A C-type lectin induces NLRP3 inflammasome activation via TLR4 interaction in human peripheral blood mononuclear cells.

Lectins are a large group of proteins found in many snake venoms. BjcuL is a C-type lectin from Bothrops jararacussu snake venom that does not present cytotoxicity action on human peripheral blood mononuclear cells (PBMCs) at concentrations of 5 and 10 µg/mL. BjcuL demonstrates an immunomodulatory role in PBMCs with the production of pro- and anti-inflammatory cytokines (IL-2, IL-10, IFN-γ, IL-6, TNF-α, and IL-17) in addition to stimulate T cells to produce reactive oxygen species (ROS) that could play a role in the acute inflammatory reaction observed in the victims. Inflammasomes are an essential arm in cells of innate immunity to detect and sense a range of endogenous or exogenous, sterile, or infectious stimuli to elicit cellular responses and effector mechanisms. NLRP3 inflammasome is a significant target for this study, because the lectin is responsible for leukocyte activation stimulating the release of inflammatory mediators, which results in dynamic cellular responses to remove the detrimental process to the body in snakebites. Thus, this study aimed to investigate how isolated BjcuL from B. jararacussu venom affects NLRP3 inflammasome activation on PBMCs. For this, the cells were isolated by density gradient and incubated with BjcuL at different periods and concentrations for the evaluation of the activation of the NLRP3 inflammasome through gene and protein expressions of ASC, CASPASE-1, and NLRP3 by RT-qPCR, Western blot, and immunofluorescence, as well as the participation of Toll-like receptor 4 (TLR4) and ROS in the IL-1ß production, a product resultant of the NLRP3 inflammasome activation. Herein, BjcuL interacts with TLR4 as demonstrated by in vitro and in silico studies and induces cytokines release via NF-κB signaling. By genic and protein expression assays, BjcuL activates NLRP3 inflammasome, and the pharmacological modulation with LPS-RS, an antagonist of TLR4; LPS-SM, an agonist of TLR4; MCC950, a specific NLRP3 inhibitor, and rotenone, an inhibitor of mitochondrial ROS, confirmed the participation of TLR4 and ROS in the NLRP3 inflammasome activation and IL-1ß liberation. The effects of BjcuL on the regulation and activation of the NLRP3 inflammasome complex via TLR4 activation with ROS participation may be determinant for the development of the inflammatory local effects seen in snakebite victims. In addition, in silico together with in vitro studies provide information that may be useful in the rational design of TLR agonists as well as new adjuvants for immunomodulatory therapy.

Patients with laboratory criteria of anti-phospholipid syndrome and 'non-criteria' manifestations: a multicenter cohort.

OBJECTIVES: Patients with laboratory criteria for anti-phospholipid syndrome (APS) but presenting only 'non-criteria' clinical manifestations are scarcely characterized in the literature. We aimed to analyse a cohort of these patients regarding the most prevalent manifestations, antibody profile, and treatments, while establishing a comparison with definite APS patients. METHOD: A retrospective analysis was conducted of individuals fulfilling APS laboratory criteria assessed in two tertiary European hospitals between 2005 and 2020. Patients without clinical criteria but with non-criteria manifestations (termed 'clinical non-criteria') and age-/gender-matched controls were included. RESULTS: Altogether, 75 clinical non-criteria patients were analysed, with haematological (thrombocytopenia, haemolytic anaemia) and 'mild' neurological manifestations (white-matter lesions, migraine) as the most prevalent non-obstetric involvements. These patients displayed more thrombocytopenia [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.7-7.6; p = 0.001] than controls with APS, but severe manifestations, such as valvular heart disease (p < 0.001), livedoid vasculopathy, seizures, chorea, transverse myelitis, bone necrosis, and alveolar haemorrhage, occurred only in definite APS patients. Corticosteroids were required by 40% of patients with thrombocytopenia. Manifestations in anticoagulated patients included white-matter lesions, nephropathy, superficial vein thrombosis, amaurosis fugax, and livedoid vasculopathy. Suspicion of progression towards systemic lupus erythematosus (SLE) occurred in 19% of non-SLE individuals. CONCLUSION: 'Clinical non-criteria' patients displayed significant treatment use, predominantly haematological involvement, and less severe manifestations than definite APS controls. Some patients may additionally progress to future SLE. The impact of certain manifestations flags them as potential future contributors to classifying individuals as definite APS.

Bothrops atrox mice experimental envenoming treatment using light-emitting diode (led) as an adjunct therapy to conventional serum therapy.

The use of anti-venom is one of the main control measures for snakebite envenoming when applied immediately after the snakebite. Systemic effects of the envenoming are usually reversed; however, neutralization of local effects is hardly achieved. The need for adjuvant therapies associated with serum therapy can improve the treatment for local effects of envenoming, with greater effectiveness in preventing or delaying the progression of damage, reducing the clinical signs and symptoms of victims of snakebites. The purpose of the study was to evaluate the photobiomodulation therapy using LED and/or dexamethasone associated with conventional serum therapy for the treatment of local damage caused by Bothrops atrox envenomation in a murine model. For this, experimental envenoming was carried out in the gastrocnemius muscle of male Swiss mice weighing 18 to 22 g divided into 8 groups of animals, distributed in groups non-treat, treated with anti-bothropic serum, dexamethasone, and LED, or the associated treatments, by intramuscular inoculation of 50 µg of venom or sterile PBS (control). After 30 min, the proposed treatments were administered alone or in combination. After 3 h, blood and muscle samples were collected for myotoxicity, cytotoxicity, histological analysis, and IL-1ß assays. The evaluation of the treatment alone showed that serum therapy is not effective for the treatment of local damage and photobiomodulation demonstrated to be an effective therapy to reduce leukocyte infiltration, hemorrhage, and myotoxicity in experimental envenoming; dexamethasone proved to be a good resource for the treatment of the inflammatory process reducing the leukocyte infiltration. The association of serum therapy, LED, and dexamethasone was the best treatment to reduce the local effects caused by Bothrops atrox venom. All in all, the association of photobiomodulation therapy using LED with conventional serum therapy and the anti-inflammatory drug is the best treatment for reducing the undesirable local effects caused by snakebite accidents involving B. atrox species.

Daily consumption of ultra-processed foods and cardiometabolic risk factors in children aged 7 to 10 years in Northeast Brazil.

Background: Ultra-processed foods (UPFs) consumption is associated with pediatric overweight and obesity. Aim: To evaluate the UPFs consumption in children classified either as eutrophic or with excess weight (overweight and obesity). It was also described the fasting plasma glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) and the correlation between UPFs consumption and cardiometabolic risk factors. Methods: A total of 139 children aged 7-10years of both sexes, living in Northeast Brazil were classified as eutrophic (n = 65) or excess weight (n = 62). Waist circumference (WC), percentage of body fatness (% BF), fat-free-mass and fat mass were evaluated. Fasting blood sample were collected for biochemical analysis. Food consumption was classified according to the degree of processing. Results: Children with excess weight had a reduction in plasma HDL concentration (45.00; IQR:36.00-54.50 mg/dL vs. 40.00; IQR:35.75-45.25 mg/dL; p = 0.021) and an increase in blood glucose (82.00; IQR:79.00-86.00 mg/dL vs. 86.00; IQR:81.00-90.00 mg/dL; p < 0.001) and TG (64.00; IQR:45.00-92.50 mg/dL vs. 81.00; IQR:57.50-111.75 mg/dL; p < 0.021) when compared with the eutrophic children. UPFs accounted for 43.43% of the total calories consumed by children. Children with excess weight had higher total energy consumption resulting from consumption of UPFs (714.30 ± 26.32 kcal vs. 848.06 ± 349.46 kcal; p = 0.011). The absolute consumption of the UPFs showed a positive correlation with WC (r = 0.202; p = 0.023) and %BF (r = 0.198; p = 0.026). Conclusion: UPFs consumption was higher for children with excess weight and positively correlated with two cardiometabolic risk factors, suggesting the need for strengthening public policies that discourage the consumption of these foods.

Potential of vermicomposting with mixtures of animal manure and vegetable leaves in the development of Eisenia foetida, microbial biomass, and enzymatic activity under semi-arid conditions.

Vermicomposting is the bio-oxidation and stabilization of organic matter involving relationships between the action of earthworms and microorganisms and the activation and dynamics of several enzyme activities. Semi-arid farmers to make (extra) money and organic production, produce their vermicompost using plant residues and animal manure, but there is no information about the final product generated. Thus, this study aimed to analyze the potential of vermicomposting with mixtures of animal manure and vegetable leaves in the development of Eisenia foetida, microbial biomass, and enzymatic activity in the semi-arid region, Brazil. The experimental design applied was randomized block in a 6 × 4 factorial scheme with four replicates, with six treatments (mixtures of cattle manure, goat manure, cashew leaves, and catanduva leaves) and evaluated at four-time intervals (30, 60, 90, and 120 days of vermicomposting). The treatments were placed in polyethylene pots in the same site, environmental conditions, and residues proportions as used by farmers. The characteristics analyzed were the number of earthworms (NE), total earthworm biomass (TEB) and earthworm multiplication index (MI), microbial biomass carbon (MBC), and activities of enzymes ß-glucosidase, dehydrogenase, alkaline and acid phosphatases. The cattle manure vermicomposted shows the highest average values observed for NE, MI, TEB, MBC, and enzymatic activity, regardless of the plant leaves mix. In general, the enzymes activities were found in the descending order of ß-glucosidase > alkaline phosphatase > dehydrogenase > acid phosphatase. The maturation dynamics of vermicompost were characterized by a decline in the microbial population and number and biomass of earthworms in the substrate and consequently a decrease in new enzyme synthesis and degradation of the remaining enzyme pool. Microbial biomass and enzymatic activity were indicators for changes in the quality of vermicompost.

Effect of growth rates on hormonal and pubertal status in Nellore heifers early weaned.

This study aimed to determine the effect of growth rates on the hormonal status and puberty onset. Forty-eight Nellore heifers were weaned at 3.0 ± 0.1 (means ± standard error of the mean) months old were blocked according to body weight at weaning (84 ± 2 kg) and randomly assigned to treatments. The treatments were arranged in 2 × 2 factorial according to the feeding program. The first program was high (H; 0.79 kg/day) or control (C; 0.45 kg/day) average daily gain (ADG) from 3rd to 7th month of age (growing phase I). The second program was also high (H; 0.70 kg/day) or control (C; 0.50 kg/day) ADG from the 7th month until puberty (growing phase II), resulting in four treatments: HH (n = 13), HC (n = 10), CH (n = 13), and CC (n = 12). To achieve desired gains, heifers in high ADG program were fed ad libitum dry matter intake (DMI), and the control group was offered around 50% of ad libitum DMI of high group. All heifers received a diet with similar composition. Puberty was assessed weekly by ultrasound examination, and the largest follicle diameter was evaluated every month. Blood samples were collected to quantify leptin, insulin growth factor-1 (IGF1) and luteinizing hormone (LH). At 7 months of age, heifers in high ADG were 35 kg heavier than the control. Heifers in the HH had greater DMI compared with CH in phase II. The puberty rate at 19 months old was greater in the HH treatment (84%) than in the CC (23%), but there was no difference between HC (60%) and CH (50%) treatments. Heifers from HH treatment had greater serum leptin concentration than others at 13 months old, and serum leptin was greater in HH compared with CH and CC at 18 months old. High heifers in phase I had greater serum IGF1 concentration than the control. In addition, HH heifers had a greater diameter of the largest follicle than CC. There was no interaction between phases and age in any variable relative to the LH profile. However, the heifers' age was the main factor that increased the frequency of LH pulse. In conclusion, increasing ADG was associated with greater ADG, serum leptin and IGF-1 concentration, and puberty onset; however, LH concentration was affected mainly by age of the animal. The increasing growth rate at younger age made heifers more efficient.

Colitis caused by Clostridioides difficile infection in a domestic dog: A case report.

Clostridioides difficile has been identified as one of the primary etiologic agents of nosocomial diarrhea and pseudomembranous colitis in humans and other mammals associated following broad-spectrum antibiotics use. In Rio de Janeiro, Brazil we describe a case of C. difficile infection (CDI) in a 13-year-old male dog.

Salutogenesis in oral health research in preschool children: A scoping review.

