Ariel - Volume 10 Number 3

Executive Editors Madalyn Schaefgen David Reich Business Manager David Reich News Editors Medical College Edward Zurad CAHS John Guardiani World Mark Zwanger Features Editors Meg Trexler Jim O\u27Brien Editorials Editor Jeffrey Banyas Photography and Sports Editor Stuart Singer Commons Editor Brenda Peterso

Better data for teachers, better data for learners, better patient care: college-wide assessment at Michigan State University's College of Human Medicine

When our school organized the curriculum around a core set of medical student competencies in 2004, it was clear that more numerous and more varied student assessments were needed. To oversee a systematic approach to the assessment of medical student competencies, the Office of College-wide Assessment was established, led by the Associate Dean of College-wide Assessment. The mission of the Office is to ‘facilitate the development of a seamless assessment system that drives a nimble, competency-based curriculum across the spectrum of our educational enterprise.’ The Associate Dean coordinates educational initiatives, developing partnerships to solve common problems, and enhancing synergy within the College. The Office also works to establish data collection and feedback loops to guide rational intervention and continuous curricular improvement. Aside from feedback, implementing a systems approach to assessment provides a means for identifying performance gaps, promotes continuity from undergraduate medical education to practice, and offers a rationale for some assessments to be located outside of courses and clerkships. Assessment system design, data analysis, and feedback require leadership, a cooperative faculty team with medical education expertise, and institutional support. The guiding principle is ‘Better Data for Teachers, Better Data for Learners, Better Patient Care.’ Better data empowers faculty to become change agents, learners to create evidence-based improvement plans and increases accountability to our most important stakeholders, our patients

Evaluación productiva y de emisiones de gases de efecto invernadero en dos sistemas de cría bovina contrastantes del Chaco Seco argentino = Production and greenhouse gas emissions evaluation in two contrasting bovine farming systems in the Argentine Chaco Seco

El desafío actual de los sistemas bovinos del Chaco Seco está centrado en el incremento de la producción a través de la intensificación, sin la necesidad de expandir la frontera agropecuaria hacia ecosistemas naturales y disminuyendo las externalidades negativas. El objetivo de este estudio fue cuantificar la diferencia en la producción de peso vivo (PV) y en la intensidad de emisión de gases de efecto invernadero en dos módulos experimentales contrastantes de cría bovina en su nivel de intensificación, localizados en el Chaco Seco argentino. El trabajo se realizó en el Instituto de Investigación Animal del Chaco Semiárido (INTA), utilizando módulos experimentales y un modelo de simulación. Un módulo experimental se denominó Cría Pastoril (CrP) y se basó en una alimentación pastoril y una carga animal moderada (0,64 vacas/ha/año) para la zona. El otro se denominó módulo de Cría Intensiva (CrI), y utilizó un sistema de alimentación pastoril con apoyo de silaje de maíz como suplemento alimenticio para las vacas, y una carga animal elevada (1,66 vacas/ha/año). La producción de peso vivo fue 98 y 264 kg PV/ha/año para CrP y CrI respectivamente (Tukey; p < 0,05). No se encontraron diferencias significativas en la intensidad de emisiones, con valores de 16,5 y 16,0 kg CO2 eq/kg PV producido para CrP y CrI respectivamente. El Chaco Seco es una región ganadera en desarrollo, pero con restricciones en la expansión de la superficie productiva, y este trabajo evidencia que es posible incrementar la producción ganadera regional y en paralelo disminuir la intensidad de las emisiones de gases de efecto invernadero.The current challenge of the Chaco Seco beef cattle system is focused on increasing production through intensification, without expanding the agricultural frontier towards natural ecosystems and reducing externalities. The aim of this study was to quantify the difference in live weight (LW) productivity and in greenhouse gases emission intensity of two contrasting cow-calf modules differing in their intensification level. This work was carried out at the Instituto de Investigación Animal del Chaco Semiárido (INTA) using two experimental modules and a simulation model. The grazing cow-calf module (CrP) was based on a grazing system with a moderate stocking rate (0.64 cows/he/year). The intensive cow-calf module (CrI) used a grazing system, but supported by corn silage as supplement for cows, and a high stocking rate (1.66 cows/ha/year). Live weight production was 98 and 264 kg LW/ha/year for CrP and CrI respectively (Tukey; p < 0.05). Non-significant differences were found in the emission intensity, with values ranging from 16.5 and 16.0 kg CO2 eq/kg LW produced for CrP and CrI respectively. The Chaco Seco is a developing cattle region but with restrictions in the expansion of the productive surface, and this work throws evidence that it is possible to increase regional livestock production and decrease greenhouse gas emissions intensity.Instituto de Investigación Animal del Chaco SemiáridoFil: Nasca, Jose Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido; Argentina.Fil: Banegas, Natalia Romina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido; ArgentinaFil: Banegas, Natalia Romina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Garcia Posse, Fernando Raúl. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido; ArgentinaFil: Martin, Alfredo Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido; ArgentinaFil: Martin, Alfredo Alberto. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Della Rosa, María Milagros. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido; ArgentinaFil: Molina Arias, Alvaro Marcelo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido; Argentina.Fil: Fernéndez, P. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Animal del Chaco Semiárido; Argentina.Fil: Fernández, P. Consejo Nacional de Investigación Científica y Tecnológica. Instituto De Ecología Regional; Argentin

