Effects of Probiotics on Inflammatory Biomarkers and Its Associations With Cardiac Autonomic Function in Women With Arterial Hypertension: A Secondary Analysis of a Randomized Clinical Trial.

Preclinical evidence suggests that probiotic administration may exert an anti-inflammatory effect and reduce autonomic dysfunction and blood pressure. This study evaluated the effects of probiotic therapy on inflammatory biomarkers and characterized the correlations between inflammation and cardiac autonomic function in women with arterial hypertension. Women were randomized into probiotics (n = 20) or placebo (n = 20). The probiotic group received 109 CFU/day of Lactobacillus (L.) paracasei LPC-37, L. rhamnosus HN001, L. acidophilus NCFM, and Bifidobacterium lactis HN019, and the placebo group received polydextrose. Clinical, electrocardiogram, heart rate variability (HRV) analysis, and cytokine levels were assessed at baseline and after 8 weeks. Women who received probiotics for 8 weeks had increased serum levels of IL-17A (p = 0.02) and decreased INF-γ (p = 0.02) compared to baseline. Probiotic supplementation increased serum levels of IL-10 compared to the placebo group (p = 0.03). Probiotic or placebo administration did not change serum levels of TNFα and IL-6. Serum levels of IL-2 (p = 0.001, and p = 0.001) and IL-4 (p = 0.001, and p = 0.001) were reduced in women receiving placebo or probiotics, respectively. Correlations between HRV indices and inflammatory variables showed that INF-γ was positively correlated with heart rate (HR) and sympathetic HRV indices and negatively correlated with vagal HRV indices. IL-10 was negatively correlated with HR and sympathetic HRV indices. IL-6 was negatively correlated with parasympathetic HRV indices and positively correlated with SD2/SD1 ratio. Probiotic therapy has a discreet anti-inflammatory effect in hypertensive women, and pro-inflammatory cytokines were negatively correlated with vagal modulation and positively correlated with sympathetic modulation of HRV. The clinical trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-9mj2dt.

Exploring Inflammatory Asthma Phenotypes: Proteomic Signatures in Serum and Induced Sputum.

Asthma drug responses may differ due to inflammatory mechanisms triggered by the immune cells in the pulmonary microenvironment. Thus, asthma phenotyping based on the local inflammatory profile may aid in treatment definition and the identification of new therapeutic targets. Here, we investigated protein profiles of induced sputum and serum from asthma patients classified into eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma, according to inflammatory phenotypes. Proteomic analyses were performed using an ultra-performance liquid chromatography (ultra-HPLC) system coupled to the Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. Fifty-two (52) proteins showed significant differences in induced sputum among the groups, while only 12 were altered in patients' sera. Five proteins in the induced sputum were able to discriminate all phenotypic groups, while four proteins in the serum could differentiate all except the neutrophilic from the paucigranulocytic inflammatory pattern. This is the first report on comparative proteomics of inflammatory asthma phenotypes in both sputum and serum samples. We have identified a potential five-biomarker panel that may be able to discriminate all four inflammatory phenotypes in sputum. These findings not only provide insights into potential therapeutic targets but also emphasize the potential for personalized treatment approaches in asthma management.

Roles of viable but non-culturable state in the survival of Campylobacter jejuni.

Despite being considered fragile and fastidious, Campylobacter jejuni is the most prevalent cause of foodborne bacterial gastroenteritis, and chicken meat is considered the main vehicle of transmission to humans. This agent can survive adverse conditions in the form of biofilms, but extreme stress (nutritional, oxidative and thermal) promotes the acquisition of a state called viable but not culturable (VBNC). The emergence of this pathogen worldwide and the recent international requirements in its control instigated us to qualitatively and quantitatively estimate the time required for the acquisition of the VBNC form in 27 strains of C. jejuni, characterize morphological aspects, determine its adaptive and invasive potential and perform comparative metabolomic evaluation. Extreme stress promoted the complete acquisition of the VBNC form in a mean time of 26 days. Starting from an average initial count of 7.8 log CFU/mL, the first four days determined the greatest average reduction of the culturable form of 3.2 log CFU/mL. The scanning and transmission image analyses showed a transition from the typical viable form (VT) to the VBNC form, with initial acquisition of the straight rod shape, followed by loss of the flagella and subdivision into two to 11 imperfect cocci arranged in a chain and rich in cellular content, until their individual release. RT-PCR identified the presence of ciaB and p19 transcripts in the 27 cultivable C. jejuni strains, a character maintained in the VBNC form only for p19 and in 59.3% (16/27) of the VBNC strains for the ciaB gene. The average inoculation of 1.8 log CFU/mL of C. jejuni VBNC into primary chicken embryo hepatocyte cells promoted the occurrence of apoptosis processes significantly after 24 hours of contact by one of the strains tested. In C. jejuni VBNC, we detected higher expression of metabolites linked to protective and adaptation mechanisms and of volatile organic precursor compounds indicative of metabolism interruption. The oscillations in the time of acquisition of the VBNC form together with the presence of transcripts for ciaB and p19, the identification of cell lysis and metabolites that ensure the maintenance of the pathogen alert to the fact that C. jejuni VBNC remains virulent and adapted to stress, which makes evident the potential danger of this latent form, which is not detectable by official methodologies.

Characterization of faba bean (Vicia faba L.) rhizosphere associating rhizobacteria against Botrytis fabae AAUBF-12 and their plant growth-promoting properties.

The rhizobacteria are known to protect plants from different pathogens acting as biocontrol agents and promote growth of plants. This study was conducted to isolate, screen and identify faba bean associating rhizobacteria for their antagonistic properties against Botrytis fabae AAUBF-12 and plant growth-promoting properties under in vitro conditions. In the dual culture assay, the isolates inhibited the mycelia growth of B. fabae AAUBF-12 (6-40 %) upon 3 days of incubation, and the inhibition increased to 9-43 %, 16-50 %, and 24-68 % after five, seven and 9 days of incubation, respectively. The inhibitory activity increased from 6 to 82 % using the culture filtrates of the isolates. Isolate AAUB95 displayed the highest mycelial inhibition (27 %) at 5 % concentration of culture filtrate, followed by AAUB146b that exhibited 21 % inhibition at the same concentration. AAUB146b and AAUB100 effectively inhibited B. fabae AAUBF-12 by 79 % and 80 % at 20 % concentrations of the culture filtrate. The qualitative study demonstrated 75 % of the isolates positive for protease and 60 % for lipase synthesis. Furthermore, the isolates that showed antagonistic activity against B. fabae AAUBF-12, produced IAA and ammonia with 65 % and 60 %, respectively. Moreover, 310-760 µg mL-1 and 200-620 µg mL-1 of tricalcium phosphate (TCP) was released on the 3rd and 6th days of incubation, respectively, due to rhizobacterial solubilization. Nevertheless, the Pearson's correlation analysis between pH and TCP solubilization revealed an inverse relationship (r = -.422∗∗). Based on 16S rRNA sequences analysis, isolate AAUB95, AAUB146b, AAUB100 and AAUB92 were identified as B. subtilis AAUB95, S. nematodiphila AAUB146b, B. tequilensis AAUB100 and B. subtilis AAUB92, respectively. Of the isolates, B. subtilis AAUB95 showed best antagonism of B. fabae AAUBF-12 with multiple plant growth-promoting properties.

Invasive mechanical ventilation and biomarkers as predictors of bronchopulmonary dysplasia in preterm infants.

OBJECTIVES: To evaluate the impact of invasive mechanical ventilation associated with two serum inflammatory cytokines and clinical indicators, on the second day of life, as predictors of bronchopulmonary dysplasia in very low birth weight preterm infants. It was hypothesized that the use of invasive mechanical ventilation in the first hours of life is associated with biomarkers that may predict the chances of preterm infants to develop bronchopulmonary dysplasia. METHODS: Prospective cohort of 40 preterm infants with gestational age <34 weeks and birth weight <1500 g. The following were analyzed: clinical variables; types of ventilator support used (there is a higher occurrence of bronchopulmonary dysplasia when oxygen supplementation is performed by long periods of invasive mechanical ventilation); hospitalization time; quantification of two cytokines (granulocyte and macrophage colony stimulating factor [GM-CSF] and eotaxin) in blood between 36 and 48 h of life. The preterm infants were divided in two groups: with and without bronchopulmonary dysplasia. RESULTS: The GM-CSF levels presented a significantly higher value in the bronchopulmonary dysplasia group (p = 0.002), while eotaxin presented higher levels in the group without bronchopulmonary dysplasia (p = 0.02). The use of continuous invasive mechanical ventilation was associated with increased ratios between GM-CSF and eotaxin (100% sensitivity and 80% specificity; receiver operating characteristic area = 0.9013, CI = 0.7791-1.024, p < 0.0001). CONCLUSIONS: The duration of invasive mechanical ventilation performed in the first 48 h of life in the very low birth weight infants is a significant clinical predictor of bronchopulmonary dysplasia. The use of continuous invasive mechanical ventilation was associated with increased ratios between GM-CSF and eotaxin, suggesting increased lung injury and consequent progression of the disease.

Frequency of microorganisms in vaginal discharges of high-risk pregnant women from a hospital in Caruaru, Pernambuco, Brazil / Prevalência de microrganismos em secreção vaginal de gestantes de alto risco de uma maternidade em Caruaru, Pernambuco, Brasil

ABSTRACT Introduction: During pregnancy, estrogen and progesterone levels may favor vaginal colonization by pathogenic microorganisms that can be associated with obstetric complications and neonatal infections. These pathogens include Candida spp., Trichomonas vaginalis, Gardnerella vaginalis and Streptococcus agalactiae. Objective: To determine the frequency of such microorganisms amongst high-risk pregnant women receiving prenatal care at a hospital in Caruaru, Pernambuco. Material and method: Analytical study in which samples of vaginal discharge were collected from women experiencing high-risk pregnancies, without restriction of age or gestational period. The samples were submitted to Gram-stained direct smear, as well as to fresh wet-mount examination and to cultures in Sabouraud and blood agar. Results: From May to December 2018, 92 patients were selected for sampling. The frequency of Candida spp. was found to be 31.52%. Concerning Gardnerella vaginalis, the frequency was 1.25%. The rate of colonization by Streptococcus agalactiae was 3.23%. No cases of Trichomonas vaginalis were found in this study. Discussion: The frequency of Candida that was found corroborates the literature, as it is a common infection during pregnancy due to hormonal increase. However, the frequencies of colonization by G. vaginalis, T. vaginalis and S. agalactiae were lower than those found in other studies. Conclusion: Due to the risks that these microorganisms can bring to a pregnant woman and a fetus, health professionals should be alert to signs and symptoms, requesting the screening of these pathogens, as well as treating gestating women when necessary.

RESUMEN Introducción: Durante el embarazo, los niveles de estrógeno y progesterona pueden favorecer la colonización vaginal por microorganismos, incluyendo Candida spp., Trichomonas vaginalis, Gardnerella vaginalis y Streptococcus agalactiae, asociados o no a complicaciones obstétricas e infecciones neonatales. Objetivo: Estimar la prevalencia de eses microorganismos en mujeres embarazadas de alto riesgo de una maternidad en la ciudad de Caruaru, Pernambuco, Brasil. Material y métodos: Estudio analítico en el que se tomaron muestras de flujo vaginal de mujeres embarazadas de alto riesgo, sin restricción de edad o edad gestacional. Las muestras iban destinadas a la realización del frotis con tinción de Gram, examen de montaje en fresco y cultivos en agar Sabouraud y sangre. Resultados: En el periodo de mayo a diciembre de 2018, se eligieron 92 mujeres embarazadas. Se encontró una prevalencia de Candida del 31,52%. La prevalencia de Gardnerella vaginalis fue del 1,25%. La tasa de colonización por Streptococcus agalactiae fue del 3,23%. No se encontró ningún caso de Trichomonas vaginalis en este estudio. Discusión: La prevalencia de Candida está de acuerdo con la literatura, puesto que es una infección común durante el embarazo debido al aumento hormonal. Sin embargo, las prevalencias de G. vaginalis, T. vaginalis y S. agalactiae fueron bajas en comparación con otros estudios. Conclusión: Debido al riesgo que estos microorganismos representan para la mujer embarazada y el feto, los profesionales deben vigilar los signos y síntomas, solicitando investigación sobre esos patógenos, además de comenzar el tratamiento de la paciente, cuando necesario.

RESUMO Introdução: Durante a gestação, os níveis de estrogênio e progesterona podem favorecer a colonização vaginal por microrganismos, incluindo Candida spp., Trichomonas vaginalis, Gardnerella vaginalis e Streptococcus agalactiae, associados ou não a complicações obstétricas e infecções neonatais. Objetivo: Determinar a prevalência desses microrganismos em gestantes de alto risco de uma maternidade na cidade de Caruaru, Pernambuco, Brasil. Material e métodos: Estudo analítico em que amostras de secreção vaginal foram coletadas de gestantes de alto risco, sem restrição de idade ou período gestacional. As amostras foram destinadas à realização de esfregaço corado por Gram, exame a fresco e culturas em ágar Sabouraud e sangue. Resultados: No período de maio a dezembro de 2018, 92 gestantes foram selecionadas. A prevalência encontrada de Candida foi de 31,52%. Quanto à Gardnerella vaginalis, a prevalência foi de 1,25%. A taxa de colonização por Streptococcus agalactiae foi de 3,23%. Nenhum caso de Trichomonas vaginalis foi encontrado neste estudo. Discussão: A prevalência de Candida encontrada está de acordo com a literatura, visto que é uma infecção comum durante a gestação em razão do aumento hormonal. Entretanto, as prevalências de G. vaginalis, T. vaginalis e S. agalactiae foram baixas em comparação com outros estudos. Conclusão: Devido ao risco que esses microrganismos podem trazer à gestante e ao feto, os profissionais devem estar atentos aos sinais e sintomas, solicitando pesquisa desses patógenos, além de iniciar o tratamento da paciente, quando necessário.

The Anthelmintic Effect on Strongyloides venezuelensis Induced by BnSP- 6, a Lys49-phospholipase A2 Homologue from Bothrops pauloensis Venom.

BACKGROUND: Phospholipases A2 (PLA2) from snake venoms have a broad potential as pharmacological tools on medicine. In this context, strongyloidiasis is a neglected parasitic disease caused by helminths of the genus Strongyloides. Currently, ivermectin is the drug of choice for treatment, however, besides its notable toxicity, therapeutic failures and cases of drug resistance have been reported. BnSP-6, from Bothorps pauloensis snake venom, is a PLA2 with depth biochemical characterization, reporting effects against tumor cells and bacteria. OBJECTIVE: The aim of this study is to demonstrate for the first time the action of the PLA2 on Strongyloides venezuelensis. METHODS: After 72 hours of treatment with BnSP-6 mortality of the infective larvae was assessed by motility assay. Cell and parasite viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, autophagic vacuoles were labeled with Monodansylcadaverine (MDC) and nuclei of apoptotic cells were labeled with Propidium Iodide (PI). Tissue degeneration of the parasite was highlighted by Transmission Electron Microscopy (TEM). RESULTS: The mortality index demonstrated that BnSP-6 abolishes the motility of the parasite. In addition, the MTT assay attested the cytotoxicity of BnSP-6 at lower concentrations when compared with ivermectin, while autophagic and apoptosis processes were confirmed. Moreover, the anthelmintic effect was demonstrated by tissue degeneration observed by TEM. Furthermore, we report that BnSP-6 showed low cytotoxicity on human intestinal cells (Caco-2). CONCLUSION: Altogether, our results shed light on the potential of BNSP-6 as an anthelmintic agent, which can lead to further investigations as a tool for pharmaceutical discoveries.

