Racial inequalities in the development of multimorbidity of chronic conditions: results from a Brazilian prospective cohort.

BACKGROUND: The occurrence of multimorbidity and its impacts have differentially affected population subgroups. Evidence on its incidence has mainly come from high-income regions, with limited exploration of racial disparities. This study investigated the association between racial groups and the development of multimorbidity and chronic conditions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Data from self-reported white, brown (pardos or mixed-race), and black participants at baseline of ELSA-Brasil (2008-2010) who were at risk for multimorbidity were analysed. The development of chronic conditions was assessed through in-person visits and self-reported diagnosis via telephone until the third follow-up visit (2017-2019). Multimorbidity was defined when, at the follow-up visit, the participant had two or more morbidities. Cumulative incidences, incidence rates, and adjusted incidence rate ratios (IRRs) were estimated using Poisson models. RESULTS: Over an 8.3-year follow-up, compared to white participants: browns had a 27% greater incidence of hypertension and obesity; and blacks had a 62% and 45% greater incidence, respectively. Blacks also had 58% more diabetes. The cancer incidence was greater among whites. Multimorbidity affected 41% of the participants, with a crude incidence rate of 57.5 cases per 1000 person-years (ranging from 56.3 for whites to 63.9 for blacks). Adjusted estimates showed a 20% higher incidence of multimorbidity in black participants compared to white participants (IRR: 1.20; 95% CI: 1.05-1.38). CONCLUSIONS: Significant racial disparities in the risk of chronic conditions and multimorbidity were observed. Many associations revealed a gradient increase in illness risk according to darker skin tones. Addressing fundamental causes such as racism and racial discrimination, alongside considering social determinants of health, is vital for comprehensive multimorbidity care. Intersectoral, equitable policies are essential for ensuring health rights for historically marginalized groups.

Genomic Comparative of Pseudomonas aeruginosa Small Colony Variant, Mucoid and Non-mucoid Phenotypes Obtained from a Patient with Cystic Fibrosis During Respiratory Exacerbations.

Pseudomonas aeruginosa, the most prevalent opportunistic pathogen in chronic obstructive pulmonary disease, associated with high morbidity and mortality in patients with cystic fibrosis (CF), is practically impossible to be eradicated from the airways in chronicity. Its extraordinary genomic plasticity is possibly associated with high antimicrobial resistance, virulence factors, and its phenotypic diversity. The occurrence of P. aeruginosa isolates promoting airway infection, showing mucoid, non-mucoid, and small colony variant (SCV) phenotypes, was observed simultaneously, in the present study, in sputum cultures obtained from a male CF young patient with chronic pulmonary infection for over a decade. The isolates belonged to a new ST (2744) were obtained in two moments of exacerbation of the respiratory disease, in which he was hospitalized. Genetic background and phenotypic analysis indicated that the isolates exhibited multi- and pan-antimicrobial resistant profiles, as well as non-susceptible to polymyxin and predominantly hypermutable (HPM) phenotypes. Whole genome sequencing showed variations in genome sizes, coding sequences and their determinants of resistance and virulence. The annotated genomes were compared for antimicrobial resistance, hypermutability, and SCV characteristics. We highlight the lack of reported genetic determinants of SCV emergence and HPM phenotypes, which can be explained in part due to the very short time between collections of isolates. To the best of our knowledge, this is the first report of genome sequencing of P. aeruginosa SCV from a CF patient in Brazil.

An overview of soil and plant assessment for predicting site quality and recovery strategies of one the largest tailings dam failures worldwide.

