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The hypomethylating agent 5-azacytidine (AZA) is the first-line treatment for AML patients unfit for intensive chemotherapy. The effect of AZA results in part from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) deriving from hypermethylated genomic regions such as cancer-testis antigens (CTAs), or endogenous retroelements (EREs). However, evidence supporting higher ERE MAPs presentation after AZA treatment is lacking. Therefore, using proteogenomics, we examined the impact of AZA on the repertoire of MAPs and their source transcripts. AZA-treated AML upregulated both CTA and ERE transcripts, but only CTA MAPs were presented at greater levels. Upregulated ERE transcripts triggered innate immune responses against double-stranded RNAs but were degraded by autophagy, and not processed into MAPs. Autophagy resulted from the formation of protein aggregates caused by AZA-dependent inhibition of DNMT2. Autophagy inhibition had an additive effect with AZA on AML cell proliferation and survival, increased ERE levels, increased pro-inflammatory responses, and generated immunogenic tumor-specific ERE-derived MAPs. Finally, autophagy was associated with a lower abundance of CD8+ T-cell markers in AML patients expressing high levels of EREs. This work demonstrates that AZA-induced EREs are degraded by autophagy and shows that inhibiting autophagy can improve the immune recognition of AML blasts in treated patients.

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Objective: To identify beliefs and knowledge about tummy time (TT) practice and its repercussions on motor development. Methods: Longitudinal study carried out with parents/caregivers of infants older than 30 days of life. Two assessments were performed. A structured interview was conducted, while the babies were between one and six months old to identify beliefs, knowledge about TT, and the motor milestone achievement expected for the age. At six to 12 months, the risk of motor development delay was tracked using the survey of well-being of young infant questionnaire (SWYC). Results: 41 families responded to the SWYC questionnaire (21 were allocated to the TT group). 31.70% reported that it was not important to put the infants in a prone position while awake, and 70.70% said they are afraid their babies would become breathless when positioned in a prone position. 85.70% of infants from the TT group showed typical development, while 55% of the control group showed atypical development for their age (p = 0.01). Only three infants from the control group were at risk of delayed motor development (p = 0.10). Conclusions: Most of the families feel insecure about proning their babies and fear breathlessness when positioned. Acquisition of motor milestones prevailed in the TT group, suggesting an association between TT practice and motor milestone achievement.

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BACKGROUND: Mosquito species from the Anopheles gambiae complex and the Anopheles funestus group are dominant African malaria vectors. Mosquito microbiota play vital roles in physiology and vector competence. Recent research has focused on investigating the mosquito microbiota, especially in wild populations. Wild mosquitoes are preserved and transported to a laboratory for analyses. Thus far, microbial characterization post-preservation has been investigated in only Aedes vexans and Culex pipiens. Investigating the efficacy of cost-effective preservatives has also been limited to AllProtect reagent, ethanol and nucleic acid preservation buffer. This study characterized the microbiota of African Anopheles vectors: Anopheles arabiensis (member of the An. gambiae complex) and An. funestus (member of the An. funestus group), preserved on silica desiccant and RNAlater® solution. METHODS: Microbial composition and diversity were characterized using culture-dependent (midgut dissections, culturomics, MALDI-TOF MS) and culture-independent techniques (abdominal dissections, DNA extraction, next-generation sequencing) from laboratory (colonized) and field-collected mosquitoes. Colonized mosquitoes were either fresh (non-preserved) or preserved for 4 and 12 weeks on silica or in RNAlater®. Microbiota were also characterized from field-collected An. arabiensis preserved on silica for 8, 12 and 16 weeks. RESULTS: Elizabethkingia anophelis and Serratia oryzae were common between both vector species, while Enterobacter cloacae and Staphylococcus epidermidis were specific to females and males, respectively. Microbial diversity was not influenced by sex, condition (fresh or preserved), preservative, or preservation time-period; however, the type of bacterial identification technique affected all microbial diversity indices. CONCLUSIONS: This study broadly characterized the microbiota of An. arabiensis and An. funestus. Silica- and RNAlater®-preservation were appropriate when paired with culture-dependent and culture-independent techniques, respectively. These results broaden the selection of cost-effective methods available for handling vector samples for downstream microbial analyses.

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Fundamento: Síndrome metabólica é um importante fator de risco cardiovascular, e sua prevalência aumenta após a menopausa. Ainda é incerto, porém, se a menopausa é fator de risco independente para a síndrome metabólica. Uma das bases fisiopatológicas para síndrome metabólica é a resistência insulínica, que pode ser calculada pelo método Homeostatic Model Assessment-Insulin Resitance (HOMA-IR), sendo pouco conhecida a relação entre resistência insulínica e menopausa. Objetivos: Avaliar a relação entre síndrome metabólica e resistência insulínica em mulheres climatéricas. Métodos: Estudo descritivo, que avaliou 150 mulheres, com idades entre 40 e 65 anos, atendidas em um ambulatório de ginecologia em um hospital terciário público, entre maio e dezembro de 2013. A amostra foi dividida em dois grupos, sendo o Grupo I com pacientes na pré-menopausa e o II com pacientes na pós-menopausa. Foi avaliada a presença de síndrome metabólica, bem como de seus componentes, além da ocorrência de resistência insulínica nos dois grupos. A associação do estado menopausal e as variáveis estudadas foi realizada com os testes Mann-Whitney, qui quadrado e exato de Fisher. O nível de significância foi de 5%. A análise estatística foi feita por meio do STATA 12.0. Resultados: A síndrome metabólica foi mais prevalente nas mulheres pós-menopausa, bem como todos seus componentes tiveram maior frequência também nesse grupo. As mulheres pós-menopausa também apresentaram maior prevalência de resistência insulínica, mas não foi observada relação estatística entre os achados. Conclusão: O estado menopausal não se associou significativamente com síndrome metabólica e resistência insulínica. A resistência insulínica foi considerada fator de risco independente para o desenvolvimento de síndrome metabólica apenas no grupo pós-menopausa

Background: Metabolic syndrome is an important cardiovascular risk factor, and its prevalence increases after menopause. However, it is still uncertain whether menopause is an independent risk factor for metabolic syndrome. One of the pathophysiological basis for metabolic syndrome is insulin resistance, which can be calculated by the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) method, and the association between insulin resistance and menopause is little known. Objective: To evaluate the association between metabolic syndrome and insulin resistance in menopausal women. Method: Descriptive study, which evaluated 150 women, aged 40 to 65, treated at a Gynecology Outpatient Clinic of a tertiary public hospital, from May to December of 2013. The sample was divided into two groups: Group I, comprising women in the premenopausal period and Group II, comprising women in the post-menopausal period. The presence of metabolic syndrome and its components were evaluated, as well as occurrence of insulin resistance in both groups. The association of menopausal status and the assessed variables was assessed using the Mann-Whitney, Chi-square and Fisher's exact tests. The significance level was set at 5%. The statistical analysis was performed using STATA 12.0. Results: Metabolic syndrome and its components were more prevalent in postmenopausal women. Postmenopausal women also had a higher prevalence of insulin resistance, but no statistical association was observed between the findings. Conclusion: The menopausal status was not significantly associated with metabolic syndrome and insulin resistance. Insulin resistance was considered an independent risk factor for the development of metabolic syndrome only in the postmenopausal group

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The current study has assessed whether the oral and/or dermal exposure of C57Bl/6 J mice to tannery effluent (a complex pollutant consisting of xenobiotic mixtures) could damage their olfactory functions, as well as whether it changes their aversive behavior in the inhibitory avoidance test. Accordingly, the animals were distributed in groups which were exposed or not to this xenobiotic through two different routes (oral and dermal), for 15 days. The effluent group subjected to oral exposure received drinking water containing 5% tannery effluent, whereas the animals in the dermal group were exposed to raw tannery effluent for 1 h/day. The animals dermally exposed to the tannery effluent (males and females) have shown the highest latency to find palatable food in the buried food test. The shortest time spent by the animals (orally or dermally) exposed to tannery effluent in the safety zone of the apparatus used in the predator exposure test, as well as the longest time spent by them in the aversive zone, have shown failures in their perception to the risk represented by the presence of the predator (cat). The passive avoidance test results have shown that the dermal exposure to tannery effluent led to partial memory deficit in male and female mice; therefore, the present study has confirmed the tannery effluent toxicity to mammals. Moreover, the present study was pioneer in demonstrating that the dermal exposure to this xenobiotic, even for a short period-of-time, can change the olfactory and cognitive functions of animals, as well as lead to harmful consequences to their health.

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Previous studies involving the oral exposure of mice to tannery effluents have found neurotoxic effects. However, studies about the effects the dermal exposure to pollutant have on the cognitive function of females have not been found in the literature. Thus, the aim of the current study is to investigate whether the dermal exposure of female Swiss mice to tannery effluents (2 h/day for 20 days) can cause cognitive impairment, as it was already evidenced in male Swiss mice. Furthermore, based on the administration of vitamin C (before or after the exposure to the xenobiotic), the current study also aims to assess the protective effect of vitamin C in female Swiss mice dermally-exposed to the tannery effluent. Female Swiss mice exposed to the tannery effluent (without vitamin supplementation) have shown lower novel object recognition index during the test session of the novel object recognition task, and they have descended significantly faster from the inhibitory avoidance platform when they were compared to mice belonging to the other groups, therefore evidencing memory deficit. However, the test performance of females receiving vitamin C was similar to that of control animals. Thus, the current study confirms the initial hypothesis that the dermal exposure to the pollutant, even for a short period, causes cognitive deficit in female Swiss mice. The herein presented findings also provide evidence that the mechanisms of action of the tannery effluent in these animals are related to oxidative damages in specific brain regions directed to the formation of short memory to perform aversive and object recognition tasks.

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The main aim of the present paper is to assess whether the parental generation exposure to such discharges could cause object recognition deficits in their offspring. Male and female C57Bl/6J mice were put to mate after they were exposed to 7.5% and 15% tannery effluents or water (control group), for 60 days. The male mice were withdrawn from the boxes after 15 days and the female mice remained exposed to the treatment during the gestation and lactation periods. The offspring were subjected to the object recognition test after weaning in order to assess possible cognition losses. The results of the analysis of the novel object recognition index found in the testing session (performed 1 h after the training session) applied to offspring from different experimental groups appeared to be statistically different. The novel object recognition index of the offspring from female mice exposed to tannery effluents (7.5% and 15% groups) was lower than that of the control group, and it demonstrated object recognition deficit in the studied offspring. The present study is the first to report evidences that parental exposure to effluent of tannery (father and mother) can cause object recognition deficit in the offspring, which is related to problems in the central nervous system.

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Tannery effluents constitute highly polluting residues, which can cause negative impacts to people's health and the environment. However, studies that have investigated the effects of the exposure to these xenobiotics on the central nervous system of mammal experimental models are rare, the few that have been published focusing on the exposure via oral intake (ingestion of water containing tannery effluent concentrations). In this sense, and with the objective of expanding the knowledge beyond the neurotoxic effects observed when water contaminated by these xenobiotics is ingested, the neurobehavioral effects of dermal exposure of male C57Bl/6J and Swiss mice were analyzed. The animals were exposed to raw (wet blue-type) tannery effluent for two hours during five days, totalizing 15 days of exposure. Afterwards, the animals underwent the elevated plus-maze (predictive of anxiety) and the object recognition tests (identification of memory deficit). Our data show that the dermal exposure to the tannery effluent caused an anxiogenic behavior in these animals, when compared those that did not have direct contact with these xenobiotics. It was also observed that the animals exposed to the tannery effluent obtained lower novel object recognition indices, thus evidencing memory deficit and indicating a possible influence of the tannery effluent constituents in animal cognition. The present study attests the hypothesis that dermal exposure to tannery effluents containing neurotoxic substances causes behavioral disorders in C57Bl/6J and Swiss mice.

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Although it is known that tannery effluents constitute highly toxic pollutants whose effects in humans represent public health problems in several countries, studies involving experimental mammalian models are rare. In this context, the objective of the present study was to assess the effect of the exposure to tannery effluent on the memory of male and female Swiss mice. Animals of each sex were distributed into two experimental groups: the control group, in which the animals received only drinking water and the effluent group, in which the mice received 1% of gross tannery effluent diluted in water. The animals were exposed to the effluent by gavage, oral dosing, for 15days, ensuring the administration of 0.1mL of liquid (water or effluent)/10g of body weight/day. On the 14th and 15th experimental days the animals were submitted to the object recognition test. It was observed that the new object recognition indices calculated for the animals exposed to the effluent (males and females) were significantly lower than those obtained with the control group. The exposure to tannery effluent caused memory deficit in Swiss mice in a similar way for both sexes, reinforcing previous findings that these pollutants affect the central nervous system. It contributes to the knowledge in the area by attesting harmful effects to the cognition of such animals.

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