Laboratory and field evaluation of the impact of exercise on the performance of regular and polymer-based deet repellents

Studies were done in Manitoba, Canada, to evaluate the impact of exercise on repellent performance against mosquitoes. Two products containing the active ingredient N,N-diethyl-3-methylbenzamide (deet) were tested; one product was a polymer-based cream (3M Ultrathon Insect Repellent) and the other product was an alcohol-based pump spray formulation (Muskol Insect Repellent). Assessments were done in the laboratory using Aedes aegypti (L.) and in the field with naturally occurring populations of mosquitoes. Repellent was applied to the forearms (laboratory) or a lower leg (field) of test subjects at 1.5 g of test product per 600 cm2 surface area (0.75 or 0.83 mg deet/cm2). For a given test day, subjects exercised or did not. Exposure to mosquito attack was for 1 min at 30-min intervals in laboratory procedures, and it was continuous in field tests. Performance was measured as complete protection time (CPT). Moderate levels of physical activity resulted in a >40% decline in mean CPT, from 468 to 267 min in the laboratory experiments and from 359 to 203 min in field tests. Repellent product did not affect the magnitude of the decline. Mean biting pressure during field trials was 21.3 bites per min, and mosquito collections were made up primarily of Ochlerotatus sticticus (Meigen) and Aedes vexans (Meigen).     

Impaired NLRP3 inflammasome activity during fetal development regulates IL‐1β production in human monocytes

Interleukin‐1β (IL‐1β) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed the extent of variability within the Toll‐like receptor (TLR)/NLRP3 inflammasome pathways in human neonates. We show that immature low CD14 expressing/CD16^pos monocytes predominate before 33 weeks of gestation, and that these cells lack production of the pro‐IL‐1β precursor protein upon LPS stimulation. In contrast, high levels of pro‐IL‐1β are produced within high CD14 expressing monocytes, although these cells are unable to secrete mature IL‐1β. The lack of secreted IL‐1β in these monocytes parallels a reduction of NLRP3 induction following TLR stimulation resulting in a lack of caspase‐1 activity before 29 weeks of gestation, whereas expression of the apoptosis‐associated speck‐like protein containing a CARD and function of the P2×7 receptor are preserved. Our analyses also reveal a strong inhibitory effect of placental infection on LPS/ATP‐induced caspase‐1 activity in cord blood monocytes. Lastly, secretion of IL‐1β in preterm neonates is restored to adult levels during the neonatal period, indicating rapid maturation of these responses after birth. Collectively, our data highlight important developmental mechanisms regulating IL‐1β responses early in gestation, in part due to a downregulation of TLR‐mediated NLRP3 expression. Such mechanisms may serve to limit potentially damaging inflammatory responses in a developing fetus.     

Comparison of two technics of cardiopulmonary bypass (conventional and mini CPB) in the trans-and postoperative periods of cardiac surgery

Objective

This study aimed to compare the effects of two different perfusion techniques: conventional cardiopulmonary bypass and miniature cardiopulmonary bypass in patients undergoing cardiac surgery at the University Hospital of Santa Maria - RS.

Methods

We perform a retrospective, cross-sectional study, based on data collected from the patients operated between 2010 and 2013. We analyzed the records of 242 patients divided into two groups: Group I: 149 patients undergoing cardiopulmonary bypass and Group II - 93 patients undergoing the miniature cardiopulmonary bypass.

Results

The clinical profile of patients in the preoperative period was similar in the cardiopulmonary bypass and miniature cardiopulmonary bypass groups without significant differences, except in age, which was greater in the miniature cardiopulmonary bypass group. The perioperative data were significant of blood collected for autotransfusion, which were higher in the group with miniature cardiopulmonary bypass than the cardiopulmonary bypass and in transfusion of packed red blood cells, which was higher in cardiopulmonary bypass than in miniature cardiopulmonary bypass. In the immediate, first and second postoperative period the values of hematocrit and hemoglobin were higher and significant in miniature cardiopulmonary bypass than in the cardiopulmonary bypass, although the bleeding in the first and second postoperative days was higher and significant in miniature cardiopulmonary bypass than in the cardiopulmonary bypass.

Conclusion

The present results suggest that the miniature cardiopulmonary bypass was beneficial in reducing the red blood cell transfusion during surgery and showed slight but significant increase in hematocrit and hemoglobin in the postoperative period.     

Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2

As the COVID-19 pandemic grows, several therapeutic candidates are being tested or undergoing clinical trials. Although prophylactic vaccination against SARS-CoV-2 infection has been shown to be effective, no definitive treatment exists to date in the event of infection. The rapid spread of infection by SARS-CoV-2 and its variants fully warrants the continued evaluation of drug treatments for COVID-19, especially in the context of repurposing of already available and safe drugs. Here, we explored the therapeutic potential of melatonin and melatonergic compounds in attenuating COVID-19 pathogenesis in mice expressing human ACE2 receptor (K18-hACE2), strongly susceptible to SARS-CoV-2 infection. Daily administration of melatonin, agomelatine, or ramelteon delays the occurrence of severe clinical outcome with improvement of survival, especially with high melatonin dose. Although no changes in most lung inflammatory cytokines are observed, treatment with melatonergic compounds limits the exacerbated local lung production of type I and type III interferons, which is likely associated with the observed improved symptoms in treated mice. The promising results from this preclinical study should encourage studies examining the benefits of repurposing melatonergic drugs to treat COVID-19 and related diseases in humans.     

Perinatal exposure to antiretroviral therapy is associated with increased blood mitochondrial DNA levels and decreased mitochondrial gene expression in infants

BACKGROUND: The effects of perinatal antiretroviral therapy (ART) on infant mitochondrial function are not well known. We compared blood mitochondrial DNA (mtDNA) levels and mtDNA gene expression (mtRNA) in human immunodeficiency virus (HIV)-uninfected, ART-exposed infants born to HIV-positive mothers with mtDNA levels and mtDNA gene expression in control infants born to uninfected women. METHODS: In this prospective cohort study, longitudinal mtDNA:nuclear DNA and mtRNA:beta-actin mRNA ratios were compared in blood samples obtained at various time points from birth to 8 months, using generalized estimating equation linear regression models. RESULTS: Log(10) mtDNA levels at birth were higher in ART-exposed infants, compared with levels in control infants, although the difference did not reach statistical significance ([Formula: see text] for comparison of samples obtained 0-3 days after birth). ART-exposed infants' mtDNA levels increased further during the zidovudine prophylaxis period-from age 4 days to age 6 weeks-([Formula: see text]) and remained significantly higher than the levels observed in control infants until the end of the study. In contrast, log(10) mtRNA levels at birth were lower in ART-exposed infants than in control infants ([Formula: see text]), but were not statistically different later. CONCLUSIONS: When control infants and ART-exposed infants were compared, the mtDNA level was increased but mitochondrial gene expression was decreased in ART-exposed infants. These differences persisted after zidovudine was discontinued, suggesting that changes in mitochondrial proliferation and/or expression take place during and after ART exposure. These changes are likely the effects of the antiretroviral drugs on mitochondria. The clinical relevance and long-term impact of these alterations must be studied.     

The Beneficial Effect of Anthocyanidin‐Rich Vitis vinifera L. Grape Skin Extract on Metabolic Changes Induced by High‐Fat Diet in Mice Involves Antiinflammatory and Antioxidant Actions

We hypothesized that a polyphenol‐rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high‐fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti‐inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF‐α, IL‐6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF‐fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd.