Dietary Fiber Drives IL-1ß-Dependent Peritonitis Induced by Bacteroides fragilis via Activation of the NLRP3 Inflammasome.

Intestinal barrier is essential for dietary products and microbiota compartmentalization and therefore gut homeostasis. When this barrier is broken, cecal content overflows into the peritoneal cavity, leading to local and systemic robust inflammatory response, characterizing peritonitis and sepsis. It has been shown that IL-1ß contributes with inflammatory storm during peritonitis and sepsis and its inhibition has beneficial effects to the host. Therefore, we investigated the mechanisms underlying IL-1ß secretion using a widely adopted murine model of experimental peritonitis. The combined injection of sterile cecal content (SCC) and the gut commensal bacteria Bacteroides fragilis leads to IL-1ß-dependent peritonitis, which was mitigated in mice deficient in NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome components. Typically acting as a damage signal, SCC, but not B. fragilis, activates canonical pathway of NLRP3 promoting IL-1ß secretion in vitro and in vivo. Strikingly, absence of fiber in the SCC drastically reduces IL-1ß production, whereas high-fiber SCC conversely increases this response in an NLRP3-dependent manner. In addition, NLRP3 was also required for IL-1ß production induced by purified dietary fiber in primed macrophages. Extending to the in vivo context, IL-1ß-dependent peritonitis was worsened in mice injected with B. fragilis and high-fiber SCC, whereas zero-fiber SCC ameliorates the pathology. Corroborating with the proinflammatory role of dietary fiber, IL-1R-deficient mice were protected from peritonitis induced by B. fragilis and particulate bran. Overall, our study highlights a function, previously unknown, for dietary fibers in fueling peritonitis through NLRP3 activation and IL-1ß secretion outside the gut.

The Brazilian national prospective active surveillance (AS) cohort of patients with low-risk prostate cancer in the public health system: vigiaSUS study protocol.

BACKGROUND: Prostate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system. METHODS: This is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/ml, will be enrolled. Archival prostate cancer tissue will be centrally reviewed. Patients enrolled in the study will follow the AS strategy, which involves PSA and physical examination every 6 months as well as multiparametric MRI (mpMRI) every two years and prostate biopsy at month 12 and then every two years. The primary objective is to evaluate the reclassification rate at 12 months, and secondary objectives include determining the treatment-free survival rate, metastasis-free survival, and specific and overall survival. Exploratory objectives include the evaluation of quality of life and anxiety, the impact of PTEN loss and the economic impact of AS on the Brazilian public health system. DISCUSSION: This is the first Brazilian prospective study of patients with low-risk prostate cancer under AS. To our knowledge, this is one of the largest AS study cohort with a majority of nonwhite patients. We believe that this study is an opportunity to better understand the outcomes of AS in populations underrepresented in studies. Based on these data, an AS national clinical guideline will be developed, which may have a beneficial impact on the quality of life of patients and on public health. TRIAL REGISTRATION: Clinicaltrials registration is NCT05343936.

Validation of stability-indicating LC method, degradation study, and impact on antioxidant and antifungal activities of Eugenia uniflora leaves extract.

The aim of this study is to demonstrate the stability-indicating capacity of an analytical method for Eugenia uniflora, enhance understanding of the stability of myricitrin, and assess the effect of degradation of spray-dried extract (SDE) on antioxidant and antifungal activities. Validation of the stability-indicating method was carried out through a forced degradation study of SDE and standard myricitrin. The antioxidant and antifungal activities of SDE were evaluated both before and after degradation. The quantification method described was found to be both accurate and precise in measuring myricitrin levels in SDE from E. uniflora, with excellent selectivity that confirmed its stability-indicating capability. The forced degradation study revealed that the marker myricitrin is sensitive to hydrolysis, but generally stable under other stress conditions. By contrast, the standard myricitrin displayed greater susceptibility to degradation under forced degradation conditions. Analysis of the antioxidant activity of SDE before and after degradation showed a negative impact in this activity due to degradation, while no significant effect was observed on antifungal activity. The method described can be a valuable tool in the quality control of E. uniflora, and the findings can assist in determining the optimal conditions and storage of products derived from this species.

Chromosome diversity in Buthidae and Chactidae scorpions from Brazilian fauna: Diploid number and distribution of repetitive DNA sequences.

In this work, we analyzed cytogenetically eight Chactidae and Buthidae, including the localization of repetitive DNA sequences. The chactids possess monocentric chromosomes and the highest diploid numbers (2n=50 in Brotheas amazonicus, 2n=36 in Chactopsis amazonica, 2n=30 in Neochactas sp.) when compared with buthids (2n=10 in Tityus bahiensis, 2n=14 in Tityus apiacas and Tityus metuendus, 2n=18 in Tityus aba, 2n=26 in Ischnotelson peruassu). The localization of rDNA genes and (TTAGG)n sequences exhibited a conserved pattern of two terminal/subterminal ribosomal cistrons and terminal telomere signals. However, the comparison between the data of C-banding, DAPI after FISH and Cot-DNA fraction indicated a variable quantity and distribution of these regions, as follow: (i) positive heterochromatin and Cot-DNA signals (B. amazonicus and I. peruassu), (ii) small blocks of heterochromatin with large Cot-DNA signals (T. metuendus), (iii) positive heterochromatic regions and absence of Cot-DNA signals (T. aba and T. apiacas), and (iv) negative heterochromatin and Cot-DNA signals (T. bahiensis). Therefore, our results revealed that there still is not a clear relation between quantity of heterochromatin and presence of monocentric or holocentric chromosomes and occurrence of chromosomal rearrangements, indicating that repetitive regions in scorpions must be analyzed using different cytogenetic approaches.

Low transmission rates of Equine infectious anemia virus (EIAV) in foals born to seropositive feral mares inhabiting the Amazon delta region despite climatic conditions supporting high insect vector populations.

BACKGROUND: Marajó Island, within in the Amazon River Delta, supports numerous bands of feral equids including the genetically distinct Marajoara horses. Approximately 40% of the equids on the island are infected with Equine infectious anemia virus (EIAV). This high seropositivity rate coupled with the need to preserve rare breeds such as the Marajoara horse precludes euthanasia as the primary means for controlling EIAV in this region. In the absence of iatrogenic transmission, spread of this lentivirus is mediated primarily by hematophagous insects, whose year-round prevalence on the island is supported by favorable climatic conditions. In addition, cases of vertical EIAV transmission have been observed suggesting inclusion of seropositive mares in restorative breeding programs could result in their progeny becoming infected with this virus either pre-parturition or post-partum via hematophagous insects. Therefore, the aim of this study was to evaluate EIAV vertical and post-partum insect-mediated transmission rates among foals born to seropositive feral mares until natural weaning. Serum samples from foals born to seropositive feral mares within the Soure municipality, of Marajó Island, were collected to investigate their serological status, using an indirect ELISApgp45, with positive samples confirmed using the classical agar gel immunodiffusion (AGID) assay. RESULTS: The serological status of 28 foals were monitored over a 2-year period with some subjects, depending on their date of birth, being sampled up to six times. All foals remained with their respective mares until fully weaned at approximately 10 months of age. Only 2 foals (7.14%) in the study group became seropositive against EIAV. CONCLUSION: The results demonstrate that in most cases it is possible to obtain seronegative foals born to and eventually weaned by EIA positive mares, even in equatorial regions where substantial rainfall and high temperatures favor the proliferation of insect vectors.

A machine learning proposal method to detect milk tainted with cheese whey.

Cheese whey addition to milk is a type of fraud with high prevalence and severe economic effects, resulting in low yield for dairy products, nutritional reduction of milk and milk-derived products, and even some safety concerns. Nevertheless, methods to detect fraudulent addition of cheese whey to milk are expensive and time consuming, and are thus ineffective as screening methods. The Fourier-transform infrared (FTIR) spectroscopy technique is a promising alternative to identify this type of fraud because a large number of data are generated, and useful information might be extracted to be used by machine learning models. The objective of this work was to evaluate the use of FTIR with machine learning methods, such as classification tree and multilayer perceptron neural networks to detect the addition of cheese whey to milk. A total of 520 samples of raw milk were added with cheese whey in concentrations of 1, 2, 5, 10, 15, 20, 25, and 30%; and 65 samples were used as control. The samples were stored at 7, 20, and 30°C for 0, 24, 48, 72, and 168 h, and analyzed using FTIR equipment. Complementary results of 520 samples of authentic raw milk were used. Selected components (fat, protein, casein, lactose, total solids, and solids nonfat) and freezing point (°C) were predicted using FTIR and then used as input features for the machine learning algorithms. Performance metrics included accuracy as high as 96.2% for CART (classification and regression trees) and 97.8% for multilayer perceptron neural networks, with precision, sensitivity, and specificity above 95% for both methods. The use of milk composition and freezing point predicted using FTIR, associated with machine learning techniques, was highly efficient to differentiate authentic milk from samples added with cheese whey. The results indicate that this is a potential method to be used as a high-performance screening process to detected milk adulterated with cheese whey in milk quality laboratories.

Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Associated with Bacteremia and Monocyte Evasion, Rio de Janeiro, Brazil.

We typed 600 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 51 hospitals in the Rio de Janeiro, Brazil, metropolitan area during 2014-2017. We found that multiple new clonal complex (CC) 5 sequence types had replaced previously dominant MRSA lineages in hospitals. Whole-genome analysis of 208 isolates revealed an emerging sublineage of multidrug-resistant MRSA, sequence type 105, staphylococcal cassette chromosome mec II, spa t002, which we designated the Rio de Janeiro (RdJ) clone. Using molecular clock analysis, we hypothesized that this lineage began to expand in the Rio de Janeiro metropolitan area in 2009. Multivariate analysis supported an association between bloodstream infections and the CC5 lineage that includes the RdJ clone. Compared with other closely related isolates, representative isolates of the RdJ clone more effectively evaded immune function related to monocytic cells, as evidenced by decreased phagocytosis rate and increased numbers of viable unphagocytosed (free) bacteria after in vitro exposure to monocytes.

Effects of gonadotropin inducible ovarian transcription factor 1 in the paraventricular nucleus on fluid intake after dehydration of ovariectomized female rats.

NEW FINDINGS: What is the central question of this study? Giot1, the gene for gonadotropin inducible ovarian transcription factor 1 (GIOT1), is upregulated in osmotically challenged rats: does Giot1 gene expression in the paraventricular nucleus have a role in controlling fluid intake following dehydration and what is the role of ovarian hormones in the modulation of GIOT1 actions? What is the main finding and its importance? GIOT1 acts to regulate water and salt intake as well as hormone secretion after dehydration. The identification of genes that participate in the hormone and behavioural responses involved with hydromineral homeostasis is essential for future exploration of novel drug targets for the treatment of metabolic disease. ABSTRACT: In order to maintain body fluid balance after dehydration, hypothalamic neurons of the paraventricular nucleus (PVN) are activated to promote secretion of vasopressin (AVP) and oxytocin (OXT) from the neurohypophysis, and to modulate the behavioural allostatic responses of thirst and salt appetite. Gonadotropin inducible transcription factor (GIOT1) is a Krüppel-type zinc finger protein induced by gonadotropins and oestradiol (E2). This transcription factor is expressed in the hypothalamus, specifically in the PVN where expression of Giot1 mRNA increases following hydromineral challenges such as water deprivation or salt loading, although its physiological role is not clear. We hypothesize that GIOT1 has a central role in the integrated homeostatic and allostatic responses to disturbances in hydromineral balance, especially in the presence of female gonadal hormones. Female rats with intact ovaries or ovariectomized rats were subjected to specific microinjection of a lentiviral vector mediating Giot1 knockdown in the PVN. Three weeks after injection, rats were subjected to 48 h water deprivation, and thereafter water and salt intake were evaluated. Giot1 knockdown in PVN reduced water and saline intake as well as AVP and OXT secretion. Furthermore, Giot1 knockdown had profound effects on gene expression in the PVN, reducing the abundance of transcripts encoded by the Avp, Oxt, Nr4a1 and Crh genes. In conclusion, the present study shows for the first time that GIOT1 in the PVN regulates both transcription and fluid intake, although any connection to ovarian hormones remains to be established.

Factors influencing the patient safety climate in intensive care units: cross-sectional study.

BACKGROUND: Measuring the patient safety climate of a health service provides important information about the safety status at a given time. This study aimed to determine the factors influencing the patient safety climate in Intensive Care Units. METHODS: An analytical and cross-sectional study conducted in 2017 and 2018 in two adult Intensive Care Units of a Brazilian Teaching Hospital. The Safety Attitudes Questionnaire instrument was applied with the multidisciplinary teams to determine the factors influencing the patient safety climate. Data were double entered into a database and processed using the R (version 3.5.0) statistical software. Position, central tendency and dispersion measures were taken and absolute and relative frequencies, mean and confidence intervals were calculated for the quantitative variables. Linear regression was performed to verify the effect of variables on the SAQ domains. Variables with a p-value of less than 0.25 were selected for multivariate analysis. RESULTS: A total of 84 healthcare providers participated in the study. The mean Safety Attitudes Questionnaire score was 59.5, evidencing a negative climate. The following factors influenced the safety climate: time since course completion, professional category, type of employment contract, complementary professional training, and weekly workload. CONCLUSIONS: The factors identified indicate items for planning improvements in communication, teamwork, work processes, and management involvement, aiming to ensure care safety and construct a supportive safety climate.

Risk of Zika virus-associated birth defects in congenital confirmed cases in the Brazilian Amazon.

OBJECTIVE: To establish the risk of microcephaly in neonates born to women infected with ZIKV during pregnancy. METHODS: A cohort of laboratory-confirmed ZIKV cases of congenital infections (109 mothers infected during pregnancy and 101 newborns) among 308 suspect cases was followed in Belem, Pará, Brazil, from October 2015 to December 2017. RESULTS: A microcephaly risk of 1.98% (95% CI 0.54-6.93%) was found, or 2 cases among the 101 neonates infected with ZIKV during pregnancy. 72% of the pregnant women had ZIKV infection confirmed by RT-qPCR during gestation. CONCLUSIONS: Results showed a low incidence of ZIKV-associated birth defects, stillbirth, and miscarriage, which contrasts with previous studies in other Brazilian regions. Previous exposure to yellow fever vaccine and/or multiserotype DENV infection could be implicated in the protection from ZIKV congenital infection.

OBJETIVO: Establecer el riesgo de microcefalia en los recién nacidos de mujeres infectadas con ZIKV durante el embarazo. MÉTODOS: Se siguió a una cohorte de casos con infección congénita por ZIKV confirmada por laboratorio (109 madres infectadas durante el embarazo, 101 recién nacidos) conformada a partir de 308 casos sospechosos en Belem, Pará, Brasil, de octubre de 2015 a diciembre de 2017. RESULTADOS: Se encontró un riesgo de microcefalia de 1,98% (IC95% 0,54-6,93%), o 2 casos entre los 101 neonatos infectados con ZIKV durante el embarazo. En el 72% de las mujeres embarazadas se confirmó mediante RT-qPCR la infección por ZIKV durante la gestación. CONCLUSIONES: Los resultados mostraron una baja incidencia de malformaciones congénitas, mortinatos y abortos asociados al ZIKV, lo que contrasta con estudios anteriores de otras regiones de Brasil. La exposición previa a la vacuna contra la fiebre amarilla o la infección previa por varios serotipos de virus del dengue podrían estar implicados en la protección contra la infección congénita por ZIKV.

Influence of surface treatment on the fluorescence of composite resins subjected to in situ bleaching.

OBJECTIVE: Use fluorescence analysis to evaluate the effect of polishing and surface sealant on the color of composite resin bleached with carbamide peroxide and subjected to staining. MATERIALS AND METHODS: Forty-eight composite resin specimens (Z250/Z350XT) were fabricated. After 24 hours stored in distilled water, all specimens were submitted to in situ bleaching with 16% home peroxide for 8 hours daily for a period of 14 days. Subsequently specimens were separated in three groups according to surface treatment proposed (group 1-polishing Sof-Lex; group 2-BisCover; group 3-control). After this, all the specimens were stained with red wine. A spectrofluorometer was used to evaluate the fluorescence in two readouts (L0-after surface treatment and L1-after staining).Data were analyzed by applying ANOVA using a statistical software program. RESULTS: No differences were shown for the factor treatment and other interactions. The lowest mean fluorescence value was found for Z350XT resin (1759.18 ± 0.13) when compared with Z250 (6863.92 ± 0.13). There was significant difference in the mean fluorescence values for all surface treatments between the two different readouts L0 (4820.93 ± 0.05) and L1 (3802.17 ± 0.05). CONCLUSION: The results suggested that all surface treatments proposed did not influenced the results of wine staining of bleached resins when compared with the control evaluated by the fluorescence method. CLINICAL SIGNIFICANCE: The purposes of this research was to find solutions, by means of surfaces treatment, to achieve restorations with a satisfactory and similar final aspect in relation to the teeth, and avoid discrepancies related to the esthetics and longevity of the restoration.

Synthetic (E)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1.

Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a-d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC50 values of all compounds in the range of 1.51-7.70 M in HTLV-1-infected and non-infected cells. Furthermore, it was observed that 5b could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for 5b could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (5a-d) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:5a-d is spontaneous and moderate (Ka ~ 104 M-1) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream.

Characterization of Triniti virus supports its reclassification in the family Peribunyaviridae.

Triniti virus (TNTV) has been isolated in Trinidad and Tobago and in Brazil. To date little is known about this virus, which is classified as an ungrouped virus within the family Togaviridae. Here, three isolates of TNTV were characterized both genetically and antigenically. The genome was shown to contain three RNA segments: small (S), medium (M) and large (L). Genome organization, protein sizes and protein motifs were similar to those of viruses in the genus Orthobunyavirus, family Peribunyaviridae. Antigenic reactivity revealed the three TNTV isolates to be closely related, but no serologic cross-reaction with other orthobunyaviruses. Morphological observation by transmission electron microscopy indicated that virus size and symmetry were compatible with those of viruses in the family Peribunyaviridae. Our serological, morphological and molecular results support the taxonomic reclassification of TNTV as a member of the genus Orthobunyavirus, family Peribunyaviridae.

In vitro and in vivo cytotoxic activity and human serum albumin interaction for a methoxy-styryl-thiosemicarbazone.

Thiosemicarbazone is a class of compounds with potential applications in medicine, presenting high capacity to inhibit the growth of cancer cells as well as low toxicity. Because of high interest in anticancer studies involving thiosemicarbazones as new chemotherapeutic agents, a synthetic thiosemicarbazone derivative, 4-N-(2'-methoxy-styryl)-thiosemicarbazone (MTSC) was evaluated in vivo against Ehrlich carcinoma in an animal model. In vivo results demonstrated that MTSC treatment induced the survival of mice and altered significantly the body weight of the surviving mice 12 days after tumor inoculation. Treatment with 30 mg/kg of MTSC exhibited effective cytotoxic activity with T/C values of 150.49% (1 dose) and 278% (2 doses). Its interaction with human serum albumin (HSA), which plays a crucial role in the biodistribution of a wide variety of ligands, was investigated by multiple spectroscopic techniques at 296 K, 303 K, and 310 K, as well as by theoretical calculations. The interaction between HSA and MTSC occurs via ground-state association in the subdomain IIA (Sudlow's site I). The binding is moderate (Ka ≈ 104 M-1), spontaneous, entropically, and enthalpically driven. Molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces. Overall, the interaction HSA:MTSC could provide therapeutic benefits, improving its cytotoxic efficacy and tolerability.

An improved immobilized enzyme reactor-mass spectrometry-based label free assay for butyrylcholinesterase ligand screening.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are key cholinesterase enzymes responsible for the hydrolysis of acetylcholine into choline and acetic acid, an essential process for the restoration of the cholinergic neuron. The loss of cholinergic function in the central nervous system contributes to the cognitive decline associated with advanced age and Alzheimer's disease (AD). Inhibitions assays represent a significant role in the drug discovery process. Herein, we describe an improved label free method to screen and characterize new BChE ligands. The liquid chromatography system uses an immobilized capillary enzyme reactor (ICER) as a low affinity and high selectivity column coupled to a mass spectrometer (MS). The enzyme activity was evaluated by monitoring the choline's precursor ion [M + H]+m/z 104 for a brief period. The method was validated using two known cholinesterase inhibitors tacrine and galanthamine. The IC50 values were 0.03 ±â€¯0.006 µM and 0.88 ±â€¯0.2 for tacrine and galanthamine respectively, and Ki was 0.11 ±â€¯0.2 for galanthamine. The efficient combination of the huBChE-ICER with sensitive enzymatic assay detection such as MS, improved the reliable, fast identification of new ligands. Moreover, specific direct quantitation of the product contributes to the reduction of false positive and negative results.

Effect of lanthanum loading on nanosized CeO2-ZnO solid catalysts supported on cordierite for diesel soot oxidation.

We report the application of a solid lanthanum-ceria-zinc catalyst in the catalytic regeneration of diesel particulate filters (DPF) in diesel engines. We synthesized a CeO2-ZnO-La2O3 (Ce-Zn-La) mixed oxide by a lactic acid-mediated sol-gel method, which efficiently coated cordierite substrates for soot capture and combustion. We studied the effects of La loading on the physicochemical and catalytic properties of Ce-Zn mixed oxide during low-temperature soot combustion processes. We characterized the synthesized catalysts by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), N2 adsorption, Raman spectroscopy, oxygen storage capacity (OSC), and scanning and transmission electron microscopy (SEM and TEM). Thermogravimetric and differential thermal analysis (TGA/DTA) confirmed that the catalysts effectively reduced the soot oxidation temperature. The ternary Ce-Zn-La mixed oxide catalyst with Ce/Zn/La atomic ratio of 2:1:0.5 had the highest catalytic activity and promoted soot oxidation at temperatures below 390°C. This indicated that the large number of oxygen vacancies in the catalyst structure generated oxygen species at low temperatures. Raman spectroscopy measurements revealed the presence of oxygen vacancies and lattice defects in Ce-Zn-La samples, which were key parameters concerning the stability and redox properties of the prepared catalysts.

Characterization of the Bujaru, frijoles and Tapara antigenic complexes into the sandfly fever group and two unclassified phleboviruses from Brazil.

The genus Phlebovirus includes the sandfly fever viruses and tick-transmitted uukuviruses. Sandfly fever group viruses have been isolated from various vertebrate species and from phlebotomines and occasionally alternative arthropods, e.g. mosquitoes, or ceratopogonids of the genus Culicoides. Uukuniemi serogroup viruses have been isolated from various vertebrate species and from ticks. Despite the public health importance of some viruses of the genus, the genomic diversity of phleboviruses that could be incriminated as causative of human or veterinary diseases remains underestimated. Here we describe the nearly complete sequences and genomic characterization of two phleboviruses belonging to the Bujaru antigenic complex: the prototype species and the Munguba virus. Furthermore, six previously unclassified phleboviruses isolated in Brazil were also sequenced and characterized: Ambe, Anhanga, Joa, Uriurana, Urucuri and Tapara viruses. The results of the phylogenetic analysis indicated that these viruses group with viruses of three antigenic complexes (Bujaru, Tapara and frijoles clades), with two unclassified phleboviruses. We also performed genomic reassortment analysis and confirmed that there were no events for the viruses described in this study, but we found a new potential reassortment in Medjerda Valley virus, which contains S and L segments of Arbia virus, and probably a unique M segment, both viruses circulate in the same geographic region, indicating these two isolates represent two distinct viruses. This study provides insights into the genetic diversity, classification and evolution of phleboviruses.

Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats.

NEW FINDINGS: What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l-1 ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day-1 , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and glycogen accumulation. Furthermore, exercise improved the response to the deleterious effects of HFr overload by normalizing the gluconeogenesis pathway and the protein levels of interleukin-6 and tumour necrosis factor-α. The HFr rats displayed increased hepatic ACE activity and protein expression and angiotensin II concentration, which were attenuated by exercise training. Exercise training restored the ACE2/angiotensin-(1-7)/Mas receptor axis. Exercise training may favour the counter-regulatory ACE2/angiotensin-(1-7)/Mas receptor axis over the classical RAS (ACE/angiotensin II/angiotensin II type 1 receptor axis), which could be responsible for the reduction of metabolic dysfunction and the prevention of non-alcoholic fatty liver disease.

Usefulness of the comfort theory in the clinical nursing care of new mothers: critical analysis. / Utilidade da teoria do conforto para o cuidado clínico de enfermagem à puérpera: análise crítica.

OBJECTIVE: The aim of this study was to evaluate the usefulness of the comfort theory for the clinical nursing care of new mothers. METHODS: This is a reflexive-theoretical study conducted in November and December 2014, based on the usefulness criterion proposed in the critical analysis of the Barnum nursing theory. RESULTS: The comfort theory in nursing care for new mothers applied to study analysis revealed that this theory meets the criteria of usefulness because it provides applicable concepts that facilitated the clinical nursing care of women in the postpartum period and helped increase their comfort level. The verification of these concepts showed that the theory can be applied in different settings of clinical care for new mothers. CONCLUSION: The theory can be used to support and improve clinical nursing care for postpartum women, and help improve puerperal comfort.

Osmoregulation requires brain expression of the renal Na-K-2Cl cotransporter NKCC2.

The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats.