed.

Comparison of coaxial technique with sequential (non-coaxial) technique for renal mass biopsy: evaluation of diagnostic efficacy, complication rates, seeding risk, and clinical outcomes.

Background: Renal mass biopsy (RMB) enables histology-driven management. Guidelines strongly recommend RMB using a coaxial needle to minimize tumor seeding, albeit with a low level of supporting evidence.

Objectives: To evaluate if RMB in small renal masses (SRMs) with the coaxial technique was associated with lower seeding, less upstaging to pT3a, and less cancer-recurrence, compared to RMB without the coaxial technique (sequential technique).

Optimism and language proficiency predict incidence of and remission from PTSD among climate migrants.

Objective: The purpose of the present study was to examine internal and contextual predictors of two interrelated phenomena among Puerto Rican Hurricane Maria survivors who relocated to the U.S. mainland after the storm: (a) of positive posttraumatic stress disorder (PTSD) screen among hurricane survivors who had not previously screened positive and (b) from positive PTSD among those who had previously screened positive.

Development and validation of a Monte Carlo model of a mobile accelerator for intraoperative radiation therapy.

Background: Intraoperative electron radiation therapy (IOERT) relies on accurate and precise dose delivery to the tumor or tumor bed using mobile accelerators and interchangeable applicators, while critical organs are typically displaced or shielded during surgery. Treatment planning and linac commissioning are often based on water measurements, Monte Carlo (MC) simulations of the accelerator head and applicator system provide detailed insights into dose distributions and beam characteristics, offering additional support for clinical evaluation.

Purpose: This study develops an MC model of the Liac HWL mobile accelerator using a hypothetical linac head geometry, due to the limited availability of detailed information on its internal components resulting from manufacturer disclosure policies.

Synthesis of Gemcitabine-Loaded PLGA Microparticles with Green Solvents.

The use of polymeric microparticles is widely recognized as an effective strategy for enhancing the bioavailability and biodistribution of both lipophilic and hydrophilic medications. In this study, PLGA microparticles loaded with the anticancer drug gemcitabine were synthesized by using a double emulsion process known as water-in-oil-in-water solvent evaporation. Notably, this is the first time that ethyl lactate, an FDA-approved green solvent, has been used for the microparticle synthesis.

Predictors of progression after surgery in non-functioning pituitary macroadenomas: a Spanish multicenter study.

Background And Purpose: Non-functioning pituitary adenomas (NFPAs) have an unpredictable clinical course, with recurrence and progression posing significant challenges. This study aims to evaluate progression-free survival (PFS) and identify predictors and patterns of tumor progression.

Methods: We conducted a retrospective multicenter study including 472 patients with NFPAs > 1 cm from 17 Spanish hospitals (416 surgical, 56 conservative management).

Ipatasertib combined with non-taxane chemotherapy for patients with previously treated advanced triple-negative breast cancer: the PATHFINDER phase IIa trial.

Background: The PI3K/AKT pathway is frequently altered in advanced triple-negative breast cancer (aTNBC), representing a promising target. Ipatasertib, a pan-AKT inhibitor, has shown activity with taxane-based chemotherapy and acceptable safety. This study evaluated the safety and efficacy of ipatasertib with non-taxane chemotherapy for aTNBC.

Induction therapy with bortezomib, melphalan, and prednisone followed by lenalidomide and dexamethasone versus carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in older, fit patients with newly diagnosed multiple myeloma (GEM-2017FIT): a phase 3, open-label, multicentre, randomised clinical trial.

Background: Triplet and quadruplet regimens based on bortezomib, melphalan and prednisone (VMP) and lenalidomide and dexamethasone (Rd) with anti-CD38 antibodies are potential treatments for transplant-ineligible patients with newly diagnosed multiple myeloma. However, the high risk of toxic effects in this population requires frailty-based therapy adaptation. We aimed to compare the response of carfilzomib-based triplet and quadruplet regimens with a VMP-Rd regimen in newly diagnosed transplant-ineligible patients with multiple myeloma, considering patient frailty.

Exposure to respirable desert dust entering indoors prompts quick oxidative-stress and inflammatory responses in the airways of chronic heart failure patients.

A significant portion of the population is exposed to airborne PM levels exceeding WHO guidelines, particularly during desert dust events, which are increasing due to climate change. Cardiovascular mortality has been linked to PM exposure, but most studies rely on outdoor air quality data that may not reflect indoor exposure. This study, DESERT HEART, examines whether indoor PM exposure during dust events influences airway inflammation and oxidative stress in 40 patients with stable chronic heart failure (HF).

PLAG1 fusions define a third subtype of CNS embryonal tumor with PLAG family gene alteration.

CNS embryonal tumors with PLAGL amplification (ET, PLAGL) are a recently described tumor type marked by amplification of one of the PLAG family genes, PLAGL1 or PLAGL2. Separately, a supratentorial, ependymoma-like CNS tumor type with PLAG family alteration, namely PLAGL1 fusion, was also reported (NET_PLAGL1). Here, we use DNA methylation profiling in combination with copy number, RNA-seq, and histological analysis to characterize and classify a novel group of CNS embryonal tumors harboring PLAG1 gene fusions (n=12).

Colistin-loaded biodegradable nanoparticles as a promising antibacterial medication to reduce colistin-induced toxicity.

Infectious diseases cause mortality rates over 17 million people per year. Among them, bacterial infections are one of the major causes. Nosocomial infections, including pneumonia and blood stream infections, are some of the most severe bacterial diseases and many of them display antimicrobial resistance.

Additive effect of wildfires on hospital admission in the Pantanal wetland, Brazil.

Forest fires release toxic pollutants from burning vegetation, posing serious risks to human health. The Brazilian Pantanal-the world's largest continuous wetland-is currently experiencing severe wildfires. This situation may lead to a spike in hospital admissions for respiratory and cardiovascular conditions.

Metabolomics analysis of SNAT2-deficient cells: Implications for the discovery of selective small-molecule inhibitors of an amino acid transporter.

Amino acid uptake by the solute carrier family of transporter proteins is critical to support cell metabolism, and inhibition of transporter activity represents a tractable strategy to restrict nutrient availability to cancer cells. A small-molecule inhibitor of the sodium-coupled neutral amino acid transporter 2 (SNAT2), 3-(N-methyl(4-methylphenyl)sulfonamido)-N-(2-trifluoromethylbenzyl)thiophene-2-carboxamide (MMTC/57E), was recently identified and shown to inhibit cell proliferation when combined with glucose transport inhibitors in breast and pancreatic cancer cell lines. In this study, we use mass spectrometry and a model competitive substrate inhibitor, α-(methylamino)-isobutyric acid (MeAIB), to establish cell-based SNAT2 activity assays and validate target engagement of MMTC/57E.

Strategies to Increase Professional Interpreting in Clinical Settings: A Systematic Review.

Importance: Clinicians frequently communicate without professional interpreters when caring for patients who use languages other than English for medical care, despite evidence that such partnering improves health outcomes.

Objective: To systematically review the evidence for targeted behavior change strategies to increase professional interpreting in medical settings.

Evidence Review: The CINAHL, Embase, PubMed, Ovid MEDLINE, and Web of Science databases were searched on July 28, 2023, and September 2, 2024, for English-language peer-reviewed articles assessing all interventional and observational studies that included outcomes related to professional interpreting in medical settings.

Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics.

Introduction: Dysbiosis is a key mechanism in inflammatory bowel disease (IBD) pathophysiology. Previous microbiota studies in IBD generally have involved patients treated with immunosuppressive agents, which can affect the results. We aimed to elucidate the fecal microbiota composition in newly diagnosed treatment-naïve IBD patients.

Preclinical Evaluation of 99mTc-Labeled LHRH Analog as Cancer Receptor Imaging.

