Effect of condensed heat acclimation on thermophysiological adaptations, hypoxic cross-tolerance, exercise performance and de-acclimation.

Short duration heat acclimation (HA) (≤5 daily heat exposures) elicits incomplete adaptation compared to longer interventions, possibly due to the lower accumulated thermal 'dose'. It is unknown if matching thermal 'dose' over a shorter timescale elicits comparable adaptation to a longer intervention. Using a parallel-groups design, we compared: i) 'condensed' HA (CHA; =17 males) consisting of 4×75 min∙day heat exposures (target rectal temperature ()=38.

Endothelial Response to Blood-Brain Barrier Disruption in the Human Brain.

Cerebral endothelial cell (EC) injury and blood-brain barrier (BBB) permeability contribute to neuronal injury in acute neurological disease states. Preclinical experiments have used animal models to study this phenomenon, yet the response of human cerebral ECs to BBB disruption remains unclear. In our Phase 1 clinical trial (NCT04528680), we used low-intensity pulsed ultrasound with microbubbles (LIPU/MB) to induce transient BBB disruption of peri-tumoral brain in patients with recurrent glioblastoma.

Calibration verification for stochastic agent-based disease spread models.

Accurate disease spread modeling is crucial for identifying the severity of outbreaks and planning effective mitigation efforts. To be reliable when applied to new outbreaks, model calibration techniques must be robust. However, current methods frequently forgo calibration verification (a stand-alone process evaluating the calibration procedure) and instead use overall model validation (a process comparing calibrated model results to data) to check calibration processes, which may conceal errors in calibration.

A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.

The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase (PfTyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidine ribose sulfamate, ML901, as a potent reaction hijacking inhibitor of PfTyrRS. Here we examined the stage specificity of action of ML901, showing very good activity against the schizont stage, but lower trophozoite stage activity.

MAPK/ERK signaling in gliomas modulates interferon responses, T cell recruitment, microglia phenotype, and immune checkpoint blockade efficacy.

Background: Glioblastoma (GB) remains a formidable challenge in neuro-oncology, with immune checkpoint blockade (ICB) showing limited efficacy in unselected patients. We previously recently established that MAPK/ERK signaling is associated with overall survival following anti-PD-1 and anti-CTLA-4 treatment in recurrent GB. However, the causal relationship between MAPK/ERK signaling and susceptibility to ICB, as well as the mechanisms underlying this association, remain poorly understood.

Baseline Normative and Test-Retest Reliability Data for Sideline Concussion Assessment Measures in Youth.

Tools used for the identification, evaluation, and monitoring of concussion have not been sufficiently studied in youth or real-world settings. Normative and reliability data on sideline concussion assessment measures in the youth athlete population is needed. Pre-season normative data for 515 athletes (93.

An overview of ganaxolone as a treatment for seizures associated with cyclin-dependent kinase-like 5 deficiency disorder.

Introduction: Cyclin-dependent kinase-Like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental condition commonly characterized by drug-resistant, refractory epilepsy, and seizures beginning in infancy. Most patients use multiple drugs, yet seizures remain difficult to control. So far, no conventional anti-seizure medications have been proven to be effective in individuals with CDD, in well-conducted studies.

An Internet Snapshot Survey Assessing the sale of Synthetic Cannabinoid Receptor Agonists for use with Electronic Vaping Devices.

Introduction: Synthetic cannabinoid receptor agonists (SCRAs) are associated with significant toxicity and are increasingly used in electronic vaping devices. We assessed the availability of SCRA vaping products to UK purchasers on the surface web.

Methods: An internet snapshot survey was performed between October 2022 and January 2023 on 'google.

Meeting statement: Call to action for step-change in health behaviours.

Background: Enabling, supporting and promoting positive health-related behaviours is critical in addressing the major public health challenges of our time, and the multifaceted nature of behaviours requires an evidence-based approach. This statement seeks to suggest how a much-needed enhanced use of behavioural and cultural science and insights for health could be advanced.

