Practical considerations for using personal cooling garments for heat stress management in physically demanding occupations: A systematic review and meta-analysis using realist evaluation.

INTRODUCTION: Due to rising temperature extremes, workplaces are seeking new solutions, such as using personal cooling garments (PCG) to mitigate and manage workplace heat exposure. This systematic review sought to assess the physiological and perceptual effects of PCGs on workers in standard work clothing performing moderate-to-heavy intensity tasks in hot environments. METHODS: A peer-reviewed search strategy was conducted in MEDLINE, Embase, CINAHL, Scopus, Global Health, and Business Source Complete with no language or time limits. A meta-analysis using a realist evaluation framework was then performed to evaluate the effectiveness of the PCGs. RESULTS: Thirty-three studies with 764 participants (98% male; average 21 ± 34 participants per study), conducted primarily in a laboratory setting (76%) were included. The studies were 193 ± 190 min in duration and consisted of a moderate-to-heavy work effort of 3.3 ± 1.0 METs in hot ambient conditions (temperature: 35.9 ± 3.3°C, 51.4 ± 12.1% relative humidity, wet bulb globe temperature [WBGT] 31.2 ± 2.6°C). The PCGs (n = 67) facilitated heat exchange through conduction (n = 39), evaporation (n = 4), convection (n = 2), radiation (n = 2), or hybrid combinations (n = 20). Conductive and hybrid PCGs offered the greatest thermoregulatory benefit, whereby core temperature (Tc) and heart rate (HR) reductions were consistently observed (Conductive: Tc: -0.3°C, HR: -12 bpm; Hybrid: Tc::-0.2°C, HR: -10 bpm), while PCGs directed at enhancing evaporative and radiative heat exchange had no or minimal effect on the physiological outcomes assessed (i.e., TC < 0.1°C, HR: <0.7 bpm). CONCLUSION: While the PCGs had a positive overall effect, conductive options offered the most consistent benefit to workers. WBGT, clothing insulation, and duration of wear significantly affected some physiological and perceptual outcomes.

Efficacy of stellate ganglion block in treatment of electrical storm: a systematic review and meta-analysis.

Electrical storm (ES) is a life-threatening condition of recurrent ventricular arrhythmias (VA) in a short period of time. Percutaneous stellate ganglion blockade (SGB) is frequently used - however the efficacy is undefined. The objective of our systematic review was to determine the efficacy of SGB in reducing VA events and mortality among patients with ES. A search of Medline, EMBASE, Scopus, CINAHL and CENTRAL was performed on February 29, 2024 to include studies with adult patients (≥ 18 years) with ES treated with SGB. Our outcomes of interest were VA burden pre- and post-SGB, and in-hospital/30-day mortality. A total of 553 ES episodes in 542 patients from 15 observational studies were included. Treated VAs pre- and post-SGB were pooled from eight studies including 383 patients and demonstrated a decrease from 3.5 (IQR 2.25-7.25) to 0 (IQR 0-0) events (p = 0.008). Complete resolution after SGB occurred in 190 of 294 patients (64.6%). Despite this, in-hospital or 30-day mortality remained high occurring in 140 of 527 patients (random effects prevalence 22%). Repeat SGB for recurrent VAs was performed in 132 of 490 patients (random effects prevalence 21%). In conclusion, observational data suggests SGB may be effective in reducing VAs in ES. Definitive studies for SGB in VA management are needed. Study protocol: PROSPERO - registration number CRD42023430031.

A Review of Evidence Related to the Zoonotic Characteristics of the Monkeypox Virus.

The 2022 monkeypox virus (MPXV) outbreaks spurred global public health concern. In response, we undertook a living systematic review of its zoonotic characteristics, including potential reservoirs and susceptible species, transmissibility, and clinical presentation in nonhuman species. Electronic database searches yielded 148 eligible records published between 2000 and 2022. Primary reservoirs remain unidentified, with natural isolation identified in 2 species, the sooty mangabey monkey and rope squirrel. Transmission primarily occurs from animals to humans, but evidence of reverse zoonosis has emerged. Data on clinical infection and manifestations are sparse, with evidence of potentially susceptible species drawn primarily from experimental studies. Only 10% of articles were appropriate for quality assessment and most of these were rated as critically low. Overall, while evidence regarding MPXV exists, the quality of data are extremely poor, resulting in significant uncertainty regarding MPXV's zoonotic traits. High-quality empirical research to understand the impact of MPXV on animal and human populations is warranted.

Direct and indirect costs of idiopathic inflammatory myopathies in adults: A systematic review.

Idiopathic inflammatory myopathies (IIMs) are rare disorders characterized by inflammation of skeletal muscle, which can result in fatty replacement of muscle, muscle atrophy, and subsequent weakness. Therapeutic advancements have improved clinical outcomes but impose an economic impact on healthcare systems. We aimed to summarize the direct and indirect costs associated with IIMs in a systematic review (PROSPERO Registration #CRD42023443143). Electronic databases (MEDLINE, Embase, CINAHL, and Scopus) were systematically searched for full-length articles (excluding case reports) reporting costs specific to patients diagnosed with an IIM, published between database inception and April 19, 2023. Direct cost categories included inpatient, outpatient, medication, home/long-term care, and durable medical equipment such as mobility and respiratory aids. Indirect costs included lost productivity. Eligibility criteria were met by 21 of the 3,193 unique titles identified. Costs are expressed in 2023 United States of America dollars, with adjustments for differences in purchasing power applied to currency conversions. As no study reported on all cost categories, annualized cost of IIM per patient was estimated by calculating the mean cost per category, and then adding the means of the different cost categories. By this method, IIM was estimated to cost $52,210 per patient per year. Proportional contributions by category were lost productivity (0.278), outpatient care (0.214), medications (0.171), inpatient care (0.161), home/long-term care (0.122), and durable medical equipment (0.053). Newer findings with intravenous immunoglobulin considered first line therapy for IIM demonstrated markedly higher annual medication costs per patient, upwards of $33,900 compared to an average of $3,908 ± $1,042 in older studies. Future cost-effectiveness studies require updated cost-of-illness studies reflecting the evolving sub-classification and treatment options for IIM, and should consider the impact of IIM on patients and their families.

Comparison of peer-assisted learning with expert-led learning in medical school ultrasound education: a systematic review and meta-analysis.

INTRODUCTION: Teaching point-of-care ultrasonography (PoCUS) to medical students is resource intensive. Peer-assisted learning, where the teacher can be a medical student, may be a feasible alternative to expert-led learning. The objective of this systematic review and meta-analysis was to compare the PoCUS performance assessments of medical students receiving peer-assisted vs expert-led learning. METHODS: This study was submitted to PROSPERO (CRD42023383915) and reported with PRISMA guidelines. MEDLINE, Embase, ERIC, Education Source, Scopus, and Web of Science were searched from inception to November 2022. Inclusion criteria were studies comparing peer-assisted vs expert-led PoCUS teaching for undergraduate medical students. The primary outcome was performance assessment of PoCUS skills. Two reviewers independently screened citations and extracted data. The Cochrane risk-of-bias tool for randomized trials was used to assess study quality. Studies were included in the meta-analysis if mean performance assessment scores with standard deviations and sample sizes were available. A random-effects meta-analysis was conducted to estimate the accuracy score of practical knowledge test for each group. A meta-regression evaluated difference in mean scores. RESULTS: The search yielded 2890 citations; 1417 unique citations remained after removing duplicates. Nine randomized-controlled studies conducted in Germany, USA, and Israel, with 593 participants, were included in the meta-analysis. The included studies assessed teaching of abdominal, cardiac, thoracic, musculoskeletal, and ocular PoCUS skills. Most studies had some risk-of-bias concerns. The estimate accuracy score after weighting is 0.56 (95% CI [0.47, 0.65]) for peer-assisted learning and 0.59 (95% CI [0.49, 0.69]) for expert-led learning. The regression coefficient estimate is 0.0281 (95% CI [- 0.1121, 0.1683]); P value is 0.69. CONCLUSION: This meta-analysis found that peer-assisted learning was a reasonable alternative to expert-led learning for teaching PoCUS skills to medical students.

RéSUMé: INTRODUCTION: L'enseignement de l'échographie au point d'intervention (PoCUS) aux étudiants en médecine nécessite des ressources importantes. L'apprentissage assisté par les pairs, où l'enseignant peut être un étudiant en médecine, peut être une alternative possible à l'apprentissage dirigé par des experts. L'objectif de cette revue systématique et de cette méta-analyse était de comparer les évaluations de performance PoCUS d'étudiants en médecine bénéficiant d'un apprentissage assisté par des pairs par rapport à un apprentissage dirigé par des experts. MéTHODES: Cette étude a été soumise à PROSPERO (CRD42023383915) et rapportée selon les directives PRISMA. MEDLINE, Embase, ERIC, Education Source, Scopus et Web of Science ont été recherchés depuis leur création jusqu'en novembre 2022. Les critères d'inclusion étaient les études comparant l'enseignement du PoCUS assisté par des pairs à celui dirigé par des experts pour les étudiants en médecine de premier cycle. Le principal résultat était l'évaluation du rendement des compétences PoCUS. Deux évaluateurs ont indépendamment examiné les citations et extrait les données. L'outil Cochrane d'évaluation du risque de biais pour les essais randomisés a été utilisé pour évaluer la qualité des études. Les études ont été incluses dans la méta-analyse si les scores moyens d'évaluation des performances avec les écarts types et la taille des échantillons étaient disponibles. Une méta-analyse à effets aléatoires a été réalisée pour estimer le score de précision du test de connaissances pratiques pour chaque groupe. Une méta-régression a évalué la différence dans les scores moyens. RéSULTATS: La recherche a donné lieu à 2890 citations ; 1417 citations uniques ont été conservées après suppression des doublons. Neuf études contrôlées randomisées menées en Allemagne, aux États-Unis et en Israël, avec 593 participants, ont été incluses dans la méta-analyse. Les études incluses ont évalué l'enseignement des compétences PoCUS abdominales, cardiaques, thoraciques, musculo-squelettiques et oculaires. La plupart des études présentaient des risques de biais. Le score de précision estimé après pondération est de 0,56 (IC à 95 % : [0,47, 0,65]) pour l'apprentissage assisté par les pairs et de 0,59 (IC à 95 % : [0,49, 0,69]) pour l'apprentissage dirigé par des experts. L'estimation du coefficient de régression est de 0,0281 (IC à 95 % : [-0,1121, 0,1683]) ; la valeur P est de 0,69. CONCLUSION: Cette méta-analyse a montré que l'apprentissage assisté par les pairs était une alternative raisonnable à l'apprentissage dirigé par des experts pour enseigner les compétences PoCUS aux étudiants en médecine.

Prevalence of patient partner authorship and acknowledgment in child health research publications: an umbrella review.

OBJECTIVES: Children and families are increasingly involved as equal partners in child health research, however, considerations around authorship have received little attention and there is limited guidance on the topic. Our objective was to determine the frequency and nature of patient partner authorship and/or acknowledgment among articles focused on patient engagement in child health research. STUDY DESIGN AND SETTING: In this umbrella review, we searched MEDLINE, Embase, APA PsycINFO, Cochrane Database of Systematic Reviews, CINAHL, and Web of Science for systematic/scoping reviews on patient engagement in child health research. Individual articles included in eligible reviews comprised the sample of articles for analysis and were examined to identify patient partner authorship. Descriptive statistics were used to quantify patient partner authorship and/or acknowledgment and to summarize article characteristics. RESULTS: Twelve systematic/scoping reviews met eligibility criteria, from which 230 individual articles were examined. In 16/230 (7%) articles, there was at least one patient partner author, and in 6/230 (3%) articles, patient partners were included as group authors. Within article Acknowledgments sections, patient partners were acknowledged by name in 41/230 (18%) articles, and anonymously or as a group in 98/230 (43%) articles. Patient partner authorship and/or acknowledgment was more frequent among articles published more recently (after 2015) and among articles where patient engagement was explicitly reported in the article. CONCLUSION: Patient partners were more likely to be acknowledged than listed as an author on articles on patient engagement in child health research. Understanding patient partner preferences about authorship and acknowledgment, examination of the unique aspects of child and youth authorship and developing supports to empower patient partner authorship are needed.

Combinatorial Effect of Biomaterials and Extracellular Vesicle Therapy for Heart Failure with Reduced Ejection Fraction: A Systematic Review of Preclinical Studies.

Heart failure, a pervasive global health burden, necessitates innovative therapeutic strategies. Extracellular vesicles (EVs) have emerged as promising contenders for cardiac repair, owing to their profound influence on fibrosis and inflammation. Merging EVs with biomaterials holds the potential for a synergistic leap in therapeutic efficacy. In this review, the impact of combining EVs with biomaterials in preclinical heart failure models is scrutinized. Fifteen studies, predominantly employing mesenchymal stromal cell-derived EVs along with hyaluronic acid or peptides in coronary ligation models, meet these stringent criteria. The amalgamation of EVs and biomaterials consistently enhances cardiac ejection fraction (1.39; 95% CI: 0.68, 2.11; p = 0.0001) and fractional shortening (1.46, 95% CI: 0.70, 2.22; p = 0.0002) compared to EV monotherapy. Secondary outcomes similarly showcased improvement in the combined treatment group. Although the number of studies analyzed is modest, no indications of publication bias surface. In summary, combination therapy with EVs and biomaterials enhances therapeutic benefit in preclinical heart failure models. The consistent improvement observed across diverse EV sources, biomaterials, and animal models underscores the exciting potential of this synergistic approach.

A scoping review protocol on diagnostic strategies to detect occult malignancies in individuals with ischemic stroke.

BACKGROUND: Emerging data show an increased risk of ischemic stroke in patients with a new diagnosis of cancer. As the risk of stroke begins to increase 150 days before cancer is diagnosed, stroke may be the first clinical manifestation of undiagnosed cancer. About 6% of patients with cryptogenic ischemic stroke (unknown etiology after diagnostic evaluations) are diagnosed with cancer within one year. However, the optimal cancer screening strategy in this population is not known. We aim to conduct a scoping review of screening strategies for occult cancer in individuals with ischemic stroke. METHODS: Electronic databases including MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost) and Scopus will be systematically searched to identify articles that report on screening strategies for occult cancer in individuals with ischemic stroke. At least two investigators will independently perform two-stage study selection consisting of title/abstract screening and full-text review, followed by data extraction. Thereafter, a thematic analysis will be conducted to provide an overview of what diagnostic tests/strategies have been used, and their clinical utility in terms of positive and negative predictive value (when available). CONCLUSION: We anticipate that the findings of this scoping review will identify strategies used to detect occult cancer in individuals with ischemic stroke and summarize their clinical utility (if reported). Addressing this knowledge gap will help guide the development of future clinical trials on occult cancer screening patients with ischemic stroke.

Impact of coaching on physician wellness: A systematic review.

