Maternity care pathway and involvement in decision making: A mixed-methods study of women's experiences in Ireland.

Background: In Ireland, maternity care is provided through a mixture of public and private services, with type of maternity care offered varying according to availability, clinical need and geographic location.

Aim: To explore women's perceived involvement in decisions about care depending on the maternity care pathway received.

Methods: Mixed-methods secondary analysis of data from the Irish National Maternity Experience Survey 2020.

Dataset linking women's maternity care experiences with hospital environment and governance in Ireland.

Many scholars argue that there is a deepening crisis of trust in healthcare systems. What is not contested is the centrality of public trust in building reputational value in healthcare organisations. However, there is a dearth of research focused on better understanding how trust in healthcare institutions, and the healthcare workforce, can be sustainably cultivated.

System-wide analysis of qualitative hospital incident data: Feasibility of semi-automated content analysis to uncover insights.

Background: Advances in technology have increased the ease of reporting hospital incidents, resulting in large amounts of qualitative descriptive data. Health services have little experience analysing these data at scale to incorporate into routine reporting.

Objective: We aimed to explore the feasibility of applying a semi-automated content analysis (SACA) tool (Leximancer™) to qualitative descriptions of system-wide hospital incidents to provide insights into safety issues at all health service levels.

Chemical mixtures of mercury, PCBs, PFAS, and pesticides in freshwater fish in the US and the risks they pose for fish consumption.

Background: Freshwater fish are important food sources that also pose risks to human and wildlife health because of the bioaccumulation of environmental chemicals in their tissues. Although most studies, fish consumption advisories, and regulations focus on individual contaminants, fish consumers are exposed to mixtures of chemicals, including legacy contaminants and contaminants of emerging concern, that can have combined effects. Chemicals of emerging concern represent one source of hazard, but legacy contaminants can still pose threats to fish consumers due to their persistence in the environment.

Discovery and Functional Characterization of a Potent, Selective, and Metabolically Stable PROTAC of the Protein Kinases DYRK1A and DYRK1B.

Small-molecule-induced protein degradation has emerged as a promising pharmacological modality for inactivating disease-relevant protein kinases. DYRK1A and DYRK1B are closely related protein kinases that are involved in pathological processes such as neurodegeneration, cancer development, and adaptive immune homeostasis. Herein, we report the development of the first DYRK1 proteolysis targeting chimeras (PROTACs) that combine a new ATP-competitive DYRK1 inhibitor with ligands for the E3 ubiquitin ligase component cereblon (CRBN) to induce ubiquitination and subsequent proteasomal degradation of DYRK1A and DYRK1B.

Serum cytokine panels in pediatric clinical practice.

Background: Cytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine panels are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited.

Objective: We sought to analyze real-world single-center use of a multiplexed cytokine panel, correlate its results with diagnosis and severity, and explore its use in pediatric practice.

Optimising prostate biopsies and imaging for the future-a review.

Conventionally, transrectal ultrasound guided prostate biopsy (TRUS-Bx) was the main technique used for the diagnosis of prostate cancer since it was first described in 1989 [1]. However, the PROMIS trial showed that this random, nontargeted approach could miss up to 18% of clinically significant cancer (csPCa) [2]. Furthermore, risk of sepsis post TRUS-Bx can be as high as 2.

Reevaluating safety pharmacology respiratory studies within the ICH S7A core battery: A multi-company evaluation of preclinical utility and clinical translation.

Optimization of ICH safety guideline studies for inclusion into regulatory submissions is critical for resource conservation, animal use reduction, and efficient drug development. The ICH S7A guidance for Safety Pharmacology (SP) studies adopted in 2001 identified the core battery of studies to evaluate the acute safety of putative pharmaceutical molecules prior to First in Human (FIH) trials. To assess the utility of respiratory studies in predicting clinical AE's, seven pharmaceutical companies pooled preclinical and clinical respiratory findings.

Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.

Background And Objectives: Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau), atrophy, and cognition.

Perioperative systemic IL-6 and immune-adipose- metabolism transcription in tumour and tumour adjacent breast cancer.

