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1.
PLoS Biol ; 22(9): e3002791, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39255306

RESUMO

Virulence of apicomplexan parasites is based on their ability to divide rapidly to produce significant biomass. The regulation of their cell cycle is therefore key to their pathogenesis. Phosphorylation is a crucial posttranslational modification that regulates many aspects of the eukaryotic cell cycle. The phosphatase PP1 is known to play a major role in the phosphorylation balance in eukaryotes. We explored the role of TgPP1 during the cell cycle of the tachyzoite form of the apicomplexan parasite Toxoplasma gondii. Using a conditional mutant strain, we show that TgPP1 regulates many aspects of the cell cycle including the proper assembly of the daughter cells' inner membrane complex (IMC), the segregation of organelles, and nuclear division. Unexpectedly, depletion of TgPP1 also results in the accumulation of amylopectin, a storage polysaccharide that is usually found in the latent bradyzoite form of the parasite. Using transcriptomics and phospho-proteomics, we show that TgPP1 mainly acts through posttranslational mechanisms by dephosphorylating target proteins including IMC proteins. TgPP1 also dephosphorylates a protein bearing a starch-binding domain. Mutagenesis analysis reveals that the targeted phospho-sites are linked to the ability of the parasite to regulate amylopectin steady-state levels. Therefore, we show that TgPP1 has pleiotropic roles during the tachyzoite cell cycle regulation, but also regulates amylopectin accumulation.


Assuntos
Amilopectina , Proteína Fosfatase 1 , Proteínas de Protozoários , Toxoplasma , Toxoplasma/metabolismo , Toxoplasma/genética , Toxoplasma/enzimologia , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 1/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Amilopectina/metabolismo , Fosforilação , Ciclo Celular , Animais , Humanos
2.
PLoS Biol ; 21(5): e3002124, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37205711

RESUMO

Necrotizing enterocolitis (NEC) is a gastrointestinal complication of premature infants with high rates of morbidity and mortality. A comprehensive view of the cellular changes and aberrant interactions that underlie NEC is lacking. This study aimed at filling in this gap. We combine single-cell RNA sequencing (scRNAseq), T-cell receptor beta (TCRß) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions, and zonal changes in NEC. We find an abundance of proinflammatory macrophages, fibroblasts, endothelial cells as well as T cells that exhibit increased TCRß clonal expansion. Villus tip epithelial cells are reduced in NEC and the remaining epithelial cells up-regulate proinflammatory genes. We establish a detailed map of aberrant epithelial-mesenchymal-immune interactions that are associated with inflammation in NEC mucosa. Our analyses highlight the cellular dysregulations of NEC-associated intestinal tissue and identify potential targets for biomarker discovery and therapeutics.


Assuntos
Enterocolite Necrosante , Lactente , Recém-Nascido , Humanos , Enterocolite Necrosante/genética , Células Endoteliais , Intestino Delgado , Recém-Nascido Prematuro , Intestinos , Mucosa Intestinal
3.
Development ; 149(8)2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35050308

RESUMO

Maintenance of a healthy pregnancy is reliant on a successful balance between the fetal and maternal immune systems. Although the maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Consistent with recent reports in other fetal organs, T cells with memory phenotypes, although rare in abundance, were detected within the PV tissue and vasculature. Moreover, we determined that T cells isolated from PV samples may be more proliferative after T cell receptor stimulation than adult T cells at baseline. Collectively, we identified multiple subtypes of fetal immune cells within the PV and specifically highlight the enhanced proliferative capacity of fetal PV T cells.


Assuntos
Vilosidades Coriônicas/imunologia , Placenta/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Vilosidades Coriônicas/metabolismo , Feminino , Feto/imunologia , Feto/metabolismo , Citometria de Fluxo , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Ativação Linfocitária , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Células T de Memória/citologia , Células T de Memória/imunologia , Células T de Memória/metabolismo , Placenta/citologia , Placenta/metabolismo , Gravidez , Segundo Trimestre da Gravidez , Receptores de Superfície Celular/metabolismo , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Análise de Célula Única/métodos , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo
4.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39000409

RESUMO

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF-ß (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast Green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-ß inhibitor, IC50 114.3 µM), losmapimod (p38 inhibitor, IC50 17.6 µM) and SP600125 (c-Jun inhibitor, IC50 3.9 µM). This effect was independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the hearts of the patients.


Assuntos
Cardiomiopatia Chagásica , Fibrose , Camundongos Endogâmicos C57BL , Piridonas , Animais , Piridonas/farmacologia , Piridonas/uso terapêutico , Cardiomiopatia Chagásica/tratamento farmacológico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/metabolismo , Cardiomiopatia Chagásica/patologia , Camundongos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/parasitologia , Miocárdio/patologia , Miocárdio/metabolismo , Colágeno/metabolismo , Trypanosoma cruzi/efeitos dos fármacos , Humanos , Doença Crônica , Fator de Crescimento Transformador beta/metabolismo , Modelos Animais de Doenças , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Masculino , Antracenos
5.
J Environ Manage ; 355: 120540, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442658

RESUMO

This study presents a new method to incorporate the No Net Loss (NNL) principle within corporate Environmental, Social, and Governance (ESG) frameworks. This principle aims to ensure that biodiversity losses from human activities are fully offset. In this context, we tackle two main challenges: managing epistemic uncertainties in environmental modeling and accurately assessing compensatory areas needed to replace lost habitats. Focusing on Brazil's diverse biomes, which are undergoing rapid changes, we highlight the role of expert opinion surveys in addressing the uncertainties of the InVEST Habitat Quality, a model that simulates changes in landscape integrity under different land use scenarios. Our analysis across three of Brazil's regions - Caatinga Semi-arid, Cerrado Savanna, and Atlantic Forest - leverages open-source data to reveal substantial habitat losses due to activities like wind farm development, mining, and intensive agriculture, leading to a widespread decline in habitat quality. We introduce the Equivalent Biodiversity Area (EBA) metric to support NNL and Net Gain of Biodiversity efforts, measured in hectares. Findings show a reduction in EBA across all studied areas, highlighting the need for effective compensation strategies. Such strategies should merge Legal Reserves and ecological restoration into ESG policies, encourage landholder collaboration, and align with larger environmental efforts, such as watershed revitalization and Biodiversity Credits markets.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Humanos , Brasil , Conservação dos Recursos Naturais/métodos , Biodiversidade , Florestas
6.
Dentomaxillofac Radiol ; 53(6): 341-353, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38970385

RESUMO

OBJECTIVES: This study aimed to verify the accuracy of clinical protocols for the diagnosis of disc displacement (DD) compared with MRI, considering examiners' calibration. METHODS: PubMed, Cochrane (Central), Scopus, Web of Science, LILACS, Embase, Science Direct, Google Scholar, and DANS EASY Archive databases were searched. Two reviewers independently screened and selected the studies. A meta-analysis was conducted using the R Statistical software. Results are shown using sensitivity and specificity, and 95% confidence intervals. RESULTS: Of the 20 studies included in the systematic review, only three were classified as low risk of bias. Seventeen studies were included in the meta-analysis. Compared to MRI, clinical protocols showed overall sensitivity and specificity of 0.75 (0.63-0.83) and 0.73 (0.59-0.84) for DD diagnosis, respectively. For DD with reduction, sensitivity was 0.64 (0.48-0.77) and specificity was 0.72 (0.48-0.87). For DD without reduction, sensitivity was 0.58 (0.39-0.74) and specificity 0.93 (0.83-0.97). Only 8 studies reported examiner calibration when performing clinical and/or MRI evaluation; nevertheless, calibration showed a tendency to improve the diagnosis of DD. CONCLUSION: The sensitivity and specificity of clinical protocols in the diagnosis of DD are slightly below the recommended values, as well as the studies lack calibration of clinical and MRI examiners. Examiner calibration seems to improve the diagnosis of DD.


Assuntos
Luxações Articulares , Imageamento por Ressonância Magnética , Disco da Articulação Temporomandibular , Transtornos da Articulação Temporomandibular , Humanos , Calibragem , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/patologia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Sensibilidade e Especificidade , Disco da Articulação Temporomandibular/diagnóstico por imagem , Disco da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/patologia
7.
J Craniofac Surg ; 34(6): e546-e549, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37497785

RESUMO

INTRODUCTION: Congenital midline cervical cleft is a rare condition and is frequently misdiagnosed as thyroglossal duct cyst. Otherwise, the combination of congenital midline cervical cleft and thyroglossal duct fibrosis in the same patient is as rare as important to be registered with the intention to inform and offer specific managements details for the literature. CASE PRESENTATION: Eight-year-old boy with simultaneous congenital midline cervical cleft and a thyroglossal duct fibrosis. The anatomic, clinical, radiologic, and pathologic characteristics of the congenital midline cervical cleft are described as well as surgical technique for removal and repair with Z-plasty. CONCLUSION: Congenital midline cervical cleft is a rare condition and when diagnosed must be surgically treated as early as possible. Its differential diagnosis is a clinical challenge.


Assuntos
Anormalidades Craniofaciais , Procedimentos de Cirurgia Plástica , Anormalidades da Pele , Cisto Tireoglosso , Masculino , Humanos , Criança , Pescoço/cirurgia , Anormalidades da Pele/cirurgia , Anormalidades Craniofaciais/cirurgia , Cisto Tireoglosso/diagnóstico , Cisto Tireoglosso/cirurgia
8.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38069233

RESUMO

Atmospheric particulate matter (PM) with diameters below 10 µm (PM10) may enter the lungs through inhalation and are linked to various negative health consequences. Emergent evidence emphasizes the significance of cell metabolism as a sensitive target of PM exposure. However, the current understanding of the relationship between PM composition, conventional toxicity measures, and the rewiring of intracellular metabolic processes remains limited. In this work, PM10 sampled at a residential area (urban background, UB) and a traffic-impacted location (roadside, RS) of a Portuguese city was comprehensively characterized in terms of polycyclic aromatic hydrocarbons and plasticizers. Epithelial lung cells (A549) were then exposed for 72 h to PM10 organic extracts and different biological outcomes were assessed. UB and RS PM10 extracts dose-dependently decreased cell viability, induced reactive oxygen species (ROS), decreased mitochondrial membrane potential, caused cell cycle arrest at the G0/G1 phase, and modulated the intracellular metabolic profile. Interestingly, the RS sample, richer in particularly toxic PAHs and plasticizers, had a greater metabolic impact than the UB extract. Changes comprised significant increases in glutathione, reflecting activation of antioxidant defences to counterbalance ROS production, together with increases in lactate, NAD+, and ATP, which suggest stimulation of glycolytic energy production, possibly to compensate for reduced mitochondrial activity. Furthermore, a number of other metabolic variations hinted at changes in membrane turnover and TCA cycle dynamics, which represent novel clues on potential PM10 biological effects.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/análise , Espécies Reativas de Oxigênio/farmacologia , Plastificantes/farmacologia , Pulmão/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Monitoramento Ambiental
9.
Headache ; 62(6): 748-754, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35674092

RESUMO

OBJECTIVE: To evaluate the association between headache, myofascial temporomandibular disorder (TMD), and awake bruxism (AB). BACKGROUND: Bruxism seems to act as a risk factor for TMD and its associated comorbidities, such as headaches. METHODS: In total, 406 medical records of individuals who sought care at a university dental clinic were screened. The Research Diagnostic Criteria for Temporomandibular Disorders was used to assess and diagnose TMD, as well as to obtain self-reports of AB and headache. RESULTS: The sample consisted of 307 medical records. About 72.5% (221/305) of the sample reported having headaches, and 67.4% (180/267) and 68.4% (210/307) were diagnosed with AB and TMD, respectively. Individuals who reported having AB (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.09-4.7) and who were diagnosed with myofascial TMD (OR, 2.53; 95% CI, 1.15-5.5) were more likely to have had headaches in the past 6 months when compared with patients without myofascial TMD and bruxism. Also, individuals who self-reported headache were 2.27 times (95% CI, 1.09-4.7) more likely to have AB and 2.45 times (95% CI, 1.13-5.34) more likely to have myofascial pain than individuals without headaches. CONCLUSIONS: Individuals with myofascial TMD, headaches, or AB were more likely to have at least one of the other conditions.


Assuntos
Bruxismo , Transtornos da Articulação Temporomandibular , Bruxismo/complicações , Bruxismo/epidemiologia , Estudos Transversais , Cefaleia/complicações , Cefaleia/epidemiologia , Humanos , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/epidemiologia , Vigília
10.
Arch Sex Behav ; 51(3): 1799-1812, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35226281

