Risk factors for human papilomavirus infection among women in Portugal: the CLEOPATRE Portugal Study

OBJECTIVE: Human papillomavirus (HPV) is responsible for a range of diseases, including cervical cancer. The primary objectives of the CLEOPATRE Portugal study were to estimate the overall and age-stratified prevalence of cervical HPV infection and to assess HPV prevalence and type-specific distribution by cytological results among women aged 18 to 64 years, who reside in mainland Portugal. MATERIALS AND METHODS: This cross-sectional population-based study recruited women aged 18 to 64 years, according to an age-stratified sampling strategy, who attended gynecology/obstetrics or sexually transmitted disease clinics across the 5 regional health administrations in mainland Portugal between 2008 and 2009. Liquid-based cytology samples were collected and analyzed centrally for HPV genotyping (clinical array HPV 2 assay) and cytology. Prevalence estimates were adjusted for age using 2007 Portuguese census data. RESULTS: A total of 2326 women were included in the study. The overall prevalence of HPV infection in the study was 19.4% (95% confidence interval, 17.8%-21.0%), with the highest prevalence in women aged 18 to 24 years. High-risk HPV types were detected in 76.5% of infections, of which 36.6% involved multiple types. The commonest high-risk type was HPV-16. At least 1 of the HPV types 6/11/16/18 was detected in 32.6% of infections. The HPV prevalence in normal cytology samples was 16.5%. There was a statistically significant association between high-risk infection and cytological abnormalities (P < 0.001). CONCLUSIONS: This is the first population-based study to quantify and describe cervical HPV infection in mainland Portugal. This study provides baseline data for future assessment of the impact of HPV vaccination programs

Bioenergetic dysfunction in Huntington's disease human cybrids

In this work we studied the mitochondrial-associated metabolic pathways in Huntington's disease (HD) versus control (CTR) cybrids, a cell model in which the contribution of mitochondrial defects from patients is isolated. HD cybrids exhibited an interesting increase in ATP levels, when compared to CTR cybrids. Concomitantly, we observed increased glycolytic rate in HD cybrids, as revealed by increased lactate/pyruvate ratio, which was reverted after inhibition of glycolysis. A decrease in glucose-6-phosphate dehydrogenase activity in HD cybrids further indicated decreased rate of the pentose-phosphate pathway. ATP levels of HD cybrids were significantly decreased under glycolysis inhibition, which was accompanied by a decrease in phosphocreatine. Nevertheless, pyruvate supplementation could not recover HD cybrids' ATP or phosphocreatine levels, suggesting a dysfunction in mitochondrial use of that substrate. Oligomycin also caused a decrease in ATP levels, suggesting a partial support of ATP generation by the mitochondria. Nevertheless, mitochondrial NADH/NAD(t) levels were decreased in HD cybrids, which was correlated with a decrease in pyruvate dehydrogenase activity and protein expression, suggesting decreased tricarboxylic acid cycle (TCA) input from glycolysis. Interestingly, the activity of alpha-ketoglutarate dehydrogenase, a critical enzyme complex that links the TCA to amino acid synthesis and degradation, was increased in HD cybrids. In accordance, mitochondrial levels of glutamate were increased and alanine was decreased, whereas aspartate and glutamine levels were unchanged in HD cybrids. Conversely, malate dehydrogenase activity from total cell extracts was unchanged in HD cybrids. Our results suggest that inherent dysfunction of mitochondria from HD patients affects cellular bioenergetics in an otherwise functional nuclear background

Increased CK5/CK8-Positive Intermediate Cells with Stromal Smooth Muscle Cell Atrophy in the Mice Lacking Prostate Epithelial Androgen Receptor

Results from tissue recombination experiments documented well that stromal androgen receptor (AR) plays essential roles in prostate development, but epithelial AR has little roles in prostate development. Using cell specific knockout AR strategy, we generated pes-ARKO mouse with knock out of AR only in the prostate epithelial cells and demonstrated that epithelial AR might also play important roles in the development of prostate gland. We found mice lacking the prostate epithelial AR have increased apoptosis in epithelial CK8-positive luminal cells and increased proliferation in epithelial CK5-positive basal cells. The consequences of these two contrasting results could then lead to the expansion of CK5/CK8-positive intermediate cells, accompanied by stromal atrophy and impaired ductal morphogenesis. Molecular mechanism dissection found AR target gene, TGF-β1, might play important roles in this epithelial AR-to-stromal morphogenesis modulation. Collectively, these results provided novel information relevant to epithelial AR functions in epithelial-stromal interactions during the development of normal prostate, and suggested AR could also function as suppressor in selective cells within prostate

