Role of ZFHX4 in orofacial clefting based on human genetic data and zebrafish models.

Orofacial clefting (OFC) is a frequent congenital anomaly and can occur either in the context of underlying syndromes or in isolation (nonsyndromic). The two common OFC phenotypes are cleft lip with/without cleft palate (CL/P) and cleft palate only (CPO). In this study, we searched for penetrant CL/P genes, by evaluating de novo copy number variants (CNV) from an exome sequencing dataset of 50 nonsyndromic patient-parent trios.

Determining structures of RNA conformers using AFM and deep neural networks.

Much of the human genome is transcribed into RNAs, many of which contain structural elements that are important for their function. Such RNA molecules-including those that are structured and well-folded-are conformationally heterogeneous and flexible, which is a prerequisite for function, but this limits the applicability of methods such as NMR, crystallography and cryo-electron microscopy for structure elucidation. Moreover, owing to the lack of a large RNA structure database, and no clear correlation between sequence and structure, approaches such as AlphaFold for protein structure prediction do not apply to RNA.

The conformational space of RNase P RNA in solution.

RNA conformational diversity has fundamental biological roles, but direct visualization of its full conformational space in solution has not been possible using traditional biophysical techniques. Using solution atomic force microscopy, a deep neural network and statistical analyses, we show that the ribonuclease P (RNase P) RNA adopts heterogeneous conformations consisting of a conformationally invariant core and highly flexible peripheral structural elements that sample a broad conformational space, with amplitudes as large as 20-60 Å in a multitude of directions, with very low net energy cost. Increasing Mg drives compaction and enhances enzymatic activity, probably by narrowing the conformational space.

Trends in prescription opioid analgesic use in Australia from 2015 to 2022.

Background: Recent measures to curb use and harms of pharmaceutical opioids in Australia have reduced dispensings of opioid analgesics for pain, under Australia's Pharmaceutical Benefits Scheme (PBS). But information on trends in private (self-funded) dispensings and public (government-funded) hospital opioids use is not readily available. Our study describes eight-year population-level trends in Australia's prescribed opioid analgesic use, estimating PBS dispensing claims, private dispensings and hospital use.

Chemical succession of naphthenic acid fraction compounds in reclamation landscape mesocosms established on centrifuged and co-mixed fluid fine tailings from the Athabasca oil sands.

The Athabasca oil sands region of Alberta, Canada contains one of the world's largest unconventional petroleum deposits. There is concern about residual contaminants where tailings are integrated during reclamation and the related adverse effects this may have. Some of the primary toxic organic contaminants in oilsands tailings are naphthenic acid fraction compounds (NAFCs).

Longitudinal markers of cognitive procedural learning in fronto-striatal circuits and putative effects of a BDNF plasticity-related variant.

Procedural learning and automatization have widely been studied in behavioral psychology and typically involves a rapid improvement, followed by a plateau in performance throughout repeated training. More recently, brain imaging studies have implicated frontal-striatal brain circuits in skill learning. However, it is largely unknown whether frontal-striatal activation during skill learning and behavioral changes follow a similar learning curve pattern.

A discrete choice experiment: Understanding patient preferences for managing chronic non-cancer pain.

Background: The management of chronic non-cancer pain (CNCP) is complex. Concerns about adverse effects associated with opioid pain medications and a lack of funding for holistic programs present challenges for decision-making among clinicians and patients. Discrete choice experiments (DCE) are one way of assessing and valuing patient treatment preferences.

Environmentally sustainable opportunities for health systems: Metered-dose inhaler prescribing, dispensing, use and waste at a tertiary academic centre.

Background: The Canadian health sector's carbon footprint is among the highest in the world and is responsible for 4.6% of Canada's total greenhouse gas emissions, a quarter of which is linked to pharmaceuticals, with metered-dose inhalers (MDIs) contributing disproportionally high amounts.

Objectives: To describe MDI prescribing, dispensing, use and waste patterns at a Canadian tertiary care academic hospital.

Performance and safety of transparent postoperative dressings with silicone adhesive in daily practice on fragile skin.

Objective: Currently there is limited real-world research on the adhesion qualities, pain and clinical performance of specific silicone adhesives products, and their role in maintaining skin integrity and preventing medical adhesive-related skin injuries (MARSI). This paper presents a clinical evaluation of performance and safety parameters of two silicone adhesive dressings on lacerations or surgical wounds and the surrounding skin in daily practice on fragile skin.

Method: An observational, prospective, multicentre, uncontrolled post-market clinical observational study with Leukomed T skin sensitive and Leukomed T plus skin sensitive (both BSN medical GmbH, Essity Group) was undertaken at three sites across Germany between June 2021 to November 2022.

Applying a new theoretical and methodological approach for behavior-change campaign planning: identifying the critical determinants for reducing littering and evaluating the resulting large-scale campaign.

Introduction: This paper presents a theoretical concept and methodological approach for identifying critical determinants for behavior change interventions. The approach is based on established theories and constructs but represents them in an intervention- instead of questionnaire-oriented form. Six discriminant and targetable dimensions of behavior determinants are proposed: Consideration, feasibility, instrumental evaluation, norms and goals, affective evaluation, and needs and tension states.

