An Undergraduate Health Care Experience Course Increases Confidence and Improves Student Understanding of Health Care Careers.

Increasing the health care work force is critical to underserved communities. Unfortunately, students in these areas lack accessibility to the clinical experiences needed to get an introductory understanding of careers in health care. Therefore, a health care experience (HCE) course was created for undergraduate students that included didactic training, active learning exercises, and coordinated shadowing experiences. To evaluate the effect of the HCE on student interest in science, health care, and rural health a study was performed on HCE participants. This study assessed student background, interest in health care, and plans for future careers in underserved settings. Students who enrolled in the HCE demonstrated high interest in science, health care, and rural health. Evaluation of student reflections indicated students attained novel learning, gained insights, and recognized the importance of communication. The HCE course students exhibited amplified confidence in HCEs and had a significant increase in understanding of health care compared with a control group of students who had not completed the HCE. Undergraduate institutions can include courses like the HCE into curricula to increase accessibility to career experiences for students interested in health care careers.

Clinical Prediction Models Combining Routine Clinical Measures Have High Accuracy in Identifying Youth-Onset Type 2 Diabetes Defined by Maintained Endogenous Insulin Secretion: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: With high prevalence of obesity and overlapping features between diabetes subtypes, accurately classifying youth-onset diabetes can be challenging. We aimed to develop prediction models that, using characteristics available at diabetes diagnosis, can identify youth who will retain endogenous insulin secretion at levels consistent with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We studied 2,966 youth with diabetes in the prospective SEARCH for Diabetes in Youth study (diagnosis age ≤19 years) to develop prediction models to identify participants with fasting C-peptide ≥250 pmol/L (≥0.75 ng/mL) after >3 years' (median 74 months) diabetes duration. Models included clinical measures at the baseline visit, at a mean diabetes duration of 11 months (age, BMI, sex, waist circumference, HDL cholesterol), with and without islet autoantibodies (GADA, IA-2A) and a Type 1 Diabetes Genetic Risk Score (T1DGRS). RESULTS: Models using routine clinical measures with or without autoantibodies and T1DGRS were highly accurate in identifying participants with C-peptide ≥0.75 ng/mL (17% of participants; 2.3% and 53% of those with and without positive autoantibodies) (area under the receiver operating characteristic curve [AUCROC] 0.95-0.98). In internal validation, optimism was very low, with excellent calibration (slope 0.995-0.999). Models retained high performance for predicting retained C-peptide in older youth with obesity (AUCROC 0.88-0.96) and in subgroups defined by self-reported race/ethnicity (AUCROC 0.88-0.97), autoantibody status (AUCROC 0.87-0.96), and clinically diagnosed diabetes types (AUCROC 0.81-0.92). CONCLUSIONS: Prediction models combining routine clinical measures at diabetes diagnosis, with or without islet autoantibodies or T1DGRS, can accurately identify youth with diabetes who maintain endogenous insulin secretion in the range associated with T2D.

Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.

Clinical prediction models combining routine clinical measures identify participants with youth-onset diabetes who maintain insulin secretion in the range associated with type 2 diabetes: The SEARCH for Diabetes in Youth Study.

Objective: With the high prevalence of pediatric obesity and overlapping features between diabetes subtypes, accurately classifying youth-onset diabetes can be challenging. We aimed to develop prediction models that, using characteristics available at diabetes diagnosis, can identify youth who will retain endogenous insulin secretion at levels consistent with type 2 diabetes (T2D). Methods: We studied 2,966 youth with diabetes in the prospective SEARCH study (diagnosis age ≤19 years) to develop prediction models to identify participants with fasting c-peptide ≥250 pmol/L (≥0.75ng/ml) after >3 years (median 74 months) of diabetes duration. Models included clinical measures at baseline visit, at a mean diabetes duration of 11 months (age, BMI, sex, waist circumference, HDL-C), with and without islet autoantibodies (GADA, IA-2A) and a Type 1 Diabetes Genetic Risk Score (T1DGRS). Results: Models using routine clinical measures with or without autoantibodies and T1DGRS were highly accurate in identifying participants with c-peptide ≥0.75 ng/ml (17% of participants; 2.3% and 53% of those with and without positive autoantibodies) (area under receiver operator curve [AUCROC] 0.95-0.98). In internal validation, optimism was very low, with excellent calibration (slope=0.995-0.999). Models retained high performance for predicting retained c-peptide in older youth with obesity (AUCROC 0.88-0.96), and in subgroups defined by self-reported race/ethnicity (AUCROC 0.88-0.97), autoantibody status (AUCROC 0.87-0.96), and clinically diagnosed diabetes types (AUCROC 0.81-0.92). Conclusion: Prediction models combining routine clinical measures at diabetes diagnosis, with or without islet autoantibodies or T1DGRS, can accurately identify youth with diabetes who maintain endogenous insulin secretion in the range associated with type 2 diabetes.

