Highlights • We propose that increased viral loads are associated with hospitalization. • Influenza A/H3N2 had the highest viral load of the three viruses. • Increased influenza A/H3N2 viral loads ...were not associated with hospitalization. • High influenza B viral loads are associated with hospitalization/ICU admission. • Rhinovirus viral loads do not differ by age or patient setting.
Human respiratory syncytial virus (RSV) A ON1 genotype, first detected in 2010 in Ontario, Canada, has been documented in 21 countries to date. This study investigated persistence and transmission ...dynamics of ON1 by grouping 406 randomly selected RSV-positive specimens submitted to Public Health Ontario from August 2011 to August 2012; RSV-A-positive specimens were genotyped. We identified 370 RSV-A (181 NA1, 135 NA2, 51 ON1 3 GA5) and 36 RSV-B positive specimens. We aligned time-stamped second hypervariable region (330 bp) of G-gene sequence data (global, n = 483; and Ontario, n = 60) to evaluate transmission dynamics. Global data suggests that the most recent common ancestor of ON1 emerged during the 2008-2009 season. Mean evolutionary rate of the global ON1 was 4.10 × 10(-3) substitutions/site/year (95% BCI 3.1-5.0 × 10(-3)), not significantly different to that of Ontario ON1. The estimated mean reproductive number (R0 = ∼ 1.01) from global and Ontario sequences showed no significant difference and implies stability among global RSV-A ON1. This study suggests that local epidemics exhibit similar underlying evolutionary and epidemiological dynamics to that of the persistent global RSV-A ON1 population. These findings underscore the importance of continual molecular surveillance of RSV in order to gain a better understanding of epidemics.
The human gut virome and its early life development are poorly understood. Prior studies have captured single-point assessments with the evolution of the infant virome remaining largely unexplored. ...We performed viral metagenomic sequencing on stool samples collected longitudinally from a cohort of 53 infants from age 2 weeks to 3 years (80.7 billion reads), and from their mothers (9.8 billion reads) to examine and compare viromes. The asymptomatic infant virome consisted of bacteriophages, nonhuman dietary/environmental viruses, and human-host viruses, predominantly picornaviruses. In contrast, human-host viruses were largely absent from the maternal virome. Previously undescribed, sequence-divergent vertebrate viruses were detected in the maternal but not infant virome. As infants aged, the phage component evolved to resemble the maternal virome, but by age 3, the human-host component remained dissimilar from the maternal virome. Thus, early life virome development is determined predominantly by dietary, infectious, and environmental factors rather than direct maternal acquisition.
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•Stool virome analysis was performed on 53 infants from birth to age 3 and their mothers•Human-host viruses, particularly picornaviruses, are prevalent in the infant virome•Sequence-divergent viruses were detected in the maternal but not infant virome•Virome development in early life is not determined by direct maternal acquisition
Walters et al. examine the evolution of the infant virome in early life in comparison to the maternal virome. The infant virome remained dissimilar from the maternal virome to age 3, showing that the infant virome is not maternally acquired but is rather determined by dietary, infectious, and environmental factors.
Background
The effects of elexacaftor‐tezacaftor‐ivacaftor (ETI) on body composition in people with CF (pwCF) are unknown.
Methods
Dual‐energy X‐ray absorptiometry fat‐free mass and fat mass adjusted ...for height (FMI) as well as oral glucose tolerance test derived measures of insulin secretion and sensitivity were compared before and after ETI initiation in eight pwCF.
Results
Patients median age: 22 years interquartile range (IQR: 16–28), 87.5% male, median time on ETI:11 months. Weight z‐score increased from −0.52 to 0.18 (p = 0.014); FMI increased from 4.12 to 6.29 (p = 0.014). Insulin secretion (C pep iAUC/Gluc iAUC) increased from 8.71 to 14.21 (p = 0.021), insulin resistance (HOMA2 IR) increased from 0.73 to 1.25 (p = 0.014) and insulin sensitivity decreased (Matsuda) 8.88 to 5.58 (p = 0.036).
Conclusions
ETI resulted in increased weight and fat mass. BMI and muscle mass did not change. Both insulin secretion and insulin resistance increased. Longer‐term metabolic consequences of ETI need further investigation.
Growth and pubertal development are important health markers. We used the data of a longitudinal growth study on a contemporary sample of US youth to examine the relationship between peak height ...velocity (PHV) and Tanner staging. We observed a substantial variability in the timing of PHV across Tanner stages, which is an important consideration for clinicians when assessing growth.
We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could ...prevent viral, clinical upper respiratory tract infection (URTI) in university students.
We randomized 600 students into 4 treatment arms: 1) vitamin D3 and gargling, 2) placebo and gargling, 3) vitamin D3 and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively.
Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D3 reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI95:0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI95:0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D3 treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI95:0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log10 viral copies/mL (mean difference: -0.89, CI95: -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI95:0.53-1.26, p = 0.36).
These results suggest that vitamin D3 is a promising intervention for the prevention of URTI. Vitamin D3 significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections.
NCT01158560.
Investigation of disorders of sex development (DSD) has resulted in the discovery of multiple sex-determining genes. MAP3K1 encodes a signal transduction regulator in the sex determination pathway ...and is emerging as one of the more common genes responsible for 46,XY DSD presenting as complete or partial gonadal dysgenesis. Clinical assessment, endocrine evaluation, and genetic analysis were performed in six individuals from four unrelated families with 46,XY DSD. All six individuals were found to have likely pathogenic MAP3K1 variants. Three of these individuals presented with complete gonadal dysgenesis, characterized by bilateral streak gonads with typical internal and external female genitalia, while the other three presented with partial gonadal dysgenesis, characterized by incomplete testicular development, resulting in clitoral hypertrophy with otherwise typical female external genitalia. Testing for MAP3K1 variants should be considered in patients with 46,XY complete or partial gonadal dysgenesis, particularly in families with multiple members affected with 46,XY DSD. Identification of a MAP3K1 variant should prompt an evaluation for DSD in female siblings of the proband.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 ...nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.
The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic ...sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log
vs. 2.25 log
, p = 0.002), particularly from potential viral pathogens (2.78log
vs. 0.83log
, p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p = 0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.
NCDs (non-communicable diseases) are considered an important social issue and a financial burden to the health care systems in the EU which can be decreased if cost-effective policies are ...implemented, along with proactive interventions. The CrowdHEALTH project recognizes that NCD poses a burden for the healthcare sector and society and aims at focusing on NCDs' public health policies.
The aim of this paper is to present the concept of Public Health Policy (PHP), elaborate on the state-of-the-art of PHPs development, and propose a first approach to the modeling and evaluation of PHPs used in a toolkit that is going to support decision making, the Policy Development Toolkit (PDT).
The policy creation module is a part of the PDT aiming to integrate the results of the rest of the health analytics and policy components. It is the module that selects, filters, and aggregates all relevant information to help policy-makers with the decision making process. The policies creation component is connected to the visualization component to provide the final users with data visualization on different PHPs, including outcomes from data-driven models, such as risk stratification, clinical pathways mining, forecasting or causal analysis models, outcomes from cost-benefit analysis, and suggestions and recommendations from the results of different measured KPIs, using data from the Holistic Health Records (HHRs).
In the context of CrowdHEALTH project, PHP can be defined as the decisions taken for actions by those responsible in the public sector that covers a set of actions or inactions that affect a group of public and private actors of the health care system. In the CrowdHEALTH project, the Policy Development Toolkit works as the main interface between the final users and the whole system in the CrowdHEALTH platform. The three components related to policy creation are: (i) the policy modeling component, (ii) the population identification component and (iii) the policy evaluation component. In policy evaluation, KPIs are used as measurable indicators to help prevent ambiguity problems in the interpretation of the model and the structure.
This initial Policy creation component design might be modified during the project life circle according to the concept complexity.
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