Direct and indirect effects of age on dengue severity: The mediating role of secondary infection.

Severe dengue occurrence has been attributed to increasing age and different dengue virus (DENV) serotypes that cause secondary infections and immune-enhancing phenomena. Therefore, we examined if the effect of age on dengue severity was mediated by infectivity status while controlling for sex and region. Further, we assessed the spatial clustering of dengue severity for individuals with primary and secondary infection across Mexican municipalities. Health data from 2012 to 2017 was retrieved from Mexico's Ministry of Health. A mediation analysis was performed using multiple logistic regression models based on a directed acyclic graph. The models were explored for the direct effect of age on dengue severity and its indirect impact through secondary infection. In addition, severe dengue clusters were determined in some Northeastern and Southeastern municipalities through spatial analysis. We observed a nonlinear trend between age and severe dengue. There was a downward trend of severe dengue for individuals between 0 and 10 years and an upward trend above 10 years. The effect of age on dengue severity was no longer significant for individuals between 10 and 60 years after introducing infectivity status into the model. The mediating role of infectivity status in the causal model was 17%. Clustering of severe dengue among individuals with primary infection in the Northeastern region may point to the high prevalence of DENV-3 in the region. Public health efforts may prevent secondary infection among infants and the aged. In addition, there should be a further investigation into the effect of DENV-3 in individuals with primary disease.

Moderation effects of serotype on dengue severity across pregnancy status in Mexico.

BACKGROUND: Pregnancy increases a woman's risk of severe dengue. To the best of our knowledge, the moderation effect of the dengue serotype among pregnant women has not been studied in Mexico. This study explores how pregnancy interacted with the dengue serotype from 2012 to 2020 in Mexico. METHOD: Information from 2469 notifying health units in Mexican municipalities was used for this cross-sectional analysis. Multiple logistic regression with interaction effects was chosen as the final model and sensitivity analysis was done to assess potential exposure misclassification of pregnancy status. RESULTS: Pregnant women were found to have higher odds of severe dengue [1.50 (95% CI 1.41, 1.59)]. The odds of dengue severity varied for pregnant women with DENV-1 [1.45, (95% CI 1.21, 1.74)], DENV-2 [1.33, (95% CI 1.18, 1.53)] and DENV-4 [3.78, (95% CI 1.14, 12.59)]. While the odds of severe dengue were generally higher for pregnant women compared with non-pregnant women with DENV-1 and DENV-2, the odds of disease severity were much higher for those infected with the DENV-4 serotype. CONCLUSION: The effect of pregnancy on severe dengue is moderated by the dengue serotype. Future studies on genetic diversification may potentially elucidate this serotype-specific effect among pregnant women in Mexico.

Spatio-temporal dynamics of three diseases caused by Aedes-borne arboviruses in Mexico.

Background: The intensity of transmission of Aedes-borne viruses is heterogeneous, and multiple factors can contribute to variation at small spatial scales. Illuminating drivers of heterogeneity in prevalence over time and space would provide information for public health authorities. The objective of this study is to detect the spatiotemporal clusters and determine the risk factors of three major Aedes-borne diseases, Chikungunya virus (CHIKV), Dengue virus (DENV), and Zika virus (ZIKV) clusters in Mexico. Methods: We present an integrated analysis of Aedes-borne diseases (ABDs), the local climate, and the socio-demographic profiles of 2469 municipalities in Mexico. We used SaTScan to detect spatial clusters and utilize the Pearson correlation coefficient, Randomized Dependence Coefficient, and SHapley Additive exPlanations to analyze the influence of socio-demographic and climatic factors on the prevalence of ABDs. We also compare six machine learning techniques, including XGBoost, decision tree, Support Vector Machine with Radial Basis Function kernel, K nearest neighbors, random forest, and neural network to predict risk factors of ABDs clusters. Results: DENV is the most prevalent of the three diseases throughout Mexico, with nearly 60.6% of the municipalities reported having DENV cases. For some spatiotemporal clusters, the influence of socio-economic attributes is larger than the influence of climate attributes for predicting the prevalence of ABDs. XGBoost performs the best in terms of precision-measure for ABDs prevalence. Conclusions: Both socio-demographic and climatic factors influence ABDs transmission in different regions of Mexico. Future studies should build predictive models supporting early warning systems to anticipate the time and location of ABDs outbreaks and determine the stand-alone influence of individual risk factors and establish causal mechanisms.

Integrating Google Trends Search Engine Query Data Into Adult Emergency Department Volume Forecasting: Infodemiology Study.

Background: The search for health information from web-based resources raises opportunities to inform the service operations of health care systems. Google Trends search query data have been used to study public health topics, such as seasonal influenza, suicide, and prescription drug abuse; however, there is a paucity of literature using Google Trends data to improve emergency department patient-volume forecasting. Objective: We assessed the ability of Google Trends search query data to improve the performance of adult emergency department daily volume prediction models. Methods: Google Trends search query data related to chief complaints and health care facilities were collected from Chicago, Illinois (July 2015 to June 2017). We calculated correlations between Google Trends search query data and emergency department daily patient volumes from a tertiary care adult hospital in Chicago. A baseline multiple linear regression model of emergency department daily volume with traditional predictors was augmented with Google Trends search query data; model performance was measured using mean absolute error and mean absolute percentage error. Results: There were substantial correlations between emergency department daily volume and Google Trends "hospital" (r=0.54), combined terms (r=0.50), and "Northwestern Memorial Hospital" (r=0.34) search query data. The final Google Trends data-augmented model included the predictors Combined 3-day moving average and Hospital 3-day moving average and performed better (mean absolute percentage error 6.42%) than the final baseline model (mean absolute percentage error 6.67%)-an improvement of 3.1%. Conclusions: The incorporation of Google Trends search query data into an adult tertiary care hospital emergency department daily volume prediction model modestly improved model performance. Further development of advanced models with comprehensive search query terms and complementary data sources may improve prediction performance and could be an avenue for further research.

A Web-Based Digital Contact Tracing Strategy Addresses Stigma Concerns Among Individuals Evaluated for COVID-19.

Introduction: Conventional contact tracing approaches have not kept pace with the scale of the coronavirus disease 2019 (COVID-19) pandemic and the highly anticipated smartphone applications for digital contact tracing efforts are plagued by low adoption rates attributed to privacy concerns; therefore, innovation is needed in this public health capability. Materials and Methods: This study involved a cross-sectional, nonrepresentative, online survey in the United States of individuals tested for COVID-19. Testing survey items measured the performance of conventional contact tracing programs, quantified the stigma related to the notification of COVID-19 close contacts, and assessed the acceptability of a website service for digital contact tracing. Results: A sample of 668 (19.9%) individuals met the inclusion criteria and consented to participation. Among the 95 participants with COVID-19, results were received after a median of 2 days, 63.2% interacted with a contact tracing program a median of 2 days after receiving test results, 62.1% had close contacts, and 37.1% of participants with COVID-19 and close contacts did not disclose their results to all close contacts. Among all participants, 17% had downloaded a mobile application and 40.3% reported interest in a website service. One hundred and nine participants perceived stigma with the disclosure of COVID-19 test results; of these, 58.7% reported that a website service for close contact notification would decrease this stigma. Discussion: Conventional contact tracing programs did not comprehensively contact individuals who tested positive for COVID-19 nor did so within a meaningful time frame. Digital contact tracing innovations may address these shortcomings; however, the low penetration of mobile application services in the United States indicates that a suite of digital contact tracing tools, including website services, are warranted for a more exhaustive coverage of the population. Conclusions: Public health officials should develop a complementary toolkit of digital contact tracing strategies to enable effective pandemic containment strategies.

Early palliative intervention in septic patients reduces healthcare utilization.

INTRODUCTION: While the role of palliative care in the emergency department is recognized, barriers against the effective integration of palliative interventions and emergency care remain. We examined the association between goals-of-care and palliative care consultations and healthcare utilization outcomes in older adult patients who presented to the emergency department (ED) with sepsis. METHODS: We performed a retrospective review of 197 patients aged 65 years and older who presented to the ED with sepsis or septic shock. Healthcare utilization outcomes were compared between patients divided into 3 groups: no palliative care consultation, palliative care consultation within 4 days of admission (i.e., early consultation), and palliative care consultation after 4 days of admission (i.e., late consultation). RESULTS: 51% of patients did not receive any palliative consultation, 39% of patients underwent an early palliative care consultation (within 4 days), and 10% of patients underwent a late palliative care consultation (after 4 days). Patients who received late palliative care consultation had a significantly increased number of procedures, total length of stay, ICU length of stay, and cost (p < .01, p < .001, p < .05, p < .001; respectively). Regarding early palliative care consultation, there were no statistically significant associations between this intervention and our outcomes of interest; however, we noted a trend towards decreased total length of stay and decreased healthcare cost. CONCLUSION: In patients aged 65 years and older who presented to the ED with sepsis, early palliative consultations were associated with reduced healthcare utilization as compared to late palliative consultations.

Novel Thermotolerant Amylase from Bacillus licheniformis Strain LB04: Purification, Characterization and Agar-Agarose.

