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INTRODUCTION: Health behaviours such as exercise and diet strongly influence well-being and disease risk, providing the opportunity for interventions tailored to diverse individual contexts. Precise behaviour interventions are critical during adolescence and young adulthood (ages 10-25), a formative period shaping lifelong well-being. We will conduct a systematic review of just-in-time adaptive interventions (JITAIs) for health behaviour and well-being in adolescents and young adults (AYAs). A JITAI is an emerging digital health design that provides precise health support by monitoring and adjusting to individual, specific and evolving contexts in real time. Despite demonstrated potential, no published reviews have explored how JITAIs can dynamically adapt to intersectional health factors of diverse AYAs. We will identify the JITAIs' distal and proximal outcomes and their tailoring mechanisms, and report their effectiveness. We will also explore studies' considerations of health equity. This will form a comprehensive assessment of JITAIs and their role in promoting health behaviours of AYAs. We will integrate evidence to guide the development and implementation of precise, effective and equitable digital health interventions for AYAs. METHODS AND ANALYSIS: In adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we will conduct a systematic search across multiple databases, including CENTRAL, MEDLINE and WHO Global Index Medicus. We will include peer-reviewed studies on JITAIs targeting health of AYAs in multiple languages. Two independent reviewers will conduct screening and data extraction of study and participant characteristics, JITAI designs, health outcome measures and equity considerations. We will provide a narrative synthesis of findings and, if data allows, conduct a meta-analysis. ETHICS AND DISSEMINATION: As we will not collect primary data, we do not require ethical approval. We will disseminate the review findings through peer-reviewed journal publication, conferences and stakeholder meetings to inform participatory research. PROSPERO REGISTRATION NUMBER: CRD42023473117.
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Conductas Relacionadas con la Salud , Revisiones Sistemáticas como Asunto , Humanos , Adolescente , Adulto Joven , Proyectos de Investigación , Promoción de la Salud/métodos , Ejercicio FísicoRESUMEN
Mass gatherings include a diverse range of events such as sporting competitions, religious ceremonies, entertainment activities, political rallies and cultural celebrations, which have important implications for population well-being. However, if not managed properly, these events can amplify health risks including those related to communicable diseases, and place undue strain on health systems in host countries and potentially in attendees' home countries, upon their return. The coronavirus disease 2019 (COVID-19) pandemic has provided a unique opportunity to evaluate the risk factors associated with mass gatherings and the effectiveness of applying mitigation measures during infectious disease emergencies. The pandemic has also allowed event organizers and health officials to identify best practices for mass gathering planning in host countries. To guide decisions about whether to hold, postpone, modify or cancel a mass gathering during the COVID-19 pandemic, the World Health Organization and its partners developed normative guidance and derivative tools promoting a risk-based approach to mass gathering planning. This approach involves three steps to guide decision-making around mass gatherings: risk evaluation, risk mitigation and risk communication. The approach was applied in the planning and execution of several mass gathering events, including the Tokyo 2020 and Beijing 2022 Olympic and Paralympic Games. Lessons identified from these large-scale international events offer insights into the planning and implementation of mass gathering events during a pandemic, and the broader impacts of such events on society. These lessons may also further inform and refine planning for future mass gatherings.