Brazil's Fundão dam collapse is one of the world's largest disasters of tailing dam failures. Previous research has evaluated toxic metals and non-metals (Cd, Cr, Ni, Pb, As, Hg) in the same soil samples used in this study, and results have indicated that only Fe and Mn concentrations increased above the original baseline (Melo et al., 2023). Consequently, the present study's focus has shifted towards assessing and integrating changes in soil quality regarding chemical fertility and morphological, physical, and mineralogical attributes in the floodplains post-dam collapse. Soil samples from 0 to 0.2 and 0.2-0.4 m depths, and samples of Urochloa sp. were collected along ten transects, spanning 100 km perpendicular to the Doce River channel. This sampling strategy targeted specific landscape positions including areas affected by deposited iron tailings (DIT), soil tailing mixture (STM), and control soil (CS) devoid of iron tailing interference. Results showed no discernible alterations in Ca, Mg, K, and P concentrations in Urochloa sp., and the most severe negative impacts observed regarded the replacement of kaolinitic pre-disaster matrix for hematitic matrix, reduction in organic carbon, and the prevalence of sand and silt particles. These factors collectively contributed to triggering: (i) decrease in chemical fertility and cation exchange capacity and (ii) significant decline in physical quality, evidenced by increased density and reduced total porosity and macroporosity. Addressing these adverse effects would require the augment of organic matter levels and offset the dominance of the hematitic matrix in the DIT. Furthermore, it is imperative to decompact the DIT by mechanized or plant cultivation means.

SARS-CoV-2 Reinfection Cases in a Household-Based Prospective Cohort in Rio de Janeiro.

This was a household-based prospective cohort study conducted in Rio de Janeiro, in which people with laboratory-confirmed coronavirus disease 2019 (COVID-19) and their household contacts were followed from April 2020 through June 2022. Ninety-eight reinfections were identified, with 71 (72.5%) confirmed by genomic analyses and lineage definition in both infections. During the pre-Omicron period, 1 dose of any COVID-19 vaccine was associated with a reduced risk of reinfection, but during the Omicron period not even booster vaccines had this effect. Most reinfections were asymptomatic or milder in comparison with primary infections, a justification for continuing active surveillance to detect infections in vaccinated individuals. Our findings demonstrated that vaccination may not prevent infection or reinfection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Therefore we highlight the need to continuously update the antigenic target of SARS CoV-2 vaccines and administer booster doses to the population regularly, a strategy well established in the development of vaccines for influenza immunization programs.

Effects of Taurine in Mice and Zebrafish Behavioral Assays With Translational Relevance to Schizophrenia.

BACKGROUND: Altered redox state and developmental abnormalities in glutamatergic and GABAergic transmission during development are linked to the behavioral changes associated with schizophrenia. As an amino acid that exerts antioxidant and inhibitory actions in the brain, taurine is a potential candidate to modulate biological targets relevant to this disorder. Here, we investigated in mice and zebrafish assays whether taurine prevents the behavioral changes induced by acute administration of MK-801 (dizocilpine), a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist. METHODS: C57BL/6 mice were i.p. administered with saline or taurine (50, 100, and 200 mg/kg) followed by MK-801 (0.15 mg/kg). Locomotor activity, social interaction, and prepulse inhibition of the acoustic startle reflex were then assessed in different sets of animals. Zebrafish were exposed to tank water or taurine (42, 150, and 400 mg/L) followed by MK-801 (5 µM); social preference and locomotor activity were evaluated in the same test. RESULTS: MK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability and increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish. DISCUSSION: Contradicting previous clinical and preclinical data, taurine did not show antipsychotic-like effects in the present study. However, it still warrants consideration as a preventive intervention in animal models relevant to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients.

Notification of malaria cases in the Brazilian Amazon Basin from 2010 to 2020: an analysis of the reporting times.