Physician wellness is critical for patient safety and quality of care. Coaching has been successfully and widely applied across many industries to enhance well-being but has only recently been considered for physicians. This review aimed to summarize the existing evidence on the effect of coaching by trained coaches on physician well-being, distress and burnout. MEDLINE, Embase, ERIC, PsycINFO and Web of Science were searched without language restrictions to December 21, 2022. Studies of any design were included if they involved physicians of any specialty undergoing coaching by trained coaches and assessed at least one measure along the wellness continuum. Pairs of independent reviewers determined reference eligibility. Risk of bias was assessed using the Cochrane Risk of Bias Tools for Randomized Controlled Trials (RCTs) and for Non-randomized Studies of Interventions (ROBINS-I). Meta-analysis was not possible due to heterogeneity in study design and outcome measures as well as inconsistent reporting. The search retrieved 2531 references, of which 14 were included (5 RCTs, 2 non-randomized controlled studies, 4 before-and-after studies, 2 mixed-methods studies, 1 qualitative study). There were 1099 participants across all included studies. Risk of bias was moderate or serious for non-RCTs, while the 5 RCTs were of lower risk. All quantitative studies reported effectiveness of coaching for at least one outcome assessed. The included qualitative study reported a perceived positive impact of coaching by participants. Evidence from available RCTs suggests coaching for physicians can improve well-being and reduce distress/burnout. Non-randomized interventional studies have similar findings but face many limitations. Consistent reporting and standardized outcome measures are needed.

The Impact of Patient and Family Engagement in Child Health Research: A Scoping Review.

OBJECTIVE: To identify impacts of patient and family engagement in child health research on the research process, research teams, and patient and family partners. STUDY DESIGN: A scoping review was conducted using the MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and Web of Science databases. English-language studies were included if they described ≥1 impact of patient and family engagement on child health research (age <18 years), researchers, or patient and family partners. Data were retrieved by 2 independent extractors. RESULTS: Of the 7688 studies identified, 25 were included in our analysis. Impacts of patient and family engagement were mostly on the research process (n = 24 studies; 96%), 11 (44%) determined impacts on the research team, and 17 (68%) reported impacts on patient and family partners. Less than one-half (n = 11; 44%) had a primary purpose of determining the impact of patient engagement, and no study used a specific evaluation tool. CONCLUSIONS: Patient and family engagement can strengthen the relevance and feasibility of research and empower researchers and patient partners. Measuring and reporting the impact of engagement is rare. Systematic and standardized evaluation of engagement is needed to understand how, when, and why to engage patients and families.

All-cause mortality after major gastrointestinal bleeding among patients receiving direct oral anticoagulants: a protocol for a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal (GI) bleeding represents the single most frequent site of anticoagulant-related bleeding. Adverse outcomes after major GI bleeding including mortality are not well characterized and, as a result, may be underappreciated in clinical practice. We aim to conduct a systematic review and meta-analysis of the risk for 30-day all-cause mortality after major GI bleeding among patients receiving DOACs. METHODS: Electronic databases including MEDLINE, EMBASE, and Cochrane CENTRAL will be systematically searched to identify randomized controlled trials and prospective and retrospective cohort studies reporting 30-day all-cause mortality in adults with DOAC-related major GI bleeding. At least two investigators will independently perform study selection, risk of bias assessment, and data extraction. The proportion of deaths following a major GI event relative to the number of major GI bleeding events will be calculated for each individual study, and results across studies will be pooled using random-effects meta-analysis. We will assess risk of bias using criteria proposed by the GRADE group for prognostic studies. DISCUSSION: The findings of this systematic review and meta-analysis will provide clinicians and patients with estimates of mortality after the most common major bleeding event to support shared decision making about anticoagulation management. TRIAL REGISTRATION: PROSPERO CRD42022295815.

Legal concerns in health-related artificial intelligence: a scoping review protocol.

