Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Background Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (= 65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. Methods In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5 degrees by 5 degrees grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. Findings We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0.3 months [95% CI -0.3 to 0.9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3.8 months [3.6 to 4.0]) in temperate sites and longer duration (5.2 months [4.9 to 5.5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4.6 months [4.3 to 4.8]), as it was for metapneumovirus (4.8 months [4.4 to 5.1]). By comparison, parainfluenza virus had longer duration of epidemics (6.3 months [6.0 to 6.7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0.2 months [-0.6 to 0.1]; respiratory syncytial virus 0.1 months [-0.2 to 0.4]). Interpretation This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd

Experiences and Perspectives of Polycystic Kidney Disease Patients following a Diet of Reduced Osmoles, Protein, and Acid Precursors Supplemented with Water:A Qualitative Study

Background Salt, protein, acid precursors, and fluid intake have been identified as factors that influence cyst growth in ADPKD. Unfortunately, the feasibility of following these dietary restrictions/enhancements from a patient's point-of-view has yet to be studied. The purpose of this study is to understand better the experiences of patients following a relatively complex dietary prescription targeting these factors. Methods Twelve adults with ADPKD and kidney function >30ml/min/1.73m(2) were recruited from the University of Kansas Medical Center Polycystic Kidney Disease clinic. In a qualitative design, semi-structured interviews of participants were conducted following a four week dietary intervention (experimental diet lower in sodium, protein, and acid precursors, and supplemented with water) either face-to-face or by telephone. All interviews were recorded, transcribed verbatim, and checked for accuracy. Transcripts were analyzed thematically for emerging themes. Results Participants reported that eating less meat and more fruits and vegetables were the easiest components of the diet, whereas reaching the daily goal amount of fruits and vegetables and tracking the diet constantly were the most difficult components. Participants had little difficulty with fluid intake and reported the prescribed fluid goal as achievable. The tracking system for fruits and vegetables and protein was reported to be both helpful and intuitive, but tracking their intake on paper was tedious. Eating out was the most significant barrier to following the diet with some individuals avoiding restaurants in order to comply with the dietary prescription. Conclusion Participants on the experimental diet heightened their awareness of the consumption of dietary salt, protein, acid precursors, and fluid intake. Additionally, most participants believed adherence to the prescribed diet was feasible. However, participants wanted less cumbersome ways to track and monitor the diet, especially given that the prescribed diet is designed for lifelong adherence. Future studies should focus on targeting these specific dietary factors in larger groups of more ethnically and culturally diverse populations to help inform clinicians and how best to help diverse populations adhere to the dietary intervention

Development and validation of the Arizona Cognitive Test Battery for Down syndrome

Neurocognitive assessment in individuals with intellectual disabilities requires a well-validated test battery. To meet this need, the Arizona Cognitive Test Battery (ACTB) has been developed specifically to assess the cognitive phenotype in Down syndrome (DS). The ACTB includes neuropsychological assessments chosen to 1) assess a range of skills, 2) be non-verbal so as to not confound the neuropsychological assessment with language demands, 3) have distributional properties appropriate for research studies to identify genetic modifiers of variation, 4) show sensitivity to within and between sample differences, 5) have specific correlates with brain function, and 6) be applicable to a wide age range and across contexts. The ACTB includes tests of general cognitive ability and prefrontal, hippocampal and cerebellar function. These tasks were drawn from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) and other established paradigms. Alongside the cognitive testing battery we administered benchmark and parent-report assessments of cognition and behavior. Individuals with DS (n = 74, ages 7–38 years) and mental age (MA) matched controls (n = 50, ages 3–8 years) were tested across 3 sites. A subsample of these groups were used for between-group comparisons, including 55 individuals with DS and 36 mental age matched controls. The ACTB allows for low floor performance levels and participant loss. Floor effects were greater in younger children. Individuals with DS were impaired on a number ACTB tests in comparison to a MA-matched sample, with some areas of spared ability, particularly on tests requiring extensive motor coordination. Battery measures correlated with parent report of behavior and development. The ACTB provided consistent results across contexts, including home vs. lab visits, cross-site, and among individuals with a wide range of socio-economic backgrounds and differences in ethnicity. The ACTB will be useful in a range of outcome studies, including clinical trials and the identification of important genetic components of cognitive disability