The TopClosure® 3S System, for skin stretching and a secure wound closure

The principle of stretching wound margins for primary wound closure is commonly practiced and used for various skin defects, leading at times to excessive tension and complications during wound closure. Different surgical techniques, skin stretching devices and tissue expanders have been utilized to address this issue. Previously designed skin stretching devices resulted in considerable morbidity. They were invasive by nature and associated with relatively high localized tissue pressure, frequently leading to necrosis, damage and tearing of skin at the wound margins. To assess the clinical effectiveness and performance and, to determine the safety of TopClosure® for gradual, controlled, temporary, noninvasive and invasive applications for skin stretching and secure wound closing, the TopClosure® device was applied to 20 patients for preoperative skin lesion removal and to secure closure of a variety of wound sizes. TopClosure® was reinforced with adhesives, staples and/or surgical sutures, depending on the circumstances of the wound and the surgeon’s judgment. TopClosure® was used prior to, during and/or after surgery to reduce tension across wound edges. No significant complications or adverse events were associated with its use. TopClosure® was effectively used for preoperative skin expansion in preparation for dermal resection (e.g., congenital nevi). It aided closure of large wounds involving significant loss of skin and soft tissue by mobilizing skin and subcutaneous tissue, thus avoiding the need for skin grafts or flaps. Following surgery, it was used to secure closure of wounds under tension, thus improving wound aesthetics. A sample case study will be presented. We designed TopClosure®, an innovative device, to modify the currently practiced concept of wound closure by applying minimal stress to the skin, away from damaged wound edges, with flexible force vectors and versatile methods of attachment to the skin, in a noninvasive or invasive manner

Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy

Mitochondria are highly dynamic organelles, undergoing continuous fission and fusion. The DNM1L gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family, responsible for fission of mitochondria, and having a role in the division of peroxisomes, as well. DRP1 impairment is implicated in several neurological disorders and associated with either de novo dominant or compound heterozygous mutations. In five patients presenting with severe epileptic encephalopathy we identified 5 de novo dominant DNM1L variants, the pathogenicity of which was validated in a yeast model. Fluorescence microscopy revealed abnormally elongated mitochondria and aberrant peroxisomes in mutant fibroblasts, indicating impaired fission of these organelles. Moreover, a very peculiar finding in our cohort of patients was the presence, in muscle biopsy, of core like areas with oxidative enzyme alterations, suggesting an abnormal distribution of mitochondria in the muscle tissue

ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy

Objective: Dominant optic atrophy (DOA) is the most common inherited optic neuropathy, with a prevalence of 1:12,000 to 1:25,000. OPA1 mutations are found in 70% of DOA patients, with a significant number remaining undiagnosed. Methods: We screened 286 index cases presenting optic atrophy, negative for OPA1 mutations, by targeted next generation sequencing or whole exome sequencing. Pathogenicity and molecular mechanisms of the identified variants were studied in yeast and patient-derived fibroblasts. Results: Twelve cases (4%) were found to carry novel variants in AFG3L2, a gene that has been associated with autosomal dominant spinocerebellar ataxia 28 (SCA28). Half of cases were familial with a dominant inheritance, whereas the others were sporadic, including de novo mutations. Biallelic mutations were found in 3 probands with severe syndromic optic neuropathy, acting as recessive or phenotype-modifier variants. All the DOA-associated AFG3L2 mutations were clustered in the ATPase domain, whereas SCA28-associated mutations mostly affect the proteolytic domain. The pathogenic role of DOA-associated AFG3L2 mutations was confirmed in yeast, unraveling a mechanism distinct from that of SCA28-associated AFG3L2 mutations. Patients' fibroblasts showed abnormal OPA1 processing, with accumulation of the fission-inducing short forms leading to mitochondrial network fragmentation, not observed in SCA28 patients' cells. Interpretation: This study demonstrates that mutations in AFG3L2 are a relevant cause of optic neuropathy, broadening the spectrum of clinical manifestations and genetic mechanisms associated with AFG3L2 mutations, and underscores the pivotal role of OPA1 and its processing in the pathogenesis of DOA. ANN NEUROL 2020

