Genetic characterization of influenza A(H3N2) viruses circulating in coastal Kenya, 2009-2017

Background Influenza viruses evolve rapidly and undergo immune driven selection, especially in the hemagglutinin (HA) protein. We report amino acid changes affecting antigenic epitopes and receptor‐binding sites of A(H3N2) viruses circulating in Kilifi, Kenya, from 2009 to 2017. Methods Next‐generation sequencing (NGS) was used to generate A(H3N2) virus genomic data from influenza‐positive specimens collected from hospital admissions and health facility outpatients presenting with acute respiratory illness to health facilities within the Kilifi Health and Demographic Surveillance System. Full‐length HA sequences were utilized to characterize A(H3N2) virus genetic and antigenic changes. Results From 186 (90 inpatient and 96 outpatient) influenza A virus‐positive specimens processed, 101 A(H3N2) virus whole genomes were obtained. Among viruses identified in inpatient specimens from 2009 to 2015, divergence of circulating A(H3N2) viruses from the vaccine strains A/Perth/16/2009, A/Texas/50/2012, and A/Switzerland/9715293/2013 formed 6 genetic clades (A/Victoria/208/2009‐like, 3B, 3C, 3C.2a, 4, and 7). Among viruses identified in outpatient specimens from 2015 to 2017, divergence of circulating A(H3N2) viruses from vaccine strain A/Hong Kong/4801/2014 formed clade 3C.2a, subclades 3C.2a2 and 3C.2a3, and subgroup 3C.2a1b. Several amino acid substitutions were associated with the continued genetic evolution of A(H3N2) strains in circulation. Conclusions Our results suggest continuing evolution of currently circulating A(H3N2) viruses in Kilifi, coastal Kenya and suggest the need for continuous genetic and antigenic viral surveillance of circulating seasonal influenza viruses with broad geographic representation to facilitate prompt and efficient selection of influenza strains for inclusion in future influenza vaccines

Looking Back on 50 Years of Literature to Understand the Potential Impact of Influenza on Extrapulmonary Medical Outcomes

We conducted a scoping review of the epidemiological literature from the past 50 years to document the contribution of influenza virus infection to extrapulmonary clinical outcomes. We identified 99 publications reporting 243 associations using many study designs, exposure and outcome definitions, and methods. Laboratory confirmation of influenza was used in only 28 (12%) estimates, mostly in case-control and self-controlled case series study designs. We identified 50 individual clinical conditions associated with influenza. The most numerous estimates were of cardiocirculatory diseases, neurological/neuromuscular diseases, and fetal/newborn disorders, with myocardial infarction the most common individual outcome. Due to heterogeneity, we could not generate summary estimates of effect size, but of 130 relative effect estimates, 105 (81%) indicated an elevated risk of extrapulmonary outcome with influenza exposure. The literature is indicative of systemic complications of influenza virus infection, the requirement for more effective influenza control, and a need for robust confirmatory studies

Tacrine-allyl/propargylcysteine-benzothiazole trihybrids as potential anti-Alzheimer's drug candidates

The authors acknowledge the Portuguese Fundação para a Ciência e Tecnologia (FCT) for the project UID/QUI/00100/2013, postdoctoral fellowships (RSK and KC). We also thank the doctoral fellowship from Erasmus Namaste program (AH).On continuing our research on new drug candidates for Alzheimer's disease (AD), we have designed, synthesized and evaluated a series of multifunctional trihybrid agents. The design strategy was based on the incorporation of a benzothiazole (BTA) moiety on a series of very recently reported bihybrids, resulting from the conjugation of a tacrine (TAC) with natural based moieties, namely S-allylcysteine (SAC) (garlic constituent) and S-propargylcysteine (SPRC). Thus, in addition to the acetylcholinesterase inhibition (AChEI) and anti-ROS capacity of the bihybrids (TAC-SAC/SPRC), the new trihybrids (TAC-SAC/SPRC-BTA) were endowed with 5-fold capacity for inhibition of the amyloid beta-peptide (Aβ) aggregation. The BTA moiety led also to considerable enhancement of the AChEI on the trihybrids, which molecular modeling suggested to be due to the simultaneous binding to the catalytic active site and peripheral anionic site of AChE. The trihybrids were also assessed for the MAO inhibition, but resulted in lower activity than expected, ascribed to the low accessibility of the propargyl groups to the enzyme active site. Finally, the effects of the compounds on the viability of neuroblastome cells stressedwith Aβ42 and H2O2 showed moderate cell protection. Overall, the performed studies illustrate the importance (and limitations) of enclosing several molecular scaffolds in one molecular entity to allow the modulation of multiple AD targets.PostprintPeer reviewe

