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1.
Front Mol Neurosci ; 16: 1298560, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38115821

RESUMO

Parkinson's disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415-0.987; OR = 0.000, 95% CI = 0.000-0.075; OR = 0.550, 95% CI = 0.368-0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model's diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.

2.
Front Endocrinol (Lausanne) ; 14: 1108313, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484940

RESUMO

Background and objective: Observations of overweight and obesity in association with neuropsychological performance (NP) vary over the adult life course depending on baseline levels, biological sex, age, race, temporality of measurements, and other factors. Therefore, similar published analyses across cohorts are inconsistent. In our sample of women living with HIV (WLWH) and women without HIV (WWOH), we conducted comparable analyses as those published in men with and without HIV. We examined cross-sectional and longitudinal associations between body mass index (BMI) and waist circumference (WC) and NP. Methods: Four hundred thirty two 432 virologically-suppressed WLWH and 367 WWOH, ≥40 years in the Women's Interagency HIV Study (WIHS) with anthropometry and NP assessments every two years from 2009-2019 were included in the study. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV status were used to examine cross-sectional associations of BMI and WC by NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Covariates included sociodemographic, behavioral, and HIV-related characteristics. Results: At baseline among all women, the median age was 45 years, 65% were Non-Latinx Black women, and 45% were obese women. Obese WLWH (BMI≥30.0 kg/m2) had poorer executive function (ß=-2.27, 95%CI [-4.46, -0.07]) versus WLWH with healthy BMI (18.5-24.9 kg/m2). Longitudinally over ~8 years, obese versus overweight WWOH improved on memory (ß=2.19, 95%CI [0.13, 4.26]), however overweight versus healthy WWOH experienced declining memory (ß= -2.67, 95%CI [-5.40, -0.07]). Increasing WC was associated with declining executive, processing speed, and motor function (p's<0.05); an at-risk WC was associated with improved memory (ß=1.81, 95%CI [0.19, 3.44]) among WWOH. Among WLWH, increasing BMI was associated with improved learning (ß=0.07, 95%CI [0.00, 0.15]. Conclusion: Our cross-sectional and longitudinal analyses evaluating the associations of BMI and WC and NP were mixed compared to previous reports. This illustrates the importance of sociodemographic characteristics, baseline levels of exposures and outcomes, HIV status, temporality of measurements, and other factors when evaluating aging HIV epidemiology study results.


Assuntos
Infecções por HIV , Sobrepeso , Masculino , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Índice de Massa Corporal , Sobrepeso/complicações , Adiposidade , HIV , Estudos Transversais , Obesidade , Obesidade Abdominal/complicações , Infecções por HIV/complicações , Infecções por HIV/epidemiologia
3.
Child Abuse Negl ; 137: 106054, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36709732

RESUMO

INTRODUCTION: Although previous studies have demonstrated high intercorrelations among deviant peer affiliation, substance use, externalizing and internalizing symptoms in adolescence, these studies have been limited because they did not examine 1) the associations over time by assuming one particular sequence; and 2) child maltreatment effects. METHODS: This study included 617 adolescents (54.3 % girls, 55.6 % Black) at-risk of maltreatment living in the U.S and primarily low-income. Deviant peer affiliation was assessed at ages 12, 14, and 16 using 13 items from the modified version of the Youth Risk Behavior and Monitoring the Future Survey. Externalizing and internalizing symptoms were measured at ages 12, 14, and 16 using the Child Behavior Checklist. The number of substances used (ages 12, 14, 16, and 18) were created by summing the self-reported alcohol, tobacco, and marijuana use. Each type of maltreatment (birth to age 12) was assessed using the self-report. RESULTS: Autoregressive cross-lagged structural equation modeling explained the stability effects within each domain, as well as how different maltreatment types affect diverse developmental processes. Cross-lagged results showed the socialization effects of peers on substance use, whereas the peer selection effects on externalizing symptoms. Physical abuse was only associated with externalizing symptoms, while sexual abuse was associated with both externalizing and internalizing symptoms. Additionally, emotional abuse was associated with deviant peer affiliation and substance use. CONCLUSIONS: Identifying the underlying reciprocal processes offers a deeper understanding of peer relationships in the substance use and externalizing symptoms among at-risk of maltreatment sample.


