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Mitochondria are organelles known primarily for generating ATP via the oxidative phosphorylation process. Environmental signals are sensed by whole organisms or cells and markedly affect this process, leading to alterations in gene transcription and, consequently, changes in mitochondrial function and biogenesis. The expression of mitochondrial genes is finely regulated by nuclear transcription factors, including nuclear receptors and their coregulators. Among the best-known coregulators is the nuclear receptor corepressor 1 (NCoR1). Muscle-specific knockout of NCoR1 in mice induces an oxidative phenotype, improving glucose and fatty acid metabolism. However, the mechanism by which NCoR1 is regulated remains elusive. In this work, we identified the poly(A)-binding protein 4 (PABPC4) as a new NCoR1 interactor. Unexpectedly, we found that silencing of PABPC4 induced an oxidative phenotype in both C2C12 and MEF cells, as indicated by increased oxygen consumption, mitochondria content, and reduced lactate production. Mechanistically, we demonstrated that PABPC4 silencing increased the ubiquitination and consequent degradation of NCoR1, leading to the derepression of PPAR-regulated genes. As a consequence, cells with PABPC4 silencing had a greater capacity to metabolize lipids, reduced intracellular lipid droplets, and reduced cell death. Interestingly, in conditions known to induce mitochondrial function and biogenesis, both mRNA expression and PABPC4 protein content were markedly reduced. Our study, therefore, suggests that the lowering of PABPC4 expression may represent an adaptive event required to induce mitochondrial activity in response to metabolic stress in skeletal muscle cells. As such, the NCoR1-PABPC4 interface might be a new road to the treatment of metabolic diseases.
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Receptores Citoplasmáticos e Nucleares , Fatores de Transcrição , Animais , Camundongos , Proteínas Correpressoras/metabolismo , Correpressor 1 de Receptor Nuclear/genética , Correpressor 1 de Receptor Nuclear/metabolismo , Fosforilação Oxidativa , Receptores Citoplasmáticos e Nucleares/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. METHOD: This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. RESULTS: The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability. CONCLUSION: Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.
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Artrite Reumatoide , Proteômica , Humanos , Estudos de Coortes , Artrite Reumatoide/diagnóstico , Biomarcadores/metabolismo , Análise por ConglomeradosRESUMO
PURPOSE: Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS: The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS: Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION: In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Quimiorradioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Carcinoma Pulmonar de Células não Pequenas/terapia , Intervalo Livre de Doença , Estônia , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Índia , Jordânia , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Paquistão , Estudos Prospectivos , Controle de Qualidade , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Resultado do Tratamento , Turquia , VietnãRESUMO
This study evaluated the thermoregulation and spermatogenic changes by scrotal temperature gradient using infrared thermography in testicular compromised bulls. Bulls were insulated (n = 6) for 72 hr and control animals (n = 3) remained without insulation during all the experimental period. Seminal evaluation was performed prior, at insult removal and once per week for 13 consecutive weeks. Mean temperature gradient in insulated animals was lower at the time of insulation removal compared to the week prior and after the insult (p < .05). Two weeks after insult, sperm motility was lower in insulated compared to control animals (p < .01) and spermatozoa total defects were higher in insulated compared to control animals (p < .05). Two and seven weeks after insult, the major defects were higher in insulated compared to control animals (p < .05). Scrotal temperature gradient showed a positive correlation with sperm mass motion (p < .01) and a negative correlation with ocular globe temperature (p < .01) in insulated animals. The infrared thermography can be used to evaluate ocular globe temperature in bulls; however, it is only effective to detect changes in scrotal temperature gradient at the insult removal.
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Escroto/diagnóstico por imagem , Espermatogênese/fisiologia , Testículo/diagnóstico por imagem , Termografia/métodos , Animais , Bovinos , Masculino , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/fisiologia , Testículo/fisiologiaRESUMO
Backgrounds/Objectives:The activity of brown/beige adipose tissue (B/BAT) is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at reducing body mass present an increase of B/BAT activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of B/BAT in obese non-diabetic (OND) and obese diabetic (OD) subjects. SUBJECTS/METHODS: This is an observational study. Fourteen OND, 14 OD and 11 subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and 8 months after surgery. B/BAT was evaluated by (18F)-FDG-PET/CT scan and determination of signature transcript expression in specimens obtained in biopsies. RESULTS: Before surgery, mean B/BAT activity and the expression of signature transcripts were similar between OND and OD groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of B/BAT was increased in OND and unchanged in OD subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in OND subjects as compared with OD subjects. CONCLUSIONS: Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.