Study Design And Methods: and methods: Public health authorities of Europe and Central Asia and international partner organizations in September 2023 met in Copenhagen, Denmark, to discuss the way forward.

Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1): 61.

Benzoyl Valine Quasiracemates: Pairing CF Quasienantiomers with H to -Butyl.

Understanding the interplay of structural features responsible for molecular assembly is essential for molecular crystal engineering. When assembling molecules with encoded motifs, supramolecular strategies almost always include robust directional nonbonded contacts. Quasiracemic materials, considered near racemates since cocrystallization occurs with chemically unique components, lack a molecular framework or functional group restrictions, highlighting the importance of molecular shape to molecular assembly.

The Management of Aneurysmal Degeneration of Lower Extremity Cryopreserved Saphenous Vein Bypass Grafts.

Background: The use of cryopreserved saphenous veins (CSVs) for the treatment of lower extremity peripheral arterial disease is an attractive option when there is no available autogenous vein. Prior studies found CSVs are at risk for aneurysmal degeneration requiring reoperation. As the management of these complications and patient outcomes is not well described, the objective of this case series is to describe the open and endovascular management of degenerative CSVs at a tertiary community center.

COVID-19 Personal Protective Behaviors during Large Social Events: The Value of Behavioral Observations.

Within the context of reopening society in the summer of 2021, as the UK moved away from 'lockdowns', the Government of Wales piloted the return of organized 'mass gatherings' of people at a number of test events. The current study reports behavioral observations that were made at two of the test events to inform this process. The researchers were particularly interested in four key factors: how (1) context within a venue, (2) environmental design, (3) staffing and social norms, and (4) time across an event, affected the personal protective behaviors of social distancing and face-covering use.

Comparative genomics of symbiotic using highly contiguous genome assemblies from long read sequences.

This study presents the assembly and comparative genomic analysis of luminous strains isolated from the light organs of 12 fish species using Oxford Nanopore Technologies (ONT) sequencing. The majority of assemblies achieved chromosome-level continuity, consisting of one large (>3 Mbp) and one small (~1.5 Mbp) contig, with near complete BUSCO scores along with varying plasmid sequences.

Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma.

Unlabelled: Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models.

ERK1/2 Phosphorylation Predicts Survival in Recurrent Glioblastoma Following Intracerebral and Adjuvant PD-1/CTLA-4 Immunotherapy: A REMARK-guided Analysis.

Purpose: Evidence suggests that MAPK pathway activation, as measured by ERK1/2 phosphorylation (p-ERK), predicts overall survival (OS) in patients with recurrent glioblastoma receiving anti-PD-1 therapy. We aimed to validate these findings in independent cohorts.

Experimental Design: In a 24-patient clinical trial on recurrent glioblastoma and high-grade gliomas, we examined the link between p-ERK levels and OS.

Strain-level diversity of symbiont communities between individuals and populations of a bioluminescent fish.

The bioluminescent symbiosis involving the urchin cardinalfish, Siphamia tubifer, and Photobacterium mandapamensis, a luminous member of the Vibrionaceae, is highly specific compared to other bioluminescent fish-bacteria associations. Despite this high degree of specificity, patterns of genetic diversity have been observed for the symbionts from hosts sampled over relatively small spatial scales. We characterized and compared sub-species, strain-level symbiont diversity within and between S.

Effect of perioperative anticoagulant prophylaxis in patients with traumatic subdural hematoma and a history of anticoagulant use: a propensity-matched National Trauma Data Bank analysis.

Objective: The use of anticoagulation to prevent venous thromboembolism (VTE) is controversial in the setting of neurosurgical decompression for traumatic subdural hematoma (SDH). In these patients, there is concern that anticoagulation may cause secondary hemorrhage, increasing the risk of death and other complications. Patients with a history of anticoagulant use are at further risk of VTE, but the effect of VTE prophylaxis (VTEP) following neurosurgery for SDH has not been thoroughly investigated in this population.