Assuntos
Comportamento do Adolescente , Maus-Tratos Infantis , Transtornos Relacionados ao Uso de Substâncias , Criança , Feminino , Humanos , Adolescente , Masculino , Maus-Tratos Infantis/psicologia , Grupo Associado , Transtornos Relacionados ao Uso de Substâncias/psicologia , Comportamento do Adolescente/psicologia , Socialização , Estudos Longitudinais
4.
J Mol Cell Cardiol ; 169: 13-27, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35569213

RESUMO

Three-dimensional (3D) bioprinting of cellular or biological components are an emerging field to develop tissue structures that mimic the spatial, mechanochemical and temporal characteristics of cardiovascular tissues. 3D multi-cellular and multi-domain organotypic biological constructs can better recapitulate in vivo physiology and can be utilized in a variety of applications. Such applications include in vitro cellular studies, high-throughput drug screening, disease modeling, biocompatibility analysis, drug testing and regenerative medicine. A major challenge of 3D bioprinting strategies is the inability of matrix molecules to reconstitute the complexity of the extracellular matrix and the intrinsic cellular morphologies and functions. An important factor is the inclusion of a vascular network to facilitate oxygen and nutrient perfusion in scalable and patterned 3D bioprinted tissues to promote cell viability and functionality. In this review, we summarize the new generation of 3D bioprinting techniques, the kinds of bioinks and printing materials employed for 3D bioprinting, along with the current state-of-the-art in engineered cardiovascular tissue models. We also highlight the translational applications of 3D bioprinting in engineering the myocardium cardiac valves, and vascular grafts. Finally, we discuss current challenges and perspectives of designing effective 3D bioprinted constructs with native vasculature, architecture and functionality for clinical translation and cardiovascular regeneration.


Assuntos
Bioimpressão , Engenharia Tecidual , Bioimpressão/métodos , Miocárdio , Impressão Tridimensional , Células-Tronco , Engenharia Tecidual/métodos , Alicerces Teciduais
5.
Ann Work Expo Health ; 66(1): 102-112, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34378018

RESUMO

Leisure-time physical activity (LTPA) is a crucial behavior to reduce the global burden of disease. The objective of this study was to understand the relationship between LTPA, employment status, and physical workload (PWL). This study analyzed data from 38 449 individuals interviewed in the National Health Survey (NHS), representative of the Brazilian population. This paper examines LTPA in the last 30 days and whether participants achieved the recommended physical activity (≥150 min week-1) according to employment status and PWL utilizing Poisson regression models. One third and » of the participants reported LTPA in the last 30 days and achieved the recommended LTPA, respectively. Intense PWL was reported by 28.7% [95% confidence interval (CI): 27.8-29.6%] of participants; 32.2% among men (95% CI: 31.0-33.5%); 24.3% among women (95% CI: 23.1-25.5%). Precarious employment was associated with a lower prevalence of physical activity among men [adjusted prevalence ratio (PRa) = 0.92; P = 0.016], but not among women (PRa = 1.11; P = 0.039). Employment policies and protection of the work environment are relevant aspects to stimulate physical activity, and may vary by gender.


Assuntos
Atividades de Lazer , Exposição Ocupacional , Brasil/epidemiologia , Emprego , Exercício Físico , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino
6.
Neurosci Lett ; 754: 135901, 2021 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-33865938

RESUMO

Clinical criteria diagnose Parkinson's disease (PD), therefore, it is crucial to find biological elements that could support diagnosis or even act as prognostic tools of PD. The SNCA gene codifies a protein called α - synuclein; several studies associate genetic and biochemical factors of SNCA with PD, including transcript and plasmatic protein levels, however, contradictory evidence indicates inconclusive results. We aim to compare SNCA mRNA expression, plasmatic α-syn protein and rs356219 SNP between PD cases and a control group, and to identify a potential biomarker in Mexican mestizos', focusing on these three components determined in blood. We included 88 PD patients and 88 age-matched controls. We observed higher α-syn protein and decreased SNCA mRNA levels in PD subjects, compared to control group (p = 0.044 and p < 0.001, respectively). A statistically significant difference was found in allelic and genotypic frequencies of SNP rs356219 between PD patients and normal subjects (p = 0.006 and p = 0.023, respectively). Logistic regression analysis determined as optimal predictors of PD the GG genotype of SNP rs356219 (OR 2.49; p = 0.006) in a recessive model and α-syn protein (OR 1.057; p = 0.033). Furthermore, the G allele of SNP rs356219 was associated with higher plasmatic α-syn and mRNA levels in PD subjects. The receiver operating curves (ROC) distinguished PD from healthy controls with good sensitivity and specificity considering the plasmatic α-syn protein (AUC = 0.693, Sensitivity = 66.7 %, Specificity = 63.9 %) or a predictive probability of plasmatic α-syn protein and SNP rs356219 in a single model (AUC = 0.692, Sensitivity = 62.3 %, Specificity = 62.5 %). The performance of this classifier model in PD at early stage (n = 31) increase the discriminant power in both, plasmatic α-syn protein (AUC = 0.779, Sensitivity = 72.7 %, Specificity = 73.9 %) and predictive probability (AUC = 0.707, Sensitivity = 63.6 %, Specificity = 62.5 %). We propose that α-syn protein and SNP rs356219 together may work as a good signature of PD, and they can be suggested as a non-invasive biomarker of PD risk.


