Cardiorespiratory fitness is an important marker of childhood health and low fitness levels are a risk factor for disease later in life. Levels of children's fitness have declined in recent decades. ...Whether school-based physical activity interventions can increase fitness at the population level remains unclear.
To evaluate the effect of an internet-based intervention on children's cardiorespiratory fitness across a large number of schools.
In this cluster randomized clinical trial, 22 government-funded elementary schools (from 137 providing consent) including 1188 students stratified from grades 3 and 4 in New South Wales, Australia, were randomized. The other schools received the intervention but were not included in the analysis. Eleven schools received the internet-based intervention and 11 received the control intervention. Recruitment and baseline testing began in 2016 and ended in 2017. Research assistants, blinded to treatment allocation, completed follow-up outcome assessments at 12 and 24 months. Data were analyzed from July to August 2020.
The internet-based intervention included standardized online learning for teachers and minimal in-person support from a project mentor (9-10 months).
Multistage 20-m shuttle run test for cardiorespiratory fitness.
Of 1219 participants (49% girls; mean SD age, 8.85 0.71 years) from 22 schools, 1188 students provided baseline primary outcome data. At 12 months, the number of 20-m shuttle runs increased by 3.32 laps (95% CI, 2.44-4.20 laps) in the intervention schools and 2.11 laps (95% CI, 1.38-2.85 laps) in the control schools (adjusted difference = 1.20 laps; 95% CI, 0.17-2.24 laps). By 24 months, the adjusted difference was 2.22 laps (95% CI, 0.89-3.55 laps). The cost per student was AUD33 (USD26).
In this study, a school-based intervention improved children's cardiorespiratory fitness when delivered in a large number of schools. The low cost and sustained effect over 24 months of the intervention suggests that it may have potential to be scaled at the population level.
http://anzctr.org.au Identifier: ACTRN12616000731493.
Patients with Lafora disease have a mutation in
EPM2A
or
EPM2B
, resulting in dysregulation of glycogen metabolism throughout the body and aberrant glycogen molecules that aggregate into Lafora ...bodies. Lafora bodies are particularly damaging in the brain, where the aggregation drives seizures with increasing severity and frequency, coupled with neurodegeneration. Previous work employed mouse genetic models to reduce glycogen synthesis by approximately 50%, and this strategy significantly reduced Lafora body formation and disease phenotypes. Therefore, an antisense oligonucleotide (ASO) was developed to reduce glycogen synthesis in the brain by targeting glycogen synthase 1 (
Gys1
). To test the distribution and efficacy of this drug, the Gys1-ASO was administered to
Epm2b-/-
mice via intracerebroventricular administration at 4, 7, and 10 months. The mice were then sacrificed at 13 months and their brains analyzed for Gys1 expression, glycogen aggregation, and neuronal excitability. The mice treated with Gys1-ASO exhibited decreased Gys1 protein levels, decreased glycogen aggregation, and reduced epileptiform discharges compared to untreated
Epm2b-/-
mice. This work provides proof of concept that a Gys1-ASO halts disease progression of
EPM2B
mutations of Lafora disease.
Evaluate differences in tracheal intubation-associated events and process variances (i.e., multiple intubation attempts and oxygen desaturation) between pediatric cardiac ICUs and noncardiac PICUs in ...children with underlying cardiac disease.
Retrospective cohort study using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children).
Thirty-six PICUs (five cardiac ICUs, 31 noncardiac ICUs) from July 2012 to March 2016.
Children with medical or surgical cardiac disease who underwent intubation in an ICU.
None.
Our primary outcome was the rate of any adverse tracheal intubation-associated event. Secondary outcomes were severe tracheal intubation-associated events, multiple tracheal intubation attempt rates, and oxygen desaturation. There were 1,502 tracheal intubations in children with underlying cardiac disease (751 in cardiac ICUs, 751 in noncardiac ICUs) reported. Cardiac ICUs and noncardiac ICUs had similar proportions of patients with surgical cardiac disease. Patients undergoing intubation in cardiac ICUs were younger (median age, 1 mo interquartile range, 0-6 mo) compared with noncardiac ICUs (median 3 mo interquartile range, 1-11 mo; p < 0.001). Tracheal intubation-associated event rates were not different between cardiac ICUs and noncardiac ICUs (16% vs 19%; adjusted odds ratio, 0.74; 95% CI, 0.54-1.02; p = 0.069). However, in a sensitivity analysis comparing cardiac ICUs with mixed ICUs (i.e., ICUs caring for children with either general pediatric or cardiac diseases), cardiac ICUs had decreased odds of adverse events (adjusted odds ratio, 0.71; 95% CI, 0.52-0.97; p = 0.033). Rates of severe tracheal intubation-associated events and multiple attempts were similar. Desaturations occurred more often during intubation in cardiac ICUs (adjusted odds ratio, 1.61; 95% CI, 1.04-1.15; p = 0.002).
In children with underlying cardiac disease, rates of adverse tracheal intubation-associated events were not lower in cardiac ICUs as compared to noncardiac ICUs, even after adjusting for differences in patient characteristics and care models.
Pertussis can cause life-threatening illness in infants. Data regarding neurodevelopment after pertussis remain scant. The aim of this study was to assess cognitive development of infants with ...critical pertussis 1 year after PICU discharge.
Prospective cohort study.
Eight hospitals comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 18 additional sites across the United States.
Eligible patients had laboratory confirmation of pertussis infection, were less than 1 year old, and were admitted to the PICU for at least 24 hours.
The Mullen Scales of Early Learning was administered at a 1-year follow-up visit. Functional status was determined by examination and parental interview.
Of 196 eligible patients, 111 (57%) completed the Mullen Scales of Early Learning. The mean scores for visual reception, receptive language, and expressive language domains were significantly lower than the norms (p < 0.001), but not fine and gross motor domains. Forty-one patients (37%) had abnormal scores in at least one domain and 10 (9%) had an Early Learning Composite score 2 or more SDs below the population norms. Older age (p < 0.003) and Hispanic ethnicity (p < 0.008) were associated with lower mean Early Learning Composite score, but presenting symptoms and PICU course were not.
Infants who survive critical pertussis often have neurodevelopmental deficits. These infants may benefit from routine neurodevelopmental screening.
Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production ...during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these postmortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high-power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by reduced 13C enrichment into glycogen, glycolysis, and the tricarboxylic acid (TCA) cycle. Reduced glucose metabolism correlated with a marked decrease in GLUT2 expression and several metabolic enzymes in unique brain regions. In conclusion, our study supports the incorporation of microwave fixation for more accurate studies of brain metabolism in rodent models.
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•Direct in situ fixation of rodent brain by high-powered, focused microwave•Microwave fixation preserves glycogen and glycolytic metabolites•Glucose hypometabolism demonstrated type 1 diabetes mellitus mouse model brains•Decreased enzyme levels observed in the same T1DM mouse model
Brain metabolism directly connects to brain physiology and neuronal function, but challenges remain to capturing an accurate snapshot of the physiological brain metabolome in healthy and diseased rodent models. One challenge is that brain metabolism does not cease at the moment of animal sacrifice, and in conventional protocols, there is typically a delay between animal sacrifice and surgical isolation of the tissue for snap freezing and/or fixation, during which time postmortem conditions such as hypoxia may start to influence the pools of metabolites in the sample. To overcome this barrier, we employed high-power, focused microwave for the simultaneous euthanasia and fixation of mouse brain tissue in situ to preserve metabolite pools prior to surgical removal and dissection of brain regions.
Juras et al. demonstrate the use of a high-power, focused microwave for the simultaneous euthanasia and fixation of mouse brain to preserve metabolite pools prior to surgical dissection and metabolomic studies. They apply this approach to characterize brain glucose metabolism in a mouse model of type 1 diabetes mellitus.
The degree to which changes in community composition mediate the probability of colonization and spread of non-native species is not well understood, especially in animal communities. High species ...richness may hinder the establishment of non-native species. Distinguishing between this scenario and cases in which non-native species become established in intact (lacking extensive anthropogenic soil disturbance) communities and subsequently diminish the abundance and richness of native species is challenging on the basis of observation alone. The red imported fire ant (Solenopsis invicta), an invasive species that occurs throughout much of the southeastern United States, is such an example. Rather than competitively displacing native species, fire ants may become established only in disturbed areas in which native species richness and abundance are already reduced. We used insecticide to reduce the abundance of native ants and fire ants in four experimental plots. We then observed the reassembly and reestablishment of the ants in these plots for 1 year after treatment. The abundance of fire ants in treated plots did not differ from abundance in control plots 1 year after treatment. Likewise, the abundance of native ants increased to levels comparable to those in control plots after 1 year. Our findings suggest that factors other than large reductions in ant abundance and species density (number of species per unit area) may affect the establishment of fire ants and that the response of native ants and fire ants to disturbance can be comparable. El grado en que los cambios en una comunidad median la probabilidad de colonización y dispersión de especies no nativas no está bien comprendido, especialmente en comunidades animales. Alta riqueza de especies puede impedir el establecimiento de especies no nativas. La distinción entre este escenario y casos en los que especies no nativas se establecen en comunidades intactas (carentes de perturbación antropogénica de suelo) y subsecuentemente disminuye la abundancia y riqueza de especies nativas es un reto basándose solo en observaciones. La hormiga de fuego importada (Solenopsis invicta), una especie invasora que ocurre extensivamente en el sureste de Estados Unidos, es un ejemplo de lo anterior. En lugar de desplazar competitivamente a especies nativas, las hormigas de fuego pueden establecerse solo en áreas perturbadas donde la riqueza y abundancia de especies nativas ya están reducidas. Utilizamos insecticida para reducir la abundancia de hormigas nativas y hormigas de fuego en 4 parcelas experimentales. Posteriormente observamos la reagrupación y restablecimiento de las hormigas en estas parcelas 1 año después del tratamiento. Asimismo, la abundancia de hormigas nativas incrementó a niveles comparables a los de las parcelas control después de un año. Nuestros hallazgos sugieren que factores distintos a las reducciones en la abundancia de hormigas y la densidad de especies (número de especies por unidad de área) pueden afectar el establecimiento de hormigas de fuego y que la respuesta de hormigas nativas y hormigas de fuego a la perturbación pueden ser comparables.
Hospitalization for severe influenza infection in childhood may result in postdischarge sequelae.
To evaluate inpatient management and postdischarge sequelae in children with critical respiratory ...illness owing to influenza with or without preexisting asthma.
This was a prospective, observational multicenter study of children (aged 8 months to 17 years) admitted to a pediatric intensive care or high-acuity unit (in November 2019 to April 2020) for influenza. Results were stratified by preexisting asthma. Prehospital status, hospital treatments, and outcomes were collected. Surveys at approximately 90 days after discharge evaluated postdischarge health resource use, functional status, and respiratory symptoms.
A total of 165 children had influenza: 56 with preexisting asthma (33.9%) and 109 without it (66.1%; 41.1% and 39.4%, respectively, were fully vaccinated against influenza). Fifteen patients with preexisting asthma (26.7%) and 34 without it (31.1%) were intubated. More patients with versus without preexisting asthma received pharmacologic asthma treatments during hospitalization (76.7% vs 28.4%). Of 136 patients with 90-day survey data (82.4%; 46 with preexisting asthma 33.8% and 90 without it 66.1%), a similar proportion had an emergency department/urgent care visit (4.3% vs 6.6%) or hospital readmission (8.6% vs 3.3%) for a respiratory condition. Patients with preexisting asthma more frequently experienced asthma symptoms (78.2% vs 3.3%) and had respiratory specialist visits (52% vs 20%) after discharge. Of 109 patients without preexisting asthma, 10 reported receiving a new diagnosis of asthma (11.1%).
Respiratory health resource use and symptoms are important postdischarge outcomes after influenza critical illness in children with and without preexisting asthma. Less than half of children were vaccinated for influenza, a tool that could mitigate critical illness and its sequelae.
Wound healing is a response to injury that is initiated to reconstruct damaged tissue. In skin, reepithelialization involves both epithelial cells and fibroblasts and contributes to the reformation ...of a barrier between the external environment and internal milieu. Growth factors including epidermal growth factor (EGF) play important roles in promoting this process. In the present studies we employed CV-1 fibroblasts in a tissue culture model of reepithelialization to develop strategies for optimizing wound closure stimulated by EGF. We found that EGF enhanced cell motility within 6-8 h of EGF treatment in serum-free medium but wounds failed to close within 24 h. However, if medium on these cultures was exchanged for medium containing serum, cells pretreated with EGF closed new scrape wounds more rapidly than did cells that were not pretreated. These results indicate that serum factors work in concert with EGF to coordinate cell motility for efficient wound closure. Indeed, EGF enhanced the rate of wound closure in the presence of serum, and this effect also persisted for at least 24 h after EGF was removed. This coordination of EGF-induced cell motility was accompanied by an increase in the transient phosphorylation of ERK1 and ERK2. The persistent effects of EGF were blocked by transient exposure to reversible inhibitors of transcription and translation, indicating that the expression of new proteins mediated this response. We propose that EGF-stimulated CV-1 fibroblast motility is coordinated by a serum component that induces cell-cell adhesive properties consistent with an epithelial phenotype, thereby enhancing the reepithelialization process.
Onychomycosis is a challenging fungal infection to treat topically, likely due to the unique properties of the nail plate. This seemingly impenetrable barrier has high resistance to the passage of ...antifungal drugs in sufficient concentrations to kill the causative fungi deep in the nail bed. Recently, a new class of antifungal agent was described, termed oxaboroles, which have broad‐spectrum activity. These oxaboroles were designed with properties believed to be required to allow for easier transit through the nail plate. Herein, we report (i) the nail penetration results of four oxaboroles that led to the selection of AN2690, (ii) the results of the nail penetration of AN2690 from four vehicles, and (iii) the nail penetration of AN2690 in its chosen vehicle compared to a commercial control, ciclopirox. AN2690has superior penetration compared to ciclopirox, and achieves levels within and under the nail plate that suggest it has the potential to be an effective topical treatment for onychomycosisand the American Pharmacists Association J Pharm Sci 96: 2622–2631, 2007
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