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1.
PurposeHaploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS.MethodsWe report 24 additional unrelated patients with STISS with various truncating single nucleotide variants or copy-number variant deletions involving PSMD12. We explore disease etiology by assessing patient cells and CRISPR/Cas9-engineered cell clones for various cellular pathways and inflammatory status.ResultsThe expressivity of most clinical features in STISS is highly variable. In addition to previously reported DD/ID, speech delay, cardiac and renal anomalies, we also confirmed preaxial hand abnormalities as a feature of this syndrome. Of note, 2 patients also showed chilblains resembling signs observed in interferonopathy. Remarkably, our data show that STISS patient cells exhibit a profound remodeling of the mTORC1 and mitophagy pathways with an induction of type I interferon-stimulated genes.ConclusionWe refine the phenotype of STISS and show that it can be clinically recognizable and biochemically diagnosed by a type I interferon gene signature.  相似文献   
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Metabolic Brain Disease - Cholecalciferol deficiency has been associated with stress-related psychiatric disorders, particularly depression. Therefore, the present study investigated the...  相似文献   
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Clinical Rheumatology - The onset of rheumatic disease affects each patient differently and may impact quality of life with progression. We investigated the relationship between patient-reported...  相似文献   
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Background

Health-related quality of life (HRQoL) is frequently assessed in randomised clinical trials (RCTs) in the intensive care unit (ICU), but data are limited regarding the proportions of patients without responses or not surviving to HRQoL follow-up and the handling of this. We aimed to describe the extent and pattern of missing HRQoL data in intensive care trials and describe how these data and deaths were handled statistically.

Methods

We conducted a systematic review and meta-analysis following a published protocol. We searched PubMed, EMBASE, CINAHL and Cochrane Library for RCTs involving adult ICU patients reporting HRQoL as an outcome and excluded RCTs unobtainable in full text. We performed risk of bias assessment independently and in duplicate.

Results

We included 196 outcomes from 88 RCTs published in the years 2002–2022; the numbers of patients alive and eligible to respond HRQoL were reported in 76% of trials. At follow-up, median 27% (interquartile range 14%–39%) of patients had died, and median 20% (9%–38%) of survivors did not respond across outcomes. Analyses of 80% of outcomes were restricted to complete cases only. The handling of non-survivors in analyses were reported for 46% of outcomes, with 26% of all outcomes reported as including non-survivors (using the value zero or the worst possible score).

Conclusion

For HRQoL outcomes in ICU trials, we found that mortality at time of follow-up was high and non-response among survivors frequent. The reporting and statistical handling of these issues were insufficient, which may have biased results.  相似文献   
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Abstract

Aim: While diversity, equity, and inclusion are much proclaimed aspirational goals in education programs, the clinical learning environment (CLE) frequently falls short of meaningful incorporation of these concepts in processes, policies, and local culture. In this paper, we explore how inclusion, diversity, and equity can and should be defined and operationalized within medical education.

Methods: Three cases, organized around Hafferty’s curricular framework (formal, informal, and hidden), we illustrate lapses and potential best practices in inclusion in the CLE.

Results: The essential “best-practice” of programs inclusive of diverse individuals is the design of policies, processes, and behavioral norms co-creatively with all community members. Potential pitfalls to greater inclusion include nostalgic reference to “the past”, a neutrality that is operationalized without the rudder of explicit values and not recognizing that ethical obligations between teachers, learners, and programs are at the heart of the discussion of how inclusive learning and work environments are built.

Conclusion: Inclusive CLE’s provide space for co-creation, understand the need to ensure the voices of the vulnerable (i.e. learners) are heard and valued and through this promote the flourishing of diverse human capital, in keeping with a model that views diversity as a key attribute or organizational excellence.  相似文献   
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Background

To our knowledge this is the first published estimate of the charges of the care of burns in Sweden. The Linköping Burn Interventional Score has been used to calculate the charges for each burned patient since 1993. The treatment of burns is versatile, and depends on the depth and extension of the burn. This requires a flexible system to detect the actual differences in the care provided. We aimed to describe the model of burn care that we used to calculate the charges incurred during the acute phase until discharge, so it could be reproduced and applied in other burn centres, which would facilitate a future objective comparison of the expenses in burn care.

Methods

All patients admitted with burns during the period 2010–15 were included. We analysed clinical and economic data from the daily burn scores during the acute phase of the burn until discharge from the burn centre.

Results

Total median charge/patient was US$ 28 199 (10th–90th centiles 4668-197 781) for 696 patients admitted. Burns caused by hot objects and electricity resulted in the highest charges/TBSA%, while charges/day were similar for the different causes of injury. Flame burns resulted in the highest mean charges/admission, probably because they had the longest duration of stay. Mean charges/patient increased in a linear fashion among the different age groups.

Conclusion

Our intervention-based estimate of charges has proved to be a valid tool that is sensitive to the procedures that drive the costs of the care of burns such as large TBSA%, intensive care, and operations. The burn score system could be reproduced easily in other burn centres worldwide and facilitate the comparison regardless of the differences in the currency and the economic circumstances.  相似文献   
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