This study analyzed the thermostability and effect of calcium ions on the enzymatic activity of α-amylase produced by Bacillus licheniformis strain LB04 isolated from Espinazo Hot springs in Nuevo Leon, Mexico. The enzyme was immobilized by entrapment on agar-agarose beads, with an entrapment yield of 19.9%. The identification of the bacteria was carried out using 16s rDNA sequencing. The enzyme was purified through ion exchange chromatography (IEX) in a DEAE-Sephadex column, revealing a protein with a molecular weight of ≈130 kDa. The enzyme was stable at pH 3.0 and heat stable up to 80 °C. However, the optimum conditions were reached at 65 °C and pH 3.0, with a specific activity of 1851.7 U mg-1 ± 1.3. The agar-agarose immobilized α-amylase had a hydrolytic activity nearly 25% higher when compared to the free enzyme. This study provides critical information for the understanding of the enzymatic profile of B. licheniformis strain LB04 and the potential application of the microorganisms at an industrial level, specifically in the food industry.

Changes in the Nutrient Composition of Barley Grain (Hordeum vulgare L.) and of Morphological Fractions of Sprouts.

The objectives of the current study were (1) to evaluate the effect of sprouting on protein, amino acids, fats, fatty acids, starch, total soluble carbohydrates, and ß-D-glucan content of barley grains and (2) to know the content of these nutrients in the morphological fractions of sprouts: green shoot, residual structure of sprouted grain (RSSG), residual structure of sprouted grain plus unsprouted grain (RSSG plus UG), and root fractions and to determine the proportion of each of these fractions (on fresh and dry basis) in the sprout biomass. Barley grain was sprouted in a commercial germination chamber for a period of 6 days. Raw grain was used as a control. Results showed that crude protein, ether extract, total soluble carbohydrates, and cellulose content increased, whereas starch and ß-D-glucan content decreased in sprouted when compared with the control grain. Amino acid and fatty acid profiles were also affected. Thus, aspartic acid, threonine, alanine, valine, isoleucine, lysine, and tryptophan content increased and only that of glutamic acid decreased after sprouting. Regarding fatty acids, an increase in the relative concentration of C18 : 0 and C18:3n-3 and a decrease in that of C18:1n-9 were detected. Partitioning of sprouted barley into three morphological component fractions showed that the residual structures of sprouted grains plus unsprouted grain fraction made up 82.9% and 93.6% of sprout biomass, on fresh and DM basis, respectively, and the remainder was provided by the root fraction, 10.3% and 3.2%, respectively, and by the green shoot fraction, 6.8% and 3.1%, respectively. The three morphological fractions differed in the content of the most analyzed nutrients.

Metal content in stranded pelagic vs deep-diving cetaceans in the Canary Islands.

The Canary Islands are home to many cetacean species, many of which are resident species. The present work aims to analyze, for the first time to the best of the authors' knowledge, the macronutrients, micronutrients and trace elements and toxic heavy metals in muscle and liver tissue of six species of stranded cetaceans in the Canary Islands. The study species were: Tursiops truncatus, Stenella frontalis, Delphinus delphis, Grampus griseus, Globicephala macrorynchus and Physeter macrocephalus. Statistical analysis studied the significant differences between the concentrations in muscle and liver tissues, with the differences in element content depending on the type of diving and length of the species. The results indicate that there are differences between muscle and liver for Ca, Cd, Co, Cu, K, Mg, Mn, Mo, Ni, Pb, Sr, V and Zn. Deep-diving animals differ in their concentrations of Cr, Cu, Mg, Mn, Mo, and Zn with respect to shallow-diving animals in muscle and in liver in Al, B, Cr, K, Mn and Mo. As for the differences between sex, the males present differences in their concentrations of B, Cd, K and Mg in muscle tissue with respect to the females, while differences in the liver were only detected in the Fe content. The study of the correlations shows that as the size of the animal increases, the concentration of Cd increases while the concentrations of Al, Cu and Zn decrease. The specimens foraging in shallower waters had the highest concentration of the macronutrient.

Deep-diving beaked whales dive together but forage apart.

Echolocating animals that forage in social groups can potentially benefit from eavesdropping on other group members, cooperative foraging or social defence, but may also face problems of acoustic interference and intra-group competition for prey. Here, we investigate these potential trade-offs of sociality for extreme deep-diving Blainville's and Cuvier's beaked whales. These species perform highly synchronous group dives as a presumed predator-avoidance behaviour, but the benefits and costs of this on foraging have not been investigated. We show that group members could hear their companions for a median of at least 91% of the vocal foraging phase of their dives. This enables whales to coordinate their mean travel direction despite differing individual headings as they pursue prey on a minute-by-minute basis. While beaked whales coordinate their echolocation-based foraging periods tightly, individual click and buzz rates are both independent of the number of whales in the group. Thus, their foraging performance is not affected by intra-group competition or interference from group members, and they do not seem to capitalize directly on eavesdropping on the echoes produced by the echolocation clicks of their companions. We conclude that the close diving and vocal synchronization of beaked whale groups that quantitatively reduces predation risk has little impact on foraging performance.

Use of survival rates of the barnacle Chthamalus stellatus as a bioindicator of pollution.

