Association between growth and blood pressure during the life course in children and adolescents

Background: Little is known on the relative importance of growth at different periods between birth and adolescence on blood pressure (BP). Objective: To assess the association between birth weight, change in body weight (growth) and BP across the entire span of childhood and adolescence. Methods: School-based surveys were conducted annually between 1998 and 2006 among all children in four school grades (kindergarten, 4th, 7th, and 10th year of compulsory school) in the Seychelles, Indian Ocean. Height and weight and BP were measured. Three cohorts of children examined twice were analyzed: 1606 children surveyed at age 5.5 and 9.1, 2557 at age 9.2 and 12.5, and 2065 at age 12.5 and 15.5, respectively. Weights at birth and at one year were extracted from medical files. Weights were expressed as Z-scores and growth was defined as a change in weight Z-scores (corresponding to weight centile crossing). The association between BP (at age 5.5, 9.2, 12.5, and 15.5) and weight at different times was assessed by linear regression. Using results of regression models of BP on all successive weights, life course plots were drawn by plotting regression coefficients against age at which weight was measured. The figure shows a life course plot of systolic BP in boys aged 15.5. Results: Without adjustment for current weight (at the time of BP measurement), birth weight was not associated with current BP, irrespective of age, excepted for girls at age 15.5 for whom a modest positive association was found. When adjusted for current weight, birth weight was negatively and modestly associated with current BP. BP was strongly associated with current weight, irrespective of age. Life course plots showed that BP was strongly associated with growth during the few preceding years but not with growth during earlier years, except for growth during the first year of life which tended to be associated with systolic BP. Conclusions: Our findings suggest that BP during childhood and adolescence is mainly determined by current body weight and recent growth.

Birth weight, weight change, and blood pressure during childhood and adolescence: a school-based multiple cohort study.

OBJECTIVE: We assessed the association between birth weight, weight change, and current blood pressure (BP) across the entire age-span of childhood and adolescence in large school-based cohorts in the Seychelles, an island state in the African region. METHODS: Three cohorts were analyzed: 1004 children examined at age 5.5 and 9.1 years, 1886 children at 9.1 and 12.5, and 1575 children at 12.5 and 15.5, respectively. Birth and 1-year anthropometric data were gathered from medical files. The outcome was BP at age 5.5, 9.1, 12.5 or 15.5 years, respectively. Conditional linear regression analysis was used to estimate the relative contribution of changes in weight (expressed in z-score) during different age periods on BP. All analyses were adjusted for height. RESULTS: At all ages, current BP was strongly associated with current weight. Birth weight was not significantly associated with current BP. Upon adjustment for current weight, the association between birth weight and current BP tended to become negative. Conditional linear regression analyses indicated that changes in weight during successive age periods since birth contributed substantially to current BP at all ages. The strength of the association between weight change and current BP increased throughout successive age periods. CONCLUSION: Weight changes during any age period since birth have substantial impact on BP during childhood and adolescence, with BP being more responsive to recent than earlier weight changes.

Mycelial compatibility and aggressiveness of Sclerotinia sclerotiorum isolates from Brazil and the United States

The objective of this work was to evaluate the genetic diversity among Sclerotinia sclerotiorum isolates from Brazil and the USA, assess their aggressiveness variability, and verify the existence of an isolate-cultivar interaction. Isolate variability was determined by mycelial compatibility grouping (MCG), and isolate aggressiveness by cut-stem inoculations of soybean cultivars. Two experiments for MCGs and two for aggressiveness were conducted with two sets of isolates. The first set included nine isolates from the same soybean field in Brazil and nine from the Midwest region of the USA. The second set included 16 isolates from several regions of Brazil and one from the USA. In the first set, 18 isolates formed 12 different MCGs. In the second set, 81% of the isolates from Brazil grouped into a single MCG. No common MCGs were observed among isolates from Brazil and the USA. The isolates showed aggressiveness differences in the first set, but not in the second. Although aggressiveness differed in the first set, soybean cultivars and isolates did not interact significantly. Cultivar rank remained the same, regardless of the genetic diversity, aggressiveness difference, and region or country of origin of the isolate. Results from screening of soybean cultivars, performed by the cut-stem method in the USA, can be used as reference for researchers in Brazil.

Systematic review protocol to define classical IgE-associated diseases from birth to adolescence: the MeDALL study

BACKGROUND: Classical disease phenotypes are mainly based on descriptions of symptoms and the hypothesis that a given pattern of symptoms provides a diagnosis. With refined technologies there is growing evidence that disease expression in patients is much more diverse and subtypes need to be defined to allow a better targeted treatment. One of the aims of the Mechanisms of the Development of Allergy Project (MeDALL,FP7) is to re-define the classical phenotypes of IgE-associated allergic diseases from birth to adolescence, by consensus among experts using a systematic review of the literature and identify possible gaps in research for new disease markers. This paper describes the methods to be used for the systematic review of the classical IgE-associated phenotypes applicable in general to other systematic reviews also addressing phenotype definitions based on evidence. METHODS/DESIGN: Eligible papers were identified by PubMed search (complete database through April 2011). This search yielded 12,043 citations. The review includes intervention studies (randomized and clinical controlled trials) and observational studies (cohort studies including birth cohorts, case-control studies) as well as case series. Systematic and non-systematic reviews, guidelines, position papers and editorials are not excluded but dealt with separately. Two independent reviewers in parallel conducted consecutive title and abstract filtering scans. For publications where title and abstract fulfilled the inclusion criteria the full text was assessed. In the final step, two independent reviewers abstracted data using a pre-designed data extraction form with disagreements resolved by discussion among investigators. DISCUSSION: The systematic review protocol described here allows to generate broad,multi-phenotype reviews and consensus phenotype definitions. The in-depth analysis of the existing literature on the classification of IgE-associated allergic diseases through such a systematic review will 1) provide relevant information on the current epidemiologic definitions of allergic diseases, 2) address heterogeneity and interrelationships and 3) identify gaps in knowledge.

Current Issues in the Diagnosis and Classification of Peripheral T-Cell Lymphomas

Mature T-cell and T/NK-cell neoplasms are both uncommon and heterogeneous, among the broad category of non-Hodgkin's lymphomas. Due to the lack of specific genetic alterations in the vast majority of cases, most currently defined entities show overlapping morphologic and immunophenotypic features and therefore pose a challenge to the diagnostic pathologist. The goal of the symposium is to address current criteria for the recognition of specific subtypes of T-cell lymphoma, and to highlight new data regarding emerging immunophenotypic or molecular markers. This activity has been designed to meet the needs of practicing pathologists, and residents and fellows enrolled in training programs in anatomic and clinical pathology. It should be a particular benefit to those with an interest in hematopathology. Upon completion of this activity, participants should be better able to: -To be able to state the basis for the classification of mature T-cell malignancies involving nodal and extranodal sites. -To recognize and accurately diagnose the various subtypes of nodal and extranodal peripheral T-cell lymphomas. -To utilize immunohistochemical and molecular tests to characterize atypical T-cell proliferations. -To recognize and accurately diagnose T-cell lymphoproliferative lesions involving the skin and gastrointestinal tract, and be able to provide guidance regarding their clinical aggressiveness and management -To be able to utilize flow cytometric data to identify diverse functional T-cell subsets.

Emotional and effortful control abilities in 42-month-old very preterm and full-term children.

