Highly divergent and diverse viral community infecting sylvatic mosquitoes from Northeast Brazil.

Mosquitoes can transmit several pathogenic viruses to humans, but their natural viral community is also composed of a myriad of other viruses such as insect-specific viruses (ISVs) and those that infect symbiotic microorganisms. Besides a growing number of studies investigating the mosquito virome, the majority are focused on few urban species, and relatively little is known about the virome of sylvatic mosquitoes, particularly in high biodiverse biomes such as the Brazilian biomes. Here, we characterized the RNA virome of 10 sylvatic mosquito species from Atlantic forest remains at a sylvatic-urban interface in Northeast Brazil employing a metatranscriptomic approach. A total of 16 viral families were detected. The phylogenetic reconstructions of 14 viral families revealed that the majority of the sequences are putative ISVs. The phylogenetic positioning and, in most cases, the association with a high RNA-dependent RNA polymerase amino acid divergence from other known viruses suggests that the viruses characterized here represent at least 34 new viral species. Therefore, the sylvatic mosquito viral community is predominantly composed of highly divergent viruses highlighting the limited knowledge we still have about the natural virome of mosquitoes in general. Moreover, we found that none of the viruses recovered were shared between the species investigated, and only one showed high identity to a virus detected in a mosquito sampled in Peru, South America. These findings add further in-depth understanding about the interactions and coevolution between mosquitoes and viruses in natural environments. IMPORTANCE: Mosquitoes are medically important insects as they transmit pathogenic viruses to humans and animals during blood feeding. However, their natural microbiota is also composed of a diverse set of viruses that cause no harm to the insect and other hosts, such as insect-specific viruses. In this study, we characterized the RNA virome of sylvatic mosquitoes from Northeast Brazil using unbiased metatranscriptomic sequencing and in-depth bioinformatic approaches. Our analysis revealed that these mosquitoes species harbor a diverse set of highly divergent viruses, and the majority comprises new viral species. Our findings revealed many new virus lineages characterized for the first time broadening our understanding about the natural interaction between mosquitoes and viruses. Finally, it also provided several complete genomes that warrant further assessment for mosquito and vertebrate host pathogenicity and their potential interference with pathogenic arboviruses.

Glutamine metabolism improves left ventricular function but not macrophage-mediated inflammation following myocardial infarction.

Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved LV function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI, and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism.

Mitochondria-Derived Reactive Oxygen Species Contribute to Synergistic Interaction of Diabetes and Hypertension in Causing Chronic Kidney Injury.

Diabetes (DM) and hypertension (HTN) are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. The combination of DM and HTN significantly accelerates development of renal injury; however, the underlying mechanisms of this synergy are still poorly understood. This study assessed whether mitochondria (MT) dysfunction is essential in developing renal injury in a rat model with combined DM and HTN. Type 1 DM was induced in Wistar rats by streptozotocin (STZ). HTN was induced six weeks later by inter-renal aorta constriction between the renal arteries, so that right kidneys were exposed to HTN while left kidneys were exposed to normotension. Kidneys exposed to DM or HTN alone had only mild glomerular injury and urinary albumin excretion (UAE). In contrast, kidneys exposed to DM plus 8 weeks HTN had significantly increased UAE and glomerular structural damage with reduced glomerular filtration rate. Marked increases in MT-derived reactive oxygen species (ROS) were also observed in right kidneys exposed to HTN+DM. We further tested whether treatment with MT-targeted antioxidant (MitoTEMPO) after the onset of HTN attenuates renal injury in rats with DM+HTN. Results show that kidneys in DM+AC+MitoTEMPO rats had lower UAE, less glomerular damage, and preserved MT function compared to untreated DM+AC rats. Our studies indicate that MT-derived ROS play a major role in promoting kidney dysfunction when DM is combined with HTN. Preserving MT function might be a potential therapeutic approach to halt the development of renal injury when DM coexists with HTN.

Parental obesity predisposes offspring to kidney dysfunction and increased susceptibility to ischemia-reperfusion injury in a sex-dependent manner.

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.

Synergistic effects of glial cell line-derived neurotrophic factor and base-medium on in vitro culture of testicular tissue derived from prepubertal collared peccary.