RESUMO

The Perceptions of Dating Infidelity Scale (PDIS) assesses how people perceive infidelity through specific behaviors. Originally developed by Wilson et al. (2011), it contains 12 items distributed into three factors: (1) ambiguous, (2) deceptive, and (3) explicit behaviors. In the present research, translation, cross-cultural adaptation, and validation of the PDIS in Brazilian Portuguese were performed. First, qualitative analyses took place: translation, translation synthesis, content validation, pre-test, and reverse translation. Then, quantitative analyses were conducted: psychometric parameter tests with confirmatory factor analysis and reliability. A total of 252 participants were recruited, 160 of whom were female (63.5%). The results indicated consistent PDIS adequacy (conceptual and idiomatic equivalences); satisfactory content validity coefficients regarding language clarity, practical pertinence, and theoretical relevance; and an almost perfect level of consensus regarding the theoretical dimension. The application of the pre-test was proven to be a good parameter for estimating the comprehension of the instrument in the culture for which it was intended. Confirmatory factor analysis showed good indices of adjustment quality of the tested trifactorial model (three factors being identified with ambiguous, deceptive, and explicit behaviors). Therefore, the structure indicated in the original version was corroborated and the instrument's reliability confirmed. The Brazilian Portuguese PDIS is a useful tool for evaluating infidelity perceptions in the Brazilian culture.


Assuntos
Comparação Transcultural , Idioma , Brasil , Feminino , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
11.
Arch Phys Med Rehabil ; 103(2): 245-254, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34480887

RESUMO

OBJECTIVE: To investigate the effects of transcranial direct current stimulation (tDCS) associated with functional exercise on pain, functional performance, psychological symptoms, and quality of life of patients with fibromyalgia (FM). DESIGN: Randomized controlled trial. Participants were randomized by blocks into 2 groups: tDCS associated with functional exercise (n=17) and sham-tDCS associated with functional exercise (n=14). SETTING: Laboratory of neuromuscular performance in the department of physical therapy. PARTICIPANTS: Women with FM (N=31) according to American College of Rheumatology-2010 criteria. INTERVENTIONS: Anodal tDCS or sham-tDCS was applied over the left motor cortex for 5 consecutive days during the first week of intervention (2 mA; 20min). All volunteers also engaged in 8 weeks of functional exercises 3 times per week. MAIN OUTCOME MEASURES: Pain intensity, functional performance, psychological symptoms, and quality of life were assessed pre-exercise and immediately after the first, fourth, and eighth weeks of intervention. RESULTS: Pain intensity, functional performance, psychological symptoms, and quality of life increased significantly in both groups (P<.05); however, no significant differences between groups were found in all outcomes (P>.05). CONCLUSION: tDCS associated with functional exercises did not enhance the effects of physical exercise on pain, functional performance, psychological symptoms, and quality of life of patients with FM.


Assuntos
Fibromialgia , Estimulação Transcraniana por Corrente Contínua , Exercício Físico , Terapia por Exercício , Feminino , Fibromialgia/terapia , Humanos , Dor , Manejo da Dor , Qualidade de Vida
12.
Environ Geochem Health ; 44(3): 861-872, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34110527

RESUMO

Establishing quality reference values (QRVs) for rare earth elements (REEs) in soils is essential for the screening of these emergent contaminants. Currently, Brazil has the second-largest reserve of REEs, but data regarding background concentrations and distributions in soils remain scarce. The aim of this study was to establish the QRVs and assess the spatial distribution of REEs in soils, including REE fractionations and anomalies in (Piauí) state (251,529.186 km2), northeastern Brazil. This study reports the most detailed data on REE geochemistry in Brazilian soils. A total of 243 composite soil samples was collected at 0-20 cm depth. The mean background concentrations in soils followed the abundance of the earth's upper crust: Ce > La > Nd > Pr > Sm > Dy > Gd > Er > Yb > Eu > Tb > Lu. The ∑REEs (mg kg-1) showed the following order based on the individual mesoregions of Piauí state: Southeast (262.75) > North and Central-North (89.68) > Southwest (40.33). The highest QRVs were observed in the Southeast mesoregion. The establishment of QRVs based on the mesoregion scale improves data representativeness and the monitoring of natural REE values by identifying hot spots. Geostatistical modeling indicated significant local variability, especially in the Southeast mesoregion. The levels of these elements in this spatial zone are naturally higher than the other values across Piauí state and the mesoregion itself and indicate a high potential to exceed the QRVs. Our approach provides much needed data to help strengthen policies for both human health and environmental protection.


Assuntos
Metais Terras Raras , Poluentes do Solo , Monitoramento Ambiental , Política Ambiental , Geologia , Humanos , Metais Terras Raras/análise , Solo , Poluentes do Solo/análise
13.
Rural Remote Health ; 21(3): 6055, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34229443

RESUMO

INTRODUCTION: Boardwalk Cisterns is a government program that aims to attend a population with precarious access to water in Brazil. Developed as part of the Zero Hunger strategy, it intends to increase food security and contribute to the realization of the human right to food. The objective of this study was to assess farmers' perceptions of the Boardwalk Cisterns program and its impact on the food security situation of beneficiary households. METHODS: Data were collected through a descriptive cross-sectional quali-quantitative survey. Questionnaires were applied to farming families selected from two municipalities in the state of Alagoas (Northeast Brazil), containing questions on sociodemographic characteristics, production methods, and food security status. The Free Evocation Technique for social representation, analyzed through the software Ensemble of Programs Permettant L'analyze des Évocations, was used to ascertain farmers' perceptions of the program. RESULTS: The study showed a positive perception of the interviewees in relation to the boardwalk cisterns. The program brought some improvement in the agricultural production conditions and, consequently, in the food security situation of the households. Corn, beans and cassava were the most common crops, with almost half of this production (48.3%) destined for consumption by the families themselves. Farmers also reported having more water, allowing them to plant more fruit trees, as well as medicinal and ornamental plants. Nevertheless, 79.1% of the households interviewed were still in a situation of food insecurity, of which 28.1% were classified as mild food insecurity, 26% as moderate food insecurity, and 25% as severe food insecurity. CONCLUSION: Farmers were correct in their perception that the Boardwalk Cisterns program improved their food security situation. The program resulted in greater access to water, and greater production and consumption of food. However, by itself, the Boardwalk Cisterns program was not enough to raise beneficiary families above their food-insecure status. The program alleviated the problem of food insecurity, but other complementary government interventions are needed to guarantee the food security of families living in extreme poverty.


Assuntos
Fazendeiros , Segurança Alimentar , Brasil , Estudos Transversais , Abastecimento de Alimentos , Humanos , Percepção
14.
Artigo em Inglês | MEDLINE | ID: mdl-32340990

RESUMO

A case of Mycobacterium leprae rifampin resistance after irregular antileprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Hanseníase/tratamento farmacológico , Mutação , Mycobacterium leprae/genética , Recidiva , Rifampina/farmacologia
15.
BMC Infect Dis ; 20(1): 59, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959123

RESUMO

BACKGROUND: Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. METHODS: Patients were divided into four groups: Group 1- TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2- HIV+ (n = 24), Group 3- TB+ (n = 24) and Group 4- healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. RESULTS: Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR = 2.39, P = 0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR = 0.23, P = 0.03, and aOR = 0.33, P = 0.01, respectively). Not carrying KIR2DL3 (aOR = 0.18, P = 0.03) and carrying HLA-C*07 (aOR = 0.32, P = 0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ≤500 cells/mm3 (aOR = 18.23, P = 0.016); carrying the KIR2DS2 gene (aOR = 27.22, P = 0.032), the HLA-B*41 allele (aOR = 68.84, P = 0.033), the KIR2DS1 + HLA-C2 pair (aOR = 28.58, P = 0.024); and not carrying the KIR2DL3 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), and the KIR2DL1 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), CONCLUSIONS: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/genética , HIV-1 , Síndrome Inflamatória da Reconstituição Imune/etiologia , Síndrome Inflamatória da Reconstituição Imune/genética , Tuberculose/complicações , Tuberculose/genética , Brasil , Coinfecção/tratamento farmacológico , Coinfecção/genética , Coinfecção/patologia , Feminino , Seguimentos , Frequência do Gene/genética , Marcadores Genéticos , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Síndrome Inflamatória da Reconstituição Imune/patologia , Masculino , Receptores KIR/genética , Fatores Sexuais , Tuberculose/tratamento farmacológico , Tuberculose/patologia
16.
BMC Med Res Methodol ; 19(1): 188, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547804

RESUMO

BACKGROUND: The Pain Medication Questionnaire (PMQ) assesses the risk of opioid abuse in people with non-oncological chronic pain. METHODS: This is a methodological study conducted at a hemotherapy centre in Recife, Pernambuco state, Brazil. A Cross-cultural adaptation was carried out by a committee of nine specialists, and we applied the PMQ to a pre-final sample of 40 individuals with sickle cell anemia, in addition to a sociodemographic and clinical questionnaire. RESULTS: The mean agreement indexes for PMQ equivalences were the following: semantic (0.996), idiomatic (0.970), experiential (0.991), conceptual (0.953), language clarity (0.991), practical relevance (0.906), and theoretical relevance (0.945). Assessment of the PMQ showed that 50% of participants obtained a score equivalent to medium risk of opioid abuse. Cronbach's alpha coefficient for the adapted PMQ instrument was 0.705, ranging from 0.641 to 0.736 among its items. CONCLUSION: The cross-cultural adaptation of the Pain Medication Questionnaire was satisfactory and easy to apply in the Brazilian population. It is clinically relevant, contributing professional practice and enlightening patients with sickle cell anemia on their behavioral dynamics with respect to opioid consumption. It will also contribute to teaching and research, because it is a useful tool for investigating the risk of abusive behavior in people with chronic pain.


Assuntos
Dor Crônica/prevenção & controle , Idioma , Inquéritos e Questionários , Traduções , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anemia Falciforme/complicações , Brasil , Dor Crônica/diagnóstico , Dor Crônica/etiologia , Comparação Transcultural , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/etiologia , Reprodutibilidade dos Testes , Fatores de Risco , Adulto Jovem
17.
Int J Mol Sci ; 20(19)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569452

RESUMO

Transforming growth factor beta (TGF-ß) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of Trypanosoma cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF), and L6E9 skeletal myoblasts to TGF-ß. Cultures of CM, CF, and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-ß (1-10 ng/mL, 1 h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-ß, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 was less stimulated in CF than CM and L6E9. T. cruzi infection resulted in localized FN disorganization in CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-ß showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-ß after T. cruzi infection.


Assuntos
Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Matriz Extracelular/metabolismo , Interações Hospedeiro-Patógeno , Fator de Crescimento Transformador beta/metabolismo , Trypanosoma cruzi/fisiologia , Animais , Biomarcadores , Linhagem Celular , Células Cultivadas , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Miócitos Cardíacos/metabolismo , Transdução de Sinais
19.
BMC Infect Dis ; 17(1): 606, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28874142

RESUMO

BACKGROUND: Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. METHODS: This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. RESULTS: Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4+ T cell counts <200 cells/mm3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4+ T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4+ T cell counts at follow-up visits of ≥200 cells/mm3. CONCLUSIONS: These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Tuberculose/imunologia , Adulto , Alcinos , Fármacos Anti-HIV/uso terapêutico , Antígenos de Bactérias/imunologia , Benzoxazinas/administração & dosagem , Benzoxazinas/uso terapêutico , Ciclopropanos , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Síndrome Inflamatória da Reconstituição Imune/imunologia , Interferon gama/metabolismo , Estudos Longitudinais , Masculino , Mycobacterium tuberculosis/imunologia , Fatores de Risco , Tenofovir/uso terapêutico , Tuberculina/imunologia , Tuberculose/virologia
20.
Acta Neuropsychiatr ; 29(1): 35-42, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27725006

RESUMO

OBJECTIVE: Diffuse axonal injury (DAI) is prevalent in traumatic brain injury (TBI), and is often associated with poor outcomes and cognitive impairment, including memory deficits. Few studies have explored visual memory after TBI and its relationship to executive functioning. Executive functioning is crucial for remembering an object's location, operating devices, driving, and route finding. We compared visual memory performance via the Rey-Osterrieth Complex Figure (ROCF) test 6 and 12 months after DAI. METHOD: In total, 40 patients (mean age 28.7 years; 87.5% male) with moderate-to-severe DAI following a road traffic accident completed the 1-year follow-up. There was a three-phase prospective assessment. In phase 1 (1-3 months after trauma), patients completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). In phases 2 (6 months) and 3 (12 months), they completed the BDI, STAI, and a neuropsychological battery [ROCF copy and recall, digit span forward/backward, Grooved Pegboard test, intelligence quotient (IQ) by Wechsler Adult Intelligence Scale-III (WAIS-III)]. RESULTS: There was an improvement in ROCF recall over time (p=0.013), but not ROCF copy (p=0.657).There was no change in executive function (Savage scores) copy (p=0.230) or recall (p=0.155). Age, years of education, severity of the trauma, and IQ did not influence ROCF recall improvement. CONCLUSION: There are time-dependent improvements in visual memory in patients with DAI. Neuroplasticity in the 1st months after trauma provides an opportunity for visuospatial memory learning. The present findings may be useful to formulate management plans for long-term TBI rehabilitation.


Assuntos
Lesão Axonal Difusa/psicologia , Função Executiva/fisiologia , Rememoração Mental/fisiologia , Reconhecimento Psicológico/fisiologia , Recuperação de Função Fisiológica , Adulto , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Reconhecimento Visual de Modelos/fisiologia , Estudos Prospectivos , Desempenho Psicomotor , Adulto Jovem
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