Patient and Provider Perspectives on How Trust Influences Maternal Vaccine Acceptance Among Pregnant Women in Kenya

Background Pregnant women and newborns are at high risk for infectious diseases. Altered immunity status during pregnancy and challenges fully vaccinating newborns contribute to this medical reality. Maternal immunization is a strategy to protect pregnant women and their newborns. This study aimed to find out how patient-provider relationships affect maternal vaccine uptake, particularly in the context of a lower middle- income country where limited research in this area exists. Methods We conducted semi-structured, in-depth narrative interviews of both providers and pregnant women from four sites in Kenya: Siaya, Nairobi, Mombasa, and Marsabit. Interviews were conducted in either English or one of the local regional languages. Results We found that patient trust in health care providers (HCPs) is integral to vaccine acceptance among pregnant women in Kenya. The HCP-patient relationship is a fiduciary one, whereby the patients’ trusts is primarily rooted in the provider’s social position as a person who is highly educated in matters of health. Furthermore, patient health education and provider attitudes are crucial for reinstating and fostering that trust, especially in cases where trust was impeded by rumors, community myths and misperceptions, and religious and cultural factors. Conclusion Patient trust in providers is a strong facilitator contributing to vaccine acceptance among pregnant women in Kenya. To maintain and increase immunization trust, providers have a critical role in cultivating a positive environment that allows for favorable interactions and patient health education. This includes educating providers on maternal immunizations and enhancing knowledge of effective risk communication tactics in clinical encounters

Spontaneous CO release from Ru(II)(CO)2-protein complexes in aqueous solution, cells, and mice.

We demonstrate that Ru(II)(CO)2-protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac-RuCl(κ(2)-H2NCH2CO2)(CO)3] (CORM-3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO-responsive turn-on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM-3. CO released from a synthetic bovine serum albumin (BSA)-Ru(II)(CO)2 complex leads to downregulation of the cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α in cancer cells. Finally, administration of BSA-Ru(II)(CO)2 in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of Ru(II)(CO)2-protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.We thank the FCT, the EU, and the EPSRC for funding. G.J.L.B. is a Royal Society University Research Fellow.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/anie.201409344/abstract

Quantitative methods and studies of psychic disorders and job satisfaction of teachers of the prison system in the Amazon, Brazil

Objective: To analyze the level of mental suffering and the level of job satisfaction in 85% of the teachers of the state education network who work in the prison units in the city of Porto Velho, Rondonia, Amazonia, Brazil. Method: This is a cross-sectional study; and for the data collection, three structured instruments were used: the sociodemographic questionnaire; the Self-Report-Questionnaire Questionnaire (SRQ-20), and the OSI-Occupational Stress Indicator Scale, Measured by Likert Scale. Results: The results showed that 12.5% of the teachers presented minor psychic disorders, considered as indicators of evidence of mental distress. Satisfaction in the work had indexes similar to those found in the literature, presenting the highest proportion in the intermediate variables, that is, their highest frequencies are in the range of some dissatisfaction, with 32.28%; and 32.04% with some satisfaction. The highest index of dissatisfaction is in the variable that refers to salary, with 29.4%. Conclusions: From the results, it is possible to indicate a possible association between job satisfaction and mental suffering. This study will provide great reflections on the teaching practice in prison units and will contribute to the occupational health of teachers working in prison units, allowing a rethinking of public policies in education and health in the context of the prison system

Hospital Utilization Rates for Influenza and RSV:A Novel Approach and Critical Assessment

Abstract Background Influenza and respiratory syncytial virus (RSV) contribute significantly to the burden of acute lower respiratory infection (ALRI) inpatient care, but heterogeneous coding practices and availability of inpatient data make it difficult to estimate global hospital utilization for either disease based on coded diagnoses alone. Methods This study estimates rates of influenza and RSV hospitalization by calculating the proportion of ALRI due to influenza and RSV and applying this proportion to inpatient admissions with ALRI coded as primary diagnosis. Proportions of ALRI attributed to influenza and RSV were extracted from a meta-analysis of 360 total sources describing inpatient hospital admissions which were input to a Bayesian mixed effects model over age with random effects over location. Results of this model were applied to inpatient admission datasets for 44 countries to produce rates of hospital utilization for influenza and RSV respectively, and rates were compared to raw coded admissions for each disease. Results For most age groups, these methods estimated a higher national admission rate than the rate of directly coded influenza or RSV admissions in the same inpatient sources. In many inpatient sources, International Classification of Disease (ICD) coding detail was insufficient to estimate RSV burden directly. The influenza inpatient burden estimates in older adults appear to be substantially underestimated using this method on primary diagnoses alone. Application of the mixed effects model reduced heterogeneity between countries in influenza and RSV which was biased by coding practices and between-country variation. Conclusions This new method presents the opportunity of estimating hospital utilization rates for influenza and RSV using a wide range of clinical databases. Estimates generally seem promising for influenza and RSV associated hospitalization, but influenza estimates from primary diagnosis seem highly underestimated among older adults. Considerable heterogeneity remains between countries in ALRI coding (i.e., primary vs non-primary cause), and in the age profile of proportion positive for influenza and RSV across studies. While this analysis is interesting because of its wide data utilization and applicability in locations without laboratory-confirmed admission data, understanding the sources of variability and data quality will be essential in future applications of these methods

