Divergent phenotypes in constitutive versus conditional mutant mouse models of Sifrim-Hitz-Weiss syndrome.

Chromatin remodellers are among the most important risk genes associated with neurodevelopmental disorders (NDDs), however, their functions during brain development are not fully understood. Here, we focused on Sifrim-Hitz-Weiss Syndrome (SIHIWES)-an intellectual disability disorder caused by mutations in the CHD4 chromodomain helicase gene. We utilized mouse genetics to excise the Chd4 ATPase/helicase domain-either constitutively, or conditionally in the developing telencephalon. Conditional heterozygotes exhibited no change in cortical size and cellular composition, and had only subtle behavioral phenotypes. Telencephalon-specific conditional knockouts had marked reductions in cortical growth, reduced numbers of upper-layer neurons, and exhibited alterations in anxiety and repetitive behaviors. Despite the fact that whole-body heterozygotes exhibited comparable growth defects, they were unaffected in these behaviors, but instead exhibited female-specific alterations in learning and memory. These data reveal unexpected phenotypic divergence arising from differences in the spatiotemporal deployment of loss-of-function manipulations, underscoring the importance of context in chromatin remodeller function during neurodevelopment.

The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells.

Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.

The Effectiveness and Safety of Hyperbaric Oxygen Therapy in Various Phenotypes of Inflammatory Bowel Disease: Systematic Review With Meta-analysis.

BACKGROUND: Accumulating evidence suggests that hyperbaric oxygen therapy (HBOT) may be effective for inflammatory bowel disease (IBD). Our systematic review aimed to quantify the effectiveness and safety of HBOT in various IBD phenotypes. METHODS: We performed a proportional meta-analysis. Multiple databases were systematically searched from inception through November 2020 without language restriction. We included studies that reported effectiveness and/or safety of HBOT in IBD. Weighted summary estimates with 95% confidence intervals (Cis) were calculated for clinical outcomes for each IBD phenotype using random-effects models. Study quality was assessed using the Cochrane evaluation handbook and National Institute of Health criteria. RESULTS: Nineteen studies with 809 patients total were eligible: 3 randomized controlled trials and 16 case series. Rates of clinical remission included 87% (95% CI, 10-100) for ulcerative colitis (n = 42), 88% (95% CI, 46-98) for luminal Crohn's disease (CD, n = 8), 60% (95% CI, 40-76) for perianal CD (n = 102), 31% (95% CI, 16-50) for pouch disorders (n = 60), 92% (95% CI, 38-100) for pyoderma gangrenosum (n = 5), and 65% (95% CI, 10-97) for perianal sinus/metastatic CD (n = 7). Of the 12 studies that reported on safety, 15% of patients (n = 30) had minor adverse events. Study quality was low in the majority of studies due to an absence of comparator arms, inadequate description of concomitant interventions, and/or lack of objective outcomes. CONCLUSIONS: Limited high-quality evidence suggests that HBOT is safe and associated with substantial rates of clinical remission for multiple IBD phenotypes. Well-designed randomized controlled trials are warranted to confirm the benefit of HBOT in IBD.

Chromatin Remodeling in the Brain-a NuRDevelopmental Odyssey.

During brain development, the genome must be repeatedly reconfigured in order to facilitate neuronal and glial differentiation. A host of chromatin remodeling complexes facilitates this process. At the genetic level, the non-redundancy of these complexes suggests that neurodevelopment may require a lexicon of remodelers with different specificities and activities. Here, we focus on the nucleosome remodeling and deacetylase (NuRD) complex. We review NuRD biochemistry, genetics, and functions in neural progenitors and neurons.

Measuring the teamwork performance of operating room teams: a systematic review of assessment tools and their measurement properties.

