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1.
AIDS Behav ; 28(4): 1173-1185, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37523050

RESUMO

Daily adherence to antiretroviral therapy (ART) increases the length and quality of life of people living with HIV (PLHIV). We explored whether socioeconomic status directly impacts ART adherence and whether part of the effect is mediated by pathways through alcohol misuse or food insecurity. A cross-sectional study was conducted in Rio de Janeiro/Brazil (November/2019 to March/2020) with PLHIV aged ≥ 18 years. Validated instruments were used to measure alcohol use, food insecurity, and ART adherence. Using structural equation modeling we assessed the direct and indirect effects of variables on ART adherence. Participants reported significant challenges: hunger: 12%, alcohol use: 64%, and missing ART doses: 24%. Results showed that lower socioeconomic status increased poor adherence and that this effect was mediated through higher food insecurity. Alcohol misuse also increased poor adherence through a strong direct effect. Providing socio-economic support coupled with interventions to mitigate alcohol's harmful impact can aid HIV care.


RESUMEN: La adherencia diaria a la terapia antirretroviral (TAR) aumenta la duración y calidad de vida de las personas que viven con el VIH (PVVIH). Exploramos si el estatus socioeconómico afecta directamente la adherencia al TAR y si parte del efecto está mediado por vías a través del abuso del alcohol o la inseguridad alimentaria. Se realizó un estudio en Río de Janeiro/Brasil (noviembre/2019 a marzo/2020) con PVVIH con edad ≥ 18 años. Utilizando modelos de ecuaciones estructurales evaluamos los efectos directos e indirectos. Los participantes informaron desafíos significativos: hambre: 12%, consumo de alcohol: 64%, mala adherencia: 24%. Los resultados mostraron que un nivel socioeconómico más bajo aumentaba la mala adherencia por un efecto mediado por mayor inseguridad alimentaria. Abuso de alcohol también aumentó la mala adherencia por un fuerte efecto directo. Brindar apoyo socioeconómico con intervenciones para mitigar el impacto nocivo del alcohol puede ayudar la atención clínica.


Assuntos
Alcoolismo , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Estudos Transversais , Qualidade de Vida , Alcoolismo/epidemiologia , Abastecimento de Alimentos , Adesão à Medicação , Brasil/epidemiologia , Insegurança Alimentar
2.
BMC Endocr Disord ; 24(1): 7, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38200480

RESUMO

BACKGROUND: Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. METHODS: Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. RESULTS: A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. CONCLUSION: We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.


Assuntos
Cirurgia Bariátrica , Estado Pré-Diabético , Feminino , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Seguimentos , Estado Pré-Diabético/epidemiologia , Estudos Longitudinais , Hemoglobinas Glicadas
3.
PLoS Pathog ; 17(8): e1009772, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34352039

RESUMO

Understanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, imposing the need to monitor SARS-CoV2 evolution and dynamics in the population. Determining signatures in SARS-CoV-2 that render the virus resistant to neutralizing antibodies is critical. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations in the spike protein, including all defining mutations in the variants of concern, to identify the effect of single and synergic amino acid substitutions in promoting immune escape. We confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations. In silico analysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and with mutations able to increase binding to ACE2, such as N501Y. Our analysis of synergic mutations provides a signature for hotspots for immune evasion and for targets of therapies, vaccines and diagnostics.


Assuntos
Anticorpos Neutralizantes/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Substituição de Aminoácidos/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Linhagem Celular , Humanos , Evasão da Resposta Imune , Mutação/genética , Ligação Proteica , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Arch Microbiol ; 205(5): 208, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37103635

RESUMO

The use of force spectroscopy approaches performed with optical tweezers can be very useful in determining the binding modes and the physical chemistry of DNA interactions with ligands, from small drugs to proteins. Helminthophagous fungi, on the other hand, have important enzyme secretion mechanisms for various purposes, and the interactions between such enzymes and nucleic acids are very poorly studied. Therefore, the main goal of the present work was to investigate, at the molecular level, the mechanisms of interaction between fungal serine proteases and the double-stranded (ds) DNA molecule. Experimental assays performed with this single molecule technique consist in exposing different concentrations of the protease of this fungus to dsDNA until saturation while monitoring the changes on the mechanical properties of the macromolecular complexes formed, from where the physical chemistry of the interaction can be deduced. It was found that the protease binds strongly to the double-helix, forming aggregates and changing the persistence length of the DNA molecule. The present work thus allowed us to infer information at the molecular level on the pathogenicity of these proteins, an important class of biological macromolecules, when applied to a target specimen.


Assuntos
Ascomicetos , Serina Proteases , Serina Proteases/genética , Ascomicetos/genética , Serina Endopeptidases , DNA
5.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769215

RESUMO

Immunohistochemical evaluation of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status stratify the different subtypes of breast cancer and define the treatment course. Triple-negative breast cancer (TNBC), which does not register receptor overexpression, is often associated with worse patient prognosis. Mass spectrometry imaging transcribes the molecular content of tissue specimens without requiring additional tags or preliminary analysis of the samples, being therefore an excellent methodology for an unbiased determination of tissue constituents, in particular tumor markers. In this study, the proteomic content of 1191 human breast cancer samples was characterized by mass spectrometry imaging and the epithelial regions were employed to train and test machine-learning models to characterize the individual receptor status and to classify TNBC. The classification models presented yielded high accuracies for estrogen and progesterone receptors and over 95% accuracy for classification of TNBC. Analysis of the molecular features revealed that vimentin overexpression is associated with TNBC, supported by immunohistochemistry validation, revealing a new potential target for diagnosis and treatment.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Receptor ErbB-2/metabolismo , Proteômica , Biomarcadores Tumorais/metabolismo , Estrogênios , Receptores de Progesterona/metabolismo , Espectrometria de Massas
6.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139364

RESUMO

This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients' mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1-2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes.


Assuntos
Imunoterapia , Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Idoso , Humanos , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Receptor 1 de Quimiocina CX3C , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias não Músculo Invasivas da Bexiga/terapia , Transdução de Sinais , Receptor 4 Toll-Like/uso terapêutico , Microambiente Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Imunoterapia/métodos , Sistemas de Liberação de Fármacos por Nanopartículas
7.
Anal Chem ; 94(23): 8194-8201, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35658398

RESUMO

Many studies have demonstrated that tissue phenotyping (tissue typing) based on mass spectrometric imaging data is possible; however, comprehensive studies assessing variation and classifier transferability are largely lacking. This study evaluated the generalization of tissue classification based on Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometric imaging (MSI) across measurements performed at different sites. Sections of a tissue microarray (TMA) consisting of different formalin-fixed and paraffin-embedded (FFPE) human tissue samples from different tumor entities (leiomyoma, seminoma, mantle cell lymphoma, melanoma, breast cancer, and squamous cell carcinoma of the lung) were prepared and measured by MALDI-MSI at different sites using a standard protocol (SOP). Technical variation was deliberately introduced on two separate measurements via a different sample preparation protocol and a MALDI Time of Flight mass spectrometer that was not tuned to optimal performance. Using standard data preprocessing, a classification accuracy of 91.4% per pixel was achieved for intrasite classifications. When applying a leave-one-site-out cross-validation strategy, accuracy per pixel over sites was 78.6% for the SOP-compliant data sets and as low as 36.1% for the mistuned instrument data set. Data preprocessing designed to remove technical variation while retaining biological information substantially increased classification accuracy for all data sets with SOP-compliant data sets improved to 94.3%. In particular, classification accuracy of the mistuned instrument data set improved to 81.3% and from 67.0% to 87.8% per pixel for the non-SOP-compliant data set. We demonstrate that MALDI-MSI-based tissue classification is possible across sites when applying histological annotation and an optimized data preprocessing pipeline to improve generalization of classifications over technical variation and increasing overall robustness.


Assuntos
Carcinoma de Células Escamosas , Adulto , Diagnóstico por Imagem , Humanos , Lasers , Inclusão em Parafina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
8.
Molecules ; 27(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35956764

RESUMO

Cancer-related deaths are very commonly attributed to complications from metastases to neighboring as well as distant organs. Dissociate response in the treatment of pancreatic adenocarcinoma is one of the main causes of low treatment success and low survival rates. This behavior could not be explained by transcriptomics or genomics; however, differences in the composition at the protein level could be observed. We have characterized the proteomic composition of primary pancreatic adenocarcinoma and distant metastasis directly in human tissue samples, utilizing mass spectrometry imaging. The mass spectrometry data was used to train and validate machine learning models that could distinguish both tissue entities with an accuracy above 90%. Model validation on samples from another collection yielded a correct classification of both entities. Tentative identification of the discriminative molecular features showed that collagen fragments (COL1A1, COL1A2, and COL3A1) play a fundamental role in tumor development. From the analysis of the receiver operating characteristic, we could further advance some potential targets, such as histone and histone variations, that could provide a better understanding of tumor development, and consequently, more effective treatments.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/patologia , Histonas , Humanos , Neoplasias Pancreáticas/patologia , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Neoplasias Pancreáticas
9.
Health Econ ; 30(11): 2686-2700, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34342070

RESUMO

We evaluate the role of behavioral attributes in predicting engagement in an intervention program. Distinct from the previous studies, we investigate how parental preferences influence their engagement behavior in a health program when the targeted outcomes relate to the health of their children, as opposed to their own. We use an artifactual field experiment where the participants were former parent enrollees in a child health management program in Australia. Our findings suggest that parents' time preference and risk tolerance are robust predictors of engagement, measured by program attendance. Attendance is positively associated with patience and risk tolerance in the health domain, after controlling for a host of personality traits and socioeconomic factors. By improving our understanding of the behavioral risk factors for attrition, these findings offer important insights for enhancing participant engagement in intervention programs that are beset with the problem of high attrition.


Assuntos
Saúde da Criança , Pais , Austrália , Criança , Humanos
10.
BMC Pregnancy Childbirth ; 21(1): 632, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535094

RESUMO

BACKGROUND: Immunological protection via breastfeeding is well known. The immunological profile of human milk changes during lactation. No clinical trials have been conducted in lactating women with the newest mRNA vaccines against SARS- CoV-2. A Few studies have shown the presence of antibodies in breastmilk after vaccination. The aim of this work is to study possible antibodies transfer via breastmilk and also the immunological characteristics of lactating women compared to non-lactating women, after using the BNT162b2 Pfizer vaccine. METHODS: This is a prospective cohort study with a convenience homogenous sample of 24 healthcare workers (14 lactating and 10 non-lactating women) enrolled at the time of COVID-19 vaccination. Clinical data was registered in a questionnaire. Titers of SARS-CoV-2 spike IgG, IgA and IgM were quantified in post vaccination blood and human milk. Antibody quantification was performed by an in-house ELISA to SARS-CoV-2 trimeric spike protein. RESULTS: All women showed immunity after vaccination with positive antibodies for IgM, IgA and IgG antibodies. The dominant serum antibody response was IgG. Modest levels of antibodies in breastmilk of lactating mothers were observed in this study, especially IgG in 42.9%. There was a moderate association between higher titers of IgG and a longer duration of breastfeeding (R= 0.55, p=0.041). CONCLUSIONS: Evidence of antibody transfer in human milk after COVID-19 vaccination is scarce. The presence of antibodies in human milk is reported, but immunization through breastfeeding is still to be established.


Assuntos
Anticorpos Antivirais/metabolismo , Aleitamento Materno , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Lactação/imunologia , Leite Humano/imunologia , SARS-CoV-2/imunologia , Adulto , Vacina BNT162 , Biomarcadores/metabolismo , COVID-19/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunização Passiva , Estudos Prospectivos
11.
Molecules ; 26(21)2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34771129

RESUMO

We report herein a set of 3'-azido-3'-deoxythymidine (AZT) derivatives based on triazoles and triazolium salts for HIV-1 infection. The compounds were synthesized via click chemistry with Cu(I) and Ru(II) catalysts. Triazolium salts were synthesized by reaction with methyl iodide or methyl triflate in good yields. The antiviral activity of the compounds was tested using two methodologies: In method one the activity was measured on infected cells; in method two a pre-exposure prophylaxis experimental model was employed. For method one the activity of the compounds was moderate, and in general the triazolium salts showed a decreased activity in relation to their triazole precursors. With method two the antiviral activity was higher. All compounds were able to decrease the infection, with two compounds able to clear almost all the infection, while a lower antiviral activity was noted for the triazolium salts. These results suggest that these drugs could play an important role in the development of pre-exposure prophylaxis therapies.


Assuntos
Fármacos Anti-HIV/farmacologia , Desenvolvimento de Medicamentos , HIV-1/efeitos dos fármacos , Triazóis/farmacologia , Zidovudina/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Sais/síntese química , Sais/química , Sais/farmacologia , Triazóis/síntese química , Triazóis/química , Zidovudina/síntese química , Zidovudina/química
12.
Mem Inst Oswaldo Cruz ; 114: e190350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32022169

RESUMO

BACKGROUND: Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES: We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS: The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS: Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS: This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/virologia , Ferro da Dieta/efeitos adversos , Carga Viral/efeitos dos fármacos , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Homeostase , Humanos , Ferro da Dieta/análise , Masculino , Estado Nutricional , Fatores Socioeconômicos , Inquéritos e Questionários
13.
Trop Anim Health Prod ; 52(4): 1733-1738, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31898020

RESUMO

The influence of shade in the silvopastoral system on the performance and degree of parasitism by endo- and ectoparasites in Angus x Nellore heifers was assessed. The experiment was conducted with 72 heifers, with an initial mean weight of 276 ± 5.67 kg and 9 months of age, in a total area of 25 ha, divided into 12 paddocks, with three treatments and four replicates. The experimental design was a randomized complete block design, to evaluate the conventional grazing system (CGS) without shade and silvopastoral systems with simple line (SPS1) or triple lines (SPS3) of eucalyptus. The evaluations were carried out every 28 days, from June 2017 to April 2018. During the trial, the number of eggs per gram of feces (EPG) presented a gradual increase in the three systems. Differences (P < 0.05) in the variables analyzed were recorded only in two occasions: the CGS group EPG mean ± standard error (1269 ± 105) was higher than the SPS1 group mean (402 ± 129 EPG) in March, and tick average of the CGS group (13 ± 2.7) was lower than the SPS3 (32 ± 5.3) in October. There were no significant differences (P ≥ 0.05) between groups in relation to horn fly counts, the numbers of infective nematode larvae on pasture, hematological variables, and weight gain. It was concluded that in comparison with the CGS system, the shading in the SPS1 and SPS3 systems did not have any major influence on the degree of parasitism or in the performance of the heifers.


Assuntos
Criação de Animais Domésticos , Doenças dos Bovinos/parasitologia , Contagem de Ovos de Parasitas/veterinária , Doenças Parasitárias em Animais/parasitologia , Animais , Bovinos , Fezes/parasitologia , Feminino , Óvulo , Luz Solar , Aumento de Peso
14.
J Neurogenet ; 33(1): 10-20, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30516420

RESUMO

The bidirectional and positive relation between the ingestion of fat and alcohol has become the subject of extensive discussion. However, this relation is more studied in animal models of binge eating with intermittent access of high-fat diet or in a model of short period of this diet consumption. Here, we developed a model to elucidate how chronic high-fat diet and its withdrawal influence alcohol intake (two-bottle choice) and anxiety behavior (marble burying test). In the first experimental stage, animals were fed on standard (AIN93G) or high sugar and butter (HSB) diet for 8 weeks. Then, a protocol of free-choice between water and a 10% alcohol solution was introduced, and the HSB diet was replaced with AIN93G in two experimental groups. The result obtained with this model point out that the relation among high-fat diet consumption and alcohol intake appears to depend on the presence or absence of the diet when alcohol intake is evaluated, and that an imbalance in the mesocorticolimbic dopaminergic pathway, observed by the transcriptional regulation of the dopamine receptors (Drd1/Drd2) and GABAB receptors subunit (Gabbr1/Gabbr2), can be driving the alcohol intake.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Encéfalo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Receptores Dopaminérgicos/metabolismo , Receptores de GABA-B/metabolismo , Animais , Ansiedade/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/metabolismo
15.
Inflamm Res ; 65(2): 169-78, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26650032

RESUMO

OBJECTIVE: The purpose of the study was to develop a novel diet based on standard AIN93G diet that would be able to induce experimental obesity and impair immune regulation with high concentrations of both carbohydrate and lipids. METHODS: To compare the effects of this high sugar and butter (HSB) diet with other modified diets, male C57BL/6 mice were fed either mouse chow, or AIN93G diet, or high sugar (HS) diet, or high-fat (HF) diet, or high sugar and butter (HSB) diet for 11 weeks ad libitum. HSB diet induced higher weight gain. Therefore, control AIN93G and HSB groups were chosen for additional analysis. Regulatory T cells were studied by flow cytometry, and cytokine levels were measured by ELISA. RESULTS: Although HF and HSB diets were able to induce a higher weight gain compatible with obesity in treated mice, HSB-fed mice presented the higher levels of serum glucose after fasting and the lowest frequency of regulatory T cells in adipose tissue. In addition, mice that were fed HSB diet presented higher levels of cholesterol and triglycerides, hyperleptinemia, increased resistin and leptin levels as well as reduced adiponectin serum levels. Importantly, we found increased frequency of CD4(+)CD44(+) effector T cells, reduction of CD4(+)CD25(+)Foxp3(+) and Th3 regulatory T cells as well as decreased levels of IL-10 and TGF-ß in adipose tissue of HSB-fed mice. CONCLUSION: Therefore, HSB represents a novel model of obesity-inducing diet that was efficient in triggering alterations compatible with metabolic syndrome as well as impairment in immune regulatory parameters.


Assuntos
Tecido Adiposo/imunologia , Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Síndrome Metabólica/imunologia , Obesidade/imunologia , Linfócitos T Reguladores/imunologia , Adipocinas/sangue , Animais , Glicemia/análise , Colesterol/sangue , Gorduras na Dieta/efeitos adversos , Interleucina-10/sangue , Interleucina-10/imunologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Camundongos Transgênicos , Obesidade/sangue , Obesidade/etiologia , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/imunologia , Triglicerídeos/sangue
16.
BMC Genomics ; 15: 792, 2014 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-25218200

RESUMO

BACKGROUND: Galileo is one of three members of the P superfamily of DNA transposons. It was originally discovered in Drosophila buzzatii, in which three segregating chromosomal inversions were shown to have been generated by ectopic recombination between Galileo copies. Subsequently, Galileo was identified in six of 12 sequenced Drosophila genomes, indicating its widespread distribution within this genus. Galileo is strikingly abundant in Drosophila willistoni, a neotropical species that is highly polymorphic for chromosomal inversions, suggesting a role for this transposon in the evolution of its genome. RESULTS: We carried out a detailed characterization of all Galileo copies present in the D. willistoni genome. A total of 191 copies, including 133 with two terminal inverted repeats (TIRs), were classified according to structure in six groups. The TIRs exhibited remarkable variation in their length and structure compared to the most complete copy. Three copies showed extended TIRs due to internal tandem repeats, the insertion of other transposable elements (TEs), or the incorporation of non-TIR sequences into the TIRs. Phylogenetic analyses of the transposase (TPase)-encoding and TIR segments yielded two divergent clades, which we termed Galileo subfamilies V and W. Target-site duplications (TSDs) in D. willistoni Galileo copies were 7- or 8-bp in length, with the consensus sequence GTATTAC. Analysis of the region around the TSDs revealed a target site motif (TSM) with a 15-bp palindrome that may give rise to a stem-loop secondary structure. CONCLUSIONS: There is a remarkable abundance and diversity of Galileo copies in the D. willistoni genome, although no functional copies were found. The TIRs in particular have a dynamic structure and extend in different ways, but their ends (required for transposition) are more conserved than the rest of the element. The D. willistoni genome harbors two Galileo subfamilies (V and W) that diverged ~9 million years ago and may have descended from an ancestral element in the genome. Galileo shows a significant insertion preference for a 15-bp palindromic TSM.


Assuntos
Elementos de DNA Transponíveis , Drosophila/genética , Variação Genética , Genoma , Animais , Sequência de Bases , Biologia Computacional , Drosophila/classificação , Dosagem de Genes , Ordem dos Genes , Genômica , Dados de Sequência Molecular , Motivos de Nucleotídeos , Filogenia , Matrizes de Pontuação de Posição Específica , Recombinação Genética , Alinhamento de Sequência , Sequências Repetidas Terminais
17.
Beilstein J Org Chem ; 10: 2765-2773, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25550742

RESUMO

Due to their outstanding properties nanodiamonds are a promising nanoscale material in various applications such as microelectronics, polishing, optical monitoring, medicine and biotechnology. Beyond the typical diamond characteristics like extreme hardness or high thermal conductivity, they have additional benefits as intrinsic fluorescence due to lattice defects without photobleaching, obtained during the high pressure high temperature process. Further the carbon surface and its various functional groups in consequence of the synthesis, facilitate additional chemical and biological modification. In this work we present our recent results on chemical modification of the nanodiamond surface with phosphate groups and their electrochemically assisted immobilization on titanium-based materials to increase adhesion at biomaterial surfaces. The starting material is detonation nanodiamond, which exhibits a heterogeneous surface due to the functional groups resulting from the nitrogen-rich explosives and the subsequent purification steps after detonation synthesis. Nanodiamond surfaces are chemically homogenized before proceeding with further functionalization. Suspensions of resulting surface-modified nanodiamonds are applied to the titanium alloy surfaces and the nanodiamonds subsequently fixed by electrochemical immobilization. Titanium and its alloys have been widely used in bone and dental implants for being a metal that is biocompatible with body tissues and able to bind with adjacent bone during healing. In order to improve titanium material properties towards biomedical applications the authors aim to increase adhesion to bone material by incorporating nanodiamonds into the implant surface, namely the anodically grown titanium dioxide layer. Differently functionalized nanodiamonds are characterized by infrared spectroscopy and the modified titanium alloys surfaces by scanning and transmission electron microscopy. The process described shows an adsorption and immobilization of modified nanodiamonds on titanium; where aminosilanized nanodiamonds coupled with O-phosphorylethanolamine show a homogeneous interaction with the titanium substrate.

18.
Obes Surg ; 34(5): 1432-1441, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467900

RESUMO

INTRODUCTION: It is estimated that most people undergoing bariatric surgery are women of reproductive age; nonetheless, its effects on pregnancy outcomes are not yet fully understood. METHODS: Retrospective observational study, conducted in a tertiary center in Portugal, included participants in two groups: (1) pregnant women with a history of bariatric surgery (n = 89) and (2) pregnant women with a BMI ≥ 35 kg/m2, without previous bariatric surgery (n = 176). Data was collected from the medical files. Multivariate analysis was conducted to adjust for confounders. RESULTS: Pregnancy after bariatric surgery was associated with lower risk of gestational diabetes (15.7% vs. 30.1%, p = 0.002) and cesarean delivery (20.7% vs. 33.5%, p = 0.007), and a higher gestational weight gain (10.58 ± 9.95 vs. 7.33 ± 6.00 kg, p < 0.001). Participants in the bariatric surgery who experienced a gestational weight gain ≤ 10.0 kg had a higher risk of preterm delivery (16.7% vs. 2.5%, p = 0.031). No significant differences were found regarding hypertensive diseases of pregnancy between groups (4.5% vs 11.4%, p = 0.147). Pregnancy after bariatric surgery was associated with lower neonate weight percentile (34.24 ± 21.09 vs. 48.77 ± 27.94, p < 0.001), higher risk of fetal growth restriction (5.6% vs. 0.6%, p = 0.018), and lower risk of fetal macrosomia (0.0% vs. 7.5%, p = 0.005). There were no significant differences in the risk of SGA (12.5% vs. 7.0%, p = 0.127) or LGA neonates (2.3% vs. 6.4%, p = 0.069). CONCLUSION: Pregnancy after bariatric surgery is associated with both risks and benefits, which should be considered by healthcare providers. Pregnancy after bariatric surgery requires individualized care, to ensure adequate gestational weight and avoid micronutrient deficiencies.


