Hypothalamic SIRT1-mediated regulation of the hormonal trigger of ovulation and its repression in energy deficit.

Female reproduction is highly sensitive to body energy stores; persistent energy deficit, as seen in anorexia or strenuous exercise, is known to suppress ovulation via ill-defined mechanisms. We report herein that hypothalamic SIRT1, a key component of the epigenetic machinery that links nutritional status and puberty onset via modulation of Kiss1, plays a critical role in the control of the preovulatory surge of gonadotropins, i.e.

Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators.

In silico trials for drug safety assessment require many high-fidelity 3D cardiac simulations to predict drug-induced QT interval prolongation, which is often computationally prohibitive. To streamline this process, we developed sex-specific emulators for a fast prediction of QT interval, trained on a dataset of 900 simulations. Our results show significant differences between 3D and 0D single-cell models as risk levels increase, underscoring the ability of 3D modeling to capture more complex cardiac responses.

Optimization of Clozapine Treatment: Study of Variables Affecting Response in Uruguayan Patients With Schizophrenia.

Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.

Clinical phenotypes in acute and chronic infarction explained through human ventricular electromechanical modelling and simulations.

Sudden death after myocardial infarction (MI) is associated with electrophysiological heterogeneities and ionic current remodelling. Low ejection fraction (EF) is used in risk stratification, but its mechanistic links with pro-arrhythmic heterogeneities are unknown. We aim to provide mechanistic explanations of clinical phenotypes in acute and chronic MI, from ionic current remodelling to ECG and EF, using human electromechanical modelling and simulation to augment experimental and clinical investigations.

Effects of alcohol-related problems on the costs of frequent emergency department use: an economic analysis of a case-control study in Spain.

Introduction: Alcohol-related problems increase the probability of frequent emergency department (ED) use. In this study, we compared the direct healthcare expenses incurred during a single visit among frequent and non-frequent ED users and analyzed the impact of alcohol-related issues in healthcare costs arising from ED usage.

Methods: The study relied on secondary analyses of economic data from a 1:1 matched case-control study with the primary aim of identifying the clinical characteristics of hospital ED frequent users in a Mediterranean European environment with a public, universal, and tax-funded health system.

Integration of spatial multiplexed protein imaging and transcriptomics in the human kidney tracks the regenerative potential timeline of proximal tubules.

The organizational principles of nephronal segments are based on longstanding anatomical and physiological attributes that are closely linked to the homeostatic functions of the kidney. Novel molecular approaches have recently uncovered layers of deeper signatures and states in tubular cells that arise at various timepoints on the spectrum between health and disease. For example, a dedifferentiated state of proximal tubular cells with mesenchymal stemness markers is frequently seen after injury.

Tree polynomials identify a link between co-transcriptional R-loops and nascent RNA folding.

R-loops are a class of non-canonical nucleic acid structures that typically form during transcription when the nascent RNA hybridizes the DNA template strand, leaving the non-template DNA strand unpaired. These structures are abundant in nature and play important physiological and pathological roles. Recent research shows that DNA sequence and topology affect R-loops, yet it remains unclear how these and other factors contribute to R-loop formation.

Understanding the health system drivers of delayed cancer diagnosis in public healthcare networks of Chile, Colombia and Ecuador: A qualitative study with health professionals, managers and policymakers.

Although the greatest delays in cancer diagnosis in Latin America occur in the provider interval little is known about the related factors. This study aims to analyze factors influencing access to cancer diagnosis -from initial contact with health services to confirmation- from institutional stakeholders' perspective in public healthcare networks of Chile, Colombia, and Ecuador. A qualitative, descriptive-interpretative study was conducted in two networks per country, using semi-structured individual interviews (n = 118; 23 to 58, per country) with a criterion sample of health professionals and administrative personnel from primary care (PC) (n = 41) and secondary/tertiary care hospitals (n = 47), network managers and policymakers (n = 30).

Estradiol impacts Müller glia and endothelial cell responses in hyperglycemic microenvironments with advanced glycation end products.

Diabetic retinopathy is a leading cause of vision loss in working adults, with disproportionate impact on women with lowered estrogen. Sex hormones and their receptors are significant to neuroprotection of the inner blood-retinal barrier (iBRB), a tissue that regulates transport across the neuroretina and vasculature. Moreover, high glucose levels in diabetes lead to the formation of advanced glycation end products (AGEs), which promote inflammation and iBRB breakdown to result in vision loss.

Pharmacists' Answer to the COVID-19 Pandemic: Contribution of the Federal Retail Pharmacy Program to COVID-19 vaccination across Sociodemographic Characteristics-United States.

Background: The Federal Retail Pharmacy Program (FRPP) integrated pharmacies as partners in the national effort to maximize vaccination during the COVID-19 public health emergency.

Objective: The objective of this study was to quantify the contribution of pharmacies participating in FRPP to COVID-19 vaccination efforts during December 2020-September 2023 across sociodemographic groups in the United States.

Methods: Data on COVID-19 vaccine doses administered reported to Centers for Disease Control and Prevention by FRPP and jurisdictional immunization information systems of all 50 states, the District of Columbia, and U.

Rapid diagnosis and severity scale of post-COVID condition using advanced spectroscopy.

The COVID-19 pandemic has resulted in a persistent health challenge known as Post-COVID Condition (PCC), characterized by symptoms lasting at least three months after the initial SARS-CoV-2 infection and potentially persisting for several years. While studies on PCC using lipidomics and proteomics have been conducted, these methods are costly and time-consuming. The comprehensive analysis of UV-VIS-NIR-MIR spectroscopy is explored here as an alternative for the rapid and cheap diagnosis and quantification of the severity of PCC.