BACKGROUND: Very preterm (VP) infants are at greater risk for cognitive difficulties that may persist during school-age, adolescence and adulthood. Behavioral assessments report either effortful control (part of executive functions) or emotional reactivity/regulation impairments. AIMS: The aim of this study is to examine whether emotional recognition, reactivity, and regulation, as well as effortful control abilities are impaired in very preterm children at 42 months of age, compared with their full-term peers, and to what extent emotional and effortful control difficulties are linked. STUDY DESIGN: Children born very preterm (VP; < 29 weeks gestational age, n=41) and full-term (FT) aged-matched children (n=47) participated in a series of specific neuropsychological tests assessing their level of emotional understanding, reactivity and regulation, as well as their attentional and effortful control abilities. RESULTS: VP children exhibited higher scores of frustration and fear, and were less accurate in naming facial expressions of emotions than their aged-matched peers. However, VP children and FT children equally performed when asked to choose emotional facial expression in social context, and when we assessed their selective attention skills. VP performed significantly lower than full terms on two tasks of inhibition when correcting for verbal skills. Moreover, significant correlations between cognitive capacities (effortful control) and emotional abilities were evidenced. CONCLUSIONS: Compared to their FT peers, 42 month-olds who were born very preterm are at higher risk of exhibiting specific emotional and effortful control difficulties. The results suggest that these difficulties are linked. Ongoing behavioral and emotional impairments starting at an early age in preterms highlight the need for early interventions based on a better understanding of the relationship between emotional and cognitive difficulties.

The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): A review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals.

Progressive pseudorheumatoid dysplasia (PPRD) is a genetic, non-inflammatory arthropathy caused by recessive loss of function mutations in WISP3 (Wnt1-inducible signaling pathway protein 3; MIM 603400), encoding for a signaling protein. The disease is clinically silent at birth and in infancy. It manifests between the age of 3 and 6 years with joint pain and progressive joint stiffness. Affected children are referred to pediatric rheumatologists and orthopedic surgeons; however, signs of inflammation are absent and anti-inflammatory treatment is of little help. Bony enlargement at the interphalangeal joints progresses leading to camptodactyly. Spine involvement develops in late childhood and adolescence leading to short trunk with thoracolumbar kyphosis. Adult height is usually below the 3rd percentile. Radiographic signs are relatively mild. Platyspondyly develops in late childhood and can be the first clue to the diagnosis. Enlargement of the phalangeal metaphyses develops subtly and is usually recognizable by 10 years. The femoral heads are large and the acetabulum forms a distinct "lip" overriding the femoral head. There is a progressive narrowing of all articular spaces as articular cartilage is lost. Medical management of PPRD remains symptomatic and relies on pain medication. Hip joint replacement surgery in early adulthood is effective in reducing pain and maintaining mobility and can be recommended. Subsequent knee joint replacement is a further option. Mutation analysis of WISP3 allowed the confirmation of the diagnosis in 63 out of 64 typical cases in our series. Intronic mutations in WISP3 leading to splicing aberrations can be detected only in cDNA from fibroblasts and therefore a skin biopsy is indicated when genomic analysis fails to reveal mutations in individuals with otherwise typical signs and symptoms. In spite of the first symptoms appearing in early childhood, the diagnosis of PPRD is most often made only in the second decade and affected children often receive unnecessary anti-inflammatory and immunosuppressive treatments. Increasing awareness of PPRD appears to be essential to allow for a timely diagnosis. © 2012 Wiley Periodicals, Inc.

Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents.

Dual-energy X-ray absorptiometry (DXA) is the most widely used technical instrument for evaluating bone mineral content (BMC) and density (BMD) in patients of all ages. However, its use in pediatric patients, during growth and development, poses a much more complex problem in terms of both the technical aspects and the interpretation of the results. For the adults population, there is a well-defined term of reference: the peak value of BMD attained by young healthy subjects at the end of skeletal growth. During childhood and adolescence, the comparison can be made only with healthy subjects of the same age, sex and ethnicity, but the situation is compounded by the wide individual variation in the process of skeletal growth (pubertal development, hormone action, body size and bone size). The International Society for Clinical Densitometry (ISCD) organized a Pediatric Position Development Conference to discuss the specific problems of bone densitometry in growing subjects (9-19 years of age) and to provide essential recommendations for its clinical use.

Les marquages corporels à l'adolescence : expression d'un mal-être profond? : se marquer pour se démarquer : du repérage des signes au choix des réponses adaptées

La problématique des marquages corporels en tant que pratiques ancestrales s'insèrent dans des formes contemporaines d'inscription corporelle. Nous nous sommes permis d'essayer de savoir s'il s'agissait toujours d'une expression d'un malaise psychologique important ? Quelles peuvent en être les conséquences ? Pourquoi marquer le corps ? La mise en oeuvre de ce travail s'est articulée en deux phases, au départ, nous avons opéré par une pré-enquête d'envergure qui a regroupé 200 adolescents (10 filles et 190 garçons). Ensuite et dans un deuxième temps nous avons interrogé dix adolescents qui se marquent la peau dont trois garçons, âgés de quinze à dix-neuf ans. Grâce à une « tri approche » : Entretien clinique, tests du Rorschach et du TAT. Les résultats auxquels nous sommes parvenus peuvent être résumés comme suit : ces pratiques expriment une souffrance qui peine à trouver une voie d'expression symbolique autre que le corps, l'angoisse et la relation d'objet du type anaclitique, l'organisation défensive renseigneraient essentiellement sur des défenses narcissiques, centrées notamment autour du clivage et le retournement sur soi, une identité fragile marquée par une image du corps et représentation de soi fragiles et un sur (dés) investissement des limites. Il s'agit d'une emprise sur le corps et sur les marques mêmes, permettant de retrouver l'objet et le recréer. À partir des principaux résultats obtenus, nous envisageons de travailler, en filigrane sur les spécificités des types de marquages corporels existant en Algérie. En effet si le présent travail s'est étayé sur une analyse prônant la globalité, un comparatif entre les types de marquages, de même, l'établissement d'un lien entre la symbolique de certaines pratiques et les soubassements psychodynamiques qui l'entourent, serait d'un apport considérable dans la compréhension du fait étudié dans ses moindres « recoins ». -- The problem of the physical markings as ancestral practices fit into contemporary forms of physical registration. We allowed to try to know if it was always about an expression of an important psychological illness? What can be the consequences? Why to mark the body? The application of this work articulated in two phases, at first, we operated by a large-scale pre- inquiry which grouped together 200 teenagers (10 girls and 190 boys). Then and in the second time we interrogated ten teenagers who mark the skin among which three boys, from fifteen to nineteen years old. Thanks to one « sorting approaches »: clinical Interview, tests of Rorschach and TAT. The results which we reached can be summarized as follows: these practices express a suffering which has difficulty in finding a way of symbolic expression other one than the body, the fear and the relation of object of the type anaclitique, the defensive organization would inform essentially about narcissistic defences, centred notably around the cleavage and the reversal on one, a fragile identity marked by an image of the body and the representation of one fragile and one on investment of the limits. It is about an influence on the body and on the marks, allowing to find the object and to recreate it. From the main obtained results, we intend to work, between the lines on the specificities of the types of physical markings existing in Algeria. Indeed if the present work supported on an analysis lauding the global nature, a comparative degree between the types of markings, also, the establishment of a link between the symbolism of certain practices and the bases psychodynamiques who surround him, would be of a considerable contribution in the understanding of the fact studied in its slightest « hidden recesses ».

Performance of parental history for the targeted screening of hypertension in children.

OBJECTIVES: Several guidelines recommend universal screening for hypertension in childhood and adolescence. Targeted screening to children with parental history of hypertension could be a more efficient strategy than universal screening. Therefore, we assessed the association between parental history of hypertension and hypertension in children, and estimated the sensitivity, specificity, negative, and positive predictive values of parental history of hypertension for hypertension in children. METHODS: The present study was a school-based cross-sectional study including 5207 children aged 10-14 years from all public 6th grade classes in the Canton of Vaud, Switzerland. Children had hypertension if they had sustained elevated blood pressure over three separate visits. RESULTS: In children, the prevalence of hypertension was 2.2%. Some 8.5% of mothers and 12.9% of fathers reported to be hypertensive. Maternal history of hypertension (odds ratio 2.0, 95% confidence interval 1.2-3.3) and paternal history of hypertension (odds ratio 2.2, 95% confidence interval 1.4-3.6) were independent risk factors for hypertension in children. Nevertheless, the sensitivity of parental history of hypertension for the identification of hypertension in children was low (from 4% for both parents' positive history up to 41% for at least one parent's positive history). Positive predictive values were also low (between 4 and 5%). CONCLUSION: Children with hypertensive parents were at higher risk of hypertension. Nevertheless, parental history of hypertension helped only marginally to identify hypertension in offspring. Targeting screening only toward children with a parental history of hypertension may not be a substantially better strategy to identify hypertension in children compared with universal screening.

Spanish adaptation of the Expectancy Questionnaire (EQ) about alcohol effects in adolescents

Background: Alcohol-related expectancies are especially relevant in relation to alcohol consumption during adolescence. The main aim of this study was to adapt and translate into Spanish (Castilian) the Expectancy Questionnaire (EQ), and to study its psychometric properties in adolescents. Method: The sample was composed of 514 adolescents (57.20% female, mean age = 15.21; SD = .63) who completed the EQ and the alcohol consumption questionnaire AIS-UJI. Results: Confi rmatory factor analysis indicated that an eight-factor model, grouped into two general factors of positive and negative expectancies, had acceptable fi t indices. Cronbach’s alphas ranged from .75 to .96. Finally, the structural equation model showed that positive expectancies were positively related to alcohol use, whereas negative expectancies were negatively related to drinking. Conclusions: Results showed that the Spanish version of the EQ for adolescents is a valid and reliable questionnaire to measure expectancies about alcohol effects.

Transition en transplantation rénale [Transition in kidney transplantation].

La transition en transplantation rénale constitue une étape importante dans la vie d'un jeune adolescent greffé. Durant cette période, les impératifs de la greffe se heurtent aux changements physiologiques et psychologiques de l'adolescence, avec un risque augmenté de non-observance thérapeutique et donc de perte du greffon. Il n'existe pas encore un modèle optimal de transition unanimement accepté, mais il a été démontré que la mise en place d'une équipe multidisciplinaire de professionnels pédiatres et adultes, ayant une formation dans la gestion des adolescents et jeunes adultes, est bénéfique. Cette équipe doit assurer une transition progressive des jeunes patients vers la clinique adulte selon un plan bien défini. Transition from pediatric to adult care in renal transplantation has emerged as a critical step in the life of a young kidney recipient. During this phase, young patients are faced with the physiological and psychological changes associated with adolescence that can lead to non-compliance and potentially graft loss. To date, there is not a unique accepted model of transition, however it has been proved that the presence of a multidisciplinary team including specialists in adolescent management and in the transition from pediatric to adult transplant care is beneficial during this at-risk phase. The goal of this team is to ensure a progressive transition of the patients according to a precise plan and time line.

