An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial.

Effective, scalable dementia prevention interventions are needed to address modifiable risk factors given global burden of dementia and challenges in developing disease-modifying treatments. A single-blind randomized controlled trial assessed an online multidomain lifestyle intervention to prevent cognitive decline over 3 years. Participants were dementia-free community-dwelling Australians aged 55-77 years with modifiable dementia risk factors.

Ketamine Versus Midazolam as the First-Line Continuous Infusion for Status Epilepticus in Children with Cardiac Disease.

Background: The treatment of status epilepticus (SE) in children with cardiac disease is challenging given their often-tenuous hemodynamic state. We aim to determine whether ketamine is safe and effective in children with cardiac disease as the first-line continuous infusion for the treatment of refractory SE (RSE) and to compare ketamine to midazolam for the treatment of RSE in this population.

Methods: This is a single-center retrospective cohort study of pediatric patients with cardiac disease and RSE admitted to the cardiac intensive care unit at a tertiary children's hospital between January 1, 2017 and June 30, 2023.

Description of STRIVE-ON Study Protocol: Safety and Tolerability of GTX-104 (Nimodipine Injection for IV Infusion) Compared with Oral Nimodipine in Patients Hospitalized for Aneurysmal Subarachnoid Hemorrhage (aSAH): A Prospective, Randomized, Phase III Trial (STRIVE-ON).

Oral nimodipine is the only drug approved in North America for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is variable and frequently poor, leading to fluctuations in peak plasma concentrations that cause dose-limiting hypotension. Furthermore, administration is problematic in patients who cannot swallow.

Low-Cost Strategies for the Development of Neurocritical Care in Resource-Limited Settings.

This review explores low-cost neurocritical care interventions for resource-limited settings, including economical devices, innovative care models, and disease-specific strategies. Devices like inexpensive ventilators, wearable technology, smartphone-based ultrasound, brain4care, transcranial Doppler, and smartphone pupillometry offer effective diagnostic and monitoring capabilities. Initiatives such as intermediate care units, minimally equipped stroke units, and tele-neurocritical care have demonstrated benefits by reducing hospital stays, preventing complications, and improving clinical and economic outcomes.

Structured surgical training in minimally invasive esophagectomy (MIE) increases textbook outcome-a risk-adjusted learning curve.

Background: Minimally Invasive Esophagectomy (MIE) is a complex surgical procedure that has become a cornerstone in the management of esophageal cancer. This study aims to delineate the learning curve associated with MIE and its impact on patient outcomes.

Methods: A retrospective analysis was conducted on 191 patients who underwent MIE between 2015 and 2022.

Coeliac disease: complications and comorbidities.

Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an effective treatment, this diet is burdensome with practical difficulties and frequent inadvertent gluten exposure.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Current insights into molecular mechanisms of environmental stress tolerance in Cyanobacteria.

The photoautotrophic nature of cyanobacteria, coupled with their fast growth and relative ease of genetic manipulation, makes these microorganisms very promising factories for the sustainable production of bio-products from atmospheric carbon dioxide. However, both in nature and in cultivation, cyanobacteria go through different abiotic stresses such as high light (HL) stress, heavy metal stress, nutrient limitation, heat stress, salt stress, oxidative stress, and alcohol stress. In recent years, significant improvement has been made in identifying the stress-responsive genes and the linked pathways in cyanobacteria and developing genome editing tools for their manipulation.

Can response to ADHD medication be predicted?

Predictors for the pharmacological effect of ADHD medication in children and adolescents are lacking. This study examined clinically relevant factors in a large (N = 638) prospective cohort reflecting real-world evidence. Children and adolescents aged 6-17 diagnosed with ADHD were evaluated at baseline and three months following ADHD medication initiation.

Hypersensitivity Reactions to Anticonvulsants.

Background: Antiepileptics are the mainstay of treatment for seizure management. Immediate and delayed hypersensitivity reactions associated with antiepileptics are common. It is important to differentiate between these reactions as management and prognosis varies.

Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.

Age-related dopamine (DA) neuron loss is a primary feature of Parkinson's disease. However, whether similar biological processes occur during healthy aging, but to a lesser degree, remains unclear. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans.

Mutant p53 regulates a distinct gene set by a mode of genome occupancy that is shared with wild type.

To directly examine the interplay between mutant p53 or Mdm2 and wild type p53 in gene occupancy and expression, an integrated RNA-seq and ChIP-seq analysis was performed in vivo using isogenically matched mouse strains. Response to radiation was used as an endpoint to place findings in a biologically relevant context. Unexpectedly, mutant p53 and Mdm2 only inhibit a subset of wild type p53-mediated gene expression.

Urology on a changing planet: links between climate change and urological disease.

Urological diseases and their varied forms of management warrant special attention in the setting of climate change. Regarding urological cancers, climate change will probably increase the incidence and severity of cancer diagnoses through exposures to certain environmental risk factors, while simultaneously disrupting cancer care delivery and downstream outcomes. Regarding benign urological diseases, a burgeoning body of work exists on climate-related heat waves, dehydration, urolithiasis, renal injury and infectious and vector-borne diseases.

Semi-mechanistic efficacy model for PARP + ATR inhibitors-application to rucaparib and talazoparib in combination with gartisertib in breast cancer PDXs.

Background: Promising cancer treatments, such as DDR inhibitors, are often challenged by the heterogeneity of responses in clinical trials. The present work aimed to build a computational framework to address those challenges.

Methods: A semi-mechanistic pharmacokinetic-pharmacodynamic model of tumour growth inhibition was developed to investigate the efficacy of PARP and ATR inhibitors as monotherapies, and in combination.

Unveiling inverted D genes and D-D fusions in human antibody repertoires unlocks novel antibody diversity.

Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, D genes were thought to recombine only in the forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us to question whether these symmetrical sequences might enable bidirectional recombination.

Leveraging synthetic data to improve regional sea level predictions.

The rapid increase in sea levels driven by climate change presents serious risks to coastal communities around the globe. Traditional prediction models frequently concentrate on developed regions with extensive tide gauge networks, leaving a significant gap in data and forecasts for developing countries where the tide gauges are sparse. This study presents a novel deep learning approach that combines TimesGAN with ConvLSTM to enhance regional sea level predictions using the more widely available satellite altimetry data.

Essential and risk elements in horses affect haematology, serum biochemistry and oxidative status parameters.

The abundance of chemical elements in the blood of horses can indicate the physiological balance, health of animal as well as can be taken as an indicator of environmental pollution. The aim of this work was to analyse haematological, biochemical parameters, TOS, FRAP, SOD, Gpx, TAS and their correlations with concentrations of essential and risk elements in blood of horses stabled in two different locations: The National Stud Farm Topoľčianky (n = 11; 11 stallions, consisting of the breeds 6 Lipizzan, 3 Slovak warmblood, 2 Holsteiner) and Experimental Centre at Institute of Animal Husbandry, SUA in Nitra (n = 10; 4 stallions, 5 geldings, 1 mare, 4 stallions, 5 geldings and 1 mare, consisting of the breeds 3 Slovak warmblood, 4 Czech warmblood, 3 Holsteiner). Blood samples were obtained from horses (n = 21) from two localities in the Slovak Republic during May.

A morphometric signature to identify ductal carcinoma in situ with a low risk of progression.

Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early breast cancer, many women with harmless DCIS face overtreatment. To identify features associated with progression, we developed an artificial intelligence-based DCIS morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections.

An optimal workflow scheduling in IoT-fog-cloud system for minimizing time and energy.

Today, with the increasing use of the Internet of Things (IoT) in the world, various workflows that need to be stored and processed on the computing platforms. But this issue, causes an increase in costs for computing resources providers, and as a result, system Energy Consumption (EC) is also reduced. Therefore, this paper examines the workflow scheduling problem of IoT devices in the fog-cloud environment, where reducing the EC of the computing system and reducing the MakeSpan Time (MST) of workflows as main objectives, under the constraints of priority, deadline and reliability.

Association between changes in genital immune markers and vaginal microbiome transitions in bacterial vaginosis.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients.

Evaluation of ampicillin plus ceftobiprole combination therapy in treating Enterococcus faecalis infective endocarditis and bloodstream infection.

Enterococcus faecalis is responsible for numerous serious infections, and treatment options often include ampicillin combined with an aminoglycoside or dual beta-lactam therapy with ampicillin and a third-generation cephalosporin. The mechanism of dual beta-lactam therapy relies on the saturation of penicillin-binding proteins (PBPs). Ceftobiprole exhibits high affinity binding to nearly all E.

OCT-based diagnosis of glaucoma and glaucoma stages using explainable machine learning.

Glaucoma poses a growing health challenge projected to escalate in the coming decades. However, current automated diagnostic approaches on Glaucoma diagnosis solely rely on black-box deep learning models, lacking explainability and trustworthiness. To address the issue, this study uses optical coherence tomography (OCT) images to develop an explainable artificial intelligence (XAI) tool for diagnosing and staging glaucoma, with a focus on its clinical applicability.

Argonaute2 modulates megakaryocyte development and sex-specific control of platelet protein expression and reactivity.

Platelets are enriched in miRNAs and harbor Ago2 as the principal RNA silencing Argonaute. However, roles in thrombopoiesis and platelet function remain poorly understood. We generated megakaryocyte/platelet-specific Ago2-deleted (Ago2 KO) mice and assessed proteomic and functional effects.