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1.
Oxid Med Cell Longev ; 2020: 7986071, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089780

RESUMO

The human thymus is a primary lymphoepithelial organ which supports the production of self-tolerant T cells with competent and regulatory functions. Paradoxically, despite the crucial role that it exerts in T cell-mediated immunity and prevention of systemic autoimmunity, the thymus is the first organ of the body that exhibits age-associated degeneration/regression, termed "thymic involution." A hallmark of this early phenomenon is a progressive decline of thymic mass as well as a decreased output of naïve T cells, thus resulting in impaired immune response. Importantly, thymic involution has been recently linked with cellular senescence which is a stress response induced by various stimuli. Accumulation of senescent cells in tissues has been implicated in aging and a plethora of age-related diseases. In addition, several lines of evidence indicate that oxidative stress, a well-established trigger of senescence, is also involved in thymic involution, thus highlighting a possible interplay between oxidative stress, senescence, and thymic involution.

2.
Cells ; 8(7)2019 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-31284597

RESUMO

Cellular senescence refers to a stress response aiming to preserve cellular and, therefore, organismal homeostasis. Importantly, deregulation of mitochondrial homeostatic mechanisms, manifested as impaired mitochondrial biogenesis, metabolism and dynamics, has emerged as a hallmark of cellular senescence. On the other hand, impaired mitostasis has been suggested to induce cellular senescence. This review aims to provide an overview of homeostatic mechanisms operating within mitochondria and a comprehensive insight into the interplay between cellular senescence and mitochondrial dysfunction.


Assuntos
Senescência Celular , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Homeostase , Humanos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
4.
Pharmacol Ther ; 193: 31-49, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30121319

RESUMO

Cellular senescence is a stress response mechanism ensuring homeostasis. Its temporal activation during embryonic development or normal adult life is linked with beneficial properties. In contrast, persistent (chronic) senescence seems to exert detrimental effects fostering aging and age-related disorders, such as cancer. Due to the lack of a reliable marker able to detect senescence in vivo, its precise impact in age-related diseases is to a large extent still undetermined. A novel reagent termed GL13 (SenTraGorTM) that we developed, allowing senescence recognition in any type of biological material, emerges as a powerful tool to study the phenomenon of senescence in vivo. Exploiting the advantages of this novel methodological approach, scientists will be able to detect and connect senescence with aggressive behavior in human malignancies, such as tolerance to chemotherapy in classical Hodgkin Lymphoma and Langerhans Cell Histiocytosis. The latter depicts the importance of developing the new and rapidly expanding field of senotherapeutic agents targeting and driving to cell death senescent cells. We discuss in detail the current progress of this exciting area of senotherapeutics and suggest its future perspectives and applications.


Assuntos
Antineoplásicos/uso terapêutico , Senescência Celular , Neoplasias/tratamento farmacológico , Animais , Humanos
5.
Methods Mol Biol ; 1896: 119-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30474845

RESUMO

Lipofuscin accumulation is a hallmark of senescence. This nondegradable material aggregates in the cytoplasm of stressed or damaged cells due to metabolic imbalance associated with aging and age-related diseases. Indications of a soluble state of lipofuscin have also been provided, rendering the perspective of monitoring such processes via lipofuscin quantification in liquids intriguing. Therefore, the development of an accurate and reliable method is of paramount importance. Currently available assays are characterized by inherent pitfalls which demote their credibility. We herein describe a simple, highly specific and sensitive protocol for measuring lipofuscin levels in any type of liquid. The current method represents an evolution of a previously described assay, developed for in vitro and in vivo senescent cell recognition that exploits a newly synthesized Sudan Black-B analog (GL13). Analysis of human clinical samples with the modified protocol provided strong evidence of its usefulness for the exposure and surveillance of age-related conditions.


Assuntos
Envelhecimento , Compostos Azo , Biomarcadores/sangue , Senescência Celular , Lipofuscina/sangue , Naftalenos , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Coloração e Rotulagem , Adulto Jovem
7.
Int J Mol Sci ; 18(8)2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28829360

RESUMO

Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA. Despite the extensive research that has been made regarding nuclear genome instability, the importance of mitochondrial genome integrity has only recently begun to be elucidated. The specific architecture and repair mechanisms of mitochondrial DNA, as well as the dynamic behavior that mitochondria exert regarding fusion, fission, and autophagy participate in mitochondrial genome stability, and therefore, cell homeostasis.