Maternal health and pregnancy outcomes in autosomal dominant tubulointerstitial kidney disease.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of chronic kidney disease. ADTKD pregnancy outcomes have not previously been described. Methods: A cross-sectional survey was sent to women from ADTKD families. Results: Information was obtained from 85 afffected women (164 term pregnancies) and 23 controls (50 pregnancies). Only 16.5% of genetically affected women knew they had ADTKD during pregnancy. Eighteen percent of ADTKD mothers had hypertension during pregnancy versus 12% in controls (p = 0.54) and >40% in comparative studies of chronic kidney disease in pregnancy. Eleven percent of births of ADTKD mothers were <37 weeks versus 0 in controls (p < 0.0001). Cesarean section occurred in 19% of pregnancies in affected women versus 38% of unaffected individuals (p = 0.06). Only 12% of babies required a neonatal intensive care unit stay. Conclusions: ADTKD pregnancies had lower rates of hypertension during pregnancy versus other forms of chronic kidney disease, which may have contributed to good maternal and fetal outcomes.

Survey of stigma across healthcare workers in an urban, academic medical center regarding perinatal patients using opioids.

BACKGROUND AND OBJECTIVES: To examine healthcare workers' attitudes towards pregnant woman using opioids across provider type, specialty, and years of service. METHODS: Cross-sectional, anonymous survey of healthcare workers at an urban, academic medical center regarding attitudes towards pregnant women using opioids. RESULTS: One hundred and nineteen surveys were completed. Nurses were less likely to feel sympathetic towards pregnant women that use opioids (p = .016). DISCUSSION AND CONCLUSIONS: Differences in attitudes towards pregnant women using opioids were found between clinicians and nurses. SCIENTIFIC SIGNIFICANCE: Training and experience may contribute to attitude differences towards pregnant women using opioids.

Revisiting our approach to behavioral health referrals.

This system of matching referrals to behavioral health practitioners' historical effectiveness seeks to strengthen patient outcomes.

A Longitudinal View of Disparities in Insulin Pump Use Among Youth with Type 1 Diabetes: The SEARCH for Diabetes in Youth Study.

Objective: To evaluate changes in insulin pump use over two decades in a national U.S. sample. Research Design and Methods: We used data from the SEARCH for Diabetes in Youth study to perform a serial cross-sectional analysis to evaluate changes in insulin pump use in participants <20 years old with type 1 diabetes by race/ethnicity and markers of socioeconomic status across four time periods between 2001 and 2019. Multivariable generalized estimating equations were used to assess insulin pump use. Temporal changes by subgroup were assessed through interactions. Results: Insulin pump use increased from 31.7% to 58.8%, but the disparities seen in pump use persisted and were unchanged across subgroups over time. Odds ratio for insulin pump use in Hispanic (0.57, confidence interval [95% CI] 0.45-0.73), Black (0.28, 95% CI 0.22-0.37), and Other race (0.49, 95% CI 0.32-0.76) participants were significantly lower than White participants. Those with ≤high school degree (0.39, 95% CI 0.31-0.47) and some college (0.68, 95% CI 0.58-0.79) had lower use compared to those with ≥bachelor's degree. Those with public insurance (0.84, 95% CI 0.70-1.00) had lower use than those with private insurance. Those with an annual household income <$25K (0.43, 95% CI 0.35-0.53), $25K-$49K (0.52, 95% CI 0.43-0.63), and $50K-$74K (0.79, 95% CI 0.66-0.94) had lower use compared to those with income ≥$75,000. Conclusion: Over the past two decades, there was no improvement in the racial, ethnic, and socioeconomic inequities in insulin pump use, despite an overall increase in use. Studies that evaluate barriers or test interventions to improve technology access are needed to address these persistent inequities.

Moving the Needle: Evidence of an Effective Study Strategy Intervention in a Community College Biology Course.

Many science, technology, engineering, and math (STEM) community college students do not complete their degree, and these students are more likely to be women or in historically excluded racial or ethnic groups. In introductory courses, low grades can trigger this exodus. Implementation of high-impact study strategies could lead to increased academic performance and retention. The examination of study strategies rarely occurs at the community college level, even though community colleges educate approximately half of all STEM students in the United States who earn a bachelor's degree. To fill this research gap, we studied students in two biology courses at a Hispanic-serving community college. Students were asked their most commonly used study strategies at the start and end of the semester. They were given a presentation on study skills toward the beginning of the semester and asked to self-assess their study strategies for each exam. We observed a significantly higher course grade for students who reported spacing their studying and creating drawings when controlling for demographic factors, and usage of these strategies increased by the end of the semester. We conclude that high-impact study strategies can be taught to students in community college biology courses and result in higher course performance.

Dyspareunia: Keys to biopsychosocial evaluation and treatment planning.

Asking the questions identified here can guide your care. Knowing which treatment options are-and aren't-supported by the evidence is also key.

Utility of Diabetes Type-Specific Genetic Risk Scores for the Classification of Diabetes Type Among Multiethnic Youth.

OBJECTIVE: Genetic risk scores (GRS) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S. RESEARCH DESIGN AND METHODS: We generated type 1 diabetes (T1D)- and type 2 diabetes (T2D)-specific GRS in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA+/-) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other). RESULTS: T1D and T2D GRS were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA+/IS group and lowest in the DAA-/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA+/IR and DAA-/IS individuals had a greater probability of T1D than T2D. In DAA- individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency. CONCLUSIONS: Diabetes type-specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA- children.

Instructor facilitation mediates students' negative perceptions of active learning instruction.

Studies have demonstrated students' resistance to active learning, despite evidence illustrating that their learning is improved relative to students in lectures. Specifically, while active learning and group work are effective at engaging students in their learning process, studies report that students' perceptions of active learning approaches are not always positive. What remains underexplored is whether students' perceptions of active learning improve with effective instructor facilitation and whether there exists differential perceptions between racially minoritized students and represented students. Here, we estimate students' perceptions of effective instructor facilitation as the mediator in the relationship between active learning and perceptions of learning and perceived utility for class activities (task value). Then, we examine differences by racial identification. We collected classroom observation data to empirically categorize courses as active learning or lecture-based and surveyed 4,257 college students across 25 STEM classrooms at a research-intensive university. We first examined the relationship between active learning on student perceptions and found a negative relationship between active learning and perceptions of learning and task value for both racially minoritized students and represented students. Next, we assessed whether students' perceptions of instructor effectiveness in facilitating group activities mediate these negative relationships. We found that, on average, students of all races were more likely to positively perceive instructor facilitation in active learning classes relative to lectures. In turn, the positive perceptions of instructor facilitation partially suppressed the negative relationship between active learning and perceptions of learning and task value. These results demonstrate that effective instructor facilitation can influence both students' self-assessment of learning and perceived utility of the learning activities, and underscores the importance of developing pedagogical competence among college instructors.

Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors.

Adenosine A2A receptor mediates the promotion of wound healing and revascularization of injured tissue, in healthy and animals with impaired wound healing, through a mechanism depending upon tissue plasminogen activator (tPA), a component of the fibrinolytic system. In order to evaluate the contribution of plasmin generation in the proangiogenic effect of adenosine A2A receptor activation, we determined the expression and secretion of t-PA, urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and annexin A2 by human dermal microvascular endothelial cells stimulated by the selective agonist CGS-21680. The plasmin generation was assayed through an enzymatic assay and the proangiogenic effect was studied using an endothelial tube formation assay in Matrigel. Adenosine A2A receptor activation in endothelial cells diminished the release of PAI-1 and promoted the production of annexin A2, which acts as a cell membrane co-receptor for plasminogen and its activator tPA. Annexin A2 mediated the increased cell membrane-associated plasmin generation in adenosine A2A receptor agonist treated human dermal microvascular endothelial cells and is required for tube formation in an in vitro model of angiogenesis. These results suggest a novel mechanism by which adenosine A2A receptor activation promotes angiogenesis: increased endothelial expression of annexin A2, which, in turn, promotes fibrinolysis by binding tPA and plasminogen to the cell surface.

Seven practical strategies to add active learning to a science lecture.

Multiple research studies have shown active learning can increase student performance, reduce fail rates, and increase the success of marginalized students in STEM. In this mini-review we discuss a simple framework for planning and implementing active learning in the classroom. We provide seven strategies to support faculty members who want to implement this framework, with five suggested teaching activities and two mechanisms of creating space in the lecture to use the activities. Each strategy is given with a foundational research paper describing the evidence that it improves learning, engagement and inclusion in the classroom. We include our own experiences using these strategies in large biology lectures that had segments devoted to neuroscience topics, but they are effective in smaller classes as well.

The Next Step in Integrated Care: Universal Primary Mental Health Providers.