We evaluated the influence of different media plus various concentrations of Glial cell line-derived neurotrophic factor (GDNF) during the in vitro culture (IVC) of testicular tissues from prepubertal collared peccary. Testes from 5 individuals were collected, fragmented and cultured for 28 days (34°C and 5% CO2). Culture media were Dulbecco's modified essential medium (DMEM) or stem cell serum free media (StemPro-34™ SFM), both supplemented with various concentrations of GDNF (0, 10, or 20 ng/mL). Fragments were cultured on the flat surface of 0.75% agarose gel and were evaluated every 7 days for fragment area, histomorphology, cellular viability, and proliferative activity. Data were expressed as mean ± standard error and analyzed by Kruskal-Wallis's and Tukey test. Fragments area decreased over the 28 days-culture, regardless of the treatment. For morphology, the StemPro-37 SFM medium plus 10 ng/mL GDNF provided higher scores at all time points in comparison to DMEM using any GDNF concentration (p < .05). After 28 days, similar cellular viability (~70%) was observed in all treatments (p > .05). For proliferating cell nuclear antigen assay, only DMEM plus 10 ng/mL GDNF improved (p < .05) cellular proliferation on Days 14 and 28. Looking at argyrophilic nucleolar organizing regions, after 28 days, there were no differences among treatments regarding cell proliferative capacity for both spermatogonia and Sertoli cells (p > .05). In summary, the DMEM and StemPro-34 SFM are adequate medium for IVC of prepubertal peccary testicular tissue. Supplementation with GDNF, especially at a 10 ng/mL concentration, appears to be essential for the maintenance of cell survival and proliferation.

Catalytic deracemization of chiral allenes by sensitized excitation with visible light.

Chiral compounds exist as enantiomers that are non-superimposable mirror images of each other. Owing to the importance of enantiomerically pure chiral compounds1-for example, as active pharmaceutical ingredients-separation of racemates (1:1 mixtures of enantiomers) is extensively performed2. Frequently, however, only a single enantiomeric form of a chiral compound is required, which raises the question of how a racemate can be selectively converted into a single enantiomer. Such a deracemization3 process is entropically disfavoured and cannot be performed by a conventional catalyst in solution. Here we show that it is possible to photochemically deracemize chiral compounds with high enantioselectivity using irradiation with visible light (wavelength of 420 nanometres) in the presence of catalytic quantities (2.5 mole per cent) of a chiral sensitizer. We converted an array of 17 chiral racemic allenes into the respective single enantiomers with 89 to 97 per cent enantiomeric excess. The sensitizer is postulated to operate by triplet energy transfer to the allene, with different energy-transfer efficiencies for the two enantiomers. It thus serves as a unidirectional catalyst that converts one enantiomer but not the other, and the decrease in entropy is compensated by light energy. Photochemical deracemization enables the direct formation of enantiopure materials from a racemic mixture of the same compound, providing a novel approach to the challenge of creating asymmetry.

Preoperative risk factors for early postoperative bleeding after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis.

PURPOSE: Although bariatric surgery is an effective intervention for obesity, it comes with risks such as early postoperative bleeding (EPB). Identifying preoperative risk factors for this complication can help patients' risk stratification and optimization. We performed a systematic review and meta-analysis to find predictors for early postoperative bleeding after Roux-en-Y gastric bypass (RYGB). METHODS: We conducted a systematic review, searching PubMed, Cochrane Library, and Web of Science until November 2023. We performed a random-effects meta-analysis to explore preoperative risk factors associated with early postoperative bleeding after RYGB. Sources of heterogeneity were explored by leave-one-out analyses. RESULTS: 23 studies were included, comprising 232,488 patients. Male gender (meta-analytical RR = 1.42, 95%CI = 1.21-1.66, I2 = 18%, Q Cochran test p-value = 0.29) and revisional surgery (meta-analytical RR = 1.35, 95%CI = 1.12-1.62, I2 = 22%, Q Cochran test p = 0.21) were associated with higher risk of EPB. On average, patients with EPB were older than the remainder (MD for the mean age = 2.82 years, 95%CI = 0.97-4.67, I2 = 0.00%, Q Cochran test p = 0.46). Except for hypertension (meta-analytical RR = 1.33, 95%CI = 1.02-1.73, I2 = 66%, Q Cochran test p < 0.0001), comorbidities were not associated with a higher risk of EPB. CONCLUSION: Preoperative risk factors, including age, gender, hypertension, and revisional bariatric surgery, are associated with early postoperative bleeding after RYGB. Further primary studies, with higher methodological quality, are required to detail more risk factors.

