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The present observational study was designed to characterize the integrative profile of serum soluble mediators to describe the immunological networks associated with clinical findings and identify putative biomarkers for diagnosis and prognosis of active tuberculosis. The study population comprises 163 volunteers, including 84 patients with active pulmonary tuberculosis/(TB), and 79 controls/(C). Soluble mediators were measured by multiplexed assay. Data analysis demonstrated that the levels of CCL3, CCL5, CXCL10, IL-1ß, IL-6, IFN-γ, IL-1Ra, IL-4, IL-10, PDGF, VEGF, G-CSF, IL-7 were increased in TB as compared to C. Patients with bilateral pulmonary involvement/(TB-BI) exhibited higher levels of CXCL8, IL-6 and TNF with distinct biomarker signatures (CCL11, CCL2, TNF and IL-10) as compared to patients with unilateral infiltrates/(TB-UNI). Analysis of biomarker networks based in correlation power graph demonstrated small number of strong connections in TB and TB-BI. The search for biomarkers with relevant implications to understand the pathogenetic mechanisms and useful as complementary diagnosis tool of active TB pointed out the excellent performance of single analysis of IL-6 or CXCL10 and the stepwise combination of IL-6 â CXCL10 (Accuracy = 84 %; 80 % and 88 %, respectively). Together, our finding demonstrated that immunological networks of serum soluble biomarkers in TB patients differ according to the unilateral or bilateral pulmonary involvement and may have relevant implications to understand the pathogenetic mechanisms involved in the clinical outcome of Mtb infection.
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Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Humanos , Interleucina-10 , Citocinas , Interleucina-6 , BiomarcadoresRESUMEN
Chagas disease is a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagas disease cardiomyopathy (CCC) is the most prominent clinical form and can lead to heart failure, thromboembolism, and sudden death. While previous reports have supported a role for CD4+ T lymphocytes in the pathogenesis of CCC a comprehensive analysis of these cells during different clinical forms is lacking. Here, we used high-dimensional flow cytometry to assess the diversity of circulating CD4+ T cells in patients with distinct clinical forms. We found increased frequencies of CD4+CD69+ T cells in patients compared to controls. CD39+ regulatory T cells, represented by mesocluster 6 were reduced in mild CCC patients compared to controls. Cytotoxic CD4+ T cells co-expressing granzyme B and perforin were expanded in patients with Chagas disease and were higher in patients with mild CCC compared to controls. Furthermore, patients with mild CCC displayed higher frequencies of multifunctional effector memory CD4+ T cells. Our results demonstrate an expansion in activated CD4+ T cells and a decrease in a functional subset of regulatory T cells associated with the onset of Chagas cardiomyopathy, suggesting their role in the establishment of cardiac lesions and as potential biomarkers for disease aggravation.
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Cardiomiopatías , Enfermedad de Chagas , Insuficiencia Cardíaca , Humanos , Recuento de Linfocitos , Linfocitos T Reguladores , Enfermedad de Chagas/complicacionesRESUMEN
BACKGROUND: Few studies have explored regional asymmetries and their implications for health policies regarding episodes of falls among the population of ≥80 years old in continental and developing countries like Brazil with deep inequalities and sociocultural differences. OBJECTIVE: To evaluate the occurrence of falls and their association with functional capacity and nutritional status in the longest oldest-old living in two municipalities in the Northeast and Southeast of Brazil. METHODS: This is a cross-sectional study, with primary data collection in which were included in the research seniors aged 80 years or more, of both sexes, belonging to two Brazilian municipalities of discrepant socioeconomic aspects. The dependent variable was the occurrence of falls in the last year. The independent variables were grouped into demographic aspects, functional capacity and nutritional status. To identify variables that contribute to the occurrence of falls, the multiple logistic regression model, adopts a significance level of 5%. RESULTS: The sample was composed of 415 oldest-old adults. From the total, 32.3% reported having fallen in the last year, 24.7% in Brejo dos Santos and 37.8% in São Paulo. Among the former population, the mean value of walking speed for those who had falls was 0.27 m/s and for those who had no occurrence of falls was 0.33 m/s; and, among the seniors from São Paulo, the mean values were 0.51 m/s and 0.58 m/s, respectively. Significant correlations between walking speed and falls were verified for both populations, showing that the lower the walking speed, the higher the predisposition to falls. In the final regression model, the occurrence of falls was associated with moderate balance (OR = 5.28; CI: 1.11-25.18) among the longevous people Brejo dos Santos and with very poor functional performance (OR = 16.09; CI:1.46-177.06) among those from São Paulo. CONCLUSION: The results pointed out a lower prevalence of falls in longevous people from Brejo dos Santos than in those from São Paulo and differences regarding the associated factors, showing heterogeneity between the two populations; indicating the need for public policies and effective programmes aimed at preventing falls based on the maintenance or increase of functional capacity.
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Longevidad , Femenino , Masculino , Humanos , Anciano de 80 o más Años , Brasil/epidemiología , Estudios Transversales , Recolección de Datos , GenotipoRESUMEN
BACKGROUND: Among the oldest old, aged 80 years and over, the prevalence of disability is higher than in other age groups and can be considered a predictor of mortality. OBJECTIVE: To evaluate how psychosocial aspects and support networks influence the disability of these oldest-old individuals, performing a comparison between two longevous populations, one living in one of the poorest regions of Brazil, in the backlands of Paraíba, and another living in one of the largest urban centres in Latin America. METHOD: A cross-sectional study in which 417 oldest-old persons aged 80 years and older were interviewed, with data collected through the "Health, Welfare and Ageing" survey conducted in two Brazilian cities. Disability was assessed by reporting the need for assistance in Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs). Bivariate and multiple analyses were performed using R statistical software. RESULTS: Food insufficiency in the first years of life had negative repercussions on the disability of oldest old people living in the northeast. On the other hand, in this region, older people have a higher rate of support and live longer with their peers, which may contribute to reducing feelings of loneliness, depressive symptoms, and worse self-perception of health. In the Southeast, financial constraints, subjective poverty, and unmet needs may favour the development of functional limitations between long-lived people. CONCLUSION: Our findings indicate that regional differences in Brazil may influence the disability of older people aged 80 and older. In northeast Brazil, having no partner may contribute to disability for ADLs and IADLs; while, in the longevous population of São Paulo, having a worse self-rated health may contribute to disability for IADLs.
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Actividades Cotidianas , Personas con Discapacidad , Anciano , Anciano de 80 o más Años , Envejecimiento , Brasil/epidemiología , Estudios Transversales , HumanosRESUMEN
BACKGROUND: Since the 1980s, when dengue was reintroduced in Brazil, outbreaks and epidemics caused by different arbovirus strains transmitted by vector mosquitoes such as Aedes aegypti have been an annual occurrence. The aim of this study was to evaluate the behavioural change of high school students and teachers who participated in an educational intervention for the prevention and vector control of arboviral diseases. METHODS: In this school-based intervention, a self-reported questionnaire was used in a pre-post intervention methodology to assess environmental risk factors, sociodemographic variables and to measure attitudes and behaviours. In all, 883 high school students and teachers from the city of Campina Grande, in the state of Paraíba, northeastern Brazil, participated. The e-health intervention consisted of a competition between schools to comply with preventive actions via content production for social networks, and the monitoring was performed over a period of three months through the ZikaMob software developed by the researchers. RESULTS: Out of the 883 survey participants, 690 were students ranging in age from 14 to 41 years, with an average of 17 ± 2 years; and 193 were teachers from 22 to 64 years old, averaging 38 ± 9 years. The analysis of the data shows that significant differences in most of the target behaviours were apparent after the intervention, with an increase of about 10% in the performance of inspection actions; a 7% greater separation of recyclables and a 40% increase in the screening of windows among students. Students showed lower fear of, and a lower self-perception of the risk of, acquiring arboviruses than teachers on average. CONCLUSIONS: ZikaMob is an innovative strategy with the potential to be replicated in any location that has an internet network and can involve an unlimited number of participants.
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Aedes , Infecciones por Arbovirus , Arbovirus , Dengue , Adolescente , Adulto , Animales , Infecciones por Arbovirus/epidemiología , Infecciones por Arbovirus/prevención & control , Brasil/epidemiología , Dengue/epidemiología , Dengue/prevención & control , Humanos , Persona de Mediana Edad , Mosquitos Vectores , Adulto JovenRESUMEN
Breast cancer (BC) is mainly considered a disease in women, but male BC (MaBC) accounts for approximately 1.0% of BC diagnoses and 0.5% of malignant neoplasms in the western population. The stigmatization of MaBC, the fact that men are less likely to undergo regular health screenings, and the limited knowledge of health professionals about MaBC contribute to men being diagnosed at more advanced stages. The aim of this article is to increase the visibility of MaBC among urologists, who have more contact with male patients. This review highlights key points about the disease, the risk factors associated with MaBC, and the options for treatment. Obesity and increased population longevity are among the important risk factors for MaBC, but published studies have identified family history as extremely relevant in these patients and associated with a high penetrance at any age. There is currently no screening for MaBC in the general population, but the possibility of screening in men at high risk for developing BC can be considered. The treatment of MaBC is multidisciplinary, and, because of its rarity, there are no robust clinical studies evaluating the role of systemic therapies in the management of both localized and metastatic disease. Therefore, in current clinical practice, treatment strategies for men with breast cancer are extrapolated from information arising from studies in female patients.
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Neoplasias de la Mama Masculina , Neoplasias de la Mama Masculina/diagnóstico , Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/terapia , Femenino , Humanos , Masculino , UrólogosRESUMEN
Admixed populations have not been examined in detail in cancer genetic studies. Here, we inferred the local ancestry of cancer-associated single nucleotide polymorphisms (SNPs) and haplotypes of a highly admixed Brazilian population. SNP array was used to genotype 73 unrelated individuals aged 80-102 years. Local ancestry inference was performed by merging genotyped regions with phase three data from the 1000 Genomes Project Consortium using RFmix. The average ancestry tract length was 9.12-81.71 megabases. Strong linkage disequilibrium was detected in 48 haplotypes containing 35 SNPs in 10 cancer driver genes. All together, 19 risk and eight protective alleles were identified in 23 out of 48 haplotypes. Homozygous individuals were mainly of European ancestry, whereas heterozygotes had at least one Native American and one African ancestry tract. Native-American ancestry for homozygous individuals with risk alleles for HNF1B, CDH1, and BRCA1 was inferred for the first time. Results indicated that analysis of SNP polymorphism in the present admixed population has a high potential to identify new ancestry-associated alleles and haplotypes that modify cancer susceptibility differentially in distinct human populations. Future case-control studies with populations with a complex history of admixture could help elucidate ancestry-associated biological differences in cancer incidence and therapeutic outcomes.
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BACKGROUND: Inflammatory/immunological serum markers are useful for the early detection of organ dysfunction, helping the diagnosis of sepsis. Although the detection of blood biomarkers is a standard practice, the use of noninvasive samples (eg saliva) would be beneficial. AIM: To investigate the saliva of hospitalized patients with and without sepsis and identify the levels of inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL-6) and nitric oxide (NO). METHODS: Saliva samples were collected from 26 patients in intensive care unit with diagnosis of sepsis and from 26 without sepsis (control). The levels of CRP were determined by using latex agglutination test, whereas those of procalcitonin and IL-6 by ELISA and NO by the Griess reaction. RESULTS: Of 26 patients with sepsis, 14 were males (54%) with a mean age of 63.81 ± 3.48 years. The control group had the same distribution for gender, with mean age 65.04 ± 4.07 years. Sepsis group showed higher salivary concentrations of CRP, PCT, IL-6 and NO, with only levels of IL-6 being statistically different (P = .0001). CONCLUSIONS: Patients with sepsis had significantly higher levels of IL-6 in their saliva, suggesting that this biological sample could be useful in the diagnosis of this condition.
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Proteína C-Reactiva/análisis , Interleucina-6/análisis , Óxido Nítrico/análisis , Polipéptido alfa Relacionado con Calcitonina/análisis , Saliva/química , Sepsis/diagnóstico , Anciano , Proteína C-Reactiva/inmunología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Etilenodiaminas , Femenino , Hospitalización , Humanos , Interleucina-6/inmunología , Pruebas de Fijación de Látex , Masculino , Persona de Mediana Edad , Óxido Nítrico/inmunología , Polipéptido alfa Relacionado con Calcitonina/inmunología , Sepsis/inmunología , SulfanilamidasRESUMEN
OBJECTIVES: In Brazil, the National Policy for Dengue Control seeks to incorporate the lessons of national and international experience in dengue control, emphasising the need for health education activities. The objective of this study was to evaluate and compare knowledge, attitudes and behaviours related to the prevention of arboviruses before and after a two-month educational intervention using a learning platform on mobile devices. METHODS: This quasi-experimental study corresponds to the first phase of the project 'Impact of mobile learning in the prevention and management of complications caused by arboviruses (Zika, Dengue, Chikungunya) - ZIKAMOB', sponsored as part of the British Council Newton Fund. RESULTS: Thirty of the 93 participants were first-year undergraduate university students (36.7% male), and 63 were police officers (84.1% male). The pattern of attitudes and behaviour was very similar in both groups before the intervention. The students changed their attitudes and behaviour (P = 0.032) in relation to their engagements in actions for the prevention of arboviral diseases and several other activities related to house inspections and precautions with water tanks (P < 0.01). However, recycling and surveillance activities were not as effective in changing behaviour. Female participants showed more motivation to participate in preventive activities, but living alone and working were barriers to participation. Individuals who already perform selective waste collection and are cultivating gardens demonstrated both a positive attitude and a positive behaviour towards actions for the prevention of arboviral diseases. CONCLUSION: Mobile learning and behaviour change theories might be successful as the basis for school-based and community-based interventions to avoid arboviruses. These outcomes need to be confirmed in broader future studies.
OBJECTIFS: Au Brésil, la politique nationale de lutte contre la dengue cherche à intégrer les leçons tirées des expériences nationales et internationales en matière de lutte contre la dengue, en insistant sur la nécessité d'activités d'éducation sur la santé. L'objectif de cette étude était d'évaluer et de comparer les connaissances, les attitudes et les comportements liés à la prévention des arbovirus avant et après une intervention éducative de deux mois à l'aide d'une plate-forme d'éducation basée sur des appareils mobiles. MÉTHODES: Cette étude quasi expérimentale correspond à la première phase du projet "Impact de l'éducation mobile dans la prévention et la prise en charge des complications causées par les arbovirus (Zika, Dengue, Chikungunya) - ZIKAMOB", parrainé dans le cadre du British Council Newton Fund. RÉSULTATS: Trente des 93 participants étaient des étudiants de première année d'université (36,7% d'hommes) et 63 étaient des agents de police (84,1% d'hommes). Le modèle des attitudes et de comportement était très similaire dans les deux groupes avant l'intervention. Les étudiants ont changé leurs attitudes et comportements (P = 0,032) en ce qui concerne leur participation à des actions de prévention des maladies à arbovirus et à plusieurs autres activités liées aux inspections des maisons et aux précautions d'utilisation des réservoirs d'eau (P < 0,01). Cependant, les activités de recyclage et de surveillance n'étaient pas aussi efficaces pour le changement de comportement. Les participantes étaient plus motivées à participer aux activités de prévention, mais le fait de vivre seul et de travailler constituait un obstacle à la participation. Les personnes qui effectuent déjà une collecte sélective des déchets et cultivent des jardins ont démontré à la fois une attitude positive et un comportement positif à l'égard des actions de prévention des maladies à arbovirus. CONCLUSION: Les théories sur l'éducation mobile et le changement de comportement pourraient être couronnées de succès en tant que base d'interventions en milieu scolaire et communautaire visant à éviter les arbovirus. Ces résultats doivent être confirmés dans des études supplémentaires plus larges.
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Infecciones por Arbovirus/epidemiología , Teléfono Celular , Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Aedes/fisiología , Animales , Infecciones por Arbovirus/prevención & control , Brasil/epidemiología , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/prevención & control , Dengue/epidemiología , Dengue/prevención & control , Femenino , Humanos , Masculino , Policia , Evaluación de Programas y Proyectos de Salud , Estudiantes , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/prevención & controlRESUMEN
Maize is highly responsive to the application of nitrogen to achieve high productivity. Inoculation with diazotrophic bacteria can improve plant growth with low N fertilization. The objective was to evaluate the inoculation of two species of diazotrophs on N metabolism in maize plants, in the presence of two concentrations of nitrogen in a hydroponic system. A factorial arrangement composed of two N levels (3.0 and 0.3 mM), with the presence of Hs-Herbaspirillum seropedicae, and Ab-Azospirillum brasilense or not. The parameters used were dry mass; N, P, and K accumulation; nitrate reductase activity; soluble fractions in roots and leaves. The inoculation altered the N metabolism and promoted greater development of maize plants, as well as a higher accumulation of P and K in the shoots. A more intensive process of N assimilation was evidenced when the plants were inoculated with H. seropedicae, leading to increased levels of NO3- and reduced N-amino, sugars, and NH4+ in leaves associated with high N level, opposite of A. brasilense.
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Azospirillum brasilense/fisiología , Herbaspirillum/fisiología , Nitrógeno/metabolismo , Zea mays/metabolismo , Zea mays/microbiología , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismoRESUMEN
BACKGROUND: Spastic paraplegia, optic atrophy and neuropathy (Spoan syndrome) is an autosomal recessive disease with approximately 70 cases recorded in Brazil and Egypt. METHODS: This is a prospective longitudinal study performed with 47 patients affected with Spoan syndrome of seven communities of Rio Grande do Norte (Brazil) to investigate changes in motor function based on comparative data obtained from a 10-year follow-up. RESULTS: The mean age of the participants was 47.21 ± 12.42 years old, and the mean age at loss of ambulation and hand function were 10.78 ± 5.55 and 33.58 ± 17.47 years old, respectively. Spearman's correlation analysis between the score on the Modified Barthel Index and the investigated variables evidenced statistical significance for age (p < 0.001) and right- and left-hand grip strength (p = 0.042 and p = 0.021, respectively). Statistical significance was not evidenced for the remainder of the variables, including age at onset of symptoms (p = 0.634), age at loss of ambulation (p = 0.664) and age at loss of hand function (p = 0.118). CONCLUSIONS: Our analysis allows asserting that the participants exhibited slight dependence until age 35. The greatest losses occurred from ages 35 to 41, and starting at 50, practically all patients become completely dependent. These findings are relevant for determining the prognosis as well as suitable treatment, rehabilitation and assistive technology for these individuals.
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Neuropatía Hereditaria Motora y Sensorial/complicaciones , Trastornos Motores/etiología , Atrofia Óptica/complicaciones , Paraplejía/complicaciones , Adolescente , Adulto , Edad de Inicio , Brasil , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Deliberate reflection when practising the diagnosis of clinical cases has been shown to develop medical students' diagnostic competence. Adding guidance by cueing reflection or providing modelling of reflection increased the benefits of reflection for advanced (Years 5-6) students. The present study investigated whether we could replicate and extend these findings by comparing the effects of free, cued and modelled reflection on novice students' diagnostic competence. METHODS: A total of 80 third-year medical students participated in a two-phase experiment. In the learning phase, students diagnosed nine clinical cases under one of three conditions: free reflection; cued reflection, and modelled reflection. Two weeks later, all students diagnosed four new examples of the diseases studied in the learning phase and four cases of non-studied related diseases ('adjacent diseases'). The main outcome measurements were diagnostic accuracy scores (range 0-1) on studied and adjacent diseases. RESULTS: For studied diseases, there was a significant effect of experimental condition on diagnostic accuracy (p < 0.02), with the cued-reflection group (mean = 0.58, standard deviation [SD] = 0.23) performing significantly better than the free-reflection group (mean = 0.41, SD = 0.20; p < 0.02). The cued-reflection and modelled-reflection groups (mean = 0.54, SD = 0.22) did not differ in diagnostic accuracy (p > 0.05), nor did the modelled-reflection group perform better than the free-reflection group (p > 0.05). For adjacent diseases, the three groups scored extremely low, without significant differences in performance (p > 0.05). Cued reflection and free reflection were rated as requiring similar effort (p > 0.05) and both were more demanding than studying examples of reflection (both p < 0.001) in the learning phase. CONCLUSIONS: Simply cueing novice students' reflection to focus it on relevant diseases was sufficient to increase diagnostic performance relative to reflection without any guidance. Cued reflection and studying examples of reflection appear to be equally useful approaches for teaching clinical diagnosis to novice students. Students found studying examples of reflection required less effort but cued reflection will certainly demand much less investment from teachers.
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Toma de Decisiones Clínicas/métodos , Aprendizaje Basado en Problemas/métodos , Estudiantes de Medicina/psicología , Competencia Clínica , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
The aim of this cross-sectional study was to investigate beliefs, attitudes and reproductive behaviours in relation to consanguinity in a population living in the backlands of north-eastern Brazil. Data were collected by face-to-face interview from 147 high school students aged 13-20 years and from 532 elderly individuals aged 60 years and over from Brejo dos Santos in the state of Paraíba in 2017. The frequency of consanguineous marriage was found to have increased over the generations, being 15.9% in the parents of the elderly participants, 17.1% in the elderly participants themselves and 20.5% in their descendants. Although 258 (50.9%) of the elderly interviewees opposed consanguineous union, 341 (65.3%) would approve of the marriage of their children with relatives. Both the young (n=108 or 78.3%) and elderly (n=398 or 80.4%) interviewees believed that consanguineous marriages were no more durable than non-consanguineous marriages (p=0.578). Additionally, 408 (82.4%) of the elderly individuals and 108 (80.6%) of the students recognized that spouses in consanguineous unions experience conflicts, just like other couples do (p=0.625). In both groups, the majority of the participants did not believe that consanguinity increased the risk of having children with disabilities. The regression of the two continuous variables 'age' and 'positive attitudes score' showed a significant correlation, suggesting that younger individuals are more susceptible to the influence of cultural factors contributing to consanguinity, such as the opinions of their parents and grandparents. The belief that consanguineous unions are more durable showed a significant difference between elderly individuals in consanguineous and non-consanguineous unions (p=0.001); the former were 2.42 more likely to believe that marriages between relatives contributes to marriage durability.
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Actitud , Consanguinidad , Relaciones Intergeneracionales , Matrimonio/psicología , Adolescente , Adulto , Factores de Edad , Anciano , Brasil , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducta Reproductiva/psicología , Medio Social , Adulto JovenRESUMEN
In seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, a balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, as a proinflammatory microenvironment modulated by interleukin-10 (IL-10) is shown to be relevant to potentiate anti-Trypanosoma cruzi drug activity. This study aimed to identify the potential immunomodulatory activities of the anti-T. cruzi K777, pyronaridine (PYR), and furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected (NI) subjects and chronic Chagas disease (CD) patients. Our results showed low cytotoxicity to PBMC populations, with 50% cytotoxic concentrations (CC50) of 71.0 µM (K777), 9.0 µM (PYR), and greater than 20 µM (FUR). In addition, K777 showed no impact on the exposure index (EI) of phytohemagglutinin-stimulated leukocytes (PHA), while PYR and FUR treatments induced increased EI of monocytes and T lymphocytes at late stages of apoptosis in NI subjects. Moreover, K777 induced a more prominent proinflammatory response (tumor necrosis factor alpha-positive [TNF-α+] CD8+/CD4+, gamma interferon-positive [IFN-γ+] CD4+/CD8+ modulated by interleukin-10-positive [IL-10+] CD4+ T/CD8+ T) than did PYR (TNF-α+ CD8+, IL-10+ CD8+) and FUR (TNF-α+ CD8+, IL-10+ CD8+). Signature analysis of intracytoplasmic cytokines corroborated the proinflammatory/modulated (K777) and proinflammatory (PYR and FUR) profiles previously found. In conclusion, the lead compound K777 may induce beneficial changes in the immunological profile of patients presenting the chronic phase of Chagas disease and may contribute to a more effective therapy against the disease.
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Factores Inmunológicos/farmacología , Trypanosoma cruzi/efectos de los fármacos , Apoptosis/efectos de los fármacos , Enfermedad de Chagas/prevención & control , Furazolidona/farmacología , Leucocitos/efectos de los fármacos , Naftiridinas/farmacología , Fitohemaglutininas/farmacologíaRESUMEN
OBJECTIVE: This study aimed to investigate the influence of Lactobacillus rhamnosus intake on the development of candidiasis and cytokines release. MATERIAL AND METHODS: Candida suspensions were inoculated into the oral cavity of experimentally immunosuppressed mice for candidiasis induction. The animals were divided into experimental groups: candidiasis with no probiotic intake (F), candidiasis with probiotic intake during Candida inoculation (FP), and candidiasis with probiotic intake 14 days before inoculation with Candida (FPP); and control groups: (C), (CP), and (CPP) without inducing candidiasis with probiotic intake in the same manner as groups F, FP, and FPP, respectively. After these periods, samples were collected from the oral cavity for yeast counts and, after euthanasia, the tongues of the animals were removed for histological analysis. Sera samples were also collected for analysis of IL-1 beta, TNF-alpha, INF-gamma, IL-12, IL-4, and IL-10. RESULTS: FP group showed lower Candida counts in the oral cavity, and the presence of Candida was almost not detected in FPP group. In tissues, the counts of fungi were significantly lower in FPP group, followed by FP. Groups that consumed probiotics also had lower histological and inflammatory infiltrates compared to F. Cytokines analysis demonstrated low concentrations of TNF-α, IL-12, IL-4, and IL-10 in all the groups, and no statistical difference between them. The production of IL-6 could be better detected, and the experimental groups that consumed the probiotic showed significant lower levels of this cytokine. CONCLUSIONS: The results suggest that L. rhamnosus intake, especially preventively, may avoid or decrease the development of candidiasis in immunosuppressed mice. CLINICAL RELEVANCE: This work adds scientific evidences that probiotics intake can avoid the development of candidiasis.