Assuntos
Doença de Parkinson/diagnóstico , alfa-Sinucleína/sangue , alfa-Sinucleína/genética , Idade de Início , Idoso , Alelos , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Curva ROC , Medição de Risco/métodos
7.
Front Immunol ; 11: 483296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244314

RESUMO

Somatic mutations in cancers affecting protein coding genes can give rise to potentially therapeutic neoepitopes. These neoepitopes can guide Adoptive Cell Therapies and Peptide- and RNA-based Neoepitope Vaccines to selectively target tumor cells using autologous patient cytotoxic T-cells. Currently, researchers have to independently align their data, call somatic mutations and haplotype the patient's HLA to use existing neoepitope prediction tools. We present ProTECT, a fully automated, reproducible, scalable, and efficient end-to-end analysis pipeline to identify and rank therapeutically relevant tumor neoepitopes in terms of potential immunogenicity starting directly from raw patient sequencing data, or from pre-processed data. The ProTECT pipeline encompasses alignment, HLA haplotyping, mutation calling (single nucleotide variants, short insertions and deletions, and gene fusions), peptide:MHC binding prediction, and ranking of final candidates. We demonstrate the scalability, efficiency, and utility of ProTECT on 326 samples from the TCGA Prostate Adenocarcinoma cohort, identifying recurrent potential neoepitopes from TMPRSS2-ERG fusions, and from SNVs in SPOP. We also compare ProTECT with results from published tools. ProTECT can be run on a standalone computer, a local cluster, or on a compute cloud using a Mesos backend. ProTECT is highly scalable and can process TCGA data in under 30 min per sample (on average) when run in large batches. ProTECT is freely available at https://www.github.com/BD2KGenomics/protect.


Assuntos
Antígenos de Neoplasias , Epitopos de Linfócito T , Imunoterapia , Neoplasias , Software , Linfócitos T Citotóxicos/imunologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Valor Preditivo dos Testes
8.
HIV Res Clin Pract ; 21(5): 130-139, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33211636

RESUMO

BACKGROUND: SARS-CoV-2 infection among People Living With HIV (PLWH) is not well-described. OBJECTIVE: To study COVID-19 symptoms and SARS-CoV-2 PCR-based swab testing among participants of the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). METHODS: A telephone survey was collected April-June 30, 2020. Symptom and testing prevalence were explored. Multivariable logistic regression was used to examine the factors associated with SARS-CoV-2 positivity. RESULTS: The survey was completed by 3411 participants, including 2078 (61%) PLWH and 1333 HIV-seronegative (SN) participants from across the US. Thirteen percent (n = 441) were tested for SARS-CoV-2 infection (13.4% of PLWH vs 12.2% of SN). Among those tested, positivity was higher in PLWH than SN (11.2% vs 6.1%, p = 0.08). Reasons for not being tested included testing not being available (30% of participants) and not knowing where to get tested (16% of participants). Most symptoms reported since January 2020 were similar in PLWH and SN, including headache (23% vs. 24%), myalgias (19% vs 18%), shortness of breath (14% vs 13%), chills (12% vs 10%), fever (6% vs 6%) and loss of taste or smell (6% vs 7%). Among PLWH who tested positive for SARS-CoV-2 DNA, the most common symptoms were headache (71%), myalgia (68%), cough (68%) and chills (65%). In multivariable analysis among those tested, the odds of SARS-CoV-2 positivity were higher among PLWH than SN (aOR = 2.22 95%CI = 01.01-4.85, p = 0.046) and among those living with others versus living alone (aOR = 2.95 95%CI = 1.18-7.40). CONCLUSION: Prevalence and type of COVID-19 symptoms were similar in PLWH and SN. SARS-CoV-2 infection may be elevated among PLWH.


Assuntos
COVID-19/fisiopatologia , COVID-19/virologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ageusia/epidemiologia , Ageusia/virologia , Anosmia/epidemiologia , Anosmia/virologia , COVID-19/epidemiologia , Calafrios/epidemiologia , Calafrios/virologia , Coinfecção , Tosse/epidemiologia , Tosse/virologia , Dispneia/epidemiologia , Dispneia/virologia , Feminino , Febre/epidemiologia , Febre/virologia , Infecções por HIV/epidemiologia , Cefaleia/epidemiologia , Humanos , Pessoa de Meia-Idade , Prevalência , SARS-CoV-2/isolamento & purificação , Estados Unidos/epidemiologia
9.
Int J Mol Sci ; 20(22)2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31752306

RESUMO

The synthesis of ethyl butyrate catalyzed by lipases A (CALA) or B (CALB) from Candida antarctica immobilized onto magnetic nanoparticles (MNP), CALA-MNP and CALB-MNP, respectively, is hereby reported. MNPs were prepared by co-precipitation, functionalized with 3-aminopropyltriethoxysilane, activated with glutaraldehyde, and then used as support to immobilize either CALA or CALB (immobilization yield: 100 ± 1.2% and 57.6 ± 3.8%; biocatalysts activities: 198.3 ± 2.7 Up-NPB/g and 52.9 ± 1.7 Up-NPB/g for CALA-MNP and CALB-MNP, respectively). X-ray diffraction and Raman spectroscopy analysis indicated the production of a magnetic nanomaterial with a diameter of 13.0 nm, whereas Fourier-transform infrared spectroscopy indicated functionalization, activation and enzyme immobilization. To determine the optimum conditions for the synthesis, a four-variable Central Composite Design (CCD) (biocatalyst content, molar ratio, temperature and time) was performed. Under optimized conditions (1:1, 45 °C and 6 h), it was possible to achieve 99.2 ± 0.3% of conversion for CALA-MNP (10 mg) and 97.5 ± 0.8% for CALB-MNP (12.5 mg), which retained approximately 80% of their activity after 10 consecutive cycles of esterification. Under ultrasonic irradiation, similar conversions were achieved but at 4 h of incubation, demonstrating the efficiency of ultrasound technology in the enzymatic synthesis of esters.


Assuntos
Butiratos/metabolismo , Candida/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Nanopartículas de Magnetita/química , Biocatálise , Esterificação/fisiologia , Glutaral/metabolismo , Ondas Ultrassônicas
10.
Am J Ind Med ; 62(11): 1007-1013, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31483067

RESUMO

BACKGROUND: Workers holding intermediate hierarchical positions in an institution may have a higher risk of occupational stress-related, ill health. This study examined the prevalence rates and odds ratios (ORs) of anxiety disorders among a hierarchical group of firefighters. METHODS: This cross-sectional study samples firefighters from Minas Gerais, Brazil, who answered a structured questionnaire in 2011 (survey completion rate = 89.5%). The outcome of interest was a medical diagnosis of anxiety disorder. Bivariate and multivariate analyses were conducted among five hierarchical occupational positions: privates (lowest position), corporals, sergeants (intermediate position), sub lieutenants, and officers (highest position). RESULTS: Overall, 8.4% of the sample reported an anxiety disorder, with the highest rate observed among intermediate workers (sergeants = 14.2%), followed by corporals (10%), privates (5.6%), sub lieutenants (5%), and officers (2.1%). Compared with privates, the unadjusted OR for sergeants was 2.49 (95% confidence interval, 1.35, 4.58). This finding remained statistically significant after adjustment for several control variables but was eliminated by age. CONCLUSION: The mental health of firefighters is affected by social class position. Mental health promotion efforts should focus on longitudinal research and work toward interventions aimed at modifying the hierarchical structure of workplaces.


Assuntos
Transtornos de Ansiedade/epidemiologia , Bombeiros/psicologia , Doenças Profissionais/epidemiologia , Adulto , Brasil/epidemiologia , Estudos Transversais , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Saúde Ocupacional , Estresse Ocupacional , Prevalência , Fatores de Risco , Classe Social , Adulto Jovem
11.
Biotech Histochem ; 94(1): 1-9, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30092668

RESUMO

We investigated the immunohistochemical staining characteristics of cytochrome P450 1A1 (CYP1A1), CYPB1, CYP2E1, and glutathione S-transferase P1 (GSTP1), GSTT1, GSTO1, GSTK1 in colon tumor and surrounding normal colon tissues. Tissues were obtained from 47 patients with colon adenocarcinoma and the staining intensity of tumor and control tissues was compared. CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTT1, GSTO1 and GSTK1 expressions in colon cancer cells were significantly greater than those in normal colon epithelial cells. No significant relation was found between the isoenzyme expressions and age, gender, smoking status, tumor grade and tumor stage. The higher expressions of CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTO1, GSTT1 and GSTK1 in tumor than in normal colon tissues may be important for colon cancer progression and development.


Assuntos
Colo/metabolismo , Neoplasias do Colo/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Glutationa Transferase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/genética , Sistema Enzimático do Citocromo P-450/genética , Feminino , Glutationa Transferase/genética , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Gerontol Nurs ; 44(11): 44-50, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30358887

RESUMO

Disparities exist in the recognition and treatment of mental health issues among Hispanic community-dwelling older adults. Previous researchers have focused on accessing mental health services, with limited attention to older Hispanic immigrants' perceptions of mental health issues. A qualitative descriptive research design was used to understand older Hispanic immigrants' perceptions of mental health issues, especially those related to stress, anxiety, and depression. Seventeen older adults from the Dominican Republic, Colombia, and Guatemala were interviewed. Despite having experienced significant personal tragedies, participants did not initially describe emotional distress or any mental health issues. When specifically questioned, depression was the most recognized illness. Depression was commonly described as sadness, whereas stress and anxiety had multiple definitions among participants. Understanding older Hispanic immigrants' perceptions of mental health issues and establishing a therapeutic relationship between the health care provider and patient may be helpful in recognizing and treating individuals who may be at high risk for emotional distress, anxiety, and depression. [Journal of Gerontological Nursing, 44(11), 44-50.].


Assuntos
Atitude Frente a Saúde/etnologia , Emigrantes e Imigrantes/psicologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Hispânico ou Latino/psicologia , Transtornos Mentais/etnologia , Transtornos Mentais/psicologia , Idoso , Idoso de 80 Anos ou mais , Colômbia , República Dominicana , Feminino , Guatemala , Humanos , Masculino , Estados Unidos
15.
Front Immunol ; 9: 99, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29441070

RESUMO

The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation (ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the X-ray structures of the two peptides bound to HLA-B*15:01 reveals drastically different conformations with measurable changes in the stability of the protein complexes, while the self-epitope is excluded from binding due to steric hindrance in the MHC groove. To evaluate the range of HLA alleles that could display the ALK neoepitopes, we used structure-based Rosetta comparative modeling calculations, which accurately predict several additional high affinity interactions and compare our results with commonly used prediction tools. Subsequent determination of the X-ray structure of an HLA-A*01:01 bound neoepitope validates atomic features seen in our Rosetta models with respect to key residues relevant for MHC stability and T cell receptor recognition. Finally, MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes are recognized by CD8+ T cells. This work provides a rational approach toward high-throughput identification and further optimization of putative neoantigen/HLA targets with desired recognition features for cancer immunotherapy.


Assuntos
Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/imunologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Epitopos/genética , Epitopos/imunologia , Mutação , Alelos , Sequência de Aminoácidos , Quinase do Linfoma Anaplásico/metabolismo , Antígenos de Neoplasias/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Biologia Computacional/métodos , Epitopos/química , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Modelos Moleculares , Peptídeos/genética , Peptídeos/imunologia , Peptídeos/metabolismo , Conformação Proteica , Multimerização Proteica , Relação Estrutura-Atividade
16.
Eur J Microbiol Immunol (Bp) ; 7(3): 229-233, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29034112

RESUMO

It is not clear whether infection with cytomegalovirus (CMV) is associated with hypertensive disorders in pregnant women. Through a case-control study design, 146 women suffering from hypertensive disorders in pregnancy (cases) and 146 age-matched normotensive pregnant women (controls) were examined for the presence of anti-CMV IgG and IgM antibodies with enzyme-linked immunoassays. IgM seropositive samples were further assayed by enzyme-linked fluorescent assay (ELFA). Anti-CMV IgG antibodies were found in 138 (94.5%) controls and in 136 (93.2%) cases (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.30-2.05; P = 0.62). High (>18 IU/ml) levels of anti-CMV IgG antibodies were found in 37.7% of the 138 seropositive controls and in 34.6% of the 136 seropositive cases (OR = 0.87; 95% CI: 0.53-1.43; P = 0.59). Anti-CMV IgM antibodies were found in 1 (0.7%) of the controls but in none of the cases using ELFA (P = 1.0). Seropositivity to CMV was not associated with a previous preeclampsia and was similar among cases regardless their mean systolic and diastolic blood pressures, and mean arterial blood pressure. No serological evidence of an association between CMV infection and hypertensive disorders of pregnancy was found. Further research to elucidate the role of CMV in hypertensive disorders in pregnancy should be conducted.

17.
Int J Biomed Sci ; 13(2): 79-83, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28824344

RESUMO

The mannose-binding lectin (MBL) 2 gene has an important function in the innate immune response and activation of the third pathway of the complement system. Some studies have assessed the association of the MBL2 gene polymorphisms with cervicovaginal infections (CVI); however, there is no information about this association in Mexican women. This study aimed to determine the association between the MBL2 codons 54 and 57 gene polymorphisms with CVI in a sample of Mexican women. Through a cross-sectional study, blood samples and cervicovaginal cultures were obtain from 354 women. MBL2 genotyping was performed by real-time polymerase chain reaction with Taqman probes. Of the 354 women studied, 128 (36.2%) had CVI and 226 (63.8%) were healthy. The frequencies of the C and T variants in codon 54 in women with CVI were 83% and 17%, respectively; whereas the frequencies of these variants in healthy women were 82% and 18%, respectively. The frequencies of variants C/C, C/T, and T/T in women with CVI were 68%, 31%, and 1%, respectively; whereas the frequencies of these variants in healthy women were 68%, 29%, and 3%, respectively. With respect to codon 57, the frequencies of variants C and T were identical in women with CVI and in healthy women (97% and 3%, respectively). The frequencies of variants C/C, C/T, and T/T were identical in women with CVI and in healthy women (94%, 6%, and 0%, respectively). We conclude that MBL2 codons 54 and 57 gene polymorphisms do not associate with CVI in Mexican women.

18.
J Clin Med Res ; 9(6): 508-511, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28496551

RESUMO

BACKGROUND: Very little is known about the association between infection with Toxoplasma gondii (T. gondii) and diabetes mellitus. We perform an age- and gender-matched case-control study to determine the association of T. gondii infection and diabetes mellitus. METHODS: Cases included 156 patients with diabetes mellitus and 156 controls without diabetes mellitus who attended in two public clinics in Durango City, Mexico. Sera of cases and controls were tested for the presence of anti-Toxoplasma IgG and IgM antibodies using commercially available enzyme-linked fluorescence assays (ELFA). RESULTS: Anti-T. gondii IgG antibodies were found in 10 (6.4%) of the 156 cases and in five (3.2%) of the 156 controls (odds ratio (OR): 2.06; 95% confidence interval (CI): 0.69 - 6.19; P = 0.18). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels in seropositive cases (1/10: 10.0%) was comparable to the one (1/5: 20%) in seropositive controls (OR: 0.44; 95% CI: 0.02 - 9.03; P = 1.00). None of the 10 cases and five controls with seropositivity to anti-T. gondii IgG antibodies were positive for anti-T. gondii IgM antibodies. Stratification by gender showed similar frequencies of T. gondii infection in female cases (7/107: 6.5%) and female controls (4/107: 3.7%) (OR: 1.80; 95% CI: 0.51 - 6.34; P = 0.53), and in male cases (3/49: 6.1%) and male controls (1/49: 2.0%) (OR: 3.13; 95% CI: 0.31 - 31.19; P = 0.61). CONCLUSIONS: We conclude that there is not serological evidence of an association between T. gondii infection and diabetes mellitus in the studied subjects in Durango City, Mexico. Further studies to elucidate the role of T. gondii in diabetes should be conducted.

