The uncertainty surrounding the burden of post-acute consequences of dengue infection

Post-acute consequences currently form a significant component of the dengue disability-adjusted life year (DALY) burden estimates. However, there is considerable uncertainty regarding the incidence, duration, and severity of these symptoms. Further research is needed to more accurately estimate the health and economic burden of these dengue manifestations

Projected costs associated with school-based screening to inform deployment of Dengvaxia: Vietnam as a case study

Background: After new analysis, Sanofi Pasteur now recommends their dengue vaccine (Dengvaxia) should only be given to individuals previously infected with dengue and the World Health Organization's recommendations regarding its use are currently being revised. As a result, the potential costs of performing large-scale individual dengue screening and/or dengue serosurveys have become an important consideration for decision making by policymakers in dengue-endemic areas. Methods: We used an ingredients-based approach to estimate the financial costs for conducting both a school-based dengue serosurvey and school-based individual dengue screening within a typical province in Vietnam, using an existing commercial indirect immunoglobulin G enzyme-linked immunosorbent assay kit. This costing is hypothetical and based on estimates regarding the resources that would be required to perform such activities. Results: We estimated that performing a school-based individual screening of 9-year-olds would cost US$9.25 per child tested or US$197,827 in total for a typical province. We also estimated that a school-based serosurvey would cost US$10,074, assuming one class from each of the grades that include 8- to 11-year-olds are sampled at each of the 12 selected schools across the province. Conclusions: The study indicates that using this vaccine safely on a large-scale will incur noteworthy operational costs. It is crucial that these be considered in future cost-effectiveness analyses informing how and where the vaccine is deployed

The estimates of the health and economic burden of dengue in Vietnam

Dengue has been estimated to cause a substantial health and economic burden in Vietnam. The most recent studies have estimated that it is responsible for 39884 disability-adjusted life years (DALYs) annually, representing an economic burden of US$94.87 million per year (in 2016 prices). However, there are alternative burden estimates that are notably lower. This variation is predominantly due to differences in how the number of symptomatic dengue cases is estimated. Understanding the methodology of these burden calculations is vital when interpreting health economic analyses of dengue. This review aims to provide an overview of the health and economic burden estimates of dengue in Vietnam. We also highlight important research gaps for future studies

Challenges in Real-Time Prediction of Infectious Disease: A Case Study of Dengue in Thailand.

Epidemics of communicable diseases place a huge burden on public health infrastructures across the world. Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks. However, scientists and public health officials face many obstacles in trying to create such real-time forecasts of infectious disease incidence. Dengue is a mosquito-borne virus that annually infects over 400 million people worldwide. We developed a real-time forecasting model for dengue hemorrhagic fever in the 77 provinces of Thailand. We created a practical computational infrastructure that generated multi-step predictions of dengue incidence in Thai provinces every two weeks throughout 2014. These predictions show mixed performance across provinces, out-performing seasonal baseline models in over half of provinces at a 1.5 month horizon. Additionally, to assess the degree to which delays in case reporting make long-range prediction a challenging task, we compared the performance of our real-time predictions with predictions made with fully reported data. This paper provides valuable lessons for the implementation of real-time predictions in the context of public health decision making

A systematic review of the data, methods and environmental covariates used to map Aedes-borne arbovirus transmission risk

BACKGROUND: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. METHODS: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). RESULTS: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. CONCLUSIONS: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping

Catalytic Hydrogen Production by Ruthenium Complexes from the Conversion of Primary Amines to Nitriles: Potential Application as a Liquid Organic Hydrogen Carrier

The potential application of the primary amine/nitrile pair as a liquid organic hydrogen carrier (LOHC) has been evaluated. Ruthenium complexes of formula [(p-cym)Ru(NHC)Cl2] (NHC=N-heterocyclic carbene) catalyze the acceptorless dehydrogenation of primary amines to nitriles with the formation of molecular hydrogen. Notably, the reaction proceeds without any external additive, under air, and under mild reaction conditions. The catalytic properties of a ruthenium complex supported on the surface of graphene have been explored for reutilization purposes. The ruthenium-supported catalyst is active for at least 10 runs without any apparent loss of activity. The results obtained in terms of catalytic activity, stability, and recyclability are encouraging for the potential application of the amine/nitrile pair as a LOHC. The main challenge in the dehydrogenation of benzylamines is the selectivity control, such as avoiding the formation of imine byproducts due to transamination reactions. Herein, selectivity has been achieved by using long-chain primary amines such as dodecylamine. Mechanistic studies have been performed to rationalize the key factors involved in the activity and selectivity of the catalysts in the dehydrogenation of amines. The experimental results suggest that the catalyst resting state contains a coordinated amine.The authors thank the financial support from MINECO (CTQ2015-69153-C2-2-R), Generalitat Valenciana (AICO/2015/ 039), and the UniversitatJaume I(P1.1B2015-09).The authors are very grateful to the “Serve is Centrals d’Instr umentac ij Cien- t&fica (SCIC)” of the Universitat Jaume I

Coordinated waves of actomyosin flow and apical cell constriction immediately after wounding

© 2013 Antunes et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).Epithelial wound healing relies on tissue movements and cell shape changes. Our work shows that, immediately after wounding, there was a dramatic cytoskeleton remodeling consisting of a pulse of actomyosin filaments that assembled in cells around the wound edge and flowed from cell to cell toward the margin of the wound. We show that this actomyosin flow was regulated by Diaphanous and ROCK and that it elicited a wave of apical cell constriction that culminated in the formation of the leading edge actomyosin cable, a structure that is essential for wound closure. Calcium signaling played an important role in this process, as its intracellular concentration increased dramatically immediately after wounding, and down-regulation of transient receptor potential channel M, a stress-activated calcium channel, also impaired the actomyosin flow. Lowering the activity of Gelsolin, a known calcium-activated actin filament-severing protein, also impaired the wound response, indicating that cleaving the existing actin filament network is an important part of the cytoskeleton remodeling process.info:eu-repo/semantics/publishedVersio

Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues

Nur77 regulates lipolysis in skeletal muscle cells - Evidence for cross-talk between the beta-adrenergic and an orphan nuclear hormone receptor pathway

Skeletal muscle is a major mass peripheral tissue that accounts for similar to 40% of total body weight and 50% of energy expenditure and is a primary site of glucose disposal and fatty acid oxidation. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. Excessive caloric intake is sensed by the brain and induces beta-adrenergic receptor (beta-AR)- mediated adaptive thermogenesis. beta-AR null mice develop severe obesity on a high fat diet. However, the target gene(s), target tissues(s), and molecular mechanism involved remain obscure. We observed that 30 - 60 min of beta-AR agonist ( isoprenaline) treatment of C2C12 skeletal muscle cells strikingly activated (> 100-fold) the expression of the mRNA encoding the nuclear hormone receptor, Nur77. In contrast, the expression of other nuclear receptors that regulate lipid and carbohydrate metabolism was not induced. Stable transfection of Nur77-specific small interfering RNAs (siNur77) into skeletal muscle cells repressed endogenous Nur77 mRNA expression. Moreover, we observed attenuation of gene and protein expression associated with the regulation of energy expenditure and lipid homeostasis, for example AMP-activated protein kinase gamma 3, UCP3, CD36,adiponectin receptor 2, GLUT4, and caveolin-3. Attenuation of Nur77 expression resulted in decreased lipolysis. Finally, in concordance with the cell culture model, injection and electrotransfer of siNur77 into mouse tibialis cranialis muscle resulted in the repression of UCP3 mRNA expression. This study demonstrates regulatory cross-talk between the nuclear hormone receptor and beta-AR signaling pathways. Moreover, it suggests Nur77 modulates the expression of genes that are key regulators of skeletal muscle lipid and energy homeostasis. In conclusion, we speculate that Nur77 agonists would stimulate lipolysis and increase energy expenditure in skeletal muscle and suggest selective activators of Nur77 may have therapeutic utility in the treatment of obesity

Disruption of the IS6-AID Linker Affects Voltage-gated Calcium Channel Inactivation and Facilitation

Two processes dominate voltage-gated calcium channel (CaV) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The CaVβ/CaVα1-I-II loop and Ca2+/calmodulin (CaM)/CaVα1–C-terminal tail complexes have been shown to modulate each, respectively. Nevertheless, how each complex couples to the pore and whether each affects inactivation independently have remained unresolved. Here, we demonstrate that the IS6–α-interaction domain (AID) linker provides a rigid connection between the pore and CaVβ/I-II loop complex by showing that IS6-AID linker polyglycine mutations accelerate CaV1.2 (L-type) and CaV2.1 (P/Q-type) VDI. Remarkably, mutations that either break the rigid IS6-AID linker connection or disrupt CaVβ/I-II association sharply decelerate CDI and reduce a second Ca2+/CaM/CaVα1–C-terminal–mediated process known as calcium-dependent facilitation. Collectively, the data strongly suggest that components traditionally associated solely with VDI, CaVβ and the IS6-AID linker, are essential for calcium-dependent modulation, and that both CaVβ-dependent and CaM-dependent components couple to the pore by a common mechanism requiring CaVβ and an intact IS6-AID linker