National Differences in the Prevalence of Depressive Symptoms in Mania: a Naturalistic Study Using the Dsm-5 'with Mixed Features' Specifier M.I.N.I. Module

Introduction In bipolar I disorder (BD1), manic episodes with depressive symptoms are generally more severe than pure manic episodes, but are not easily identified. The DSM-5 'With Mixed Features' specifier, and accompanying patient-rated Mini-International Neuropsychiatric Interview (M.I.N.I.) module, were designed to aid diagnosis. Objectives To examine patients with BD1 who have mania with depressive symptoms, across countries. Aims To improve the identification of depressive symptoms during a BD1 manic episode. Methods This naturalistic study surveyed psychiatrists and their patients with BD1 (manic episode within previous 3 months), in Germany, Italy, Spain, UK, Turkey, Australia, Brazil and Canada. Psychiatrists provided information on depressive symptoms (DSM-5 'With Mixed Features' specifier plus patient-rated M.I.N.I. module); anxiety, irritability, and agitation; suicide attempts; and treatment response. Results Of 1,035 bipolar patients, 34% had mania 'With Mixed Features'(≥05;3 depressive symptoms), and displayed more severe symptoms, and higher rates of attempted suicide than patients without mixed features. Across countries, severe anxiety occurred in 3.5–19.5% of patients; severe irritability in 4.3–17.0%; and severe agitation in 4.3–19.6%. The proportion of patients experiencing 'prominent dysphoria or depressed mood' was highest in Italy (64.2%). Recurrent suicidal ideation ranged from 8.0% (Germany) to 25.7% (Spain); lifetime rate of attempted suicide was highest in Canada (64.7%). Between-country differences were also reflected in the M.I.N.I. module outcomes. Conclusion Patients with BD1 'With Mixed Features', suffer from a greater burden of disease than patients with pure mania, and there is variation between countries – as detected by physician and patient evaluations

Priming nonlinear searches for pathway identification

BACKGROUND: Dense time series of metabolite concentrations or of the expression patterns of proteins may be available in the near future as a result of the rapid development of novel, high-throughput experimental techniques. Such time series implicitly contain valuable information about the connectivity and regulatory structure of the underlying metabolic or proteomic networks. The extraction of this information is a challenging task because it usually requires nonlinear estimation methods that involve iterative search algorithms. Priming these algorithms with high-quality initial guesses can greatly accelerate the search process. In this article, we propose to obtain such guesses by preprocessing the temporal profile data and fitting them preliminarily by multivariate linear regression. RESULTS: The results of a small-scale analysis indicate that the regression coefficients reflect the connectivity of the network quite well. Using the mathematical modeling framework of Biochemical Systems Theory (BST), we also show that the regression coefficients may be translated into constraints on the parameter values of the nonlinear BST model, thereby reducing the parameter search space considerably. CONCLUSION: The proposed method provides a good approach for obtaining a preliminary network structure from dense time series. This will be more valuable as the systems become larger, because preprocessing and effective priming can significantly limit the search space of parameters defining the network connectivity, thereby facilitating the nonlinear estimation task

