Perceptions of 24/7 In‐house Attending Coverage on Fellow Education and Autonomy in a Pediatric Cardiothoracic Intensive Care Unit

BackgroundThe 24/7 in‐house attending coverage is emerging as the standard of care in intensive care units. Implementation costs, workforce feasibility, and patient outcomes resulting from changes in physician staffing are widely debated topics. Understanding the impact of staffing models on the learning environment for medical trainees and faculty is equally warranted, particularly with respect to trainee education and autonomy.ObjectiveThis study aims to elicit the perceptions of pediatric cardiology fellows and attendings toward 24/7 in‐house attending coverage and its effect on fellow education and autonomy.MethodsWe surveyed pediatric cardiology fellows and attendings practicing in the pediatric cardiothoracic intensive care unit (PCTU) of a large, university‐affiliated medical center, using structured Likert response items and open‐ended questions, prior to and following the transition to 24/7 in‐house attending coverage.ResultsAll (100%) trainees and faculty completed all surveys. Both prior to and following transition to 24/7 in‐house attending coverage, all fellows, and the majority of attendings agreed that the overnight call experience benefited fellow education. At baseline, trainees identified limited circumstances in which on‐site attending coverage would be critical. Preimplementation concerns that 24/7 in‐house attending coverage would negatively affect the education of fellows were not reflected following actual implementation of the new staffing policy. However, based upon open‐ended questions, fellow autonomy was affected by the new paradigm, with fellows and attendings reporting decreased “appropriateness” of autonomy after implementation.ConclusionsOur prospective study, showing initial concerns about limiting the learning environment in transitioning to 24/7 in‐house attending coverage did not result in diminished perceptions of the educational experience for our fellows but revealed an expected decrease in fellow autonomy. The study indirectly facilitated open discussions about methods to preserve fellow education and warranted autonomy in our PCTU; however, continued efforts are needed to achieve the optimal balance between supervised training and the transition to autonomous practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111990/1/chd12261.pd

Oral health knowledge, attitudes and practices of people living with diabetes in South Asia : a scoping review

Diabetes increases the risk of oral health complications. This review aimed to synthesise the current evidence on the oral health knowledge, attitudes and practices of people living with diabetes in South Asian countries and provide recommendations on possible strategies for addressing the gaps in oral health care in this population, including the role of non-dental professionals. Using a scoping review framework, six electronic databases (Ovid Medline, CINAHL, ProQuest Central, Scopus, Web of Science and Embase) were searched to identify the relevant literature published between January 2000 and December 2021. The data were extracted into three main categories based on the review’s aims, and further refined into sub-categories. A total of 23 studies were included. The review identified that while people with diabetes living in South Asian countries had some level of awareness about oral health and limited care practices to maintain good oral health, there were gaps in knowledge, and there were areas where their oral health practices and attitudes could be improved. The findings suggest a need for developing targeted oral health policies as well as implementing integrated oral health care interventions involving non-dental professionals to improve the oral health outcomes of people with diabetes

The Tudor-domain protein TDRD7, mutated in congenital cataract, controls the heat shock protein HSPB1 (HSP27) and lens fiber cell morphology

