The miR(21/10b) ratio as a prognostic marker in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer in the adult kidney, and the prognosis of metastatic ccRCC remains poor with high mortality. In ccRCC, microRNAs (miRs) differentially expressed in tumour tissue have been identified and have been proposed to predict prognosis. The purpose of this study was to evaluate candidate miR markers identified from analysis of The Cancer Genome Atlas (TCGA) datasets in a large RCC cohort and to elucidate whether a ratio of miRs provided additional prognostic information

Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney.

Acute tubular necrosis (ATN), elicited by ischemia and/or toxicity, is a potentially life-threatening condition. Histologically, ATN corresponds to necrosis and detachment of renal tubular epithelial cells. However, the tubules possess a considerable regenerative capacity and may be restored. We have previously identified a scattered population of progenitor-like cells within the proximal tubules, sharing marker expression with the parietal epithelial cells of Bowman's capsule as well as with renal tubules regenerating after ATN. In the present analysis, we use transmission electron microscopy, immunoelectron microscopy and immunofluorescence of human kidney cortex to further explore these cells. We demonstrate that the cells are smaller and have drastically fewer mitochondria than the surrounding proximal tubule cells. They also display strong expression of several structural proteins such as vimentin, collagen-7A1 and the tight junction protein claudin-1. To functionally assess these cells, we also developed a novel human kidney explant model of ATN demonstrating that the cells are more resilient to injury than the surrounding proximal tubular cells. Taken together the results suggest a novel robust cell type with a contrasting biological role to that of the bulk of proximal tubular epithelium

The Notch and TGF-β Signaling Pathways Contribute to the Aggressiveness of Clear Cell Renal Cell Carcinoma

Despite recent progress, therapy for metastatic clear cell renal cell carcinoma (CCRCC) is still inadequate. Dysregulated Notch signaling in CCRCC contributes to tumor growth, but the full spectrum of downstream processes regulated by Notch in this tumor form is unknown

Application of Multivariate Analysis, Support Vector Machines and Artificial Neural Network to the Processing of Nuclear Magnetic Resonance data of olive oil and fish oil samples for classification of geographic origin and discrimination between wild and farm fish.

Motivations Traceability and control of origin of food products are very important for the Consumers and for the European enforcement laboratories. For instance, The high added value of olive oil makes its control an important goal for EU producers and consumers. There is thus a need in developing analytical methods to ensure compliance with labeling, i.e.the control of geographical origin giving also support to the denominated protected origin (DPO) policy, and the determination of the genuineness of the product by the detection of eventual adulterations. Futhermore , EU regulations requires that origin, wild or farmed as well as geographic origin, of fish sold on the retail market be available to the consumers. Modern analytical techniques such as Nuclear Magnetic Resonance (NMR) provide very informative data on the composition in fatty acids and in other constituents of vegetable oils and fish oils. The combination of 1H NMR fingerprinting with multivariate analysis provides an original approach to study the profile of these oils in relation with geographical origin of olive oil or for discrimination between wild or farm origin for fish like salmons. Methods Concerning the experiment on fish oil, we used Support vector machines (SVMs) as a novel learning machine in the authentication of the origin of salmon. SVMs have the advantage of relying on a well-developed theory and have already proved to be successful in a number of practical applications. The method requires a very simple sample preparation of the fish oils extracted from the white muscle of salmon samples. Multivariate (chemometric) techniques are able to filter out the most relevant information from a spectrum, e.g. for a classification. In the experiment on olive oil samples, the principal component analysis (PCA) was carried out on the ~12,000 variables (chemical shifts) and four data sets were defined prior to PCA. Linear discriminant analysis (LDA) of the first 50 PC\u2019s was applied for classification of olive oil samples according to the geographic origin and year of production. The data analysis has been carried out with and without outliers, as well. Variable selection for LDA was achieved using: (i) the best five variables and (ii) an interactive forward stepwise manner. Results The use of SVMs for the discrimination between wild and farm salmon provides a new and effective method that eliminates the possibility of fraud through misrepresentation of the country of origin of salmon. The SVM has been able to distinguish correctly between the wild and farmed salmon; however ca. 5% of the country of origins were misclassified. Using LDA on the external validation sets the correct classification of olive oil varied between 47 and 75% (random selection), and between 35 and 92% (Kennard\u2013Stone selection (KS)) depending on geographic origin (country) and production years. A similar success rate could be achieved using partial least squares discriminant analysis (PLS DA). The success rate can be considerably improved by using probabilistic neural networks (PNN). Correct classification by PNN varied between 58 and 100% on the external validation sets. Other chemometric techniques, such as multiple linear regression, or generalized pair-wise correlation, did not give better results. Acknowledgements The authors are grateful to the Europeanproject COFAWS (European Commission DG RTD FP5 project GRD2\u20132000\u201331813) and to all the collaborators from the partners of this project (Eurofins Scientific (Nantes- France), North Atlantic Fisheries College (Scalloway, Shetland Islands - United Kingdom), SINTEF Fisheries and Aquaculture (Trondheim-Norway), Joint Research Centre (Ispra-Italy)) who contributed to the collection and preparation of fish samples, and for the authorization to exploit their NMR data in this work

Improving Clinical Prediction of Bipolar Spectrum Disorders in Youth.

This report evaluates whether classification tree algorithms (CTA) may improve the identification of individuals at risk for bipolar spectrum disorders (BPSD). Analyses used the Longitudinal Assessment of Manic Symptoms (LAMS) cohort (629 youth, 148 with BPSD and 481 without BPSD). Parent ratings of mania symptoms, stressful life events, parenting stress, and parental history of mania were included as risk factors. Comparable overall accuracy was observed for CTA (75.4%) relative to logistic regression (77.6%). However, CTA showed increased sensitivity (0.28 vs. 0.18) at the expense of slightly decreased specificity and positive predictive power. The advantage of CTA algorithms for clinical decision making is demonstrated by the combinations of predictors most useful for altering the probability of BPSD. The 24% sample probability of BPSD was substantially decreased in youth with low screening and baseline parent ratings of mania, negative parental history of mania, and low levels of stressful life events (2%). High screening plus high baseline parent-rated mania nearly doubled the BPSD probability (46%). Future work will benefit from examining additional, powerful predictors, such as alternative data sources (e.g., clinician ratings, neurocognitive test data); these may increase the clinical utility of CTA models further

Stability of Satellite Planes in M31 II: Effects of the Dark Subhalo Population

The planar arrangement of nearly half the satellite galaxies of M31 has been a source of mystery and speculation since it was discovered. With a growing number of other host galaxies showing these satellite galaxy planes, their stability and longevity have become central to the debate on whether the presence of satellite planes are a natural consequence of prevailing cosmological models, or represent a challenge. Given the dependence of their stability on host halo shape, we look into how a galaxy plane's dark matter environment influences its longevity. An increased number of dark matter subhalos results in increased interactions that hasten the deterioration of an already-formed plane of satellite galaxies in spherical dark halos. The role of total dark matter mass fraction held in subhalos in dispersing a plane of galaxies present non trivial effects on plane longevity as well. But any misalignments of plane inclines to major axes of flattened dark matter halos lead to their lifetimes being reduced to < 3 Gyrs. Distributing > 40% of total dark mass in subhalos in the overall dark matter distribution results in a plane of satellite galaxies that is prone to change through the 5 Gyr integration time period.Comment: 11 pages, 9 figures, accepted to MNRAS September 22 201

Factors Influencing Mental Health Service Utilization by Children with Serious Emotional and Behavioral Disturbance: Results from the LAMS Study

The official published article is available online at http://doi.org/10.1176/appi.ps.62.6.650.OBJECTIVE: To describe service utilization of a cohort of children with emotional and behavioral disorders who visited outpatient mental health clinics in four Midwest cities. METHOD: Data come from the Longitudinal Assessment of Manic Symptoms (LAMS) Study. 707 youth (ages 6–12 years) and their parents completed diagnostic assessments, demographic information and an assessment of mental health service utilization. Analyses examined the relationship of demographics, diagnoses, impairment, and comorbidity to the type and level of services utilized. RESULTS: Service utilization is multimodal with half of the youth receiving both outpatient and school services during their lifetime. Non-need factors including age, sex, race, and insurance, were related to types of services used. Youth diagnosed with a bipolar spectrum disorder had higher utilization of inpatient services and two or more services at one time compared to youth diagnosed with depressive or disruptive disorders. More than half of youth diagnosed with bipolar or depressive disorders had received both medication and therapy during their lifetime whereas for youth diagnosed with a disruptive disorder therapy only was more common. Impairment and comorbidity were not related to service utilization. CONCLUSIONS: Use of mental health services for children begins at a very young age and occurs in multiple service sectors. Type of service use is related to insurance and race/ethnicity, underscoring the need for research on treatment disparities. Contrary to findings from results based on administrative data, medication alone was infrequent. However, the reasonably low use of combination therapy suggests that clinicians and families need to be educated on the effectiveness of multimodal treatment

Altered development of white matter in youth at high familial risk for bipolar disorder: a diffusion tensor imaging study

Objective: To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy offspring having a parent with BD were compared with those in healthy controls. Method: A total of 45 offspring participated, including 20 healthy offspring with a parent diagnosed with BD (HBO) and 25 healthy control offspring of healthy parents (CONT). All were free of medical and psychiatric disorders. Mean fractional anisotropy (FA), radial diffusivity (RD), and longitudinal diffusivity were examined using whole-brain analyses, co-varying for age. Results: Group-by-age interactions showed a linear increase in FA and a linear decrease in RD in CONT in the left corpus callosum and right inferior longitudinal fasciculus. In HBO, there was a linear decrease in FA and an increase in RD with age in the left corpus callosum and no relation between FA or RD and age in the right inferior longitudinal fasciculus. Curve fitting confirmed linear and showed nonlinear relations between FA and RD and age in these regions in CONT and HBO. Conclusions: This is the first study to examine WM in healthy offspring at high familial risk for BD. Results from this cross-sectional study suggest altered development of WM in HBO compared with CONT in the corpus callosum and temporal associative tracts, which may represent vulnerability markers for future BD and other psychiatric disorders in HBO. J. Am. Acad. Child Adolesc. Psychiatry, J. Am. Acad. Child Adolesc. Psychiatry, 2010; 49(12):1249 -1259. Key words: bipolar disorder, familial risk, white matter, diffusion tensor imaging, neurodevelopment B ipolar disorder (BD) is a serious psychiatric illness affecting 1% to 3% of the adult population and remains a leading cause of morbidity, functional impairment, and completed suicide. 1 BD is characterized by difficulties in the regulation of emotions and behavior, as indicated by episodes of mania and depression. BD is highly heritable: the risk of BD is much greater in first-degree relatives of individuals diagnosed with BD. 2,3 Recent evidence has indicated that offspring of parents with BD are at increased risk for BD and other psychiatric disorders, including BD spectrum disorder, anxiety, and depression disorders. 2 Although genetic and environmental factors and their interactions are important in the development of BD, abnormalities of brain structure and function that most likely mediate these effects have yet to be elucidated. Converging evidence from epidemiologic, genetic, and neuroimaging studies has suggested that abnormalities in the development of white matter (WM) may play an important role in the neuropathophysiology of BD

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

Effects of comorbid anxiety disorders on the longitudinal course of pediatric bipolar disorders

OBJECTIVE: To examine the longitudinal effects of comorbid anxiety disorders in youth with bipolar spectrum disorder (BP). METHOD: As part of the Course and Outcome of Bipolar Youth study, 413 youth, who were 7 through 17 years or age and who met criteria for DSM-IV BP-I (n = 244), BP-II (n = 28), and operationally defined bipolar disorder not otherwise specified (BP-NOS) (n = 141) were included. Subjects were followed on average 5 years using the Longitudinal Interval Follow-up Evaluation. Effects of anxiety on the time to mood recovery and recurrence and percentage of time with syndromal and subsyndromal mood symptomatology during the follow-up period were analyzed. RESULTS: At intake and during the follow-up, 62% of youth with BP met criteria for at least 1 anxiety disorder. About 50% of the BP youth with anxiety had ≥2 anxiety disorders. Compared to BP youth without anxiety, those with anxiety had significantly more depressive recurrences and significantly longer median time to recovery. The effects of anxiety on recovery disappeared when the severity of depression at intake was taken into account. After adjusting for confounding factors, BP youth with anxiety, particularly those with ≥2 anxiety disorders, spent significantly less follow-up time asymptomatic and more time with syndromal mixed/cycling and subsyndromal depressive symptomatology compared to those without anxiety. CONCLUSIONS: Anxiety disorders are common and adversely affect the course of BP in youth, as characterized by more mood recurrences, longer time to recovery, less time euthymic, and more time in mixed/cycling and depressive episodes. Prompt recognition and the development of treatments for BP youth with anxiety are warranted