CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro

The direct relationship between the aging process and the incidence and prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) implies that certain risk factors associated with the development of both diseases increase with the aging process. In particular, both diseases share an overly proliferative phenotype, suggesting that mechanisms that normally act to suppress cellular proliferation are disrupted or rendered dysfunctional as a consequence of the aging process. We propose that one such mechanism involves changes in the prostate microenvironment, which ‘evolves’ during the aging process and disrupts paracrine interactions between epithelial and associated stromal fibroblasts. We show that stromal fibroblasts isolated from the prostates of men 63–81 years of age at the time of surgery express and secrete higher levels of the CXCL12 chemokine compared with those isolated from younger men, and stimulate CXCR4-mediated signaling pathways that induce cellular proliferation. These studies represent an important first step towards a mechanistic elucidation of the role of aging in the etiology of benign and malignant prostatic diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73356/1/j.1474-9726.2005.00173.x.pd

Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium

The present study demonstrates that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in an in vitro coculture system. Human prostatic carcinoma-associated fibroblasts grown with initiated human prostatic epithelial cells dramatically stimulated growth and altered histology of the epithelial population. This effect was not detected when normal prostatic fibroblasts were grown with the initiated epithelial cells under the same experimental conditions. In contrast, carcinoma-associated fibroblasts did not affect growth of normal human prostatic epithelial cells under identical conditions. From these data, we conclude that in this human prostate cancer model, carcinoma-associated fibroblasts stimulate progression of tumorigenesis. Thus, carcinoma-associated fibroblasts can direct tumor progression of an initiated prostate epithelial cell

Infective Endocarditis Complicated by Large Aortic Pseudoaneurysm after Cardiac Surgery

A 66-year-old female with Streptococcus viridans aortic and tricuspid infective endocarditis develops, during the course of antibiotic therapy, rupture of a right coronary sinus of Valsalva aneurysm to the right ventricle. An urgent cardiac surgery is preformed with implantation of a mechanical aortic prosthesis and a right coronary sinus plasty. Six months later a huge aortic pseudoaneurysm is diagnosed and she is submitted to a second uneventful surgery. A review is done for the significant features with discussion of diagnosis and therapy

Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis

PURPOSE: To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumor growth and in its prevention. RESULTS: The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (V) CEL reduced MDA formation in serum (p < 0.001) and liver (p < 0.05) and also showed a trend to reduction in kidney. METHODS: Drug treatments were performed during the first 8 w, followed by 12 w for tumor expression/prevention, in the following groups: control-vehicle; carcinogen-0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL)-10 mg/kg/day and preventive CEL + BBN. The bladders were analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status. CONCLUSIONS: Celecoxib has demonstrated an outstanding inhibitory effect on bladder cancer chemoprevention, which might be due to its expected anti-inflammatory actions, as well as by anti-proliferatory and antioxidant actions. This data supports a pivotal role of cancer chemoprevention strategies based on COX-2 inhibition

Evaluation of MCM-2 Expression in TMA Cervical Specimens

Background:Minichromosome maintenance proteins (MCM) are highly expressed in actively replicating cells. The need for biological markers for cervical carcinoma and its precursor lesions is emerging. Our main aim was to determine the immunohistochemical expression of MCM-2 in HIV-positive and -negative dysplastic cervical specimens. Methods:Immunohistochemical analysis of MCM-2 was performed in a total of 352 cervical TMA specimens of normal control, low-grade CIN, high-grade CIN and invasive tumor. 38 specimens were from HIV-positive women. A receiver operating characteristic (ROC) curve was constructed to determine the best cutoff to diagnose high-grade CIN and invasive cervical cancer. Results:In the progression from normal epithelium to high-grade CIN and invasive tumor we found significant differences in the MCM-2 expression (p,0.05). Based on the ROC curve of 80% with an area under the curve (AUC) of 0.78, expression of MCM-2 to diagnose high-grade CIN and invasive tumor resulted in sensitivity of 81%, specificity of 66%, a positive predictive value (PPV) of 86% and a negative predictive value (NPV) of 57%. HIV-positive cervices revealed a decreasing expression of MCM-2 in both LGCIN and HGCIN compared with HIV-negative specimens (p,0.0001). Conclusions:The present study suggests that immunohistochemical MCM-2 may not be a promising biomarker for diagnosing high-grade CIN and invasive cance

