Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: Relevance to schizophrenia.

A series of studies in schizophrenic patients report a decrease of glutathione (GSH) in prefrontal cortex (PFC) and cerebrospinal fluid, a decrease in mRNA levels for two GSH synthesizing enzymes and a deficit in parvalbumin (PV) expression in a subclass of GABA neurons in PFC. GSH is an important redox regulator, and its deficit could be responsible for cortical anomalies, particularly in regions rich in dopamine innervation. We tested in an animal model if redox imbalance (GSH deficit and excess extracellular dopamine) during postnatal development would affect PV-expressing neurons. Three populations of interneurons immunolabeled for calcium-binding proteins were analyzed quantitatively in 16-day-old rat brain sections. Treated rats showed specific reduction in parvalbumin immunoreactivity in the anterior cingulate cortex, but not for calbindin and calretinin. These results provide experimental evidence for the critical role of redox regulation in cortical development and validate this animal model used in schizophrenia research.

Epidemiology of multiple congenital anomalies in Europe: a EUROCAT population-based registry study.

BACKGROUND: This study describes the prevalence, associated anomalies, and demographic characteristics of cases of multiple congenital anomalies (MCA) in 19 population-based European registries (EUROCAT) covering 959,446 births in 2004 and 2010. METHODS: EUROCAT implemented a computer algorithm for classification of congenital anomaly cases followed by manual review of potential MCA cases by geneticists. MCA cases are defined as cases with two or more major anomalies of different organ systems, excluding sequences, chromosomal and monogenic syndromes. RESULTS: The combination of an epidemiological and clinical approach for classification of cases has improved the quality and accuracy of the MCA data. Total prevalence of MCA cases was 15.8 per 10,000 births. Fetal deaths and termination of pregnancy were significantly more frequent in MCA cases compared with isolated cases (p < 0.001) and MCA cases were more frequently prenatally diagnosed (p < 0.001). Live born infants with MCA were more often born preterm (p < 0.01) and with birth weight < 2500 grams (p < 0.01). Respiratory and ear, face, and neck anomalies were the most likely to occur with other anomalies (34% and 32%) and congenital heart defects and limb anomalies were the least likely to occur with other anomalies (13%) (p < 0.01). However, due to their high prevalence, congenital heart defects were present in half of all MCA cases. Among males with MCA, the frequency of genital anomalies was significantly greater than the frequency of genital anomalies among females with MCA (p < 0.001). CONCLUSION: Although rare, MCA cases are an important public health issue, because of their severity. The EUROCAT database of MCA cases will allow future investigation on the epidemiology of these conditions and related clinical and diagnostic problems.

Paper 2: EUROCAT public health indicators for congenital anomalies in Europe.

OBJECTIVE: The purpose of this article is to present the specific public health indicators recently developed by EUROCAT that aim to summarize important aspects of the public health impact of congenital anomalies in a few quantitative measures. METHODS: The six indicators are: (1) congenital anomaly perinatal mortality, (2) congenital anomaly prenatal diagnosis prevalence, (3) congenital anomaly termination of pregnancy, (4) Down syndrome livebirth prevalence, (5) congenital anomaly pediatric surgery, and (6) neural tube defects (NTD) total prevalence. Data presented for this report pertained to all cases (livebirths, fetal deaths, or stillbirths after 20 weeks of gestation and terminations of pregnancy for fetal anomaly [TOPFA]) of congenital anomaly from 27 full member registries of EUROCAT that could provide data for at least 3 years during the period 2004 to 2008. Prevalence of anomalies, prenatal diagnosis, TOPFA, pediatric surgery, and perinatal mortality were calculated per 1000 births. RESULTS: The overall perinatal mortality was approximately 1.0 per 1000 births for EUROCAT registries with almost half due to fetal and the other half due to first week deaths. There were wide variations in perinatal mortality across the registries with the highest rates observed in Dublin and Malta, registries in countries where TOPFA are illegal, and in Ukraine. The overall perinatal mortality across EUROCAT registries slightly decreased between 2004 and 2008 due to a decrease in first week deaths. The prevalence of TOPFA was fairly stable at about 4 per 1000 births. There were variations in livebirth prevalence of cases typically requiring surgery across the registries; however, for most registries this prevalence was between 3 and 5 per 1000 births. Prevalence of NTD decreased by about 10% from 1.05 in 2004 to 0.94 per 1000 in 2008. CONCLUSION: It is hoped that by publishing the data on EUROCAT indicators, the public health importance of congenital anomalies can be clearly summarized to policy makers, the need for accurate data from registries emphasized, the need for primary prevention and treatment services highlighted, and the impact of current services measured.