Assuntos
Cirurgia Bariátrica , Diabetes Gestacional , Ganho de Peso na Gestação , Obesidade Mórbida , Complicações na Gravidez , Recém-Nascido , Gravidez , Feminino , Humanos , Masculino , Obesidade Mórbida/cirurgia , Resultado da Gravidez , Diabetes Gestacional/epidemiologia , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos
19.
Obes Facts ; 17(1): 90-97, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38096794

RESUMO

INTRODUCTION: The COVID-19 pandemic has led to a worldwide lockdown, which affected physical exercise habits, as well as having a detrimental effect on psychological health and follow-up visits of patients submitted to bariatric surgery. The aim of this study was to evaluate the impact of COVID-19 lockdown on the 2-year weight loss of patients submitted to bariatric surgery in our center. METHODS: This was an observational study comparing the weight loss of patients who underwent bariatric surgery from January to March 2020 with a control group submitted to surgery between January and March 2017. Percentage of total weight loss (% TWL) and excess weight loss (% EWL) were assessed 6, 12, and 24 months after surgery. RESULTS: A total number of 203 patients were included in this study, 102 had bariatric surgery during the selected period in 2020 and 101 underwent surgery during the same period in 2017. There was no statistically significant difference in weight loss between the 2017 and 2020 groups which was reported as % TWL (mean 27.08 ± 7.530 vs. 28.03 ± 7.074, 33.87 ± 8.507 vs. 34.07 ± 8.979 and 34.13 ± 9.340 vs. 33.98 ± 9.993; p = 0.371) and % EWL (mean 66.83 ± 23.004 vs. 69.71 ± 17.021, 83.37 ± 24.059 vs. 84.51 ± 21.640 and 83.47 ± 24.130 vs. 84.27 ± 23.651; p = 0.506) at 6, 12, and 24 months post-surgery. CONCLUSION: Despite social limitations imposed by the COVID-19 lockdown, we found no significant difference between weight loss at 2 years postoperatively in the 2020 group when compared with a control group who underwent bariatric surgery in 2017. These results show that the outcomes of bariatric surgery during the COVID-19 lockdown were comparable with those recorded before the pandemic, supporting the efficacy of bariatric procedures' metabolic effects during the first 2 years after surgery, regardless of lifestyle habits.


Assuntos
Cirurgia Bariátrica , COVID-19 , Obesidade Mórbida , Humanos , Cirurgia Bariátrica/métodos , Controle de Doenças Transmissíveis , Obesidade Mórbida/cirurgia , Obesidade Mórbida/epidemiologia , Pandemias , Resultado do Tratamento , Redução de Peso
20.
Appl Neuropsychol Adult ; : 1-7, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37708840

RESUMO

The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening instrument that is known for its good psychometric properties and sensitivity to detect mild cognitive impairment (MCI). After ten years, it became relevant to update the previous Portuguese normative study due to changes in the population and some limitations present in the study itself. The study sample was composed of 860 cognitively healthy adults, stratified according to verified distribution of the Portuguese population across several sociodemographic variables. All participants completed a neuropsychological assessment battery, in which the MoCA was included. The analysis of the relationships between the sociodemographic variables and the MoCA show that age and educational level had a significant effect on MoCA scores, with educational level being the better predictor. These results foster the consideration of age and educational level in the development of normative data. The present study contributes to a reliable update of the normative data of MoCA. The new age groups and more stratified norms comply with the natural changes on the Portuguese population, providing an increase of power and clinical accuracy. The presented norms consider the cognitive domains subscores, consequently improving the comprehension and utility of the results obtained from the MoCA test.

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