PURA and GLUT1: Sweet partners for brain health.

PURA, also known as Pur-alpha, is an evolutionarily conserved DNA/RNA-binding protein crucial for various cellular processes, including DNA replication, transcriptional regulation, and translational control. Comprising three PUR domains, it engages with nucleic acids and has a role in protein-protein interactions. The manifestation of PURA syndrome, arising from mutations in the PURA gene, presents neurologically with developmental delay, hypotonia, and seizures. In our prior work from 2018, we highlighted the unique case of a PURA patient displaying hypoglycorrhachia, suggesting a potential association with GLUT1 dysfunction in this syndrome. In this current study, we expand the patient cohort with PURA mutations exhibiting hypoglycorrhachia and aim to unravel the molecular basis of this phenomenon. We established an in vitro model in HeLa cells to modulate PURA expression and investigated GLUT1 function and expression. Our findings indicate that PURA levels directly impact glucose uptake through the functioning of GLUT1, without influencing significantly GLUT1 expression. Moreover, our study reveals evidence for a possible physical interaction between PURA and GLUT1, demonstrated by colocalization and co-immunoprecipitation of both proteins. Computational analyses, employing molecular dynamics, further corroborates these findings, demonstrating that PURA:GLUT1 interactions are plausible, and that the stability of the complex is altered when PURA is truncated and/or mutated. In conclusion, our results suggest that PURA plays a pivotal role in driving the function of GLUT1 for glucose uptake, potentially forming a regulatory complex. Additional investigations are warranted to elucidate the precise mechanisms governing this complex and its significance in ensuring proper GLUT1 function.

Working Toward a Gold Standard: The Severity of Ethanol Withdrawal Scale (SEWS) Versus the Clinical Institute Withdrawal Assessment Alcohol Scale (CIWA-Ar).

AIM: Proving the Severity of Ethanol Withdrawal Scale (SEWS) significantly reduces Alcohol Withdrawal Syndrome (AWS) treatment Time on Medication Protocol (TOMP). METHOD: Head-to-head Quality Assurance outcome compared separate cohorts of SEWS or Clinical Institute Withdrawal Assessment Alcohol Scale, Revised (CIWA-Ar) data using Student's t and Wilcoxon tests. RESULTS: SEWS-driven treatment (n = 244) reduced TOMP to 2.2 days versus 3.4 days for CIWA-Ar (n = 137); P < 0.0001. CONCLUSION: The SEWS is the superior measure of AWS symptoms.

A multisite randomized trial of implicit versus explicit modeling in clinical teaching.

PURPOSE: Faculty modeling of desired behaviors has historically been a part of the apprenticeship model of clinical teaching, yet little is known about best practices for modeling. This study compared the educational impact of implicitly versus explicitly modeled communication skills among U.S. medical students. METHOD: Fourth-year medical students from six U.S. academic medical centers were randomly assigned one simulated clinical encounter in which faculty provided either implicit or explicit modeling of important communication skills. Outcomes were assessed by electronic surveys immediately before and after the simulations. Students were blinded to the purpose of the study. RESULTS: Students in the explicit arm were more likely to correctly cite two of the three key specific communication elements modeled by faculty: deliberate body position (53.3% vs. 18.6%, p < 0.001) and summarizing patient understanding (62.2% vs. 11.6%, p < 0.001). More students in the explicit study arm reported faculty 'demonstrated a key behavior that they wanted me to be able to perform in the future' (93.2% versus 62.8%, p = 0.002). Participating faculty stated they would modify their teaching approach in response to their experiences in the study. CONCLUSIONS: In a multi-center randomized trial, explicit faculty role-modeling led to greater uptake of communication knowledge, greater recognition of skills, and a greater sense that faculty expected these skills to be adopted by students. These results must be considered in the context, however, of a simulated environment and a short timeframe for assessing learning with students who volunteered for a simulated experience.

Double Trouble: A Unique Case of Hypercalcemia Caused by Two Underlying Etiologies.