BACKGROUND: Oral health research in children has focused both on identifying the risk factors for dental caries and on the impact the disease has on children's life. AIM: Identifying studies that used the salutogenic theory to investigate positive aspects to promote a healthy condition in preschool children. DESIGN: A literature scoping review was conducted to answer the question: 'What has been produced in scientific literature about children's oral health with a salutogenic theoretical reference?' The checklist preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) was applied. The research was conducted on the databases PubMed, Scopus, and Web of Science with no language, design, country or date restrictions. Three independent reviewers selected the studies to be included in the research, extracted data, and assessed the studies' contribution to the review. RESULTS: Among the 38 studies retained, 10 were included, those were published between 2009 and 2018: five in Brazil, two in the United States of America, and one in Canada, China and India, respectively. All articles were published in English language. Nine studies investigated the relation between the parents'/caretakers' sense of coherence and aspects related to the children's oral health condition. One study investigated health factors among the parents of caries-free children. CONCLUSION: Salutogenic orientation must be included in oral health research, so that salutary and risk factors may coexist, contributing to a new perspective for oral health promotion among children.

Prevalence of asthma, allergic rhinitis and pollinosis in a city of Brazil: A monitoring study.

BACKGROUND: Allergic respiratory diseases such as asthma and allergic rhinitis have increased considerably in the last decades. OBJECTIVE: The present study estimates prevalence trends of asthma, allergic rhinitis and pollinosis in the population of a city of Southern Brazil, without restriction of age, from 2011 to 2018, using the ISAAC standardized questionnaire. METHODS: Data was collected from March to June of 2011 and during the same months in 2018, in order to verify trends in the prevalence of these allergic conditions. The total sample consisted of 3132 individuals of both sexes living in the municipality of Santo Ângelo, in the state of Rio Grande do Sul, Brazil. RESULTS: No differences were observed in the prevalence of asthma diagnosis (15.1% in 2011 and 13.8% in 2018), however the prevalence of current wheeze was significantly reduced from 24.7% in 2011 to 21.2% in 2018 (p<0.05). Regarding allergic conditions in 2011 and in 2018, a significant reduction was observed (p<0.001) in reported current rhinitis (63.3% vs. 50.5%), rhinoconjunctivitis (48.9% vs. 38.8%), hay fever (52.0% vs. 43.3%), and pollinosis (29.0% vs 17.0%). Moreover, we observed an inverse relation between age and rhinoconjunctivitis and hay fever, and all symptoms were more frequent in females. Rhinoconjunctivitis and hay fever, as well as current rhinitis and pollinosis were highly prevalent among 30-39 years-old individuals, whereas current wheeze affected mainly the age group 10-19 years-old. CONCLUSION: While the prevalence of asthma remained similar after seven years, allergic rhinitis and pollinosis declined between 2011 and 2018.

Effectiveness of contact tracing and quarantine on reducing COVID-19 transmission: a retrospective cohort study.

OBJECTIVES: Contact tracing and quarantine are common measures used in the management of infectious disease outbreaks. However, few studies have measured their impact on the control of the COVID-19 pandemic. This study aimed to assess the effectiveness of those measures on reducing transmission of severe acute respiratory syndrome coronavirus 2 in a community setting. STUDY DESIGN: The study design is a retrospective cohort study. METHODS: A retrospective cohort study of COVID-19 cases notified in Eastern Porto from March 1st to April 30th, 2020 was performed. Intervention and control cohorts were defined based on whether cases were subjected to contact tracing and quarantine measures before the laboratory confirmation of disease. The number of secondary cases per index case and the proportion of cases with subsequent secondary cases were the primary outcomes. Secondary outcomes included the time from symptom onset to specimen collection and the number of close contacts. The analysis was stratified according to whether national lockdown measures had already been implemented. RESULTS: The intervention and control cohorts comprised 98 and 453 cases, respectively. No differences were observed concerning primary outcomes. The intervention group had a shorter time between symptom onset and specimen collection (median: 3 days, interquartile range [IQR]: 1-6, vs. median: 5 days, IQR: 2-7, P-value = 0.004) and fewer close contacts (median: 0, IQR: 0-2, vs. median: 2, IQR: 1-4, P-value<0.001). The stratified analysis returned similar results. CONCLUSION: Local public health measures were effective in reducing the time between symptom onset and laboratory diagnosis and the number of close contacts per case. No effect was apparent on secondary case figures, suggesting that further measures may be required.