Pièges dans l'interprétation de la pathologie infiltrative et de l'exposition à l'amiante.

Messages à retenir: L'identification des anomalies pleurales et parenchymateuses liées à une exposition à l'amiante est essentielle pour la reconnaissance de maladie professionnelle, avec de lourdes conséquences économiques. Le scanner thoracique est l'outil le plus fiable de ce dépistage. La détection d'anomalies dans les régions basales et sous-pleurales doit conduire à la réalisation de coupes complémentaires en procubitus sur ces régions. Le diagnostic TDM des anomalies pleurales et parenchymateuses liées à l'amiante repose sur des critères diagnostiques et un vocabulaire précis. De nombreuses images pièges peuvent mimer des plaques ou une asbestose. Une bonne connaissance de l'anatomie de l'interface pleuro-parenchymateuse et des principaux diagnostics différentiels permet souvent de redresser le diagnostic. Résumé: Le scanner multicoupe est l'outil de référence pour le dépistage des pathologies pleurales et parenchymateuses liées à l'exposition à l'amiante. Le diagnostic de plaques pleurales repose sur une surélévation quadrangulaire et nette de l'interface pleuro-parenchymateuse, dans une ou des localisation(s) évocatrice(s). Les pièges responsables de fausses images de plaques sont nombreux : structures anatomiques et variantes de la normale, opacités postéro-basales liées à des troubles ventilatoires, sarcoïdose... Les plaques doivent être différenciées des autres anomalies pleurales bénignes pouvant être rencontrées dans ce contexte, mais non spécifiques d'une exposition à l'amiante : épaississements pleuraux diffus, fibrose de la plèvre viscérale, images en pieds de corneille. La reconnaissance d'une asbestose nécessite de s'affranchir de troubles ventilatoires liés à la déclivité ou à des contraintes mécaniques focales, chroniques, telles que des ostéophytes para-vertébraux. Les coupes en procubitus permettent d'affirmer l'existence d'une pathologie interstitielle débutante dans les régions sous-pleurales et basales. Des anomalies interstitielles isolées ne peuvent être attribuées à une asbestose, de même que des anomalies interstitielles non spécifiques, associées ou non à une pathologie diffuse fibrosante.

Early Tithonian Saturnalidae (Radiolaria) from the Solnhofen area (Southern Franconian Alb, Southern Germany)

In order to complete the study of the very rich early Tithonian (Hybonoticeras hybonotum Zone) radiolarian fauna from the Muhlheim Member of the Mornsheim Formation outcropping in the Solnhofen area, the taxa of the family Saturnalidae are described. Although rather rare, the Saturnalidae of this member contain 14 species, ten of which are new. These species belong to four genera, one of which is new (Moebicircus n. gen.), and two subfamilies (Hexasaturnalinae and Saturnalinae). The taxonomy at generic level of these late Jurassic radiolarians is founded on the basis of the position of the blades along the ring and number and morphology of the spines. Type of spines (simple or forked) has either species level value or none, depending on species. Special attention was given to anomalies, which sometimes are rather frequent, since they can give information of paleobiological and paleoecological orders. Among them frequent cases of open ring and additional spines with Dicerosaturnalis and Siamese twins skeletons with Spongosaturninus and Dicerosaturnalis are to be noted. The authors hope that this new taxonomy will give a better image of the evolution and radiation of the Saturnalidae during the Tithonian.

