Circadian variation in gastric vagal afferent mechanosensitivity

Food intake is coordinated to cellular metabolism by clock gene expression with a master clock in the suprachiasmatic nucleus synchronized by light exposure. Gastric vagal afferents play a role in regulating food intake, but it is unknown whether they exhibit circadian variation in their mechanosensitivity. We aimed to determine whether gastric vagal afferents express clock genes and whether their response to mechanical stimuli oscillates throughout the light/dark cycle. Nodose ganglia were collected from 8-week-old female C57BL/6 mice every 3 h starting at lights off (1800 h) to quantify Bmal1, Per1, Per2, and Nr1d1 mRNA by qRT-PCR. Additionally in vitro single-fiber recordings of gastric vagal mechanoreceptors were taken at all time points. Per1, Per2, Bmal1, and Nr1d1 mRNA is expressed in the nodose ganglia and levels oscillated over a 24 h period. In mice fed ad libitum, gastric content was 3 times higher at 0000 h and 0300 h than 1200 h. The response of tension receptors to 3 g stretch was reduced by up to 70% at 2100 h, 0000 h, and 0300 h compared with 1200 h. Gastric mucosal receptor response to stroking with a 50 mg von Frey hair was 3 times greater at 1200 h and 1500 h than the response at 0000 h. Similar findings were obtained in mice fasted for 6 h or maintained in darkness for 3 d before study. Therefore, these changes do not result from food intake or the light/dark cycle. Thus, gastric vagal mechanoreceptors display circadian rhythm, which may act to control food intake differentially at different times of the day.Stephen J. Kentish, Claudine L. Frisby, David J. Kennaway, Gary A. Wittert, and Amanda J. Pag

Text Messaging in the Patient-Centered Medical Home to Improve Glucose Control and Retinopathy Screening.

Purpose: To evaluate the effectiveness of a text messaging program (TMP) to improve glucose control, retinopathy screening (RS) rates, and self-care behaviors in patients with uncontrolled type 2 diabetes. Methods: A single-group design with a quasi-systematic random sample (n=20) received educational/exhortational text messages on their cellular phones for 3 months. Subjects, 12 of whom identified as a minority ethnicity, were mostly male, aged 27-73 years. Results: Glucose control and RS rates improved significantly. Subjects (\u3e70%) reported changes in self-care behaviors. Conclusion: Leveraging ubiquitous technology, a TMP for patients with limited access to healthcare education, holds promis

Rethinking how we view gang members: An examination into affective, behavioral, and mental health predictors of UK gang-involved youth

Mental health difficulties, conduct problems, and emotional maladjustment predict a range of negative outcomes, and this may include gang involvement. However, few studies have examined how behavioral, mental health, socio-cognitive, and emotional factors all relate to adolescent gang involvement. This study examined 91 adolescents to compare non-gang and gang-involved youth on their conduct problems, emotional distress, guilt proneness, anxiety and depression, and use of moral disengagement and rumination. Analyses revealed that gang-involved youth had higher levels of anxiety, depression, moral disengagement, and rumination. Gang-involved youth also had higher levels of conduct disorder and exposure to violence, but they did not differ from non-gang youth on levels of emotional distress and guilt proneness. Discriminant function analysis further showed that conduct problems, moral disengagement, and rumination were the most important predictors of gang involvement. Discussion focuses on how intervention and prevention efforts to tackle gang involvement need to consider the mental health and behavioral needs of gang-involved youth. Further research is also needed to build an evidence-base that identifies the cause/effect relationship between mental health and gang involvement to inform best practice when tackling gang membership

Fold Family-Regularized Bayesian Optimization for Directed Protein Evolution

Directed Evolution (DE) is a technique for protein engineering that involves iterative rounds of mutagenesis and screening to search for sequences that optimize a given property (ex. binding affinity to a specified target). Unfortunately, the underlying optimization problem is under-determined, and so mutations introduced to improve the specified property may come at the expense of unmeasured, but nevertheless important properties (ex. subcellular localization). We seek to address this issue by incorporating a fold-specific regularization factor into the optimization problem. The regularization factor biases the search towards designs that resemble sequences from the fold family to which the protein belongs. We applied our method to a large library of protein GB1 mutants with binding affinity measurements to IgG-Fc. Our results demonstrate that the regularized optimization problem produces more native-like GB1 sequences with only a minor decrease in binding affinity. Specifically, the log-odds of our designs under a generative model of the GB1 fold family are between 41-45% higher than those obtained without regularization, with only a 7% drop in binding affinity. Thus, our method is capable of making a trade-off between competing traits. Moreover, we demonstrate that our active-learning driven approach reduces the wet-lab burden to identify optimal GB1 designs by 67%, relative to recent results from the Arnold lab on the same data

Implementing a graduate nursing program at a distance through an urban-rural partnership.