Les rassemblements de masse désignent un large éventail d'événements tels que des compétitions sportives, cérémonies religieuses, activités de divertissement, manifestations politiques et fêtes culturelles. Tous ont un impact considérable sur le bien-être de la population. Toutefois, s'ils ne sont pas gérés correctement, ils peuvent augmenter les risques sanitaires, notamment concernant les maladies transmissibles, et exercer une pression excessive sur les systèmes de santé des pays hôtes, voire sur ceux des pays d'origine des participants après leur retour. La pandémie de maladie à coronavirus 2019 (COVID-19) a offert une occasion unique d'évaluer les facteurs de risque associés aux rassemblements de masse, ainsi que l'efficacité des mesures visant à limiter la propagation dans des situations d'urgence liées à des maladies infectieuses. Cette pandémie a également permis aux organisateurs d'événements et responsables de santé d'identifier les bonnes pratiques à appliquer dans les pays hôtes pendant les rassemblements de masse. Afin de guider les décisions relatives au maintien, au report, à la modification ou à l'annulation d'un rassemblement de masse durant la pandémie de COVID-19, l'Organisation mondiale de la Santé et ses partenaires ont mis au point des orientations normatives et des outils dérivés favorisant une approche tenant compte des risques au moment de la planification. Cette approche comprend trois étapes contribuant à la prise de décision: l'évaluation, la réduction et la communication des risques. Elle a été déployée lors de la planification et de l'exécution de nombreux rassemblements de masse, comme les Jeux olympiques et paralympiques de Tokyo 2020 et Beijing 2022. Les leçons tirées de ces événements internationaux à grande échelle fournissent des informations sur leur organisation et leur mise en Åuvre en cas de pandémie, ainsi que les impacts de tels événements sur la société. Elles sont en outre susceptibles de faciliter et d'améliorer la planification des futurs rassemblements de masse.
Las concentraciones masivas incluyen una gran variedad de eventos, como competiciones deportivas, ceremonias religiosas, actividades de entretenimiento, mítines políticos y celebraciones culturales, que tienen importantes implicaciones para el bienestar de la población. Sin embargo, si no se gestionan adecuadamente, estos eventos pueden amplificar los riesgos para la salud, incluidos los relacionados con las enfermedades transmisibles, y suponer una carga excesiva para los sistemas sanitarios de los países anfitriones y, potencialmente, de los países de origen de los participantes a su regreso. La pandemia de la enfermedad por coronavirus de 2019 (COVID-19) ha brindado una oportunidad única para evaluar los factores de riesgo asociados a las concentraciones masivas y la eficacia de aplicar medidas de mitigación durante las emergencias por enfermedades infecciosas. La pandemia también ha permitido a los organizadores de eventos y a las autoridades sanitarias identificar las mejores prácticas para la planificación de concentraciones masivas en los países anfitriones. Para orientar las decisiones sobre la celebración, el aplazamiento, la modificación o la cancelación de una concentración masiva durante la pandemia de la COVID-19, la Organización Mundial de la Salud y sus asociados elaboraron orientaciones normativas y herramientas derivadas que promueven un enfoque de la planificación de concentraciones masivas basado en los riesgos. Este enfoque consta de tres pasos para orientar la toma de decisiones en torno a las concentraciones masivas: la evaluación, la mitigación y la comunicación de riesgos. El enfoque se aplicó en la planificación y ejecución de varias concentraciones masivas, incluidos los Juegos Olímpicos y Paralímpicos de Tokio 2020 y Pekín 2022. Las conclusiones extraídas de estos eventos internacionales a gran escala permiten comprender mejor la planificación y ejecución de concentraciones masivas durante una pandemia, así como las repercusiones más generales de estos eventos en la sociedad. Estas lecciones también pueden informar y perfeccionar la planificación de futuras concentraciones masivas.
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COVID-19 , Reuniones Masivas , SARS-CoV-2 , Deportes , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Gestión de Riesgos/métodos , Gestión de Riesgos/organización & administración , Organización Mundial de la Salud , Medición de Riesgo , InternacionalidadRESUMEN
The diet during pregnancy, or antenatal diet, influences the offspring's intestinal health. We previously showed that antenatal butyrate supplementation reduces injury in adult murine offspring with dextran sulfate sodium (DSS)-induced colitis. Potential modulators of butyrate levels in the intestine include a high fiber diet or dietary supplementation with probiotics. To test this, we supplemented the diet of pregnant mice with high fiber, or with the probiotic bacteria Lactococcus lactis subspecies cremoris or Lactobacillus rhamnosus GG. We then induced chronic colitis with DSS in their adult offspring. We demonstrate that a high fiber antenatal diet, or supplementation with Lactococcus lactis subspecies cremoris during pregnancy diminished the injury from DSS-induced colitis in offspring. These data are evidence that antenatal dietary interventions impact offspring gut health and define the antenatal diet as a therapeutic modality to enhance offspring intestinal health.