Depleted arc volcanism in the Alboran Sea and shoshonitic volcanism in Morocco: geochemical and isotopic constraints on Neogene tectonic processes

Samples of volcanic rocks from Alboran Island, the Alboran Sea floor and from the Gourougou volcanic centre in northern Morocco have been analyzed for major and trace elements and Sr-Nd isotopes to test current theories on the tectonic geodynamic evolution of the Alboran Sea. The Alboran Island samples are low-K tholeiitic basaltic andesites whose depleted contents of HFS elements (similar to0.5xN-MORB), especially Nb (similar to0.2xN-MORB), show marked geochemical parallels with volcanics from immature intra-oceanic arcs and back-arc basins. Several of the submarine samples have similar compositions, one showing low-Ca boninite affinity. Nd-143/Nd-144 ratios fall in the same range as many island-arc and back-arc basin samples, whereas Sr-87/Sr-86 ratios (on leached samples) are somewhat more radiogenic. Our data point to active subduction taking place beneath the Alboran region in Miocene times, and imply the presence of an associated back-arc spreading centre. Our sea floor suite includes a few more evolved dacite and rhyolite samples with (Sr-87/Sr-86)(0) up to 0.717 that probably represent varying degrees of crustal melting. The shoshonite and high-K basaltic andesite lavas from Gourougou have comparable normalized incompatible-element enrichment diagrams and Ce/Y ratios to shoshonitic volcanics from oceanic island arcs, though they have less pronounced Nb deficits. They are much less LIL- and LREE-enriched than continental arc analogues and post-collisional shoshonites from Tibet. The magmas probably originated by melting in subcontinental lithospheric mantle that had experienced negligible subduction input. Sr-Nd isotope compositions point to significant crustal contamination which appears to account for the small Nb anomalies. The unmistakable supra-subduction zone (SSZ) signature shown by our Alboran basalts and basaltic andesite samples refutes geodynamic models that attribute all Neogene volcanism in the Alboran domain to decompression melting of upwelling asthenosphere arising from convective thinning of over-thickened lithosphere. Our data support recent models in which subsidence is caused by westward rollback of an eastward-dipping subduction zone beneath the westemmost Mediterranean. Moreover, severance of the lithosphere at the edges of the rolling-back slab provides opportunities for locally melting lithospheric mantle, providing a possible explanation for the shoshonitic volcanism seen in northern Morocco and more sporadically in SE Spain. (C) 2004 Elsevier B.V. All rights reserved.

Multi-scale support vector algorithms for hot spot detection and modelling

The algorithmic approach to data modelling has developed rapidly these last years, in particular methods based on data mining and machine learning have been used in a growing number of applications. These methods follow a data-driven methodology, aiming at providing the best possible generalization and predictive abilities instead of concentrating on the properties of the data model. One of the most successful groups of such methods is known as Support Vector algorithms. Following the fruitful developments in applying Support Vector algorithms to spatial data, this paper introduces a new extension of the traditional support vector regression (SVR) algorithm. This extension allows for the simultaneous modelling of environmental data at several spatial scales. The joint influence of environmental processes presenting different patterns at different scales is here learned automatically from data, providing the optimum mixture of short and large-scale models. The method is adaptive to the spatial scale of the data. With this advantage, it can provide efficient means to model local anomalies that may typically arise in situations at an early phase of an environmental emergency. However, the proposed approach still requires some prior knowledge on the possible existence of such short-scale patterns. This is a possible limitation of the method for its implementation in early warning systems. The purpose of this paper is to present the multi-scale SVR model and to illustrate its use with an application to the mapping of Cs137 activity given the measurements taken in the region of Briansk following the Chernobyl accident.