The purposes of this poster presentation are to 1) describe the implementation of a master’s of science in nursing (MSN) program by providing access to rigorous distance education to students living in rural Pennsylvania; 2) discuss building a critical mass of master’s prepared advanced practice nurse experts in rural communities; and 3) share formative and summative evaluation information. Through funding from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Bureau of Health Professions, Division of Nursing, the Jefferson School of Nursing (JSN) expanded its MSN program currently offered at the urban Philadelphia campus to the rural campus in Danville. Using the methodologies of live web-casting and live video over the Internet, distance students are afforded the opportunity to participate in a live classroom setting rather than experience the static distance methodology of reading through lectures themselves. For example, during the clinical courses, the faculty teaches onsite in Philadelphia webcasting to students in their rural homes so that they can view and hear the lecture. These newer technologies make possible real-time faculty-student dialogue, student-to-student dialogue, and enhance socialization. Furthermore, the use of advanced technologies allows distance students to discuss with peers and faculty alike, in real time, the problems, successes, and questions which arise during class and clinical practica, thereby enhancing critical thinking and diagnostic reasoning skills. This urban-rural partnership addresses increasing demands for educating greater numbers of master’s prepared advanced practice nurses to work in north and central rural Pennsylvania thus promoting access to health care in rural underserved communities

Implementing a Practice Doctorate Program at a Distance through an Urban-Rural Partnership

The purposes of this poster presentation are to 1) describe the implementation of a doctor of nursing practice (DNP) program by providing access to rigorous distance education to students living in rural Pennsylvania; 2) discuss building a critical mass of doctorally prepared advanced practice nurse experts in both urban and rural communities; and 3) share formative and summative evaluation information. Through funding from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Bureau of Health Professions, Division of Nursing, the Jefferson School of Nursing (JSN) expanded its DNP program currently offered at the urban Philadelphia campus to the rural campus in Danville. Using the methodologies of live web-casting and live video over the Internet, distance students are afforded the opportunity to participate in a live classroom setting rather than experience the static distance methodology of reading through lectures themselves. For example, during the applied biostatistics course, the faculty teaches onsite in Philadelphia projecting the SPSS and the database on screen so that students on both campuses can simultaneously view, hear, and interact with the discussion. There is a doctorally prepared faculty member onsite in Danville as a resource for the students. These newer technologies make possible real-time faculty-student dialogue, student-to-student dialogue, and enhance socialization. Furthermore, the use of advanced technologies allows distance students to discuss with peers and faculty alike, in real time, the problems, successes, and questions which arise during class and clinical practica, thereby enhancing critical thinking and diagnostic reasoning skills. This unique urban-rural partnership, made possible through advanced technologies, addresses increasing demands for educating greater numbers of doctorally prepared advanced practice nurses to work in north and central rural Pennsylvania, thus promoting access to health care in rural underserved communities. Other than in academia, there are no doctorally prepared advanced practice nurses employed in practice in the area

An operational measure of physician lifelong learning: its development, components and preliminary psychometric data

Despite the emphasis placed on physicians’ lifelong learning, no psychometrically sound instrument has been developed to provide an operational measure of the concept and its components among physicians. The authors designed this study to develop a tool for measuring physician lifelong learning, to identify its underlying components and to assess its psychometric properties. A 37-item questionnaire was developed, based on a review of literature and the results of two pilot studies. Psychometric analyses of the responses of 160 physicians identified 19 items that were included in the Jefferson Scale of Physician Lifelong Learning. Factor analysis of the 19 items showed five meaningful factors that were consistent with the definition and major features of lifelong learning. They were ‘need recognition’, ‘research endeavor’, ‘self-initiation’, ‘technical skills’ and ‘personal motivation’. The method of contrasted groups provided evidence in support of the validity of the five factors. The factors’ reliability was assessed by coefficient alpha. It is concluded that lifelong learning is a multifaceted concept, and its operational measure is feasible for evaluating different educational programs and for studying group differences among physicians

Development of an Instrument to Measure Lifelong Learning Among Physicians

No abstract available

Opioid agonist treatment and risk of death or rehospitalization following injection drug use–associated bacterial and fungal infections: A cohort study in New South Wales, Australia

Background AU Injecting-related: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly bacterial and fungal infections are associated : with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection. Methods and findings Data came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants’ index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages. Conclusions Following hospitalizations with injection drug use–associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder

Effect of incarceration and opioid agonist treatment transitions on risk of hospitalisation with injection drug use-associated bacterial infections: A self-controlled case series in New South Wales, Australia

Background: Transitional times in opioid use, such as release from prison and discontinuation of opioid agonist treatment (OAT), are associated with health harms due to changing drug consumption practices and limited access to health and social supports. Using a self-controlled (within-person) study design, we aimed to understand if these transitions increase risks of injection drug use-associated bacterial infections. Methods: We performed a self-controlled case series among a cohort of people with opioid use disorder (who had all previously accessed OAT) in New South Wales, Australia, 2001-2018. The outcome was hospitalisation with injecting-related bacterial infections. We divided participants’ observed days into time windows related to incarceration and OAT receipt. We compared hospitalization rates during focal (exposure) windows and referent (control) windows (i.e., 5-52 weeks continuously not incarcerated or continuously receiving OAT). We estimated adjusted incidence rate ratios (aIRR) using conditional logistic regression, adjusted for time-varying confounders. Results: There were 7590 participants who experienced hospitalisation with injecting-related bacterial infections (35% female; median age 38 years; 78% hospitalised with skin and soft-tissue infections). Risk for injecting-related bacterial infections was elevated for two weeks following release from prison (aIRR 1.45; 95%CI 1.22–1.72). Risk was increased during two weeks before (aIRR 1.89; 95%CI 1.59–2.25) and after (aIRR 1.91; 95%CI 1.54–2.36) discontinuation of OAT, and during two weeks before (aIRR 3.63; 95%CI 3.13–4.22) and after (aIRR 2.52; 95%CI 2.09–3.04) OAT initiation. Conclusion: Risk of injecting-related bacterial infections varies greatly within-individuals over time. Risk is raised immediately after prison release, and around initiation and discontinuation of OAT. Social contextual factors likely contribute to excess risks at transitions in incarceration and OAT exposure