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.

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

PURPOSE: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. MATERIALS AND METHODS: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. RESULTS: Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. CONCLUSIONS: D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

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.

Effect of annealing temperature on the structure and optical properties of ZnO thin films.

The effect of annealing temperature on the microstructure, defects and optical properties of ZnO thin films are investigated using sol-gel based spin coating method for a range of annealing temperatures from 200∘C to 500∘C. The correlation among the microstructure, defects, impurity content and the optical band gap of films of thickness about 10-12 nm is elucidated. The particle size increases and the optical band gap reduces with the annealing temperature. At 200∘C, amorphous films were formed with particle size less than 10 nm with an optical band gap of about 3.41 eV. As the temperature increases the grain size increases and the defect, impurity content as well as the optical band gap reduces. This could be due to the reduction in the lattice strain. For an average grain size of about 35 nm and above, the band gap asymptotically approaches the theoretical value of ZnO (3.37 eV). The photoluminescence (PL) spectra show a systematic red-shift in the excitonic levels corresponding to the variation in the optical band-gap. The defect emission from Zn-vacancies is observed in the PL spectra and are further supported by the positron annihilation measurements.

Safety, feasibility, and short-term-outcome of anal endoscopic submucosal dissection for anal intraepithelial neoplasia: an option for focal lesions?

BACKGROUND: Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3. METHODS: We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed. RESULTS: Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm2. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period. CONCLUSIONS: Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear. TRIAL REGISTRATION: Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.

Evolution of point defects in pulsed-laser-melted Ge1-xSnxprobed by positron annihilation lifetime spectroscopy.

Direct-band-gap Germanium-Tin alloys (Ge1-xSnx) with high carrier mobilities are promising materials for nano- and optoelectronics. The concentration of open volume defects in the alloy, such as Sn and Ge vacancies, influences the final device performance. In this article, we present an evaluation of the point defects in molecular-beam-epitaxy grown Ge1-xSnxfilms treated by post-growth nanosecond-range pulsed laser melting (PLM). Doppler broadening - variable energy positron annihilation spectroscopy and variable energy positron annihilation lifetime spectroscopy are used to investigate the defect nanostructure in the Ge1-xSnxfilms exposed to increasing laser energy density. The experimental results, supported with ATomic SUPerposition calculations, evidence that after PLM, the average size of the open volume defects increases, which represents a raise in concentration of vacancy agglomerations, but the overall defect density is reduced as a function of the PLM fluence. At the same time, the positron annihilation spectroscopy analysis provides information about dislocations and Ge vacancies decorated by Sn atoms. Moreover, it is shown that the PLM reduces the strain in the layer, while dislocations are responsible for trapping of Sn and formation of small Sn-rich-clusters.

Anti-HEV seroprevalence and rate of viremia in a German cohort of dogs, cats, and horses.

Hepatitis E virus (HEV) genotype 3 infections in Germany are mainly transmitted zoonotically through the consumption of swine meat. Furthermore, there is evidence that pets might come into contact with HEV, but the relevance of companion animals as possible sources of HEV transmission in Germany still needs to be defined. A monitoring study was therefore carried out on dogs, cats, and horses from Germany. In total 365 serum samples from pets (124 dogs, 119 cats, and 122 horses) were tested for HEV by PCR and for anti-HEV antibodies by a commercial ELISA. The HEV seroprevalence determined by the sero-assay varied significantly between dogs (10%), cats (6%), and horses (2%). Liver injury-related enzymes, alanine transaminase (ALT), and aspartate transaminase (AST) showed no differences between HEV-positive or negative animals. None of the pet serum samples tested positive for PCR. This serological study suggests that dogs and cats are significantly exposed to HEV in Germany, while horses are of minor relevance.

Weight loss induced alleviation of sleep-disordered breathing is associated with improvement of non-alcoholic fatty liver disease.

INTRODUCTION: Sleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. METHODS: Obese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. RESULTS: 48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. CONCLUSION: Preexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.

Whole systems approach to diet and healthy weight: a longitudinal process evaluation in East Scotland.

AIMS: Obesity contributes to morbidity and early mortality, affecting people of all ages and sociodemographic backgrounds. Despite attempts to address obesity, efforts to date have only had limited success. Adopting a whole systems approach (WSA) may potentially address obesity and emphasise complex inter-relating factors beyond individual choice. This study aimed to assess implementation of WSA to diet and healthy weight in two council areas of Scotland, longitudinally exploring enablers and barriers. One area followed a Leeds Beckett WSA model (LBM) of implementation, while the other used a hybrid model incorporating existing working systems. METHODS: To assess the process of implementing a WSA, interviews and focus groups were conducted after initiation and 1 year later. RESULTS: Main enablers included: belief in WSA effectiveness; positive relationships between key personnel; buy-in at community and national levels; funding availability; the working group responsible for coordinating the system development comprising individuals with diverse expertise; good communication; and existing governance structures. Barriers included: insufficient funding; high staff turnover; inadequate training in WSA methodology; engaging all relevant stakeholders and reverting to 'old ways' of non-WSA working. The LBM provided a framework for system setup and generating an action plan. CONCLUSION: This study provides the first independent longitudinal process evaluation of WSAs that have incorporated Leeds Beckett methodology, and offers insights into how a WSA can be implemented to address diet and healthy weight.

Potential role of soluble CD40 receptor in chronic inflammatory diseases.

The CD40 receptor and its ligand CD154 are widely expressed in various immune-competent cells. Interaction of CD154 with CD40 is essential for B-cell growth, differentiation, and immunoglobulin class switching. Many other immune-competent cells involved in innate and adaptive immunity communicate through this co-stimulatory ligand-receptor dyad. CD40-CD154 interaction is involved in the pathogenesis of numerous inflammatory and autoimmune diseases. While CD40 and CD154 are membrane-bound proteins, their soluble counterparts are generated by proteolytic cleavage or alternative splicing. This review summarises current knowledge about the impact of single nucleotide polymorphisms in the human CD40 gene and compensatory changes in the plasma level of the soluble CD40 receptor (sCD40) isoform in related pro-inflammatory diseases. It discusses regulation patterns of the disintegrin metalloprotease ADAM17 function leading to ectodomain shedding of transmembrane proteins, such as pro-inflammatory adhesion molecules or CD40. The role of sCD40 as a potential biomarker for chronic inflammatory diseases will also be discussed.

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.

Orchid Micropropagation Using Conventional Semi-Solid and Temporary Immersion Systems: A Review.

Orchids, with their astonishingly stunning flowers, dominate the international floricultural market. They are considered prized assets for commercial applications in pharmaceutical and floricultural industries as they possess high therapeutic properties and superior ornamental values. The alarming depletion of orchid resources due to excessive unregulated commercial collection and mass habitat destruction makes orchid conservation measures an extreme priority. Conventional propagation methods cannot produce adequate number of orchids, which would meet the requirement of these ornamental plants for commercial and conservational purposes. In vitro orchid propagation using semi-solid media offers an outstanding prospect of rapidly producing quality plants on a large scale. However, the semi-solid (SS) system has shortcomings with low multiplication rates and high production costs. Orchid micropropagation using a temporary immersion system (TIS) overcomes the limitations of the SS system by reducing production costs and making scaleup and full automation possible for mass plant production. The current review highlights different aspects of in vitro orchid propagation using SS and TIS and their benefits and drawbacks on rapid plant generation.

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.