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1.
N Engl J Med ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924756

RESUMO

BACKGROUND: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

2.
J Geriatr Psychiatry Neurol ; : 8919887241237220, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436576

RESUMO

Dementia is a global public health challenge, and its impact on Portugal is yet unclear. This study forecasts dementia prevalence in Portugal until 2080. Using the Gonçalves-Pereira et al (2021) method, we estimated dementia cases among older adults (≥65 years) in the community. Applying age-sex specific prevalence rates of the Gonçalves-Pereira study to population projections for Portugal between 2020-2080, based on the 10/66 Dementia Research Group criteria (10/66 DRG) and the Diagnostic and Statistical Manual of Mental Disorders IV criteria (DSM-IV), to Portugal's population projections (2020-2080) under various growth scenarios (low, medium, and high). We anticipate a more than 2-fold increase in dementia prevalence from 2020 to 2080, both for 10/66 DRG [2.1%-5.0%] and DSM-IV [.8%-2.0%]. By 2080, those aged ≥80 years are projected to constitute 75.0% (vs 59.0% in 2020) of all dementia cases, particularly affecting women. Addressing dementia growth in Portugal calls for a comprehensive global response, while country-level estimates facilitate informed public health planning, policy-making, and resource allocation.

3.
Crit Rev Food Sci Nutr ; 63(27): 8796-8807, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35373671

RESUMO

The present systematic review with meta-analysis summarized studies that investigated the effect of carbohydrate (CHO) mouth rinse on muscle strength and muscular endurance. The search was performed in six databases. Thirteen randomized clinical trials were selected and the standardized mean difference between CHO mouth rinse and placebo for maximal strength and muscular endurance was determined via a random-effects model using Review Manager 5.4 software. Meta-regression was also performed to explore the influence of load, number of sets, number of exercises, fasting time, CHO concentration, and number of mouth rinses on the main outcomes. There was no significant effect of CHO mouth rinse on maximal strength (mean difference= 0.25 kg, 95%CI - 1.81 to 2.32 kg, z = 0.24, p = 0.810). However, there was a significant positive effect of CHO mouth rinse on muscular endurance (mean difference = 1.24 repetitions, 95%CI 0.70 to 1.77 repetitions, z = 4.55, p < 0.001). Meta-regression identified that CHO mouth rinse has greater benefits on muscular endurance when using high workloads, multiple exercises, and a smaller number of mouth rinses (p = 0.001). In conclusion, CHO mouth rinse has no effect on maximal muscle strength but has a positive effect on muscular endurance and seems to optimize when fewer mouth rinses, high workloads and numbers of exercises are used.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2057417.


Assuntos
Antissépticos Bucais , Resistência Física , Antissépticos Bucais/farmacologia , Resistência Física/fisiologia , Carboidratos da Dieta , Exercício Físico/fisiologia , Força Muscular/fisiologia
4.
Dement Geriatr Cogn Disord ; 52(4): 205-213, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37257431

RESUMO

INTRODUCTION: Literature shows poor dementia training and competencies among health and social professionals. Due to the growing prevalence of people with dementia and all the related care demands, specialized training is increasingly needed but must be effective in terms of impact on knowledge, behaviors, and attitudes. We aimed to analyze the impact of a first-level dementia training course for staff of a new specialized center for people with dementia, considering the first three levels of Kirkpatrick's evaluation framework, namely, staff reaction (satisfaction), skills and learning (knowledge and dementia attitudes), and behavior changes. METHODS: This is a single-center group pre-post design study of a 12-session online course. An online questionnaire was administered to measure satisfaction, expectations, knowledge/learning, attitudes (Dementia Attitude Scale), and new behaviors/practices. We compared perceived knowledge (Wilcoxon signed-rank test) and attitudes (paired t test). Thematic analysis explored new behaviors/practices. RESULTS: Eighty-five professionals and 1 volunteer were included (median age 31, 92% female). Satisfaction with the training was high (median 4/5). Perceived knowledge improved (median 3-4; p < 0.001). The knowledge test median score was 70.8%. After training, participants showed better attitudes toward dementia (mean 116.5, SD 10.3, to mean 122.2, SD 11.5; p < 0.001). Most (93%) said their behavior/practice changed. Thematic analysis yielded four new behavior/practice dimensions: care provision/interaction, communication, family/caregivers, and self-confidence. CONCLUSIONS: The course improved all dimensions evaluated, suggesting it effectively provides first-level dementia training. This may be transferable to similar settings.


Assuntos
Demência , Humanos , Feminino , Masculino , Demência/terapia , Atitude , Cuidadores , Comunicação , Aprendizagem
5.
BMC Med Educ ; 22(1): 83, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130892

RESUMO

INTRODUCTION: The influence of burnout, academic engagement, and their interaction in dropout intention among medical students should be further studied. Current research shows its consequences are relevant, however, there is little understanding on burnout and academic engagement moderation in dropout intention. The current study tested a model that relates the effects of coping strategies, social support satisfaction, general distress on academic engagement, burnout, and dropout intention, on medical students. METHODS: Through an online survey a non-probabilistic sample of one Medical Faculty's 1st- and 2nd-year students was recruited. Cross-sectional data were collected using psychometric instruments (Maslach Burnout Inventory - Student Survey, Social Support Satisfaction Scale for College Students, Brief COPE Scale for College Students, University Student Engagement Inventory, and Depression, Anxiety and Stress Scale), sociodemographic and academic variables, and analyzed using structural equation modeling. RESULTS: 532 students (76% response rate) enrolled in the study. Latent variables structural model presented a satisfactory fit to the data and confirmed the expected negative path between burnout and dropout intention (ßDI<-SB=0.430; p<.001) and the latent moderation burnout x engagement (ßDI<-SB*SE=-0.218; p<.001). CONCLUSION: Academic engagement attenuates the impact of burnout on dropout intention, working as a protective factor. Social support satisfaction and adaptive coping are associated with increased levels of academic engagement, and general distress and maladaptive coping are associated with burnout. Medical Schools should develop interventions to prevent dropout intention, tackle students' stress and academic challenges, and develop their academic engagement levels.


Assuntos
Esgotamento Profissional , Estudantes de Medicina , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico , Estudos Transversais , Humanos , Intenção , Inquéritos e Questionários
6.
Clin Gerontol ; 45(3): 525-537, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32065071

RESUMO

Objectives: Brief screening instruments are useful in busy clinical practice to identify those requiring further assessment. This study aims to translate and validate a Portuguese version of the four-item Zarit Burden Interview (ZBI-4) to identify caregiver burden in a community-based sample in Northern Portugal.Methods: We collected data from 203 informal caregivers of community-dwellers aged ≥80 years. Internal consistency and factors were measured using Cronbach's alpha. Pearson's correlation was used to examine construct validity against negative and positive aspects of caregiving from the Caregiving Appraisal Scale. Discriminative ability was evaluated from the area under the receiver operating characteristic curve (AUC). Optimal cutoffs were calculated using Youden´s Index.Results: The internal consistency of the Portuguese version of the ZBI-4 was good (alpha = 0.71). Concurrent validity was acceptable, showing strong correlation with the negative (rho = 0.66) and medium correlation with positive (rho = -0.33) aspects of the Caregiving Appraisal Scale. Discriminative accuracy for caregiver burden was also good (AUC = 0.86). Youden's index produced an optimal cutoff of ≥7 points for burden.Conclusions: The Portuguese version of the ZBI-4 screen demonstrates good psychometric properties.Clinical implications: These results show the utility of the Portuguese version of ZBI-4 as a short screen for caregiver burden for use in the community to facilitate rapid screening for this important and complex stressor.


Assuntos
Sobrecarga do Cuidador , Cuidadores , Humanos , Portugal , Psicometria , Reprodutibilidade dos Testes
7.
Pharmacogenomics J ; 21(2): 222-232, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33161412

RESUMO

Ovarian cancer (OC) represents the most lethal gynaecological neoplasia. Conversely, venous thromboembolism (VTE) and OC are intricately connected, with many haemostatic components favouring OC progression. In light of this bilateral relationship, genome-wide association studies (GWAS) have reported several single-nucleotide polymorphisms (SNPs) associated with VTE risk that could be used as predictors of OC clinical outcome for better therapeutic management strategies. Thus, the present study aimed to analyse the impact of VTE GWAS-identified SNPs on the clinical outcome of 336 epithelial ovarian cancer (EOC) patients. Polymorphism genotyping was performed using the TaqMan® Allelic Discrimination methodology. Carriers with the ZFPM2 rs4734879 G allele presented a significantly higher 5-year OS, 10-year OS and disease-free survival (DFS) compared to AA genotype patients with FIGO I/II stages (P = 0.009, P = 0.001 and P = 0.003, respectively). Regarding SLC19A2 rs2038024 polymorphism, carriers with the CC genotype presented a significantly lower 5-year OS, 10-year OS and DFS compared to A allele carriers in the same FIGO subgroup (P < 0.001, P = 0.004 and P = 0.005, respectively). As for CNTN6 rs6764623 polymorphism, carriers with the CC genotype presented a significantly lower 5-year OS compared to A allele carriers with FIGO I/II stages (P = 0.015). As for OTUD7A rs7164569, F11 rs4253417 and PROCR rs10747514, no significant impact on EOC patients' survival was observed. However, future studies are required to validate these results and uncover the biological mechanisms underlying our results.


Assuntos
Carcinoma Epitelial do Ovário/genética , Neoplasias Ovarianas/genética , Tromboembolia Venosa/genética , Alelos , Contactinas/genética , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Proteínas de Membrana Transportadoras/genética , Polimorfismo de Nucleotídeo Único/genética
8.
Exp Dermatol ; 30(6): 831-840, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33394553

RESUMO

Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central-Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non-coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune-related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune-related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC-PINT and LY86-AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein-coding genes). Among them, the LINC-PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86-AS1*rs12192707 mark lowest LY86-AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.


Assuntos
Antígenos de Superfície/genética , Pênfigo/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética , Antígenos de Superfície/imunologia , Predisposição Genética para Doença , Humanos , Pênfigo/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , RNA Longo não Codificante/imunologia
9.
Adv Exp Med Biol ; 1227: 107-129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32072502

RESUMO

The Notch signaling is a crucial pathway involved in cellular development, progression, and differentiation. Deregulation of Notch signaling pathway commonly impacts tissue homeostasis, being highly associated with proliferative disorders. The long noncoding RNAs (lncRNAs), which are transcripts with more than 200 nucleotides that do not code for proteins, were already described as Notch signaling pathway-interacting molecules. Many of them act as important transcriptional and posttranscriptional regulators, affecting gene expression and targeting other regulatory molecules, such as miRNAs. Due to their strong impact on function and gene expression of Notch-related molecules, lncRNAs influence susceptibility to cancer and other diseases, and can be regarded as potential biomarkers and therapeutic targets. Along this chapter, we summarize the cross talk between the Notch signaling pathway and their most important modulating lncRNAs, as well as the pathological consequences of these interactions, in different tissues.


Assuntos
Homeostase , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Diferenciação Celular , Homeostase/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética
10.
J Gene Med ; 21(1): e3065, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30549380

RESUMO

We review the most well characterized long non-coding RNAs (lncRNAs) with important roles in hallmarks of cancer, additionally including lncRNAs with a higher potential for clinical application. LncRNAs are transcripts larger than 200 nucleotides in length that do not appear to have protein-coding potential, although some of those may produce small functional peptides. These transcripts have attracted significant attention from researchers as a result of their role in genetic regulation, including epigenetic, transcriptional and post-transcriptional regulation, being involved in numerous biological processes, as well as being associated with multifactorial diseases, including tumorigenesis. The hallmarks of cancer include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis and activating invasion/metastasis. Additionally, genome instability, inflammation, reprogramming of energy metabolism and evading immune destruction and lncRNAs are implicated in all hallmarks of cancer. Based on the great number of studies describing lncRNAs associated with diverse aspects of most tumor types, lncRNAs have essential roles in potentially all biological features of cancer cells and show great utility as diagnostic and prognostic markers, as exemplified by PCA3 lncRNA detection in prostate cancer diagnosis.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Neoplasias/genética , RNA Longo não Codificante/genética , Animais , Transformação Celular Neoplásica , Metabolismo Energético , Estudos de Associação Genética , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/terapia , Transdução de Sinais , Microambiente Tumoral
11.
Pharmacogenomics J ; 19(1): 25-32, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30287910

RESUMO

The identification of predictive biomarkers for the first-line treatment of epithelial ovarian cancer (EOC) remains a challenge. Although genome-wide association studies (GWAS) have identified several genetic polymorphisms as predictors of EOC clinical outcome, the subsequent validation has not yet been performed. This study aims to validate the influence of Neuregulin 3 (NRG3) rs1649942 and Brain and reproductive organ-expressed (TNFRSF1A modulator) (BRE) rs7572644 GWAS-identified variants in an independent cohort of EOC patients from the North region of Portugal (n = 339) submitted to first-line treatment. Polymorphism genotypes were determined by real-time PCR using validated assays. Patients carrying the NRG3 rs1649942 A allele presented a significantly longer overall survival (OS) when compared to GG-genotype patients (log-rank test, P = 0.011) in the FIGO IV stage subgroup. No impact was observed for early-stage patients or considering disease-free survival (DFS) as an outcome. For FIGO I/II stage patients, BRE rs7572644 C allele carriers exhibit a decreased OS (P = 0.014) and DFS (P = 0.032) when compared to TT-homozygous patients. Furthermore, a Multivariate Cox regression analysis revealed a three-fold increase in the risk of death (HR, 3.09; P = 0.015) and recurrence (HR, 3.33; P = 0.009) for FIGO I/II C allele carriers. No significant impact was observed for late-stage patients. The BRE rs7572644 and NRG3 rs1649942 genetic variants were validated in an independent cohort of EOC Portuguese patients, particularly in specific subgroups considering FIGO staging. Further functional post-GWAS analyses are indispensable to understand the biological mechanisms underlying the observed results.


Assuntos
Carcinoma Epitelial do Ovário/genética , Proteínas do Tecido Nervoso/genética , Neurregulinas/genética , Polimorfismo de Nucleotídeo Único/genética , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Farmacogenética/métodos , Estudos Retrospectivos , Resultado do Tratamento
12.
Int J Immunogenet ; 46(3): 139-145, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30884100

RESUMO

Pemphigus foliaceus (PF) is an autoimmune skin disease characterized by autoantibodies directed mainly against desmoglein-1. The purpose of this study was to determine whether differential susceptibility to endemic PF in Brazil (fogo selvagem) is associated with polymorphisms at the cytogenetic location 1p13.2. Four single nucleotide polymorphisms that together tag 28 SNPs on a segment of approximately 312,000 bp encompassing the protein-coding genes MAGI3, PHTF1, RSBN1, PTPN22, BCL2L15, AP4B1, DCLRE1B, the pseudogenes MTND5P20, RPS2P14 (AL133517.1) and the long non-coding RNA genes AL137856.1, and AP4B1-AS1 were used as markers for association analysis in a case-control study. Allele, genotype and haplotype frequencies of rs33996649, rs2476601, rs3789604 and rs3195954 were compared between patient and control samples. No significant association was found. Lack of association with rs2476601 of the PTPN22 gene agrees with previous results for pemphigus vulgaris and the Tunisian form of endemic pemphigus foliaceus. The other three SNPs had never been analysed before in any form of pemphigus. We conclude that variants in structural and regulatory sites of region 1p13.2 are not susceptibility factors for fogo selvagem. We suggest careful investigation of this genomic region in diseases that had been previously associated with PTPN22, since there are several other genes relevant for immune-mediated diseases located in 1p13.2.


Assuntos
Cromossomos Humanos Par 1/genética , Pênfigo/genética , Brasil/epidemiologia , Predisposição Genética para Doença , Humanos , Pênfigo/epidemiologia , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , RNA Longo não Codificante/genética
13.
Int J Qual Health Care ; 31(4): 312-318, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30020471

RESUMO

OBJECTIVE: To examine the unmet needs of older clients with perceived mental health problems who attend primary healthcare services. DESIGN: Unmet needs were derived from (i) the health concerns and caregiver network availability provided by a General Practitioner (GPs) and from (ii) a qualitative analysis of an open question about needs completed by informal caregivers (ICs) of those clients. PARTICIPANTS: The sample comprised 436 clients with mean age of 75.2 years and 110 ICs with mean age of 56.7 years. SETTING: Primary healthcare centers in the North of Portugal. MAIN OUTCOME MEASURE: The Community Assessment of Risk Instrument-CARI (Clarnette RM, Ryan JP, O'Herlihy E, et al. The community assessment of risk instrument: investigation of inter-rater reliability of an instrument measuring risk of adverse outcomes. J Frailty Aging 2015;4: 80-9; O'Caoimh R, Healy E, Connell EO, et al. The Community Assessment of Risk Tool (CART): investigation of inter-rater reliability for a new instrument measuring risk of adverse outcomes in community dwelling older adults. Irish J Med Sci 2012.) and qualitative data about needs. RESULTS: Several needs were observed in relation to (1) mental state (e.g. cognition, anxiety/depression); (2) functionality (e.g. IADLS, bathing, mobility); (3) medical state (e.g. chronic diseases, vision deficits) and (4) IC ability to meet clients' needs. From the categorical analysis of the ICs' answers, an amount of unmet needs not only health related but also related with referrals and legal issues were found. CONCLUSIONS: This study shows a large number of unmet needs of older people. The evaluation of the clients combined with the evaluation of the testimonials of ICs enables the understanding of difficulties of both clients and caregivers, and which needs should be prioritized.


Assuntos
Cuidadores/psicologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Transtornos Mentais , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos , Feminino , Humanos , Masculino , Portugal/epidemiologia , Atenção Primária à Saúde/normas , Qualidade de Vida
14.
Adapt Phys Activ Q ; 36(1): 42-60, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30537859

RESUMO

This study aimed to identify the social representations of sports for Brazilian athletes with disabilities and to understand the extent to which sports can contribute to their empowerment. A total of 153 Brazilian athletes of various sports and with different types of disabilities took part in the study (122 men and 31 women; M = 31.91 years, SD = 9.46). The research was performed by an online survey by means of the free word association technique. All analyses were carried out using the Iramuteq computer program. The results indicated that the social representations of sports are related to individual and collective gains derived from practicing sports and that the representations are distinct according to the discipline practiced by the athlete. These results are discussed in light of the advantages of valuing the collective experience of athletes with disabilities as a group rather than as cases of individual overcoming. Social implications and possible future directions for research are presented.


Assuntos
Atletas/psicologia , Pessoas com Deficiência/psicologia , Poder Psicológico , Esportes para Pessoas com Deficiência/psicologia , Adolescente , Adulto , Brasil , Feminino , Processos Grupais , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Prática Psicológica , Inquéritos e Questionários , Adulto Jovem
15.
Biochim Biophys Acta ; 1859(10): 1306-13, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27424220

RESUMO

Genetic variations mapping to 3' untranslated regions (3'UTRs) may overlap with microRNA (miRNA) binding sites, therefore potentially interfering with translation inhibition or messenger RNA (mRNA) degradation. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) located within the 3'UTRs of six candidate genes and predicted to interfere with miRNA ligation could account for disease-relevant differential mRNA levels. Focusing on pemphigus foliaceus (PF) - an autoimmune blistering skin condition with unique endemic patterns - we investigated whether nine 3'UTR SNPs from the CD1D, CTLA4, KLRD1, KLRG1, NKG7, and TNFSF13B genes differentially expressed in PF were disease-associated. The heterozygous genotype of the KLRG1 rs1805672 polymorphism was associated with increased predisposition to PF (A/G vs. A/A: P=0.038; OR=1.60), and a trend for augmented susceptibility was observed for carriers of the G allele (P=0.094; OR=1.44). In silico analyses suggested that rs1805672 G allele could disrupt binding of miR-584-5p, and indicated rs1805672 as an expression Quantitative Trait Locus (eQTL), with an effect on KLRG1 gene expression. Dual-luciferase assay showed that miR-584-5p mediated approximately 50% downregulation of the reporter gene's activity through the 3'UTR of KLRG1 harboring rs1805672 A allele (vs. miRNA-negative condition, P=0.006). This silencing relationship was lost after site-directed mutation to G allele (vs. miRNA-negative condition, P=0.391; vs. rs1805672 A allele, P=0.005). Collectively, these results suggest that a disease-associated SNP located within the 3'UTR of KLRG1 directly interferes with miR-584-5p binding, allowing for KLRG1 mRNA differential accumulation, which in turn may contribute to pathogenesis of autoimmune diseases, such as pemphigus.


Assuntos
Regiões 3' não Traduzidas , Predisposição Genética para Doença , Lectinas Tipo C/genética , MicroRNAs/genética , Pênfigo/genética , Polimorfismo de Nucleotídeo Único , Transativadores/genética , Alelos , Antígenos CD1d/genética , Antígenos CD1d/metabolismo , Fator Ativador de Células B/genética , Fator Ativador de Células B/metabolismo , Sequência de Bases , Sítios de Ligação , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Estudos de Casos e Controles , Análise Mutacional de DNA , Regulação da Expressão Gênica , Frequência do Gene , Haplótipos , Humanos , Lectinas Tipo C/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Mutação , Subfamília D de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília D de Receptores Semelhantes a Lectina de Células NK/metabolismo , Pênfigo/diagnóstico , Pênfigo/metabolismo , Pênfigo/patologia , Receptores Imunológicos , Transativadores/metabolismo
17.
Int J Aging Hum Dev ; 84(4): 366-377, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27655954

RESUMO

There is a large gap between life expectancy and healthy life years at age 65. To reduce this gap, it is necessary that people with medical concerns perceived at higher risk of adverse outcomes are readily identified and treated. The same goes for the need to implement prevention plans. The main objectives of this study are to, in a first step, (a) estimate the percentage of medical concerns, (b) identify factors associated with this concern; in a second step, (c) estimate the perceived risk of death, and (d) evaluate the ability of medical concerns to predict this risk. Results show that the existence and severity of medical concerns are crucial in the prediction of perceived risk of death. Early identification of severity of medical concerns and the availability and adequacy of informal caregiving should allow healthcare professionals to promptly initiate an appropriate assessment and treatment of older patients.


Assuntos
Morte , Nível de Saúde , Atenção Primária à Saúde/métodos , Medição de Risco/métodos , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Atenção Primária à Saúde/normas , Prognóstico , Medição de Risco/normas
18.
Eur J Immunol ; 45(7): 2052-60, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25867094

RESUMO

Although HLA-A3 and A11 have been reported to be ligands for KIR3DL2, evidence for any in vivo relevance of this interaction is still missing. To explore the functional importance of KIR3DL2 allelic variation, we analyzed the autoimmune disease pemphigus foliaceus, previously associated (lower risk) with activating KIR genes. KIR3DL2*001 was increased in patients (odds ratio (OR) = 2.04; p = 0.007). The risk was higher for the presence of both KIR3DL2*001 and HLA-A3 or A11 (OR = 3.76, p = 0.013), providing the first evidence that HLA-A3 and A11 may interact with KIR3DL2 in vivo. The nonsynonymous single nucleotide polymorphism 1190T (rs3745902) was associated with protection (OR = 0.52, p = 0.018). This SNP results in a threonine-to-methionine substitution. Individuals who have methionine in this position exhibit a lower percentage of KIR3DL2-positive natural killer (NK) cells and also lower intensity of KIR3DL2 on expressing natural killer cells; additionally, we show that the expression of KIR3DL2 is independent of other killer cell immunoglobulin-like receptors. Pemphigus foliaceus is a very unique complex disease strongly associated with immune-related genes. It is the only autoimmune disease known to be endemic, showing a strong correlation with environmental factors. Our data demonstrate that this relatively unknown autoimmune disease may facilitate understanding of the molecular mechanisms of KIR3DL2 ligand recognition.


Assuntos
Predisposição Genética para Doença/genética , Antígeno HLA-A11/genética , Antígeno HLA-A11/metabolismo , Antígeno HLA-A3/genética , Pênfigo/genética , Receptores KIR3DL2/genética , Citometria de Fluxo , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Ligação Proteica
19.
BMC Cancer ; 16: 535, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27460659

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis. METHODS: Expressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry. RESULTS: All proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting. CONCLUSION: These findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC.


Assuntos
Basigina/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transportador de Glucose Tipo 1/metabolismo , Neoplasias Hepáticas/secundário , Linfonodos/patologia , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Simportadores/metabolismo , Biomarcadores Tumorais/metabolismo , Glicólise , Humanos , Imuno-Histoquímica , Ácido Láctico/metabolismo , Metástase Linfática , Pessoa de Meia-Idade , Estudos Prospectivos , Regulação para Cima
20.
Scand J Caring Sci ; 30(1): 65-73, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25856726

RESUMO

PURPOSE OF THE STUDY: This study explored the effectiveness of psychoeducational programme for informal caregivers called 'Caring at home'. DESIGN AND METHODS: The sample included 60 informal caregivers of elderly people (≥60 years) living in the community. Socio-demographic information of informal caregivers and care receivers was collected with the COPE Index. The assessment protocol comprised four scales: 12-item Short-Form Health Survey, General Health Questionnaire-12, Positive Aspects of Caregiving and Caregiver Strain Index Modified. There were five assessment moments: a pretest, a post-test and three follow-ups. RESULTS: Informal caregivers had an average age of 52.08 years (SD = 9.11) and were mainly women (90.0%), married/partnered (75.0%) and children of the care recipients (61.7%). The median time spent in care was 12 hours/day (IQR = 18). Results showed a favourable evolution after the psychoeducational intervention, a significant improvement in caregivers' mental health (p = 0.03) from pretest to 1st follow-up (2/3 months after the psychoeducational intervention) and the maintenance of the other assessed dimensions of the caregivers' behaviour. IMPLICATIONS: The psychoeducational intervention seems to promote improvements in mental health and the maintenance of other favourable conditions at baseline. These results may indicate that psychoeducational programme are beneficial to minimise or prevent adverse effects of caregiving.


Assuntos
Cuidadores/educação , Cuidadores/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade
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