A probable -acting genetic modifier of Huntington disease frequent in individuals with African ancestry.

Huntington disease (HD)is a dominantly inherited neurodegenerative disorder caused by the expansion of a polyglutamine encoding CAG repeat in the huntingtin gene. Recently, it has been established that disease severity in HD is best predicted by the number of pure CAG repeats rather than total glutamines encoded. Along with uncovering DNA repair gene variants as -acting modifiers of HD severity, these data reveal somatic expansion of the CAG repeat as a key driver of HD onset.

Provocative Discography: Diagnostic Efficacy and Safety in Symptomatic Degenerative Disk Disease.

Study Design: This was a retrospective cohort analysis.

Objective: The objective of this study was to report the efficacy and safety profile of provocative discography.

Summary Of Background Data: It is reported that the provocative discogram as a diagnostic test for symptomatic degenerative disk disease induces disk degeneration.

Gelatin Methacryloyl Hydrogels for Musculoskeletal Tissue Regeneration.

Musculoskeletal disorders are a significant burden on the global economy and public health. Hydrogels have significant potential for enhancing the repair of damaged and injured musculoskeletal tissues as cell or drug delivery systems. Hydrogels have unique physicochemical properties which make them promising platforms for controlling cell functions.

Choose Wisely: Surgical Selection of Candidates for Outpatient Anterior Cervical Surgery Based on Early Complications Among Inpatients.

Background: Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are attractive targets for transition to the outpatient setting. We assessed the prevalence of rapid responses and major complications in the inpatient setting following 1 or 2-level ACDFs and CDAs. We evaluated factors that may place patients at greater risk for a rapid response or a postoperative complication.

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6   6   6 m liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light.

Modelling Interfaces in Thin-Film Photovoltaic Devices.

Developing effective device architectures for energy technologies-such as solar cells, rechargeable batteries or fuel cells-does not only depend on the performance of a single material, but on the performance of multiple materials working together. A key part of this is understanding the behaviour at the interfaces between these materials. In the context of a solar cell, efficient charge transport across the interface is a pre-requisite for devices with high conversion efficiencies.

Multisite phosphorylation and binding alter conformational dynamics of the 4E-BP2 protein.

Intrinsically disordered proteins (IDPs) play critical roles in regulatory protein interactions, but detailed structural/dynamic characterization of their ensembles remain challenging, both in isolation and when they form dynamic "fuzzy" complexes. Such is the case for mRNA cap-dependent translation initiation, which is regulated by the interaction of the predominantly folded eukaryotic initiation factor 4E (eIF4E) with the intrinsically disordered eIF4E binding proteins (4E-BPs) in a phosphorylation-dependent manner. Single-molecule Förster resonance energy transfer showed that the conformational changes of 4E-BP2 induced by binding to eIF4E are non-uniform along the sequence; while a central region containing both motifs that bind to eIF4E expands and becomes stiffer, the C-terminal region is less affected.

Nonhematopoietic IRAK1 drives arthritis via neutrophil chemoattractants.

IL-1 receptor-activated kinase 1 (IRAK1) is involved in signal transduction downstream of many TLRs and the IL-1R. Its potential as a drug target for chronic inflammatory diseases is underappreciated. To study its functional role in joint inflammation, we generated a mouse model expressing a functionally inactive IRAK1 (IRAK1 kinase deficient, IRAK1KD), which also displayed reduced IRAK1 protein expression and cell type-specific deficiencies of TLR signaling.

Aspirin for Primary Stroke Prevention; Evidence for a Differential Effect in Men and Women.

Background: The use of aspirin for primary prevention of cardiovascular events in men and women remains controversial. Our study aimed to investigate the role of aspirin in primary stroke prevention in men and women and the effect of aspirin on risk of ischemic stroke in patients with covert cerebral small vessel disease (ccSVD).

Methods: We performed systematic searches of the PubMed, and Cochrane Library databases, covering the period from the inception of each database to May 2021.

Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer Survivors (The AIM Trial): Rationale, Design, and Methods.

Background: Obesity is a significant contributor to breast cancer recurrence and mortality. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise interventions to target chronic inflammation has a potential to improve obesity- and breast cancer-related outcomes; however, no studies have investigated the roles of exercise in modulating adipose tissue inflammation in breast cancer survivors.

Analysis of therapy monitoring in the International Congenital Adrenal Hyperplasia Registry.

Objective: Congenital adrenal hyperplasia (CAH) requires exogenous steroid replacement. Treatment is commonly monitored by measuring 17-OH progesterone (17OHP) and androstenedione (D4).

Design: Retrospective cohort study using real-world data to evaluate 17OHP and D4 in relation to hydrocortisone (HC) dose in CAH patients treated in 14 countries.

