Careywoodard0493
The role of the gut in diabetes remission after Roux-en-Y gastric bypass (RYGB) is incompletely understood. We assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes.
Longitudinal, prospective measures of β-cell function were assessed after oral glucose intake and graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n = 29), 12 (n = 24), and 24 (n = 20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center.
The decreases in body weight, fat mass, waist circumference, and insulin resistance after surgery (all P < 0.001 at 12 and 24 months) did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose intake differed by remission status (P = 0.04) greater (6.5-fold; P < 0.01) and sustained in those in full remission, moderate and not sustained past 12 months in those with partial remission (3.3-fold; P < 0.001), and minimal in those not experiencing remission (2.7-fold; P = not significant). The improvement in β-cell function after IV glucose administration was not apparent until 12 months, significant only in those in full remission, and only ∼33% of that observed after oral glucose intake. Preintervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not.
Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.
Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.Front-line healthcare professionals have experienced rapid changes to workload and pressures during the COVID-19 pandemic, resulting in anxiety, depression and mental health stressors. For working professionals engaged in pharmacy postgraduate distance learning, access to educators was seen as a means to relay some of these stories and offload the stress caused by these unprecedented circumstances. The postgraduate pharmacy education team at De Montfort University felt a moral responsibility to provide extra support and extended their roles towards offering greater wellbeing support. In this commentary we detail the emergence of this new role and offer insights into how this was fashioned and its significance for catering to the mental health needs of pharmacists. This role has largely gone undetected and research is needed into the acceptability and feasibility of such a model and its plausibility and sustainability in the long term.Objective. Clinical documentation is an important element of patient care that pharmacy students traditionally learn through Subjective-Objective-Assessment-Plan (SOAP) notes. In clinical practice, pharmacists often document more succinctly both in regard to length and time; utilizing formats such as consult notes. The objective of this study was to assess consult note assignments for third-year pharmacy students (P3).Methods. Consult note assignments were implemented in a P3 skills laboratory course by converting SOAP notes to consult notes. The series began with an introduction and a practice consult note. Four graded notes were then completed throughout the semester with time allotted for writing decreasing throughout the semester. To assess the series, grades and estimated time for completion were collected for each graded note. A pre-post survey assessed student self-confidence in 1) overall documentation, 2) specific elements of consult notes, and 3) concerns related to writing. Friedman's tests were utilized to compare grades and time. Wilcoxon Signed Rank tests were used to compare self-assessments.Results. Median consult note grades were 92%, 88%, 80%, and 90% for each note. Median time for completion were 75 minutes, 120 minutes, 60 minutes, and 60 minutes. Student self-confidence in writing consult notes significantly increased as did five of the six individual elements.Conclusion. The consult note assignments allowed students to practice documenting patient care in a succinct format with consideration for time efficiency. Further work should evaluate best pedagogies for teaching documentation skills and assess the impact on performance during advanced pharmacy practice experiences.Perfluorinated carboxylic acids (PFCAs) are environmental pollutants for which human exposure has been documented. PFCAs at high doses were known regulate xenobiotic transporters partly through PPARα and CAR in rodents. Less is known regarding how various PFCAs at a lower concentration modulate transporters for endogenous substrates such as amino acids in human hepatocytes. Such studies are of particular importance because amino acids are involved in chemical detoxification and their transport system may serve as promising therapeutic targets for structurally similar xenobiotics. selleck chemicals The focus of this study was to further elucidate how PFCAs modulate transporters involved in intermediary metabolism and xenobiotic biotransformation. We tested the hepatic transcriptomic response of HepaRG cells exposed to 45 µM PFOA, PFNA, or PFDA in triplicates for 24 h (vehicle 0.1% DMSO), as well as the prototypical ligands for PPARα (WY-14643, 45 µM) and CAR (CITCO, 2 µM). PFCAs with increasing carbon chain lengths (C8-C10) regtransporters to limit further toxic exposures at concentrations lower than what was used in literature.Screening for cytochrome P450 (CYP) induction potential is routine in drug development. Induction results in a net increase in CYP protein and is assessed typically by measuring indirect endpoints, i.e., enzyme activity and mRNA in vitro. Recent methodological advancements have made CYP protein quantification by liquid chromatography-mass spectrometry in vitro induction studies more accessible and amenable to routine testing. In this study, we evaluated CYP3A4 concentration dependence of induction response for 11 compounds (rifampin, rifabutin, carbamazepine, efavirenz, nitrendipine, flumazenil, pioglitazone, rosiglitazone, troglitazone, pazopanib, and ticagrelor) in plated hepatocytes from two or three donors incorporating in the assessment all three endpoints. In addition, the time-dependence of the induction was examined over 1, 2, or 3 days of treatment. For most compounds, mRNA, enzyme activity, and protein endpoints exhibited similarity in induction responses. Pazopanib and ticagrelor were notable excepty is more complex than thought previously.
To assess whether incorporating a machine learning (ML) method for accurate prediction of postoperative anterior chamber depth (ACD) improves cataract surgery refraction prediction performance of a commonly used ray tracing power calculation suite (OKULIX).
A dataset of 4357 eyes of 4357 patients with cataract was gathered at the Kellogg Eye Center, University of Michigan. A previously developed machine learning (ML)-based method was used to predict the postoperative ACD based on preoperative biometry measured with the Lenstar LS900 optical biometer. Refraction predictions were computed with standard OKULIX postoperative ACD predictions and ML-based predictions of postoperative ACD. The performance of the ray tracing approach with and without ML-based ACD prediction was evaluated using mean absolute error (MAE) and median absolute error (MedAE) in refraction prediction as metrics.
Replacing the standard OKULIX postoperative ACD with the ML-predicted ACD resulted in statistically significant reductions in both MAE (1.7% after zeroing mean error) and MedAE (2.1% after zeroing mean error). ML-predicted ACD substantially improved performance in eyes with short and long axial lengths (p<0.01).
Using an ML-powered postoperative ACD prediction method improves the prediction accuracy of the OKULIX ray tracing suite by a clinically small but statistically significant amount, with the greatest effect seen in long eyes.
Using an ML-powered postoperative ACD prediction method improves the prediction accuracy of the OKULIX ray tracing suite by a clinically small but statistically significant amount, with the greatest effect seen in long eyes.
Classifying individuals at high chronic obstructive pulmonary disease (COPD)-risk creates opportunities for early COPD detection and active intervention.
To develop and validate a statistical model to predict 10-year probabilities of COPD defined by post-bronchodilator airflow obstruction (post-BD-AO; forced expiratory volume in 1 s/forced vital capacity<5th percentile).
General Caucasian populations from Australia and Europe, 10 and 27 centres, respectively.
For the development cohort, questionnaire data on respiratory symptoms, smoking, asthma, occupation and participant sex were from the Tasmanian Longitudinal Health Study (TAHS) participants at age 41-45 years (n=5729) who did not have self-reported COPD/emphysema at baseline but had post-BD spirometry and smoking status at age 51-55 years (n=2407). The validation cohort comprised participants from the European Community Respiratory Health Survey (ECRHS) II and III (n=5970), restricted to those of age 40-49 and 50-59 with complete questionnairer 40s at high 10-year COPD-risk in the general population with potential to facilitate active monitoring/intervention in predicted 'COPD cases' at a much earlier age.
This novel and validated risk-prediction model could identify adults aged in their 40s at high 10-year COPD-risk in the general population with potential to facilitate active monitoring/intervention in predicted 'COPD cases' at a much earlier age.
Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.
A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population.
Ethics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences.
NCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).
NCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).