Active intervals between sets and exercise of resistance exercises potentiate the magnitude of post-exercise hypotension in middle-aged hypertensive women.

BACKGROUND: Walking/run promotes greater post-exercise hypotension (PEH) than resistance exercise (RE) which can be associated nitric oxide production. Then, we investigated if adding walking between RE increases PEH. METHODS: Thirteen hypertensive women (48 ± 1.9 years; 26.8 ± 0.3 kg/m2) performed five experimental sessions: 1-traditional RE with passive interval (PIBS); 2-RE with active interval between sets (AIBS); 3-RE with active interval between exercises (AIEX); 4-aerobic exercise (AE); 5-no exercise. Blood pressure was measured before and immediately after exercise and every 10 min of a 60-min post-exercise recovery period. Plasma nitrite (NO) and malondialdehyde (MDA) were also measured. RESULTS: AIBS, AIEX, and AE sessions promoted systolic PEH (12 ± 1.53; 16 ± 2.13; 18 ± 1.34 mmHg, respectively) and diastolic PEH (8 ± 1.38; 8 ± 0.79; 8 ± 0.58 mmHg). In AIBS, AIEX and AE sessions, significant PEH was noted at 10 or 20 min; in PIBS, PEH was significant only at 40 min. In the PIBS session, NO did not change, but presented higher values after AIBS, AIEX and AE sessions. MDA showed no changes between sessions. CONCLUSIONS: Passive or active intervals in resistance exercise promote PEH in hypertensive women. Active intervals shorten the PEH onset time as additional benefit.

Bilateral Peters' anomaly, aniridia and Wilms tumour (WAGR syndrome) in monozygotic twins.

AIM: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). METHODS: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. RESULTS: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. CONCLUSION: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome.

Antimicrobial and anthelmintic effects of copper nanoparticles against Koi carp parasites and their toxicity.

This study investigated the in vitro antimicrobial and anthelmintic effect of copper nanoparticles (CuNPs) against the bacterium Aeromonas hydrophila, the monogeneans Dactylogyrus minutus, Dactylogyrus extensus, Gyrodactylus cyprini, and the cestode Schyzocotyle acheilognathi, as well as their toxicity to Cyprinus carpio Koi. In the antimicrobial in vitro test, the inhibition zone method and minimum inhibitory concentration (MIC) were performed. In order to determine the time and efficacy of monogenean parasite mortality, the parasites were exposed to CuNP concentrations of 20, 50, 100, 150, 200, and 300 mg L-1, and a control group with tank water and one with copper sulphate pentahydrate (CuSO4.5H2O) at a concentration of 0.3 mg L-1, performed in triplicate. The parasites were observed every 10 min for 300 min, and mortality was recorded. For the cestodes, parasites were immersed in CuNP concentrations of 50, 100, 150, and 300 mg L-1. At the end of the in vitro tests, the anthelmintic efficacy of each treatment was calculated. To assess the tolerance and toxicity in fish, they were exposed to CuNP concentrations of 0.6, 1.25, 2.5, 5, 10, 20, and 50 mg L-1 for 12 h. The MIC demonstrated that CuNPs effectively inhibited the growth of A. hydrophila up to a dilution of 12,500 mg L-1 and showed an inhibition zone of 14.0 ± 1.6 mm for CuNPs. The results of anthelmintic activity showed a dose-dependent effect of concentration for both groups of parasites, with the most effective concentration being 300 mg L-1 in 120 min. In the toxicity test, the carps showed tolerance to lower concentrations. The study indicated that CuNPs were effective against the studied pathogens. However, it proved to be toxic to fish at high concentrations. The use of low concentrations is recommended still requires further investigation.

Public parks in the city of Rio de Janeiro, southeast Brazil, and the risk of parasitosis transmission by freshwater gastropods.

