The effect of carbamazepine, a strong CYP3A inducer, on the pharmacokinetics of zongertinib in healthy male volunteers.

Introduction: Zongertinib (BI 1810631) is a potent, selective, and epidermal growth factor receptor (EGFR) wild-type sparing human epidermal growth factor receptor 2 (HER2) inhibitor. Based on in vitro data, the oxidative hepatic metabolism of zongertinib is principally driven by cytochrome P450 (CYP) 3A4/5. Therefore, zongertinib may be affected by strong CYP3A inducers, like carbamazepine.

Comparison of different disinfection protocols against contamination of ceramic surfaces with biofilm.

Environmental contamination with biofilm can be a source of healthcare-associated infections. Disinfection with various biocidal active substances is usually the method of choice to remove contamination with biofilm. In this study we tested 13 different disinfection protocols using gaseous ozone, citric acid, and three working concentrations of benzalkonium chloride-based professional disinfecting products on 24-hour-old biofilms formed by two strains on ceramic tiles.

Trends in use of antiseizure medication and treatment pattern during the first trimester in the German Embryotox cohort.

Because of their developmental toxicity, some antiseizure medication (ASM) should be avoided during pregnancy. This may lead to discontinuation or switching of ASM after recognition of pregnancy, but some of these changes may be suboptimal. Trends in ASM use at conception were analyzed in 3,763 pregnancies prospectively ascertained by a teratology information service in Germany between 2000 and 2018.

Health disparities in diabetes treatment: The challenge of G6PD deficiency.

Aims: To assess the impact of Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an enzymatic deficiency prevalent in individuals of African or Asian descent, on Hemoglobin A1c (HbA1c) levels, diabetes medication purchases, and the cumulative incidence of diabetes related complications.

Methods: A large cohort study was conducted within a national health organization, comparing 3,913 G6PD-deficient patients to a matched control group without G6PD deficiency over two decades. The main measures and outcomes were the HbA1c levels, patterns of diabetes medication purchases, and the incidence of severe diabetes-related complications.

The interplay between lung galectins and pro-fibrotic markers in post-COVID-19 fibrogenesis: A pilot study.

Aims: COVID-19, caused by the SARS-CoV-2 virus, can lead to serious lung conditions, notably interstitial pulmonary fibrosis.

Main Methods: Our study tracked the progression of fibrosis markers in serial bronchoalveolar lavage (BAL) measurements collected from 16 COVID-19 patients at 1, 3, and 6 months post-infection. Additionally, BAL samples from 10 healthy control subjects were included.

Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants.

N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that is known for its short-lasting effects when administered intravenously. Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking.

Dose-volume predictors of cardiac adverse events after high-dose thoracic radiation therapy for lung cancer: a systematic review and meta-analysis.

Background: Lung cancer is a leading cause of cancer mortality and may require high-dose thoracic radiation therapy (RT). However, RT significantly increases the risk of radiation-induced cardiac events, such as pericarditis, cardiomyopathy, and ischemic heart diseases. Despite evidence from clinical trials showing that higher RT doses are associated with poorer survival outcomes due to these cardiac effects, data on dose-volume predictors of such events in lung cancer remain sparse.

Cytochrome P450 phenotyping using the Geneva cocktail improves metabolic capacity prediction in a hospitalized patient population.

Aims: Liver cytochromes (CYPs) play an important role in drug metabolism but display a large interindividual variability resulting both from genetic and environmental factors. Most drug dose adjustment guidelines are based on genetics performed in healthy volunteers. However, hospitalized patients are not only more likely to be the target of new prescriptions and drug treatment modifications than healthy volunteers, but will also be more subject to polypharmacy, drug-drug interactions, or to suffer from disease or inflammation affecting CYP activities.

Required minimal protein domain of flower for synaptobrevin2 endocytosis in cytotoxic T cells.

Flower, a highly conserved protein, crucial for endocytosis and cellular fitness, has been implicated in cytotoxic T lymphocyte (CTL) killing efficiency through its role in cytotoxic granule (CG) endocytosis at the immune synapse (IS). This study explores the molecular cues that govern Flower-mediated CG endocytosis by analyzing uptake of Synaptobrevin2, a protein specific to CG in mouse CTL. Using immunogold electron microscopy and total internal fluorescence microscopy, we found that Flower translocates in a stimulus-dependent manner from small vesicles to the IS, thereby ensuring specificity in CG membrane protein recycling.

Relative Forgiveness of Different Allopurinol Implementation Patterns in People with Gout and their Impact on Clinical Outcomes: a Simulation Study.

Background And Objective: Adherence to urate-lowering therapy among people with gout is poor, so it is important to understand which day-to-day medication-taking ('implementation') patterns are most likely to lead to suboptimal serum urate concentrations and worsen clinical outcomes. This study aimed to (1) determine the relative forgiveness (RF) of allopurinol with hypothetical and real-life implementation patterns in people with gout, (2) explore the use of RF as a means of identifying suboptimal implementation patterns, (3) assess the impact of suboptimal implementation patterns on clinical outcomes.

Methods: A simulation study was conducted using a pharmacokinetic-pharmacodynamic model for allopurinol and serum urate to determine the RF of allopurinol implementation patterns.

Antibiofilm Effects of Novel Compounds in Otitis Media Treatment: Systematic Review.

Otitis media (OM) is a frequent disease with incidence rate of 5300 cases per 100,000 people. Recent studies showed that polymicrobial biofilm formation represents a significant pathogenic mechanism in recurrent and chronic forms of OM. Biofilm enables bacteria to resist antibiotics that would typically be recommended in guidelines, contributing to the ineffectiveness of current antimicrobial strategies.

Role of Oxidative Stress and Inflammation in Postoperative Complications and Quality of Life After Laryngeal Cancer Surgery.