Introduction: Breast cancer is the main cause of cancer-related mortality in women in the developed world. In particular, receptors of luteinizing hormone-releasing hormone (LHRH or GnRH) are overexpressed in this malignant disease. The aim of this study was to develop a new molecular probe [99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/tricine/nicotinic acid (NA) as a novel molecular imaging agent for breast cancer.

Pharmacological Preconditioning with Diazoxide Upregulates HCN4 Channels in the Sinoatrial Node of Adult Rat Cardiomyocytes.

Cardioprotection against ischemia is achieved using openers of mitochondrial ATP-sensitive K (mitoKATP) channels such as diazoxide (DZX), leading to pharmacological preconditioning (PPC). We previously reported that PPC decreases the abundance of ventricular Cav1.2 channels, but PPC's effects on other channels remain largely unexplored.

Impact of 3D Reconstruction and Printing on Surgical Outcomes in Renal Tumour Surgery.

Background And Purpose: With the advances in imaging technology that have enabled the widespread adoption of nephron-sparing surgical techniques, the incidence of renal tumours has concurrently risen. Current guidelines recommend partial nephrectomy for all tumours smaller than 7 cm and, when feasible, even for larger lesions. However, the increasing use of nephron-sparing surgery and advancements in imaging have highlighted the substantial variability in renal hilar anatomy, which poses challenges during surgical procedures.

Unveiling novel pharmacophores and hit compounds for the development of anti-virals to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The respiratory infection COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which continues to spread worldwide causing more than a million deaths yearly. Despite the rapid development of vaccines for prevention, a critical need remains for therapeutic agents to combat the established infection. With this goal in mind, we conducted a target- (SARS-CoV-2 chemotrypsin-like protease, M) and phenotypic-based screening of a subset of compounds from our in-house chemo-library.

Bacterioruberin extract from Haloferax mediterranei induces apoptosis and cell cycle arrest in myeloid leukaemia cell lines.

Carotenoids, a diverse group of naturally occurring pigments, have gained attention for their potential anticancer properties. Among them, bacterioruberin (BR), a rare C50 carotenoid, has shown promising bioactivities. This study evaluates the antiproliferative and cytotoxic effects of a bacterioruberin-rich carotenoid extract (BRCE) derived from Haloferax (H.

Assessment of the effect of pomegranate seed extracts on prostate cancer through cellular and animal models.

Pomegranate seed is a high-protein food by-product with demonstrated in vitro antioxidant activity. In this work, we evaluated the effect of pomegranate seed protein isolates (PIs) and hydrolysates, obtained with high-intensity focused ultrasounds (HIFU) and pressurized liquids (PLE), in several cancer-related processes using prostate cancer cells (PC-3) and immunodeficient mice. Specifically, cell viability, migration, clonogenicity, adhesion, cell cycle, metalloproteinase (MMP) activity, vascular endothelial growth factor (VEGF) expression, and physical tumors parameters were assessed.

The Spectrum of Neurologic Phenotypes Associated With NUS1 Pathogenic Variants: A Comprehensive Case Series.

Objective: A growing body of evidence indicates a strong genetic overlap between developmental and epileptic encephalopathies (DEEs) and movement disorders. De novo loss-of-function variants in NUS1 have been recently identified in DEE cases. Herein, we report a large cohort of cases with pathogenic NUS1 variants and describe their clinical presentation and the details of the associated epilepsy and movement disorders.

[Ventilator-associated pneumonia. Update and intersociety consensus, Argentine Society of Infectology - Argentine Society of Intensive Therapy 2024].

Representatives from the Argentine Society of Infectology (SADI) and the Argentine Society of Intensive Care (SATI) joined forces to develop a consensus on the diagnosis, treatment, and prevention of ventilator-associated pneumonia (VAP). The methodology used consisted of a qualitative analysis of the evidence published since the last update in 2018, complemented by expert opinions and local data. This document updates the incidence and epidemiology of VAP, addresses the limitations of clinical diagnosis, and explores the role of lung ultrasound.