19.
Hum Resour Health ; 15(1): 30, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28431553

RESUMO

BACKGROUND: Health personnel are key players in developing and improving healthcare systems, caring for individuals and their communities, and helping improve quality of life. However, these professionals are often exposed to long working hours because of the pressing need for their services at potentially any time of day. The long working hours they endure are a major risk factor for both acute and chronic health problems. The present study aimed to analyze occurrences of long working hours and their association with individual characteristics and employment factors among workers in the municipal healthcare system in Belo Horizonte, Brazil. METHODS: In this cross-sectional study, a ramdomly selected proportional sample of 1549 participants was analyzed from among the total of 13 602 workers in the Belo Horizonte municipal healthcare system in 2009. "Long" working hours were defined as >44 h/week. A self-administered questionnaire was used for accumulating data. Associations with outcomes were estimated using logistic regression, in univariate and multivariate models. RESULTS: The rate of occurrence of long working hours was 31.4% (95% CI 29.1-33.7). Lower educational level (high school, technical, or uncompleted undergraduate [OR 0.60, 95% CI 0.47-0.78 p < 0.001], or elementary [OR 0.33, 95% CI 0.19-0.55 p < 0.001]) was associated with a lower likelihood of self-reporting long working hours in relation to the group with the highest educational level (completed undergraduate or postgraduate). Male sex (OR 1.62, 95% CI 1.26-2.09 p < 0.001), having children (PR 1.54, 95% CI 1.20-1.97 p = 0.001), and being in the healthcare provider group (OR 1.82, 95% CI 1.40-2.35 p < 0.001) were factors associated with greater likelihood of long working hours. CONCLUSIONS: It was observed that number of long weekly working hours was related to individual characteristics and employment factors.


Assuntos
Pessoal de Saúde/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Local de Trabalho/estatística & dados numéricos , Adulto , Brasil , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Sexuais , Fatores de Tempo
20.
Injury ; 48(2): 349-352, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28038786

RESUMO

OBJECTIVE: The aim of this study is three fold: 1) to introduce epidemiologic data of patients with trauma-related amputations as a 10-year experience of a rehabitation center; 2) to determine comorbidities and secondary conditions of lower limb loss; 3) to determine the rehospitalization reasons for lower limb amputee patients. MATERIALS AND METHODS: This retrospective study was conducted in a tertiary rehabilitation center in Turkey. Clinical and demographic data of amputees including sex, age, employment status, time since amputation, time after amputation to first hospitalization, length of hospitalization, how many times the patient was hospitalized, reason for hospitalization, stump complications, comorbid conditions, amputation level and K classifacation were documented. RESULTS: Three hundred ninetynine patients with a mean age of 23,48±6,04 (4-74) years were included in this study. Mean duration after amputation was 119,71±68,86months. Patients were 3,43±2,53 times hospitalized. Landmine explosion was the most common etiology of amputation with 370 patients (92.7%). Below knee amputation was the most common amputation level with 230 (50,77%) amputations. 399 patients were hospitalized 1369 times and the most common hospitalization reason were stump complications (356 times, 26,00%). Spur formation (202 times) was the most common stump complications. Pyscologic disorders were the most common comorbidity with 68 patient (37,56%). CONCLUSION: Patients with traumatic limb amputations are likely to experience several complications and comorbidities. Prevention of secondary conditions affecting those living with the loss of a limb is an important part of amputee rehabilitation and may prevent rehospitalization.


Assuntos
Cotos de Amputação/patologia , Amputação Traumática/reabilitação , Amputados/estatística & dados numéricos , Exostose/cirurgia , Traumatismos da Perna/cirurgia , Extremidade Inferior/cirurgia , Readmissão do Paciente/estatística & dados numéricos , Acidentes , Amputação Traumática/epidemiologia , Amputação Traumática/psicologia , Amputados/psicologia , Amputados/reabilitação , Traumatismos por Explosões , Queimaduras , Comorbidade , Exostose/patologia , Exostose/psicologia , Feminino , Humanos , Traumatismos da Perna/complicações , Traumatismos da Perna/epidemiologia , Extremidade Inferior/patologia , Masculino , Centros de Reabilitação , Estudos Retrospectivos , Turquia/epidemiologia , Adulto Jovem
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