BACKGROUND: As controlling malaria transmission remains a public-health challenge in the Brazilian Amazon basin, the National Surveillance System for Malaria (SIVEP-MALARIA) has registered malaria notifications for over fifteen years helping in the decision-making on control and elimination. As a surveillance database, the system is prone to reporting delays, and knowledge about reporting patterns is essential in decisions. METHODS: This study contains an analysis of temporal and state trends of reporting times in a total of 1,580,617 individual malaria reports from January 2010 to December 2020, applying procedures for statistical distribution fitting. A nowcasting technique was applied to show an estimation of number of cases using a statistical model of reporting delays. RESULTS: Reporting delays increased over time for the states of Amazonas, Rondônia, Roraima, and Pará. Amapá has maintained a similar reporting delay pattern, while Acre decreased reporting delay between 2010 and 2020. Predictions were more accurate in states with lower reporting delays. The temporal evolution of reporting delays only showed a decrease in malaria reports in Acre from 2010 to 2020. CONCLUSION: Malaria notifications may take days or weeks to enter the national surveillance database. The reporting times are likely to impact incidence estimation over periods when data is incomplete, whilst the impact of delays becomes smaller for retrospective analysis. Short-term assessments for the estimation of malaria incidence from the malaria control programme must deal with reporting delays.

The spatio-temporal distribution of acute encephalitis syndrome and its association with climate and landcover in Vietnam.

BACKGROUND: Acute encephalitis syndrome (AES) differs in its spatio-temporal distribution in Vietnam with the highest incidence seen during the summer months in the northern provinces. AES has multiple aetiologies, and the cause remains unknown in many cases. While vector-borne disease such as Japanese encephalitis and dengue virus and non-vector-borne diseases such as influenza and enterovirus show evidence of seasonality, associations with climate variables and the spatio-temporal distribution in Vietnam differs between these. The aim of this study was therefore to understand the spatio-temporal distribution of, and risk factors for AES in Vietnam to help hypothesise the aetiology. METHODS: The number of monthly cases per province for AES, meningitis and diseases including dengue fever; influenza-like-illness (ILI); hand, foot, and mouth disease (HFMD); and Streptococcus suis were obtained from the General Department for Preventive Medicine (GDPM) from 1998-2016. Covariates including climate, normalized difference vegetation index (NDVI), elevation, the number of pigs, socio-demographics, JEV vaccination coverage and the number of hospitals were also collected. Spatio-temporal multivariable mixed-effects negative binomial Bayesian models with an outcome of the number of cases of AES, a combination of the covariates and harmonic terms to determine the magnitude of seasonality were developed. RESULTS: The national monthly incidence of AES declined by 63.3% over the study period. However, incidence increased in some provinces, particularly in the Northwest region. In northern Vietnam, the incidence peaked in the summer months in contrast to the southern provinces where incidence remained relatively constant throughout the year. The incidence of meningitis, ILI and S. suis infection; temperature, relative humidity with no lag, NDVI at a lag of one month, and the number of pigs per 100,000 population were positively associated with the number of cases of AES in all models in which these covariates were included. CONCLUSIONS: The positive correlation of AES with temperature and humidity suggest that a number of cases may be due to vector-borne diseases, suggesting a need to focus on vaccination campaigns. However, further surveillance and research are recommended to investigate other possible aetiologies such as S. suis or Orientia tsutsugamushi.

Effects of Tranexamic Acid in Patients with Subarachnoid Hemorrhage in Brazil: A Prospective Observational Study with Propensity Score Analysis.

BACKGROUND: Rebleeding from a ruptured aneurysm increases the risk of unfavorable outcomes after subarachnoid hemorrhage (SAH) and is prevented by early aneurysm occlusion. The role of antifibrinolytics before aneurysm obliteration remains controversial. We investigated the effects of tranexamic acid on long-term functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: This was a single-center, prospective, observational study conducted in a high-volume tertiary hospital in a middle-income country from December 2016 to February 2020. We included all consecutive patients with aSAH who either received or did not receive tranexamic acid (TXA) treatment. Multivariate logistic regression analysis using propensity score was used to evaluate the association of TXA use with long-term functional outcomes, measured by the modified Rankin Scale (mRS) at 6 months. RESULTS: A total of 230 patients with aSAH were analyzed. The median (interquartile range) age was 55 (46-63) years, 72% were women, 75% presented with good clinical grade (World Federation of Neurological Surgeons grade 1-3), and 83% had a Fisher scale of 3 or 4. Around 80% of patients were admitted up to 72 h from ictus. The aneurysm occlusion method was surgical clipping in 80% of the patients. A total of 129 patients (56%) received TXA. In multivariable logistic regression using inverse probability treatment weighting, the long-term rate of unfavorable outcomes (modified Rankin scale 4-6) was the same in the TXA and non-TXA groups (61 [48%] in TXA group vs. 33 [33%] in non-TXA group; odds ratio [OR] 1.39, 95% confidence interval [CI] 0.67-2.92; p = 0.377). The TXA group had higher in-hospital mortality (33 vs. 11% in non-TXA group; OR 4.13, 95% CI 1.55-12.53, p = 0.007). There were no differences between the groups concerning intensive care unit length of stay (16 ± 11.22 days in TXA group vs. 14 ± 9.24 days in non-TXA group; p = 0.2) or hospital (23 ± 13.35 days in TXA group vs. 22 ± 13.36 days in non-TXA group; p = 0.9). There was no difference in the rates of rebleeding (7.8% in TXA group vs. 8.9% in non-TXA group; p = 0.31) or delayed cerebral ischemia (27% in TXA group vs. 19% in non-TXA group; p = 0.14). For the propensity-matched analysis, 128 individuals were selected (64 in TXA group and 64 in non-TXA group), and the rates of unfavorable outcomes at 6 months were also similar between groups (45% in TXA group and 36% in non-TXA group; OR 1.22, 95% CI 0.51-2.89; p = 0.655). CONCLUSIONS: Our findings in a cohort with delayed aneurysm treatment reinforce previous data that TXA use before aneurysm occlusion does not improve functional outcomes in aSAH.

Industrial wastewater treatment by plant-based bio-filtration.

Constructed wetlands (CWs) represent a natural wastewater treatment process, offering economic and environmental advantages. These systems can remove several components that may cause negative impacts on the environment. Media types and plant species are crucial influencing factors for the removal of contaminants in CWs. The goal of this study is to evaluate the capacity of a CW using Tamarix spp. with three filter media to treat FGD wastewater. Planted and unplanted CWs were set up with varying types of biofilm support media: 3 bioreactors were operated with 50% gravel and 50% zeolite (v/v), 3 with 100% gravel, and 3 with 50% gravel, 25% zeolite, and 25% silage. Planted CWs had the greatest potential to reduce the concentrations of B, K, and NH4+-N in 64.9%, 91.1%, and 92.5%, respectively, when used in addition to the filter composed by 50% gravel + 50% zeolite, which was the only media keeping the plants alive for 60 days. The results showed that the optimal selection of filter media depends on the purpose for which the treatment has been projected for, considering that the types of substrates influenced the nature of the contaminant removal in the CW.

Salinity impact on Constructed wetlands (CWs) is still scarce in the literature. The novelty is the choice of a salt cedar (Tamarix spp.) combined with three filter media types ((1) gravel; (2) gravel and zeolite; (3) gravel, zeolite, and silage) to treat flue gas desulfurization wastewater in CWs. Our findings demonstrate that filter media containing 50% gravel + 50% zeolite can decrease the toxicity of contaminants from FGD wastewater in plants.

Micronized Curcumin Causes Hyperlocomotion in Zebrafish Larvae.

Zebrafish larvae have been widely used in neuroscience and drug research and development. In the larval stage, zebrafish present a broad behavioral repertoire and physiological responses similar to adults. Curcumin (CUR), a major component of Curcuma longa L. (Zingiberaceae), has demonstrated the ability to modulate several neurobiological processes relevant to mental disorders in animal models. However, the low bioavailability of this compound can compromise its in vivo biological potential. Interestingly, it has been shown that micronization can increase the biological effects of several compounds. Thus, in this study, we compared the effects of acute exposure for 30 min to the following solutions: water (control), 0.1% DMSO (vehicle), 1 µM CUR, or 1 µM micronized curcumin (MC) in zebrafish larvae 7 days post-fertilization (dpf). We analyzed locomotor activity (open tank test), anxiety (light/dark test), and avoidance behavior (aversive stimulus test). Moreover, we evaluated parameters of oxidative status (thiobarbituric acid reactive substances and non-protein thiols levels). MC increased the total distance traveled and absolute turn angle in the open tank test. There were no significant differences in the other behavioral or neurochemical outcomes. The increase in locomotion induced by MC may be associated with a stimulant effect on the central nervous system, which was evidenced by the micronization process.

On multifactorial drivers for malaria rebound in Brazil: a spatio-temporal analysis.

BACKGROUND: Malaria incidence in Brazil reversed its decreasing trend when cases from recent years, as recent as 2015, exhibited an increase in the Brazilian Amazon basin, the area with the highest transmission of Plasmodium vivax and Plasmodium falciparum. In fact, an increase of more than 20% in the years 2016 and 2017 revealed possible vulnerabilities in the national malaria-control programme. METHODS: Factors potentially associated with this reversal, including migration, economic activities, and deforestation, were studied. Past incidences of malaria cases due to P. vivax and P. falciparum were analysed with a spatio-temporal Bayesian model using more than 5 million individual records of malaria cases from January of 2003 to December of 2018 in the Brazilian Amazon to establish the municipalities with unexpected increases in cases. RESULTS: Plasmodium vivax incidence surpassed the past trends in Amazonas (AM), Amapá (AP), Acre (AC), Pará (PA), Roraima (RR), and Rondônia (RO), implying a rebound of these states between 2015 and 2018. On the other hand, P. falciparum also surpassed the past trends in AM, AC, AP, and RR with less severity than P. vivax incidence. Outdoor activities, agricultural activities, accumulated deforestation, and travelling might explain the rebound in malaria cases in RR, AM, PA, and RO, mainly in P. vivax cases. These variables, however, did not explain the rebound of either P. vivax and P. falciparum cases in AC and AP states or P. falciparum cases in RR and RO states. CONCLUSION: The Amazon basin has experienced an unexpected increase in malaria cases, mainly in P. vivax cases, in some regions of the states of Amazonas, Acre, Pará, Amapá, Roraima, and Rondônia from 2015 to 2018 and agricultural activities, outdoor activities, travelling activities, and accumulated deforestation appear linked to this rebound of cases in particular regions with different impact. This shows the multifactorial effects and the heterogeneity of the Amazon basin, boosting the necessity of focusing the malaria control programme on particular social, economic, and environmental conditions.

Racial inequalities in multimorbidity: baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Evidence of multimorbidity has come mainly from high-income regions, while disparities among racial groups have been less explored. This study examined racial differences in multimorbidity in the multiracial cohort of the Longitudinal Study of Adult Health (Estudo Longitudinal de Saúde do Adulto), ELSA-Brasil. METHODS: The study examined baseline (2008-2010) data for 14 099 ELSA-Brasil participants who self-reported being white, mixed-race, or black. A list of 16 morbidities was used to evaluate multimorbidity, operationalised by simple count into ≥ 2, ≥ 3, ≥ 4, ≥ 5 and ≥ 6 morbidities, in addition to evaluating the number of coexisting conditions. Prevalence ratios (PR) were estimated from logistic models and a quantile model was used to examine racial differences graphically in the distribution quantiles for the number of morbidities. RESULTS: Overall prevalence of multimorbidity (≥ 2 morbidities) was 70% and, after controlling for age and sex, was greater among mixed-race and black participants - by 6% (PR: 1.06; 95% CI: 1.03-1.08) and 9% (PR: 1.09; 95% CI: 1.06-1.12), respectively - than among white participants. As the cutoff value for defining multimorbidity was raised, so the strength of the association increased, especially among blacks: if set at ≥ 6 morbidities, the prevalence was 27% greater for those of mixed-race (PR: 1.27; 95% CI: 1.07-1.50) and 47% greater for blacks (PR: 1.47; 95% CI: 1.22-1.76) than for whites. The disparities were smaller in the lower morbidity distribution quantiles and larger in the upper quantiles, indicating a heavier burden of disease, particularly on blacks. CONCLUSIONS: Multimorbidity was common among adults and older adults in a Brazilian cohort, but important racial inequalities were found. Raising the cutoff point for defining multimorbidity revealed stronger associations between race/skin colour and multimorbidity, indicating a higher prevalence of multimorbidity among mixed-race and black individuals than among whites and that the former groups coexisted more often with more complex health situations (with more coexisting morbidities). Interventions to prevent and manage the condition of multimorbidity that consider the social determinants of health and historically discriminated populations in low- and middle-income regions are necessary.

