A medical student elective promoting humanism, communication skills, complementary and alternative medicine and physician self-care: an evaluation of the HEART program.

ObjectiveIn 2002 the American Medical Student Association (AMSA) created a fourth-year medical student elective known as the Humanistic Elective in alternative medicine, Activism, and Reflective Transformation (HEART) that provided the opportunity for students to explore humanism in medicine, self-care, complementary and alternative medicine modalities, communication, activism, and community building in a four-week immersion experience. The educational effects of this elective, and whether it has met its stated goals, are unknown.MethodThe authors conducted a web-based, cross-sectional survey of the first eight cohorts of HEART graduates in 2010. Survey questions assessed respondents' demographics and perspectives on the educational impact of the elective. Descriptive statistics were used to characterize the sample and qualitative analyses were guided by grounded theory.ResultsOf 168 eligible alumni, 122 (73%) completed the survey. The majority were female (70%), age ≤35 (77%) years, and trained in primary care specialties (66%). Half were attendings in practice. The majority of respondents felt the elective taught professionalism (89%) and communication skills (92%) well or very well. The majority highly agreed that the elective helped them better cope with stress during residency training (80%), taught them self-care skills (75%), and improved their ability to empathize and connect with patients (71%). Qualitative analysis of the personal and professional impact of the elective identified twelve common themes with self-discovery, self-care, and collegial development/community most frequently cited.ConclusionsThe majority of HEART graduates endorse learning important skills and benefiting from the experience both personally and professionally. Aspects of the HEART curriculum may help training programs teach professionalism and improve trainee well-being

C-reactive protein and the risk of developing type 2 diabetes in Aboriginal Australians

OBJECTIVE: To investigate the association between C-reactive protein (CRP) and the risk of developing diabetes in Aboriginal Australians. RESEARCH DESIGN AND METHODS: High sensitivity CRP levels were measured in 620 Aboriginal participants aged 20-74 years free from diabetes at baseline in a remote community in the Northern Territory of Australia. Participants were followed for a median of 11 years to identify newly diagnosed cases of diabetes. Cox proportional hazards models were used to assess the relationship of CRP levels with the risk of developing diabetes over the follow-up period. RESULTS: A total of 109 participants were newly diagnosed with diabetes. Incident rates were 10.8, 16.6 and 28.8 per 1000 person-years for people in the lower, middle and upper tertile groups of baseline CRP levels, respectively. After adjusting for age, sex, BMI, baseline glucose regulation status, total cholesterol, urine albumin to creatinine ratio, systolic blood pressure, smoking and alcohol drinking, the association between diabetes and CRP remained significant, with a hazard ratio of 1.23 (95% confidence interval (CI) 1.05, 1.45) corresponding to a doubling in CRP values. Similarly, the adjusted hazard ratio for development of diabetes in people in the upper tertile versus the bottom two tertiles of CRP was 1.75 (95% CI 1.19, 2.56). CONCLUSIONS: CRP is independently associated with the development of diabetes in Aboriginal people. Our findings support a role of inflammation in the etiology of diabetes in the high risk population of Aboriginal Australians

Changes in Practice/Outcomes of Pediatric/Congenital Catheterization in Response to the First Wave of COVID.

BACKGROUND: The COVID-19 pandemic has posed tremendous stress on the health care system. Its effects on pediatric/congenital catheterization program practice and performance have not been described. OBJECTIVES: The purpose of this study was to evaluate how case volumes, risk-profile, and outcomes of pediatric/congenital catheterization procedures changed in response to the first wave of COVID-19 and after that wave. METHODS: A multicenter retrospective observational study was performed using Congenital Cardiac Catheterization Project on Outcomes Registry (C3PO) data to study changes in volume, case mix, and outcomes (high-severity adverse events [HSAEs]) during the first wave of COVID (March 1, 2020, to May 31, 2020) in comparison to the period prior to (January 1, 2019, to February 28, 2020) and after (June 1, 2020, to December 31, 2020) the first wave. Multivariable analyses adjusting for case type, hemodynamic vulnerability, and age group were performed. Hospital responses to the first wave were captured with an electronic study instrument. RESULTS: During the study period, 12,557 cases were performed at 14 C3PO hospitals (with 8% performed during the first wave of COVID and 32% in the postperiod). Center case volumes decreased from a median 32.1 cases/month (IQR: 20.7-49.0 cases/month) before COVID to 22 cases/month (IQR: 13-31 cases/month) during the first wave (P = 0.001). The proportion of cases with risk factors for HSAE increased during the first wave, specifically proportions of infants and neonates (P < 0.001) and subjects with renal insufficiency (P = 0.02), recent cardiac surgery (P < 0.001), and a higher hemodynamic vulnerability score (P = 0.02). The observed HSAE risk did not change significantly (P = 0.13). In multivariable analyses, odds of HSAE during the first wave of COVID (odds ratio: 0.75) appeared to be lower than that before COVID, but the difference was not significant (P = 0.09). CONCLUSIONS: Despite increased case-mix complexity, C3PO programs maintained, if not improved, their performance in terms of HSAE. Exploratory analyses of practice changes may inform future harm-reduction efforts

Interim guidelines for the assessment and treatment of pain in children with multiple sclerosis

IntroductionPain in multiple sclerosis (MS) is common, but literature on pain in children with MS remains scarce. Pain has physical, psychological, and social implications in MS, and both comprehensive assessment and interdisciplinary management approaches are needed. We sought to develop an interdisciplinary interim guideline for the assessment and management of pain in children with MS.Methods and materialsWe convened a modified Delphi panel composed of 13 experts in pediatric and adult MS neurology, physiotherapy, pain, patient lived-experience, advanced practice nursing, psychology, physiatry, and MS research. A survey was sent to panelists for anonymous completion. The panel discussed survey themes extracted by the panel chair. The process was repeated twice.ResultsThirteen assessment and treatment recommendations were produced regarding pain in children with MS.DiscussionFuture studies will assess implementation of these pain assessment and treatment guidelines in the clinical setting

Changes in weight and health behaviors after pregnancies complicated by gestational diabetes mellitus: The CARDIA Study

We compared pre- to post-pregnancy change in weight, body mass index (BMI), waist circumference, diet and physical activity in women with and without gestational diabetes mellitus (GDM).Using the Coronary Artery Risk Development in Young Adults (CARDIA) study we identified women with at least one pregnancy during 20 years of follow-up (n=1,488 with 3,125 pregnancies). We used linear regression with generalized estimating equations to compare pre- to post-pregnancy changes in health behaviors and anthropometric measurements between 137 GDM pregnancies and 1,637 non GDM pregnancies, adjusted for parity, age at delivery, outcome measure at the pre-pregnancy exam, race, education, mode of delivery, and interval between delivery and post-pregnancy examination.Compared with women without GDM in pregnancy, women with GDM had higher pre-pregnancy mean weight (158.3 vs. 149.6 lb, p=0.011) and BMI (26.7 vs. 25.1 kg/m2, p=0.002), but non-significantly lower total daily caloric intake and similar levels of physical activity. Both GDM and non GDM groups had higher average postpartum weight of 7–8 lbs and decreased physical activity on average 1.4 years after pregnancy. Both groups similarly increased total caloric intake but reduced fast food frequency. Pre- to post- pregnancy changes in body weight, BMI, waist circumference, physical activity and diet did not differ between women with and without GDM in pregnancy.Following pregnancy women with and without GDM increased caloric intake, BMI and weight, decreased physical activity, but reduced their frequency of eating fast food. Given these trends, postpartum lifestyle interventions, particularly for women with GDM, are needed to reduce obesity and diabetes risk

P04-41. Kinetics of Antibody Neutralization and Viral Evolution Following Envelope Vaccination in SIV-infected Rhesus Monkeys

Poster presentation. Conclusion: Our results indicate that env vaccination is associated with an accelerated development of autologous neutralizing antibodies. These antibodies were focused at least in part on the V1 region of Env, since there was selective pressure in this region of the envelope for the evolution of mutational changes

Ubiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling

Canonical Wnt signaling is controlled intracellularly by the level of β-catenin protein, which is dependent on Axin scaffolding of a complex that phosphorylates β-catenin to target it for ubiquitylation and proteasomal degradation. This function of Axin is counteracted through relocalization of Axin protein to the Wnt receptor complex to allow for ligand-activated Wnt signaling. AXIN1 and AXIN2 protein levels are regulated by tankyrase-mediated poly(ADP-ribosyl)ation (PARsylation), which destabilizes Axin and promotes signaling. Mechanistically, how tankyrase limits Axin protein accumulation, and how tankyrase levels and activity are regulated for this function, are currently under investigation. By RNAi screening, we identified the RNF146 RING-type ubiquitin E3 ligase as a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins. RNF146 also destabilizes tankyrases TNKS1 and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels. We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. RNF146 is a cytoplasmic protein that also prevents tankyrase protein aggregation at a centrosomal location. Tankyrase auto-PARsylation and PARsylation of Axin is known to lead to proteasome-mediated degradation of these proteins, and we demonstrate that, through ubiquitylation, RNF146 mediates this process to regulate Wnt signaling

Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1

We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1–5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1–5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV–macaque mucosal infection model for HIV-1 vaccine and microbicide research

Virus inhibition activity of effector memory CD8+ T cells determines simian immunodeficiency virus load in vaccinated monkeys after vaccine breakthrough infection

The goal of an effective AIDS vaccine is to generate immunity that will prevent human immunodeficiency virus 1 (HIV-1) acquisition. Despite limited progress toward this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies elicited by DNA prime-recombinant adenovirus serotype 5 (rAd5) boost vaccination with simian immunodeficiency virus strain mac239 (SIVmac239) Gag-Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge. Here, we report that SIV-specific CD8+ T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination. These SIV-specific CD8+ T cells showed strong virus-inhibitory activity (VIA) and displayed an effector memory (EM) phenotype. VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8+ T cells. Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8+ T cells. The ability to elicit such virus-specific EM CD8+ T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection

Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease

Background & aimsType 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.MethodsChildren with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.ResultsThis study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).ConclusionsChildren with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed