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.

Trends of maxillofacial injuries resulting from physical violence in Brazil.

BACKGROUND/AIM: A large proportion of interpersonal violence results in maxillofacial injuries. The monitoring of maxillofacial injuries in the context of gender violence has been little explored. The aim of this study was to analyze trends in cases of maxillofacial injuries resulting from interpersonal physical violence considering the gender of the victim and perpetrator. MATERIALS AND METHODS: A time-series study was conducted. Data regarding maxillofacial injury cases due to interpersonal physical violence were collected from reports at a forensic institute of a city in northeastern Brazil, between 2008 and 2014 (84 months). Rates of interpersonal physical violence per 100 000 inhabitants were determined for each gender. A negative binomial regression model was used to evaluate trends. The cycle plot was used to investigate the occurrence of seasonality, considering subseries for each month. RESULTS: A total of 3561 reports were analyzed, revealing higher rates of female victims and male perpetrators throughout the series. There was no indication of seasonality. The annual percentage of injuries involving male victims reduced significantly by 6.8% (P < .001), while injuries involving female victims increased significantly by 4.5% (P = .002). Regarding perpetrators, rates remained constant over time, following the same pattern for both genders. CONCLUSIONS: The data demonstrate greater victimization involving maxillofacial injuries against women perpetrated more often by men, with a trend toward an increase in female victims and a reduction in male victims.

Contextual and individual determinants of tooth loss in adults: a multilevel study.

BACKGROUND: Tooth loss represents a known marker of health inequality. The association between tooth loss and unfavorable socioeconomic conditions is evident when analyzed at an individual level. However, the effects of contextual characteristics on tooth loss need to be better investigated and understood. The objective of this study was to analyze tooth loss among Brazilian adults (35-44 years of age), in accordance with individual and contextual social characteristics. METHODS: This was a multilevel cross-sectional study with data from 9564 adult participants from the Brazilian Oral Health Survey - SBBrasil 2010. The dependent variable was the number of lost teeth and the independent variables were grouped into structural (socioeconomic & political context) and intermediary (socioeconomic position, behavioral & biological factors, and health services) determinants. Multilevel Hierarchical Negative Binomial Regression was conducted and the Mean Ratio (MR) was estimated. RESULTS: Brazilian adults lost a mean of 7.57 (95% CI 7.1-8.1) teeth. Among the contextual variables, the number of teeth lost was higher among residents of municipalities with high and medium/low Municipal Human Development Index (MHDI) and in municipalities that did not have public water fluoridation. Among the individual variables, dental loss was higher among those who declared themselves yellow/black/brown/indigenous, were older, who had lower income, who had never visited a dentist, who had used dental services for more than a year and those whose most recent visit to the dentist was due to oral health problems. On the other hand, dental loss was lower among adults with higher education levels and males. CONCLUSIONS: The number of missing teeth was associated with unfavorable contextual and individual conditions, which reinforces the need to reduce social inequality and guarantee regular, lifetime access to dental services.

The epidemiology of Clostridioides difficile infection in Brazil: A systematic review covering thirty years.

Clostridioides difficile is considered one of the main etiological agents of bacterial diarrhea associated with the use of antibiotics. It is an important nosocomial pathogen and the main cause of morbidity and mortality. In recent years, infections associated with C. difficile have led to numerous investigations. It is well known that C. difficile associated diarrhea (CDAD) is favored by the suppression or imbalance of the intestinal microbiome during or after antibiotic therapy. Other risk factors are, for instance, advanced age, long periods of hospitalization, chemotherapy, and other gastrointestinal infections. In the 2000's, the number of CDAD cases largely increased due to the emergence of the epidemic clone named BI/NAP1 ribotype 027, responsible for causing several outbreaks in developed countries, such as Canada, the United States, and the United Kingdom. The presence of the epidemic clone has been reported in Asia, Latin America and Australia, however, infections associated with C. difficile (CDI) in these geographic regions are usually caused by other ribotypes. In Brazil, for instance, epidemiological data on the incidence of CDI are still limited, especially regarding the spread of C. difficile within hospital units, the spectrum of toxigenic genes and the antimicrobial resistance profile. Some studies have demonstrated the importance of notifying cases related to CDI and taking special care measures in order to minimize the spread of epidemic strains in Brazil. Finally, epidemiological analysis of the prevalent and/or exclusive ribotypes circulating in Brazil can contribute to understand and to correlate characteristics associated with the biology of this pathogen with other globally circulating ribotypes. This review aimed to summarize all published work related to the isolation of C. difficile from human patients in Brazil, being the main focus, the methodologies used for identification of prevalent ribotypes, the antimicrobial susceptibility profile, and the diseases associated with the acquisition of CDI.

Characterization of Clostridioides difficile ribotypes in domestic dogs in Rio de Janeiro, Brazil.

Clostridioides difficile is the major etiologic agent of nosocomial bacterial diarrhoea and pseudomembranous colitis. The pathogenesis of C. difficile infection (CDI)involves two cytotoxic enzymes (TcdA, TcdB) that cause colonic epithelial damage, fluid accumulation and enteritis. CDI has been demonstrated in a variety of animal species and some reports have recently raised the importance of wild animals as a reservoir of this pathogen and possible transmission to humans and domestic animals. The aim of this study was to characterize C. difficile isolates obtained from pet dogs in Rio de Janeiro, Brazil. A total of 50 faecal samples were obtained from healthy and diarrheic dogs. Five of fifty samples (10%) grew C. difficile. Of those, three belonged to the PCR ribotype 106 (ST 42) and were toxigenic (A+B+). The other two strains belonged to the PCR ribotype 010 (ST 15) and were not toxin producers (A-B-). None of the isolates tested positive for the binary toxin genes. Considering the antimicrobial resistance patterns of all isolates using EUCAST breakpoints, all strains were sensitive to metronidazole and vancomycin. However, two strains (ribotype 106 and ribotype 010), were resistant to clindamycin (≤256 µg/mL). All strains were strong biofilm producers. Our study provides evidence that dogs can act as reservoirs for C. difficile epidemic ribotypes.

Mothers' perception about health education in brazilian primary health care: A qualitative study.

BACKGROUND: Health education actions are strategic actions aimed at health promotion. Moreover, better health education practices have been linked to comprehensive care developed by primary health services. AIM: To understand the perception of mothers about the health education developed by the Primary Health Care (PHC) services. DESIGN: We adopted a qualitative research approach, conducted using semi-structured interviews, and assuming, as the theoretical reference, the attributes derived from PHC. Pregnant women and mothers of children under 1 year old attended by Brazilian Family Health teams were included. RESULTS: Eight pregnant women and twelve mothers of children under 1 year of age participated in the study. These mothers perceive educational actions as necessary only for primiparous mothers. They value the guidance of informal networks and maternity hospitals to the detriment of primary services, and they do not adhere to care that conflicts with their previous knowledge. The evidence shows that the educational actions of the primary health services do not adequately respond to the attributes of community orientation, family focus, and cultural competence. CONCLUSION: It is necessary to modify the educational practices in order to incorporate and value the existing knowledge in the territory, thereby adapting the care guidelines to the local context.

microRNA159-targeted SlGAMYB transcription factors are required for fruit set in tomato.

The transition from flowering to fruit production, namely fruit set, is crucial to ensure successful sexual plant reproduction. Although studies have described the importance of hormones (i.e. auxin and gibberellins) in controlling fruit set after pollination and fertilization, the role of microRNA-based regulation during ovary development and fruit set is still poorly understood. Here we show that the microRNA159/GAMYB1 and -2 pathway (the miR159/GAMYB1/2 module) is crucial for tomato ovule development and fruit set. MiR159 and SlGAMYBs were expressed in preanthesis ovaries, mainly in meristematic tissues, including developing ovules. SlMIR159-overexpressing tomato cv. Micro-Tom plants exhibited precocious fruit initiation and obligatory parthenocarpy, without modifying fruit shape. Histological analysis showed abnormal ovule development in such plants, which led to the formation of seedless fruits. SlGAMYB1/2 silencing in SlMIR159-overexpressing plants resulted in misregulation of pathways associated with ovule and female gametophyte development and auxin signalling, including AINTEGUMENTA-like genes and the miR167/SlARF8a module. Similarly to SlMIR159-overexpressing plants, SlGAMYB1 was downregulated in ovaries of parthenocarpic mutants with altered responses to gibberellins and auxin. SlGAMYBs likely contribute to fruit initiation by modulating auxin and gibberellin responses, rather than their levels, during ovule and ovary development. Altogether, our results unveil a novel function for the miR159-targeted SlGAMYBs in regulating an agronomically important trait, namely fruit set.

Cell-adhesion molecules and their soluble forms: Promising predictors of "tumor progression" and relapse in leukemia.

Some surface markers are used to discriminate certain leukemic subpopulations that retain a greater oncogenic potential than others, and, for this reason, they were termed as leukemic stem cells, similar to the concept of cancer stem cells in carcinoma. Among these surface markers are proteins involved in cell-cell adhesion or cell-matrix adhesion, and they may play a role in the relapse of leukemia, similar to metastasis in carcinomas. The most important are epithelial cadherin, neural cadherin, epithelial cell-adhesion molecule, and CD44, which can be cleaved and released, and their soluble forms were found increased in serum levels of cancer patients, being implicated, in some cases, with progression, metastases, and relapse. In this review, we highlighted the role of these four adhesion molecules in carcinomas and hematological malignancies, mainly leukemia, and discuss if the serum levels of soluble forms can be correlated with the surface protein status on the leukemic cells. Accession of the soluble forms looks attractive, but their use as markers in cancer must be studied in association with other parameters, as there are significant changes in levels in other pathological conditions besides cancer. Studies correlating the levels of the forms with the status of the membrane-bound proteins in leukemic (stem) cells and correlating those parameters with relapse in leukemia may afford important knowledge and applicability of those serum markers in clinical practice. For instance, the expression of the membrane-bound forms of these adhesion proteins may have promising clinical use in leukemia and other hematological malignancies.

p62 improves AD-like pathology by increasing autophagy.

The multifunctional protein p62 is associated with neuropathological inclusions in several neurodegenerative disorders, including frontotemporal lobar degeneration, amyotrophic lateral sclerosis and Alzheimer's disease (AD). Strong evidence shows that in AD, p62 immunoreactivity is associated with neurofibrillary tangles and is involved in tau degradation. However, it remains to be determined whether p62 also plays a role in regulating amyloid-ß (Aß) aggregation and degradation. Using a gene therapy approach, here we show that increasing brain p62 expression rescues cognitive deficits in APP/PS1 mice, a widely used animal model of AD. The cognitive improvement was associated with a decrease in Aß levels and plaque load. Using complementary genetic and pharmacologic approaches, we found that the p62-mediated changes in Aß were due to an increase in autophagy. To this end, we showed that removing the LC3-interacting region of p62, which facilitates p62-mediated selective autophagy, or blocking autophagy with a pharmacological inhibitor, was sufficient to prevent the decrease in Aß. Overall, we believe these data provide the first direct in vivo evidence showing that p62 regulates Aß turnover.

Effectiveness and safety of 0·5% colchicine cream vs. photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratosis and skin field cancerization of the forearms: a randomized controlled trial.

BACKGROUND: Skin field cancerization (SFC) is a process that occurs in areas of the skin that have undergone genomic alterations induced by ultraviolet radiation. Actinic keratosis (AK) is a sign of its activity. OBJECTIVES: To evaluate the effectiveness and safety of 0·5% colchicine (COL) cream vs. methyl aminolaevulinate photodynamic therapy (MAL-PDT) in the treatment of AK and SFC. METHODS: We conducted a randomized, open, intrasubject controlled trial. A total of 36 participants with 3-10 AKs on each forearm were treated with either COL cream (twice daily for 10 days) or a single session of MAL-PDT and were reassessed after 60 days. The clinical evaluation was performed using AK count, forearm photoageing scale (PAS) and AK degree (AKD). Patients underwent central forearm biopsies and histopathological evaluation by keratinocyte intraepithelial neoplasia (KIN) assessment, epithelial atrophy and immunohistochemistry (p53/Ki67). RESULTS: Overall, 50% of patients were male. The mean age was 70·9 years (SD 8·6) and phototypes I and II were predominant (89%). Total clearance was observed in six (17%) forearms treated with COL and seven (19%) forearms treated with MAL-PDT (P = 0·76); partial clearance was observed in 44% of forearms in the COL group and 67% of forearms in the MAL-PDT group (P = 0·07). In both COL and MAL-PDT groups, reductions in PAS (-6% vs. -6%) and AKD (-45% vs. -40%) were observed. KIN normalized in 28% of patients treated with MAL-PDT and 20% of those treated with COL. Epithelial atrophy reduced after treatment (P < 0·01). Expression levels of Ki67 and p53 were also assessed. Mild or moderate adverse effects were similar for both groups. CONCLUSIONS: COL 0·5% cream and MAL-PDT are safe and effective for treating SFC.

Biological and behavioral correlates of body weight status among rural Northeast Brazilian schoolchildren.

OBJECTIVES: The increase in the prevalence of overweight/obesity in youth is a public health problem worldwide; however, few studies have investigated its prevalence and correlates in children from the Brazilian Northeast region rural zone. The purpose of this study was (1) to estimate the prevalence of children's weight status according to sex, age, and birth weight categories; and (2) to investigate the links between biological and behavioral factors and weight categories. METHODS: The sample comprises 501 children (248 girls), aged 7-10 years, classified as low weight, normal weight, overweight, and obese using body mass index cut-points. Predicted variables included birth weight, percentage of body fat (%BF), fat free mass (FFM), physical fitness, and gross motor coordination. RESULTS: Data showed differences among weight groups for the predictor variables. Results of the logistic regression revealed that sex, age, %BF, FFM, physical fitness, and motor coordination seem to be relevant predictors of children's weight status, while no significant effect was observed for birth weight. CONCLUSION: Children with lower physical fitness levels as well as those with lower motor coordination quotient are more likely to be overweight and/or obese. No significant relationship was observed between birth weight and weight status in childhood. Strategies to reduce childhood obesity should consider biological, behavioral, and also environmental predictors.