(1) Background: Laryngeal surgery due to carcinoma leads to significant tissue disruption, cellular injury, and inflammation. This leads to increased levels of reactive oxygen species (ROS), causing oxidative damage that can influence quality of life (QOL) and recovery and complicate the postoperative course. The aim of this study was to compare how postoperative quality of life and surgical complication occurrence interacted with the biomarker levels of oxidative stress (malondialdehyde, MDA; superoxide dismutase, SOD; glutathione peroxidase 1, GPX1; and catalase, CAT) and inflammation (interleukin 1, IL-1; interleukin 6, IL-6; C-reactive protein, CRP) in patients treated with conservative and radical laryngeal surgery.

Perception of medical care among women living with HIV aged 40 years or older-A European-wide survey.

Objectives: Our objective was to explore how women living with HIV aged ≥40 years perceive their care in relation to their HIV infection, comorbidities, and menopausal health and to evaluate the extent to which the care they receive meets their expectations, comparatively across World Health Organization (WHO) European regions.

Methods: We conducted a cross-sectional survey (May-December 2023) among women living with HIV aged ≥40 years from the WHO European region. Five dimensions of care were assessed: content of care, information, relationship with caregiver, organization of care, and patients' rights and privacy, in addition to management of non-HIV comorbidities and menopause.

Road Guarder (Conophis lineatus concolor: Dipsadidae): Case Documentation of a Clinically Significant Envenoming.

Detailed cases of envenoming by a non-front-fanged snake (NFFS) from North, Central, and South America have had limited representation in the toxicology and toxinology literature. The NFFS, Conophis lineatus, has been reported to deliver bites that resulted in moderately severe envenoming. However, most of these reported cases have been via personal communication, or self-reported and lacking in detailed medical evaluations.

The psychoplastogens ibogaminalog and ibogainalog induce antidepressant-like activity in naïve and depressed mice by mechanisms involving 5-HT receptor activation and serotonergic transmission.

The antidepressant-like activity of two psychoplastogens, ibogainalog (IBG) and ibogaminalog (DM506), was studied in naïve mice using the forced swim test (FST) and tail suspension test (TST). The behavioral results showed that a single administration of 25 mg/kg DM506 or 10 mg/kg IBG induced antidepressant-like activity in naïve mice in a volinanserin-sensitive manner that persisted for 72 h. Similar results were observed using the chronic immobilization stress (CIS) test, in which depression symptoms were reduced for 48 h.

EOMES establishes mesoderm and endoderm differentiation potential through SWI/SNF-mediated global enhancer remodeling.

Mammalian pluripotent cells first segregate into neuroectoderm (NE), or mesoderm and endoderm (ME), characterized by lineage-specific transcriptional programs and chromatin states. To date, the relationship between transcription factor activities and dynamic chromatin changes that guide cell specification remains ill-defined. In this study, we employ mouse embryonic stem cell differentiation toward ME lineages to reveal crucial roles of the Tbx factor Eomes to globally establish ME enhancer accessibility as the prerequisite for ME lineage competence and ME-specific gene expression.

Studies on the Stability and Microbial Biotransformation of Five Deschloroketamine Derivatives as Prerequisite for Wastewater-Based Epidemiology Screening.

Wastewater (WW)-based epidemiology (WBE) is a powerful tool for screening and surveillance of drugs (of abuse) or new psychoactive substances (NPSs) in larger population. Since the drug market changes frequently, it is crucial for WBE to define screening and surveillance biomarkers considering drug metabolism and (microbial) stability. The aims of the presented work were first to identify metabolites, potentially serving as a WBE biomarker of five deschloroketamine derivatives (DCKDs) in rat feces samples after oral administration in addition to already known urinary metabolites, and second to elucidate the microbial biotransformation and WW stability of five DCKDs and their metabolites detected in urine and feces.

Risk of congenital malformations and miscarriages following maternal use of oral fluconazole during the first trimester of pregnancy: a systematic review and meta-analysis.

The risks related to fluconazole use during the first trimester of pregnancy (T1) remain controversial. The aims of this systematic review and meta-analysis were to assess the association between oral fluconazole during T1 and major congenital malformations (MCM) overall and by subtype, minor malformations and miscarriages.We searched MEDLINE, EMBASE, Cochrane, ICTRP and ClinicalTrials.

Pharmacist-led interventions at hospital discharge: a scoping review of studies demonstrating reduced readmission rates.

Background: Substantial numbers of hospital readmissions occur due to medication-related problems. Pharmacists can implement different interventions at hospital discharge that aim to reduce those readmissions. It is unclear which pharmacist-led interventions at hospital discharge are the most promising in reducing readmissions.

The association of prenatal volatile organic compounds exposure and newborn anthropometrics: A cross-sectional study.

Background: Several studies have associated prenatal exposure to volatile organic compounds (VOCs) with adverse health outcomes among newborns. However, little is known about the associations of VOCs at relatively low concentrations with newborn outcomes. Hence, this study aimed to investigate the potential associations between prenatal exposure to VOCs and VOC mixtures with newborn anthropometric measures.

Failure of neuromuscular blockade despite high doses of rocuronium and atracurium in a patient with colorectal carcinoma: A case report.

Resistance to the effects of rocuronium and other neuromuscular blocking agents (NMBA) has been previously reported, including delayed onset of relaxation, rapid recovery and incomplete paralysis under recommended doses. These conditions have been associated with denervation injury, burns, immobilisation, infections, metabolic disorders, and drug interactions. In this report, we describe the case of a young male without any known pre-disposing factor for NMBA resistance, who failed to attain muscle relaxation with non-depolarising NMBA despite high doses of rocuronium and atracurium during two surgeries for colorectal cancer, several months apart.