Deep learning-based whole-brain B -mapping at 7T.

Purpose: This study investigates the feasibility of using complex-valued neural networks (NNs) to estimate quantitative transmit magnetic RF field (B ) maps from multi-slice localizer scans with different slice orientations in the human head at 7T, aiming to accelerate subject-specific B -calibration using parallel transmission (pTx).

Methods: Datasets containing channel-wise B -maps and corresponding multi-slice localizers were acquired in axial, sagittal, and coronal orientation in 15 healthy subjects utilizing an eight-channel pTx transceiver head coil. Training included five-fold cross-validation for four network configurations: used transversal, sagittal, coronal data, and was trained on all slice orientations.

Predicting the Release Mechanism of Amorphous Solid Dispersions: A Combination of Thermodynamic Modeling and In Silico Molecular Simulation.

Background: During the dissolution of amorphous solid dispersion (ASD) formulations, the drug load (DL) often impacts the release mechanism and the occurrence of loss of release (LoR). The ASD/water interfacial gel layer and its specific phase behavior in connection with DL strongly dictate the release mechanism and LoR of ASDs, as reported in the literature. Thermodynamically driven liquid-liquid phase separation (LLPS) and/or drug crystallization at the interface are the key phase transformations that drive LoR.

Microarchitectural properties of compacted cancellous bone allografts: A morphology micro-computed tomography analysis.

Massive bone loss poses a significant challenge in defect reconstruction. The use of compacted allografts is a valuable technique to reconstruct bone stock. This study aimed to assess the impact of compression on the microstructure of native cancellous bone chips with a micro-CT analysis.

[Genetic diagnostics of mental health disorders in adulthood].

This review article provides insights into the role of genetic diagnostics in adult mental health disorders. The importance of genetic factors in the development of mental illnesses, from rare genetic syndromes to common complex genetic disorders, is described. Current clinical characteristics that may warrant a genetic diagnostic work-up are highlighted, including intellectual disability, autism spectrum disorders and severe psychiatric conditions with specific comorbidities, such as organ malformations or epilepsy.

Superior Capsular Reconstruction Using an Acellular Dermal Xenograft or Allograft Improves Shoulder Function but Is Associated with a High Graft Failure Rate.

The purpose of the present study was to evaluate clinical and functional outcomes, graft integrity rate and progression of osteoarthritis after superior capsular reconstruction (SCR) at short-term follow-up. Consecutive patients that underwent SCR using an acellular dermal xeno- or allograft between May 2018 and June 2020 for the treatment of irreparable posterosuperior rotator cuff tears were included. Shoulder function (American Shoulder and Elbow Surgeons [ASES] score), pain (Visual Analog Scale [VAS] for pain) and active shoulder range of motion (ROM) were evaluated preoperatively and after a minimum of 24 months postoperatively.

Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids.

The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia, edema, and gynecomastia by inhibiting steroid synthesis and metabolism. Mechanisms underlying pseudohyperaldosteronism include inhibition of adrenal 11β-hydroxylase cytochrome-P450 (CYP) 11B1 and 17α-hydroxylase (CYP17A1) as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazoles have been developed.

Population size, HIV prevalence, and antiretroviral therapy coverage among key populations in sub-Saharan Africa: collation and synthesis of survey data, 2010-23.

Background: Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa.

Methods: Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents.

The Medicines Intelligence Data Platform: A Population-Based Data Resource From New South Wales, Australia.

Background: The Medicines Intelligence (MedIntel) Data Platform is an anonymised linked data resource designed to generate real-world evidence on prescribed medicine use, effectiveness, safety, costs and cost-effectiveness in Australia.

Results: The platform comprises Medicare-eligible people who are ≥18 years and residing in New South Wales (NSW), Australia, any time during 2005-2020, with linked administrative data on dispensed prescription medicines (Pharmaceutical Benefits Scheme), health service use (Medicare Benefits Schedule), emergency department visits (NSW Emergency Department Data Collection), hospitalisations (NSW Admitted Patient Data Collection) plus death (National Death Index) and cancer registrations (NSW Cancer Registry). Data are currently available to 2022, with approval to update the cohort and data collections annually.

Empowering of Oncology Patients and Informal Caregivers: Analysis of an Interdisciplinary Seminar Model for Breast Cancer and Gyneco-Oncological Patients.

Introduction: The interdisciplinary empowerment seminar aims to familiarize patients and informal caregivers (ICs) with supportive measures, focusing on understanding disease, therapy, and side effect management.

Methods: The seminar, conducted in two courses over 1-month intervals prior to chemotherapy, included lectures, supportive materials, Q and A sessions, and individual discussions with experts in nutrition, exercise, psycho-oncology, and complementary medicine. Evaluation is based on a self-developed questionnaire and questionnaires on QoL (EORTC-QLQ-C30, BR23, CX24, OV28), anxiety and depression (HADS-D) at week 0, 5, 9, and 12.