Antihypertensive treatment of end-stage renal disease patients on hemodialysis does not alter circulating ACE and ACE2 activity and angiotensin peptides.

Cardiovascular diseases (CVD) are the main causes of death in hemodialysis patients, representing a public health challenge. We investigated the effect of different antihypertensive treatments on circulating levels of renin-angiotensin system (RAS) components in end-stage renal disease (ESRD) patients on hemodialysis. ESRD patients were grouped following the prescribed antihypertensive drugs: ß-blocker, ß-blocker+ACEi and ß-blocker+AT1R blocker. ESDR patients under no antihypertensive drug treatment were used as controls. Blood samples were collected before hemodialysis sessions. Enzymatic activities of the angiotensin-converting enzymes ACE and ACE2 were measured through fluorescence assays and plasma concentrations of the peptides Angiotensin II (Ang II) and Angiotensin-(1-7) [Ang-(1-7)] were quantified using mass spectrometry (LC-MS/MS). ACE activity was decreased only in the ß-blocker+ACEi group compared to the ß-blocker+AT1R, while ACE2 activity did not change according to the antihypertensive treatment. Both Ang II and Ang-(1-7) levels also did not change according to the antihypertensive treatment. We concluded that the treatment of ESRD patients on hemodialysis with different antihypertensive drugs do not alter the circulating levels of RAS components.

Quantitative Risk Assessment of Oocyst Versus Bradyzoite Foodborne Transmission of Toxoplasma gondii in Brazil.

Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental stage of T. gondii, oocysts, is an important source of infection in Brazil; however, no studies have quantified this risk relative to other parasite stages. We developed a Bayesian quantitative risk assessment (QRA) to estimate the relative attribution of the two primary parasite stages (bradyzoite and oocyst) that can be transmitted in foods to people in Brazil. Oocyst contamination in fruits and greens contributed significantly more to overall estimated T. gondii infections than bradyzoite-contaminated foods (beef, pork, poultry). In sensitivity analysis, treatment, i.e., cooking temperature for meat and washing efficiency for produce, most strongly affected the estimated toxoplasmosis incidence rate. Due to the lack of regional food contamination prevalence data and the high level of uncertainty in many model parameters, this analysis provides an initial estimate of the relative importance of food products. Important knowledge gaps for oocyst-borne infections were identified and can drive future studies to improve risk assessments and effective policy actions to reduce human toxoplasmosis in Brazil.

Temporal trend, spatial analysis and spatiotemporal clusters of infant mortality associated with congenital toxoplasmosis in Brazil: Time series from 2000 to 2020.

OBJECTIVE: To analyse the spatial, temporal and spatial-temporal patterns of infant mortality associated with congenital toxoplasmosis in Brazil between the years 2000 and 2020. METHODS: Ecological study of time series, with spatial analysis and spatiotemporal scan of infant mortality associated with congenital toxoplasmosis from the records of deaths of the Mortality Information System of the Brazilian Ministry of Health. The rates were smoothed by the Local Empirical Bayesian model. The Global Moran Index, Global Geary's Contiguity and Getis-Ord General statistics were calculated for spatial autocorrelation assessment. The trends were evaluated by the Joinpoint method. RESULTS: We identified 1183 infant deaths associated with congenital toxoplasmosis in Brazil between 2000 and 2020. The predominant characteristics were male sex (52.1%), post-neonatal age group (51.9%), white race/colour (45.7%), and Southeast region of residence (40.0%). The infant mortality rate associated with congenital toxoplasmosis showed an increasing trend in the country in the years analysed. The spatial analysis showed heterogeneous distribution of mortality in the Brazilian territory and found no evidence of spatial autocorrelation; but spatial-temporal analysis identified three risk clusters involving 703 municipalities. CONCLUSION: Infant mortality associated with congenital toxoplasmosis is a persistent public health problem in Brazil. The risk factors male sex, indigenous race/colour, early neonatal age, North and Northeast regions and risk clusters mapped in this study should be observed for future analysis and planning of health care policies in the control of infant deaths associated with congenital toxoplasmosis. Health surveillance strategies and public health policies need to be strengthened.

ACE and ACE2 catalytic activity in the fecal content along the gut.

BACKGROUND: Angiotensin-converting enzyme (ACE) and ACE2 are two major enzymes of the renin-angiotensin-aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1-7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats. METHODS: Portions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats. Enzyme activity was evaluated by fluorometric assays using different substrates: Hippuryl-His-Leu for ACE-C-domain, Z-Phe-His-Leu for ACE-N-domain, and Mca-APK(Dnp) for ACE2. ACE and ACE2 concentration was assessed by ELISA. Ratios concerning concentrations and activities were calculated to evaluate the balance of the RAAS. Statistical analysis was performed using Friedman test followed by Dunn's multiple comparisons test or Wilcoxon matched-pairs test whenever needed. KEY RESULTS: ACE and ACE2 are catalytically active in the intestinal content along the rat gut. The ACE N-domain shows higher activity than the C-domain both in the intestinal content and in the intestinal tissue. ACE and ACE2 are globally more active in the intestinal content than in the corresponding intestinal tissue. There was a distal-to-proximal prevalence of ACE2 over ACE in the intestinal tissue. CONCLUSIONS & INFERENCES: This work is the first to report the presence of catalytically active ACE and ACE2 in the rat intestinal content, supporting future research on the regulatory role of the intestinal RAAS on gut function and a putative link to the microbiome.

Pediatric dyslipidemia is associated with increased urinary ACE activity, blood pressure values, and carotidal-femoral pulse wave velocity.

This study aimed to evaluate the enzymatic activity of the angiotensin-converting enzyme (ACE) in children and adolescents to investigate their relationship with dyslipidemia and other cardiometabolic alterations. Anthropometric measurements, blood pressure (BP), and fasting lipid concentrations were taken from 360 subjects. Categorization was done according to the levels of each lipoprotein (total cholesterol, triglycerides (TG), LDL-C, HDL-C, and non-HDL-C) into three groups: normolipidemic (NL), borderline (BL), and dyslipidemic (DL). Enzymatic activity in urine was measured using the substrates Z-FHL-OH and hippuryl-HL-OH (h-HL-OH) and the ACE activity ratio (Z-FHL-OH/h-HL-OH) was calculated. Dyslipidemic levels of HDL-C, TG, and LDL-C were observed in 23%, 9%, and 3% of the participants, respectively, and were more frequent in obese children (Chi-square, p < 0.001). ACE activity ratio was augmented in BL(HDL-C) when compared to NL(HDL-C) (5.06 vs. 2.39, p < 0.01), in DL(LDL-C) in comparison to BL(LDL-C) and NL(LDL-C) (8.7 vs. 1.8 vs. 3.0, p < 0.01), and in DL(non-HDL-C) than in BL(non-HDL-C) and in NL(non-HDL-C) (6.3 vs. 2.1 vs. 2.9, p = 0.02). The groups with impaired HDL-C and TG levels presented an increased diastolic BP percentile, and a higher systolic BP percentile was observed in BL(TG) and DL(TG). The carotidal-femoral pulse wave velocity (cfPWV) was higher in the groups with DL levels of TG and LDL-C than in NL groups. Hypertriglyceridemia was associated with higher cfPWV. No direct impact of the ACE activity on BP values was observed in this cohort, however, there was an association between hyperlipidemia and ACE upregulation which can trigger mechanisms driving to early onset of hypertension and cardiovascular disease. Graphical abstract exemplifying the cohort, categorization of subjects into the groups NL normolipidemic, BL borderline, DL dyslipidemic, methods, and main findings. Pediatric dyslipidemia was consistent with dyslipidemia secondary to obesity (DSO), associated with higher urinary angiotensin-converting enzyme (ACE) activity ratio, BP blood pressure values, and carotidal-femoral pulse wave velocity (cfPWV).

Prevalência de sífilis entre travestis e mulheres transexuais em situação vulnerável, participantes do estudo TransOdara ­ Manaus, Amazonas, 2020-2021 / Prevalence of syphilis among travestis and transsexual women in vulnerable situation, participants in the TransOdara study ­ Manaus, Brazil, 2020-2021

Objetivo: Estimar a prevalência de sífilis entre travestis e mulheres transexuais (TrMT) em situação de vulnerabilidade social. Métodos: Foram selecionadas TrMT residentes em Manaus, em situação de rua, privadas de liberdade e imigrantes, participantes do projeto multicêntrico TransOdara ­ Estudo de Prevalência da Sífilis e outras Infecções Sexualmente Transmissíveis entre TrMT no Brasil: Cuidado e Prevenção. Resultados: Foram incluídas 39 TrMT. A prevalência de sífilis, segundo resultado de teste rápido e VDRL, foi 64,1% (25/39), sendo aparentemente maior entre as TrMT em situação de rua (72,7%), seguidas das privadas de liberdade (63,2%) e das imigrantes (55,6%), porém sem diferença estatística entre os subgrupos. Cerca de 80% tinham entre 20 e 39 anos e se autorreferiram pretas/pardas. Discussão: Apesar do pequeno tamanho amostral, destaca-se a especificidade deste trabalho, que incluiu população vulnerável. Conclusão: Foi alta a prevalência de sífilis na população estudada, sendo necessário ampliar os serviços capacitados para atender essa demanda

Objective: To estimate the prevalence of syphilis among travestis and transsexual women (TrTW) in situations of social vulnerability. Methods: TrTW residents in Manaus, homeless, incarcered and immigrants, participants of the multicenter project TransOdara - Prevalence Study of Syphilis and other Sexually Transmitted Infections among TrMT in Brazil: Care and Prevention were selected. Results: 39 TrMT were included. The prevalence of syphilis, according to the result of the rapid test and VDRL, was 64.1% (25/39), being apparently higher among homeless TrMT (72.7%), followed by those incarcereted (63.2 %) and immigrants (55.6%), but with no statistical difference between the subgroups. About 80% were between 20 and 39 years old and self-reported as black/brown. Discussion: Despite the small sample size, the specificity of this work stands out, which included a vulnerable population. Conclusion:The prevalence of syphilis in the studied population was high, and it is necessary to expand the services trained to meet this demand.

Effects of Toxoplasma gondii infection on cognition, symptoms, and response to digital cognitive training in schizophrenia.

Studies indicate that neuroscience-informed digital cognitive training can remediate cognitive impairments in schizophrenia, but the factors contributing to these deficits and response to treatment remain unclear. Toxoplasma gondii is a neuroinvasive parasite linked to cognitive decline that also presents a higher prevalence in schizophrenia. Here, we compared the cognition and symptom severity of IgG seropositive (TOXO+; n = 25) and seronegative (TOXO-; n = 35) patients who participated in a randomized controlled trial of digital cognitive training. At baseline, TOXO+ subjects presented lower global cognition than TOXO- (F = 3.78, p = 0.05). Specifically, TOXO+ subjects showed worse verbal memory and learning (F = 4.48, p = 0.03), social cognition (F = 5.71, p = 0.02), and higher antibody concentrations were associated with increased negative (r = 0.42, p = 0.04) and total (r = 0.40, p = 0.04) schizophrenia symptoms. After training, the TOXO+ group showed higher adherence to the intervention (X2 = 9.31, p = 0.03), but there were no differences in changes in cognition and symptoms between groups. These findings highlight the association between seropositivity to T. gondii and deteriorated cognition and symptoms in schizophrenia. Further research is needed to assess the specific efficacy of digital cognitive training on this population.

Culture of endometrial epithelial cells collected by a cytological brush in vivo.

In cattle, mechanistic studies of endometrial function rely on cell lines or primary culture of cells harvested postmortem. Understanding the endometrial physiology in dairy cows is essential, because approximately 50% of pregnancies are lost in the first 3 wk of gestation for unknown reasons. The objective was to validate an in vivo, minimally invasive, and estrous cycle stage-specific method to obtain endometrial luminal epithelial cells for culture. The uterine body of 26 cows was sampled using a cytology brush (cytobrush) 4 d after estrus. The viability of cells was measured by flow cytometry (80% live cells) and epithelial identity was determined by anti-vimentin and anti-cytokeratin immunofluorescence and quantitative PCR for KRT18 and VIM. A pool of cells from 15 animals was passaged 4 times in culture until confluent and then treated with 0, 0.1, 1, or 10 ng/mL of recombinant bovine interferon-tau (rbIFN-τ). The relative expression of transcripts related to IFN-τ signaling (IFNAR1), early (IRF2) and late (ISG15, OAS1) response to IFN-τ stimulus, and other IFN-τ-stimulated genes (CCL8, CXCL10, and FABP3) was measured by quantitative PCR. The relative expression of KRT18 transcripts was similar across passages; the relative expression of VIM increased at passage 2, and IFNAR1 transcripts decreased in cultured compared with that in fresh cells. The relative expression of ISG15, OAS1, CCL8, and FABP3 increased in response to rbIFN-τ. In conclusion, culture of endometrial luminal cells collected by cytobrush was feasible, generating a monolayer enriched in epithelial cells, and therefore constitutes a novel model by which to study endometrial luminal epithelial cell function, including responses to IFN-τ.

Sickle cell disease chronic joint pain: Clinical assessment based on maladaptive central nervous system plasticity.

Chronic joint pain (CJP) is among the significant musculoskeletal comorbidities in sickle cell disease (SCD) individuals. However, many healthcare professionals have difficulties in understanding and evaluating it. In addition, most musculoskeletal evaluation procedures do not consider central nervous system (CNS) plasticity associated with CJP, which is frequently maladaptive. This review study highlights the potential mechanisms of CNS maladaptive plasticity related to CJP in SCD and proposes reliable instruments and methods for musculoskeletal assessment adapted to those patients. A review was carried out in the PubMed and SciELO databases, searching for information that could help in the understanding of the mechanisms of CNS maladaptive plasticity related to pain in SCD and that presented assessment instruments/methods that could be used in the clinical setting by healthcare professionals who manage chronic pain in SCD individuals. Some maladaptive CNS plasticity mechanisms seem important in CJP, including the impairment of pain endogenous control systems, central sensitization, motor cortex reorganization, motor control modification, and arthrogenic muscle inhibition. Understanding the link between maladaptive CNS plasticity and CJP mechanisms and its assessment through accurate instruments and methods may help healthcare professionals to increase the quality of treatment offered to SCD patients.

Head-to-Tail and Head-to-Head Molecular Chains of Poly(p-Anisidine): Combined Experimental and Theoretical Evaluation.

Poly(p-anisidine) (PPA) is a polyaniline derivative presenting a methoxy (-OCH3) group at the para position of the phenyl ring. Considering the important role of conjugated polymers in novel technological applications, a systematic, combined experimental and theoretical investigation was performed to obtain more insight into the crystallization process of PPA. Conventional oxidative polymerization of p-anisidine monomer was based on a central composite rotational design (CCRD). The effects of the concentration of the monomer, ammonium persulfate (APS), and HCl on the percentage of crystallinity were considered. Several experimental techniques such as X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), multifractal analysis, Nuclear Magnetic Resonance (13C NMR), Fourier-transform Infrared spectroscopy (FTIR), and complex impedance spectroscopy analysis, in addition to Density Functional Theory (DFT), were employed to perform a systematic investigation of PPA. The experimental treatments resulted in different crystal structures with a percentage of crystallinity ranging from (29.2 ± 0.6)% (PPA1HT) to (55.1 ± 0.2)% (PPA16HT-HH). A broad halo in the PPA16HT-HH pattern from 2θ = 10.0-30.0° suggested a reduced crystallinity. Needle and globular-particle morphologies were observed in both samples; the needle morphology might have been related to the crystalline contribution. A multifractal analysis showed that the PPA surface became more complex when the crystallinity was reduced. The proposed molecular structures of PPA were supported by the high-resolution 13C NMR results, allowing us to access the percentage of head-to-tail (HT) and head-to-head (HH) molecular structures. When comparing the calculated and experimental FTIR spectra, the most pronounced changes were observed in ν(C-H), ν(N-H), ν(C-O), and ν(C-N-C) due to the influence of counterions on the polymer backbone as well as the different mechanisms of polymerization. Finally, a significant difference in the electrical conductivity was observed in the range of 1.00 × 10-9 S.cm-1 and 3.90 × 10-14 S.cm-1, respectively, for PPA1HT and PPA16HT-HH.

SARS-CoV-2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes.

COVID-19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID-19. Here, we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS-CoV-2 infected Syrian hamsters. We show that SARS-CoV-2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real-time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro. SARS-CoV-2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID-19, as memory loss, confusion, and cognitive impairment.

Evaluation of the effectiveness of UV-C dose for photoinactivation of SARS-CoV-2 in contaminated N95 respirator, surgical and cotton fabric masks.

As part of efforts to combat the Covid-19 pandemic and decrease the high transmissibility of the new coronavirus, SARS-CoV-2, effective inactivation strategies, such as UV-C decontamination technologies, can be reliably disseminated and well-studied. The present study investigated the susceptibility of a high viral load of SARS-CoV-2 in filtering facepiece respirators (FFR) N95, surgical mask, cotton fabric mask and N95 straps under three different doses of UV-C, applying both real-time PCR (qPCR) and plaque formation assays to quantify viral load reduction and virus infectivity, respectively. The results show that more than 95% of the amount of SARS-CoV-2 RNA could be reduced after 10 min of UV-C exposure (0.93 J cm-2 per side) in FFR N95 and surgical masks and, after 5 min of UV-C treatment (0.46 J cm-2 per side) in fabric masks. Furthermore, the analysis of viable coronaviruses after these different UV-C treatments demonstrated that the lowest applied dose is sufficient to decontaminate all masks ([Formula: see text] 3-log10 reduction of the infective viral load, > 99.9% reduction). However, for the elastic strap of N95 respirators, a UV-C dose three times greater than that used in masks (1.4 J cm-2 per side) is required. The findings suggest that the complete decontamination of masks can be performed effectively and safely in well-planned protocols for pandemic crises or as strategies to reduce the high consumption and safe disposal of these materials in the environment.

Poly(o-methoxyaniline) Chain Degradation Based on a Heat Treatment (HT) Process: Combined Experimental and Theoretical Evaluation.

Poly(o-methoxyaniline) emeraldine-salt form (ES-POMA) was chemically synthesized using hydrochloric acid and subjected to a heat treatment (HT) process for 1 h at 100 °C (TT100) and 200 °C (TT200). The HT process promoted a progressive decrease in crystallinity. The Le Bail method revealed a decomposition from tetrameric to trimeric-folded chains after the HT process. The unheated POMA-ES presented a globular vesicular morphology with varied micrometric sizes. The heat treatment promoted a reduction in these globular structures, increasing the non-crystalline phase. The boundary length (S) and connectivity/Euler feature (χ) parameters were calculated from the SEM images, revealing that ES-POMA presented a wide distribution of heights. The TT100 and TT200 presented a narrow boundary distribution, suggesting smoother surfaces with smaller height variations. The UV-VIS analysis revealed that the transition at 343 nm (nonlocal π → π*) was more intense in the TT200 due to the electronic delocalization, which resulted from the reduced polymer chain caused by the HT process. In addition to the loss of conjugation, counter ion withdrawal reduced the ion-chain interaction, decreasing the local electron density. This result shows the influence of the chlorine counter ions on the peaks position related to the HOMO → LUMO transition, since the π → polaron transition occurs due to the creation of the energy states due to the presence of counter ions. Finally, the electrical conductivity decreased after the HT process from 1.4 × 10-4 S.cm-1 to 2.4 × 10-6 S.cm-1 as result of the polymer deprotonation/degradation. Thus, this paper proposed a systematic evaluation of the POMA molecular structure and crystallite size and shape after heat treatment.

Neurological impacts of covid-19 and worldwide scientific production about the subject: a bibliometric analysis / Impactos neurológicos da covid-19 e produção científica mundial sobre a temática: uma análise bibliométrica

Introduction: The novel Coronavirus (COVID-19) was first reported by officials in Wuhan City, in December 2019. It has rapidly spread with confirmed cases in almost every country across the world and has caused a global public health crisis.¹ The epidemiological update of the World Health Organization on 9th March 2021 showed that over 2.7 million new cases were reported. In this article, a biblometrical analysis of trending topics and what is being researched regarding COVID-19 and its neurological involvement is done. Methods: This research was conducted on the Web of Science Core Collection (WoS). For research in WoS, keywords in English were used, according to DeCS - Descriptors in Health Sciences. The search strategy with Boolean operators was: TS = (SARS-CoV-2 OR COVID-19) AND TS=(Neurologic Findings OR Neurology OR Neurologic Manifestations). Results: In total, 392 scientific productions were identified and included in this bibliometric analysis. The studies were published in the period between March 2020 and March 2021, with records prevalent in the themes of clinical neurology (n=234) and neurosciences (n=134), as well as several other areas. The thirty studies collected a total of 3395 citations, with variations from 1433 to 26 and average of 113 citations per study. All were published in 2020, with bigger prevalence in July (nine articles) and June (six articles). Conclusion: It is expected that this bibliometric survey will serve as a manner of presenting the main topics of study within neurology before COVID-19, in addition providing guidance for future research.

Introdução: O novo Coronavírus (COVID-19) foi relatado pela primeira vez por autoridades na cidade de Wuhan, em dezembro de 2019. Ele se espalhou rapidamente com casos confirmados em quase todos os países do mundo e causou uma crise global de saúde pública. A atualização epidemiológica da Organização Mundial da Saúde em 9 de março de 2021 mostrou que mais de 2,7 milhões de novos casos foram relatados. Neste artigo, é feita uma análise biblométrica dos trending topics e do que está sendo pesquisado sobre o COVID-19 e seu envolvimento neurológico. Métodos: Esta pesquisa foi realizada na Web of Science Core Collection (WoS). Para a pesquisa na WoS, foram utilizadas palavras-chave em inglês, conforme DeCS - Descritores em Ciências da Saúde. A estratégia de busca com operadores booleanos foi: TS = (SARS-CoV-2 OR COVID-19) AND TS= (Neurologic Findings OR Neurology OR Neurologic Manifestations). Resultados: No total, 392 produções científicas foram identificadas e incluídas nesta análise bibliométrica. Os estudos foram publicados no período entre março de 2020 e março de 2021, com registros prevalentes nos temas de neurologia clínica (n=234) e neurociências (n=134), além de diversas outras áreas. Os trinta estudos coletaram um total de 3.395 citações, com variações de 1.433 a 26 e média de 113 citações por estudo. Todos foram publicados em 2020, com maior prevalência em julho (nove artigos) e junho (seis artigos). Conclusão: Espera-se que este levantamento bibliométrico sirva como forma de apresentar os principais tópicos de estudo dentro da neurologia antes da COVID-19, além de fornecer orientações para pesquisas futuras.

Cationic Geminoid Peptide Amphiphiles Inhibit DENV2 Protease, Furin, and Viral Replication.

Dengue is an important arboviral infectious disease for which there is currently no specific cure. We report gemini-like (geminoid) alkylated amphiphilic peptides containing lysines in combination with glycines or alanines (C15H31C(O)-Lys-(Gly or Ala)nLys-NHC16H33, shorthand notation C16-KXnK-C16 with X = A or G, and n = 0-2). The representatives with 1 or 2 Ala inhibit dengue protease and human furin, two serine proteases involved in dengue virus infection that have peptides with cationic amino acids as their preferred substrates, with IC50 values in the lower µM range. The geminoid C16-KAK-C16 combined inhibition of DENV2 protease (IC50 2.3 µM) with efficacy against replication of wildtype DENV2 in LLC-MK2 cells (EC50 4.1 µM) and an absence of toxicity. We conclude that the lysine-based geminoids have activity against dengue virus infection, which is based on their inhibition of the proteases involved in viral replication and are therefore promising leads to further developing antiviral therapeutics, not limited to dengue.

Saccharomyces boulardii exerts renoprotection by modulating oxidative stress, renin angiotensin system and uropathogenic microbiota in a murine model of diabetes.

AIMS: We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice. MAIN METHODS: Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed. KEY FINDINGS: Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers. SIGNIFICANCE: Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes.

Comparative evaluation of dental pulp tests in pulpal status diagnostics / Evaluación comparativa de pruebas de pulpa dental en el diagnóstico del estado pulpar

Introduction: The purpose of this study was to evaluate the effectiveness and compare the accuracy of pulp tests in the diagnosis of teeth pulpal health. Material and Methods: Traumatized (n=71) and non-traumatized (n=71) teeth from 42 patients were evaluated. Each tooth underwent cold, heat, electric and oximetry tests, followed by radiographic examination and calculation of the sensitivity, specificity, PPV, NPV and accuracy. Results: Clinical and radiographic examination showed no alteration for the 71 teeth from the intact contralateral group. From the traumatized group, 29 teeth presented complete endodontic treatment, 17 presented periapical alterations that required endodontic treatment and 25 teeth did not present conclusive radiographic alteration. The cold test showed a significantly higher proportion of correct results, while the electric test showed a significantly lower proportion. The data showed higher accuracy for the cold, followed by oximeter and heat tests, while the electric test presented the lowest accuracy. Cold and oximeter tests proved superior over the electric and heat tests, while the electric test showed better parameters when diagnosing diseased pulp. Conclusion: Combining two pulp tests seems reasonable for improving the pulp diagnoses using both oximeter and cold or oximeter and heat tests to detect healthy pulp; or cold and electric tests to define diseased pulp.

Introducción: El propósito de este estudio fue evaluar la efectividad y comparar la precisión de las pruebas pulpares en el diagnóstico de la salud pulpar de los dientes. Material y Métodos: Se evaluaron dientes traumatizados (n=71) y no traumatizados (n=71) de 42 pacientes. Cada diente se sometió a pruebas de frío, calor, eléctricas y de oximetría, seguidas de examen radiográfico y cálculo de la sensibilidad, especificidad, VPP, VPN y precisión. Resultados: El examen clínico y radiográfico no mostró alteración en los 71 dientes del grupo contralateral intacto. Del grupo traumatizado, 29 dientes presentaron tratamiento endodóntico completo, 17 presentaron alteraciones peri-apicales que requirieron tratamiento endodóntico y 25 dientes no presentaron alteración radiográfica concluyente. La prueba en frío mostró una proporción significativamente mayor de resultados correctos, mientras que la prueba eléctrica mostró una proporción significativamente menor. Los datos mostraron mayor precisión para la prueba de frío, seguida de las pruebas de oxímetro y calor, mientras que la prueba eléctrica presentó la menor precisión. Las pruebas de frío y oxímetro demostraron ser superiores a las pruebas eléctricas y de calor, mientras que la prueba eléctrica mostró mejores parámetros al momento de diagnosticar pulpa enferma. Conclusión: La combinación de dos pruebas pulpares parece razonable para mejorar los diagnósticos pulpares utilizando tanto el oxímetro como las pruebas de frío u oxímetro y calor para detectar una pulpa sana; o pruebas de frío y eléctricas para definir pulpa enferma.

Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System.

Mesenchymal stem cells comprise a natural reservoir of undifferentiated cells within adult tissues. Given their self-renewal, multipotency, regenerative potential and immunomodulatory properties, MSCs have been reported as a promising cell therapy for the treatment of different diseases, including neurodegenerative and autoimmune diseases. In this study, we investigated the immunomodulatory properties of human tubal mesenchymal stem cells (htMSCs) using the EAE model. htMSCs were able to suppress dendritic cells activation downregulating antigen presentation-related molecules, such as MHCII, CD80 and CD86, while impairing IFN-γ and IL-17 and increasing IL-10 and IL-4 secretion. It further correlated with milder disease scores when compared to the control group due to fewer leukocytes infiltrating the CNS, specially Th1 and Th17 lymphocytes, associated with increased IL-10 secreting Tr1 cells. Conversely, microglia were less activated and infiltrating mononuclear cells secreted higher levels of IL-4 and IL-10 and expressed reduced chemokine receptors as CCR4, CCR6 and CCR8. qPCR of the spinal cords revealed upregulation of indoleamine-2,3-dioxygenase (IDO) and brain derived neurotrophic factor (BDNF). Taken together, here evidenced the potential of htMSCs as an alternative for the treatment of inflammatory, autoimmune or neurodegenerative diseases.