US public opinion regarding proposed limits on resident physician work hours

<p>Abstract</p> <p>Background</p> <p>In both Europe and the US, resident physician work hour reduction has been a source of controversy within academic medicine. In 2008, the Institute of Medicine (IOM) recommended a reduction in resident physician work hours. We sought to assess the American public perspective on this issue.</p> <p>Methods</p> <p>We conducted a national survey of 1,200 representative members of the public via random digit telephone dialing in order to describe US public opinion on resident physician work hour regulation, particularly with reference to the IOM recommendations.</p> <p>Results</p> <p>Respondents estimated that resident physicians currently work 12.9-h shifts (95% CI 12.5 to 13.3 h) and 58.3-h work weeks (95% CI 57.3 to 59.3 h). They believed the maximum shift duration should be 10.9 h (95% CI 10.6 to 11.3 h) and the maximum work week should be 50 h (95% CI 49.4 to 50.8 h), with 1% approving of shifts lasting >24 h (95% CI 0.6% to 2%). A total of 81% (95% CI 79% to 84%) believed reducing resident physician work hours would be very or somewhat effective in reducing medical errors, and 68% (95% CI 65% to 71%) favored the IOM proposal that resident physicians not work more than 16 h over an alternative IOM proposal permitting 30-h shifts with ≥5 h protected sleep time. In all, 81% believed patients should be informed if a treating resident physician had been working for >24 h and 80% (95% CI 78% to 83%) would then want a different doctor.</p> <p>Conclusions</p> <p>The American public overwhelmingly favors discontinuation of the 30-h shifts without protected sleep routinely worked by US resident physicians and strongly supports implementation of restrictions on resident physician work hours that are as strict, or stricter, than those proposed by the IOM. Strong support exists to restrict resident physicians' work to 16 or fewer consecutive hours, similar to current limits in New Zealand, the UK and the rest of Europe.</p

Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults

Importance: Neurologic disorders with isolated symptoms or complex syndromes are relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1 gene mutations have been shown to cause isolated and syndromic optic neuropathies. Objective: To define the spectrum of clinical phenotypes associated with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase. Design, Setting, and Participants: This study involved 12 individuals from 11 families with severe central nervous system diseases and optic atrophy. Targeted and whole-exome sequencing were performed-at Hospital Angers (France), Institute of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of Munich (Germany), and Beijing Genomics Institute (China)-to clarify the molecular diagnosis of patients. Each patient\u27s neurologic, ophthalmologic, magnetic resonance imaging, and biochemical features were investigated. This study was conducted from May 1, 2014, to June 30, 2016. Main Outcomes and Measures: Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged from isolated optic atrophy to severe encephalopathies. Results: Of the 12 individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were consanguineous) had a member or members who presented isolated optic atrophy with the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and p.Tyr51Cys amino acid changes. The 5 other families had a member or members who presented severe neurologic syndromes with a common core of symptoms, including optic atrophy, seizure, intellectual disability, growth retardation, and elevated lactate levels. Additional clinical features of those affected were deafness, abnormalities on magnetic resonance images of the brain, stridor, and abnormal electroencephalographic patterns, all of which eventually led to death before age 3 years. In these patients, novel and very rare homozygous and compound heterozygous mutations were identified that led to the absence of the protein and complex I disassembly as well as mild mitochondrial network fragmentation. Conclusions and Relevance: A broad clinical spectrum of neurologic features, ranging from isolated optic atrophy to severe early-onset encephalopathies, is associated with RTN4IP1 biallelic mutations and should prompt RTN4IP1 screening in both syndromic neurologic presentations and nonsyndromic recessive optic neuropathies

Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies

Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users