Concentrations of heavy metals and trace elements in marine environments have increasingly become a problem for several ocean ecosystems, due to increments in pollution. Habitats daily exposed to extreme conditions, such as the intertidal rocky platforms and pools, are more vulnerable to pollution effects. In the coast of Punta del Hidalgo (Tenerife, Spain), we have located a water-treatment plant that could be pouring periodically pollutants to the near shore. We studied coverage and survival rates of the cirriped Chthamalus stellatus inhabiting the intertidal near the sewage pipe of the water plant of ​Punta del Hidalgo and in a control area in a proximate location. Concurrently, water samples from intertidal pools were obtained from both affected and control areas in order to corroborate the presence of pollutants, analyzing the concentrations of metals and trace elements. The results obtained clarified that the area near the underwater outfall presented higher percentage of coverage and mortality of C. stellatus than the control zone. The analysis of metal content in water samples also showed higher concentrations of metals for the affected area compared to the control one. We therefore propose the use of survival rates of populations of C. stellatus in the intertidal as bioindicators of metal pollution.

Wheat- and barley-based diets with or without additives influence broiler chicken performance, nutrient digestibility and intestinal microflora.

BACKGROUND: To our knowledge, there is scant literature on comparative broiler response to cereal diets high in soluble non-starch polysaccharides without or with enzyme, prebiotic, probiotic or synbiotic supplementation. In the present study, the effects of a wheat- and barley-based diet with or without supplemental xylanase plus ß-glucanase, inulin, Enterococcus faecium or inulin plus Enterococcus faecium, on bird performance, digesta viscosity, nutrient digestibility and intestinal microflora were compared to a maize-based diet. RESULTS: In comparison to a maize-based diet, the wheat- and barley-based diet reduced (P < 0.05) body weight gain and feed intake, but did not affect to the feed-to-gain ratio. Apparent digestibility of crude fat and various fatty acids were decreased (P < 0.05) as well as apparent metabolisable energy corrected to zero nitrogen retention content. There was an increase (P < 0.05) in the viscosity of jejunal digesta and in the caecal numbers of Escherichia coli and lactobacilli, and a decrease in the ileal numbers of E. coli and lactobacilli. Performance parameters and nutrient digestibility were not affected (P > 0.05) by dietary inclusion of the additives used, with the exception that exogenous enzyme improved (P < 0.05) the apparent digestibility of crude fat and decreased the viscosity of jejunal digesta. Enzyme and Enterococcus faecium supplementation increased intestinal lactic acid bacteria, whereas inulin addition reduced the number of E. coli (P < 0.05). Addition of inulin-Enterococcus faecium decreased E. coli and increased bifidobacteria numbers in the caeca. CONCLUSION: Enzyme supplementation to a wheat- and barley-based diet significantly improved the apparent digestibility of dietary fat. All four additives had a beneficial effect on the intestinal microflora of broilers.

Signaling of ERBB receptor tyrosine kinases promotes neuroblastoma growth in vitro and in vivo.

BACKGROUND: ERBB receptor tyrosine kinases can mediate proliferation, migration, adhesion, differentiation, and survival in many types of cells and play critical roles in many malignancies. Recent reports suggest a role for EGFR signaling in proliferation and survival of neuroblastoma, a common form of pediatric cancer that often has an extremely poor outcome. METHODS: The authors examined ERBB family expression in neuroblastoma cell lines and patient samples by flow cytometry, western blot, and quantitative real time polymerase chain reaction (Q-PCR). Response to ERBB inhibition was assessed in vitro by cell-cycle analysis and western blot and in vivo by serial tumor-size measurements. RESULTS: A panel of neuroblastoma cell lines and primary patient tumors expressed EGFR, HER-3, and HER-4, with HER-2 in some tumors. HER-4 mRNA was expressed predominantly in cleavable isoforms. Whereas EGFR inhibition with erlotinib and pan-ERBB inhibition with CI-1033 inhibited EGF-induced phosphorylation of EGFR, AKT, and ERK1/2, only CI-1033 induced growth inhibition and dose-dependent apoptosis in vitro. Both CI-1033 and erlotinib treatment of neuroblastoma xenograft tumors resulted in decreased tumor growth in vivo, although CI-1033 was more effective. In vivo expression of EGFR was observed predominantly in vascular endothelial cells. CONCLUSIONS: Pan-ERBB inhibition is required for ERBB-related neuroblastoma apoptosis in vitro, although EGFR contributes indirectly to tumor growth in vivo. Inhibition of EGFR in endothelial cells may be an important aspect of erlotinib's impact on neuroblastoma growth in vivo. Our results suggest that non-EGFR ERBB family members contribute directly to neuroblastoma growth and survival, and pan-ERBB inhibition represents a potential therapeutic target for treating neuroblastoma.