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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 ( R 0  = ∼ 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.

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.

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 10 vs. 2.25 log 10 , p = 0.002), particularly from potential viral pathogens (2.78log 10 vs. 0.83log 10 , 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.

The primary mRNA sequence determines its secondary structure and the repertoire of interacting RNA-binding proteins (RBPs). The resulting mRNA ribonucleoprotein complex (mRNP) then influences all stages of the life of an mRNA. Here, we determined the mRNP composition of individual Kaposi sarcoma herpesviral (KSHV) mRNAs. Like all herpesviruses, KSHV switches between a latent and lytic stage of the viral life cycle. During reactivation from latency, the viral RNA regulator ORF57 ensures the translation of viral mRNAs by increasing their mRNA stability and nuclear export. We optimized an LNA/DNA mixmer RNA capture protocol for both transfection and viral infection settings. In combination with eCLIP, we confirmed that ORF57 directly binds to an AU-rich RNA motif, which may enable ORF57 to discriminate viral from cellular RNAs based on the nucleotide bias of KSHV lytic RNAs. In addition, we captured the RBPome of two ORF57-dependent viral transcripts and identified the host RNA processing factor SRSF3 as a key regulator of viral replication.

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.

Since the original guidelines were published, there has been additional work done to characterize the pathophysiology of cystic fibrosis-related diabetes (CFRD), including the role of genes related to type 2 diabetes, the role of inflammation, and the potential role of the basic CF transmembrane conductance regulator (CFTR) chloride channel defect. [A] The pathophysiology of CFRD is complex and includes the loss of pancreatic islet cells leading to both insulin and glucagon deficiency, fluctuating insulin resistance, the requirement for high caloric intake, gut abnormalities including delayed gastric emptying, altered intestinal motility, and liver disease. Factors specific to CF which impact glucose metabolism include the loss of total islets leading to both insulin and glucagon deficiency, chronic and acute inflammation and infection which cause fluctuating insulin resistance, a requirement for high caloric intake because of increased energy expenditure and malabsorption, risk of life-threatening malnutrition, and gut abnormalities including delayed gastric emptying, altered intestinal motility, and liver disease. Yes No No Insulin deficiency Nearly complete Partial, variable Severe, not complete Insulin sensitivity Somewhat decreased Severely decreased Somewhat decreased Ketones Yes Rare Rare Usual treatment Insulin Diet, oral meds, insulin Insulin Microvasular complications Yes Yes Yes Macrovascular complications Yes Yes No Metabolic syndrome No Yes No Cause of death Cardiovascular Cardiovascular Pulmonary Diagnostic criteria for CFRD and abnormal glucose tolerance The diagnostic criteria for CFRD were updated in 2010 in North America by the CFRD Guidelines Committee in a position statement co-sponsored by the American Diabetes Association (ADA) and the Cystic Fibrosis Foundation, and endorsed by the Pediatric Endocrine Society.

An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR–Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT–PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.SARS-CoV-2 in patient samples is detected in under an hour using a CRISPR-based lateral flow assay.

Abstract Disclosure: N. Solano: None. D. Baboun: None. A. Granados: None. A. Carrillo-Iregui: None. Introduction: Hereditary fructose intolerance (HFI) is an uncommon autosomal recessive metabolic disorder characterized by a deficiency of aldolase B, a crucial enzyme involved in fructose metabolism. This deficiency causes an accumulation of fructose-1-phosphate, which triggers a cascade of metabolic disturbances including hypoglycemia, lactic acidosis, and hepatic dysfunction. If left untreated, HFI can lead to severe complications, including liver failure and even death. Diagnosing HFI can be challenging due to its nonspecific clinical presentation and the absence of routine screening tests. Case presentation: A 4-year-old girl was referred from an outside hospital for hypoglycemia requiring intravenous dextrose infusion. The patient became lethargic 30 minutes after consuming a honey-based cough syrup. Upon presentation to the emergency department, her blood glucose level was 41 mg/dL. Her past medical history revealed an episode of lethargy and persistent vomiting at age 21 months, coinciding with an intussusception. A finger blood glucose test at the time was undetectable, and further evaluation revealed metabolic acidosis, elevated liver enzymes, and a normal ammonia level. Plasma amino acid, acylcarnitine, carnitine, urine acylglycine, carnitine, and urine organic acid levels were all within normal limits. Fatty acid oxidation and glycogen storage disease panels were also negative. On inquiry into her dietary habits, her parents recalled she would spit fruits out whenever tasting them, suggesting an innate aversion to fructose-rich foods. Initial comprehensive inpatient workup, including a critical sample, yielded no definitive results. She underwent a strict 24-hour inpatient fast and remained asymptomatic, with blood glucose levels above 65 mg/dL, ruling out hyperinsulinism. A broader next-generation sequencing (NGS) hypoglycemia panel was ordered, which identified a heterozygous pathogenic variant, c.178C>T (p.Arg60*) maternally inherited, and a likely pathogenic variant, c.379+1G>T (Splice donor) paternally inherited, in the aldolase B gene. Both confirmed the diagnosis of hereditary fructose intolerance (HFI). The family received comprehensive dietary and genetic counseling. Conclusion: HFI is an uncommon but potentially life-threatening inborn error of metabolism. Maintaining a high index of suspicion, considering a broad differential diagnosis, and obtaining a detailed dietary history, including fruit consumption, are crucial for identifying and managing HFI in infants and children with unexplained hypoglycemia. This case highlights the importance of early diagnosis and dietary intervention to prevent severe complications in patients with HFI. Additionally, it emphasizes the need for comprehensive dietary counseling and education for patients' families to ensure lifelong adherence to a fructose-restricted diet. Presentation: 6/2/2024

The aims of this study were to (1) determine the feasibility of a home-based resistance exercise training (RET) program in patients with cystic fibrosis and impaired glucose tolerance using virtual personal training and (2) observe the effects completion of the RET program had on glucose metabolism, pulmonary function, body composition, and physical fitness. The feasibility of the program was defined as 80% compliance. Ten participants (15.80 ± 2.20 yr, 25.1 ± 7.4 kg/m2) began a home-based resistance training program consisting of 36 sessions supervised via online videoconferencing. Compliance scores of 78.9% (all participants) and 81.8% (without one outlier) were observed. A significant increase was observed in 2-h C-peptide levels (2.1 ng/mL; p = 0.04), with a moderate decrease in fasting glucose (−5.2 mg/dL; p = 0.11) and a moderate increase in 2-h insulin (35.0 U/mL; p = 0.10). A small decrease in the fat percentage (−1.3%; p = 0.03) was observed in addition to increases in fat-free mass (1.5 kg; p = 0.01) and the fat-free mass index (0.4; p = 0.01). Small, yet statistically significant increases were observed in V̇O2peak (0.1 L/min p = 0.01), V̇CO2peak (0.1 L/min; p = 0.01), and ventilation (5.3 L/min; p = 0.04). Telehealth-based RET is feasible in adolescents with CF and impaired glucose tolerance and elicits small yet favorable changes in insulin secretion, body composition, and exercise capacity.