Assuntos
Genoma Mitocondrial , Genômica , Homeostase , Mamíferos/genética , Animais , Dano ao DNA , Reparo do DNA , DNA Mitocondrial , Evolução Molecular , Instabilidade Genômica , Variação Estrutural do Genoma , Genômica/métodos , Humanos , Dinâmica Mitocondrial/genética , /genética
8.
Eur J Clin Invest ; 47(2): 129-136, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27931089

RESUMO

BACKGROUND: The pathophysiology of acute pericarditis remains largely unknown, and biomarkers are needed to identify patients susceptible to complications. As adipose tissue has a pivotal role in cardiovascular disease pathogenesis, we hypothesized that quantification of epicardial fat volume (EFV) provides prognostic information in patients with acute pericarditis. MATERIALS AND METHODS: Fifty (n = 50) patients with first diagnosis of acute pericarditis were enrolled in this study. Patients underwent a cardiac computerized tomography (CT) scan to quantify EFV on a dedicated workstation. Patients were followed up in hospital for atrial fibrillation (AF) development and up to 18 months for the composite clinical endpoint of development of constrictive, recurrent or incessant pericarditis or poor response to nonsteroidal anti-inflammatory drugs. RESULTS: Patients presenting with chest pain had lower EFV vs. patients without chest pain (167·2 ± 21·7 vs. 105·1 ± 11·1 cm3 , respectively, P < 0·01); EFV (but not body mass index) was strongly positively correlated with pericardial effusion size (r = 0·395, P = 0·007) and associated with in-hospital AF. At follow-up, patients that reached the composite clinical endpoint had lower EFV (P < 0·05). After adjustment for age, EFV was associated with lower odds ratio for the composite clinical endpoint point of poor response to NSAIDs or the development of constrictive, recurrent or incessant pericarditis during follow-up (per 20 cm3 increase in EFV: OR = 0·802 [0·656-0·981], P < 0·05). CONCLUSIONS: We report for the first time a significant association of EFV with the clinical features and the outcome of patients with acute pericarditis. Measurement of EFV by CT may have important prognostic implications in these patients.


Assuntos
Tecido Adiposo/patologia , Pericardite/patologia , Doença Aguda , Tecido Adiposo/diagnóstico por imagem , Assistência ao Convalescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Fibrilação Atrial/etiologia , Fibrilação Atrial/patologia , Dor no Peito/etiologia , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/patologia , Pericardite/diagnóstico por imagem , Pericardite/tratamento farmacológico , Recidiva , Resultado do Tratamento
9.
Biomed Res Int ; 2016: 3567275, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27847811

RESUMO

Purpose. To investigate the effect of EPO administration on postresuscitation renal function. Methods. Twenty-four female Landrace/Large-White piglets aged 10-15 weeks with average weight of 19 ± 2 kg were randomly assigned to 2 different groups of 12 subjects each. After the end of an 8-minute ventricular fibrillation, the control group (Group C) received saline as placebo, whereas the EPO group (Group E) received EPO 5000 U/kg. The animals were resuscitated according to the 2010 European Resuscitation Council Guidelines for Resuscitation. Results. Five animals (41.67%) from Group C and 11 animals (91.67%) from Group E achieved ROSC (p = 0.027). Eight animals (66.67%, 5 surviving and 3 nonsurviving) from Group C suffered severe kidney damage or AKI compared to animals from Group E, in which none of the swine had evidence of severe kidney damage or AKI (p = 0.001). There was a statistically significant difference in all tested biochemical markers between the two groups, as well as a positive correlation of creatinine with NGAL, L-FABP, and IL-18 (summed mean values' p = 0.049, 0.01, and 0.004, resp.). Conclusions. Administration of EPO protected swine from postresuscitation acute kidney injury.