Teamwork is fundamental to surgical patient safety but is inconsistently measured. While many tools have been developed for elective intraoperative situations, it is unclear which is the most robust. This systematic review aimed to identify tools to measure the teamwork of operating room teams. Studies were included if they examined the measurement properties of these tools. PsycINFO, Embase (via OVID), CINAHL, ERIC, Medline and Medline in Process (via OVID) were searched through to May 3, 2019, as were reference lists of included studies and previously published relevant reviews. Retrieved articles were screened and data extracted in duplicate by two independent reviewers. Quality was assessed using the COSMIN checklist. Of the 2121 references identified, 14 studies of six assessment tools were included. Tools were validated across various specialties, mostly in clinical rather than simulated settings. The Observational Teamwork Assessment for Surgery (OTAS) and Operating Theater Team Non-Technical Skills Assessment Tool (NOTECHS) were the most frequently investigated tools. Though acceptable for assessing teamwork, both NOTECHS and OTAS rely on the questionable assumption that the teamwork of a team is equivalent to the sum of individual performances. Future studies may investigate other assessment tools that assess the whole team as the unit of analysis along with the potential of these tools to provide healthcare providers with meaningful feedback in clinical practice.

Reporting preclinical anesthesia study (REPEAT): Evaluating the quality of reporting in the preclinical anesthesiology literature.

Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008-2009, 2014-2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.

Interprofessional communication in the operating room: a narrative review to advance research and practice.

PURPOSE: Communication failures are often at the root of adverse events for surgical patients; however, evidence to inform best communication practice in the operating room is relatively limited. This narrative review outlines the importance of interprofessional communication for surgical patient safety, maps its barriers and facilitators, and highlights key strategies for enhancing communication quality in the operating room. Based on this review, a research agenda to inform best practices in interprofessional operating room communication is suggested. SOURCE: The non-systematic literature search included searches of relevant databases (Medline (via OVID), PubMed, Scopus, and EMBASE, PsycINFO, CINAHL), relevant grey literature sources (e.g., patient safety institute websites), and reference lists of selected articles. PRINCIPAL FINDINGS: Effective interprofessional communication plays a critical role in the operating room, but faces many challenges at the individual, team, environmental, and organizational level. Factors that support effective communication are less documented than barriers, but include team integration, flattened hierarchies, and structure/standardization. Checklists, safety briefings, and teamwork/communication training are the most common techniques used to improve communication in the operating room. Of all communication techniques, closed-loop communication may be the most practical and inexpensive strategy. CONCLUSION: The perioperative community should be encouraged to implement existing effective solutions to improve communication and investigate creative solutions to identified barriers. Improved methods of data collection are needed to enhance evidence quality, increase understanding of communication barriers and facilitators, and identify the best strategy to advance practice.

RéSUMé: OBJECTIF: Les problèmes de communication sont souvent à l'origine des événements indésirables pour les patients chirurgicaux, et les données probantes pour guider les meilleures pratiques de communication en salle d'opération sont encore relativement limitées. Ce compte rendu narratif souligne l'importance de la communication interprofessionnelle pour la sécurité des patients chirurgicaux, cartographie ses obstacles et les éléments la facilitant, et présente des stratégies clés pour améliorer la qualité de la communication en salle d'opération. Sur la base de ce compte rendu, un agenda de recherche visant à guider les meilleures pratiques en matière de communication interprofessionnelle en salle d'opération est proposé. SOURCE: Notre recherche de littérature non méthodique s'est intéressée aux bases de données pertinentes (Medline (via OVID), PubMed, Scopus, et EMBASE, PsycINFO, CINAHL), aux sources pertinentes de la littérature grise (par ex., sites Internet des instituts sur la sécurité des patients), et aux listes de références des articles sélectionnés. CONSTATATIONS PRINCIPALES: Une communication interprofessionnelle efficace joue un rôle crucial en salle d'opération, mais elle est souvent mise à l'épreuve tant aux niveaux de l'individu, de l'équipe, de l'environnement que de l'organisation. Les facteurs facilitant une communication efficace sont moins documentés que les obstacles; ils comprennent l'intégration de l'équipe, une structure organisationnelle horizontale et la structure/standardisation. Les listes de contrôle, les réunions sur la sécurité et la formation en travail d'équipe/communications sont les techniques les plus fréquemment utilisées pour améliorer la communication en salle d'opération. Parmi toutes les techniques de communication, la communication en circuit fermé pourrait constituer la stratégie la plus pratique et la moins onéreuse. CONCLUSION: La communauté périopératoire devrait être encouragée à appliquer les solutions existantes ayant prouvé leur efficacité afin d'améliorer la communication et explorer des solutions créatives pour pallier les obstacles identifiés. De meilleures méthodes de collecte de données sont nécessaires pour améliorer la qualité des données probantes, augmenter la compréhension des obstacles et des aides à la communication, et identifier les meilleures stratégies pour améliorer la pratique.

Measuring the teamwork performance of teams in crisis situations: a systematic review of assessment tools and their measurement properties.

BACKGROUND: Educational interventions to improve teamwork in crisis situations have proliferated in recent years with substantial variation in teamwork measurement. This systematic review aimed to synthesise available tools and their measurement properties in order to identify the most robust tool for measuring the teamwork performance of teams in crisis situations. METHODS: Searches were conducted in Embase (via OVID), PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Education Resources Information Center, Medline and Medline In-Process (via OVID) (through 12 January 2017). Studies evaluating the measurement properties of teamwork assessment tools for teams in clinical or simulated crisis situations were included. Two independent reviewers screened studies based on predetermined criteria and completed data extraction. Risk of bias was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. RESULTS: The search yielded 1822 references. Twenty studies were included, representing 13 assessment tools. Tools were primarily assessed in simulated resuscitation scenarios for emergency department teams. The Team Emergency Assessment Measure (TEAM) had the most validation studies (n=5), which demonstrated three sources of validity (content, construct and concurrent) and three sources of reliability (internal consistency, inter-rater reliability and test-retest reliability). Most studies of TEAM's measurement properties were at no risk of bias. CONCLUSIONS: A number of tools are available for assessing teamwork performance of teams in crisis situations. Although selection will ultimately depend on the user's context, TEAM may be the most promising tool given its measurement evidence. Currently, there is a lack of tools to assess teamwork performance during intraoperative crisis situations. Additional research is needed in this regard.

Anesthesia interventions that alter perioperative mortality: a scoping review.

BACKGROUND: With over 230 million surgical procedures performed annually worldwide, better application of evidence in anesthesia and perioperative medicine may reduce widespread variation in clinical practice and improve patient care. However, a comprehensive summary of the complete available evidence has yet to be conducted. This scoping review aims to map the existing literature investigating perioperative anesthesia interventions and their potential impact on patient mortality, to inform future knowledge translation and ultimately improve perioperative clinical practice. METHODS: Searches were conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library databases from inception to March 2015. Study inclusion criteria were adult patients, surgical procedures requiring anesthesia, perioperative intervention conducted/organized by a professional with training in anesthesia, randomized controlled trials (RCTs), and patient mortality as an outcome. Studies were screened for inclusion, and data was extracted in duplicate by pairs of independent reviewers. Data were extracted, tabulated, and reported thematically. RESULTS: Among the 10,505 publications identified, 369 RCTs (n = 147,326 patients) met the eligibility criteria. While 15 intervention themes were identified, only 7 themes (39 studies) had a significant impact on mortality: pharmacotherapy (n = 23), nutritional (n = 3), transfusion (n = 4), ventilation (n = 5), glucose control (n = 1), medical device (n = 2), and dialysis (n = 1). CONCLUSIONS: By mapping intervention themes, this scoping review has identified areas requiring further systematic investigation given their potential value for reducing patient mortality as well as areas where continued investment may not be cost-effective given limited evidence for improving survival. This is a key starting point for future knowledge translation to optimize anesthesia practice.