Hundreds of genetic barcodes of the species-rich hydroid superfamily Plumularioidea (Cnidaria, Medusozoa) provide a guide toward more reliable taxonomy

Marine hydroids are important benthic components of shallow and deep waters worldwide, but their taxonomy is controversial because diagnostic morphological characters to categorize taxa are limited. Their genetic relationships are also little investigated. We tested taxonomic hypotheses within the highly speciose superfamily Plumularioidea by integrating a classical morphological approach with DNA barcoding of the 16S and COI mitochondrial markers for 659 and 196 specimens of Plumularioidea, respectively. Adding Genbank sequences, we inferred systematic relationships among 1,114 plumularioids, corresponding to 123 nominal species and 17 novel morphospecies in five families of Plumularioidea. We found considerable inconsistencies in the systematics of nominal families, genera and species. The families Kirchenpaueriidae and Plumulariidae were polyphyletic and the Halopterididae paraphyletic. Most genera of Plumularioidea are not monophyletic. Species diversity is considerably underestimated. Within our study, at least 10% of the morphologically-distinctive morphospecies are undescribed, and about 40% of the overall species richness is represented by cryptic species. Convergent evolution and morphological plasticity therefore blur systematic relationships. Additionally, cryptic taxa occur frequently in sympatry or parapatry, complicating correspondence with type material of described species. Sometimes conspecificity of different morphotypes was found. The taxonomy of hydroids requires continued comprehensive revision.This work relied on several hydrozoan samples collected from various sites, with the aid of many people. Supplementary Table S1 refers many of the people involved in the collection and/or preservation of the samples. C.J.M. acknowledges his great buddy-divers Jaime N.-Ruiz (CIMAR, Univ. Costa Rica), Axel Calderon, Nathaniel Chu, Eleni Petrou (STRI, Smiths. Inst.), Hanae Spathias, Karen Koltes (at the Belize station, Smith. Inst.), Freya Sommer (Hopkins Marine Station), Remilson Ferreira ('Costa Norte', Sao Tome), Frederico Cardigos (DOP, Univ. Azores) and others that assisted the dives. C.J.M. also acknowledges Rita Castillo (CIMAR, Univ. Costa Rica), Plinio Gondola, Ligia Calderon, Laura Geyer, Maria Castillo (STRI, Smiths. Inst.), Gregory Ruiz (SERC, Smiths. Inst.), Paul Greenhall, William Keel (MSC, Smith. Inst.), Manuel Enes, Valentina Matos (IMAR/DOP, Univ. Azores), Filipe Porteiro, Joao Goncalves (OKEANOS/IMAR, Univ. Azores), Marina Cunha, Ascensao Ravara (CESAM, Univ. Aveiro), Shirley Pomponi (Harbor Branch, Florida Atlantic Univ.), Estrela Matilde (Fundacao Principe Trust), Monica Albuquerque, Ines Tojeira (EMEPC), Diana Carvalho (Nat. Mus. Nat. Hist., Lisbon) and many others colleagues that facilitated the morphologic classifications and deposition of the samples. Peter Schuchert (Mus. d'Hist. Nat. Geneve) kindly provided some DNA extractes. Todd Kincaid and his team of GUE divers (Project Baseline - Azores) collected valuable samples from unusual depths. Joana Boavida (CIIMAR, Univ. Algarve) facilitated some samples of the 'DeepReefs' project. Jim Drewery (Marine Scotland Science Inst.) also provided few samples. Dale Calder (Royal Ontario Museum) provided some bibliography to C.J.M. and discussed/resolved some dubios taxonomic classifications. Colleagues at the L.A.B. (NMNH, Smith. Inst.) were very supportive. The APC fees for open access publication were supported by a program of the Regional Government of the Azores ("Apoio ao funcionamento e gestao dos centros de I&D regionais: 2018 - DRCT-medida 1

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

Validação brasileira do Instrumento de Qualidade de Vida/espiritualidade, religião e crenças pessoais

OBJETIVO: Analisar propriedades psicométricas do Instrumento de Qualidade de Vida da Organização Mundial da Saúde - Módulo Espiritualidade, Religiosidade e Crenças Pessoais (WHOQOL-SRPB). MÉTODOS: O WHOQOL-SRPB, a Escala de Coping Religioso/Espiritual Abreviada (CRE-Breve), o WHOQOL-Breve e o BDI foram consecutivamente aplicados em amostra de conveniência de 404 pacientes e funcionários de hospital universitário e funcionários de universidade, em Porto Alegre, RS, entre 2006 e 2009. A amostra foi estratificada por sexo, idade, estado de saúde e religião/crença. O reteste dos dois primeiros instrumentos foi realizado com 54 participantes. Análises fatoriais exploratórias do WHOQOL-SRPB pelo método dos componentes principais foram realizadas sem delimitar o número de fatores, solicitando oito fatores e em conjunto com os itens do WHOQOL-Breve. RESULTADOS: O WHOQOL-SRPB em português brasileiro (Domínio SRPB-Geral) apresentou validade de construto, com validade discriminativa entre crentes de não-crentes (t = 7,40; p = 0,0001); validade relacionada ao critério concorrente, discriminando deprimidos de não-deprimidos (t = 5,03; p = 0,0001); validade convergente com o WHOQOL-Breve (com físico r = 0,18; psicológico r = 0,46; social r = 0,35; ambiental r = 0,29; global r = 0,23; p = 0,0001) e com o Domínio SRPB do WHOQOL-100 (r = 0,78; p = 0,0001); e validade convergente/discriminante com a Escala CRE-Breve (com CREpositivo r = 0,64; p = 0,0001/CREnegativo r = -0,03; p = 0,554). Observou-se excelente fidedignidade teste-reteste (t = 0,74; p = 0,463) e consistência interna (&#945; = 0,96; correlação intrafatorial 0,87 > r > 0,60, p = 0,0001). As análises fatoriais exploratórias realizadas corroboraram a estrutura de oito fatores do estudo multicêntrico do WHOQOL-SRPB. CONCLUSÕES: O WHOQOL-SRPB em português brasileiro apresentou boas qualidades psicométricas e uso válido e fidedigno para uso no Brasil. Sugerem-se novos estudos com populações específicas, como diferentes religiões, grupos culturais e/ou doenças.OBJETIVO: Analizar propiedades psicométricas del Instrumento de Calidad de Vida de la OMS - Módulo Espiritualidad, Religiosidad y Creencias Personales (WHOQOL-SRPB). MÉTODOS: El WHOQOL-SRPB, la Escala de Coping Religioso/Espiritual Abreviada (CRE-Breve), el WHOQOL-Breve y el BDI fueron consecutivamente aplicados en muestra de conveniencia de 404 pacientes y funcionarios de hospital universitario y funcionarios de universidad, en Porto Alegre, Sur de Brasil, entre 2006 y 2009. La muestra fue estratificada por sexo, edad, estado de salud y religión/creencia. La reevaluación de los dos primeros instrumentos fue realizada por 54 participantes. Análisis factoriales exploratorias del WHOQOL-SRPB por el método de los componentes principales fueron realizadas, sin delimitar el número de factores, solicitando ocho factores y en conjunto con los itens del WHOQOL-Breve. RESULTADOS: El WHOQOL-SRPB en portugués-brasileño (Dominio SRPB-General) presentó validez de constructo, con validez discriminativa entre creyentes de no creyentes (t=7,40; p=0,0001); validez relacionada con el criterio concurrente, discriminando deprimidos de no deprimidos (t=5,03; p=0,0001); validez convergente con el WHOQOL-Breve (con físico r=0,18; psicológico r=0,46; social r=0,35; ambiental r=0,29; global r=0,23; p=0,0001) y con el Dominio-SRPB del WHOQOL-100 (r=0,78; p=0,0001); y validez convergente/discriminante con la Escala CRE-Breve (con CRE positivo r=0,64; p=0,0001/CRE negativo r=-0,03; p=0,554). Se observó excelente fidedignidad test-retest (t=0,74; p=0,463) y consistencia interna (&#945;=0,96; correlación intrafactorial 0,87>r>0,60, p=0,0001). Los análisis factoriales exploratorios realizados corroboran la estructura de ocho factores de estudio multicéntrico del WHOQOL-SRPB. CONCLUSIONES: El WHOQOL-SRPB en portugués-brasileño presentó buenas cualidades psicométricas, siendo válido y fidedigno para uso en Brasil. Se sugieren nuevos estudios con poblaciones específicas, como diferentes religiones, grupos culturales y/o enfermedades.OBJECTIVE: To analyze the psychometric properties of the World Health Organization's Quality of Life Instrument - Spirituality, Religion and Personal Beliefs module (WHOQOL-SRPB). METHODS: The WHOQOL-SRPB, the Brief Spiritual/Religious Coping Scale (Brief-SRCOPE Scale), the WHOQOL-BREF and the Beck Depression Inventory (BDI) were consecutively applied in a convenience sample of 404 patients and workers of a university hospital and workers of a university, in the city of Porto Alegre, Southern Brazil, between 2006 and 2009. The sample was stratified by sex, age, health status and religion/belief. The retest of the two first instruments was conducted with 54 participants. Exploratory factorial analyses of the WHOQOL-SRPB with the method of main components were performed, without limiting the number of factors, and requiring eight factors concomitantly with the WHOQOL-BREF items. RESULTS: The Brazilian Portuguese version of the WHOQOL-SRPB (General SRPB-Domain) showed construct validity, with a discriminatory validity between believers and non-believers (t = 7.40; p = 0.0001); concurrent criterion-related validity, distinguishing depressed individuals from non-depressed ones (t = 5.03; p = 0.0001); convergent validity with the WHOQOL-BREF (physical r = 0.18; psychological r = 0.46; social r = 0.35; environmental r = 0.29; global r = 0.23; p = 0.0001) and with the SRPB-Domain of the WHOQOL-100 (r = 0.78; p = 0.0001); and convergent/discriminatory validity with the brief SRCOPE Scale (with positive SRCOPE r = 0.64; p = 0.0001/negative SRCOPE r = -0.03; p = 0.554). Excellent test-retest reliability (t = 0.74; p = 0.463) and internal consistency (&#945; = 0.96; intrafactorial correlation 0.87 > r > 0.60; p = 0.0001) were observed. The exploratory factorial analyses performed corroborated the eight-factor structure of the WHOQOL-SRPB multicenter study. CONCLUSIONS: The Brazilian Portuguese version of the WHOQOL-SRPB showed good psychometric qualities and use valid and reliable in Brazil. It is suggested that new studies be conducted with specific populations, such as different religions, cultural groups and/or diseases

Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy

Chronic Chagas disease cardiomyopathy (CCC) affects millions in endemic areas and is presenting in growing numbers in the USA and European countries due to migration currents. Clinical progression, length of survival and overall prognosis are significantly worse in CCC patients when compared to patients with dilated cardiomyopathy of non-inflammatory etiology. Impairment of energy metabolism seems to play a role in heart failure due to cardiomyopathies. Herein, we have analyzed energy metabolism enzymes in myocardium samples of CCC patients comparing to other non-inflammatory cardiomyopathies. We found that myocardial tissue from CCC patients displays a significant reduction of both myocardial protein levels of ATP synthase alpha and creatine kinase enzyme activity, in comparison to control heart samples, as well as idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. Our results suggest that CCC myocardium displays a selective energetic deficit, which may play a role in the reduced heart function observed in such patients