The role of ubiquitin specific peptidase 15 (USP 15) in human glioblastoma

Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumour. Despite the aggressiveness of the applied therapy, the prognosis remains poor with a median survival to of about 15 months. It is important to identify new candidate genes that could have clinical application in this disease. Previous gene expression studies from human GBM samples in our laboratory, revealed Ubiquitin Specific Peptidase 15 (USP15) as a gene with low expression, significantly associated with genomic deletions of the chromosomal region encompassing the USP15 locus. USP15 belongs to the ubiquitin-specific protease (USPs) family of which the main role is the reversion of ubiquitination and thereby stabilization of substrates. Previously, USP15 has been suggested to have a tumour suppressor function via its substrates APC and Caspase 3. We established GBM cell lines that stably express USP15 wt or its catalytic mutant. USP15 expression impairs cell growth by inhibiting cell cycle progression. On the other hand USP15 depletion in GBM cell lines induces cell cycle progression and proliferation. In order to identify the molecular pathways in which USP15 is implicated we aimed to identify protein-binding partners in the GBM cell line LN-229 by Mass spectrometry. As a result we identified eight new proteins that interact with USP15. These proteins are involved in important cellular processes like cytokinesis, cell cycle, cellular migration, and apoptosis. Three of these protein interactions were confirmed by co-immunoprecipitation in four GBM cell lines LN-229, LN428, LN18, LN-Z308. One of the binding proteins is HECTD1 E3 ligase of which the murine homologue promotes the APC-Axin interaction to negatively regulate the Wnt pathway. USP15 can de-ubiquitinate HECTD1 in the LN229 cell line while its depletion led to decrease of HECTD1 in GBM cell lines suggesting stabilizing role for USP15. Moreover, HECTD1 stable expression in LN229 inhibits cell cycle, while its depletion induces cell cycle progression. These results suggest that the USP15-HECTD1 interaction might enhance the antiproliferative effect of HECTD1 in GBM cell lines. Using the TOPflash/FOPflash luciferase system we showed that HECTD1 and USP15 overexpression can attenuate WNT pathway activity, and decrease the Axin2 expression. These data indicate that this new protein interaction of USP15 with HECTD1 results in negative regulation of the WNT pathway in GBM cell lines. Further investigation of the regulation of this interaction or of the protein binding network of HECTD1 in GBM may allow the discovery of new therapeutic targets. Finally PTPIP51 and KIF15 are the other two identified protein partners of USP15. These two proteins are involved in cell proliferation and their depletion in LN-229 cell line led to induction of cell cycle progression. USP15 displays a stabilizing role for them. Hence, these results show that the tumour suppressive role of USP15 in GBM cell line via different molecular mechanisms indicating the multidimensional function of USP15. Résumé Le glioblastome (GBM) est la tumeur primaire la plus fréquente et la plus agressive du cervau caractérisée par une survie médiane d'environ à 15 mois. De précédant travaux effectués au sein de notre laboratoire portant sur l'étude de l'expression de gènes pour des échantillons humains de GBM ont montré que le gène Ubiquitin Specific Peptidase 15 (USP1S) était significativement associée à une délétion locales à 25% des cas. Initialement, les substrats protéiques APC et CaspaseS de USP15 ont conduit à considérer cette protéine comme un suppresseur de tumeur. USP15 appartient à la famille protèsse spécifique de l'ubiquitine (USPs) dont le rôle principal est la réversion de l'ubiquitination et la stabilisation de substrats. Par conséquent, nous avons établi des lignées de cellules de glioblastome qui expriment de manière stable USP15 ou bien son mutant catalytique. Ainsi, nous avons ainsi démontré que l'expression de l'USP15 empêche la croissance cellulaire en inhibant la progression du cycle cellulaire. Inversement, la suppression de l'expression du gène USP15 dans les lignées cellulaires de glioblastome induit la progression du cycle cellulaire et la prolifération. Afin d'identifier les voies moléculaires dans lesquelles sont impliquées USP15, nous avons cherché à identifier les partenaires de liaisons protéiques par spectrométrie de masse dans la lignée cellulaire LN-229. Ainsi, huit nouvelles protéines interagissant avec USP15 ont été identifiées dont la ligase E3 HECTD1. L'homologue murin de Hectdl favorise l'interaction APC-Axin en régulant négativement la voie de signalisation de Wnt. USP15 interagit en désubiquitinant HECTD1 dans la lignée cellulaire LN-229 et provoque ainsi l'atténuation de l'activité de cette voie de signalisation. En conclusion, HECTD1, en interagissant avec USP15, joue un rôle de suppresseur de tumeur dans les lignées cellulaire de GBM.

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study.

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added as a covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors.