Project description:ObjectiveTo assess whether vitamin A deficiency alters the recovery of total respiratory resistance (TRR) following acute upper respiratory tract infection (URI).MethodsThis is a case control study of children, age 4-6 years and grouped as: URI, (n = 74), URI and wheezing, (URI-wheezing, n = 52), and healthy controls (n = 51). Vitamin A and total respiratory resistance (TRR) were assessed using the modified relative dose response (MRDR) and forced oscillometry, respectively.ResultsChildren with URI and URI-wheezing had lower retinol, 32.4 ± 13.12 and 18.3 ± 6.83 µg/dl respectively, compared to controls, 56.9 ± 29.82 µg/dl (ANOVA, P < 0.001). The MRDR was elevated in children in the URI or URI-wheezing groups 0.066 ± 0.045 and 0.021 ± 0.021, respectively, compared to controls 0.007 ± 0.006 (ANOVA, P < 0.0001). The TRR in the URI and URI-wheezing groups differed from controls. During convalescence, the TRR failed to decline in the URI-group only when the MRDR was >0.06. In the URI-wheezing group, TRR declined independently of retinol and MRDR.ConclusionVitamin A contributes to preservation of airway function during and in recovery after upper respiratory infection in children.
Project description:COVID-19 has represented an issue for global health since its outbreak in March 2020. It is now evident that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer's disease. Little is known about the molecular basis of these manifestations. Here, several strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated on cellular extracts, subcellular fractions, and brain tissue. The viral proteins spike, nucleocapsid, and membrane were overexpressed in SH-SY5Y cells, and the direct interaction and effect on Tau phosphorylation were checked using immunoblot experiments. Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer's disease and other tauopathies. Moreover, this event increases Tau's propensity to form insoluble aggregates and alters its subcellular localization. Our data support the hypothesis that SARS-CoV-2 infection in the central nervous system triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.
Project description:Identifying patients with acute respiratory distress syndrome (ARDS) is a recognized challenge. Experts often have only moderate agreement when applying the clinical definition of ARDS to patients. However, no study has fully examined the implications of low reliability measurement of ARDS on clinical studies.To investigate how the degree of variability in ARDS measurement commonly reported in clinical studies affects study power, the accuracy of treatment effect estimates, and the measured strength of risk factor associations.We examined the effect of ARDS measurement error in randomized clinical trials (RCTs) of ARDS-specific treatments and cohort studies using simulations. We varied the reliability of ARDS diagnosis, quantified as the interobserver reliability (?-statistic) between two reviewers. In RCT simulations, patients identified as having ARDS were enrolled, and when measurement error was present, patients without ARDS could be enrolled. In cohort studies, risk factors as potential predictors were analyzed using reviewer-identified ARDS as the outcome variable.Lower reliability measurement of ARDS during patient enrollment in RCTs seriously degraded study power. Holding effect size constant, the sample size necessary to attain adequate statistical power increased by more than 50% as reliability declined, although the result was sensitive to ARDS prevalence. In a 1,400-patient clinical trial, the sample size necessary to maintain similar statistical power increased to over 1,900 when reliability declined from perfect to substantial (??=?0.72). Lower reliability measurement diminished the apparent effectiveness of an ARDS-specific treatment from a 15.2% (95% confidence interval, 9.4-20.9%) absolute risk reduction in mortality to 10.9% (95% confidence interval, 4.7-16.2%) when reliability declined to moderate (??=?0.51). In cohort studies, the effect on risk factor associations was similar.ARDS measurement error can seriously degrade statistical power and effect size estimates of clinical studies. The reliability of ARDS measurement warrants careful attention in future ARDS clinical studies.
Project description:BackgroundVitamin D deficiency has been associated with acute respiratory infection (ARI) in early life, but this has not been evaluated in Indonesia. We aimed to determine the incidence of ARI in Indonesian infants, and to evaluate the association with vitamin D deficiency.MethodsFrom 23 December 2015 to 31 December 2017, we conducted a community-based prospective cohort study in Yogyakarta province. We enrolled 422 pregnant women and followed their infants from birth until 12 months of age for ARI episodes. Vitamin D status was measured at birth and at age six months. We performed Cox proportional hazard regression analysis to evaluate the association between vitamin D deficiency and pneumonia incidence.ResultsAt study completion, 95% (400/422) of infants retained with a total of 412 child years of observation (CYO). The incidence of all ARI and of WHO-defined pneumonia was 3.89 (95% CI 3.70-4.08) and 0.25 (95% CI 0.21-0.30) episodes per CYO respectively. Vitamin D deficiency at birth was common (90%, 308/344) and associated with more frequent episodes of ARI non-pneumonia (adjusted odds ratio 4.48, 95% CI:1.04-19.34). Vitamin D status at birth or six months was not associated with subsequent pneumonia incidence, but greater maternal sun exposure during pregnancy was associated with a trend to less frequent ARI and pneumonia in infants.ConclusionARI, pneumonia, and vitamin D deficiency at birth were common in Indonesian infants. Minimising vitamin D deficiency at birth such as by supplementation of mothers or safe sun exposure during pregnancy has the potential to reduce ARI incidence in infants in this setting.
Project description:No previous meta-analysis had explored the association between vitamin D supplementation in healthy pediatrics and the risk of acute respiratory tract infections (ARTIs). Thus, we meta-analyzed the current evidence in this regard to provide sufficient knowledge about this risk-benefit ratio for vitamin D supplementation in this specific age group. We searched seven databases for randomized controlled trials (RCTs) that investigated the effect of vitamin D supplementation and ARTIs risk on a healthy pediatric population (0–18 years old). Meta-analysis was performed through R software. We included eight RCTs after the screening of 326 records according to our eligibility criteria. There were comparable infection rates between Vitamin D and placebo groups (OR = 0.98, 95% CI = 0.90–1.08, P-value = 0.62), with no significant heterogeneity among the included studies (I2 = 32%; P-value = 0.22). Moreover, there was no significant difference between the two vitamin D regimens (OR = 0.85, 95% CI = 0.64–1.12, P-value = 0.32), with no considerable heterogeneity among the included studies (I2 = 37%; P-value = 0.21). However, there was a significant reduction in Influenza A rates in the high-dose vitamin D group compared to the low dose one (OR = 0.39, 95% CI = 0.26–0.59, P-value < 0.001), with no heterogeneity among the included studies (I2 = 0%; P-value = 0.72). Only two studies of 8,972 patients reported different side effects, with overall acceptable safety profile. Regardless of the dosing regimen used or the type of infection, in the healthy pediatric group, there is no evident benefit of using vitamin D to prevent or reduce the ARTI rates.