Assuntos
Lesão Renal Aguda , Eritropoetina/farmacologia , Rim/fisiopatologia , Ressuscitação/efeitos adversos , Fibrilação Ventricular/terapia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/prevenção & controle , Animais , Feminino , Rim/patologia , Suínos
10.
Biomed Res Int ; 2016: 7261960, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27504455

RESUMO

Aim. To evaluate the effects of erythropoietin administration on the adrenal glands in a swine model of ventricular fibrillation and resuscitation. Methods. Ventricular fibrillation was induced via pacing wire forwarded into the right ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups: experimental group treated with bolus dose of erythropoietin (EPO) and control group which received normal saline. Cardiopulmonary resuscitation (CPR) was performed immediately after drug administration as per the 2010 European Resuscitation Council (ERC) guidelines for Advanced Life Support (ALS) until return of spontaneous circulation (ROSC) or death. Animals who achieved ROSC were monitored, mechanically ventilated, extubated, observed, and euthanized. At necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and routinely processed. Sections were stained with hematoxylin-eosin. Results. Oedema and apoptosis were the most frequent histological changes and were detected in all animals in the adrenal cortex and in the medulla. Mild and focal endothelial lesions were also detected. A marked interindividual variability in the degree of the intensity of apoptosis and oedema at cortical and medullary level was observed within groups. Comparing the two groups, higher levels of pathological changes were detected in the control group. No significant difference between the two groups was observed regarding the endothelial changes. Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has protective effects on the adrenal gland.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Eritropoetina/administração & dosagem , Fibrilação Ventricular/tratamento farmacológico , Córtex Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Reanimação Cardiopulmonar/métodos , Modelos Animais de Doenças , Feminino , Substâncias Protetoras/administração & dosagem , Suínos
11.
J Cardiovasc Med (Hagerstown) ; 17(4): 256-62, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26090915

RESUMO

AIMS: Accumulating evidence suggests idiopathic recurrent pericarditis as a disease of probable autoinflammatory origin, and thus anakinra could be of benefit. The goal of this systematic review was to assess the efficacy and safety of anakinra in this context. METHODS: Reports relevant to anakinra administration in patients with idiopathic recurrent pericarditis published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. RESULTS: Among 12 citations retrieved, nine reports (four case series and five case reports with 34 patients, 20 men, mean age 26.8 years) were assessed. The mean disease duration was 31 months and the number of recurrences 8.2. Anakinra was generally administered as a daily subcutaneous injection of 100 mg or as a mean dose of 1.1 mg/kg/d in weight-adjusted regimens. The mean full-dose duration was 9.2 months. C-reactive protein normalized within 7.1 days, and steroids were withdrawn within 62 days. Dose tapering was adopted in 64.7% of patients, leading to recurrence in 26% of cases. In a 28.3-month follow-up, eight out of 34 patients (23.5%) were disease free without treatment, after having received anakinra for 10.4 months overall. Anakinra was proved well tolerated, with mild local reaction being reported in 44% of patients. CONCLUSION: Anakinra is a highly effective, rapidly acting, well tolerated and steroid-sparing agent. Recurrences after drug discontinuation are a matter of concern. Randomized trials are required to confirm these findings and address the most effective treatment protocol.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pericardite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Medicina Baseada em Evidências/métodos , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Recidiva
12.
J Cardiovasc Med (Hagerstown) ; 17(4): 263-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26090917

