Uncovering the impact of COVID-19-mediated bidirectional dysregulation of cytochrome P450 3A4 on systemic and pulmonary drug concentrations using physiologically based pharmacokinetic modeling.

Several clinical studies have shown that COVID-19 increases the systemic concentration of drugs in hospitalized patients with COVID-19. However, it is unclear how COVID-19-mediated bidirectional dysregulation of hepatic and pulmonary cytochrome P450 (CYP) 3A4 affects drug concentrations, especially in the lung tissue, which is most affected by the disease. Herein, physiologically based pharmacokinetic modeling was used to demonstrate the differences in systemic and pulmonary concentrations of 4 respiratory infectious disease drugs when CYP3A4 is concurrently downregulated in the liver and upregulated in the lung based on existing clinical data on COVID-19-CYP3A4 interactions at varying severity levels including outpatients, non-intensive care unit (ICU), and ICU patients.

Accelerated epigenetic aging worsens survival and mediates environmental stressors in fibrotic interstitial lung disease.

Background: The role of epigenetic aging in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter ≤2.5 μm (PM) and neighbourhood disadvantage exposures are associated with accelerated epigenetic aging, and whether epigenetic age is associated with adverse clinical outcomes in patients with fILD.

Efficacy and safety of anti-thrombotic therapy after surgical mitral valve repair: a scoping review.

Background: Mitral valve repair (MVr) is the gold standard treatment for degenerative mitral regurgitation, yet there is ongoing controversy regarding optimal anti-thrombotic therapy post-MVr. This scoping review aimed to summarise current evidence on the safety and efficacy of anti-thrombotic therapy after MVr, identify knowledge gaps and propose a future study design.

Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.

Proposing and refining a physical activity intervention for individuals living with COPD.

Preliminary test a two stage, self-determination theory (SDT) and participation-based physical activity and peer support intervention for individuals with Chronic Obstructive Pulmonary Disease (COPD). In Stage 1, four focus groups were conducted to provide insights about individuals' needs and experiences with physical activity. In Stage 2, four individuals with COPD aged 76-90 years (50% female) participated in an eight-week online physical activity and peer support intervention.

Cross-National Validation of the WHO-5 Well-Being Index Within Adolescent Populations: Findings From 43 Countries.

The five-item World Health Organization Well-Being Index (WHO-5) is among the most frequently used brief standard measures to assess hedonic well-being. Numerous studies have investigated different facets of its psychometric properties in adult populations. However, whether these results apply to adolescents is uncertain, and only few psychometric studies employed adolescent populations.

Medication-related hospitalisations in patients with SLE.

Objectives: Patients with SLE take multiple medications. Within a large prospective longitudinal SLE cohort, we characterised medication-related hospitalisations and their preventability.

Methods: We identified consecutive admissions to our tertiary hospitals between 2015 and 2020.

Physicochemical Design of Nanoparticles to Interface with and Degrade Neutrophil Extracellular Traps.

Neutrophil extracellular traps (NETs) are networks of decondensed chromatin, histones, and antimicrobial proteins released by neutrophils in response to an infection. NET overproduction can cause an exacerbated hyperinflammatory response in a variety of diseases and can lead to host tissue damage without clearance of infection. Nanoparticle drug delivery is a promising avenue for creating materials that can both target NETs and deliver sustained amounts of NET-degrading drugs to alleviate hyperinflammation.

Catecholamine synthesis and secretion by adrenal chromaffin cells is reduced in deer mice native to high altitude.

Hypoxia at high altitude can constrain aerobic metabolism and elicit physiological responses that are detrimental to health and fitness. Responses of the sympathoadrenal system are vital for coping with acute hypoxia, but can become maladaptive with prolonged activation in chronic hypoxia. We examined how adrenal function is altered in high-altitude populations of deer mice (), which have evolved to overcome chronic hypoxia in their native environment.

Assessment of Online YouTube Videos as a Source of Information and Instruction for Pulmonary Rehabilitation.

Background/objectives: Pulmonary rehabilitation (PR) benefits individuals with chronic respiratory conditions beyond COPD; however, the quality of online resources has not been evaluated. The aims of this study were to assess the content, quality, and comprehensibility of YouTube videos that provide PR to individuals with chronic lung diseases other than COPD.