Multi-Scale Analysis of the Composition, Structure, and Function of Decellularized Extracellular Matrix for Human Skin and Wound Healing Models.

The extracellular matrix (ECM) is a complex mixture of structural proteins, proteoglycans, and signaling molecules that are essential for tissue integrity and homeostasis. While a number of recent studies have explored the use of decellularized ECM (dECM) as a biomaterial for tissue engineering, the complete composition, structure, and mechanics of these materials remain incompletely understood. In this study, we performed an in-depth characterization of skin-derived dECM biomaterials for human skin equivalent (HSE) models.

Encouraging openness in health care: Policy and practice implications of a mixed-methods study in the English National Health Service.

Objective: The National Health Service (NHS) in England has introduced a range of policy measures aimed at fostering greater openness, transparency and candour about quality and safety. We draw on the findings of an evaluation of the implementation of these policies in NHS organisations, with the aim of identifying key implications for policy and practice.

Methods: We undertook a mixed-methods policy evaluation, comprising four substudies: a longitudinal analysis of data from surveys of NHS staff and service users; interviews with senior stakeholders in NHS provider organisations and the wider system; a survey of board members of NHS provider organisations and organisational case studies across acute, community and mental health, and ambulance services.

Floral organ abscission in Arabidopsis requires the combined activities of three TALE homeodomain transcription factors.

Floral organ abscission is a separation process in which sepals, petals, and stamens detach from the plant at abscission zones. Here, we investigated the collective role of three amino-acid-loop-extension (TALE) homeobox genes ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1), KNAT6 (for KNOTTED LIKE from Arabidopsis thaliana) and KNAT2, which form a module that patterns boundaries under the regulation of BLADE-ON-PETIOLE 1 and 2 (BOP1/2) co-activators. These TALE homeodomain transcription factors were shown to maintain boundaries in the flower, functioning as a unit to coordinate the growth, patterning, and activity of abscission zones.

Reflexive Practice as an Approach to Improve Healthcare Delivery for Indigenous Peoples: A Systematic Critical Synthesis and Exploration of the Cultural Safety Education Literature.

Cultural safety is increasingly being taught in tertiary programmes of study for health professionals. Reflexivity is a key skill required to engage in culturally safe practice, however, there is currently limited literature examining how reflexivity is taught or assessed within cultural safety curricula. A systematic review of the literature up until November 2021 was conducted, examining educational interventions which aimed to produce culturally safe learners.

High prevalence of fluoroquinolone-resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018-2020.

Background: Uropathogen resistance, fluoroquinolone-resistance (FQR), and extended spectrum beta-lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs).

Methods: We conducted a multi-center, observational cohort study using a network of 15 geographically diverse US EDs.

Characterisation of a nucleo-adhesome.

In addition to central functions in cell adhesion signalling, integrin-associated proteins have wider roles at sites distal to adhesion receptors. In experimentally defined adhesomes, we noticed that there is clear enrichment of proteins that localise to the nucleus, and conversely, we now report that nuclear proteomes contain a class of adhesome components that localise to the nucleus. We here define a nucleo-adhesome, providing experimental evidence for a remarkable scale of nuclear localisation of adhesion proteins, establishing a framework for interrogating nuclear adhesion protein functions.

European Stroke Organisation guidelines on stroke in women: Management of menopause, pregnancy and postpartum.

Pregnancy, postpartum and menopause are regarded as periods women are more vulnerable to ischaemic events. There are conflicting results regarding stroke risk and hormone replacement therapy (HRT) during menopause. Stroke in pregnancy is generally increasing with serious consequences for mother and child; therefore, recommendations for acute treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) are needed.

Developing high-quality value-added cereals for organic systems in the US Upper Midwest: hard red winter wheat (Triticum aestivum L.) breeding.

There is an increased demand for food-grade grains grown sustainably. Hard red winter wheat has comparative advantages for organic farm rotations due to fall soil cover, weed competition, and grain yields. However, limitations of currently available cultivars such as poor disease resistance, winter hardiness, and baking quality, challenges its adoption and use.

A Nanoscale Design Approach for Enhancing the Li-Ion Conductivity of the LiGePS Solid Electrolyte.

The discovery of the lithium superionic conductor LiGePS (LGPS) has led to significant research activity on solid electrolytes for high-performance solid-state batteries. Despite LGPS exhibiting a remarkably high room-temperature Li-ion conductivity, comparable to that of the liquid electrolytes used in current Li-ion batteries, nanoscale effects in this material have not been fully explored. Here, we predict that nanosizing of LGPS can be used to further enhance its Li-ion conductivity.