Absolute membrane protein abundance of P-glycoprotein, breast cancer resistance protein, and multidrug resistance proteins in term human placenta tissue and commonly used cell systems: Application in physiologically based pharmacokinetic modeling of placental drug disposition.

The placenta acts as a barrier, excluding noxious substances while actively transferring nutrients to the fetus, mediated by various transporters. This study quantified the expression of key placental transporters in term human placenta (n = 5) and BeWo, BeWo b30, and JEG-3 placenta cell lines. Combining these results with pregnancy physiologically based pharmacokinetic (PBPK) modeling, we demonstrate the utility of proteomic analysis for predicting placental drug disposition and fetal exposure.

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.

A Phase I/IIa Clinical Trial to Evaluate Safety and Adrenal Uptake of Para-Chloro-2-[F]Fluoroethyletomidate in Healthy Volunteers and Patients with Primary Aldosteronism.

Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA).

Complex high-risk indicated PCI (CHIP-PCI): is it safe to let fellows-in-training perform it as primary operators?

Background: Training in complex high-risk indicated percutaneous coronary intervention (CHIP-PCI) has frequently been reserved for established operators (consultants/attending) with trainees (fellows-in-training or FIT) being often discouraged from carrying out such procedures as a primary operator due to their high-risk nature. Whether the outcomes of these cases differ if the primary operator is a supervised FIT compared with a consultant is unknown.

Methods: Using multicentre PCI data from three cardiac centres in South Wales, UK (2018-2022), we identified 2295 CHIP-PCI cases with a UK-BCIS CHIP Score of 3 or more.

Impact of introducing transnasal endoscopy on expanding diagnostic endoscopy services.

Introduction: Demand for endoscopic services is outstripping capacity in the UK. Transnasal endoscopy (TNE) utilises a narrow calibre endoscope to pass through the nasal passages, thereby reducing retching and discomfort. It is better tolerated compared with standard transoral endoscopy (TOE) but is still rarely used as a diagnostic modality.

Factors associated with link workers considering leaving their role: a cross-sectional survey.

Background: Social prescribing (SP) link workers (LWs) listen to patients' concerns and difficulties, and connect them to relevant community assets (groups/organisations/charities) that can help with their non-medical issues (eg, loneliness, debt, housing). LW retention is key to sustaining SP within primary care.

Aim: To examine occupational self-efficacy, job discrepancy and other factors as potential predictors of LWs' intentions to leave or remain in their post.

S100A9 protein activates microglia and stimulates phagocytosis, resulting in synaptic and neuronal loss.

S100 calcium-binding protein A9 (S100A9, also known as calgranulin B) is expressed and secreted by myeloid cells under inflammatory conditions, and S100A9 can amplify inflammation. There is a large increase in S100A9 expression in the brains of patients with neurodegenerative diseases, such as Alzheimer's disease, and S100A9 has been suggested to contribute to neurodegeneration, but the mechanisms are unclear. Here we investigated the effects of extracellular recombinant S100A9 protein on microglia, neurons and synapses in primary rat brain neuronal-glial cell cultures.

A large hypothesis-free proteomics study investigating serum inflammatory markers as biomarkers of dry eye disease.

Purpose: To test the association between serum inflammatory markers and dry eye disease (DED) using a hypothesis-free proteomic approach in a population-based cohort.

Methods: A total of 2602 unselected community-based participants (mean age 61.5 (range 21-92 years), 94.

Cognitive hierarchy in mood disorders and relations to daily functioning.

Cognitive impairment affects approximately 50 % of patients with mood disorders during remission, which correlates with poorer daily-life functioning. The hierarchical organization of cognitive processes may mean that some cognitive deficits, e.g.

Weight-Inclusive Physical Activity: A Systematic Evaluation of Virtual Resources.

Background: Higher-weight individuals report lower rates of physical activity behavior and poorer physical activity experiences compared with their normative-weight counterparts, likely owing to the pervasiveness of weight stigma in physical activity contexts. Employing weight-inclusive strategies may improve physical activity outcomes, though little is known about the practical application of weight-inclusive principles in physical activity contexts. Furthermore, given the prominence of virtual methods of information dissemination, exploring online weight-inclusive resources is valuable.

The Influence of Relative Age and Biological Maturity on Youth Weightlifting Performance.

Purpose: Relative age effects and biological maturation are common biases within youth talent identification and development programs; however, their respective influence on youth weightlifting is unknown.

Method: Skeletal age, determined from ultrasonography, and competitive total loads (kg) were collected in 49 national age group weightlifters (boys: n = 24, age = 13.8 [2.

New N-Alkylketonetetrahydroisoquinoline derivatives exhibits antitumor effect by HA-CD44 interaction inhibition in MDA-MB-231 breast cancer.

Molecular interactions at the cell surface, in particular between hyaluronic acid (HA) and the cluster of differentiation 44 (CD44) receptor, are crucial in several biological processes and diseases such as cancer. Thus, inhibition of the HA-CD44 interaction has become a promising therapeutic strategy. Etoposide was the only antitumor compound known to inhibit the binding of CD44 to HA, thereby disrupting key functions that drive malignancy.

Advances and insights into modeling extracellular electron transfer in anaerobic bioprocesses.

Extracellular electron transfer (EET) plays an important role in maintaining redox balance in both natural and engineered anaerobic microbial systems, driving key biochemical processes such as energy generation, bioremediation, and waste degradation. While EET has been characterized in a limited number of microbes and applied in anaerobic digestion and bioelectrochemical systems, further research is needed to explore its mechanism across a broader range of microbial species and anaerobic processes. This review highlights advanced modeling frameworks that provide deeper insights into EET mechanisms and dynamics, aiming to optimize research efforts and minimize time and resource expenditure.

Predicting and optimising outcome for biliary atresia.

Biliary atresia (BA) remains a disease of significant morbidity and mortality world-wide. Early and accurate diagnosis facilitates early intervention and improves outcomes. The gold standard in diagnosing BA is a liver biopsy followed by cholangiography, usually performed intra-operatively.

Rhizosphere bacterial communities of Namib Desert plant species: Evidence of specialised plant-microbe associations.

Rhizosphere microbial communities are intimately associated with plant root surfaces. The rhizosphere microbiome is recruited from the surrounding soil and is known to impact positively on the plant host via enhanced resistance to pathogens, increased nutrient availability, growth stimulation and increased resistance to desiccation. Desert ecosystems harbour a diversity of perennial and annual plant species, generally exhibiting considerable physiological adaptation to the low-water environment.

Experiences and perspectives of patients undergoing colorectal cancer surgery: A qualitative study.

Purpose: This study aimed to explore the experiences of patients with colorectal cancer undergoing surgical treatment, capturing their perspectives from diagnosis through to post-discharge recovery.

Methods: A qualitative methodology was adopted, utilising semi-structured virtual interviews with ten patients recruited from a specialist colorectal clinic. Interviews were transcribed verbatim, and data analysed by the process of inductive thematic analysis, using interpretive description.

Muscle imaging in facioscapulohumeral muscular dystrophy research: A scoping review and expert recommendations.

Clinical trial readiness is an important topic in the field of facioscapulohumeral muscular dystrophy (FSHD). As FSHD is a slowly progressive and clinically heterogeneous disease, imaging biomarkers have been proposed to complement clinical outcome measures. Muscle magnetic resonance imaging (MRI), ultrasound and dual energy X-ray absorptiometry (DEXA) have been used to measure disease severity, activity and progression.

Alemtuzumab and thrombotic thrombocytopenic purpura: Analysis of an international surveillance database and systematic literature review.

Objectives: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy associated with severe deficiency in ADAMTS13. ADAMTS13 deficiency may be secondary to absent or dysfunctional protein production due to mutations in the ADAMTS13 gene (congenital TTP) or autoantibody-mediated clearance and/or inhibition (immune-mediated TTP). This autoimmunity may, albeit rarely, occur secondary to certain medications (eg, ticlopidine).

An exploration into the experiences of newly qualified midwives during their transition to practice in the UK: A systematic review.

Aim: The aim of this systematic review was to explore the experiences of newly qualified midwives (NQMs) during their transition to practice in the UK.

Background: It has been recognised that the transition from student to NQM is a time of significant change that has implications for staff recruitment and retention. Thus, the rationale for this review was that understanding the experiences of NQMs at this crucial time in their career is essential for developing systems of support to improve maternity care and no previous reviews were found on this topic based in the UK.

EEG correlates of acquiring race driving skills.

Objective Race driving is a complex motor task that involves multiple concurrent cognitive processes in different brain regions coordinated to maintain and optimize speed and control. Delineating the neuroplasticity accompanying the acquisition of complex and fine motor skills such as racing is crucial to elucidate how these are gradually encoded in the brain and inform new training regimes. This study aims, first, to identify the neural correlates of learning to drive a racing car using non-invasive electroencephalography (EEG) imaging and longitudinal monitoring.

Impact of Vein-to-vein Time in Patients With R/R LBCL Treated With Axicabtagene Ciloleucel.

Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory large B-cell lymphoma (R/R LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel.

A Model of Zymogen Factor XII: Insights into Protease Activation.

In plasma, the zymogens factor XII (FXII) and prekallikrein reciprocally convert each other to the proteases FXIIa and plasma kallikrein (PKa). PKa cleaves high-molecular-weight kininogen (HK) to release bradykinin, which contributes to regulation of blood vessel tone and permeability. Plasma FXII is normally in a "closed" conformation that limits activation by PKa.

Migration of Health Workers and Its Impacts on the Nigerian Health Care Sector: Protocol for a Scoping Review.

Background: Health worker migration from Nigeria poses significant challenges to the Nigerian health care sector and has far-reaching implications for health care systems globally. Understanding the factors driving migration, its effects on health care delivery, and potential policy interventions is critical for addressing this complex issue.

Objective: This study aims to comprehensively examine the factors encouraging the emigration of Nigerian health workers, map out the effects of health worker migration on the Nigerian health system, document the loss of investment in health training and education resulting from migration, identify relevant policy initiatives addressing migration, determine the effects of Nigerian health worker migration on destination countries, and identify the benefits and demerits to Nigeria of health worker migration.