Progression of autosomal-dominant polycystic kidney disease in children1

Progression of autosomal-dominant polycystic kidney disease in children.BackgroundAlthough many case reports describe manifestations of autosomal-dominant polycystic kidney disease (ADPKD) in children, no longitudinal studies have examined the natural progression or risk factors for more rapid progression in a large number of children from ADPKD families.MethodsSince 1985, we have studied 312 children from 131 families with a history, a physical examination, blood and urine chemistries, an abdominal ultrasonography, and gene linkage analysis. One hundred fifteen of 185 affected children were studied multiple times for up to 15 years. Renal volumes were determined by ultrasound imaging. Graphs of mean renal volumes according to age were compared between affected and unaffected children, ADPKD children with and without early severe disease, and children with and without high blood pressure.ResultsAffected children had faster renal growth than unaffected children. ADPKD children with severe renal enlargement at a young age continued to experience faster renal growth than those with mild enlargement or normal kidney size for their age, and affected children with high blood pressure had faster renal growth than those with lower blood pressure. Glomerular filtration rate did not decrease in any children except for two with unusually severe early onset disease.ConclusionsThe progression of ADPKD clearly occurs in childhood and manifests as an increase in cyst number and renal size. This study identifies children at risk for rapid renal enlargement who may benefit the most from future therapeutic interventions

Foliations of Isonergy Surfaces and Singularities of Curves

It is well known that changes in the Liouville foliations of the isoenergy surfaces of an integrable system imply that the bifurcation set has singularities at the corresponding energy level. We formulate certain genericity assumptions for two degrees of freedom integrable systems and we prove the opposite statement: the essential critical points of the bifurcation set appear only if the Liouville foliations of the isoenergy surfaces change at the corresponding energy levels. Along the proof, we give full classification of the structure of the isoenergy surfaces near the critical set under our genericity assumptions and we give their complete list using Fomenko graphs. This may be viewed as a step towards completing the Smale program for relating the energy surfaces foliation structure to singularities of the momentum mappings for non-degenerate integrable two degrees of freedom systems.Comment: 30 pages, 19 figure

Nonlinear AC resistivity in s-wave and d-wave disordered granular superconductors

We model s-wave and d-wave disordered granular superconductors with a three-dimensional lattice of randomly distributed Josephson junctions with finite self-inductance. The nonlinear ac resistivity of these systems was calculated using Langevin dynamical equations. The current amplitude dependence of the nonlinear resistivity at the peak position is found to be a power law characterized by exponent $\alpha$. The later is not universal but depends on the self-inductance and current regimes. In the weak current regime $\alpha$ is independent of the self-inductance and equal to 0.5 or both of s- and d-wave materials. In the strong current regime this exponent depends on the screening. We find $\alpha \approx 1$ for some interval of inductance which agrees with the experimental finding for d-wave ceramic superconductors.Comment: 4 pages, 5 figures, to appear in Phys. Rev. Let

Reliability, validity and psychometric properties of the Greek translation of the zung depression rating scale

INTRODUCTION: The current study aimed to assess the reliability, validity and psychometric properties of the Greek translation of the Zung Depression Rating Scale (ZDRS). METHODS: The study sample included 40 depressed patients 29.65 ± 9.38 years old and 120 normal comparison subjects 27.23 ± 10.62 years old. In 20 of them (12 patients and 8 comparison subjects) the instrument was re-applied 1–2 days later. Translation and Back Translation was made. Clinical Diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. Statistical Analysis included ANOVA, the Pearson Product Moment Correlation Coefficient, Principal Components Analysis and Discriminant Function Analysis and the calculation of Cronbach's alpha (α) RESULTS: Both Sensitivity and specificity exceed 90.00 at 44/45, Chronbach's alpha for the total scale was equal to 0.09, suggesting that the scale covers a broad spectrum of symptoms. Factor analysis revealed five factors (anxiety-depression, thought content, gastrenterological symptoms, irritability and social-interpersonal functioning). The test-retest reliability was satisfactory (Pearson's R between 0.92). CONCLUSION: The ZDRS-Greek translation is both reliable and valid and is suitable for clinical and research use with satisfactory properties. Its properties are similar to those reported in the international literature, although the literature is limited. However one should always have in mind the limitations inherent in the use of self-report scales

De novo mutations in EIF2B1 affecting eIF2 signaling cause neonatal/early onset diabetes and transient hepatic dysfunction