Current models of mental health care often do not address three barriers to mental health: the binary view of mental illness (healthy vs. mentally ill), stigma, and prevention. Care models where some patients are selected for referral or consultation with a mental health professional can reinforce this binary view and the stigma associated with seeing mental health services. By only selecting patients who currently are experiencing mental health problems, current integrated care models do not offer sufficient avenues for prevention. To address these barriers, this article proposes building on current models through the development of primary mental health providers (PMHPs). PMHPs-like primary care providers-would provide regular check-ups, assessments, prevention interventions, first-line treatment, or referral to more specialized professionals. This universal approach will help decrease the binary view of mental health, decrease the stigma of seeing a mental health professional through universal access, and improve prevention efforts.

Genome-Wide Association Study Identifies Loci for Liver Enzyme Concentrations in Mexican Americans: The GUARDIAN Consortium.

OBJECTIVE: Populations of Mexican American ancestry are at an increased risk for nonalcoholic fatty liver disease. The objective of this study was to determine whether loci in known and novel genes were associated with variation in aspartate aminotransferase (AST) (n = 3,644), alanine aminotransferase (ALT) (n = 3,595), and gamma-glutamyl transferase (GGT) (n = 1,577) levels by conducting the first genome-wide association study (GWAS) of liver enzymes, which commonly measure liver function, in individuals of Mexican American ancestry. METHODS: Levels of AST, ALT, and GGT were determined by enzymatic colorimetric assays. A multi-cohort GWAS of individuals of Mexican American ancestry was performed. Single-nucleotide polymorphisms (SNP) were tested for association with liver outcomes by multivariable linear regression using an additive genetic model. Association analyses were conducted separately in each cohort, followed by a nonparametric meta-analysis. RESULTS: In the PNPLA3 gene, rs4823173 (P = 3.44 × 10-10 ), rs2896019 (P = 7.29 × 10-9 ), and rs2281135 (P = 8.73 × 10-9 ) were significantly associated with AST levels. Although not genome-wide significant, these same SNPs were the top hits for ALT (P = 7.12 × 10-8 , P = 1.98 × 10-7 , and P = 1.81 × 10-7 , respectively). The strong correlation (r2 = 1.0) for these SNPs indicated a single hit in the PNPLA3 gene. No genome-wide significant associations were found for GGT. CONCLUSIONS: PNPLA3, a locus previously identified with ALT, AST, and nonalcoholic fatty liver disease in European and Japanese GWAS, is also associated with liver enzymes in populations of Mexican American ancestry.

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.

Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared with the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.

An Online, Self-Directed Curriculum of Core Research Concepts and Skills.

Introduction: Existing scholarly curricula often underemphasize basic research skills and do not address the individual learning needs of residents, whose level of prior exposure to research concepts varies widely. A supplemental educational experience was developed to address educational gaps in a family medicine residency curriculum, including systematic exploration and interpretation of the medical literature, development and exploration of clinically pertinent questions, and development of residents' written communication skills. Methods: A 2-week, online, self-directed research curriculum was developed. The five-module curriculum included (I) Research Methods and Data Analysis, (II) Article Review, (III) Board Review, (IV) Literature Search, and (V) Literature Review and Proposal. Two years after implementation, residents who completed the curriculum were surveyed to assess the overall rotation and its success in meeting learning objectives. Results: Eighteen residents completed the new rotation and demonstrated objectives through assignment completion and review. Additionally, residents reported improved skills on all objectives and were satisfied with the new curriculum and its self-led, online format. Those planning to do research after graduation were more likely to report several benefits from the rotation, including learning more about data analyses and being more likely to complete a future scholarly project. Discussion: An online, self-directed curriculum can provide a feasible and effective educational approach to efficient use of faculty and resident time, allowing time to be focused on resident-specific knowledge gaps and learning needs, rather than presenting all learning material uniformly. The online, accessible format aligned with residents' existing reliance on the internet as a primary information source.

Posttraumatic stress disorder: Often missed in primary care.

DeSean W, a 47-year-old man, returned to his primary care clinic with a new complaint of epigastric burning that had been bothering him for the past 4 months. He had tried several over-the-counter remedies, which provided no relief. He also remained concerned--despite assurances to the contrary at previous clinic visits--that he had contracted a sexually-transmitted disease (STD) after going to a bar one night 4 to 5 months ago. At 2 other clinic visits since that time, STD test results were negative. At this current visit, symptoms and details of sexual history were unchanged since the last visit, with the exception of the epigastric pain. When asked if he thought he had contracted an STD through a sexual encounter the night he went to the bar, he emphatically said he would not cheat on his wife. Surprisingly, given his concern, he avoided further discussion on modes of contracting an STD. The physician prescribed ranitidine 150 mg bid for the epigastric burning and explained, once more, the significance of the STD test results. However, he also decided to further examine Mr. W's concern about STDs and the night he may have contracted one. HOW WOULD YOU PROCEED WITH THIS PATIENT?