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Colitis , Microbioma Gastrointestinal , Lactococcus lactis , Lactococcus , Femenino , Embarazo , Animales , Ratones , Lactococcus lactis/genética , Suplementos Dietéticos , ButiratosRESUMEN
BACKGROUND: Symptoms, imaging characteristics, and early and midterm surgical outcomes for aberrant subclavian arteries (ASCA) are not well defined in the adult population. METHODS: A single-institution retrospective review was conducted of adults undergoing surgical repair of ASCA and descending aorta origin/Kommerell diverticulum (KD) from January 1, 2002, to December 31, 2021. Symptom improvement and differences in imaging characteristics between anatomic groups and the number of symptoms were assessed. RESULTS: Mean age was 46 ± 17 years. There were 23 of 37 left aortic arches with right ASCA (62%) and 14 of 37 right aortic arches with left ASCA (38%). Of these, 31 of 37 (84%) were symptomatic, and 19 of 37 (51%) had KD size/growth meeting criteria for surgical repair. KD aortic origin diameter was larger in more symptomatic patients: 20.60 mm (interquartile range [IQR], 16.42-30.68 mm) in patients with ≥3 symptoms vs 22.05 mm (IQR, 17.52-24.21 mm) for 2 symptoms vs 13.72 mm (IQR, 12.70-15.95 mm) for 1 symptom (P = .018). Aortic replacement was required in 22 of 37 (59%). There were no early deaths. Complications occurred in 11 of 37 (30%): vocal cord dysfunction (4 of 37 [11%]), chylothorax (3 of 37 [8%]), Horner syndrome (2 of 37 [5%]), spinal deficit (2 of 37 [5%]), stroke (1 of 37 [3%]), and temporary dialysis requirement (1 of 37 [3%]). Over a median follow-up of 2.3 years (IQR, 0.8-3.9 years), there was 1 endovascular reintervention and no reoperations. Dysphagia and shortness of breath resolved in 92% and 89%, respectively, whereas gastroesophageal reflux persisted in 47%. CONCLUSIONS: The KD aortic origin diameter correlates with the number of symptoms, and surgical repair of ASCA and descending aorta origin/KD effectively relieves symptoms, with low rates of reintervention. Given the operative complexity, surgical repair should be performed in patients meeting size criteria or with significant dysphagia or shortness of breath symptoms.
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Síndromes del Arco Aórtico , Implantación de Prótesis Vascular , Anomalías Cardiovasculares , Trastornos de Deglución , Divertículo , Procedimientos Endovasculares , Adulto , Humanos , Persona de Mediana Edad , Trastornos de Deglución/cirugía , Trastornos de Deglución/complicaciones , Arteria Subclavia/cirugía , Resultado del Tratamiento , Anomalías Cardiovasculares/diagnóstico por imagen , Anomalías Cardiovasculares/cirugía , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Procedimientos Endovasculares/efectos adversos , Síndromes del Arco Aórtico/complicaciones , Disnea , Estudios Retrospectivos , Implantación de Prótesis Vascular/efectos adversos , Divertículo/cirugíaRESUMEN
Background: With the shift in focus from the hard to soft tissue in orthodontic diagnosis and treatment planning, the scope of orthodontic treatment has grown beyond achieving an ideal occlusion, also to achieve ideal aesthetic facial proportions. Since time immemorial, the various horizontal and vertical proportions of an ideal face is considered to follow the golden/divine ratio. Aim: The aim of this study is to assess the vertical and horizontal proportions of the face and their relation of phi in males and females of Dakshina Kannada population. Materials and Methods: The study was carried out on 100 subjects, which included 50 males and 50 females, aged between 18 and 30 years. Photographs were taken under standardized condition and adjusted to a standardized image size (5â³ × 4â³). Adobe Photoshop CS5.1 software was used for making all the measurements. A total of 11 vertical and horizontal ratios were independently measured for males and females, and their relation to phi was assessed. The data were subjected to Shapiro-Wilk test for testing the normality. Homogeneity of variance assumption was tested by using Levene statistic homogeneity of variance. One sample t test was used for the comparison between phi and mean vertical and horizontal ratios in males and females. Results: In males and females of the Dakshina Kannada, a statistically significant correlation was seen between all the horizontal and vertical facial proportions and phi (p < 0.05). Between male and female groups, a significant difference was noted in the intertemporal/intercanthal ratio, interalae/nose width and Intereye-soft menton/ala-soft menton (p < 0.05). Conclusion: Golden proportion can be used as a guideline in orthodontic treatment planning. However, it should not be the decisive factor in determining the facial attractiveness.
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Estética Dental , Cara , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Cara/anatomía & histología , Cefalometría/métodos , Atención OdontológicaRESUMEN
The human body possesses a unique set of machinery called the molecular/biological clocks that function on a regular 24-h basis forming a circadian rhythm (CR). This aids in coordinating the human biological system with ever-changing environmental conditions, thereby maintaining a balance in its functioning. The central/core component of this system is known to be in the suprachiasmatic nucleus of the hypothalamus with a few aides in the periphery. The periodontal ligament in humans, being one of the dynamic oral tissues, has been shown to exhibit this self-sustained, innate oscillatory behavior that has gained significant attention from dental surgeons. Though substantial evidence regarding its precise role in maintaining circadian periodicity is still unclear, its indispensable role in dentofacial functioning cannot be denied. This review is an attempt in bringing to light the possible role of circadian periodicity in the functioning of oral tissues in the field of orthodontics with a special focus on its role in bone remodeling, orthodontic tooth movement, orthopedic and functional appliances, pain management, and their clinical implications. This could provide a better understanding of the various physiologic and pathologic processes and help us refine our approach toward orthodontic diagnosis and therapeutics. This review would therefore serve as an overview, opening more avenues for further research on this topic that can greatly help the orthodontic fraternity.
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Children with beta-thalassemia (BT) present with an increase in carotid intima-medial thickness, an early sign suggestive of premature atherosclerosis. However, it is unknown if there is a direct relationship between BT and atherosclerotic disease. To evaluate this, wild-type (WT, littermates) and BT (Hbbth3/+) mice, both male and female, were placed on a 3-mo high-fat diet with low-density lipoprotein receptor suppression via overexpression of proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation (D377Y). Mechanistically, we hypothesize that heme-mediated oxidative stress creates a proatherogenic environment in BT because BT is a hemolytic anemia that has increased free heme and exhausted hemopexin, heme's endogenous scavenger, in the vasculature. We evaluated the effect of hemopexin (HPX) therapy, mediated via an adeno-associated virus, to the progression of atherosclerosis in BT and a phenylhydrazine-induced model of intravascular hemolysis. In addition, we evaluated the effect of deferiprone (DFP)-mediated iron chelation in the progression of atherosclerosis in BT mice. Aortic en face and aortic root lesion area analysis revealed elevated plaque accumulation in both male and female BT mice compared with WT mice. Hemopexin therapy was able to decrease plaque accumulation in both BT mice and mice on our phenylhydrazine (PHZ)-induced model of hemolysis. DFP decreased atherosclerosis in BT mice but did not provide an additive benefit to HPX therapy. Our data demonstrate for the first time that the underlying pathophysiology of BT leads to accelerated atherosclerosis and shows that heme contributes to atherosclerotic plaque development in BT.NEW & NOTEWORTHY This work definitively shows for the first time that beta-thalassemia leads to accelerated atherosclerosis. We demonstrated that intravascular hemolysis is a prominent feature in beta-thalassemia and the resulting increases in free heme are mechanistically relevant. Adeno-associated virus (AAV)-hemopexin therapy led to decreased free heme and atherosclerotic plaque area in both beta-thalassemia and phenylhydrazine-treated mice. Deferiprone-mediated iron chelation led to deceased plaque accumulation in beta-thalassemia mice but provided no additive benefit to hemopexin therapy.
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Enfermedades de la Aorta , Aterosclerosis , Placa Aterosclerótica , Talasemia beta , Humanos , Niño , Masculino , Femenino , Ratones , Animales , Proproteína Convertasa 9/genética , Talasemia beta/complicaciones , Talasemia beta/genética , Hemopexina , Deferiprona , Hemólisis , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Ratones Noqueados , Aterosclerosis/genética , Aterosclerosis/patología , Hemo , Fenilhidrazinas , Quelantes del Hierro , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. METHODS: This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). RESULTS: Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. CONCLUSIONS: Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future.
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COVID-19 , Infecciones Relacionadas con Catéteres , Terapia de Reemplazo Renal Continuo , Adulto , Humanos , Soluciones para Diálisis , Pandemias , Estudios RetrospectivosRESUMEN
The oral microbiome is a complex community that matures with dental development while oral health is also a recognized risk factor for systemic disease. Despite the oral cavity having a substantial microbial burden, healing of superficial oral wounds occurs quickly and with little scarring. By contrast, creation of an oro-nasal fistula (ONF), often occurring after surgery to correct a cleft palate, is a significant wound healing challenge that is further complicated by a connection of the oral and nasal microbiome. In this study, we characterized the changes in the oral microbiome of mice following a freshly inflicted wound in the oral palate that results in an open and unhealed ONF. Creation of an ONF in mice significantly lowered oral microbiome alpha diversity, with concurrent blooms of Enterococcus faecalis, Staphylococcus lentus, and Staphylococcus xylosus in the oral cavity. Treatment of mice with oral antibiotics one week prior to ONF infliction resulted in a reduction in the alpha diversity, prevented E. faecalis and S. lentus, and S. xylosus blooms, but did not impact ONF healing. Strikingly, delivery of the beneficial microbe Lactococcus lactis subsp. cremoris (LLC) to the wound bed of the freshly inflicted ONF via a PEG-MAL hydrogel vehicle resulted in rapid healing of the ONF. Healing of the ONF was associated with the maintenance of relatively high microbiome alpha diversity, and limited the abundance of E. faecalis and S. lentus, and S. xylosus in the oral cavity. These data demonstrate that a freshly inflicted ONF in the murine palate is associated with a dysbiotic oral microbiome state that may prevent ONF healing, and a bloom of opportunistic pathogens. The data also demonstrate that delivery of a specific beneficial microbe, LLC, to the ONF can boost wound healing, can restore and/or preserve oral microbiome diversity, and inhibit blooms of opportunistic pathogens.
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Stimulating the Gq-coupled P2Y2 receptor (P2ry2) lowers blood pressure. Global knockout of P2ry2 increases blood pressure. Vascular and renal mechanisms are believed to participate in P2ry2 effects on blood pressure. To isolate the role of the kidneys in P2ry2 effects on blood pressure and to reveal the molecular and cellular mechanisms of this action, we test here the necessity of the P2ry2 and the sufficiency of Gq-dependent signaling in renal principal cells to the regulation of the epithelial Na+ channel (ENaC), sodium excretion, and blood pressure. Activating P2ry2 in littermate controls but not principal cell-specific P2ry2-knockout mice decreased the activity of ENaC in renal tubules. Moreover, deletion of P2ry2 in principal cells abolished increases in sodium excretion in response to stimulation of P2ry2 and compromised the normal ability to excrete a sodium load. Consequently, principal cell-specific knockout of P2ry2 prevented decreases in blood pressure in response to P2ry2 stimulation in the deoxycorticosterone acetate-salt (DOCA-salt) model of hypertension. In wild-type littermate controls, such stimulation decreased blood pressure in this model of hypertension by promoting a natriuresis. Pharmacogenetic activation of Gq exclusively in principal cells using targeted expression of Gq-designer receptors exclusively activated by designer drugs and clozapine N-oxide decreased the activity of ENaC in renal tubules, promoting a natriuresis that lowered elevated blood pressure in the DOCA-salt model of hypertension. These findings demonstrate that the kidneys play a major role in decreasing blood pressure in response to P2ry2 activation and that inhibition of ENaC activity in response to P2ry2-mediated Gq signaling lowered blood pressure by increasing renal sodium excretion.
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Acetato de Desoxicorticosterona , Hipertensión , Ratones , Animales , Presión Sanguínea/fisiología , Receptores Purinérgicos P2Y2/genética , Sodio/metabolismo , Hipertensión/metabolismo , Ratones NoqueadosRESUMEN
The intestinal microbiome has emerged as a potential contributor to the severity of sickle cell disease (SCD). We sought to determine whether SCD mice exhibit intestinal barrier dysfunction, inflammation, and dysbiosis. Using the Townes humanized sickle cell mouse model, we found a 3-fold increase in intestinal permeability as assessed via FITC-dextran (4 kDa) assay in SS (SCD) mice compared to AA (wild type) mice (n = 4, p < 0.05). This was associated with 25 to 50% decreases in claudin-1, 3, and 15 and zonula occludens-1 gene expression (n = 8-10, p < 0.05) in the small intestine. Increased Ly6G staining demonstrated more neutrophils in the SS small intestine (3-fold, n = 5, p < 0.05) associated with increased expression of TNFα, IL-17A, CXCL1, and CD68 (2.5 to 5-fold, n = 7-10, p < 0.05). In addition, we observed 30 to 55% decreases in superoxide dismutase-1, glutathione peroxidase-1, and catalase antioxidant enzyme expression (n = 7-8, p < 0.05) concomitant to an increase in superoxide (2-fold, n = 4, p < 0.05). Importantly, all significant observations of a leaky gut phenotype and inflammation were limited to the small intestine and not observed in the colon. Finally, characterization of the composition of the microbiome within the small intestine revealed dysbiosis in SS mice compared to their AA littermates with 47 phyla to species-level significant alterations in amplicon sequence variants. We conclude that the intestinal barrier is compromised in SCD, associated with decreased gene expression of tight junction proteins, enhanced inflammation, oxidative stress, and gut microbiome dysbiosis, all specific to the small intestine.
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Bicaudal D2 (BICD2) is responsible for recruiting cytoplasmic dynein to diverse forms of subcellular cargo for their intracellular transport. Mutations in the human BICD2 gene have been found to cause an autosomal dominant form of spinal muscular atrophy (SMA-LED2), and brain developmental defects. Whether and how the latter mutations are related to roles we and others have identified for BICD2 in brain development remains little understood. BICD2 interacts with the nucleoporin RanBP2 to recruit dynein to the nuclear envelope (NE) of Radial Glial Progenitor cells (RGPs) to mediate their well-known but mysterious cell-cycle-regulated interkinetic nuclear migration (INM) behavior, and their subsequent differentiation to form cortical neurons. We more recently found that BICD2 also mediates NE dynein recruitment in migrating post-mitotic neurons, though via a different interactor, Nesprin-2. Here, we report that Nesprin-2 and RanBP2 compete for BICD2-binding in vitro. To test the physiological implications of this behavior, we examined the effects of known BICD2 mutations using in vitro biochemical and in vivo electroporation-mediated brain developmental assays. We find a clear relationship between the ability of BICD2 to bind RanBP2 vs. Nesprin-2 in controlling of nuclear migration and neuronal migration behavior. We propose that mutually exclusive RanBP2-BICD2 vs. Nesprin-2-BICD2 interactions at the NE play successive, critical roles in INM behavior in RGPs and in post-mitotic neuronal migration and errors in these processes contribute to specific human brain malformations.
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Dineínas , Proteínas de Microfilamentos , Chaperonas Moleculares , Proteínas del Tejido Nervioso , Proteínas de Complejo Poro Nuclear , Niño , Humanos , Encéfalo/metabolismo , Discapacidades del Desarrollo , Dineínas/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismoRESUMEN
The mature peptide of growth differentiation factor 11 (GDF11) in Bos taurus breeds, shares 90% amino acid sequence similarity to myostatin (MSTN), where loss-of-function mutations result in muscular hyperplasia causing a phenotype known as double-muscling. Mutations in the MSTN coding sequence increase muscle mass and reduce fat and bone tissues, but also confer poor fertility, reduced stress tolerance, and increased calf mortality. GDF11 influences skeletal muscle development in mice, and muscular atrophy can be induced by exogenous GDF11 treatment. To date, there are no reports of GDF11's role in bovine carcass traits. To determine associations between GDF11 and carcass quality in beef cattle, bovine GDF11 was examined in crossbred Canadian beef cattle populations during finishing. Few coding variants were found in this functionally important gene, but an upstream variant c.1-1951Câ >â T (rs136619751) with a minor allele frequency of 0.31 was identified and further genotyped in two separate populations of crossbred steers (nâ =â 415 and 450). CC animals had lower backfat thickness, marbling percentage, and yield score than CT or TT animals (Pâ <â 0.001 andâ <â 0.05). These data suggest a role of GDF11 in carcass quality in beef cattle and may provide a selection tool to improve carcass traits in cattle.
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Objective: Schools are considered an important setting for stimulating healthy weight. The current study is unique in examining effects of a multi-component school-based social network intervention on children's body mass index z-scores (zBMI).Methods: Four schools were randomly allocated to one of four conditions: a social network intervention using influence agents focusing on water consumption, physical activity, a combination of the two, or a passive control condition. Participants included a total of 201 6- to-11-year-old children (53.7% girls; Mage = 8.51, SDage = 0.93). At baseline, 149 (76.0%) participants had a healthy weight, 29 (14.8%) had overweight and 18 (9.2%) had obesity.Results: Linear mixed effect models indicated that a multi-component school-based social network intervention targeting both water consumption and physical activity was most effective in decreasing children's zBMI.Conclusion: This study suggests that schools can contribute to the intervention of childhood obesity-even without involving the parents-by targeting both children's water consumption and physical activity through influential peers, but more research is needed to identify mechanisms of change.
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OBJECTIVE: To evaluate the effectiveness of an automated hand hygiene compliance system (AHHCS) audible alert and vibration for increasing hand hygiene compliance. DESIGN: A nonrandomized, before-and-after, quasi-experimental study of an AHHCS was implemented in several inpatient units. Over a 51-day period, the system's real-time audible alert was turned on, off, and back on. Overall, hand hygiene compliance was compared between days with activated and deactivated alerts and vibration. SETTING: This study was conducted at a level 1 trauma center, a regional academic health system with 1,564 beds. PARTICIPANTS: The AHHCS was implemented in 9 inpatient units: 3 adult medical-surgical step-down units, and 6 adult intensive care units. The AHHCS badges were assigned to patient care assistants, registered nurses, physical therapists, occupational therapists, speech therapists, respiratory therapists, and physicians. INTERVENTION: In the 9 inpatient units, selected healthcare staff were issued wearable badges that detected entry into and exit from a patient room. The audible alert was turned on for 16 days, turned off for 17 days, and then turned back on for 18 days, for a total of 51 days. RESULTS: Utilization of the AHHCS real-time audible alert reminder resulted in sustained HH compliance ≥90%. When the alert and vibration were deactivated, HH compliance dropped to an average of 74% (range, 62%-78%). Once the alert resumed, HH compliance returned to ≥90%. CONCLUSION: Utilization of an AHHCS with real-time reminder audible alerts may be an effective method to increase healthcare worker HH compliance to ≥90%. Users of AHHCSs should consider the use of real-time reminders to improve HH compliance.
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Infección Hospitalaria , Higiene de las Manos , Médicos , Adulto , Humanos , Higiene de las Manos/métodos , Personal de Salud , Unidades de Cuidados Intensivos , Adhesión a Directriz , Control de Infecciones/métodosRESUMEN
Substituting the consumption of sugar-sweetened beverages (SSB) with that of water can have a positive effect on adolescents' health. However, despite the attention on this topic in the Global North, it is relatively understudied in other regions of the world, such as the Caribbean. To guide the development of future interventions, understanding the factors determining water consumption among Caribbean adolescents is important. This study examined the behavioral determinants of water consumption among adolescents in Aruba (the Caribbean) and compared them to those in the Netherlands (Western Europe). We used a theoretical model that integrates the dominant theoretical perspectives in the field of public health, including theories of planned behavior, social norms, and intrinsic motivation. This cross-country study included 1,584 adolescents from Aruba and the Netherlands (52% girls; M = 12.34 years; SD = 2.14). The data were analyzed using regression analyses. This study found that in Aruba, adolescents with higher scores of intrinsic motivation, friends' descriptive norms, attitudes, and behavioral control regarding water consumption drank more water. Moreover, the associations between water consumption and both intrinsic motivation as well as friends' descriptive norms for adolescents in Aruba were stronger than those found in the Netherlands. These associations imply that it is even more important for Aruban adolescents than Dutch adolescents to be intrinsically motivated or to perceive their friends often consuming water to drink more water. The cross-country comparison implies that future interventions in Aruba aimed at increasing adolescents' water consumption as an alternative to SSB should focus on enhancing their intrinsic motivation while considering their friends' social norms.
RESUMEN
The activity of the epithelial Na+ channel (ENaC) in principal cells of the distal nephron fine-tunes renal Na+ excretion. The renin-angiotensin-aldosterone system modulates ENaC activity to control blood pressure, in part, by influencing Na+ excretion. NADPH oxidase activator 1-dependent NADPH oxidase 1 (NOXA1/NOX1) signaling may play a key role in angiotensin II (ANG II)-dependent activation of ENaC. The present study aimed to explore the role of NOXA1/NOX1 signaling in ANG II-dependent activation of ENaC in renal principal cells. Patch-clamp electrophysiology and principal cell-specific Noxa1 knockout (PC-Noxa1 KO) mice were used to determine the role of NOXA1/NOX1 signaling in ANG II-dependent activation of ENaC. The activity of ENaC in the luminal plasma membrane of principal cells was quantified in freshly isolated split-opened tubules using voltage-clamp electrophysiology. ANG II significantly increased ENaC activity. This effect was robust and observed in response to both acute (40 min) and more chronic (48-72 h) ANG II treatment of isolated tubules and mice, respectively. Inhibition of ANG II type 1 receptors with losartan abolished ANG II-dependent stimulation of ENaC. Similarly, treatment with ML171, a specific inhibitor of NOX1, abolished stimulation of ENaC by ANG II. Treatment with ANG II failed to increase ENaC activity in principal cells in tubules isolated from the PC-Noxa1 KO mouse. Tubules from wild-type littermate controls, though, retained their ability to respond to ANG II with an increase in ENaC activity. These results indicate that NOXA1/NOX1 signaling mediates ANG II stimulation of ENaC in renal principal cells. As such, NOXA1/NOX1 signaling in the distal nephron plays a central role in Na+ homeostasis and control of blood pressure, particularly as it relates to regulation by the renin-ANG II axis.NEW & NOTEWORTHY Activity of the epithelial Na+ channel (ENaC) in the distal nephron fine-tunes renal Na+ excretion. Angiotensin II (ANG II) has been reported to enhance ENaC activity. Emerging evidence suggests that NADPH oxidase (NOX) signaling plays an important role in the stimulation of ENaC by ANG II in principal cells. The present findings indicate that NOX activator 1/NOX1 signaling mediates ANG II stimulation of ENaC in renal principal cells.