RESUMO

AIMS: Refractory recurrent pericarditis is a major clinical challenge after colchicine failure, especially in corticosteroid-dependent patients. Human intravenous immunoglobulins (IVIGs) have been proposed as possible therapeutic options for these cases. The goal of this systematic review is to assess the efficacy and safety of IVIGs in this context. METHODS: Studies reporting the use of IVIG for the treatment of recurrent pericarditis and published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. RESULTS: Among the 18 citations retrieved, 17 reports (4 case series and 13 single case reports, with an overall population of 30 patients) were included. The mean disease duration was 14 months and the mean number of recurrences before IVIG was 3. Approximately 47% of patients had idiopathic recurrent pericarditis, 10% had an infective cause, and the remainder a systemic inflammatory disease. Nineteen out of the 30 patients (63.3%) were on corticosteroids at IVIG commencement. IVIGs were generally administered at a dose of 400-500 mg/kg/day for 5 consecutive days with repeated cycles according to the clinical response. Complications were uncommon (headache in ~3%) and not life-threatening. After a mean follow-up of approximately 33th months, recurrences occurred in 26.6% of cases after the first IVIG cycle, and 22 of the 30 patients (73.3%) were recurrence-free. Five patients (16.6%) were on corticosteroids at the end of the follow-up. CONCLUSIONS: IVIGs are rapidly acting, well tolerated, and efficacious steroid-sparing agents in refractory pericarditis.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Pericardite/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunossupressores/efeitos adversos , Recidiva
13.
Heart ; 101(18): 1463-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25926597

RESUMO

OBJECTIVE: Data on the incidence of new onset atrial fibrillation and flutter (AF/f) in patients with acute pericarditis are limited. We sought to determine the incidence and prognostic significance of AF/f in this setting. METHODS: Between January 2006 and June 2014, consecutive new cases of acute pericarditis were included in two urban referral centres for pericardial diseases. All new cases of AF/f defined as episodes lasting ≥30 s were recorded. Events considered during follow-up consisted of AF/f and pericarditis recurrence, cardiac tamponade, pericardial constriction and death. RESULTS: 822 consecutive new cases of acute pericarditis (mean age 53±15 years, 444 men) were analysed. AF/f was detected in 35 patients (4.3%, mean age 66.5±11.3 years, 18 men). Patients with AF/f were significantly older (p=0.017) and presented more frequently with pericardial effusion (p<0.001). Arrhythmias developed within 24 h of pericarditis onset in 91.4% of cases, lasted >24 h in 25.7% and spontaneously converted in 74.3% of patients. Underlying structural heart disease was present in 17% of AF/f cases. In a 30-month follow-up, patients with history of AF/f at the initial episode had a higher rate of arrhythmia occurrence (34.3% vs 0.9%, p<0.001), mostly (75%) within 3 months. No other differences were detected in additional clinical events including haemorrhagic complications in patients receiving oral anticoagulation. CONCLUSIONS: The occurrence of AF/f in acute pericarditis identifies a predisposed population to AF/f with a high recurrence risk (about 35%): in these patients, pericarditis may act as an arrhythmic trigger and oral anticoagulation should be seriously considered according to guidelines.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial , Pericardite , Doença Aguda , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pericardite/complicações , Pericardite/fisiopatologia , Prognóstico , Recidiva , Fatores de Risco , Fatores de Tempo
15.
Am J Emerg Med ; 32(8): 871-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24857249

RESUMO

BACKGROUND: In addition to its role in the endogenous control of erythropoiesis, recombinant human erythropoietin (rh-EPO) has been shown to exert tissue protective properties in various experimental models. However, its role in the cardiac arrest (CA) setting has not yet been adequately investigated. AIM: The aim of this study is to examine the effect of rh-EPO in a pig model of ventricular fibrillation (VF)-induced CA. METHODS: Ventricular fibrillation was electrically induced in 20 piglets and maintained untreated for 8 minutes before attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg, erythropoietin [EPO] group, n = 10) immediately before the initiation of chest compressions or to receive 0.9% Sodium chloride solution instead (control group, n = 10). RESULTS: Compared with the control, the EPO group had higher rates of return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48-hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary perfusion pressure during cardiopulmonary resuscitation were significantly higher in the EPO group compared with the control group. Erythropoietin-treated animals required fewer number of shocks in comparison with animals that received normal saline (P = .04). Furthermore, the neurologic alertness score was higher in the EPO group compared with that of the control group at 24 (P = .004) and 48 hours (P = .021). CONCLUSION: Administration of rh-EPO in a pig model of VF-induced CA just before reperfusion facilitates ROSC and improves survival rates as well as hemodynamic variables.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Eritropoetina/uso terapêutico , Parada Cardíaca/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Reanimação Cardiopulmonar , Modelos Animais de Doenças , Feminino , Parada Cardíaca/etiologia , Suínos , Resultado do Tratamento , Fibrilação Ventricular/complicações
17.
J Hypertens ; 32(2): 415-22, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24241057