Mutations of the RNA granule component TDRD7 (OMIM: 611258) cause pediatric cataract. We applied an integrated approach to uncover the molecular pathology of cataract in Tdrd7−/− mice. Early postnatal Tdrd7−/− animals precipitously develop cataract suggesting a global-level breakdown/misregulation of key cellular processes. High-throughput RNA sequencing integrated with iSyTE-bioinformatics analysis identified the molecular chaperone and cytoskeletal modulator, HSPB1, among high-priority downregulated candidates in Tdrd7−/− lens. A protein fluorescence two-dimensional difference in-gel electrophoresis (2D-DIGE)-coupled mass spectrometry screen also identified HSPB1 downregulation, offering independent support for its importance to Tdrd7−/− cataractogenesis. Lens fiber cells normally undergo nuclear degradation for transparency, posing a challenge: how is their cell morphology, also critical for transparency, controlled post-nuclear degradation? HSPB1 functions in cytoskeletal maintenance, and its reduction in Tdrd7−/− lens precedes cataract, suggesting cytoskeletal defects may contribute to Tdrd7−/− cataract. In agreement, scanning electron microscopy (SEM) revealed abnormal fiber cell morphology in Tdrd7−/− lenses. Further, abnormal phalloidin and wheat germ agglutinin (WGA) staining of Tdrd7−/− fiber cells, particularly those exhibiting nuclear degradation, reveals distinct regulatory mechanisms control F-actin cytoskeletal and/or membrane maintenance in post-organelle degradation maturation stage fiber cells. Indeed, RNA immunoprecipitation identified Hspb1 mRNA in wild-type lens lysate TDRD7-pulldowns, and single-molecule RNA imaging showed co-localization of TDRD7 protein with cytoplasmic Hspb1 mRNA in differentiating fiber cells, suggesting that TDRD7–ribonucleoprotein complexes may be involved in optimal buildup of key factors. Finally, Hspb1 knockdown in Xenopus causes eye/lens defects. Together, these data uncover TDRD7’s novel upstream role in elevation of stress-responsive chaperones for cytoskeletal maintenance in post-nuclear degradation lens fiber cells, perturbation of which causes early-onset cataracts

Anxiety Sensitivity and Sleep Problems among Homeless Adults

Anxiety sensitivity (AS) is a transdiagnostic individual difference factor, reflecting amplified fear about the negative consequences of anxiety-related autonomic arousal. AS has been linked to sleep problems and serious mental/physical health conditions in the domiciled population. No previous research has examined how AS affects sleep among homeless adults who are vulnerable to health disparities and living in harsh environments that may, by their nature, compromise sleep integrity. The purpose of this study was to investigate the association between AS and sleep-related problems among homeless adults. AS was significantly associated with more days of inadequate sleep (p < 0.001), fewer hours of sleep per day (p < 0.01), unintentionally falling asleep (p ≤ 0.01) in this convenience sample of predominately male homeless adults. See Tables 1 and 2. Results suggest that AS may be a risk factor conferring additional vulnerability to sleep- related problems among homeless adults. This project was completed with contributions from Michael S. Businelle from the Oklahoma Tobacco Research Center, University of Oklahoma Health Sciences Center.Psychological, Health, and Learning Sciences, Department ofHonors Colleg

Platinum (IV) azido complexes undergo copper-free click reactions with alkynes

We report our investigations into the first examples of copper-free 1,3-dipolar cycloaddition (click) reactions of electrophiles with a PtIV azido complex. The Pt-IV azido complex trans, trans, trans-[PtIV(py)2(N3)2(OH)2] (1) was reactive towards dimethyl acetylenedicarboxylate (DMAD) (2), diethyl acetylenedicarboxylate DEACD (3), N-[(1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonyl]-1,8-diamino-3,6-dioxaoctane (BCN) (11) and dibenzocyclooctyne-amine (DBCO) (12) resulting in formation of the corresponding mono (a) and bis-substituted (b) complexes. Complexes of 2 undergo further reactions between the Pt centre and the carbonyl group to form 2a′ and 2b′. This is not seen for the products of the corresponding PtII azido complex trans-[Pt(py)2(N3)2] with acetylene 2. Novel complexes 2a′, 2b′, 11a and 11b have been characterised by multinuclear NMR, IR and UV-vis spectroscopy and ESI-MS. These reactions represent new synthetic routes to novel Pt(IV) complexes.</p

Correlation of a commercial platform's results with post-vaccination SARS-CoV-2 neutralizing antibody response and clinical host factors.

IntroductionThe objective of this study was to describe the correlation between the commercially available assay for anti-S1/RBD IgG and protective serum neutralizing antibodies (nAb) against SARS-CoV-2 in an adult population after SARS-CoV-2 vaccination, and determine if clinical variables impact this correlation.MethodsWe measured IgG anti-S1/RBD using the IgG-II CMIA assay and nAb IC50 values against SARS-CoV-2 WA-1 in sera serially collected post-mRNA vaccination in veterans and healthcare workers of the Veterans Affairs Connecticut Healthcare System (VACHS) between December 2020 and January 2022. The correlation between IgG and IC50 was measured using Pearson correlation. Clinical variables (age, sex, race, ethnicity, prior COVID infection defined by RT-PCR, history of malignancy, estimated glomerular filtration rate (GFR calculated using CKD-EPI equation) were collected by manual chart review. The impact of these clinical variables on the IgG-nAb correlation was analyzed first with univariable regression. Variables with a significance of p ResultsFrom 127 sera samples in 100 unique subjects (age 20-93 years; mean 63.83; SD 15.63; 29% female; 67% White), we found a robust correlation between IgG anti-S1/RBD and nAb IC50 (R2 = 0.83, R2adj = 0.70, p ConclusionsThere was a strong correlation between IgG anti-S1/RBD and nAb IC50 after SARS-CoV-2 vaccination. Clinical comorbidities, such as prior COVID infection and renal function, impacted this correlation. These results may assist the prediction of post-vaccination immune protection in clinical settings using cost-effective commercial platforms

Nonclinical data supporting orphan medicinal product designations: lessons from rare neurological conditions

Here, we provide an in-depth literature and experience-based review of nonclinical models and data used to support orphan medicinal product designations (OMPDs) in rare neurodegenerative conditions. The Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency updates its assessment processes based on scientific progress and aims to provide transparent criteria required in support of OMPDs. Thus, we also provide an updated analysis of existing nonclinical models in selected conditions and identify key features of nonclinical studies that are crucial for the support of OMPDs. This could not only inform future drug development in rare neurological conditions, but also indicate areas where the use of nonclinical models can be made more efficient

Germline Variants Incidentally Detected via Tumor-Only Genomic Profiling of Patients with Mesothelioma

Importance: Patients with mesothelioma often have next-generation sequencing (NGS) of their tumor performed; tumor-only NGS may incidentally identify germline pathogenic or likely pathogenic (P/LP) variants despite not being designed for this purpose. It is unknown how frequently patients with mesothelioma have germline P/LP variants incidentally detected via tumor-only NGS. Objective: To determine the prevalence of incidental germline P/LP variants detected via tumor-only NGS of mesothelioma.Design, Setting, and Participants: A series of 161 unrelated patients with mesothelioma from a high-volume mesothelioma program had tumor-only and germline NGS performed during April 2016 to October 2021. Follow-up ranged from 18 months to 7 years. Tumor and germline assays were compared to determine which P/LP variants identified via tumor-only NGS were of germline origin. Data were analyzed from January to March 2023.Main Outcomes and Measures: The proportion of patients with mesothelioma who had P/LP germline variants incidentally detected via tumor-only NGS.Results: Of 161 patients with mesothelioma, 105 were male (65%), the mean (SD) age was 64.7 (11.2) years, and 156 patients (97%) self-identified as non-Hispanic White. Most (126 patients [78%]) had at least 1 potentially incidental P/LP germline variant. The positive predictive value of a potentially incidental germline P/LP variant on tumor-only NGS was 20%. Overall, 26 patients (16%) carried a P/LP germline variant. Germline P/LP variants were identified in ATM, ATR, BAP1, CHEK2, DDX41, FANCM, HAX1, MRE11A, MSH6, MUTYH, NF1, SAMD9L, and TMEM127.Conclusions and Relevance: In this case series of 161 patients with mesothelioma, 16% had confirmed germline P/LP variants. Given the implications of a hereditary cancer syndrome diagnosis for preventive care and familial counseling, clinical approaches for addressing incidental P/LP germline variants in tumor-only NGS are needed. Tumor-only sequencing should not replace dedicated germline testing. Universal germline testing is likely needed for patients with mesothelioma.</p