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Candidiasis Bucal/prevención & control , Lacticaseibacillus rhamnosus , Probióticos/farmacología , Animales , Biomarcadores/sangre , Citocinas/sangre , Modelos Animales de Enfermedad , Huésped Inmunocomprometido , Masculino , RatonesRESUMEN
SPOAN syndrome is a neurodegenerative disorder mainly characterized by spastic paraplegia, optic atrophy and neuropathy (SPOAN). Affected patients are wheelchair bound after 15 years old, with progressive joint contractures and spine deformities. SPOAN patients also have sub normal vision secondary to apparently non-progressive congenital optic atrophy. A potential causative gene was mapped at 11q13 ten years ago. Here we performed next-generation sequencing in SPOAN-derived samples. While whole-exome sequencing failed to identify the causative mutation, whole-genome sequencing allowed to detect a homozygous 216-bp deletion (chr11.hg19:g.66,024,557_66,024,773del) located at the non-coding upstream region of the KLC2 gene. Expression assays performed with patient's fibroblasts and motor neurons derived from SPOAN patients showed KLC2 overexpression. Luciferase assay in constructs with 216-bp deletion confirmed the overexpression of gene reporter, varying from 48 to 74%, as compared with wild-type. Knockdown and overexpression of klc2 in Danio rerio revealed mild to severe curly-tail phenotype, which is suggestive of a neuromuscular disorder. Overexpression of a gene caused by a small deletion in the non-coding region is a novel mechanism, which to the best of our knowledge, was never reported before in a recessive condition. Although the molecular mechanism of KLC2 up-regulation still remains to be uncovered, such example adds to the importance of non-coding regions in human pathology.
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Expresión Génica , Proteínas Asociadas a Microtúbulos/genética , Atrofias Ópticas Hereditarias/genética , Eliminación de Secuencia , Paraplejía Espástica Hereditaria/genética , Animales , Cromosomas Humanos Par 11 , Análisis Mutacional de ADN , Neuropatía Hereditaria Motora y Sensorial/genética , Humanos , Cinesinas , Síndrome , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
We have recently described a family with a condition (Santos syndrome (SS; MIM 613005)) characterized by fibular agenesis/hypoplasia, hypoplastic femora and grossly malformed/deformed clubfeet with severe oligodactyly, ungual hypoplasia/anonychia, sometimes associated with mild brachydactyly and occasional pre-axial polydactyly. Autosomal dominant inheritance with incomplete penetrance was suggested, but autosomal recessive inheritance could not be ruled out, due to the high frequency of consanguineous matings in the region where the family lived. This report deals with linkage studies and exome sequencing, disclosing a novel variant in WNT7A, c.934G>A (p.Gly312Ser), as the cause of this syndrome. This variant was present in homozygous state in five individuals typically affected by the SS syndrome, and in heterozygous state in the son of one affected homozygous individual. The heterozygous boy presented only unilateral complex polysyndactyly and we hypothesize that he either presents a distinct defect or that his phenotype results from a rare, mild clinical manifestation of the variant in heterozygous state. Variants in WNT7A are known to cause at least two other limb defect disorders, the syndromes of Fuhrmann and Al-Awadi/Raas-Rothschild. Despite their variable degree of expressivity and overlap, the three related conditions can be differentiated phenotypically in most instances.
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Enfermedades del Desarrollo Óseo/genética , Pie Equinovaro/genética , Peroné/anomalías , Dedos/anomalías , Marcadores Genéticos/genética , Deformidades Congénitas de las Extremidades/genética , Uñas Malformadas/genética , Polidactilia/genética , Proteínas Wnt/genética , Secuencia de Aminoácidos , Consanguinidad , Femenino , Ligamiento Genético , Homocigoto , Humanos , Masculino , Repeticiones de Microsatélite/genética , Mutación , Linaje , Fenotipo , Alineación de SecuenciaRESUMEN
BACKGROUND: Mutations in PROP1, HESX1 and LHX3 are associated with combined pituitary hormone deficiency (CPHD) and orthotopic posterior pituitary lobe (OPP). OBJECTIVE: To identify mutations in PROP1, HESX1 and LHX3 in a large cohort of patients with CPHD and OPP (35 Brazilian, two Argentinian). DESIGN AND METHODS: We studied 23 index patients with CPHD and OPP (six familial and 17 sporadic) as well as 14 relatives. PROP1 was sequenced by the Sanger method in all except one sporadic case studied using a candidate gene panel. Multiplex ligation-dependent probe amplification (MLPA) was applied to one familial case in whom PROP1 failed to amplify by PCR. In the 13 patients without PROP1 mutations, HESX1 and LHX3 were sequenced by the Sanger method. RESULTS: We identified PROP1 mutations in 10 index cases. Three mutations were novel: one affecting the initiation codon (c.1A>G) and two affecting splicing sites, c.109+1G>A and c.342+1G>C. The known mutations, c.150delA (p.Arg53Aspfs*112), c.218G>A (p.Arg73His), c.263T>C (p.Phe88Ser) and c.301_302delAG (p.Leu102Cysfs*8), were also detected. MLPA confirmed complete PROP1 deletion in one family. We did not identify HESX1 and LHX3 mutations by Sanger. CONCLUSION: PROP1 mutations are a prevalent cause of congenital CPHD with OPP, and therefore, PROP1 sequencing must be the first step of molecular investigation in patients with CPHD and OPP, especially in populations with a high frequency of PROP1 mutations. In the absence of mutations, massively parallel sequencing is a promising approach. The high prevalence and diversity of PROP1 mutations is associated with the ethnic background of this cohort.
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Proteínas de Homeodominio/genética , Hipopituitarismo/genética , Proteínas con Homeodominio LIM/genética , Mutación/genética , Neurohipófisis/metabolismo , Factores de Transcripción/genética , Adolescente , Adulto , Brasil , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Diazotrophs are able to stimulate plant growth. This study aimed at evaluating the effect of inoculation of five diazotrophic strains on growth promotion and nitrate reductase (NR, EC 1.7.1.1) activity in sugarcane. An experiment was carried out from three stages of cultivation: sprouting, tubes, and in hydroponics. On the first two stages, seven treatments were adopted: uninoculated control; mixed inoculation with five strains; and individual inoculation with Gluconacetobacter diazotrophicus (Gd), Herbaspirillum rubrisubalbicans (Hr), Herbaspirillum seropedicae (Hs), Nitrospirillum amazonense (Na), and Paraburkholderia tropica (Pt). The four treatments showing the best performance were transferred to the hydroponic system for analysis of NR activity. Hs, Pt, and the mixture of all strains led to the highest seedling biomass in tubes, followed by Hr. In hydroponics, the mixture and the strain Hr had the highest growth-promoting effect. NR activity was influenced by inoculation only under low N supply conditions, with positive effect of Hr, Pt, and the mixture.
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Inoculantes Agrícolas/fisiología , Burkholderiaceae/fisiología , Gluconacetobacter/fisiología , Herbaspirillum/fisiología , Nitrato-Reductasa/metabolismo , Proteínas de Plantas/metabolismo , Rhodospirillaceae/fisiología , Saccharum/microbiología , Fijación del Nitrógeno , Saccharum/enzimología , Saccharum/crecimiento & desarrolloRESUMEN
BACKGROUND: Immunosenescence is associated with several changes in adaptive and innate immune cells. Altered cytokine production is among the most prominent of these changes. The impact of age-related alterations on cytokine global profiles produced by distinct populations of leukocytes from healthy Brazilian individuals was studied. We analysed frequencies of cytokine-producing lymphocytes and innate immune cells from individuals at several ages spanning a lifetime period (0-85 years). RESULTS: Healthy adult individuals presented a balanced profile suggestive of a mature immune system with equal contributions of both innate and adaptive immunity and of both categories of cytokines (inflammatory and regulatory). In healthy newborns and elderly, innate immune cells, especially neutrophils and NK-cells, contributed the most to a balanced profile of cytokines. CONCLUSIONS: Our results support the hypothesis that ageing is not associated with a progressive pro-inflammatory cytokine production by all leukocytes but rather with distinct fluctuations in the frequency of cytokine-producing cells throughout life.