Spatial analysis of dengue transmission in an endemic city in Brazil reveals high spatial structuring on local dengue transmission dynamics.

In the last decades, dengue has become one of the most widespread mosquito-borne arboviruses in the world, with an increasing incidence in tropical and temperate regions. The mosquito Aedes aegypti is the dengue primary vector and is more abundant in highly urbanized areas. Traditional vector control methods have showing limited efficacy in sustaining mosquito population at low levels to prevent dengue virus outbreaks. Considering disease transmission is not evenly distributed in the territory, one perspective to enhance vector control efficacy relies on identifying the areas that concentrate arbovirus transmission within an endemic city, i.e., the hotspots. Herein, we used a 13-month timescale during the SARS-Cov-2 pandemic and its forced reduction in human mobility and social isolation to investigate the spatiotemporal association between dengue transmission in children and entomological indexes based on adult Ae. aegypti trapping. Dengue cases and the indexes Trap Positive Index (TPI) and Adult Density Index (ADI) varied seasonally, as expected: more than 51% of cases were notified on the first 2 months of the study, and higher infestation was observed in warmer months. The Moran's Eigenvector Maps (MEM) and Generalized Linear Models (GLM) revealed a strong large-scale spatial structuring in the positive dengue cases, with an unexpected negative correlation between dengue transmission and ADI. Overall, the global model and the purely spatial model presented a better fit to data. Our results show high spatial structure and low correlation between entomological and epidemiological data in Foz do Iguaçu dengue transmission dynamics, suggesting the role of human mobility might be overestimated and that other factors not evaluated herein could be playing a significant role in governing dengue transmission.

Optimising the surveillance of Aedes aegypti in Brazil by selecting smaller representative areas within an endemic city.

OBJECTIVES: Arboviruses, such as dengue (DENV), zika (ZIKV), and chikungunya (CHIKV), constitute a growing urban public health threat. Focusing on Aedes aegypti mosquitoes, their primary vectors, is crucial for mitigation. While traditional immature-stage mosquito surveillance has limitations, capturing adult mosquitoes through traps yields more accurate data on disease transmission. However, deploying traps presents logistical and financial challenges, demonstrating effective temporal predictions but lacking spatial accuracy. Our goal is to identify smaller representative areas within cities to enhance the early warning system for DENV outbreaks. METHODS: We created Sentinel Geographic Units (SGUs), smaller areas of 1 km2 within each stratum, larger areas, with the aim of aligning the Trap Positivity Index (TPI) and Adult Density Index (ADI) with their respective strata. We conducted a two-step evaluation of SGUs. First, we examined the equivalence of TPI and ADI between SGUs and strata from January 2017 to July 2022. Second, we assessed the ability of SGU's TPI and ADI to predict DENV outbreaks in comparison to Foz do Iguaçu's Early-Warning System, which forecasts outbreaks up to 4 weeks ahead. Spatial and temporal analyses were carried out, including data interpolation and model selection based on Akaike information criteria (AIC). RESULTS: Entomological indicators produced in small SGUs can effectively replace larger sentinel areas to access dengue outbreaks. Based on historical data, the best predictive capability is achieved 2 weeks after infestation verification. Implementing the SGU strategy with more frequent sampling can provide more precise space-time estimates and enhance dengue control. CONCLUSIONS: The implementation of SGUs offers an efficient way to monitor mosquito populations, reducing the need for extensive resources. This approach has the potential to improve dengue transmission management and enhance the public health response in endemic cities.

Wavelength and Light Intensity Affect Macro- and Micronutrient Uptake, Stomata Number, and Plant Morphology of Common Bean (Phaseolus vulgaris L.).

