Qualidade de vida relacionada à saúde em espanholas com osteoporose

OBJECTIVE: To analyze the health-related quality of life in patients with osteoporosis and to compare it with the overall population. METHODS: A cross-sectional descriptive study was carried out with 60 female patients of the rheumatology service at a university hospital, in Spain, from April to October 2003. The Short Form-36 (SF-36) questionnaire was applied in order to obtain demographic data, clinical characteristics and data about lifestyles related to health. Patients were classified in age groups. The statistics tests performed were Chi-square, general linear model, Student's t-test. RESULTS: The interviewees' average age was 65.57 years old (SD: ±9.7 years), and average time interval for diagnosis was 3.4±2.84 years. The best scores were in social functioning (89), emotional aspects (72.2), mental health (63), and vitality (53.7). The lowest scores were in general health (45.1), physical capacity (47.7), pain (52.3) and physical aspects (59.9). The patients' average scores were lower than the general Spanish population's scores in the following dimensions: functional capacity, physical aspects, pain and overall health status. The greatest differences between the average SF-36 scores for patients and for the overall Spanish population were in the age group ranging from 55 to 64 years old. Scores were lower or similar to the general Spanish population in all other dimensions of the questionnaire. No significant associations were found between the dimensions of the SF-36 contemplated in this study and the clinical, demographic and lifestyle data. CONCLUSIONS: The patients presented bad quality of life, particularly with respect to those dimensions that are most relevant with respect to osteoporosis, when compared with the overall Spanish population. The physical dimensions were the ones most affected.OBJETIVO: Analisar a qualidade de vida relacionada à saúde de pacientes com osteoporose e compará-la com a população geral. MÉTODOS: Foi realizado um estudo descritivo transversal com 60 pacientes do sexo feminino no serviço de reumatologia de um hospital universitário na Espanha, de abril a outubro de 2003. Foi aplicado o questionário Short Form-36, abordando dados demográficos, características clínicas e dados sobre estilos de vida relacionados à saúde. As pacientes foram classificadas em grupos etários. Foram utilizados os seguintes testes estatísticos: qui-quadrado, modelo linear geral, t de Student. RESULTADOS: As entrevistadas tinham idade média de 65,57 (DP: ±9,7 anos), e tempo de diagnóstico médio de 3,4±2,84 anos. As melhores pontuações foram obtidas nas dimensões aspectos sociais (89), aspectos emocionais (72,2) e saúde mental (63). As mais baixas foram em estado geral de saúde (45,1), capacidade funcional (47,7), dor (52,3) e aspectos físicos (59,9). As pontuações médias dos pacientes resultaram inferiores às pontuações conhecidas da população geral espanhola nas dimensões capacidade funcional, aspectos físicos, dor e estado geral de saúde. As máximas diferenças entre as pontuações médias do SF-36 dos pacientes e os valores populacionais espanhóis correspondem ao grupo de idade de 55 a 64 anos. Nas demais dimensões do SF-36, as pontuações foram inferiores ou similares aos valores populacionais espanhóis. Não se encontraram associações significativas entre as dimensões do SF-36 estudadas e os dados clínicos, demográficos e de estilos de vida analisados. CONCLUSÕES: Os pacientes apresentaram baixa qualidade de vida, sobretudo nas dimensões mais relevantes da enfermidade, quando comparada com valores da população espanhola em geral. As áreas físicas foram as mais afetadas

Definition of a temporal distribution index for high temporal resolution precipitation data over Peninsular Spain and the Balearic Islands: the fractal dimension; and its synoptic implications

Precipitation on the Spanish mainland and in the Balearic archipelago exhibits a high degree of spatial and temporal variability, regardless of the temporal resolution of the data considered. The fractal dimension indicates the property of self-similarity, and in the case of this study, wherein it is applied to the temporal behaviour of rainfall at a fine (10-min) resolution from a total of 48 observatories, it provides insights into its more or less convective nature. The methodology of Jenkinson & Collison which automatically classifies synoptic situations at the surface, as well as an adaptation of this methodology at 500 hPa, was applied in order to gain insights into the synoptic implications of extreme values of the fractal dimension. The highest fractal dimension values in the study area were observed in places with precipitation that has a more random behaviour over time with generally high totals. Four different regions in which the atmospheric mechanisms giving rise to precipitation at the surface differ from the corresponding above-ground mechanisms have been identified in the study area based on the fractal dimension. In the north of the Iberian Peninsula, high fractal dimension values are linked to a lower frequency of anticyclonic situations, whereas the opposite occurs in the central region. In the Mediterranean, higher fractal dimension values are associated with a higher frequency of the anticyclonic type and a lower frequency of the advective type from the east. In the south, lower fractal dimension values indicate higher frequency with respect to the anticyclonic type from the east and lower frequency with respect to the cyclonic type

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

G6PD deficiency in Latin America: systematic review on prevalence and variants

Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer

Breast cancer polygenic risk score and contralateral breast cancer risk

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18–1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02–1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547–0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies

Association analysis identifies 65 new breast cancer risk loci

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project, funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie, de la Science et de l’Innovation du Québec’ through Genome Québec, and the Quebec Breast Cancer Foundation; the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH Grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combining of the GWAS data was supported in part by The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative)

Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4