Probabilistic seasonal dengue forecasting in Vietnam: A modelling study using superensembles.

BACKGROUND: With enough advanced notice, dengue outbreaks can be mitigated. As a climate-sensitive disease, environmental conditions and past patterns of dengue can be used to make predictions about future outbreak risk. These predictions improve public health planning and decision-making to ultimately reduce the burden of disease. Past approaches to dengue forecasting have used seasonal climate forecasts, but the predictive ability of a system using different lead times in a year-round prediction system has been seldom explored. Moreover, the transition from theoretical to operational systems integrated with disease control activities is rare. METHODS AND FINDINGS: We introduce an operational seasonal dengue forecasting system for Vietnam where Earth observations, seasonal climate forecasts, and lagged dengue cases are used to drive a superensemble of probabilistic dengue models to predict dengue risk up to 6 months ahead. Bayesian spatiotemporal models were fit to 19 years (2002-2020) of dengue data at the province level across Vietnam. A superensemble of these models then makes probabilistic predictions of dengue incidence at various future time points aligned with key Vietnamese decision and planning deadlines. We demonstrate that the superensemble generates more accurate predictions of dengue incidence than the individual models it incorporates across a suite of time horizons and transmission settings. Using historical data, the superensemble made slightly more accurate predictions (continuous rank probability score [CRPS] = 66.8, 95% CI 60.6-148.0) than a baseline model which forecasts the same incidence rate every month (CRPS = 79.4, 95% CI 78.5-80.5) at lead times of 1 to 3 months, albeit with larger uncertainty. The outbreak detection capability of the superensemble was considerably larger (69%) than that of the baseline model (54.5%). Predictions were most accurate in southern Vietnam, an area that experiences semi-regular seasonal dengue transmission. The system also demonstrated added value across multiple areas compared to previous practice of not using a forecast. We use the system to make a prospective prediction for dengue incidence in Vietnam for the period May to October 2020. Prospective predictions made with the superensemble were slightly more accurate (CRPS = 110, 95% CI 102-575) than those made with the baseline model (CRPS = 125, 95% CI 120-168) but had larger uncertainty. Finally, we propose a framework for the evaluation of probabilistic predictions. Despite the demonstrated value of our forecasting system, the approach is limited by the consistency of the dengue case data, as well as the lack of publicly available, continuous, and long-term data sets on mosquito control efforts and serotype-specific case data. CONCLUSIONS: This study shows that by combining detailed Earth observation data, seasonal climate forecasts, and state-of-the-art models, dengue outbreaks can be predicted across a broad range of settings, with enough lead time to meaningfully inform dengue control. While our system omits some important variables not currently available at a subnational scale, the majority of past outbreaks could be predicted up to 3 months ahead. Over the next 2 years, the system will be prospectively evaluated and, if successful, potentially extended to other areas and other climate-sensitive disease systems.