Valeur de l'angio-TDM dans le bilan des hémoptysies

Objectifs: Évaluer l'apport de l'angioscanographie dans le cadre d'hémoptysies (1) dans la localisation des artères pathologiques, bronchiques (AB) et systémiques non bronchiques (ASNB) ou artérielles pulmonaires, (2) la localisation de la source du saignement et (3) les anomalies parenchymateuses responsables ou secondaires au saignement en comparaison avec les données angiographiques. Matériels et méthodes: 25 patients consécutifs (12 femmes, 13 hommes) d'un âge moyen de 50 ± 39 ans (min 15, max 89) ont été inclus dans l'étude. Les signes TDM ont été comparés aux signes angiographiques. Résultats: Les artères bronchiques ont été correctement identifiées dans 20 cas. Des ASNB anormales ont été identifiées dans 5 cas chez 4 patients. La TDM a correctement prédit le site d'embolisation dans 19 cas (76%). Les AB étaient responsables de l'hémoptysie dans 25 cas et les ASNB dans 4 cas. Les affections causales ou associées étaient les suivantes: carcinome bronchopulmonaire (n=11), hémangioendothéliome malin (n=1), mucoviscidose (n=7), hémoptysie cryptogénique au cours d'une BPCO (n=1), bronchectasies focales (n=4) et séquelles de tuberculose avec bronchectasies (n=1). Conclusion: Les signes directs et indirects en Angio-TDM sont utiles pour obtenir une visualisation globale des AB et ASNB anormales. Néanmoins, le site optimal d'embolisation ne peut toujours être prédit.

Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis.

PURPOSE: Investigation of the incidence and distribution of congenital structural cardiac malformations among the offspring of mothers with diabetes type 1 and of the influence of periconceptional glycemic control. METHODS: Multicenter retrospective clinical study, literature review, and meta-analysis. The incidence and pattern of congenital heart disease in the own study population and in the literature on the offspring of type 1 diabetic mothers were compared with the incidence and spectrum of the various cardiovascular defects in the offspring of nondiabetic mothers as registered by EUROCAT Northern Netherlands. Medical records were, in addition, reviewed for HbA(1c) during the 1st trimester. RESULTS: The distribution of congenital heart anomalies in the own diabetic study population was in accordance with the distribution encountered in the literature. This distribution differed considerably from that in the nondiabetic population. Approximately half the cardiovascular defects were conotruncal anomalies. The authors' study demonstrated a remarkable increase in the likelihood of visceral heterotaxia and variants of single ventricle among these patients. As expected, elevated HbA(1c) values during the 1st trimester were associated with offspring fetal cardiovascular defects. CONCLUSION: This study shows an increased likelihood of specific heart anomalies, namely transposition of the great arteries, persistent truncus arteriosus, visceral heterotaxia and single ventricle, among offspring of diabetic mothers. This suggests a profound teratogenic effect at a very early stage in cardiogenesis. The study emphasizes the frequency with which the offspring of diabetes-complicated pregnancies suffer from complex forms of congenital heart disease. Pregnancies with poor 1st-trimester glycemic control are more prone to the presence of fetal heart disease.

A t(7;12) balanced translocation with breakpoints overlapping those of the Williams-Beuren and 12q14 microdeletion syndromes.

The molecular characterization of balanced chromosomal rearrangements have always been of advantage in identifying disease-causing genes. Here, we describe the breakpoint mapping of a de novo balanced translocation t(7;12)(q11.22;q14.2) in a patient presenting with a failure to thrive associated with moderate mental retardation, facial anomalies, and chronic constipation. The localization of the breakpoints and the co-occurrence of Williams-Beuren syndrome and 12q14 microdeletion syndrome phenotypes suggested that the expression of some of the dosage-sensitive genes of these two segmental aneuploidies were modified in cells of the proposita. However, we were unable to identify chromosomes 7 and/or 12-mapping genes that showed disturbed expression in the lymphoblastoids of the proposita. This case showed that position-effect might operate in some tissues, but not in others. It also illustrates the overlap of phenotypes presented by patients with the recently described 12q14 structural rearrangements.

Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe.

The aim of this study is to quantify the prevalence and types of rare chromosome abnormalities (RCAs) in Europe for 2000-2006 inclusive, and to describe prenatal diagnosis rates and pregnancy outcome. Data held by the European Surveillance of Congenital Anomalies database were analysed on all the cases from 16 population-based registries in 11 European countries diagnosed prenatally or before 1 year of age, and delivered between 2000 and 2006. Cases were all unbalanced chromosome abnormalities and included live births, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. There were 10,323 cases with a chromosome abnormality, giving a total birth prevalence rate of 43.8/10,000 births. Of these, 7335 cases had trisomy 21,18 or 13, giving individual prevalence rates of 23.0, 5.9 and 2.3/10,000 births, respectively (53, 13 and 5% of all reported chromosome errors, respectively). In all, 473 cases (5%) had a sex chromosome trisomy, and 778 (8%) had 45,X, giving prevalence rates of 2.0 and 3.3/10,000 births, respectively. There were 1,737 RCA cases (17%), giving a prevalence of 7.4/10,000 births. These included triploidy, other trisomies, marker chromosomes, unbalanced translocations, deletions and duplications. There was a wide variation between the registers in both the overall prenatal diagnosis rate of RCA, an average of 65% (range 5-92%) and the prevalence of RCA (range 2.4-12.9/10,000 births). In all, 49% were liveborn. The data provide the prevalence of families currently requiring specialised genetic counselling services in the perinatal period for these conditions and, for some, long-term care.

Screening for foetal malformations: performance of routine ultrasonography in the population of the Swiss Canton of Vaud.

OBJECTIVE: To determine the sensitivity of ultrasonography in screening for foetal malformations in the pregnant women of the Swiss Canton of Vaud. STUDY DESIGN: Retrospective study over a period of five years. METHOD: We focused our study on 512 major or minor clinically relevant malformations detectable by ultrasonography. We analysed the global sensitivity of the screening and compared the performance of the tertiary centre with that of practitioners working in private practice or regional hospitals. RESULTS: Among the 512 malformations, 181 (35%) involved the renal and urinary tract system, 137 (27%) the heart, 71 (14%) the central nervous system, 50 (10%) the digestive system, 42 (8%) the face and 31 (6%) the limbs. Global sensitivity was 54.5%. The lowest detection rate was observed for cardiac anomalies, with only 23% correct diagnoses. The tertiary centre achieved a 75% detection rate in its outpatient clinic and 83% in referred patients. Outside the referral centre, the diagnostic rate attained 47%. CONCLUSIONS: Routine foetal examination by ultrasonography in a low-risk population can detect foetal structural abnormalities. Apart from the diagnosis of cardiac abnormalities, the results in the Canton of Vaud are satisfactory and justify routine screening for malformations in a low-risk population. A prerequisite is continuing improvement in the skills of ultrasonographers through medical education.

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study.

Transposition of great arteries and single coronary artery: a new surgical technique for the arterial switch operation.

A single coronary artery can complicate the surgical technique of arterial switch operations, impairing early and late outcomes. We propose a new surgical approach, successfully applied in a 2.1 kg neonate, aimed at reducing the risk of early and late compression and/or distortion of the newly constructed coronary artery system.

Problèmes orthopédiques du pied vieillissant : les possibilités conservatrices doivent être explorées systématiquement

Les pathologies orthopédiques du pied du sujet âgé incluent principalement les troubles dégénératifs et les séquelles de traumatismes. Le pied est également l'organe cible d'autres pathologies, telles que la polyarthrite rhumatoïde (PR), le diabète, les insuffisance artérielles et les troubles neurologiques qui peuvent avoir pour conséquence des anomalies orthopédiques.