It is already known that light quality and intensity have major influences on the growth, etiolation, germination, and morphology of many plant species, but there is limited information about the effect of wavelength and light intensity on nutrient absorption by plants. Therefore, this study was established to evaluate the plant growth, stomata formation, chlorophyll index, and absorption of macro- and micronutrients by common bean plants under six light treatments. The experimental design was completely randomized and consisted of six treatments: strong blue (blue LED at high light intensity); weak blue (blue LED at low light intensity); strong red (red LED at high light intensity); weak red (red LED at low light intensity; pink (combined red + blue LED), and white (combined red + white led). The stomatal density (stomata mm-2); the SPAD index; plant height (cm); root length (cm); plant dry weight (g); root dry weight (g); and the concentrations of N, S, K, Mg, Ca, B, Zn, Mn, and Fe on leaf analysis were influenced by all treatments. We found that plant photomorphogenesis is controlled not only by the wavelength, but also by the light intensity. Etiolation was observed in bean plants under blue light at low intensity, but when the same wavelength had more intensity, the etiolation did not happen, and the plant height was the same as plants under multichromatic lights (pink and white light). The smallest plants showed the largest roots, some of the highest chlorophyll contents, and some of the highest stomatal densities, and consequently, the highest dry weight, under white LED, showing that the multichromatic light at high intensity resulted in better conditions for the plants in carbon fixation. The effect of blue light on plant morphology is intensity-dependent. Plants under multichromatic light tend to have lower concentrations of N, K, Mg, and Cu in their leaves, but the final amount of these nutrients absorbed is higher because of the higher dry weight of these plants. Plants under blue light at high intensity tended to have lower concentrations of N, Cu, B, and Zn when compared to the same wavelength at low intensity, and their dry weight was not different from plants grown under pink light. New studies are needed to understand how and on what occasions intense blue light can replace red light in plant physiology.

Incident Coronary Calcium Score in Patients With OSA With and Without Excessive Sleepiness: Brazilian Longitudinal Study of Adult Health.

BACKGROUND: Uncertainty exists about the impact of OSA and its phenotypes on cardiovascular disease. RESEARCH QUESTION: Are OSA and clinical features such as daytime sleepiness associated with incident subclinical coronary atherosclerosis? STUDY DESIGN AND METHODS: In this prospective community-based cohort study, we administered a sleepiness questionnaire, actigraphy, and home sleep studies at baseline. Coronary artery calcium (CAC; 64-slice multidetector CT scan imaging) was measured at two different time points throughout the study (baseline, between 2010 and 2014, and follow-up, between 2016 and 2018). Incidence of subclinical atherosclerosis was defined as baseline CAC of 0 followed by CAC of > 0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression. Stratified analyses based on excessive daytime sleepiness (EDS) were performed. RESULTS: We analyzed 1,956 participants with available CAC scores at baseline (mean age, 49 ± 8 years; 57.9% female; 32.4% with OSA). In covariate-adjusted analyses (n = 1,247; mean follow-up, 5.1 ± 0.9 years), we found a significant association between OSA and incidence of subclinical atherosclerosis (OR, 1.26; 95% CI, 1.06-1.48), with stronger effects among those reporting EDS (OR, 1.66; 95% CI, 1.30-2.12; P = .028 for interaction). Interestingly, EDS per se was not associated with any CAC outcome. An exploratory analysis of the square root of CAC progression (baseline CAC > 0 followed by a numerical increase in scores at follow-up; n = 319) showed a positive association for both OSA (ß = 1.084; 95% CI, 0.032-2.136; P = .043) and OSA with EDS (ß = 1.651; 95% CI, 0.208-3.094; P = .025). INTERPRETATION: OSA, particularly with EDS, predicts the incidence and progression of CAC. These results support biological plausibility for the increased cardiovascular risk observed among patients with OSA with excessive sleepiness.

Gender Modulated the Association of Sleep Apnea and Sleep Duration with Arterial Stiffness: The ELSA-Brasil Study.

Increased arterial stiffness is independently associated with cardiovascular risk. Obstructive sleep apnea (OSA) and sleep duration (SDUR) may contribute to increased arterial stiffness, but it is unclear whether this association is modulated by gender. We aimed to evaluate the potential impact of gender in modulating the association of OSA and SDUR with arterial stiffness. Participants from the ELSA-Brasil study performed sleep assessments with portable polygraph to define OSA severity and SDUR by 1-week wrist actigraphy. Pulse wave velocity (PWV) was measured using a standard technique without access to the sleep data. We studied 1863 participants (42.2% male, age: 49±8 years, respiratory disturbance index (RDI): 9.9 (4.5-19.4) events/h, SDUR: 6.5 (5.9-7.1) hours, mean PWV: 7.3 ± 1.2 m/s). We found that men had higher PWV, higher frequency of diabetes, and higher blood pressure when compared to women. The regression analysis showed an independent association between increased RDI and PWV in men (ß: 0.007; 95% CI: 0.001-0.012), but not in women. In contrast, an independent association between SDUR and increased arterial stiffness was observed only in women (ß: 0.068; 95% CI: 0.002-0.134). In conclusion, the association of sleep disorders with arterial stiffness showed a distinct gender pattern depending on the sleep variable studied.