BACKGROUND: Medical innovations offer tremendous hope. Yet, similar innovations in governance (law, policy, ethics) are likely necessary if society is to realize medical innovations' fruits and avoid their pitfalls. As innovations in artificial intelligence (AI) advance at a rapid pace, scholars across multiple disciplines are articulating concerns in health-related AI that likely require legal responses to ensure the requisite balance. These scholarly perspectives may provide critical insights into the most pressing challenges that will help shape and advance future regulatory reforms. Yet, to the best of our knowledge, there is no comprehensive summary of the literature examining legal concerns in relation to health-related AI. We thus aim to summarize and map the literature examining legal concerns in health-related AI using a scoping review approach. METHODS: The scoping review framework developed by (J Soc Res Methodol 8:19-32, 2005) and extended by (Implement Sci 5:69, 2010) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) guided our protocol development. In close consultation with trained librarians, we will develop a highly sensitive search for MEDLINE® (OVID) and adapt it for multiple databases designed to comprehensively capture texts in law, medicine, nursing, pharmacy, other healthcare professions (e.g., dentistry, nutrition), public health, computer science, and engineering. English- and French-language records will be included if they examine health-related AI, describe or prioritize a legal concern in health-related AI or propose a solution thereto, and were published in 2012 or later. Eligibility assessment will be conducted independently and in duplicate at all review stages. Coded data will be analyzed along themes and stratified across discipline-specific literatures. DISCUSSION: This first-of-its-kind scoping review will summarize available literature examining, documenting, or prioritizing legal concerns in health-related AI to advance law and policy reform(s). The review may also reveal discipline-specific concerns, priorities, and proposed solutions to the concerns. It will thereby identify priority areas that should be the focus of future reforms and regulatory options available to stakeholders in reform processes. TRIAL REGISTRATION: This protocol was submitted to the Open Science Foundation registration database. See https://osf.io/zav7w .

A homozygous canonical splice acceptor site mutation in PRUNE1 is responsible for a rare childhood neurodegenerative disease in Manitoba Cree families.

Autosomal recessive PRUNE1 mutations are reported to cause a severe neurodevelopmental disorder with microcephaly, hypotonia, and brain malformations. We describe clinical and neuropathological features in a cohort of nine individuals of Cree descent who, because of a founder effect, are homozygous for the same PRUNE1 mutation. They follow the course of a combined neuromuscular and neurodegenerative disease, rather than a pure failure of normal development. This cohort presented in infancy with features of lower motor neuron disease, such as hypotonia, contractures, tongue fasciculations, and feeding difficulties in the absence of congenital brain anomalies and microcephaly. A neurodegenerative course followed with onset of seizures, spasticity, and respiratory insufficiency. Muscle biopsies showed denervation/reinnervation features, nonspecific atrophy and end-stage atrophy. Autopsy findings in two patients are also described, suggesting length dependent central motor axon degeneration, peripheral motor axon degeneration, possible spinal motor neuron degeneration, and accumulation of beta amyloid precursor protein inclusions in select brainstem nuclei. Exome sequencing and homozygosity mapping identified a homozygous PRUNE1 mutation in a canonical splice site, which produces two abnormal PRUNE1 mRNA products. Based on our studies and the histopathology and phenotypic data, we provide further evidence that this disorder leads to a neurodegenerative disease affecting both the peripheral and central nervous systems and suggest that the pathogenic c.521-2A>G mutation could lead to an altered effect on tubulin dynamics.

Light and COP1 regulate level of overexpressed DET1 protein.

de-etiolated 1 (det1) and constitutive photomorphogenic 1 (cop1) were initially identified as constitutively photomorphogenic Arabidopsis mutants, exhibiting light-grown phenotypes in the dark. Subsequently, both were shown to be components of Damaged DNA Binding protein 1 (DDB1)/CULLIN4-type complexes. Arabidopsis has two DDB1 homologues, DDB1A and DDB1B, and DDB1A mutants enhance det1 phenotypes. Here we examine ddb1a cop1 double mutants and find that ddb1a weakly enhances some cop1 phenotypes but not others, suggesting developmental regulation of COP1-DDB1A interaction. DET1 loss of function strongly enhances cop1 phenotypes. Here we show that MycDET1 overexpression also enhances cop1 phenotypes, thus MycDET1 overexpression in cop1 mutants also generates loss of function effects. Finally, the effect of the cop1 mutant background on the biochemical properties of MycDET1 was examined. MycDET1 levels were found to be lower in the dark than in the light and this difference required COP1. In summary, both DDB1A loss of function and MycDET1 overexpression enhance cop1 phenotypes, while cop1 mutants fail to exhibit light regulation of MycDET1 levels.

