Investigation into Drug-Induced Liver Damage Using Multimodal Mass Spectrometry Imaging.

Drug toxicity during the development of candidate pharmaceuticals is the leading cause of discontinuation in preclinical drug discovery and development. Traditionally, the cause of the toxicity is often determined by histological examination, clinical pathology, and the detection of drugs and/or metabolites by liquid chromatography-mass spectrometry (LC-MS). While these techniques individually provide information on the pathological effects of the drug and the detection of metabolites, they cannot provide specific molecular spatial information without additional experiments.

A singular theory of sensorimotor coordination: On targeted motions in space.

Gravity has long been purported to serve a unique role in sensorimotor coordination, but the specific mechanisms underlying gravity-based visuomotor realignment remain elusive. In this study, astronauts (9 males, 2 females) performed targeted hand movements with eyes open or closed, both on the ground and in weightlessness. Measurements revealed systematic drift in hand-path orientation seen only when eyes were closed and only in very specific conditions with respect to gravity.

The effect of a general practitioner's perception of a patient request for antibiotics on antibiotic prescribing for respiratory tract infections: secondary analysis of a point prevalence audit survey in 18 European countries.

Background: Illness severity, comorbidity, fever, age and symptom duration influence antibiotic prescribing for respiratory tract infections (RTI). Non-medical determinants, such as patient expectations, also impact prescribing.

Aim: To quantify the effect of general practitioners' (GPs') perception of a patient request for antibiotics on antibiotic prescribing for RTI and investigate effect modification by medical determinants and country.

Cerebral blood volume index in the era of thrombectomy-treated large and medium vessel ischemic strokes.

The cerebral blood volume index (CBV index) is a perfusion-based marker of collateral status. Several real-world data analyses from observational stroke cohorts have established relationships between this parameter and a range of favorable and unfavorable stroke outcomes. In this review, an overview is provided of the CBV index, within the context of thrombectomy-treated large vessel and medium vessel occlusion ischemic strokes.

Deciphering neutrophil heterogeneity in human blood and tumors: Methods for isolating neutrophils and assessing their effect on T-cell proliferation.

Neutrophils were historically considered a homogenous population of cells with functions limited to innate immunity against external threats. However, with the rise of immunotherapy, recent works have shown that neutrophils are also important actors in immuno-oncology. In this context, neutrophils appear as a more heterogenous population of cells.

Evaluating case definitions of respiratory disease in dairy calves: a scoping review.

Bovine respiratory disease (BRD) is one of the most common diseases observed in dairy calves in both the pre- and post-weaning periods. Despite its common occurrence, there has been no formal synthesis (e.g.

Appetite and childhood malnutrition: A narrative review identifying evidence gaps between clinical practice and research.

Severe Acute Malnutrition (SAM) is a critical global health issue, contributing to approximately one-half of all child mortality worldwide. SAM management guidelines recommend the use of appetite assessment determined by an "appetite test" to distinguish between complicated and uncomplicated SAM, subsequently guiding clinical decisions regarding outpatient versus inpatient care and discharge from hospital. Despite the widespread utilization of this recommendation, its validity lacks substantial evidence within the existing literature.

Repeat Procedures After Pulsed Field Ablation for Atrial Fibrillation: MANIFEST-REDO Study.

Background: Initial clinical studies of pulsed field ablation (PFA) to treat atrial fibrillation (AF) indicated a >90% durability rate of pulmonary vein isolation (PVI). However, these studies were largely conducted in single centers and involved a limited number of operators. The electrophysiological findings and outcomes in patients undergoing repeat ablation after an initial PF ablation for AF are incompletely understood.

Marine microbes suppressed Vibrio and enhanced biological performance of euryhaline rotifer, Brachionus plicatilis.

The excessive use of antibiotics in mariculture has surpassed permitted levels, leading to their release into surrounding waters and accumulation in cultured organisms, which poses risks to human health and highlighting the urgent need for alternatives to reduce antibiotic use. Therefore, the present study aimed to test four microbes including Debaryomyces hansenii, Ruegeria mobilis, Lactobacillus plantarum and Bacillus subtilis, on lowering Vibrio, promoting population increase and survival of Brachionus plicatilis. The digestive enzymes activity including α-amylase, lipase and protease, microbial retention and biochemical composition of rotifers were analyzed.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.

Allowed response time and estimated average body size influence visual body size estimates.

Studies show that body size estimates exhibit a contraction bias wherein participants with a lower-than-average BMI overestimate their bodies while participants with a higher-than-average BMI underestimate. We attempted to replicate this effect and test its relationship to allowed response time and estimates of average body size. Neurotypical female Dutch participants (n = 277) estimated their body size using a forced-choice task, which we modified to modulate allowed response time, and a method-of-adjustment task.

Changes in population fitness and gene co-expression networks reveal the boosted impact of toxic cyanobacteria on Daphnia magna through microplastic exposure.

The concomitant prevalence of toxic cyanobacteria blooms and plastic pollution in aquatic ecosystems is emerging as a pressing global water pollution dilemma. While toxic cyanobacteria and microplastics (MPs) can each independently exert significant impacts on aquatic biota, the magnitude and trajectory of the combined interactions remains rudimentary. In this study, we evaluated how MPs influences cyanobacterial stress on keystone grazer Daphnia, focusing on population, individual, biochemical and toxicogenomic signatures.

Synthesis and functional screening of novel inhibitors targeting the HDAC6 zinc finger ubiquitin-binding domain.