Unraveling the Phase Behavior, Mechanical Stability, and Protein Reconstitution Properties of Polymer-Lipid Hybrid Vesicles.

Hybrid vesicles consisting of natural phospholipids and synthetic amphiphilic copolymers have shown remarkable material properties and potential for biotechnology, combining the robustness of polymers with the biocompatibility of phospholipid membranes. To predict and optimize the mixing behavior of lipids and copolymers, as well as understand the interaction between the hybrid membrane and macromolecules like membrane proteins, a comprehensive understanding at the molecular level is essential. This can be achieved by a combination of molecular dynamics simulations and experiments. Here, simulations of POPC and PBD22-b-PEO14 hybrid membranes are shown, uncovering different copolymer configurations depending on the polymer-to-lipid ratio. High polymer concentrations created thicker membranes with an extended polymer conformation, while high lipid content led to the collapse of the polymer chain. High concentrations of polymer were further correlated with a decreased area compression modulus and altered lateral pressure profiles, hypothesized to result in the experimentally observed improvement in membrane protein reconstitution and resistance toward destabilization by detergents. Finally, simulations of a WALP peptide embedded in the bilayer showed that only membranes with up to 50% polymer content favored a transmembrane configuration. These simulations correlate with previous and new experimental results and provide a deeper understanding of the properties of lipid-copolymer hybrid membranes.

Excessive daytime sleepiness, but not sleep apnea, sleep duration or insomnia, was associated with poor adherence to anti-hypertensive treatment: The ELSA-Brasil study.

Hypertension is the leading risk factor for cardiovascular mortality. Poor adherence may partially explain this scenario. Beyond traditional factors, it is conceivable that sleep conditions such as Obstructive Sleep Apnea (OSA), Sleep Duration (SDUR), sleepiness and insomnia may contribute to impair adherence but the evidence is scanty. Consecutive participants with hypertension from the ELSA-Brasil study performed a home sleep monitoring and 7-days actigraphy to determine OSA (apnea-hypopnea index ≥15 events/hour) and SDUR, respectively. Excessive daytime sleepiness (EDS) and insomnia were evaluated by Epworth Sleepiness Scale (ESS) and Clinical Interview Scheduled Revised (CIS-R), respectively. The 4-itens Morisky questionnaire was used to evaluate adherence to anti-hypertensive therapy. A total of 411 patients were including in the analysis (mean age: 54 ± 8 years, 47% men). Medium/low adherence to anti-hypertensive therapy was observed in 62%. Compared to the high adherence group, the participants with medium/low adherence had lower frequencies of Whites (64.1 vs. 47.8%), high-degree education (50.6 vs. 40%), and monthly per-capita income ($1021.90 vs. $805.20). In contrast, we observed higher frequency of EDS (35.9 vs. 46.1%). No differences were observed for OSA, short SDUR (<6 h) and insomnia. Logistic regression analysis showed that race other than White (OR: 1.80; 95% IC:1.15-2.82), lower monthly income (OR: 1.74; 95% IC:1.01-3.0) and EDS (OR: 1.63; 95% IC:1.05-2.53) were independently associated with medium/low adherence to the anti-hypertensive treatment. Interestingly, EDS mediated the abdominal obesity-adherence outcome. In conclusion, among sleep-related parameters, EDS, but not OSA, short SDUR or insomnia, were associated to impaired adherence to anti-hypertensive therapy.

Sleep irregularity and the association with hypertension and blood pressure levels: the ELSA-Brasil study.

