Comparative study of phenotypic and genotypic expression of virulence factors in colonizing and pathogenic carbapenem resistant Acinetobacter baumannii (CRAB).

Carbapenem resistant Acinetobacter baumannii has evolved as the most troublesome microorganism with multiple virulence factors. Biofilm formation, porins, micronutrient capturing mechanism and quorum sensing, provide protection against desiccation, host-pathogen killing and enhance its persistence. The conservation of these factors between colonizing and pathogenic carbapenem resistant A.

Application of machine learning in depression risk prediction for connective tissue diseases.

This study retrospectively collected clinical data from 480 patients with connective tissue diseases (CTDs) at Nanjing First Hospital between August 2019 and December 2023 to develop and validate a multi-classification machine learning (ML) model for assessing depression risk. Addressing the limitations of traditional assessment tools, six ML models were constructed using univariate analysis and the LASSO algorithm, with the categorical boosting (Catboost) model emerging as the best performer, demonstrating strong predictive ability across different depression severity levels (none_F1 = 0.879, mild_F1 = 0.

A pilot study on the effects of olfactory stimulation with white musk aromatic oil on psychophysiological activity: a crossover study.

Studies on the compounds of aromatic oils and their effects on psychophysiological changes in humans are often conducted separately. To obtain better validation, a suitable protocol is needed that can be extrapolated to large-scale olfactory stimulation experiments. Unfortunately, this type of study is still rarely performed.

Students' perspective on the Dutch National Pharmacotherapy Assessment, a national survey study among final-year medical students.

Introduction: The Dutch National Pharmacotherapy Assessment (DNPA) was introduced in 2013 to improve clinical pharmacology and therapeutics (CPT) education. This study investigated final-year medical students' perceived motivation and level of preparation for the DNPA in different scenarios: mandatory vs. non-mandatory, and traditional high-stakes assessment programme vs.

The impact of summative, formative or programmatic assessment on the Dutch National Pharmacotherapy Assessment: a retrospective multicentre study.

Background: The Dutch National Pharmacotherapy Assessment (DNPA), which focuses on assessing medication safety and essential drug knowledge, was introduced to improve clinical pharmacology and therapeutics education in the Netherlands. This study investigated how the performance of final-year medical students on the DPNA was affected by the assessment programme (traditional with summative or formative assessment, and programmatic assessment).

Methods: This multicentre retrospective longitudinal observation study (2019-2023) involved final-year medical students from four medical schools in the Netherlands.

Simultaneous activation of different subtypes of dopamine receptors may lead to activation of homeostatic sleep regulatory mechanisms.

Dopaminergic system gains importance in homeostatic sleep regulation, but the role of different dopamine receptors is not well-defined. 72 h rat electrocorticogram and sleep recordings were made after single application of dopaminergic drugs in clinical use or at least underwent clinical trials. The non-selective agonist apomorphine evoked short pharmacological sleep deprivation with intense wakefulness followed by pronounced sleep rebound.

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Specific activity of mouse liver desaturases and elongases: Time course effects using n-3 and n-6 PUFA substrates and inhibitory responses of delta-6 desaturase.

The synthesis of n-3 and n-6 polyunsaturated acids (PUFAs) is associated with physiological functions in mammals, being catalyzed by Δ-5D and Δ-6D desaturases and elongases Elovl-2 and Elovl-5. In this context, we aimed to study the chief kinetic features of PUFA liver anabolism, looking upon (i) the time-dependency for the specific activity of Δ-6D, Δ-5D, Elovl2, Elovl2/5 and Elovl5, using n-3 and n-6 precursors between 0 and 240 min ex vivo in mouse liver.; and (ii) the specific activity-substrate (α-linolenic acid; ALA) concentration responses of Δ-6D in the absence and presence of linoleic acid (LA), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), an enzyme regarded as the rate-limiting step in PUFA anabolism.

The climb toward intracranial efficacy: Zorifertinib in EGFR-mutant NSCLC with CNS metastases in the EVEREST trial.

The phase III EVEREST trial evaluating zorifertinib in the treatment of metastatic EGFR-mutant NSCLC was groundbreaking in its specific inclusion of patients with brain metastases. Zorifertinib prolonged systemic and intracranial progression-free survival compared with first-generation EGFR inhibitors, yet questions remain about its efficacy and toxicity compared with osimertinib.

Integrating CTLA-4/PD-1 blockade into cervical cancer management: Results of COMPASSION-16.

