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Context: Autosomal dominant inactivating sprouty-related EVH1 domain-containing protein 1 (SPRED1) mutations have recently been described in individuals presenting mainly with café au lait macules (CALMs), axillary freckling, and macrocephaly. The extent of the clinical spectrum of this new disorder needs further delineation.Objective: To determine the frequency, mutational spectrum, and phenotype of neurofibromatosis type 1-like syndrome (NFLS) in a large cohort of patients.Design, Setting, and Participants: In a cross-sectional study, 23 unrelated probands carrying a SPRED1 mutation identified through clinical testing participated with their families in a genotype-phenotype study (2007-2008). In a second cross-sectional study, 1318 unrelated anonymous samples collected in 2003-2007 from patients with a broad range of signs typically found in neurofibromatosis type 1 (NF1) but no detectable NF1 germline mutation underwent SPRED1 mutation analysis.Main Outcome Measures: Comparison of aggregated clinical features in patients with or without a SPRED1 or NF1 mutation. Functional assays were used to evaluate the pathogenicity of missense mutations.Results: Among 42 SPRED1-positive individuals from the clinical cohort, 20 (48%; 95% confidence interval [CI], 32%-64%) fulfilled National Institutes of Health (NIH) NF1 diagnostic criteria based on the presence of more than 5 CALMs with or without freckling or an NF1-compatible family history. None of the 42 SPRED1-positive individuals (0%; 95% CI, 0%-7%) had discrete cutaneous or plexiform neurofibromas, typical NF1 osseous lesions, or symptomatic optic pathway gliomas. In the anonymous cohort of 1318 individuals, 34 different SPRED1 mutations in 43 probands were identified: 27 pathogenic mutations in 34 probands and 7 probable nonpathogenic missense mutations in 9 probands. Of 94 probands with familial CALMs with or without freckling and no other NF1 features, 69 (73%; 95% CI, 63%-80%) had an NF1 mutation and 18 (19%; 95% CI, 12%-29%) had a pathogenic SPRED1 mutation. In the anonymous cohort, 1.9% (95% CI, 1.2%-2.9%) of individuals with the clinical diagnosis of NF1 according to the NIH criteria had NFLS.Conclusions: A high SPRED1 mutation detection rate was found in NF1 mutation-negative families with an autosomal dominant phenotype of CALMs with or without freckling and no other NF1 features. Among individuals in this study, NFLS was not associated with the peripheral and central nervous system tumors seen in NF1. [ABSTRACT FROM AUTHOR]

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by a defect in cholesterol biosynthesis, associated with mental retardation and multisystem structural abnormalities. This study investigated the prevalence of congenital CNS abnormalities by MRI in a large series of patients with SLOS and the correlation of the clinical and biochemical findings with the results of MRI and 1H MRS. Eighteen patients were studied; all underwent MRI of the brain, and 16 had 1H MRS of the cerebral white matter. The ratios choline:NAA, lipid:NAA, and lipid:choline metabolite were found to be correlated with the clinical degree of disease severity, serum total sterol ratios (cholesterol/cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol) and in two cases with the effect of cholesterol therapy. Abnormal CNS findings were noted in five patients, including callosal abnormalities (n=4), Dandy-Walker variant (n=1), and arachnoid cyst (n=1). Holoprosencephaly was noted in one patient with a prevalence of 6%. Choline:NAA was elevated in seven patients. There was a statistically significant positive correlation between the lipid:choline ratio and the serum cholesterol precursor, 8-dehydrocholesterol. In two patients 1H MRS demonstrated abnormally elevated lipids prior to cholesterol therapy, which improved on therapy. The use of MRI and 1H MRS is an effective way to demonstrate brain structural abnormalities in patients with SLOS and may prove to be an effective method for the assessment of the effects of cholesterol replacement therapy in the brain. [ABSTRACT FROM AUTHOR]

Presents the medical case of a woman with a cystic hygroma. Finding of a male karyotype with additional chromosome material attached to the short arm of chromosome 9; Determination that the material came from the distal short arm of chromosome 2; Use of GTG banding, G-banding, multiplex fluorescence in-situ hybridization (M-FISH) and Rx-FISH in the diagnosis; Revised chromosomal diagnosis of partial trisomy 2p and deletion 9p.

Boston Children's Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Children's Rare Disease Collaborative (CRDC), the hospital offers CLIA-grade exome and genome sequencing, along with other sequencing types, to patients enrolled in specialized rare disease research studies. The data, consented for broad research use, are harmonized and analyzed with CRDC-supported variant interpretation tools. Since its launch, 66 investigators representing 26 divisions and 45 phenotype-based cohorts have joined the CRDC. These studies enrolled 4653 families, with 35% of analyzed cases having a finding either confirmed or under further investigation. This accessible and harmonized genomics platform also supports additional institutional data collections, research and clinical, and now encompasses 13,800+ patients and their families. This has fostered new research projects and collaborations, increased genetic diagnoses and accelerated innovative research via integration of genomics research with clinical care., Competing Interests: Competing interests: N.C.A. sits on the Boards of Directors of Novartis, Charles River Laboratories and Maze Therapeutics, and is on the Scientific Advisory Board of Dyne Therapeutics. A.J.M. is a scientific consultant for Judo Bio. M.H.W. has consulted for Illumina and Sanofi and receives speaking honoraria from Illumina and GeneDx., (© 2024. The Author(s).)

Background: Whilst information has been published on the impact, severity and causes of incidents involving medicines in care homes, it has not been systematically described. This review explored whether coroners' Preventing Future Death (PFD) reports involving medicines for people living in care homes could add to this evidence base., Methods: PFD reports made publicly available between 2017 and 2021 classified as 'care home-related deaths' were reviewed. Reports describing medicines and/or medicines processes were identified. Contributory factors within these reports were then identified., Results: Within the timeframe, 156 reports were published, and 25 described medicines (n = 27) or medicines processes (n = 5) concerning people living in care homes. The impact of medicines and/or medicines processes was quantified as no impact (n = 7), contributory (n = 6) and direct (n = 14) per report. Two key themes emerged. Four deaths had an association between their falls risk, prescribed anticoagulants, and the failure of the service to seek timely emergency care following a fall and two deaths concerned endocrine medicines, where people refused insulin or blood sugar monitoring and staff did not seek timely advice., Conclusion: This study demonstrated PFD reports provide an insight into the potential association between medicines, and other aspects of the person's care in causing harm., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Augmented Intelligence (AI) systems have the power to transform health care and bring us closer to the quadruple aim: enhancing patient experience, improving population health, reducing costs, and improving the work life of health care providers. Earning physicians' trust is critical for accelerating adoption of AI into patient care. As technology evolves, the medical community will need to develop standards for these innovative technologies and re-visit current regulatory systems that physicians and patients rely on to ensure that health care AI is responsible, evidence-based, free from bias, and designed and deployed to promote equity. To develop actionable guidance for trustworthy AI in health care, the AMA reviewed literature on the challenges health care AI poses and reflected on existing guidance as a starting point for addressing those challenges (including models for regulating the introduction of innovative technologies into clinical care)., (© 2022. The Author(s).)

Competing Interests: Conflict-of-Interest Disclosures: Michelle Gong reports receiving grants from NIH, CDC, and AHRQ unrelated to this work, and receiving personal fees from Regeneron and Phillips Healthcare. Jack Resneck reports that he is a trustee of the American Medical Association and a director at the National Quality Forum. Tait Shanafelt reports that he is co-inventor of the Well-being Index Instruments and the Participatory Management Leadership Index. Mayo Clinic holds the copyright for these instruments and has licensed them for use outside of the Mayo Clinic, and Mayo Clinic pays Dr. Shanafelt a portion of any royalties received.

Research has not definitively ascertained the circumstances that motivate people to live a healthier lifestyle. To redress this shortfall, we report two overlapping studies that examined whether people are more inclined to value health benefits that seem enduring and fundamental rather than transient or superficial-even after controlling effort and cost. In these studies, 242 participants indicated the degree to which they implement 17 health behaviours-as well as the extent to which they perceive the benefits of these behaviours as enduring and fundamental. Furthermore, participants completed a measure that gauges future clarity. Finally, they chose which of two drugs-drugs that differ only on the longevity of effects-they prefer. Participants were more inclined to implement health behaviours that seemed to generate enduring and fundamental benefits. This effect was more pronounced in people who perceive their future as vivid and certain. Furthermore, participants tended to choose the drug that was touted as generating more enduring benefits, even after controlling cost and effort. As these results imply, to encourage healthy behaviour, health practitioners should help people clarify their future goals and then advocate behaviours that generate lasting benefits., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Some research shows that people who often contemplate their future tend to be healthier. Yet the burgeoning literature on mindfulness demonstrates that people who are more attuned to their immediate experiences also enjoy many benefits. To reconcile these principles, many scholars recommend that people should distribute their attention, somewhat evenly, across the past, present, and future-but have not clarified how people should achieve this goal. We test the possibility that people who perceive their future as vivid and certain, called future clarity, might be able to both orient their attention to the future as well as experience mindfulness. Specifically, future clarity could diminish the inclination of people to reach decisions prematurely and dismiss information that contradicts these decisions, called need for closure-tendencies that diminish consideration of future consequences and mindfulness, respectively. In this cross-sectional study, 194 participants completed measures of mindfulness, consideration of future consequences, need for closure, and future clarity. Consistent with hypotheses, future clarity was positively associated with both mindfulness and consideration of future consequences. Need for closure partly mediated these relationships. Accordingly, interventions that empower people to shape and to clarify their future might generate the benefits of both mindfulness and a future orientation., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: To describe a group of children with co-incident pulmonary vein stenosis and Smith-Lemli-Opitz syndrome and to generate hypotheses as to the shared pathogenesis of these disorders., Design: Retrospective case series., Patients: Five subjects in a pulmonary vein stenosis cohort of 170 subjects were diagnosed with Smith-Lemli-Opitz syndrome soon after birth., Results: All five cases were diagnosed with Smith-Lemli-Opitz syndrome within 6 weeks of life, with no family history of either disorder. All cases had pathologically elevated 7-dehydrocholesterol levels and two of the five cases had previously reported pathogenic 7-dehydrocholesterol reductase mutations. Smith-Lemli-Opitz syndrome severity scores ranged from mild to classical (2-7). Gestational age at birth ranged from 35 to 39 weeks. Four of the cases were male by karyotype. Pulmonary vein stenosis was diagnosed in all cases within 2 months of life, earlier than most published cohorts. All cases progressed to bilateral disease and three cases developed atresia of at least one vein. Despite catheter and surgical interventions, all subjects' pulmonary vein stenosis rapidly recurred and progressed. Three of the subjects died, at 2 months, 3 months, and 11 months. Survival at 16 months after diagnosis was 43%., Conclusions: Patients with pulmonary vein stenosis who have a suggestive syndromic presentation should be screened for Smith-Lemli-Opitz syndrome with easily obtainable serum sterol tests. Echocardiograms should be obtained in all newly diagnosed patients with Smith-Lemli-Opitz syndrome, with a low threshold for repeating the study if new respiratory symptoms of uncertain etiology arise. Further studies into the pathophysiology of pulmonary vein stenosis should consider the role of cholesterol-based signaling pathways in the promotion of intimal proliferation., (© 2017 Wiley Periodicals, Inc.)

Background and Aims: Lecturers often present entertaining videos, or organize a variety of amusing demonstrations, to foster student engagement or to encourage critical analysis. Magic tricks, in particular, have been shown to activate neural circuits that underpin motivation or problem-solving and, therefore, could be beneficial during lectures. Nevertheless, we hypothesize that, unless the method that underpins these tricks is revealed, students may ruminate over possible explanations, distracting attention from the lecture material., Sample and Methods: To test these arguments, in this study, 224 participants watched a video of a magic performance, watched a video of a circus act, or watched no video at all. In half the participants who watched the magic performance, the secret that underpinned the trick was disclosed. Next, participants watched a psychology tutorial, before answering questions that assessed engagement, need for cognition, and comprehension of the material., Results: If the secret was withheld, magic tricks diminished subsequent need for cognition but did not affect comprehension. Furthermore, magic tricks tended to diminish engagement with the subsequent tutorial. These effects, however, were small., Conclusion: Future research is warranted to ascertain whether information that is embedded within a magic trick, rather than presented after the trick, is more likely to be remembered or understood later. This research could clarify when performance can enhance or disrupt student engagement., (© 2016 The British Psychological Society.)

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology., Competing Interests: The authors have none to declare.

The American Board of Medical Specialties board certification has transformed into a career-long process of learning, assessment, and performance improvement through its Program for Maintenance of Certification (MOC). Medical educators across many medical professional organizations, specialty societies, and other institutions have played important roles in shaping MOC and tailoring its overarching framework to the needs of different specialties. This Commentary addresses potential barriers to engagement in work related to MOC for medical school (MS) and academic health center (AHC) educators and identifies reasons for, and ways to accomplish, greater involvement in this work. The authors present ways that medical and other health professions educators in these settings can contribute to the continuous improvement of the MOC program including developing educational and assessment activities, engaging in debate about MOC, linking MOC with institutional quality improvement activities, and pursuing MOC-related scholarship. MS- and AHC-based educators have much to offer this still-young and continually improving program, and their engagement is sought, necessary, and welcomed.