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this recordData and resource availability. EIF2B1 mutation details have been deposited in the Decipher database (https://decipher.sanger.ac.uk/). All other data sets generated and/or analysed for this study are available from the corresponding author upon reasonable request.Permanent neonatal diabetes is caused by reduced β-cell number or impaired β-cell function. Understanding the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 permanent neonatal diabetes patients and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified 2 further patients with de novo EIF2B1 variants. In addition to diabetes, 4/5 patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation which occurs under stress conditions and triggers expression of stress-response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.European Foundation for the Study of DiabetesDiabetes UKDiabetes Research and Wellness FoundationWellcome TrustNational Institute for Health Research (NIHR)Royal Societ

Factor analysis of the Zung self-rating depression scale in a large sample of patients with major depressive disorder in primary care

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the symptomatic dimensions of depression in a large sample of patients with major depressive disorder (MDD) in the primary care (PC) setting by means of a factor analysis of the Zung self-rating depression scale (ZSDS).</p> <p>Methods</p> <p>A factor analysis was performed, based on the polychoric correlations matrix, between ZSDS items using promax oblique rotation in 1049 PC patients with a diagnosis of MDD (DSM-IV).</p> <p>Results</p> <p>A clinical interpretable four-factor solution consisting of a <it>core depressive </it>factor (I); a <it>cognitive </it>factor (II); an <it>anxiety </it>factor (III) and a <it>somatic </it>factor (IV) was extracted. These factors accounted for 36.9% of the variance on the ZSDS. The 4-factor structure was validated and high coefficients of congruence were obtained (0.98, 0.95, 0.92 and 0.87 for factors I, II, III and IV, respectively). The model seemed to fit the data well with fit indexes within recommended ranges (GFI = 0.9330, AGFI = 0.9112 and RMR = 0.0843).</p> <p>Conclusion</p> <p>Our findings suggest that depressive symptoms in patients with MDD in the PC setting cluster into four dimensions: <it>core depressive, cognitive, anxiety </it>and <it>somatic</it>, by means of a factor analysis of the ZSDS. Further research is needed to identify possible diagnostic, therapeutic or prognostic implications of the different depressive symptomatic profiles.</p

Reliability, validity and psychometric properties of the Greek translation of the Major Depression Inventory

BACKGROUND: The Major Depression Inventory (MDI) is a brief self-rating scale for the assessment of depression. It is reported to be valid because it is based on the universe of symptoms of DSM-IV and ICD-10 depression. The aim of the current preliminary study was to assess the reliability, validity and psychometric properties of the Greek translation of the MDI. METHODS: 30 depressed patients of mean age 23.41 (± 5.77) years, and 68 controls patients of mean age 25.08 (± 11.42) years, entered the study. In 18 of them, the instrument was re-applied 1–2 days later and the Translation and Back Translation made. Clinical diagnosis was reached with the use of the SCAN v.2.0 and the International Personality Disorders Examination (IPDE). The Center for Epidemiological Studies-Depression (CES-D) and the Zung Depression Rating Scale (ZDRS) were applied for cross-validation purposes. Statistical analysis included ANOVA, the Spearman Product Moment Correlation Coefficient, Principal Components Analysis and the calculation of Cronbach's α. RESULTS: Sensitivity and specificity were 0.86 and 0.94, respectively, at 26/27. Cronbach's α for the total scale was equal to 0.89. The Spearman's rho between MDI and CES-D was 0.86 and between MDI and ZDRS was 0.76. The factor analysis revealed two factors but the first accounted for 54% of variance while the second only for 9%. The test-retest reliability was excellent (Spearman's rho between 0.53 and 0.96 for individual items and 0.89 for total score). CONCLUSION: The current study provided preliminary evidence concerning the reliability and validity of the Greek translation of the MDI. Its properties are similar to those reported in the international literature, but further research is necessary

Psychosocial correlates with depressive symptoms six years after a first episode of psychosis as compared with findings from a general population sample

BACKGROUND: Depression is frequently occurring during and after psychosis. The aim of this study was to analyze if the psychosocial characteristics associated with depression/depressive symptoms in the late phase of a first episode psychosis (FEP) population were different compared to persons from the general population. METHODS: A questionnaire was sent out to all individuals six years after their FEP and to a general population sample. Depressive symptoms were recorded using a self-rating scale, the Major Depression Inventory. RESULTS: Formerly FEP persons had a higher representation of depressive symptoms/depression, unemployment, financial problems and insufficient social network. Depressive symptoms/depression were found to be associated with psychosocial problems. An age and gender effect was found in the general population, but not in the FEP sample. When the psychosocial characteristics were taken into account there were no association between having had FEP and depressive symptoms. CONCLUSIONS: The association between having been a FEP patient and depressive symptoms/depression disappeared when negative social aspects were taken into account