Differential Effects of MYH9 and APOL1 Risk Variants on FRMD3 Association with Diabetic ESRD in African Americans

Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9—a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E−7 additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E−4). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes

Hand sanitisers for reducing illness absences in primary school children in New Zealand: a cluster randomised controlled trial study protocol

<p>Abstract</p> <p>Background</p> <p>New Zealand has relatively high rates of morbidity and mortality from infectious disease compared with other OECD countries, with infectious disease being more prevalent in children compared with others in the population. Consequences of infectious disease in children may have significant economic and social impact beyond the direct effects of the disease on the health of the child; including absence from school, transmission of infectious disease to other pupils, staff, and family members, and time off work for parents/guardians. Reduction of the transmission of infectious disease between children at schools could be an effective way of reducing the community incidence of infectious disease. Alcohol based no-rinse hand sanitisers provide an alternative hand cleaning technology, for which there is some evidence that they may be effective in achieving this. However, very few studies have investigated the effectiveness of hand sanitisers, and importantly, the potential wider economic implications of this intervention have not been established.</p> <p>Aims</p> <p>The primary objective of this trial is to establish if the provision of hand sanitisers in primary schools in the South Island of New Zealand, in addition to an education session on hand hygiene, reduces the incidence rate of absence episodes due to illness in children. In addition, the trial will establish the cost-effectiveness and conduct a cost-benefit analysis of the intervention in this setting.</p> <p>Methods/Design</p> <p>A cluster randomised controlled trial will be undertaken to establish the effectiveness and cost-effectiveness of hand sanitisers. Sixty-eight primary schools will be recruited from three regions in the South Island of New Zealand. The schools will be randomised, within region, to receive hand sanitisers and an education session on hand hygiene, or an education session on hand hygiene alone. Fifty pupils from each school in years 1 to 6 (generally aged from 5 to 11 years) will be randomly selected for detailed follow-up about their illness absences, providing a total of 3400 pupils. In addition, absence information will be collected on all children from the school rolls. Investigators not involved in the running of the trial, outcome assessors, and the statistician will be blinded to the group allocation until the analysis is completed.</p> <p>Trial registration</p> <p>ACTRN12609000478213</p

Evaluation of Microorganisms Cultured from Injured and Repressed Tissue Regeneration Sites in Endangered Giant Aquatic Ozark Hellbender Salamanders

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established. Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines

Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses

Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY)-randomized weight loss trial among breast cancer survivors

Obesity is a poor prognostic factor and is negatively related to quality of life (QOL) in breast cancer survivors. Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors. Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5 % (p < 0.0001) and 3.7 versus 1.3 % (p<0.0001) at 12 and 24 months, respectively. ENERGY also was designed to answer the research question: Does weight loss significantly improve vitality and physical function (key components of QOL)? 692 breast cancer survivors (BMI: 25–45 kg/m(2)) at 4 US sites were randomized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive (control) of two in-person counseling sessions. Weight, self-reported QOL, and symptoms were measured semi-annually for two years. Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months, but not in the intervention arm, −3.45 (95 % Confidence Interval [CI] −6.10, –0.79, p = 0.0109) and 0.10 (95 %CI 0.04, 0.16, p = 0.0021), respectively. Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm −2.72 (95 % CI −5.45, 0.01, p = 0.0508). These differences diminished over time; however, depressive symptoms increased in the intervention versus control arms and became significant at 24 months, −1.64 (95 % CI −3.13, –0.15, p = 0.0308). Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors. These longer term data suggest that diet and exercise interventions improve some aspects of QOL, but these benefits may diminish over time