Methods: A search was conducted on YouTube for videos related to PR on non-COPD conditions, with the first 350 videos screened for eligibility (2004-2024).

Prostaglandin E and Akt promote stemness in Apc mutant Dclk1+ cells to give rise to colitis-associated cancer.

Background And Aims: Loss of the tumor suppressor gene Apc in Lgr5+ intestinal stem cells results in aberrant Wnt signaling and colonic tumorigenesis. In the setting of injury, however, we and others have also shown that non-stem cells can also give rise to colonic tumors. The mechanism by which inflammation leads to cellular plasticity and cancer, however, remains largely unknown.

Report on the Development of the Accreditation Council for Education in Nutrition and Dietetics' Academic "Accreditation Standards for Advanced Practice Doctoral Education in Nutrition and Dietetics".

The dietetics profession is facing a shortage of registered dietitian nutritionists (RDNs) with a terminal degree. The need for doctoral prepared RDNs was augmented with the entry-level RDN requiring a graduate degree and exacerbated by the number of retirees from the baby boomer generation. Advanced practice doctoral (APD) programs can assist in meeting the increased need for doctoral prepared RDNs.

Emerging evidence for the impact of Electric Vehicle sales on childhood asthma: Can ZEV mandates help?

Growing epidemiological studies indicate a significant fraction of asthma cases can be attributed to traffic-related air pollution (TRAP). Zero emission vehicle (ZEV) mandates-one of the most forward-looking climate policies in the United States-aim to reduce TRAP by mandating automakers to sell a certain fraction of Electric Vehicles (EVs) annually; however, their public health benefits are largely unknown. We conduct the screening step of the health impact assessment (HIA) of real-world EV sales to estimate the impact of ZEV mandates in reducing childhood asthma.

Examining How Sociocultural Appearance Pressures Relate to Positive and Negative Facets of Body Image and Eating Behaviors in Adolescents: An Exploratory Person-Centered Approach.

The present study explored how patterns of sociocultural appearance pressures were linked to positive and negative facets of body image and eating behaviors in an adolescent sample (N = 438). Latent profile analyses indicated three distinct subgroups of perceived sociocultural appearance-related pressures: a Generalized-Pressure profile (28.8%) (moderate pressure from mother, father, and peers, and relatively high pressure from the media), a High-Media-Pressure profile (38.

Minimum initiatory concentration distribution of Mecillinam in clinical Staphylococcus saprophyticus isolates from Europe.

Background: Staphylococcus saprophyticus is the second most common bacteria causing uncomplicated urinary tract infections (UTI). It is considered non-susceptible to mecillinam, with no defined breakpoint and only few available minimal inhibitory concentration (MIC) observations. However, this consideration does not correlate with clinical outcome.

Impact of Early Menopause and Hormonal Therapy Replacement on Aortic Stenosis Progression.

Background: Early menopause has been associated with several cardiovascular diseases. Its impact on the progression of aortic stenosis (AS) remains unknown. We conducted an analysis to examine the impact of early menopause without hormonal replacement therapy (HRT) on the progression of AS in postmenopausal women with AS.

The Self in Depression and Anxiety as a Transdiagnostic and Differential-diagnostic Neural Marker: A Systematic Review.

Accurate and early diagnosis of Depression and Anxiety is met with the challenge of comorbid presentations and the neglect of the basic disturbances of self in current diagnostic criteria. Here, we review studies employing functional magnetic resonance imaging (fMRI) with self-based tasks in major depressive disorder (MDD) and anxiety disorders (AD) to determine the transdiagnostic and differential-diagnostic applicability of neural markers related to the self. This systematic review identified three main findings: (I) Large-scale brain-wide changes related to self-dysfunction overlap significantly between MDD and AD.

Xylazine: An emerging threat in obstetrics.

Xylazine, an alpha-adrenergic agent, is a common adulterant in the non-prescribed opioid supply. It has multiplicative sedative effects when used with opioids and these effects can negatively impact pregnancy. Given that the opioid epidemic in Canada is not abating and continues to evolve, cases of xylazine exposure during pregnancy are beginning to present in obstetrical units and emergency departments.