Dirty habits: potential for spread of antibiotic-resistance by black-headed gulls from waste-water treatment plants.

Anthropogenic environments such as wastewater treatment plants (WWTPs) and landfills are sources of antimicrobial resistance (AMR). Black-headed gulls (Chroicocephalus ridibundus) frequently use WWTPs and may be vectors for AMR. We used GPS tracking data for 39 gulls for up to 8 months, combined with a shedding curve, to study sources and dispersal distances of AMR in Iberia.

Müller Glia Co-Regulate Barrier Permeability with Endothelial Cells in an Vitro Model of Hyperglycemia.

Diabetic retinopathy is a complex, microvascular disease that impacts millions of working adults each year. High blood glucose levels from Diabetes Mellitus lead to the accumulation of advanced glycation end-products (AGEs), which promote inflammation and the breakdown of the inner blood retinal barrier (iBRB), resulting in vision loss. This study used an in vitro model of hyperglycemia to examine how endothelial cells (ECs) and Müller glia (MG) collectively regulate molecular transport.

Visual Outcomes Following Non-Diffractive Extended-Depth-of-Focus Intraocular Lens Implantation in Patients with Epiretinal Membrane in One Eye and Bilateral Cataracts.

Background/objectives: This study aimed to characterize the visual performance in patients with bilateral cataracts and a unilateral epiretinal membrane (ERM) undergoing cataract surgery with non-diffractive extended depth of focus (EDoF) intraocular lens (IOL) placement in both eyes and phacovitrectomy in the eye with ERM.

Methods: This was a prospective, descriptive, single-arm study. Visual outcomes were measured in monocular and binocular conditions in patients with bilateral cataracts and unilateral ERM stages 2 or 3 implanted with an EDoF IOL.

Performance Assessment of an Electrostatic Filter-Diverter Stent Cerebrovascular Protection Device: Evaluation of a Range of Potential Electrostatic Fields Focusing on Small Particles.

Silent Brain Infarction (SBI) is increasingly recognized in patients with cardiac conditions, particularly Atrial Fibrillation (AF) in elderly patients and those undergoing Transcatheter Aortic Valve Implantation (TAVI). While these infarcts often go unnoticed due to a lack of acute symptoms, they are associated with a threefold increase in stroke risk and are considered a precursor to ischemic stroke. Moreover, accumulating evidence suggests that SBI may contribute to the development of dementia, depression, and cognitive decline, particularly in the elderly population.

Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches.

Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative therapeutic avenue against severe COVID-19, especially crucial for safeguarding high-risk populations. Novel mAb-based immunotherapies may help address the reduced efficacy of current vaccines and neutralizing mAbs caused by the emergence of variants of concern (VOCs). Using phage display technology, we discovered a pan-SARS-CoV-2 mAb (C10) that targets a conserved region within the receptor-binding domain (RBD) of the virus.

A porohyperelastic scheme targeted at High-Performance Computing frameworks for the simulation of the intervertebral disc.

Background And Objective: The finite element method is widely used for studying the intervertebral disc at the organ level due to its ability to model complex geometries. An indispensable requirement for proper modelling of the intervertebral disc is a reliable porohyperelastic framework that captures the elaborate underlying mechanics. The increased complexity of such models requires significant computational power that is available within high-performance computing systems.

Effectiveness of the injectable hyaluronic acid-based microparticles loaded with cannabidiol on rat sciatic nerve injury model.

We have developed an innovative peripheral nerve tissue repair approach by designing biomimetic microparticles loaded with cannabidiol (CBD) using horseradish peroxidase-mediated crosslinking within a microfluidic device. This method utilizes a water-in-oil emulsion system where a mixture of phenol-substituted hyaluronic acid (HAPh), CBD, and laccase is channeled into oil flow, forming hydrogel microparticles. The physical properties, such as their swelling rate, mechanical strength, and the sustained release of CBD, emphasize their potential in tissue engineering and drug delivery applications.

Best practice advice for asthma exacerbation prevention and management in primary care: an international expert consensus.

Primary care clinicians play a key role in asthma and asthma exacerbation management worldwide because most patients with asthma are treated in primary care settings. The high burden of asthma exacerbations persists and important practice gaps remain, despite continual advances in asthma care. Lack of primary care-specific guidance, uncontrolled asthma, incomplete assessment of exacerbation and asthma control history, and reliance on systemic corticosteroids or short-acting beta-agonist-only therapy are challenges clinicians face today with asthma care.

Development, usability, and preliminary efficacy of a virtual reality experience to promote healthy lifestyle behaviors in children: pilot randomized controlled trial.

Background: Virtual reality (VR) shows promise for supporting behavior change in children. This study used user-centered design to translate key tenets of behavioral health interventions into VR for children aged 6-12 years and their caregivers and examined the feasibility, acceptability, and preliminary efficacy of the VR experience in a pilot parallel, two-group randomized controlled trial (RCT).

Methods: The VR experience incorporates psychoeducational content from evidence-based behavioral health interventions using voiceover and an interactive go-kart game related to the concepts of "food as fuel" and nutrition guidelines.

Delivering an innovative multi-infection and female genital mutilation screening to high-risk migrant populations (ISMiHealth): study protocol of a cluster randomised controlled trial with embedded process evaluation.

Introduction: ISMiHealth is a clinical decision support system, integrated as a software tool in the electronic health record system of primary care, that aims to improve the screening performance on infectious diseases and female genital mutilation (FGM) in migrants. The aim of this study is to assess the health impact of the tool and to perform a process evaluation of its feasibility and acceptability when implemented in primary care in Catalonia (Spain).

Methods And Analysis: This study is a cluster randomised control trial where 35 primary care centres in Catalonia, Spain will be allocated into one of the two groups: intervention and control.