Histone deacetylase 6 (HDAC6) is a promising target for treating neurodegenerative disorders, several cancer types and viral infections. Unique among HDACs, the HDAC6 isoform possesses a zinc finger ubiquitin-binding domain (UBD) crucial for managing misfolded protein aggregates and facilitating viral infection. HDAC6 binds aggregated polyubiquitinated proteins through its UBD, mediating their transport to the aggresome and subsequent removal via autophagy.

The knowledge, experience, and awareness of professionals working with older adults on the auditory-cognitive interactions.

Introduction: Hearing loss is a commonly occurring condition with dementia. Research already presented a theoretical framework for the auditory-cognitive interactions, though it is still unclear if and how professionals beyond audiologists act upon this interactions in clinical practice.

Methods: An online 64-item questionnaire was developed and evaluated respondents' work setting as well as their knowledge, experience, and awareness regarding hearing loss, cognitive decline, and the auditory-cognitive link.

Phosphodiesterase 4D inhibition improves the functional and molecular outcome in a mouse and human model of Charcot Marie Tooth disease 1 A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited peripheral neuropathy caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. It is primarily marked by Schwann cell dedifferentiation and demyelination, leading to motor and sensory deficits. Cyclic adenosine monophosphate (cAMP) is crucial for Schwann cell differentiation and maturation.

Unveiling the Werner-Type Cluster Chemistry of Heterometallic 4f/Post-Transition Metals: A {DyBi} Complex Exhibiting Quantum Tunneling Steps in the Hysteresis Loops and its 1-D Congener.

A new [DyBiOCl(saph)] () Werner-type cluster has been prepared, which is the first Dy/Bi polynuclear compound with no metal-metal bond and one of the very few Ln-Bi (Ln = lanthanide) heterometallic complexes reported to date. The molecular compound has been deliberately transformed to its 1-D analogue [DyBiO(N)(saph)] () via the replacement of the terminal Cl ions by end-to-end bridging N groups. The overall metallic skeleton of (and ) can be described as consisting of a diamagnetic {Bi} unit with an elongated trigonal bipyramidal topology, surrounded by a magnetic {Dy} equilateral triangle, which does not contain μ-oxo/hydroxo/alkoxo groups.

Study protocol for a multi-center stepped-wedge cluster randomized trial to explore the usability and outcomes among young people living with HIV in Kiambu and Kirinyaga counties of Kenya, using an online health portal.

While the incidence of Human Immunodeficiency Virus (HIV) infection is decreasing in most age groups worldwide, it is rising among adolescents and young adults, who also face a higher rate of HIV-related deaths. This tech-savvy demographic may benefit from an online patient portal designed to enhance patient activation-empowering them to manage their health independently. However, the effectiveness of such digital health interventions on young HIV patients in Kenya remains uncertain.

Improving Atrial Fibrillation or Flutter Detection and Management by Smartphone-Based Photoplethysmography Rhythm Monitoring Following Cardiac Surgery: A Pragmatic Randomized Trial.

Background And Aims: Atrial fibrillation (AF) or atrial flutter (AFL) after cardiac surgery are common and associated with adverse outcomes. The increased risk related to AF or AFL may extend beyond discharge. This study aims to determine whether photoplethysmography (PPG)-based smartphone monitoring to detect AF or AFL after hospital discharge following cardiac surgery improves AF management.

Low functional change despite high taxonomic turnover characterizes the microbiome across a 2000-km salinity gradient.

The green seaweed relies on associated bacteria for morphogenesis and is an important model to study algal-bacterial interactions. -associated bacteria exhibit high turnover across environmental gradients, leading to the hypothesis that bacteria contribute to the acclimation potential of the host. However, the functional variation of these bacteria in relation to environmental changes remains unclear.

Walking or hanging: the role of habitat use for body shape evolution in lacertid lizards.

Differences in habitat use impose ecological constraints which in turn lead to functional and morphological differences through adaptation. In fact, a convergent evolutionary pattern is evident when species exhibit similar responses to similar environments. In this study we examine how habitat use influences the evolution of body shape in lizards from the family Lacertidae.

Incidence and predictors of weaning failure from veno-arterial extracorporeal membrane oxygenation therapy in patients with cardiogenic shock.

Aims: This study aimed to investigate incidence and predictors of weaning failure and in-hospital death after successful weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiogenic shock (CS).

Methods And Results: Overall, 685 patients with CS treated with VA-ECMO from 23 tertiary care centres in 7 countries were analysed (median age 57 [interquartile range 49-66] years, 542 [79.1%] male, median lactate 7.

Antiparasitic Activities of Plants from the Traditional Senegalese Pharmacopoeia: Isolation of Antitrypanosomal and Antileishmanial ellagic acid derivatives from Terminalia avicennioides.

Parasitic diseases such as trypanosomiasis and leishmaniasis pose significant health challenges in Africa. The Senegalese Pharmacopoeia, known for its many medicinal plants with anti-infectious properties, can be a source of antiparasitic natural products. This study aimed to evaluate the in vitro antiparasitic activities of 33 methanolic extracts from 24 ethnopharmacologically selected plants against Trypanosoma brucei brucei and Leishmania mexicana mexicana, as well as their cytotoxic activities on WI-38 cells.

Decoding ruminative reflection in healthy individuals: The role of triple network connectivity.

Ruminative reflection has been linked to enhanced executive control in processing internally represented emotional information, suggesting it may serve as an adaptive strategy for emotion regulation. Investigating the neural substrates of reflection can deepen our understanding of its adaptive properties. This study used network-based statistic (NBS)-Predict methodology to identify resting state functional connectivity (FC)-based predictors of ruminative reflection in a healthy sample.