RESUMO

OBJECTIVE: Little is known regarding the clinical course and prognosis of resistant hypertension (RHT). We evaluated predictors of persistent RHT and the associated cardiovascular risk. METHODS: We studied 1911 treated hypertensive patients (aged 59±11 years, 49% men) for a mean period of 3.9 years. At baseline, clinical data were collected and patients underwent echocardiographic measurements, routine blood testing and additional workup for exclusion of secondary causes of RHT (office-based uncontrolled hypertension under at least three drugs including a diuretic or controlled hypertension under four or more drugs). Endpoint of interest was the composite of coronary artery disease and stroke. MAIN RESULTS: Four groups were identified depending on presence or absence of RHT at baseline and follow-up: 1153 patients (60%) never having RHT, 189 (10%) with resolved RHT, 204 (11%) with incident RHT and 365 (19%) with persistent RHT. Two-thirds of the patients with RHT at baseline remained resistant at the end of the study. Independent variables associated with both incident and persistent RHT were diabetes mellitus, history of cardiovascular disease, hypertension duration, SBP, left ventricular hypertrophy and glomerular filtration rate. Persistent RHT compared with never-having RHT was associated with a 2.2-fold increased risk for cardiovascular morbidity (95% CI: 1.21-4.05, P = 0.01) after adjustment for risk factors. CONCLUSION: In treated hypertensive patients, among prospective RHT dynamic patterns, persistent RHT is frequent and independently associated with adverse cardiovascular prognosis.


Assuntos
Doenças Cardiovasculares/etiologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Idoso , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
18.
Inflammation ; 36(6): 1533-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23900683

RESUMO

Ιnterleukin-6 (IL-6) has been identified as an early biochemical marker of inflammation both in animal and human studies. With this study, we sought to examine the development of local inflammation of the glottic tissues in correlation with the duration of intubation in anesthetized pediatric patients. We measured IL-6 levels in the organic material isolated from the tip of the tube post-extubation in 48 children aged 7 months to 14 years old who were submitted to a total of 72 surgical procedures. A statistically significant positive correlation (ρ = 0.28, p = 0.05) was detected among duration of anesthesia and IL-6 concentration. The odds of having detectable IL-6 levels rose by 36.7 % for every 10 min of anesthetic duration (p = 0.045). In conclusion, the increase of IL-6 in relation to the duration of the intubation indicates an increased risk of inflammation.


Assuntos
Inflamação/imunologia , Interleucina-6/metabolismo , Intubação Intratraqueal/efeitos adversos , Adolescente , Anestesia/efeitos adversos , Biomarcadores/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Interleucina-6/imunologia , Masculino
19.
Anat Sci Educ ; 6(1): 48-55, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22851304

RESUMO

Despite the importance of body donation for medical education and the advancement of medical science, cadaveric donation remains suboptimal worldwide. The purpose of this study was to evaluate the willingness of body donation in Greece and determine the characteristics of donors. This cross-sectional questionnaire survey was conducted from January to June 2011. A specially designed questionnaire was distributed to 1,700 individuals who were randomly selected from five major Greek cities. It was found that higher educational levels (P = 0.002), annual family income below 30,000 Euros (P = 0.001), guaranteed employment status (P = 0.02), and the presence of comorbid conditions (P = 0.004) seemed to affect potential donors' willingness for cadaveric donation. Those with strong religious beliefs were found to be unwilling to donate their bodies to medical science. Interestingly, the majority of participants who believed that hospitalized patients are deceived or are used for harmful experiments were willing to become whole body donors (P = 0.043). In Greece, the rate of body donation to medical science remains low, and most Greek citizens are not willing to become body donors. Efforts to encourage discussions about whole body donation should be implemented in order to improve current low levels of donation.


Assuntos
Anatomia/educação , Cadáver , Educação Médica/estatística & dados numéricos , Doadores de Tecidos/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude , Estudos Transversais , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Religião , Inquéritos e Questionários , Adulto Jovem
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