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

Genetic variation in autophagy-related genes influences the risk and phenotype of Buruli ulcer

Introduction Buruli ulcer (BU) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans. Clinically, presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms. Among them, autophagy has been demonstrated as a cellular process of critical importance. Since microtubules and dynein are affected by mycolactone, the critical pathogenic exotoxin produced by M. ulcerans, cytoskeleton-related changes might potentially impair the autophagic process and impact the risk and progression of infection. Objective Genetic variants in the autophagy-related genes NOD2, PARK2 and ATG16L1 has been associated with susceptibility to mycobacterial diseases. Here, we investigated their association with BU risk, its severe phenotypes and its progression to an ulcerative form. Methods Genetic variants were genotyped using KASPar chemistry in 208 BU patients (70.2% with an ulcerative form and 28% in severe WHO category 3 phenotype) and 300 healthy endemic controls. Results The rs1333955 SNP in PARK2 was significantly associated with increased susceptibility to BU [odds ratio (OR), 1.43; P = 0.05]. In addition, both the rs9302752 and rs2066842 SNPs in NOD2 gee significantly increased the predisposition of patients to develop category 3 (OR, 2.23; P = 0.02; and OR 12.7; P = 0.03, respectively, whereas the rs2241880 SNP in ATG16L1 was found to significantly protect patients from presenting the ulcer phenotype (OR, 0.35; P = 0.02). Conclusion Our findings indicate that specific genetic variants in autophagy-related genes influence susceptibility to the development of BU and its progression to severe phenotypes.The research leading to these results received funding from the Health Services of the Fundação Calouste Gulbenkian under the grant Proc.N°94776 LJ; from the Fundação para a Ciência e Tecnologia (FCT), cofunded by Programa Operacional Regional do Norte (ON.2—O Novo 267 Norte); from the Quadro de Referência Estratégico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and from the Projeto Estratégico – LA 26 – 2013–2014 (PEst-C/SAU/LA0026/2013). JFM received an individual QREN fellowship (UMINHO/BPD/14/2014); CCu and AGF received an individual FCT fellowship (SFRH/BPD/96176/2013 and SFRH/BPD/68547/2010, respectively); and AC received an FCT contract (IF/00735/2014). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period

From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio

A polymorphic microsatellite from the Squalius alburnoides complex (Osteichthyes, Cyprinidae) cloned by serendipity can be useful in genetic analysis of polyploids

A new microsatellite locus (SAS1) for Squalius alburnoides was obtained through cloning by serendipity. The possible usefulness of this new species-specific microsatellite in genetic studies of this hybrid-species complex, was explored. The polymorphism exhibited by SAS1 microsatellite is an important addition to the set of microsatellites previously used in genetic studies in S. alburnoides complex, that mostly relied in markers described for other species. Moreover, the SAS1 microsatellite could be used to identify the parental genomes of the complex, complementing other methods recently described for the same purpose.

Is the functional interaction between adenosine A2A receptors and metabotropic glutamate 5 receptors a general mechanism in the brain? Differences and similarities between the striatum and the hippocampus

The aim of the present paper was to examine, in a comparative way, the occurrence and the mechanisms of the interactions between adenosine A2A receptors (A2ARs) and metabotropic glutamate 5 receptors (mGlu5Rs) in the hippocampus and the striatum. In rat hippocampal and corticostriatal slices, combined ineffective doses of the mGlu5R agonist 2-chloro-5-hydroxyphenylglycine (CHPG) and the A2AR agonist CGS 21680 synergistically reduced the slope of excitatory postsynaptic field potentials (fEPSPs) recorded in CA1 and the amplitude of field potentials (FPs) recorded in the dorsomedial striatum. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway appeared to be involved in the effects of CGS 21680 in corticostriatal but not in hippocampal slices. In both areas, a postsynaptic locus of interaction appeared more likely. N-methyl-D-aspartate (NMDA) reduced the fEPSP slope and FP amplitude in hippocampal and corticostriatal slices, respectively. Such an effect was significantly potentiated by CHPG in both areas. Interestingly, the A2AR antagonist ZM 241385 significantly reduced the NMDA-potentiating effect of CHPG. In primary cultures of rat hippocampal and striatal neurons (ED 17, DIV 14), CHPG significantly potentiated NMDA-induced lactate dehydrogenase (LDH) release. Again, such an effect was prevented by ZM 241385. Our results show that A2A and mGlu5 receptors functionally interact both in the hippocampus and in the striatum, even though different mechanisms seem to be involved in the two areas. The ability of A2ARs to control mGlu5R-dependent effects may thus be a general feature of A2ARs in different brain regions (irrespective of their density) and may represent an additional target for the development of therapeutic strategies against neurological disorders