Assuntos
Tecido Adiposo Bege/fisiologia , Tecido Adiposo Marrom/fisiologia , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica , Resistência à Insulina/fisiologia , Obesidade Mórbida/cirurgia , Redução de Peso/fisiologia , Adaptação Fisiológica , Adulto , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Humanos , Obesidade Mórbida/diagnóstico por imagem , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Resultado do Tratamento , Adulto JovemRESUMO
Background: The consequences of financial crises on patients' use of healthcare have been widely discussed. This paper seeks to ascertain whether the position of key players, i.e. doctors, may reveal realities other than those officially reported about the 2008 financial crisis. Methods: In 2013-14, a national survey of doctors was conducted in Portugal, which received international assistance in the wake of the financial crisis. An exploratory model comprising descriptive statistics, regression and independence analyses focused on doctors' experience of patients' use of medications, consultations, exams and treatment services, and whether they stopped treatments. Results: According to doctors, an unspecified number of patients experienced difficulties using healthcare as more patients requested prescriptions for cheaper medications or simply stopped treatments. Significant variations were found according to speciality, years of practice and sector of activity. Conclusions: Cost-containment mechanisms are regarded as necessary. However, the evidence indicated a side effect, i.e. a decrease in patients' ability to use healthcare, including in the National Health Service (NHS). It also highlighted the need to listen to health professionals as key informants on patient's behaviour and the daily functioning of health services.
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Recessão Econômica/estatística & dados numéricos , Programas Nacionais de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Médicos/psicologia , Cooperação e Adesão ao Tratamento/psicologia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PortugalRESUMO
BACKGROUND AND OBJECTIVE: Periodontal diseases are associated with bacterial challenge and the host immune response, and are also modulated by genetic factors. There is evidence that sickle cell anaemia (SCA) does not represent a risk factor for periodontal diseases. However, it is still unclear whether the heterozygous condition [sickle cell trait (SCT)] is associated with periodontal diseases. SCT is a genetic condition that can cause vaso-occlusive events, which may be associated with a propensity to bacterial infections. The aim of this study was to investigate the association of SCA and SCT with periodontal diseases by evaluating clinical and radiographic characteristics. MATERIAL AND METHODS: The sample (n = 369) was selected and divided into two groups: exposed groups [HbSS (SCA genotype) and HbAS (SCT genotype) = 246] and a nonexposed group (HbAA = 123). HbAA consisted of individuals without SCA and SCT. The clinical parameters evaluated were plaque index, gingival index, calculus index, clinical probing depth, clinical attachment level, gingival recession, tooth mobility and furcation involvement. The percentage of alveolar bone loss was measured using a Schei ruler. Binomial and Poisson regressions were used to estimate correlations of interest (α = 0.05). RESULTS: None of the periodontal parameters was associated with SCA. SCT was associated with gingivitis (p = 0.041) and periodontitis (p = 0.002). Individuals with SCT had a lower plaque index (p = 0.044) but a higher calculus index (p = 0.003) and greater alveolar bone loss (p = 0.010) compared with subjects in the HbAA group. CONCLUSIONS: SCT can act as a predictor for establishment of periodontal diseases. There was no correlation between SCA and periodontal diseases.
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Anemia Falciforme/complicações , Anemia Falciforme/imunologia , Doenças Periodontais/complicações , Doenças Periodontais/imunologia , Traço Falciforme/complicações , Traço Falciforme/imunologia , Adolescente , Adulto , Perda do Osso Alveolar/complicações , Anemia Falciforme/genética , Brasil , Criança , Pré-Escolar , Estudos de Coortes , Cálculos Dentários , Índice de Placa Dentária , Feminino , Genótipo , Retração Gengival/complicações , Gengivite/complicações , Hemoglobina A/análise , Hemoglobina Falciforme/análise , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/complicações , Índice Periodontal , Bolsa Periodontal/complicações , Periodontite/complicações , Periodontite/imunologia , Fatores de Risco , Traço Falciforme/genética , Mobilidade Dentária/complicaçõesRESUMO
This study examined the changes in resting hematological variables in ultra-endurance runners throughout a multi-stage ultra-marathon competition, and compared athletes that completed all stages with those that failed to complete at least one stage within the cut-off time of competition. 19 ultra-endurance runners competing in a 230 km multi-stage ultra-marathon, conducted over 5 consecutive days in hot ambient conditions (32-40°C T(max)), volunteered to participate in the study. Each day, whole blood samples were collected prior to stage commencement and analyzed for full cell counts by Coulter counter. Linear increases were observed for leukocytes, monocytes and lymphocytes; with increases until Stage 3 and a decrease thereafter. Granulocytes showed a cubic growth exponent, indicating decrements to baseline after the significant increments until Stage 3. Hemoglobin and hematocrit showed linear decrements throughout the multi-stage ultra-marathon. No changes in erythrocytes and platelets were observed throughout the multi-stage ultra-marathon. Granulocytes, erythrocytes, hemoglobin and hematocrit changes along the multi-stage ultra-marathon differed in runners that completed all stages compared to those who failed to complete at least one stage within the cut-off time. Multi-stage ultra-marathon in the heat has a large impact on hematological responses of ultra-endurance runners associated with altered performance.
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Testes Hematológicos , Temperatura Alta , Resistência Física/fisiologia , Corrida/fisiologia , Adulto , Contagem de Células Sanguíneas , Plaquetas/metabolismo , Eritrócitos/metabolismo , Feminino , Granulócitos/metabolismo , Hematócrito , Hemoglobinas/metabolismo , Humanos , Leucócitos/metabolismo , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismoRESUMO
Ceria (CeO2) is a promising dilute magnetic semiconductor. Several studies report that the intrinsic and extrinsic structural defects are responsible for room temperature ferromagnetism in undoped and transition metal doped CeO2 nanostructures; however, the nature of the kind of defect necessary to promote and stabilize the ferromagnetism in such a system is still a matter of debate. In the work presented here, nanorods from the system Ce1-xCuxO2-δ with x = 0, 0.01, 0.03, 0.05 and 0.10, with the more stable {111} surface exposed were synthesized by a microwave-assisted hydrothermal method. A very careful structure characterization confirms that the Cu in the samples assumes a majority 2+ oxidation state, occupying the Ce (Ce(4+) and Ce(3+)) sites with no secondary phases up to x = 0.05. The inclusion of the Cu(2+) in the CeO2 structure leads to the introduction of oxygen vacancies in a density proportional to the Cu(2+) content. It is supposed that the spatial distribution of the oxygen vacancies follows the Cu(2+) distribution by means of the formation of a defect complex consisting of Cu(2+) ion and an oxygen vacancy. Superconducting quantum interference device magnetometry demonstrated a diamagnetic behavior for the undoped sample and a typical paramagnetic Curie-Weiss behavior with antiferromagnetic interactions between the Cu(2+) ions for the single phase doped samples. We suggest that the presence of oxygen vacancies is not a sufficient condition to mediate ferromagnetism in the CeO2 system, and only oxygen vacancies in the surface of nanostructures would lead to such a long range magnetic order.
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The purpose of the study was to examine the effect of age on short-term performance indicators applying multilevel regression modeling, and whether changes induced by age were affected by maturation. The study applied a mixed longitudinal approach with 8 measurement points over a period of 4 years. Anthropometry, predicted adult stature, countermovement jump, 15-m sprint and agility test from 38 under-11 young soccer players were considered. Early maturing players were 3% taller compared to late maturers. A substantial effect of age was present in all performance indicators (P<0.05). Parameters showed improvements in performance, even when accounting for interindividual variation in somatic maturity. Vertical jump tended to be stable in early maturers during the first year, presenting an exponential increase thereafter (16%, P<0.05). Additionally, early maturing boys had lower vertical jump scores but a substantial higher rate of development with age (3% per year). Performance tends to plateau during the first 3 years following the improvements in agility (9.1%, P<0.05). In the running tests, early maturers had better performances (19%, P<0.05), while a higher rate of improvement of 1% was observed for the late maturers. Young soccer players should be expected to have substantial improvements in short-term performance, influenced by independent variation between players in maturity status.
Assuntos
Desempenho Atlético/fisiologia , Maturidade Sexual/fisiologia , Futebol/fisiologia , Adolescente , Fatores Etários , Antropometria , Criança , Humanos , Modelos Lineares , Estudos Longitudinais , MasculinoRESUMO
This study investigated the feathers' composition of South polar skua (Stercorarius maccormicki) using WDXRF, evaluating the concentration of essential and non-essential elements in the feathers, and dividing it into rachis and barb parts. We collected South polar skuas feathers from Hennequin Point, King George Island, South Shetland, Antarctic Peninsula in January of 2013. Our results show that 18 elements were observed in the composition of the feathers, with a different concentration between the rachis and barbs, qualitatively and quantitatively. Only 3 elements observed were classified as non-essentials but still mostly elements do not have a function described in the literature to the feathers. According to our knowledge, this is the first study that uses this technique to evaluate the concentration of different elements in the feathers. The findings of this study highlight the use of alternative techniques to biomonitoring elements in the ecosystem and bring baseline information for future studies.
Assuntos
Charadriiformes , Ecossistema , Animais , Plumas , Regiões Antárticas , Monitoramento BiológicoRESUMO
Sessile organisms, such as plants, developed various ways to sense and respond to external and internal stimuli to maximize their fitness through evolutionary time. Transcripts and protein regulation are, among many, the main mechanisms that plants use to respond to environmental changes. SKIP protein is one such, presenting an SNKW interacting domain, which is highly conserved among eukaryotes, where SKI interacting protein acts in regulating key processes. In the present work, many bioinformatics tools, such as phylogenetic relationships, gene structure, physical-chemical properties, conserved motifs, prediction of regulatory cis-elements, chromosomal localization, and protein-protein interaction network, were used to better understand the genome-wide SNW/SKIP domain-containing proteins. In total, 28 proteins containing the SNW/SKIP domain were identified in different plant species, including plants of agronomic interest. Two main protein clusters were formed in phylogenetic analysis, and gene structure analysis revealed that, in general, the coding region had no introns. Also, expression of these genes is possibly induced by abiotic stress stimuli. Primary structure analysis of the proteins revealed the existence of an evolutionarily conserved functional unit. But physicochemical properties show that proteins containing the SNW/SKIP domain are commonly unstable under in vivo conditions. In addition, the protein network, demonstrated that SKIP homologues could act by modulating plant fitness through gene expression regulation at the transcriptional and post-transcriptional levels. This could be corroborated by the expression number of gene copies of SKIP proteins in many species, highlighting it's crucial role in plant development and tolerance through the course of evolution.
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Genoma de Planta , Filogenia , Proteínas de Plantas , Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/genética , Plantas/metabolismo , Domínios Proteicos , Regulação da Expressão Gênica de PlantasRESUMO
AIMS: Analyze the capacity of ICO, the ratio of waist circumference (WC) and height, in predicting hemodynamic impairment in Erectile Dysfunction (ED) patients, independently and integrated in Metabolic Syndrome (MetS) definitions. METHODS: Four hundred and eighty-five ED patients followed in Urology consult from January 2008 until March 2012 were evaluated by a standardized protocol: health questionnaire, anthropometric measurements (AM), blood pressure and analysis, and Penile Duplex Doppler Ultrasound (PDDU) exam. Associations between AM and MetS definitions, including ATPIII, IDF and a new definition replacing WC by ICO in ATPIII MetS definition (ModATPIII), and PDDU were calculated. RESULTS: ICO was the measure of obesity more strongly correlated with diminished mean Peak Systolic Velocity (mPSV) (r = -0.189, p < 0.001). A positive association remained when replacing WC by ICO ≥ 0.60 (a nationally obtained ratio) in ATPIII MetS definition (ModATPIII). Patients with ModATPIII had lower mPSV when compared to non-MetS patients (30.8 versus 37.1, p < 0.001). Only the IDF definition had a significant association with AD (OR = 1853; 95%CI, 1.202-2.857). CONCLUSIONS: ICO revealed potential value to predict PDDU changes in a MetS context. However, IDF definition presented a stronger correlation with arteriogenic ED. Although longitudinal studies are necessary to confirm this hypothesis, our study highlights the importance of different MetS definitions for ED assessment.
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Impotência Vasculogênica/diagnóstico , Síndrome Metabólica/diagnóstico , Obesidade Abdominal , Valor Preditivo dos Testes , Adulto , Idoso , Antropometria , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pênis/diagnóstico por imagem , Portugal , Ultrassonografia , Circunferência da CinturaRESUMO
Extracellular matrix (ECM) proteins in the mammary gland provide structure and regulate its development and homeostasis. Alterations in its structure can regulate and support pathogenesis, like breast tumors. Aiming to identify the health and tumoral canine mammary ECM scaffold protein profile by immunohistochemistry, the decellularization process was carried out to remove the cellular content. Additionally, it was verified the influence of health and tumoral ECM on the attachment of health and tumoral cells. The types I, III, IV, and V structural collagens were scarce in the mammary tumor, and ECM fibers were disorganized. Vimentin and CD44 were more common in mammary tumor stroma, suggesting a role in cell migration that results in tumor progression. Elastin, fibronectin, laminin, vitronectin, and osteopontin were similarly detected under healthy and tumor conditions, providing the attachment of normal cells in healthy ECM, while tumoral cells were able to attach in tumoral ECM. The protein pattern demonstrates ECM alteration in canine mammary tumorigenesis, presenting new knowledge on mammary tumor ECM microenvironment.
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Proteínas da Matriz Extracelular , Neoplasias , Animais , Cães , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Laminina , Tecido Conjuntivo , Neoplasias/patologia , Microambiente TumoralRESUMO
OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.
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Índice de Gravidade de Doença , Espondilartrite/epidemiologia , Espondilartrite/fisiopatologia , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/fisiopatologia , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Fusarium head blight (FHB) is a fungal disease of wheat (Triticum aestivum.L) that causes yield losses and produces mycotoxins which could easily exceed the limits of the EU regulations. Resistance to FHB has a complex genetic architecture and accurate evaluation in breeding programs is key to selecting resistant varieties. The Area Under the Disease Progress Curve (AUDPC) is one of the commonly metric used as a standard methodology to score FHB. Although efficient, AUDPC requires significant costs in phenotyping to cover the entire disease development pattern. Here, we show that there are more efficient alternatives to AUDPC (angle, growing degree days to reach 50% FHB severity, and FHB maximum variance) that reduce the number of field assessments required and allow for fair comparisons between unbalanced evaluations across trials. Furthermore, we found that the evaluation method that captures the maximum variance in FHB severity across plots is the most optimal approach for scoring FHB. In addition, results obtained on experimental data were validated on a simulated experiment where the disease progress curve was modeled as a sigmoid curve with known parameters and assessment protocols were fully controlled. Results show that alternative metrics tested in this study captured key components of quantitative plant resistance. Moreover, the new metrics could be a starting point for more accurate methods for measuring FHB in the field. For example, the optimal interval for FHB evaluation could be predicted using prior knowledge from historical weather data and FHB scores from previous trials. Finally, the evaluation methods presented in this study can reduce the FHB phenotyping burden in plant breeding with minimal losses on signal detection, resulting in a response variable available to use in data-driven analysis such as genome-wide association studies or genomic selection.
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This study proposed to investigate further the role of oestrogens during pubertal growth of rat ventral prostate, by analysing the effect of anti-oestrogen fulvestrant (ICI 182,780) on the expression of androgen (AR) and oestrogen receptors (ESR1 and ESR2), mitogen-activated protein kinase (ERK1/2) phosphorylation, and expression of Ki-67, a biomarker for cell proliferation. Ventral prostates were obtained from 90-day-old rats treated once a week for 2 months with vehicle (control) or ICI 182,780 (10 mg/rat, s.c.). Transcripts for AR, ESR1 and ESR2 were evaluated by quantitative real-time polymerase chain reaction. Expression of AR, ESR1, ESR2, total and phospho-ERK1/2 was analysed by Western blot or immunofluorescence. Ki-67-positive cells and myosin heavy chain were detected by immunohistochemistry. Cylindrical epithelial cells slightly taller, epithelial dysplasia and an increase in smooth muscle layer were observed in the ventral prostate from ICI 182,780-treated rats. ICI 182,780 did not change the mRNA, but decreased the protein levels for AR in the ventral prostate. The expression of ESR1 (mRNA and protein) was upregulated by ICI 182,780, but no changes were observed on ESR2 expression (mRNA and protein). ICI 182,780 decreased the phosphorylation state of ERK1/2, with no changes in total ERK1/2 levels. Ki-67-positive cells in the ventral prostate were also decreased by ICI 182,780. In conclusion, ICI 182,780 induces downregulation of AR expression and may block the translocation of ESR1 and ESR2 from the nucleus to the plasma membrane, decreasing ERK1/2 phosphorylation and prostatic epithelial cell proliferation. These findings provide a basis for physiological roles of oestrogen in the ventral prostate. Further studies with fulvestrant are necessary in benign prostate hyperplasia and prostatic cancer models.
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Estradiol/análogos & derivados , Antagonistas de Estrogênios/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Próstata/efeitos dos fármacos , Animais , Western Blotting , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Imunofluorescência , Fulvestranto , Imuno-Histoquímica , Masculino , Fosforilação , Próstata/enzimologia , Próstata/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Testosterona/metabolismoRESUMO
Androgenic-anabolic steroids (AAS) have been associated with an increased incidence of tendon rupture. The aim of this study was to compare the biomechanical properties of the rat calcaneal tendon (CT), superficial flexor tendon (SFT), and deep flexor tendon (DFT), and to determine the effect of jump training in association with AAS. Animals were separated into four groups: sedentary, trained, AAS-treated sedentary rats (AAS), and AAS-treated and trained animals. Mechanical testing showed that the CT differed from the DFT and SFT, which showed similar mechanical properties. Jump caused the CT to exhibit an extended toe region, an increased resistance to tensional load, and a decreased elastic modulus, characteristics of an elastic tendon capable of storing energy. AAS caused the tendons to be less compliant, and the effects were reinforced by simultaneous training. The DFT was the most affected by training, AAS, and the interaction of both, likely because of its involvement in the toe-off step of jumping, which we suggest is related to the rapid transmission of force as opposed to energy storage. In conclusion, tendons are differently adapted to exercise, but responded equally to AAS, showing reduced flexibility, which is suggested to increase the risk of tendon rupture in AAS consumers.
Assuntos
Anabolizantes/farmacologia , Nandrolona/análogos & derivados , Tendões/efeitos dos fármacos , Suporte de Carga/fisiologia , Anabolizantes/administração & dosagem , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Masculino , Nandrolona/administração & dosagem , Nandrolona/farmacologia , Decanoato de Nandrolona , Condicionamento Físico Animal , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
Cervical cancer is one of the most common cancers in developing nations. It has had a tremendous impact on the lifetime of millions of women over the last century and continues to do so. In this collaborative clinicians' review, we highlight the incidence, treatment and clinical outcomes of cervical cancer in low-income (LICs) and low- and middle-income countries (LMICs) across Asia, South America, South Africa and Eastern Europe. With the cervical cancer burden and locally advanced cancers being high, the majority of LICs/LMICs have been striving to adhere to optimal evaluation and treatment guidelines. However, the huge gap in resource availability, rural versus urban disparity and access to resources have led to poor compliance to evaluation, treatment and post-treatment rehabilitation. To mitigate the overwhelming numbers, various treatment strategies like neoadjuvant chemotherapy, hypofractionation radiation schedules (both external and brachytherapy) have been attempted with no major success. Also, the compliance to concurrent chemoradiation in various regions is a major challenge. With the burden of advanced cancers, the lack of palliative care services and their integration in cancer care is still a reality.
Assuntos
Neoplasias do Colo do Útero , Países em Desenvolvimento , Feminino , Humanos , Incidência , Renda , Resultado do Tratamento , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapiaRESUMO
Prostate epithelial-cell apoptosis occurs in response to androgen deprivation. We have hypothesized that continued regression would require stromal changes. Studying apoptosis kinetics up to the 14th day after castration, we identified successive waves of apoptosis, with a prominent peak on day 11. This peak was associated with caspase-3 activity, nuclear translocation of apoptosis-inducing factor and clusterin expression. The apoptosis peak on day 11 was preceded by increased MMP-2 and MMP-7 activation, and MMP-9 expression on days 9 and 10. Treatment with the matrix metalloproteinases inhibitors doxycyclin, hydrocortisone, or GM6001 caused significant reduction in the apoptosis rate on day 11. The present data demonstrate that prostatic epithelial-cell deletion at the 11th day after castration was induced by focal degradation of the extracellular matrix associated with stromal remodelling.