Cyclin D1 expression in colorectal cancer is a favorable prognostic factor in men but not in women in a prospective, population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Although colorectal cancer (CRC) is generally not considered to be a hormone-dependent malignancy, several sex-related differences in incidence, molecular characteristics and survival have been reported. Epidemiological studies have consistently shown that increased exposure to female sex hormones is associated with a lower risk of CRC in women, and cyclin D1, an important downstream effector in estrogen-mediated signaling, is commonly activated in CRC. In this study, we analyzed the prognostic significance of cyclin D1 expression in CRC, with particular reference to sex-related differences, in tumors from a large, prospective, population-based cohort.</p> <p>Methods</p> <p>Using tissue microarrays and immunohistochemistry, the fraction and intensity of cyclin D1 expression was evaluated in 527 incident CRC cases from the Malmö Diet and Cancer Study. The χ²and Spearman's rho (ρ) tests were used for comparison of cyclin D1 expression and relevant clinicopathological characteristics. Kaplan-Meier analysis and Cox proportional hazards modeling were used to assess the effect of cyclin D1 expression on cancer-specific survival (CSS) in univariate and multivariate analysis, adjusted for established prognostic factors.</p> <p>Results</p> <p>Cyclin D1 intensity was significantly lower in male compared with female CRC (<it>P </it>= 0.018). In the full cohort, cyclin D1 expression was associated with a significantly prolonged CSS (hazard ratio (HR) = 0.69; 95% CI 0.49 to 0.96, <it>P </it>= 0.026) but subgroup analysis according to gender revealed a strongly accentuated prognostic effect of cyclin D1 in male CRC (HR = 0.48; 95% CI 0.31 to 0.74, <it>P </it>< 0.001), which was in contrast to female CRC, where cyclin D1 was not prognostic (HR = 1.05; 95% CI 0.62 to 1.78, <it>P </it>= 0.864) (<it>P</it>_interaction= 0.024). The prognostic value of cyclin D1 was not retained in multivariate analysis, either in the full cohort or in male CRC.</p> <p>Conclusions</p> <p>Cyclin D1 expression is strongly associated with prolonged survival in male CRC. These findings not only support an important role for cyclin D1 in colorectal carcinogenesis, but also add further weight to the accumulating evidence that CRC is indeed a hormone-dependent malignancy, for which prognostic and treatment-predictive molecular biomarkers should be evaluated differently in women and men.</p

Influence of anthropometric factors on tumour biological characteristics of colorectal cancer in men and women : a cohort study

BACKGROUND: Obesity is a well established risk factor of colorectal cancer (CRC), but how body size influences risk of colorectal cancer defined by key molecular alterations remains unclear. In this study, we investigated the relationship between height, weight, body mass index (BMI), waist- and hip circumference, waist-hip ratio (WHR) and risk of CRC according to expression of beta-catenin, cyclin D1, p53 and microsatellite instability status of the tumours in men and women, respectively.METHODS: Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status was assessed in tissue microarrays with tumours from 584 cases of incident CRC in the Malmö Diet and Cancer Study. Six anthropometric factors: height, weight, BMI, waist- and hip circumference, and WHR were categorized by quartiles of baseline measurements and relative risks of CRC according to expression of beta-catenin, cyclin D1, p53 and MSI status were calculated using multivariate Cox regression models.RESULTS: High height was associated with risk of cyclin D1 positive, and p53 negative CRC in women but not with any investigative molecular subsets of CRC in men. High weight was associated with beta-catenin positive, cyclin D1 positive, p53 negative and microsatellite stable (MSS) tumours in women, and with beta-catenin negative and p53 positive tumours in men. Increased hip circumference was associated with beta-catenin positive, p53 negative and MSS tumours in women and with beta-catenin negative, cyclin D1 positive, p53 positive and MSS tumours in men. In women, waist circumference and WHR were not associated with any molecular subsets of CRC. In men, both high WHR and high waist circumference were associated with beta-catenin positive, cyclin D1 positive and p53 positive tumours. WHR was also associated with p53 negative CRC, and waist circumference with MSS tumours. High BMI was associated with increased risk of beta-catenin positive and MSS CRC in women, and with beta-catenin positive, cyclin D1 positive and p53 positive tumours in men.CONCLUSIONS: Findings from this large prospective cohort study indicate sex-related differences in the relationship between obesity and CRC risk according to key molecular characteristics, and provide further support of an influence of lifestyle factors on different molecular pathways of colorectal carcinogenesis

Prof. Dr. med. Bernhard Riedel (1846-1916) und seine Leistungen auf dem Gebiet der Abdominalchirurgie: eine Analyse seiner Jenaer Operationstagebücher im Zeitraum von 1888 bis 1910

Mit der Entdeckung der Narkose im Jahre 1846 begann in der Medizin eine neue Ära, der ein enormer Aufschwung, insbesondere in der Chirurgie, in der zweiten Hälfte des 19. Jahrhunderts folgte. Im gleichen Jahr dieses Wendepunktes wurde auch Bernhard Carl Ludwig Moritz Riedel am 18. September in Laage in Mecklenburg geboren. In der vorliegenden Dissertation steht als Beitrag zur Geschichte der Medizinischen Fakultät Jenas Bernhard Riedels Leben und Wirken im Mittelpunkt. Dabei wird insbesondere die Zeit seines Chirurgischen Ordinariats an der Universität Jena von 1888 bis 1910 einschließlich seiner Lehrtätigkeit und Schüler wie Heinrich Haeckel (geb. 1859) oder Wilhelm Röpke (1873-1945) thematisiert. Als Zeugnisse seines Schaffens in Jena sind zwölf Bände seiner Operationstagebücher erhalten geblieben, die der Friedrich-Schiller-Universität Jena durch Riedels Nachkommen im April 1998 zur wissenschaftlichen Auswertung übergeben wurden. Die Analyse dieser Tagebücher bildet neben der Biografie Riedels einen weiteren Schwerpunkt der Arbeit. Abschließend wurden daraus Fallbeispiele ausgewählt, zu denen Bezüge aus Riedels wissenschaftlichen Schriften hergestellt werden. Bei der Auseinandersetzung mit dem Leben und Schaffen von Bernhard Riedel lernt man ihn als vielseitigen und ehrgeizigen Chirurgen kennen, durch dessen Ordinariat die Alma mater Jenensis über die thüringischen Grenzen hinaus Anerkennung erlangen konnte

A multivariate prediction model for microarray cross-hybridization

BACKGROUND: Expression microarray analysis is one of the most popular molecular diagnostic techniques in the post-genomic era. However, this technique faces the fundamental problem of potential cross-hybridization. This is a pervasive problem for both oligonucleotide and cDNA microarrays; it is considered particularly problematic for the latter. No comprehensive multivariate predictive modeling has been performed to understand how multiple variables contribute to (cross-) hybridization. RESULTS: We propose a systematic search strategy using multiple multivariate models [multiple linear regressions, regression trees, and artificial neural network analyses (ANNs)] to select an effective set of predictors for hybridization. We validate this approach on a set of DNA microarrays with cytochrome p450 family genes. The performance of our multiple multivariate models is compared with that of a recently proposed third-order polynomial regression method that uses percent identity as the sole predictor. All multivariate models agree that the 'most contiguous base pairs between probe and target sequences,' rather than percent identity, is the best univariate predictor. The predictive power is improved by inclusion of additional nonlinear effects, in particular target GC content, when regression trees or ANNs are used. CONCLUSION: A systematic multivariate approach is provided to assess the importance of multiple sequence features for hybridization and of relationships among these features. This approach can easily be applied to larger datasets. This will allow future developments of generalized hybridization models that will be able to correct for false-positive cross-hybridization signals in expression experiments

DISTRIBUCIÓN DE LAS ÁREAS VERDES, ÍNDICE DE MARGINACIÓN Y JUSTICIA AMBIENTAL EN LEÓN, GUANAJUATO

Las áreas verdes constituyen un elemento estratégico para la sostenibilidad de las ciudades, ya que poseen cualidades que derivan en la mejora de la calidad de vida y el bienestar social. No obstante, la ciudad de León, Guanajuato, muestra una distribución desigual y deficitaria en la dotación de áreas verdes, lo cual se manifiesta en una exclusión socio-espacial de los beneficios que estos espacios brindan a toda la población. El trabajo evidencia que las zonas con menor índice de áreas verdes coinciden con las zonas de mayor índice de marginación, especialmente en el caso de los siete polígonos de pobreza de ciudad. El reto que subyace para la ciudad es lograr una distribución justa y equitativa de las áreas verdes, mediante instrumentos de planificación que permitan lograr la sostenibilidad urbana, con justicia ambiental y correlacionarse positivamente con los índices de marginación

Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>We recently demonstrated that increased expression of the RNA-binding protein RBM3 is associated with a favourable prognosis in breast cancer. The aim of this study was to examine the prognostic value of RBM3 mRNA and protein expression in epithelial ovarian cancer (EOC) and the cisplatin response upon RBM3 depletion in a cisplatin-sensitive ovarian cancer cell line.</p> <p>Methods</p> <p>RBM3 mRNA expression was analysed in tumors from a cohort of 267 EOC cases (Cohort I) and RBM3 protein expression was analysed using immunohistochemistry (IHC) in an independent cohort of 154 prospectively collected EOC cases (Cohort II). Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS). Immunoblotting and IHC were used to examine the expression of RBM3 in a cisplatin-resistant ovarian cancer cell line A2780-Cp70 and its cisplatin-responsive parental cell line A2780. The impact of RBM3 on cisplatin response in EOC was assessed using siRNA-mediated silencing of RBM3 in A2780 cells followed by cell viability assay and cell cycle analysis.</p> <p>Results</p> <p>Increased RBM3 mRNA expression was associated with a prolonged RFS (HR = 0.64, 95% CI = 0.47-0.86, <it>p = 0.003</it>) and OS (HR = 0.64, 95% CI = 0.44-0.95, <it>p = 0.024</it>) in Cohort I. Multivariate analysis confirmed that RBM3 mRNA expression was an independent predictor of a prolonged RFS, (HR = 0.61, 95% CI = 0.44-0.84, <it>p = 0.003</it>) and OS (HR = 0.62, 95% CI = 0.41-0.95; <it>p = 0.028</it>) in Cohort I. In Cohort II, RBM3 protein expression was associated with a prolonged OS (HR = 0.53, 95% CI = 0.35-0.79, <it>p = 0.002</it>) confirmed by multivariate analysis (HR = 0.61, 95% CI = 0.40-0.92, <it>p = 0.017</it>). RBM3 mRNA and protein expression levels were significantly higher in the cisplatin sensitive A2780 cell line compared to the cisplatin resistant A2780-Cp70 derivative. siRNA-mediated silencing of RBM3 expression in the A2780 cells resulted in a decreased sensitivity to cisplatin as demonstrated by increased cell viability and reduced proportion of cells arrested in the G2/M-phase.</p> <p>Conclusions</p> <p>These data demonstrate that RBM3 expression is associated with cisplatin sensitivity <it>in vitro </it>and with a good prognosis in EOC. Taken together these findings suggest that RBM3 may be a useful prognostic and treatment predictive marker in EOC.</p

Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT)

Background: Life expectancy is reduced by 19 years in men and 17 in women with psychosis in Sweden, largely due to cardiovascular disease. Aim: Assess whether a psychosocial health promotion intervention improves cardiometabolic risk factors, quality of life, and severity of illness in patients with psychotic disorders more than treatment as usual. Methods: A pragmatic intervention trial testing a manual-based multi-component health promotion intervention targeting patients with psychosis. The Swedish intervention was adapted from IMPaCT therapy, a health-promotion program based on motivational interviewing and cognitive behavioral therapy, designed to be incorporated into routine care. The intervention group consisted of 119 patients and a control group of 570 patients from specialized psychosis departments. Outcome variables were assessed 6 months before intervention during the run-in period, again at the start of intervention, and 12 months after the intervention began. The control group received treatment as usual. Results: The intervention had no significant effect on any of the outcome variables. However, BMI, waist circumference, systolic BP, heart rate, HbA1c, general health, and Clinical Global Impressions Scale score improved significantly during the run-in period before the start of the active intervention (observer effect). The multi-component design meant that treatment effects could only be calculated for the intervention as a whole. Conclusion: The results of the intervention are similar to those of the U.K. IMPaCT study, in which the modular health-promotion intervention had little effect on cardiovascular risk indicators. However, in the current study, the run-in period had a positive effect on cardiometabolic risk factors