Content analysis of current role/job descriptors for Band 5/junior physiotherapists and mapping of these to Physiotherapy Professional standards of practice.

Background: KNOWBEST was a mixed methods study exploring the KNOWledge, BEhaviours and Skills required of the modern physioTherapy graduate.

Objectives: To undertake a content analysis of current role descriptors (RDs) for Band5/junior physiotherapists and map these to the knowledge, skills, behaviours and attributes required for contemporary physiotherapy practice.

Design: Content analyses and mapping.

Examining the acceptability and feasibility of the Compassionate Mindful Resilience (CMR) programme in adults living with chronic kidney disease: the COSMIC study findings.

Background: Individuals with chronic kidney disease experience difficult physical and psychological symptoms, that impact quality of life, and are at increased risk of anxiety and depression. Access to specialist psychological support is limited. This study aimed to support a new service development project, in collaboration with Kidney Care UK, to implement the Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, which provides accessible mindfulness techniques and practices to enhance compassion and resilience, and explore its feasibility for people living with stage 4 or 5 kidney disease and transplant.

Experiences of People with Kidney Disease Following the Implementation of the Compassionate Mindful Resilience Programme: Qualitative Findings from the COSMIC Study.

Background: Kidney disease is a progressive, debilitating condition. Patients experience challenging physical and psychological symptoms and are at increased risk of anxiety, depression, and poor mental wellbeing. Access to specialist psychological or social support is limited, with inadequate provision of psychosocial support available across UK renal units.

Consensus on a netball video analysis framework of descriptors and definitions by the netball video analysis consensus group.

Using an expert consensus-based approach, a netball video analysis consensus (NVAC) group of researchers and practitioners was formed to develop a video analysis framework of descriptors and definitions of physical, technical and contextual aspects for netball research. The framework aims to improve the consistency of language used within netball investigations. It also aims to guide injury mechanism reporting and identification of injury risk factors.

Examining the Acceptability and Feasibility of the Compassionate Mindful Resilience (CMR) Programme in Adult Patients with Chronic Kidney Disease: The COSMIC Study Protocol.

Kidney disease is often progressive, and patients experience diminished health-related quality of life. In addition, the impact of the coronavirus (COVID-19) pandemic, and its associated restrictions, has brought many additional burdens. It is therefore essential that effective and affordable systems are explored to improve the psychological health of this group that can be delivered safely during the COVID-19 pandemic.

Mindfulness as a well-being initiative for future nurses: a survey with undergraduate nursing students.

Background: Mindfulness can potentially positively impact well-being and resilience in undergraduate nursing students. The psychological well-being of such students undertaking clinical training is paramount to ensure optimal learning, and to equip them with skills to manage their wellbeing in future clinical practice. The aim of our study was to explore the views of undergraduate nursing students in relation to understanding and engaging with mindfulness, and how mindfulness could best be delivered within their university programme.

Changes in mood and health-related quality of life in Look AHEAD 6 years after termination of the lifestyle intervention.

Objective: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012.

Methods: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured.

Islet Autoimmunity in Adults With Impaired Glucose Tolerance and Recently Diagnosed, Treatment Naïve Type 2 Diabetes in the Restoring Insulin SEcretion (RISE) Study.

The presence of islet autoantibodies and islet reactive T cells (T+) in adults with established type 2 diabetes (T2D) have been shown to identify those patients with more severe β-cell dysfunction. However, at what stage in the progression toward clinical T2D does islet autoimmunity emerge as an important component influencing β-cell dysfunction? In this ancillary study to the Restoring Insulin SEcretion (RISE) Study, we investigated the prevalence of and association with β-cell dysfunction of T+ and autoantibodies to the 65 kDa glutamic acid decarboxylase antigen (GADA) in obese pre-diabetes adults with impaired glucose tolerance (IGT) and recently diagnosed treatment naïve (Ndx) T2D. We further investigated the effect of 12 months of RISE interventions (metformin or liraglutide plus metformin, or with 3 months of insulin glargine followed by 9 months of metformin or placebo) on islet autoimmune reactivity.

Precision and accuracy of hyperglycemic clamps in a multicenter study.

Application of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Two-stage hyperglycemic clamps with glucose targets of 200 mg/dL and >450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements.

Within-Trial Cost-Effectiveness of a Structured Lifestyle Intervention in Adults With Overweight/Obesity and Type 2 Diabetes: Results From the Action for Health in Diabetes (Look AHEAD) Study.

Objective: To assess the cost-effectiveness (CE) of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, as implemented in the Action for Health in Diabetes study.

Research Design And Methods: Data were from 4,827 participants during their first 9 years of study participation from 2001 to 2012. Information on Health Utilities Index Mark 2 (HUI-2) and HUI-3, Short-Form 6D (SF-6D), and Feeling Thermometer (FT), cost of delivering the interventions, and health expenditures was collected during the study.

Structural attributes influencing unbound tissue distribution.

Unbound tissue-to-plasma partition coefficients (K) were determined for 56 structurally diverse compounds in rats following intravenous infusion. Five tissues were included in the study: white adipose, brain, heart, liver, and skeletal muscle. The rank ordering of the median tissue K values was: liver (4.

Evaluation of Fraction Unbound Across 7 Tissues of 5 Species.

Binding to various tissues and species is frequently assessed in drug discovery and development to support safety and efficacy studies. To reduce time, cost, and labor requirements for binding experiments, we conducted a large comparison study to evaluate the correlation of fraction unbound (f) across 7 tissues of 5 species, including white adipose, brain, heart, kidney, liver, lung, and skeletal muscle of mouse, rat, dog, monkey, and human. The results showed that there were no significant species differences of f for tissue binding, and a single-species (e.

Association of Habitual Daily Physical Activity With Glucose Tolerance and β-Cell Function in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes From the Restoring Insulin Secretion (RISE) Study.

Objective: We examined the relationship between habitual daily physical activity and measures of glucose tolerance, insulin sensitivity, and β-cell responses in adults with impaired glucose tolerance (IGT) or drug-naive, recently diagnosed type 2 diabetes.

Research Design And Methods: Participants included 230 adults (mean ± SD age 54.5 ± 8.

A Novel Unified Approach to Predict Human Hepatic Clearance for Both Enzyme- and Transporter-Mediated Mechanisms Using Suspended Human Hepatocytes.

The accurate prediction of human pharmacokinetics is critically important in modern drug discovery since it drives both pharmacological and toxicological effects. Although significant progress has been made in predicting drug disposition by hepatic drug-metabolizing enzymes, predicting transporter-mediated clearance is still highly uncertain. Furthermore, different approaches are often used to predict clearance with and without transporter involvement, hence the major clearance pathway for a compound must first be determined to know which approach to use.

Metabolism and excretion of ()-6-(3-cyclopentyl-2-(4-trifluoromethyl)-1-imidazol-1-yl)propanamido)nicotinic acid (PF-04991532), a hepatoselective glucokinase activator, in humans: confirmation of the MIST potential noted in first-in-Human metabolite scouting studies.

1. The absorption, metabolism, and excretion of a single oral 450-mg dose of [C]-()-6-(3-cyclopentyl-2-(4-trifluoromethyl)-1-imidazol-1-yl)propanamido)nicotinic acid (PF-04991532), a hepatoselective glucokinase activator, was investigated in humans. Mass balance was achieved with ∼94.

Discovery of a Novel Small-Molecule Modulator of C-X-C Chemokine Receptor Type 7 as a Treatment for Cardiac Fibrosis.

C-X-C chemokine receptor type 7 (CXCR7) is involved in cardiac and immune pathophysiology. We report the discovery of a novel 1,4-diazepine CXCR7 modulator, demonstrating for the first time the role of pharmacological CXCR7 intervention in cardiac repair. Structure-activity-relationship (SAR) studies demonstrated that a net reduction in lipophilicity (log D) and an incorporation of saturated ring systems yielded compounds with good CXCR7 potencies and improvements in oxidative metabolic stability in human-liver microsomes (HLM).

Liver-Targeted Small-Molecule Inhibitors of Proprotein Convertase Subtilisin/Kexin Type 9 Synthesis.

Targeting of the human ribosome is an unprecedented therapeutic modality with a genome-wide selectivity challenge. A liver-targeted drug candidate is described that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered undruggable by small molecules. Key to the concept was the identification of pharmacologically active zwitterions designed to be retained in the liver.

Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.

The chemokine receptor CXCR7 is an attractive target for a variety of diseases. While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity. We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.

Novel Method to Predict In Vivo Liver-to-Plasma K for OATP Substrates Using Suspension Hepatocytes.

The ability to predict human liver-to-plasma unbound partition coefficient (K) is of great importance to estimate unbound liver concentration, develop PK/PD relationships, predict efficacy and toxicity in the liver, and model the drug-drug interaction potential for drugs that are asymmetrically distributed into the liver. A novel in vitro method has been developed to predict in vivo K with good accuracy using cryopreserved suspension hepatocytes in InVitroGRO HI media with 4% BSA. Validation was performed using six OATP substrates with rat in vivo K data from i.

Efficient Liver Targeting by Polyvalent Display of a Compact Ligand for the Asialoglycoprotein Receptor.

A compact and stable bicyclic bridged ketal was developed as a ligand for the asialoglycoprotein receptor (ASGPR). This compound showed excellent ligand efficiency, and the molecular details of binding were revealed by the first X-ray crystal structures of ligand-bound ASGPR. This analogue was used to make potent di- and trivalent binders of ASGPR.

In Vitro-In Vivo Extrapolation of Intestinal Availability for Carboxylesterase Substrates Using Portal Vein-Cannulated Monkey.

Prediction of intestinal availability (FF) of carboxylesterase (CES) substrates is of critical importance in designing oral prodrugs with optimal properties, projecting human pharmacokinetics and dose, and estimating drug-drug interaction potentials. A set of ester prodrugs were evaluated using in vitro permeability (parallel artificial membrane permeability assay and Madin-Darby canine kidney cell line-low efflux) and intestinal stability (intestine S9) assays, as well as in vivo portal vein-cannulated cynomolgus monkey. In vitro-in vivo extrapolation (IVIVE) of FF was developed with a number of modeling approaches, including a full physiologically based pharmacokinetic (PBPK) model as well as a simplified competitive-rate analytical solution.

Evaluation of a new topical skin protectant (RD1433) for the prevention and treatment of incontinence-associated dermatitis.

Context Incontinence-associated dermatitis (IAD) is a type of moisture-associated dermatitis caused by repeated skin exposure to urine or stool. A product that could mitigate such symptoms would have a significant impact on cost of care and patients' quality of life. Objective This study compared the clinical efficacy of RD1433 and a comparator product (Vaseline®) in preventing and treating experimental IAD skin lesions.

The detection of Felis catus papillomavirus 3 DNA in a feline bowenoid in situ carcinoma with novel histologic features and benign clinical behavior.

Bowenoid in situ carcinoma (BISC; papillomavirus-associated squamous cell carcinoma in situ) is an uncommon skin neoplasm of cats that can result in euthanasia because of the development of multiple lesions or because of progression to invasive squamous cell carcinoma. BISCs are currently thought to be caused by Felis catus papillomavirus 2 (FcaPV-2). The presently described cat developed a single 0.

Connectivity: An emerging concept for physiotherapy practice.

Having spent their first century anchored to a biomedical model of practice, physiotherapists have been increasingly interested in exploring new models and concepts that will better equip them for serving the health-care needs of 21st century clients/patients. Connectivity offers one such model. With an extensive philosophical background in phenomenology, symbolic interactionism, structuralism, and postmodern research, connectivity resists the prevailing western biomedical view that health professionals should aim to increase people's independence and autonomy, preferring instead to identify and amplify opportunities for collaboration and co-dependence.