Interactions between Arabidopsis DNA repair genes UVH6, DDB1A, and DDB2 during abiotic stress tolerance and floral development.

Plants must protect themselves from a spectrum of abiotic stresses. For example, the sun is a source of heat, intense light, and DNA-damaging ultraviolet (UV) rays. Damaged DNA binding protein 1A (DDB1A), DDB2, and UV hypersensitive 6 (UVH6)/XPD are all involved in the repair of UV-damaged DNA - DDB1A and DDB2 in the initial damage recognition stage, while the UVH6/XPD helicase unwinds the damaged strand. We find that, as predicted, Arabidopsis ddb1a and ddb2 mutants do not affect uvh6/xpd UV tolerance. In addition, uvh6 is heat sensitive, and ddb1a and ddb2 weakly enhance this trait. The uvh6 ddb1a and uvh6 ddb2 double mutants also exhibit sensitivity to oxidative stress, suggesting a role for DDB1 complexes in heat and oxidative stress tolerance. Finally, we describe a new uvh6 phenotype, the low penetrance production of flowers with five petals and five sepals. ddb1a and ddb2 suppress this phenotype in uvh6 mutants. Interestingly, heat treatment also induces five-petalled flowers in the ddb1a and ddb2 single mutants. Thus UVH6, DDB1A, and DDB2 all contribute to UV tolerance, heat tolerance and floral patterning.

A novel mutation in KIAA0196: identification of a gene involved in Ritscher-Schinzel/3C syndrome in a First Nations cohort.

BACKGROUND: Ritscher-Schinzel syndrome (RSS) is a clinically heterogeneous disorder characterised by distinctive craniofacial features in addition to cerebellar and cardiac anomalies. It has been described in different populations and is presumed to follow autosomal recessive inheritance. In an effort to identify the underlying genetic cause of RSS, affected individuals from a First Nations (FN) community in northern Manitoba, Canada, were enrolled in this study. METHODS: Homozygosity mapping by SNP array and Sanger sequencing of the candidate genes in a 1Mb interval on chromosome 8q24.13 were performed on genomic DNA from eight FN RSS patients, eight of their parents and five unaffected individuals (control subjects) from this geographic isolate. RESULTS: All eight patients were homozygous for a novel splice site mutation in KIAA0196. RNA analysis revealed an approximate eightfold reduction in the relative amount of a KIAA0196 transcript lacking exon 27. A 60% reduction in the amount of strumpellin protein was observed on western blot. CONCLUSIONS: We have identified a mutation in KIAA0196 as the cause of the form of RSS characterised in our cohort. The ubiquitous expression and highly conserved nature of strumpellin, the product of KIAA0196, is consistent with the complex and multisystem nature of this disorder.

Genetic interactions between Arabidopsis DET1 and UVH6 during development and abiotic stress response.

Plants must adapt to a variety of abiotic inputs, including visible light, ultraviolet (UV) light, and heat. In Arabidopsis thaliana, DE-ETIOLATED 1 (DET1) plays a role in visible light signaling, UV tolerance, and development. UV-HYPERSENSITIVE 6 (UVH6) mutants are UV and heat sensitive, as well as dwarf and pale, like det1. In this study, we examine the genetic interactions between these two genes. In dark-grown seedlings, uvh6 exhibits a weak de-etiolated phenotype but does not affect the stronger de-etiolated phenotype of det1. In the light, det1 is epistatic to uvh6 with regard to chlorophyll level, but their effect on all size parameters is additive and therefore independent. With regard to UV tolerance, det1 UV resistance is epistatic to uvh6 UV sensitivity. In heat stress experiments, det1 enhances heat-induced tissue damage in the uvh6 background but suppresses heat-induced growth inhibition. Thus, det1 acts epistatically to uvh6 with respect to de-etiolation, chlorophyll level, UV tolerance, and heat-induced growth inhibition, whereas det1 and uvh6 act additively to regulate plant size and heat-induced cell death. These data provide insight into interplay between light and heat signaling.