Desempenho de pacientes esquizofrênicos no Stroop Color Word Test e responsividade eletrodérmica após administração aguda de canabidiol (CBD)

OBJECTIVE: The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. METHOD: The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300mg or cannabidiol 600mg or placebo. RESULTS: The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300mg performing better than those who received cannabidiol 600mg. CONCLUSION: The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.OBJETIVO: Descobertas relativas a possíveis disfunções do sistema canabinóide endógeno na esquizofrenia e sua relação com o prejuízo cognitivo característico da doença têm aumentado durante a última década. Estudos com modelos animais, voluntários saudáveis e pacientes psicóticos sugerem claramente que o canabidiol possui efeitos antipsicóticos. Este estudo investigou os efeitos do canabidiol sobre a atenção seletiva por meio do Stroop Color Word Test e a responsividade eletrodérmica a estímulos auditivos em 28 pacientes com esquizofrenia. MÉTODO: Duas sessões experimentais foram realizadas, a primeira sem a administração de drogas. Na segunda sessão, os sujeitos foram divididos em três grupos que receberam dose única de canabidiol 300mg, canabidiol 600mg ou placebo. RESULTADOS: Os três grupos não diferiram significativamente no que se refere às medidas eletrodérmicas nas duas sessões experimentais. Os três grupos apresentaram melhora da primeira para a segunda avaliação, com os grupos placebo e canabidiol 300mg superiores ao grupo canabidiol 600mg. CONCLUSÃO: A administração aguda de canabidiol em dose única parece não ter efeitos benéficos sobre o desempenho de pacientes com esquizofrenia no Stroop Color Word Test, embora estes dados não sejam suficientes para refutar a hipótese de que a administração continuada de canabidiol possa resultar em melhora no funcionamento cognitivo em esquizofrenia

Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States. METHODS: We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants' first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis. RESULTS: According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants' first RSV season occurred among term infants without known comorbidities. CONCLUSIONS: Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants' first RSV season. Future prevention efforts should consider all infants

Global and national influenza-associated hospitalisation rates:Estimates for 40 countries and administrative regions

BACKGROUND: WHO estimates that seasonal influenza epidemics result in three to five million cases of severe illness (hospitalisations) every year. We aimed to improve the understanding of influenza-associated hospitalisation estimates at a national and global level. METHODS: We performed a systematic literature review of English- and Chinese-language studies published between 1995 and 2020 estimating influenza-associated hospitalisation. We included a total of 127 studies (seven in Chinese) in the meta-analysis and analyzed their data using a logit-logistic regression model to understand the influence of five study factors and produce national and global estimates by age groups. The five study factors assessed were: 1) the method used to calculate the influenza-associated hospitalisation estimates (rate- or time series regression-based), 2) the outcome measure (divided into three envelopes: narrow, medium, or wide), 3) whether every case was laboratory-confirmed or not, 4) whether the estimates were national or sub-national, 5) whether the rates were based on a single year or multiple years. RESULTS: The overall pooled influenza-associated hospitalisation rate was 40.1 (95% confidence interval (CI) = 23.3-69.1) per 100 000 persons, with rates varying substantially by age: 137.8 (95% CI = 70.6-268.7) in children aged 0-4 years and 71.6 (95% CI = 39.9-127.7) in the elderly aged >65 years. The overall pooled hospitalisation rates varied by calculation method; for all ages, the rates were significantly higher when they were based on rate-based methods or calculated on a single season and significantly lower when cases were laboratory-confirmed. The national hospitalisation rates (all ages) varied considerably, ranging from 11.7 (95% CI = 3.8-36.3) per 100 000 in New Zealand to 122.1 (95% CI = 41.5-358.4) per 100 000 in India (all age estimates). CONCLUSIONS: Using the pooled global influenza-associated hospitalisation rate, we estimate that seasonal influenza epidemics result in 3.2 million cases of severe illness (hospitalisations) per annum. More extensive analyses are required to assess the influence of other factors on the estimates (e.g. vaccination and dominant virus (sub)types) and efforts to harmonize the methods should be encouraged. Our study highlights the high rates of influenza-associated hospitalisations in children aged 0-4 years and the elderly aged 65+ years