Development and testing of a generic patient decision aid for end-of-life care.

Objectives: The objective of this study was to develop and test a patient decision aid for end-of-life care to be used when some or all life-sustaining treatments have been withheld or withdrawn.

Methods: A multi-professional, multi-sectorial group together with patients and relatives used a systematic process to develop and test the patient decision aid, including alpha and beta testing.

Results: Healthcare professionals, patients and relatives were involved in the development and testing.

Constructing representative group networks from tractography: lessons from a dynamical approach.

Human group connectome analysis relies on combining individual connectome data to construct a single representative network which can be used to describe brain organisation and identify differences between subject groups. Existing methods adopt different strategies to select the network structural features to be retained or optimised at group level. In the absence of ground truth, however, it is unclear which structural features are the most suitable and how to evaluate the consequences on the group network of applying any given strategy.

A qualitative study of dentists' and dental students' preparedness to support patients with lived experience of intimate partner violence and abuse.

Introduction Intimate partner violence and abuse (IPVA) is a public health crisis with long-term implications for an individual's mental and physical health. IPVA can result in head and neck trauma, including oral injuries, placing dentists in a unique position to be able to identify at-risk patients. It is therefore important to understand any barriers dentists may experience when supporting IPVA patients.

Towards non-invasive imaging through spinal-cord generated magnetic fields.

Non-invasive imaging of the human spinal cord is a vital tool for understanding the mechanisms underlying its functions in both healthy and pathological conditions. However, non-invasive imaging presents a significant methodological challenge because the spinal cord is difficult to access with conventional neurophysiological approaches, due to its proximity to other organs and muscles, as well as the physiological movements caused by respiration, heartbeats, and cerebrospinal fluid (CSF) flow. Here, we discuss the present state and future directions of spinal cord imaging, with a focus on the estimation of current flow through magnetic field measurements.

Task difficulty of visually guided gait modifications involves differences in central drive to spinal motor neurons.

Walking in natural environments requires visually guided modifications, which can be more challenging when involving sideways steps rather than longer steps. This exploratory study investigated whether these two types of modifications involve different changes in the central drive to spinal motor neurons of leg muscles. Fifteen adults [age: 36 ± 6 (SD) years] walked on a treadmill (4 km/h) while observing a screen displaying the real-time position of their toes.

Transfusion strategy trials excluding patients transfused outside the trial study period are more likely to report a trend favoring restrictive strategies: a meta-analysis.

Objectives: Some large, randomized trials investigating red cell transfusion strategies have significant numbers of transfusions administered outside the trial study period. We sought to investigate the potential impact of this methodological issue.

Study Design And Setting: Meta-analysis of randomized controlled trials (RCTs) comparing liberal vs restrictive transfusion strategies in cardiac surgery and acute myocardial infarction patients.

American Heart Association Cardiogenic Shock Registry: Design and Implementation.

Background: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States.

Methods: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity.

Technical Assistance for Systemic Change: Lessons Learned From a National Technical Assistance Center.

Despite the millions of dollars awarded annually by the United States Department of Education to build implementation capacity through technical assistance (TA), data on TA effectiveness are severely lacking. Foundational to the operationalization and consistent research on TA effectiveness is the development and use of standardized TA core competencies, practices, and structures. Despite advances toward a consistent definition of TA, a gap still exists in understanding how these competencies are used within an operationalized set of TA practices to produce targeted outcomes at both individual and organizational levels to facilitate implementation of evidence-based practices.

An exploration of footwear preferences, attitudes and beliefs in people with knee osteoarthritis: A qualitative study.

Background: Although footwear can improve pain and function in individuals with knee osteoarthritis (OA), perspectives about footwear in this population have not been explored.

Objectives: This qualitative study explored preferences, attitudes and beliefs about footwear in adults with knee OA.

Methods: Twenty individuals with a clinical diagnosis of knee OA (aged 45-79 years, 65% women) participated in semi-structured interviews about factors which influence footwear selection, the effect of footwear on knee symptoms, and footwear modifications.

Engineering of glycoside hydrolase family 7 cellobiohydrolases directed by natural diversity screening.

Protein engineering and screening of processive fungal cellobiohydrolases (CBHs) remain challenging due to limited expression hosts, synergy-dependency, and recalcitrant substrates. In particular, glycoside hydrolase family 7 (GH7) CBHs are critically important for the bioeconomy and typically difficult to engineer. Here, we target the discovery of highly active natural GH7 CBHs and engineering of variants with improved activity.

CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver.

Increased de novo lipogenesis (DNL) in white adipose tissue is associated with insulin sensitivity. Under both Normal-Chow-Diet and High-Fat-Diet, mice expressing a kinase inactive Cyclin-dependent kinase 6 (Cdk6) allele (K43M) display an increase in DNL in visceral white adipose tissues (VAT) as compared to wild type mice (WT), accompanied by markedly increased lipogenic transcriptional factor Carbohydrate-responsive element-binding proteins (CHREBP) and lipogenic enzymes in VAT but not in the liver. Treatment of WT mice under HFD with a CDK6 inhibitor recapitulates the phenotypes observed in K43M mice.

Endolysosomal trafficking controls yolk granule biogenesis in vitellogenic Drosophila oocytes.

Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly from studies in yeast and cultured mammalian cells, one challenge is to systematically evaluate the findings from these cell-based studies in multicellular organisms under physiological settings. One potentially valuable in vivo system to address this challenge is the vitellogenic oocyte in Drosophila, which undergoes extensive endocytosis by Yolkless (Yl), a low-density lipoprotein receptor (LDLR), to uptake extracellular lipoproteins into oocytes and package them into a specialized lysosome, the yolk granule, for storage and usage during later development.

Iatrogenic Alzheimer's disease in recipients of cadaveric pituitary-derived growth hormone.

Alzheimer's disease (AD) is characterized pathologically by amyloid-beta (Aβ) deposition in brain parenchyma and blood vessels (as cerebral amyloid angiopathy (CAA)) and by neurofibrillary tangles of hyperphosphorylated tau. Compelling genetic and biomarker evidence supports Aβ as the root cause of AD. We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt-Jakob disease (iCJD) after childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds.

Patient blood management guideline for adults with critical bleeding.

Introduction: The management of patients with critical bleeding requires a multidisciplinary approach to achieve haemostasis, optimise physiology, and guide blood component use. The 2011 Patient blood management guidelines: module 1 - critical bleeding/massive transfusion were updated and published. Systematic reviews were conducted for pre-specified research questions, and recommendations were based on meta-analyses of included studies.

Changes in attitudes, beliefs, and experiences related to pregnancy during graduate medical education training from 2005 to 2021.

Today, 50% of medical students are women, and residency and fellowship training years overlap with peak times for starting families. The authors describe attitudes toward pregnancy during residency and fellowship and report pregnancy rates and complications for female residents and resident partners across several decades. A web-based survey was emailed to 1,057 residents in 2005 (period 1) and 1,860 residents in 2021 (period 2).

Effects of variation in sample storage conditions and swab order on 16S vaginal microbiome analyses.

The composition of the human vaginal microbiome has been linked to a variety of medical conditions including yeast infection, bacterial vaginosis, and sexually transmitted infection. The vaginal microbiome is becoming increasingly acknowledged as a key factor in personal health, and it is essential to establish methods to collect and process accurate samples with self-collection techniques to allow large, population-based studies. In this study, we investigate if using AssayAssure Genelock, a nucleic acid preservative, introduces microbial biases in self-collected vaginal samples.

A Continuing Pharmacy Education (CPE) Program Assessing Cannabidiol (CBD) Knowledge and Confidence Among Practicing Pharmacists.

Increased patient utilization of cannabidiol (CBD) leads to potential drug interactions with various medications and questions posed to pharmacists. To quantify the knowledge gap of pharmacists on CBD and CBD-containing products and assess the degree a continuing pharmacy education (CPE) program alters pharmacist confidence and competency on CBD knowledge. A 1-h CPE activity was offered as a home study from May 9, 2022, through September 30, 2022.

Pathological beige remodeling induced by cancer cachexia depends on the disease severity and involves mainly the trans-differentiation of mature white adipocytes.

In cancer associated cachexia (CAC), white adipose tissue undergoes morphofunctional and inflammatory changes that lead to tissue dysfunction and remodeling. In addition to metabolic changes in white adipose tissues (WAT), adipose tissue atrophy has been implicated in several clinical complications and poor prognoses associated with cachexia. Adipocyte atrophy may be associated with increased beige remodeling in human CAC as evidenced by the "beige remodeling" observed in preclinical models of CAC.

CDK6 is essential for mesenchymal stem cell proliferation and adipocyte differentiation.

Overweight or obesity poses a significant risk of many obesity-related metabolic diseases. Among all the potential new therapies, stem cell-based treatments hold great promise for treating many obesity-related metabolic diseases. However, the mechanisms regulating adipocyte stem cells/progenitors (precursors) are unknown.

Adrenergic Reprogramming of Preexisting Adipogenic Trajectories Steer Naïve Mural Cells Toward Beige Differentiation.

In adult white adipose tissue, cold or β3-adrenoceptor activation promotes the appearance of thermogenic beige adipocytes. Our comprehensive single-cell analysis revealed that these cells arise through the reprogramming of existing adipogenic trajectories, rather than from a single precursor. These trajectories predominantly arise from SM22-expressing vascular mural progenitor cells.

VMHdm/c neuronal circuits regulate skeletal muscle PGC1-α via the sympathoadrenal drive.

Objective: To adapt to metabolically challenging environments, the central nervous system (CNS) orchestrates metabolism of peripheral organs including skeletal muscle. The organ-communication between the CNS and skeletal muscle has been investigated, yet our understanding of the neuronal pathway from the CNS to skeletal muscle is still limited. Neurons in the dorsomedial and central parts of the ventromedial hypothalamic nucleus (VMHdm/c) expressing steroidogenic factor-1 (VMHdm/c neurons) are key for metabolic adaptations to exercise, including increased basal metabolic rate and skeletal muscle mass in mice.

mutation in humans with pubertal failure alters GnRH transcript expression.

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to gonadotropin-releasing hormone (GnRH) deficits. Exome sequencing of two independent cohorts of IHH patients identified 12 rare missense variants in in 15 patients. encodes two distinct isoforms.