Urban parks are not only important for the wellbeing of the human population, but are also widely considered to be potentially important sites for the conservation of biodiversity. However, they may offer risk parasitic infections, such as schistosomiasis and fascioliasis, which are both transmitted by freshwater snails. The present study investigated the occurrence of freshwater gastropods in urban parks of the Brazilian city of Rio de Janeiro, and their possible infection by helminths of medical-veterinary importance. Gastropods were collected from six parks (2021 - 2022) and examined for the presence of larval helminths. In all, 12 gastropod species from different families were collected: Ampullariidae, Assimineidae, Burnupidae, Lymnaeidae, Physidae, Planorbidae, Succineidae, and Thiaridae. The parasitological examination revealed cercaria of three types in five snail species, with the Pleurolophocerca cercariae type in Melanoides tuberculata (the most abundant species), Echinostoma cercariae in Physella acuta and Pomacea maculata, and Virgulate cercariae, in Pomacea sp. and Pomacea maculata. None of the Biomphalaria tenagophila and Pseudosuccinea columella (the most frequent species) specimens were parasitized by Schistosoma mansoni or Fasciola hepatica, respectively. Even so, some parks may represent a considerable potential risk for transmission of both Schistosoma mansoni and Fasciola hepatica, given the presence of these gastropod vectors and the frequent contact of visitors with the waterbodies.

Clinical and radiographic outcomes of a two-piece ceramic implant: one year results from a prospective clinical trial.

OBJECTIVE: To describe the clinical and radiographic performance and survival rate of a new two-piece ceramic implant system after at least 12 months of follow-up. MATERIALS AND METHODS: Sixty-five implants were placed and followed up for at least 12 months (12.3 ± 1.5), in 50 patients. The implants were installed both in fresh extraction sockets and in healed sites and received provisional restoration when the clinical insertion torque was greater than 35Ncm. The primary results describe the survival rate of these implants. Clinical performance was evaluated through the evaluation of the Pink Esthetic Score (PES) and the degree of satisfaction of the patients. Bone loss was measured through radiographic measurements of the marginal bone loss in the mesial (MBLM) and distal (MBLD) sites. RESULTS: The survival rate was 98.5%. The average MBLM was 0.24 mm (± 0.53) and the MBLD was 0.27 mm (± 0.57). A statistical difference was observed only when comparing immediate implants with delayed ones (MBLM - p = 0.046 and MBLD - p = 0.028) and when they received immediate provisionalization or not (MBLM - p = 0.009 and MBLD - p = 0.040). The PES before the intervention (T0) was 13.4 (± 0.8) and the PES at T2 (12-month follow-up) was 12.9 (± 1.5) (p = 1.14). CONCLUSION: The new two-piece ceramic implant used in the present study showed predictable and reliable results, similar to those found with titanium implants after one year of follow-up. CLINICAL RELEVANCE: These implants can be used as an alternative to titanium implants in terms of the marginal bone loss and the degree of patient satisfaction.

Bone Density of the Midpalatal Suture After Surgically Assisted Rapid Maxillary Expansion: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the bone density in the midpalatal suture after 10 months of surgically assisted rapid maxillary expansion (SARME) with the separation of the maxilla into 2 segments. METHODS: Sixty multislice computed tomography (MCT) from 20 patients undergoing SARME were analyzed in 3 periods of time (1 MCT per patient on each occasion): (1) 1 week before surgery, (2) postsurgery immediately after completing the expander activation, and (3) 10 months after the expander activation. On all occasions, the bone density was measured in Hounsfield units on MCT scans in axial and coronal sections, in the anterior (A1), middle (A2), and posterior (A3) regions of the midpalatal suture. RESULTS: The mean percentage values of bone density in Hounsfield units, from the 10-month postactivation period to preoperative in the A1, A2, and A3 regions were 68.38%, 38.21%, and 55.90%, respectively, in the axial norm, and 64.06%, 36.81%, and 55.50% in coronal norm (A1 = A3>A2), with no significant difference in the tomographic cuts (P >0.05). There was no correlation between patient age or amount of expansion in the expander and bone density. CONCLUSIONS: The bone density in the midpalatal suture 10 months after SARME is lower than preexpansion. A denser new bone formation along the suture concentrates closer to the extremities rather than in the central region. Although the maturation of the new bone formation in the midpalatal suture is lower 10 months after SARME, it appears to be sufficient for satisfactory clinical results, regardless of patient age or the amount of expansion in the expander.

Integrating sEMG and IMU Sensors in an e-Textile Smart Vest for Forward Posture Monitoring: First Steps.

Currently, the market for wearable devices is expanding, with a growing trend towards the use of these devices for continuous-monitoring applications. Among these, real-time posture monitoring and assessment stands out as a crucial application given the rising prevalence of conditions like forward head posture (FHP). This paper proposes a wearable device that combines the acquisition of electromyographic signals from the cervical region with inertial data from inertial measurement units (IMUs) to assess the occurrence of FHP. To improve electronics integration and wearability, e-textiles are explored for the development of surface electrodes and conductive tracks that connect the different electronic modules. Tensile strength and abrasion tests of 22 samples consisting of textile electrodes and conductive tracks produced with three fiber types (two from Shieldex and one from Imbut) were conducted. Imbut's Elitex fiber outperformed Shieldex's fibers in both tests. The developed surface electromyography (sEMG) acquisition hardware and textile electrodes were also tested and benchmarked against an electromyography (EMG) gold standard in dynamic and isometric conditions, with results showing slightly better root mean square error (RMSE) values (for 4 × 2 textile electrodes (10.02%) in comparison to commercial Ag/AgCl electrodes (11.11%). The posture monitoring module was also validated in terms of joint angle estimation and presented an overall error of 4.77° for a controlled angular velocity of 40°/s as benchmarked against a UR10 robotic arm.

Generalized anxiety disorder in Brazilian undergraduate dental students during the COVID-19 pandemic: A cross-sectional study.

OBJECTIVE: Explore the prevalence of generalized anxiety disorder (GAD) and associated factors in undergraduate dental students during the first wave of the COVID-19 pandemic in Brazil. MATERIALS AND METHODS: Cross-sectional study. A semi-structured questionnaire addressing the variables of interest was shared with dental students between July 8 and 27 2020. The outcome was determined using the seven-item generalized anxiety disorder (GAD-7) scale. A 'positive' diagnosis was defined as a total of ≥10 points on the scale. Statistical analysis involved descriptive, bivariate and multivariate analyses, with the significance level set at 5%. RESULTS: Among the 1050 students evaluated, 53.8% had a positive diagnosis for GAD. The multivariate analysis revealed that the prevalence of symptoms was higher among individuals who resided with more than three people, those enrolled at teaching institutions that suspended all clinical and laboratory activities, those who did not have an adequate home situation to maintain distance learning, those who had been diagnosed with COVID-19, those who felt anxious about having to see patients with a suspicion or diagnosis of COVID-19 and those who preferred to interrupt in-person academic activities until the population is vaccinated for the COVID-19 virus. CONCLUSION: The prevalence of GAD was high. Aspects related to the composition and organization of the home, the suspension of academic activities, a history of COVID-19 contamination, feelings of anxiety in providing dental care to patients with symptoms/suspected of COVID-19 infection and the preference to interrupt in-person academic activities until the population is vaccinated for COVID-19 were factors predisposing the students to anxiety during the first wave of the pandemic.

Sex differences in weight gain, blood pressure control, and responses to melanocortin-4 receptor antagonism in offspring from lean and obese parents.

We examined potential sex differences in appetite and blood pressure (BP) responses to melanocortin-4 receptor (MC4R) blockade in offspring from lean and obese parents. Offspring from normal (N) diet-fed parents were fed N (NN) or high-fat (H) diets (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were also fed N (HN) or H diets (HH). Adult male and female offspring were implanted with BP telemetry probes and intracerebroventricular cannulas to infuse MC4R antagonist or vehicle. Infusion of the MC4R antagonist SHU-9119 (1 nmol/h) for 7 days caused larger increases in calorie intake and body weight in obese compared with lean offspring. In male offspring, HH and HN groups exhibited higher baseline BP compared with NN and NH, and HH showed a greater reduction in BP during SHU-9119 infusion. In female offspring, HH also showed higher baseline BP and greater reduction in BP during MC4R blockade. SHU-9119 reduced heart rate in all groups, but reductions were more pronounced in offspring from lean parents. Combined α and ß-adrenergic blockade reduced BP more in male HH offspring compared with NN controls. Losartan reduced BP more in male NH, HN, and HH offspring compared with NN controls. Losartan and α- and ß-adrenergic blockade reduced BP similarly in all female groups. These results suggest that endogenous MC4R activity contributes to elevated BP in obese offspring from obese parents. Our findings also indicate important sex differences in the mechanisms of BP control in male and female offspring of obese parents.