Although there is anti-tumor efficacy of dual CTLA-4/PD-1 blockade in advanced/recurrent cervical cancer, it is unclear whether combination with chemotherapy is synergistic. In COMPASSION-16, Wu et al. demonstrated improved survival outcomes of cadolinimab plus chemotherapy compared to chemotherapy alone for first-line systemic therapy for advanced/recurrent cervical cancer, suggesting a potential role of bispecific CTLA-4/PD-1 inhibitors in the frontline setting.

Advancing siRNA Therapeutics targeting MCT-4: A Multifaceted approach integrating Arithmetical Designing, Screening, and molecular dynamics validation.

Monocarboxylate transporter 4 (MCT-4) is involved in various metabolic processes which are crucial in maintaining cellular pH and energy metabolism, and thus influence the tumor microenvironment. The study is aimed to rationally design effective Small interfering RNA (siRNA) that can silence MCT-4. We utilized a comprehensive workflow integrating multiple tools such as siDirect version 2.

Gliricidia sepium (Jacq.) Kunth. ex. Walp. leaves-derived biogenic nanohydrogel accelerates diabetic wound healing in rats over 21 days.

This study focused on the potential of Gliricidia sepium (Jacq.) Kunth. ex.

Ginsenoside Re suppresses high glucose-induced apoptosis of placental trophoblasts through endoplasmic reticulum stress-related CHOP/GADD153.

Gestational diabetes mellitus (GDM) is a metabolic disorder that arises during pregnancy and heightens the risk of placental dysplasia. Ginsenoside Re (Re) may stabilize insulin and glucagon to regulate glucose levels, which may improve diabetes-associated diseases. This study aims to investigate the mechanism of Re in high glucose (HG)-induced apoptosis of trophoblasts through endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153.

Trehalose Inhibits ferroptosis Through Activating SIRT3/SOD2 Signaling Axis and Alleviates Brain Injury After Traumatic Brain Injury.

Trehalose has neuroprotective effects in neurodegenerative diseases. This study aimed to explore the impact of trehalose on traumatic brain injury (TBI) by investigating its role in neuroprotection. The TBI mice model was established utilizing the cortical impact technique followed by trehalose treatment.

Improving Understanding of Fexofenadine Pharmacokinetics to Assess Pgp Phenotypic Activity in Older Adult Patients Using Population Pharmacokinetic Modeling.

Background And Objective: Fexofenadine is commonly used as a probe substrate to assess P-glycoprotein (Pgp) activity. While its use in healthy volunteers is well documented, data in older adult and polymorbid patients are lacking. Age- and disease-related physiological changes are expected to affect the pharmacokinetics of fexofenadine.

Dietary purslane (Portulaca oleracea L.) leaf powder maintains growth and intestinal health in Oreochromis niloticus under chronic water-borne cadmium exposure by strengthening the gut barriers, modulating the intestinal nutrient transporters, and relieving oxidative stress.

High cadmium (Cd) concentrations pose a threat to aquatic life globally. This study examined the efficiency of adding purslane (Portulaca oleracea L.) leaf powder (PLP) to Oreochromis niloticus diets on Cd's negative effects.

Sexual dysfunctions associated with antipsychotic drug intake: a retrospective analysis of the FDA adverse events reporting system (FAERS).

Sexual dysfunctions (SD) are common and debilitating side effects of antipsychotics. The current study analyzes the occurrence of antipsychotic-related SD using data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). FAERS was queried for sexual dysfunction adverse events (encoded by 35 different MedDRA preferred terms) secondary to amisulpride, aripiprazole, chlorprothixene, clozapine, haloperidol, loxapine, olanzapine, pipamperone, quetiapine, risperidone, and ziprasidone from 2000 to 2023.

Suppressing the progression of bladder cancer using cyclovirobuxine D based on network pharmacology and bioinformatics approaches.

Limited treatment options are available for bladder cancer (BCa) resulting in extremely high mortality rates. Cyclovirobuxine D (CVB-D), a naturally alkaloid, reportedly exhibits notable antitumor activity against diverse tumor types. However, its impact on CVB-D on BCa and its precise molecular targets remain unexplored.

Didemnins as marine-derived anticancer agents: mechanistic insights and clinical potential.

Didemnins, a class of cyclic depsipeptides derived from marine organisms exhibit notable anticancer properties. Among them, Didemnin B has been extensively researched for its strong antitumor activity and progression to clinical trials. Nonetheless, its clinical application has been impeded by challenges like poor bioavailability and dose-limiting toxicity.

The role of the Mediterranean diet in reducing the risk of cognitive impairement, dementia, and Alzheimer's disease: a meta-analysis.

Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer's disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet-characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil-has been widely recognized for its cardiovascular benefits and may also reduce the risk of cognitive decline and dementia.