Systemic Severity and Organ Dysfunction in Subarachnoid Hemorrhage: A Large Retrospective Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Acute physiologic derangements and multiple organ dysfunction are common after subarachnoid hemorrhage. We aimed to evaluate the simplified acute physiology score 3 (SAPS-3) and the sequential organ failure assessment (SOFA) scores for the prediction of in-hospital mortality in a large multicenter cohort of SAH patients. METHODS: This was a retrospective analysis of prospectively collected data from 45 ICUs in Brazil, during 2014 and 2015. Patients admitted with non-traumatic subarachnoid hemorrhage (SAH) were included. Clinical and outcome data were retrieved from an electronic ICU quality registry. SAPS-3 and SOFA scores, without the neurological components (i.e., nSAPS-3 and nSOFA, respectively) were recorded, as well as the World Federation of Neurological Surgeons (WFNS) scale. We used multilevel logistic regression analysis to identify factors associated with in-hospital mortality. We evaluated performance using the area under the receiver operating characteristic curve (AUROC), as well as calibration belts and precision-recall plots. RESULTS: The study included 997 patients, from which 426 (43%) had poor clinical grade (WFNS 4 or 5) and in-hospital mortality was 34%. Median nSAPS-3 and nSOFA score at admission were 46 (IQR: 38-55) and 2 (0-5), respectively. Non-survivors were older, had higher nSAPS-3 and nSOFA, and more often poor grade. After adjustment for age, poor grade and withdrawal of life sustaining therapies, multivariable analysis identified nSAPS-3 and nSOFA score as independent clinical predictors of in-hospital mortality. The AUROC curve that included nSAPS-3 and nSOFA scores significantly improved the already good discrimination and calibration of age and WFNS to predict in-hospital mortality (AUROC: 0.89 for the full final model vs. 0.85 for age and WFNS; P < 0.0001). CONCLUSIONS: nSAPS-3 and nSOFA scores were independently associated with in-hospital mortality after SAH. The addition of these scores improved early prediction of hospital mortality in our cohort and should be integrated to other specific prognostic indices in the early assessment of SAH.

Identification of potential allosteric binding sites in cathepsin K based on intramolecular communication.

Network theory methods and molecular dynamics (MD) simulations are accepted tools to study allosteric regulation. Indeed, dynamic networks built upon correlation analysis of MD trajectories provide detailed information about communication paths between distant sites. In this context, we aimed to understand whether the efficiency of intramolecular communication could be used to predict the allosteric potential of a given site. To this end, we performed MD simulations and network theory analyses in cathepsin K (catK), whose allosteric sites are well defined. To obtain a quantitative measure of the efficiency of communication, we designed a new protocol that enables the comparison between properties related to ensembles of communication paths obtained from different sites. Further, we applied our strategy to evaluate the allosteric potential of different catK cavities not yet considered for drug design. Our predictions of the allosteric potential based on intramolecular communication correlate well with previous catK experimental and theoretical data. We also discuss the possibility of applying our approach to other proteins from the same family.

The cost-effectiveness of controlling dengue in Indonesia using wMel Wolbachia released at scale: a modelling study.

BACKGROUND: Release of virus-blocking Wolbachia-infected mosquitoes is an emerging disease control strategy that aims to control dengue and other arboviral infections. Early entomological data and modelling analyses have suggested promising outcomes, and wMel Wolbachia releases are now ongoing or planned in 12 countries. To help inform government, donor, or philanthropist decisions on scale-up beyond single city releases, we assessed this technology's cost-effectiveness under alternative programmatic options. METHODS: Using costing data from existing Wolbachia releases, previous dynamic model-based estimates of Wolbachia effectiveness, and a spatially explicit model of release and surveillance requirements, we predicted the costs and effectiveness of the ongoing programme in Yogyakarta City and three new hypothetical programmes in Yogyakarta Special Autonomous Region, Jakarta, and Bali. RESULTS: We predicted Wolbachia to be a highly cost-effective intervention when deployed in high-density urban areas with gross cost-effectiveness below $1500 per DALY averted. When offsets from the health system and societal perspective were included, such programmes even became cost saving over 10-year time horizons with favourable benefit-cost ratios of 1.35 to 3.40. Sequencing Wolbachia releases over 10 years could reduce programme costs by approximately 38% compared to simultaneous releases everywhere, but also delays the benefits. Even if unexpected challenges occurred during deployment, such as emergence of resistance in the medium-term or low effective coverage, Wolbachia would remain a cost-saving intervention. CONCLUSIONS: Wolbachia releases in high-density urban areas are expected to be highly cost-effective and could potentially be the first cost-saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritised.