Loss of hepatic PPARα in mice causes hypertension and cardiovascular disease.

The leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is cardiovascular disease (CVD). However, the mechanisms are unknown. Mice deficient in hepatocyte proliferator-activated receptor-α (PPARα) (PparaHepKO) exhibit hepatic steatosis on a regular chow diet, making them prone to manifesting NAFLD. We hypothesized that the PparaHepKO mice might be predisposed to poorer cardiovascular phenotypes due to increased liver fat content. Therefore, we used PparaHepKO and littermate control mice fed a regular chow diet to avoid complications with a high-fat diet, such as insulin resistance and increased adiposity. After 30 wk on a standard diet, male PparaHepKO mice exhibited elevated hepatic fat content compared with littermates as measured by Echo MRI (11.95 ± 1.4 vs. 3.74 ± 1.4%, P < 0.05), hepatic triglycerides (1.4 ± 0.10 vs. 0.3 ± 0.01 mM, P < 0.05), and Oil Red O staining, despite body weight, fasting blood glucose, and insulin levels being the same as controls. The PparaHepKO mice also displayed elevated mean arterial blood pressure (121 ± 4 vs. 108 ± 2 mmHg, P < 0.05), impaired diastolic function, cardiac remodeling, and enhanced vascular stiffness. To determine mechanisms controlling the increase in stiffness in the aorta, we used state-of-the-art PamGene technology to measure kinase activity in this tissue. Our data suggest that the loss of hepatic PPARα induces alterations in the aortas that reduce the kinase activity of tropomyosin receptor kinases and p70S6K kinase, which might contribute to the pathogenesis of NAFLD-induced CVD. These data indicate that hepatic PPARα protects the cardiovascular system through some as-of-yet undefined mechanism.

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy.

The immune response is crucial for coronavirus disease 19 (COVID-19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to induce neutrophil activation by CLEC5A and Toll-like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS-CoV-2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS-CoV-2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID-19 patients in comparison with mild COVID-19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID-19. In hamsters, we detected CLEC5A gene expression during 3-15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS-CoV-2, promoting inflammatory cytokine production, probably through an interaction with the receptor-binding domain in the N-acetylglucosamine binding site (NAG-601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID-19 progression; therapy with a monoclonal antibody could be a good strategy for COVID-19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

Relative enhancement index can be used to quantify liver function in cirrhotic patients that undergo gadoxetic acid-enhanced MRI.

OBJECTIVES: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups. METHODS: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation. RESULTS: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho = - 0.816; p < 0.001); REI and MELD score (rho = - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity). CONCLUSIONS: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast. KEY POINTS: • REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. • REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. • The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation.

Peppermint essential oil (Mentha piperita L.) increases time to exhaustion in runners.

PURPOSE: This study aimed to evaluate the capacity of peppermint essential oil to improve the physical performance of runners in running protocol until exhaustion. METHODS: In a clinical, randomized, double-blind, cross-over and controlled study, fourteen male recreational runners (37.1 ± 2.0 years; 24 ± 1.1 kg/m2; 53.1 ± 1.7 mL kg min) performed two runs to exhaustion at 70% of VO2max, after intake of 500 mL of water added with 0.05 mL of peppermint essential oil (PEO) or placebo (PLA), plus 400 mL of the drink during the initial part of the exercise. Records were made of body temperature (BT), thermal sensation (TS), thermal comfort (TC), subjective perception of effort (SPE), sweat rate (SR), and urine volume and density. RESULTS: Time to exhaustion was 109.9 ± 6.9 min in PEO and 98.5 ± 6.2 min in PLA (p = 0.009; effect size: 0.826). No significant changes were observed in the values of BT, TS, TC, SPE, SR, lost body mass, and urine volume and density (p > 0.05). CONCLUSION: Peppermint essential oil added to water before and during a race significantly increases the time to exhaustion of recreational runners but without altering BT, TS, TC, or hydration status, so the mechanisms involved were not clarified in this study. BRAZILIAN REGISTRY OF CLINICAL TRIALS (REBEC): RBR-75zt25z.