OBJECTIVE: To evaluate the associations of sleep irregularity with hypertension (HTN) and blood pressure (BP) levels. METHODS: Adult participants from the ELSA-Brasil performed a clinical evaluation including objective sleep duration (actigraphy), insomnia, and a sleep study for defining obstructive sleep apnoea (OSA). To quantify sleep irregularity, we used two parameters obtained through actigraphy: 7-day standard deviation (SD) of sleep duration and 7-day SD of sleep-onset timing. A multivariate analysis was used to determine the independent associations of sleep irregularity with HTN and SBP/DBP values. RESULTS: We studied 1720 participants (age 49 ±â€Š8 years; 43.4% men) and 27% fulfilled the HTN diagnosis. After adjustments for age, gender, race, BMI, excessive alcohol consumption, physical activity intensity, urinary sodium excretion, insomnia, objective sleep duration and OSA (apnoea-hypopnoea index ≥15 events/h), we found that the continuous analysis of 7-day SD of sleep duration was modestly associated with prevalent HTN. However, 7-day SD of sleep duration more than 90 min was independently associated with SBP [ ß : 1.55; 95% confidence interval (CI) 0.23-2.88] and DBP ( ß : 1.07; 95% CI 0.12-2.01). Stratification analysis excluding participants with OSA revealed that a 7-day SD of sleep duration greater than 90 min was associated with a 48% higher chance of having HTN (OR: 1.48; 95% CI: 1.05-2.07). No significant associations were observed for the SD of sleep-onset timing. CONCLUSION: Objective measurement of sleep irregularity, evaluated by SD of sleep duration for 1 week, was associated with HTN and higher BP levels, especially in participants without OSA.

Repurposing of 5-nitrofuran-3,5-disubstituted isoxazoles: A thriving scaffold to antitrypanosomal agents.

Chagas disease (CD) is a neglected disease caused by the protozoan Trypanosoma cruzi. The two drugs used in the treatment schedules exhibit adverse effects and severe toxicity. Thus, searching for new antitrypanosomal agents is urgent to provide improved treatments to those affected by this disease. 5-Nitrofuran-isoxazole analogs were synthesized by cycloaddition reactions [3+2] between chloro-oximes and acetylenes in satisfactory yields. We analyzed the structure-activity relationship of the analogs based on Hammett's and Hansch's parameters. The 5-nitrofuran-isoxazole analogs exhibited relevant in vitro antitrypanosomal activity against the amastigote forms of T. cruzi. Analog 7s was the trending hit of the series, showing an IC50 value of 40 nM and a selectivity index of 132.50. A possible explanation for this result may be the presence of an electrophile near the isoxazole core. Moreover, the most active analogs proved to act as an in vitro substrate of type I nitroreductase rather than the cruzain, enzymes commonly investigated in molecular target studies of CD drug discovery. These findings suggest that 5-nitrofuran-isoxazole analogs are promising in the studies of agents for CD treatment.

Association between objective sleep measures and cognitive performance: a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study.

Sleep disturbances often co-exist, which challenges our understanding of their potential impact on cognition. We explored the cross-sectional associations of insomnia and objective measures of sleep with cognitive performance in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study stratified by middle-aged and older adults. Participants aged ≥55 years underwent cognitive evaluations, polygraphy for 1 night, and actigraphy for 7 days. Insomnia was evaluated using the Clinical Interview Scheduled Revised. Obstructive sleep apnea (OSA) and short sleep duration (SSD) were defined by an apnea-hypopnea index (AHI) of ≥15 events/h and <6 h/ night, respectively. In 703 participants (mean [SD] age 62 [6] years, 44% men), cognition was evaluated using a 10-word list, verbal fluency, and trail-making tests. The frequencies of insomnia, SSD, and OSA were 11%, 24%, and 33%, respectively. In all, 4% had comorbid OSA and insomnia, and 11% had both OSA and SSD. Higher wake after sleep onset (ß = -0.004, 95% confidence interval [CI] -0.008, -0.001) and the number of awakenings (ß = -0.006, 95% CI -0.012, -0.001) were associated with worse verbal fluency performance. Compared to those without insomnia, older participants with insomnia had worse global performance (ß = -0.354, 95% CI -0.671, -0.038). Insomnia was an effect modifier in the associations between AHI and executive function performance (p for the interaction between insomnia and AHI = 0.004) and between oxygen saturation <90% and memory performance (p for the interaction between insomnia and oxygen saturation = 0.02). Although some associations between sleep measures and cognition were significant, they should be considered with caution due to the large sample size and multiple testing performed in this study.

Full-waveform inversion based on generalized Rényi entropy using patched Green's function techniques.