Surgical resection is the primary treatment approach for patients with breast cancer. Despite optimal multimodal treatment, metastatic recurrence remains a risk. Surgery-mediated systemic inflammation and local tissue inflammation generate an immunosuppressive and wound-healing environment that may accelerate cancer recurrence and metastasis post-operatively.

The Clinical Utility of Powdered and Flowable Matrices in Wound Repair and Tissue Regeneration.

Cellular and matrix-like products come in many forms. Among them, powdered and micronized formulations have become increasingly available and popular owing to their unique properties and advantages. Powders have increased tissue contact which many believe can enhance granulation tissue formation, they fill irregular and deep cavities, and they can be used in concert with sheet-like products and skin grafts for improved healing.

Elicitation of expert prior opinion to design the BARJDM trial in juvenile dermatomyositis.

Objectives: To elicit and quantify expert opinion concerning the relative merits of two treatments for a rare inflammatory disease: Juvenile dermatomyositis (JDM). The formal expression of expert opinion reported in this paper will be used in a Bayesian analysis of a forthcoming randomised controlled trial known as BARJDM (baricitinib for juvenile dermatomyositis).

Methods: A Bayesian prior elicitation meeting was convened, following a previously described methodological template.

The contribution of community-based conservation models to conserving large herbivore populations.

In East Africa, community-based conservation models (CBCMs) have been established to support the conservation of wildlife in fragmented landscapes like the Tarangire Ecosystem, Tanzania. To assess how different management approaches maintained large herbivore populations, we conducted line distance surveys and estimated seasonal densities of elephant, giraffe, zebra, and wildebeest in six management units, including three CBCMs, two national parks (positive controls), and one area with little conservation interventions (negative control). Using a Monte-Carlo approach to propagate uncertainties from the density estimates and trend analysis, we analyzed the resulting time series (2011-2019).

Blood protein assessment of leading incident diseases and mortality in the UK Biobank.

The circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality in the UK Biobank (n = 47,600). We report 3,209 associations between 963 protein levels and 21 incident outcomes.

Innovative approaches to cardiovascular safety pharmacology assessment.

This editorial prefaces the annual themed issue on safety pharmacology (SP) methods which has been published since 2004 in the Journal of Pharmacological and Toxicological Methods (JPTM). Here we highlight content derived from the 2023 Safety Pharmacology Society (SPS) meeting held in Brussels, Belgium. The meeting generated 138 abstracts, reproduced in the current volume of JPTM.

Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.

Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition.

Impact of Simulation Exercises on Total Laparoscopic Hysterectomy Surgical Outcomes: A Systematic Review and Meta-Analysis.

Background: As resources into gynecological surgical simulation training increase, research showing an association with improved clinical outcomes is needed.

Objective: To evaluate the association between surgical simulation training for total laparoscopic hysterectomy (TLH) and rates of intraoperative vascular/visceral injury (primary outcome) and operative time.

Search Strategy: We searched Medline OVID, Embase, Web of Science, Cochrane, and CINAHL databases from the inception of each database to April 5, 2022.

Reaction dynamics of S(P) with 1,3-butadiene and isoprene: crossed-beam scattering, low-temperature flow experiments, and high-level electronic structure calculations.

Sulfur atoms serve as key players in diverse chemical processes, from astrochemistry at very low temperature to combustion at high temperature. Building upon our prior findings, showing cyclization to thiophenes following the reaction of ground-state sulfur atoms with dienes, we here extend this investigation to include many additional reaction products, guided by detailed theoretical predictions. The outcomes highlight the complex formation of products during intersystem crossing (ISC) to the singlet surfaces.

Investigating racial/ethnic differences in procedure experience in obstetrics & gynecology trainees at a single academic institution: a retrospective cohort study.

Background: Discrimination is common in medical education. Resident physicians of races and ethnicities underrepresented in medicine experience daily discrimination which has been proven to negatively impact training. There is limited data on the impact of resident race/ethnicity on OB/GYN surgical training.