Dental self-perception and clinical dental description of participants in the Open University programme for elderly people / Autopercepção e características clínico-odontológicas dos participantes da Universidade aberta a terceira idade

ABSTRACT Objective: This study verified both the self-perception and oral characteristics of a group of elderly participants of the Open University for the Elderly (UNATI). Methods: The sample consisted of a cross-sectional epidemiological study with elderly subjects (50 years of age or older), who attended the UNATI-UNIFAL/MG program. Data collection was carried out using a semi-structured questionnaire consisting of open- and closed-ended questions regarding oral health, its interference with self-esteem and nutrition, among other features. In addition, an application form based on the proposals by the Oral Health Survey 2010, was used. Univariate and multivariate descriptive analyses were performed. Results: The study sample consisted of 106 subjects (mean age of 62.4 years), of whom 59.4% had attended a dental appointment in the last year for routine and/or aesthetic examinations (38.7%). The clinical conditions showed that only 19.8% of the subjects were completely edentulous, an average DMFT of 26.1, and 37.7% used some kind of complete upper dentures, complete lower dentures, or both. Regarding self-perception of oral conditions, 34.9% considered it a regular perception, however in the applied statistics the presence of pain demonstrated a worse perception which was not correlated with teeth loss, presence of dentures and/or restored teeth. Conclusion: The self-perception of oral conditions is regular and the clinical and odontological characteristics evaluated revealed partial edentulous subjects with high DMFT. By evaluating the odontological aspects, it was observed that the majority of the subjects did not have difficulties to look for a dentist, they attended dental appointments in the last year and the preventive treatment had been the most required.

RESUMO Objetivo: Este estudo verificou a autopercepção, as características bucais e os aspectos odontológicos dos participantes da Universidade Aberta a Terceira Idade (UNATI). Métodos: Refere-se a um estudo epidemiológico transversal com indivíduos a partir de 50 anos de idade que frequentam o programa UNATI-UNIFAL/MG. O instrumento de coleta de dados consistiu em um questionário semiestruturado, composto por perguntas referentes à saúde bucal, interferência da mesma na autoestima e alimentação, entre outros. Além disso, foi utilizada uma ficha clínica baseada nas propostas do Levantamento em Saúde Bucal 2010. Foram realizadas análises descritivas, uni e multivariadas. Resultados: A amostra foi composta por 106 indivíduos, com idade média de 62,4 anos, dentre os quais 59,4% visitaram o cirurgião-dentista no último ano para exames de rotina e/ou estética (38,7%). As condições clínicas evidenciaram que apenas 19,8% dos indivíduos eram desdentados totais, o CPOD médio de 26,1 e 37,7% usava algum tipo de prótese total superior, inferior ou ambas. Quanto a autopercepção das condições bucais, 34,9% se refere regular, contudo, na estatística aplicada a presença de dor determinou uma pior percepção e não esteve correlacionada com a perda de dentes, presença de próteses e/ou dentes restaurados. Conclusão: A autopercepção das condições bucais é regular e as características clínico-odontológicas avaliadas revelaram indivíduos desdentados parciais com elevado CPOD. Ao avaliar os aspectos odontológicos a maioria não apresentou dificuldades ao procurar o cirurgião-dentista, visitaram esse profissional no último ano e o tratamento mais procurado por eles foi o preventivo.

Altered Leukocyte Sphingolipid Pathway in Breast Cancer.

Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC) patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P) receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients. To the best of our knowledge, this is the first characterization of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles favoring high SPHK1 expression toward S1P production during BC development was observed, which was reversed by chemotherapy treatment, and reached similar levels to those found in healthy donors. Such levels were also correlated with high levels of TNF-α. Our data revealed an important role of the sphingolipid pathway in immune cells in BC with skewed signaling of S1P receptors, which favored cancer development even under chemotherapy, and may probably be a trigger of cancer resistance. Thus, these molecules must be considered as a target pathway for combined BC therapeutics.

Biological analysis and imaging applications of CdSe/CdSxSe1-x/CdS core-shell magic-sized quantum dot.

Although colloidal magic-sized quantum dots present great promise for biological applications due to their high stability and strong luminescence, nanotoxicological analyses are scarcely reported and biomedical applications have not been demonstrated. This is the first report on biological effects of CdSe/CdSxSe1-x/CdS core-shell magic-sized quantum dot (CS-MSQD) with specific application in breast cancer cell detection. The 2-nm CS-MSQD presents a broad bandwidth emission from 450 to 750nm, low toxicity, non-immunogenicity and biocompatibility. The CS-MSQD was conjugated to a breast cancer-specific Fab antibody, and passively diffused into cells for in vitro detection of a breast cancer cell line, demonstrating to be an unprecedented tool for biomedical applications.

Tempo decorrido entre a primeira consulta e o tratamento definitivo nos casos de câncer de mama no Sistema de Saúde público da cidade de Jundiaí / The elapsed time from the first outpatient visit to the definitive treatment in breast cancer cases of public health system in the city of Jundiaí

Os autores avaliaram o tempo decorrido entre a primeira consulta nas Unidades Básicas de Saúde e o tratamento cirúrgico do câncer de mama no Serviço de Mastologia na cidade de Jundiaí. Retrospectivamente, foram analisados os 80 novos casos de câncer de mama tratados no setor de mastologia do serviço público de Jundiaí, diagnosticados no ano de 2004, com análise do número de dias transcorridos entre a primeira consulta na UBS, a realização da mamografia e ultra-sonografia (se necessário), e a biópsia e o tratamento cirúrgico definitivo, por meio da avaliação de prontuários e dados informatizados ou entrevistas. Verificou-se que o tempo médio entre a primeira consulta e o tratamento cirúrgico foi de 270 dias. O maior intervalo de tempo ocorreu entre a realização da biópsia e a cirurgia definitiva: em média 79 dias. O agendamento da mamografia foi após aproximadamente dois meses. O intervalo entre o encaminhamento para o atendimento terciário e a consulta pelo especialista foi de 30 dias em média. Os resultados demonstram a necessidade de atuação na rede pública de Saúde com o intuito de agilização do fluxograma de atendimento, diminuindo o tempo entre o rastreamento, o diagnóstico e o tratamento do câncer de mama, melhorando, assim, o prognóstico da doença.

The study aimed to evaluate the elapsed time from the first outpatient visit in the Health Basic Units to the surgical treatment of breast cancer in the Mastology Department, in Jundiaí, southeastem Brazil. The study included the evaluation of eighty new cases of breast cancer that were diagnosed in 2004 retrospectively and treated in the Mastology Department of Jundiaí Public Healthcare, with analysis of the number of time elapsed with the first outpatient visit in HBU, the execution of mammography and ultrasonography (if necessary), biopsy and definitive surgical treatment through medical records, computerized data or interview. It was found that the mean time from the first outpatient visit to the surgical treatment was 270 days. The bigger elapsed time between the biopsy execution and the definitive surgery was about 79 days. The mammography scheduling took about two months, and one month more to conduct the schedule to the specialized sector. The results ratify the need of better function in Public Health System in order to make the flow chart service more agile, reducing the time between the breast cancer diagnosis and treatment, improving in that way the disease prognosis.