Measuring the contribution of human mobility to malaria persistence.

BACKGROUND: To achieve malaria elimination, it is important to determine the role of human mobility in parasite transmission maintenance. The Alto Juruá basin (Brazil) exhibits one of the largest vivax and falciparum malaria prevalence in the Amazon. The goal of this study was to estimate the contribution of human commutes to malaria persistence in this region, using data from an origin-destination survey. METHODS: Data from an origin-destination survey were used to describe the intensity and motivation for commutations between rural and urban areas in two Alto Juruá basin (Brazil) municipalities, Mâncio Lima and Rodrigues Alves. The relative time-person spent in each locality per household was estimated. A logistic model was developed to estimate the effect of commuting on the probability of contracting malaria for a certain residence zone inhabitant commuting to another zone. RESULTS: The main results suggest that the assessed population is not very mobile. A total of [Formula: see text] households reported spending over [Formula: see text] of their annual person-hour in areas within the same residence zone. Study and work were the most prevalent commuting motivations, calculated at [Formula: see text] and [Formula: see text] respectively. Spending person-hours in urban Rodrigues Alves conferred relative protection to urban Mâncio Lima residents. The opposite effect was observed for those spending time in rural areas of both municipalities. CONCLUSION: Residence area is a stronger determinant for contracting malaria than commuting zones in the Alto Juruá region. As these municipalities are a hotspot for Plasmodium transmission, understanding the main local human fluxes is essential for planning control strategies, since the probability of contracting malaria is dependent on the transmission intensity of both the origin and the displacement area. The natural conditions for the circulation of certain pathogens, such as Plasmodium spp., combined with the Amazon human mobility pattern indicate the need for disease control perspective changes. Therefore, intersectoral public policies should become the basis for health mitigation actions.

A modelling approach for correcting reporting delays in disease surveillance data.

One difficulty for real-time tracking of epidemics is related to reporting delay. The reporting delay may be due to laboratory confirmation, logistical problems, infrastructure difficulties, and so on. The ability to correct the available information as quickly as possible is crucial, in terms of decision making such as issuing warnings to the public and local authorities. A Bayesian hierarchical modelling approach is proposed as a flexible way of correcting the reporting delays and to quantify the associated uncertainty. Implementation of the model is fast due to the use of the integrated nested Laplace approximation. The approach is illustrated on dengue fever incidence data in Rio de Janeiro, and severe acute respiratory infection data in the state of Paraná, Brazil.

Whole genome sequencing of a ST2594 MRSA strain causing non-mucosal preoperative colonization and low-grade postoperative infection.

We present a post-operative infection caused by a methicillin-resistant Staphylococcus aureus strain, previously isolated in the preoperative screening, in a patient submitted to femoral osteosynthesis, successfully treated with oral ciprofloxacin. The isolate exhibited in vitro resistance to ciprofloxacin, Staphylococcal Cassette Chromosome mec type IV, it was negative for the lukS-PV Panton-Valentine leucocidin gene and belonged to ST2594 in multilocus sequence typing analysis. Whole genome sequencing revealed a genome size of 2,818,289 base pairs. The annotated genomes of ST2594 and N315 strains were compared, looking for genes related to virulence and resistance. The lack of the tst, sec, sel genes, associated with a mutation in the clfA gene, may partially explain the low morbity in this case.