The estimation of physical parameters from data analyses is a crucial process for the description and modeling of many complex systems. Based on Rényi α-Gaussian distribution and patched Green's function (PGF) techniques, we propose a robust framework for data inversion using a wave-equation based methodology named full-waveform inversion (FWI). From the assumption that the residual seismic data (the difference between the modeled and observed data) obeys the Rényi α-Gaussian probability distribution, we introduce an outlier-resistant criterion to deal with erratic measures in the FWI context, in which the classical FWI based on l2-norm is a particular case. The new misfit function arises from the probabilistic maximum-likelihood method associated with the α-Gaussian distribution. The PGF technique works on the forward modeling process by dividing the computational domain into outside target area and target area, where the wave equation is solved only once on the outside target (before FWI). During the FWI processing, Green's functions related only to the target area are computed instead of the entire computational domain, saving computational efforts. We show the effectiveness of our proposed approach by considering two distinct realistic P-wave velocity models, in which the first one is inspired in the Kwanza Basin in Angola and the second in a region of great economic interest in the Brazilian pre-salt field. We call our proposal by the abbreviation α-PGF-FWI. The results reveal that the α-PGF-FWI is robust against additive Gaussian noise and non-Gaussian noise with outliers in the limit α → 2/3, being α the Rényi entropic index.

New derivatives from dehydrodieugenol B and its methyl ether displayed high anti-Trypanosoma cruzi activity and cause depolarization of the plasma membrane and collapse the mitochondrial membrane potential.

In the present work, dehydrodieugenol B (1) and its methyl ether (2), isolated from Nectandra leucantha twigs, were used as starting material for the preparation of two new derivatives (1a and 2a) containing an additional methoxycarbonyl unit on allyl side chains. Compounds 1a and 2a demonstrated activity against trypomastigotes (EC50 values of 13.5 and 23.0 µM, respectively) and against intracellular amastigotes (EC50 values of 10.2 and 6.1 µM, respectively). Additionally, compound 2a demonstrated no mammalian cytotoxicity up to 200 µM whereas compound 1a exhibited a CC50 value of 139.8 µM. The mechanism of action studies of compounds 1a and 2a demonstrated a significant depolarization of the plasma membrane potential in trypomastigotes, followed by a mitochondrial membrane potential collapse. Neither calcium level nor reactive oxygen species alterations were observed after a short-time incubation. Considering the potential of compound 2a against T. cruzi and its simple preparation from the natural product 2, isolated from N. leucantha, this compound could be considered a new hit for future drug design studies in Chagas disease.

Citywide Integrated Aedes aegypti Mosquito Surveillance as Early Warning System for Arbovirus Transmission, Brazil.

Arbovirus epidemiology lacks efficient and timely surveillance systems with accurate outbreak alert signals. We devised a citywide integrated surveillance system combining entomologic, epidemiologic, and entomo-virologic data gathered during 2017-2020 in Foz do Iguaçu, Brazil. We installed 3,476 adult mosquito traps across the city and inspected traps every 2 months. We compared 5 entomologic indices: traditional house and Breteau indices for larval surveys and trap positivity, adult density, and mosquitoes per inhabitant indices for adult trapping. We screened for dengue, Zika, and chikungunya viruses in live adult Aedes aegypti mosquitoes collected from traps. Indices based on adult mosquito sampling had higher outbreak predictive values than larval indices, and we were able to build choropleth maps of infestation levels <36 h after each round of trap inspection. Locating naturally infected vectors provides a timely support tool for local public health managers to prioritize areas for intervention response to prevent virus outbreaks.

Antileishmanial activity and insights into the mechanisms of action of symmetric Au(I) benzyl and aryl-N-heterocyclic carbenes.

Leishmania amazonensis and L. braziliensis are the main etiological agents of the American Tegumentary Leishmaniasis (ATL). Taking into account the limited effectiveness and high toxicity of the current drug arsenal to treat ATL, novel options are urgently needed. Inspired by the fact that gold-based compounds are promising candidates for antileishmanial drugs, we studied the biological action of a systematic series of six (1)-(6) symmetric Au(I) benzyl and aryl-N-heterocyclic carbenes. All compounds were active at low micromolar concentrations with 50% effective concentrations ranging from 1.57 to 8.30 µM against Leishmania promastigotes. The mesityl derivative (3) proved to be the best candidate from this series, with a selectivity index ~13 against both species. The results suggest an effect of the steric and electronic parameters of the N-substituent in the activity. Intracellular infections were drastically reduced after 24h of (2)-(5) incubation in terms of infection rate and amastigote burden. Further investigations showed that our compounds induced significant parasites' morphological alterations and membrane permeability. Also, (3) and (6) were able to reduce the residual activity of three Leishmania recombinant cysteine proteases, known as possible targets for Au(I) complexes. Our promising results open the possibility of exploring gold complexes as leishmanicidal molecules to be further screened in in vivo models of infection.

Self-reported versus actigraphy-assessed sleep duration in the ELSA-Brasil study: analysis of the short/long sleep duration reclassification.

PURPOSE: This study was aimed to determine the magnitude and predictors of self-reported short/long sleep duration (SDUR) reclassifications using objective measurements. METHODS: Adult participants from the ELSA-Brasil study performed self-reported SDUR, 7-day wrist actigraphy, and a portable sleep study. We explored two strategies of defining self-reported SDUR reclassification: (1) short and long SDUR defined by <6 and ≥8h, respectively; (2) reclassification using a large spectrum of SDUR categories (<5, 5-6, 7-8, 8-9, and >9 h). RESULTS: Data from 2036 participants were used in the final analysis (43% males; age: 49±8 years). Self-reported SDUR were poorly correlated (r=0.263) and presented a low agreement with actigraphy-based total sleep time. 58% of participants who self-reported short SDUR were reclassified into the reference (6-7.99 h) or long SDUR groups using actigraphy data. 88% of participants that self-reported long SDUR were reclassified into the reference and short SDUR. The variables independently associated with higher likelihood of self-reported short SDUR reclassification included insomnia (3.5-fold), female (2.5-fold), higher sleep efficiency (1.35-fold), lowest O2 saturation (1.07-fold), higher wake after sleep onset (1.08-fold), and the higher number of awakening (1.05-fold). The presence of hypertension was associated with a 3.4-fold higher chance of self-reported long SDUR reclassification. Analysis of five self-reported SDUR categories revealed that the more extreme is the SDUR, the greater the self-reported SDUR reclassification. CONCLUSION: In adults, we observed a significant rate of short/long SDUR reclassifications when comparing self-reported with objective data. These results underscore the need to reappraise subjective data use for future investigations addressing SDUR.

Stress behaviors in captive robust capuchins: Effects of humidity, visitors, management and sex.

Wild robust capuchins (Sapajus spp.) are omnivorous neotropical primates that live in relatively large groups in extensive home and daily ranges with activity budgets dominated by traveling, foraging, and object manipulation, meaning that enclosed spaces can result in significant deprivation. Space restriction, manipulation by caretakers, and the chronic presence of visitors, can disrupt the animals' welfare, altering their normal activities and inducing stress behaviors. We aimed to study the behavioral repertoire, activity budget, and frequency of stress behaviors (stereotypes and self-directed behaviors) between two captive groups of robust capuchins in a public zoo in Foz do Iguaçu, Brazil, to understand how much their behavioral homeostasis has been affected. More specifically, we assessed the effect of environmental variables (temperature, relative air humidity, number of visitors, and food management) and sex on the frequency of stress behaviors. Capuchins showed a high frequency of stress behaviors, which represented around 10% of their activity budget (though the frequencies were unevenly distributed among the individuals), and traveling was positively correlated with stereotypes. We found that high relative air humidity appears to induce more stereotypes, high numbers of visitors appear to increase self-directed and vigilance behaviors and reduce stereotypes, food management can increase both kinds of stress behaviors, and females demonstrated more frequent stress behaviors than males, but individual variation may play a role. Capuchins in the group with a greater space restriction showed more stereotypes, while those in the group with more individuals showed more self-directed behaviors. Our study shows that the stress behaviors performed by the capuchins are complex and it is difficult to determine a single cause, because many traits could be involved. Despite that, this study enlightens us to direct some approaches to help these animals to meet their ecological and social needs, mitigating their stress.

Urolithiasis and sleeve gastrectomy: a prospective assessment of urinary biochemical variables.

INTRODUCTION: to evaluate urinary biochemical alterations related to urolithogenesis processes after sleeve gastrectomy (SG). MATERIALS AND METHODS: : prospective study with 32 individuals without previous diagnosis of urolithiasis who underwent SG. A 24-h urine test was collected seven days prior to surgery and at 6-month follow-up. The studied variables were urine volume, urinary pH, oxalate, calcium, citrate, and magnesium and calcium oxalate super saturation (CaOx SS). RESULTS: patients were mainly women (81.2%), with mean age of 40.6 years. Mean pre- and postoperative BMI were 47.1 ± 8.3 Kg/m2 and 35.5 ± 6.1 Kg/m2, respectively (p<0.001). Urine volume was significantly lower at the postoperative evaluation in absolute values (2,242.50 ± 798.26 mL x 1,240.94 ± 352.39 mL, p<0.001) and adjusted to body weight (18.58 ± 6.92 mL/kg x 13.92 ± 4.65 mL/kg, p<0.001). CaOx SS increased significantly after SG (0.11 ± 0.10 x 0.24 ± 0.18, p<0.001). Moreover, uric acid levels were significantly lower at the postoperative evaluation (482.34 ± 195.80 mg x 434.75 ± 158.38 mg, p=0.027). Urinary pH, oxalate, calcium, citrate, and magnesium did not present significant variations between the pre- and postoperative periods. CONCLUSION: SG may lead to important alterations in the urinary profile. However, it occurs in a much milder way than that of RYGB.

Obstructive Sleep Apnea, Sleep Duration, and Associated Mediators With Carotid Intima-Media Thickness: The ELSA-Brasil Study.

[Figure: see text].

Obstructive sleep apnea is associated with lower adiponectin and higher cholesterol levels independently of traditional factors and other sleep disorders in middle-aged adults: the ELSA-Brasil cohort.

PURPOSE: Obstructive sleep apnea (OSA) may contribute to metabolic and inflammatory deregulation but previous studies failed to consider sleep duration, sleep fragmentation, insomnia, and daytime sleepiness as potential confounders. METHODS: Consecutive non-diabetic middle-aged participants from the ELSA-Brasil cohort were invited to perform a clinical evaluation, home sleep study for 1 night, and wrist actigraphy for 7 days. OSA was defined by an apnea-hypopnea index ≥ 15 events/h. Participants were stratified according to the presence of OSA measuring the following markers: fasting glucose, glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR) index, fasting insulin, insulin after 2 h of glucose load, glycated hemoglobin, total cholesterol and their fractions, triglycerides, C-reactive protein, TNF-alpha, interleukin-6, interleukin-10, leptin, adiponectin, E-selectin, ADMA, MCP-1, TGF, apolipoprotein B, fibrinogen, and lipoprotein(a). Differences between groups were identified by chi-square test and ANOVA. RESULTS: We studied 708 participants (mean age: 46 ± 5 years, men: 44%, BMI 26.1 ± 4.1 kg/m2). Compared to no OSA, participants with OSA presented higher levels while fasting and after 2 h glucose load of insulin, HOMA-IR, cholesterol, triglycerides, and C-reactive protein (all p < 0.001). After linear regression analysis adjusting for traditional risk factors plus sleep duration, fragmentation, insomnia, and daytime sleepiness, OSA was negatively associated with adiponectin (ß = - 0.271 CI 95% - 0.456 - 0.085) and positively associated with cholesterol (ß = 9.707 CI 95% 2.737 16.678). Sex-stratification revealed that these associations were significant for men but not women. CONCLUSIONS: In non-diabetic middle-age adults, men with OSA presented with lower adiponectin and higher cholesterol levels independently of sleep duration, sleep fragmentation, insomnia, and daytime sleepiness.

Endocytosis and the Participation of Glycosaminoglycans Are Important to the Mechanism of Cell Death Induced by ß-Hairpin Antimicrobial Peptides.

The cytotoxic mode of action of four antimicrobial peptides (AMPs) (gomesin, tachyplesin, protegrin, and polyphemusin) against a HeLa cell tumor model is discussed. A study of cell death by AMP stimulation revealed some similarities, including annexin-V externalization, reduction of mitochondrial potential, insensitivity against inhibitors of cell death, and membrane permeabilization. Evaluation of signaling proteins and gene expression that control cell death revealed wide variation in the responses to AMPs. However, the ability to cross cell membranes emerged as an important characteristic of AMP-dependent cell death, where endocytosis mediated by dynamin is a common mechanism. Furthermore, the affinity between AMPs and glycosaminoglycans (GAGs) and GAG participation in the cytotoxicity of AMPs were verified. The results show that, despite their primary and secondary structure homology, these peptides present different modes of action, but endocytosis and GAG participation are an important and common mechanism of cytotoxicity for ß-hairpin peptides.