Hypercalcemia has a variety of causes, with primary hyperparathyroidism and malignancies being the most frequently reported. We present the case of a patient presenting with chronic abdominal pain, constipation, and weight loss who was found to have hypercalcemia. The patient was initially diagnosed with colonic actinomycosis, but further investigations revealed an intra-abdominal diffuse large B-cell lymphoma (DLBCL). We suspect that the leading cause of hypercalcemia was the DLBCL, likely exacerbated by actinomycosis. Actinomycosis and DLBCL can have a similar presentation, so misdiagnosis or coexistence of both conditions should be suspected when a lack of response to one specific therapy is observed.

Development and Validation of a Test for Competence in Evidence-Based Medicine.

BACKGROUND: Medical educators need valid, reliable, and efficient tools to assess evidence-based medicine (EBM) knowledge and skills. Available EBM assessment tools either do not assess skills or are laborious to grade. OBJECTIVE: To validate a multiple-choice-based EBM test-the Resident EBM Skills Evaluation Tool (RESET). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 304 medicine residents from five training programs and 33 EBM experts comprised the validation cohort. MAIN MEASURES: Internal reliability, item difficulty, and item discrimination were assessed. Construct validity was assessed by comparing mean total scores of trainees to experts. Experts were also asked to rate importance of each test item to assess content validity. KEY RESULTS: Experts had higher total scores than trainees (35.6 vs. 29.4, P < 0.001) and also scored significantly higher than residents on 11/18 items. Cronbach's alpha was 0.6 (acceptable), and no items had a low item-total correlation. Item difficulty ranged from 7 to 86%. All items were deemed "important" by > 50% of experts. CONCLUSIONS: The proposed EBM assessment tool is a reliable and valid instrument to assess competence in EBM. It is easy to administer and grade and could be used to guide and assess interventions in EBM education.

PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature.

BACKGROUND: De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. OBJECTIVES: To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. METHODS: Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes. RESULTS: We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. CONCLUSION: We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.

Impact of Altered Medication Administration Time on Interdisciplinary Bedside Rounds on Academic Medical Ward.

Interdisciplinary rounds provide a valuable venue for delivering patient-centered care but are difficult to implement due to time constraints and coordination challenges. In this article, we describe a unique model for fostering a culture of bedside interdisciplinary rounds through adjustment of the morning medication administration time, auditing physician communication with nurses, and displaying physician performance in public areas. Implementation of this model led to measurable improvements in physician-to-nurse communication on rounds, teamwork climate, and provider job satisfaction.

Attending rounds in the current era: what is and is not happening.

IMPORTANCE: General medicine rounds by attending physicians provide the foundation for patient care and education in teaching hospitals. However, the detailed activities of these rounds in the current era are not well characterized. OBJECTIVE: To describe the characteristics of attending rounds for internal medicine inpatients in a large teaching hospital system. DESIGN: A cross-sectional observational study of attending rounds in internal medicine. Rounds were observed directly by research assistants. SETTING: Four teaching hospitals associated with a large public medical school. PARTICIPANTS: Fifty-six attending physicians and 279 trainees treating 807 general medicine inpatients. MAIN OUTCOMES AND MEASURES: Duration and location of rounds, composition of teams, and frequency of 19 potential activities during rounds. RESULTS: We observed 90 days of rounds. A typical rounding day consisted of 1 attending with 3 trainees visiting a median of 9 (range, 2-18 [SD, 2.9]) patients for a median of 2.0 hours (range, 25-241 [SD, 2.7] minutes). On rounds, teams most frequently discussed the patient care plan (96.7% of patients), reviewed diagnostic studies (90.7%), communicated with patients (73.4%), and discussed the medication list (68.8%). Teams infrequently discussed invasive lines or tubes (9.3%) or nursing notes (6.2%) and rarely communicated with nurses (12.0%) or taught physical examination skills (14.6%), evidence-based medicine topics (7.2%), or learner-identified topics (3.2%). Many commonly performed activities occurred infrequently at the bedside. CONCLUSIONS AND RELEVANCE: Most activities on attending rounds do not take place at the bedside. The teams discuss patient care plans and test results most of the time but fail to include many items that may be of significant value, including specific aspects of patient care, interprofessional communication, and learner-centered education. Future studies are needed to further assess the implications of these observations.