Screening for an ivermectin slow-release formulation suitable for malaria vector control

BACKGROUND: The prospect of eliminating malaria is challenged by emerging insecticide resistance and vectors with outdoor and/or crepuscular activity. Ivermectin can simultaneously tackle these issues by killing mosquitoes feeding on treated animals and humans. A single oral dose, however, confers only short-lived mosquitocidal plasma levels. METHODS: Three different slow-release formulations of ivermectin were screened for their capacity to sustain mosquito-killing levels of ivermectin for months. Thirty rabbits received a dose of one, two or three silicone implants containing different proportions of ivermectin, deoxycholate and sucrose. Animals were checked for toxicity and ivermectin was quantified periodically in blood. Potential impact of corresponding long-lasting formulation was mathematically modelled. RESULTS: All combinations of formulation and dose released ivermectin for more than 12 weeks; four combinations sustained plasma levels capable of killing 50% of Anopheles gambiae feeding on a treated subject for up to 24 weeks. No major adverse effects attributable to the drug were found. Modelling predicts a 98% reduction in infectious vector density by using an ivermectin formulation with a 12-week duration. CONCLUSIONS: These results indicate that relatively stable mosquitocidal plasma levels of ivermectin can be safely sustained in rabbits for up to six months using a silicone-based subcutaneous formulation. Modifying the formulation of ivermectin promises to be a suitable strategy for malaria vector control

Exploring host genetic polymorphisms involved in SARS-CoV infection autcomes: implications for personalized medicine in COVID-19

Objective. To systematically explore genetic polymorphisms associated with the clinical outcomes in SARS-CoV infection in humans. Methods. This comprehensive literature search comprised available English papers published in PubMed/Medline and SCOPUS databases following the PRISMA-P guidelines and PICO/AXIS criteria. Results. Twenty-nine polymorphisms located in 21 genes were identified as associated with SARS-CoV susceptibility/resistance, disease severity, and clinical outcomes predominantly in Asian populations. Thus, genes implicated in key pathophysiological processes such as the mechanisms related to the entry of the virus into the cell and the antiviral immune/inflammatory responses were identified. Conclusions. Although caution must be taken, the results of this systematic review suggest that multiple genetic polymorphisms are associated with SARS-CoV infection features by affecting virus pathogenesis and host immune response, which could have important applications for the study and understanding of genetics in SARS-CoV-2/COVID-19 and for personalized translational clinical practice depending on the population studied and associated environments

Interactive Role of Surrogate Liver Fibrosis Assessment and Insulin Resistance on the Incidence of Major Cardiovascular Events

Introduction: The combination of easy-to-obtain validated biomarkers is interesting in the prognostic evaluation of patients at cardiovascular risk in a precision medicine scenario. The evaluation of the effect modification of insulin resistance and liver fibrosis with the Triglyceride-Glucose index (TyG) and Fibrosis-4 index (FIB4) might provide prognostic information in patients at cardiovascular risk. Patients and methods: A retrospective cohort study was performed with 2055 patients recruited in the Vascular Metabolic CUN cohort. The studied outcome was the incidence rate of major cardiovascular events (MACE). The Systematic Coronary Risk Evaluation (SCORE), FIB4 and TyG indexes were calculated according to validated formulas. Results: FIB4 and TyG showed a synergistic interaction using validated cut-offs for both indexes in the prediction of MACE (Hazard ratio (HR) 1.05 CI95% 1.01–1.08) which remained after adjustment by age, sex, SCORE subgroup, presence of diabetes, or previous MACE using standardized cut-off (HR 2.29 CI95% 1.33–3.94). Finally, a subgroup with significant TyG and FIB4 showed a higher cardiovascular risk in the study population (adjusted HR 3.34 CI 95% 1.94–5.77). Conclusion: The combined interpretation of TyG and FIB4 indexes might have a potential predictive value of major cardiovascular events

Performance of SAPS II and SAPS 3 in Intermediate Care

Objective: The efficacy and reliability of prognostic scores has been described extensively for intensive care, but their role for predicting mortality in intermediate care patients is uncertain. To provide more information in this field, we have analyzed the performance of the Simplified Acute Physiology Score (SAPS) II and SAPS 3 in a single center intermediate care unit (ImCU). Materials and Methods: Cohort study with prospectively collected data from all patients admitted to a single center ImCU in Pamplona, Spain, from April 2006 to April 2012. The SAPS II and SAPS 3 scores with respective predicted mortality rates were calculated according to standard coefficients. Discrimination was evaluated by calculating the area under receiver operating characteristic curve (AUROC) and calibration with the Hosmer-Lemeshow goodness of fit test. Standardized mortality ratios (SMR) with 95% confidence interval (95% CI) were calculated for each model. Results: The study included 607 patients. The observed in-hospital mortality was 20.1% resulting in a SMR of 0.87 (95% CI 0.73-1.04) for SAPS II and 0.56 (95% CI 0.47-0.67) for SAPS 3. Both scores showed acceptable discrimination, with an AUROC of 0.76 (95% CI 0.71-0.80) for SAPS II and 0.75 (95% CI 0.71- 0.80) for SAPS 3. Calibration curves showed similar performance based on Hosmer-Lemeshow goodness of fit C-test: (X2=12.9, p=0.113) for SAPS II and (X2=4.07, p=0.851) for SAPS 3. Conclusions: Although both scores overpredicted mortality, SAPS II showed better discrimination for patients admitted to ImCU in terms of SMR

Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient ' s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients

Longitudinal association of dietary acid load with kidney function decline in an older adult population with metabolic syndrome

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR (n = 5,874) or UACR (n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase. Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, β: -0.64 ml/min/1.73 m2; 95% CI: -1.21 to -0.08 and NEAP, β: -0.56 ml/min/1.73 m2; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load. Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome. Keywords: albuminuria; chronic kidney disease (CKD); dietary acid load; glomerular filtration rate (GFR); kidney function; net endogenous acid production (NEAP); potential renal acid load (PRAL); renal nutrition

Longitudinal association of dietary acid load with kidney function decline in an older adult population with metabolic syndrome

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR (n = 5,874) or UACR (n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase. Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, β: –0.64 ml/min/1.73 m2; 95% CI: –1.21 to –0.08 and NEAP, β: –0.56 ml/min/1.73 m2; 95% CI: –1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07–1.54 and NEAP, OR: 1.24; 95% CI: 1.03–1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04–1.46) compared to individuals with lower dietary acid load. Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality