WorldWideScience

Sample records for early onset obesity

  1. Early Onset Childhood Obesity and Risk of Metabolic Syndrome

    Centers for Disease Control (CDC) Podcasts

    2017-10-09

    This podcast features Lorena Pacheco, a doctoral student at the University of California San Diego and one of the winners of PCD’s 2017 Student Research Paper Contest. Lorena answers questions about her winning research, which focuses on the relationship between early onset obesity as a risk factor for increased metabolic syndrome in Chilean children.  Created: 10/9/2017 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/9/2017.

  2. Concordance of bioactive vs. total immunoreactive serum leptin levels in children with severe early onset obesity.

    Science.gov (United States)

    Stanik, Juraj; Kratzsch, Jürgen; Landgraf, Kathrin; Scheuermann, Kathrin; Spielau, Ulrike; Gausche, Ruth; Gasperikova, Daniela; Kiess, Wieland; Körner, Antje

    2017-01-01

    Leptin secreted from adipose tissue signals peripheral energy status to the brain. Monogenic leptin deficiency results in severe early onset obesity with hyperphagia. Recently, a similar phenotype of inactivating leptin mutations but with preserved immunoreactivity and hence normal circulating immunoreactive leptin has been reported. We aimed to evaluate the proportion of bioactive leptin serum levels (compared to immunoreactive leptin) as a biomarker for the screening of leptin gene mutations causing monogenic obesity. Furthermore, we aimed to compare the immunoreactive and bioactive leptin levels associations with parameters of insulin resistance and insulin secretion in obese children and adolescents. We measured bioactive and immunoreactive leptin levels by enzyme-linked immunosorbent assays in fasting serum samples of 70 children with severe (BMI SDS >3) non-syndromic obesity with onset leptin gene was performed in probands with proportion of bioactive/immunoreactive leptin leptin were almost identical (41.1±25.2 vs. 41.1±25.4ng/mL). In three probands with the lowest bioactive leptin proportion (leptin gene. Compared to immunoreactive leptin, bioactive leptin showed similar and slightly better statistical associations with indices of insulin resistance in correlation and multivariate analyses. In our sample selected for severe early onset childhood obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin. Nevertheless, the bioactive leptin levels were stronger associated with selected insulin secretion/resistance indices than the immunoreactive leptin levels.

  3. Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation

    Directory of Open Access Journals (Sweden)

    Eng Christine M

    2011-07-01

    Full Text Available Abstract Isolated hypocortisolism due to ACTH deficiency is a rare condition that can be caused by homozygous or compound heterozygous mutations in the gene encoding proopiomelanocortin (POMC. Loss of function mutations of POMC gene typically results in adrenal insufficiency, obesity and red hair. We describe an 18 month old Hispanic female with congenital adrenal insufficiency, a novel POMC mutation and atypical clinical features. The patient presented at the age of 9 months with hypoglycemia and the endocrine evaluation resulted in a diagnosis of ACTH deficiency. She developed extreme weight gain prompting sequence analysis of POMC, which revealed a homozygous c.231C > A change which is predicted to result in a premature termination codon. The case we report had obesity, hypocortisolism but lacked red hair which is typical for subjects with POMC mutations. Mutations of POMC should be considered in individuals with severe early onset obesity and adrenal insufficiency even when they lack the typical pigmentary phenotype.

  4. Mutation screen and association studies for the fatty acid amide hydrolase (FAAH gene and early onset and adult obesity

    Directory of Open Access Journals (Sweden)

    Rief Winfried

    2010-01-01

    Full Text Available Abstract Background The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH. The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity. Methods We initially assessed association of five single nucleotide polymorphisms (SNPs in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05 were further analysed in 8,491 adult individuals of a population-based cohort (KORA for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity. Results The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978 with childhood obesity (two-sided p-values between 0.06 and 0.10. Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75, the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632 with early onset extreme obesity (p-values between 0.02 and 0.03. No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05. Conclusions As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity

  5. Do rapid BMI growth in childhood and early-onset obesity offer cardiometabolic protection to obese adults in mid-life?

    DEFF Research Database (Denmark)

    Howe, Laura D; Zimmermann, Esther; Weiss, Ram

    2014-01-01

    -onset obesity may be associated with MHO. We aimed to assess whether body mass index (BMI) in childhood and early-onset obesity are associated with MHO. SETTING: General population longitudinal cohort study, Denmark. PARTICIPANTS: From 362 200 young men (mean age 20) examined for Danish national service between...... 1943 and 1977, all obese men (BMI ≥31 kg/m(2), N=1930) were identified along with a random 1% sample of the others (N=3601). Our analysis includes 2392 of these men attending a research clinic in mid-life (mean age 42). For 613 of these men, data on childhood BMI are available. We summarised childhood...... that rapid BMI growth in childhood or early-onset obesity was associated with either MHO or the MANW phenotype, for example, among obese men in mid-life, the OR for MHO comparing early-onset obesity with non-early-onset obesity was 0.97 (95% CI 0.85 to 1.10). CONCLUSIONS: We found no robust evidence...

  6. Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity

    Directory of Open Access Journals (Sweden)

    Crinò Antonino

    2009-03-01

    Full Text Available Abstract Background Melanocortin-4-receptor (MC4R mutations represent the most frequent genetic cause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show a particular phenotype characterized by early onset, severe obesity and high stature. To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype. Methods To perform this study, a multicentric approach was designed. Particularly, to be enrolled in the study subjects needed to meet the following criteria: Body mass index ≥ 3 deviation scores according to age and sex, familiar history of obesity (at least one parent obese, obesity onset before the 10 years old, height ≥ 2 deviation scores. The coding region of MC4R gene was screened in 240 obese children (mean age 8.3 ± 3.1, mean BMI 30.8 ± 5.4 and in 200 controls (mean age 8.1 ± 2.8; mean BMI 14.2 ± 2.5. Results Three mutations have been found in five obese children. The S127L (C380T, found in three unrelated children, had been described and functionally characterized previously. The Q307X (C919T and the Y332H (T994C mutations were found in two patients. Functional studies showed that only Q307X impaired protein function. Conclusion The low prevalence of MC4R mutations (1.6% in this group of obese children selected according to the obesity degree, the tall stature and the family history of obesity was similar to the prevalence observed in previous screenings performed in obese adults and in not phenotypically selected obese children.

  7. Genome wide association (GWA study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO variants.

    Directory of Open Access Journals (Sweden)

    Anke Hinney

    Full Text Available BACKGROUND: Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA for early onset (extreme obesity. METHODOLOGY/PRINCIPAL FINDINGS: a GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 single nucleotide polymorphisms for early onset extreme obesity based on 487 extremely obese young German individuals and 442 healthy lean German controls; b confirmatory analyses on 644 independent families with at least one obese offspring and both parents. We aimed to identify and subsequently confirm the 15 SNPs (minor allele frequency > or =10% with the lowest p-values of the GWA by four genetic models: additive, recessive, dominant and allelic. Six single nucleotide polymorphisms (SNPs in FTO (fat mass and obesity associated gene within one linkage disequilibrium (LD block including the GWA SNP rendering the lowest p-value (rs1121980; log-additive model: nominal p = 1.13 x 10(-7, corrected p = 0.0494; odds ratio (OR(CT 1.67, 95% confidence interval (CI 1.22-2.27; OR(TT 2.76, 95% CI 1.88-4.03 belonged to the 15 SNPs showing the strongest evidence for association with obesity. For confirmation we genotyped 11 of these in the 644 independent families (of the six FTO SNPs we chose only two representing the LD bock. For both FTO SNPs the initial association was confirmed (both Bonferroni corrected p<0.01. However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium. CONCLUSIONS/SIGNIFICANCE: Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only

  8. Do rapid BMI growth in childhood and early-onset obesity offer cardiometabolic protection to obese adults in mid-life? Analysis of a longitudinal cohort study of Danish men.

    Science.gov (United States)

    Howe, Laura D; Zimmermann, Esther; Weiss, Ram; Sørensen, Thorkild I A

    2014-04-15

    Some obese individuals have no cardiometabolic abnormalities; they are 'metabolically healthy, but obese' (MHO). Similarly, some non-obese individuals have cardiometabolic abnormalities, that is, 'metabolically at risk, normal weight' (MANW). Previous studies have suggested that early-onset obesity may be associated with MHO. We aimed to assess whether body mass index (BMI) in childhood and early-onset obesity are associated with MHO. General population longitudinal cohort study, Denmark. From 362 200 young men (mean age 20) examined for Danish national service between 1943 and 1977, all obese men (BMI ≥31 kg/m(2), N=1930) were identified along with a random 1% sample of the others (N=3601). Our analysis includes 2392 of these men attending a research clinic in mid-life (mean age 42). For 613 of these men, data on childhood BMI are available. We summarised childhood BMI growth (7-13 years) using a multilevel model. Early-onset obesity was defined as obesity at examination for national service. We defined metabolic health at the mid-life clinic as non-fasting serum cholesterol obesity (BMI ≥30 kg/m(2)) and metabolic health in mid-life. 297 of 1097 (27.1%) of obese men were metabolically healthy; 826 of 1295 (63.8%) non-obese men had at least one metabolic abnormality. There was no evidence that rapid BMI growth in childhood or early-onset obesity was associated with either MHO or the MANW phenotype, for example, among obese men in mid-life, the OR for MHO comparing early-onset obesity with non-early-onset obesity was 0.97 (95% CI 0.85 to 1.10). We found no robust evidence that early-onset obesity or rapid BMI growth in childhood is protective for cardiometabolic health.

  9. Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

    DEFF Research Database (Denmark)

    den Hoed, M; Luan, J; Langenberg, C

    2013-01-01

    BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population......10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r (2)>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age(2) in adults...... and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods. RESULTS: We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were...

  10. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants.

    Science.gov (United States)

    Serra-Juhé, Clara; Martos-Moreno, Gabriel Á; Bou de Pieri, Francesc; Flores, Raquel; González, Juan R; Rodríguez-Santiago, Benjamín; Argente, Jesús; Pérez-Jurado, Luis A

    2017-05-01

    Obesity is a multifactorial disorder with high heritability (50-75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in obesity (EOO: body mass index >3 standard deviations above the mean at obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

  11. Dietary regimens modify early onset of obesity in mice haploinsufficient for Rai1.

    Directory of Open Access Journals (Sweden)

    Joseph T Alaimo

    Full Text Available Smith-Magenis syndrome is a complex genomic disorder in which a majority of individuals are obese by adolescence. While an interstitial deletion of chromosome 17p11.2 is the leading cause, mutation or deletion of the RAI1 gene alone results in most features of the disorder. Previous studies have shown that heterozygous knockout of Rai1 results in an obese phenotype in mice and that Smith-Magenis syndrome mouse models have a significantly reduced fecundity and an altered transmission pattern of the mutant Rai1 allele, complicating large, extended studies in these models. In this study, we show that breeding C57Bl/6J Rai1+/- mice with FVB/NJ to create F1 Rai1+/- offspring in a mixed genetic background ameliorates both fecundity and Rai1 allele transmission phenotypes. These findings suggest that the mixed background provides a more robust platform for breeding and larger phenotypic studies. We also characterized the effect of dietary intake on Rai1+/- mouse growth during adolescent and early adulthood developmental stages. Animals fed a high carbohydrate or a high fat diet gained weight at a significantly faster rate than their wild type littermates. Both high fat and high carbohydrate fed Rai1+/- mice also had an increase in body fat and altered fat distribution patterns. Interestingly, Rai1+/- mice fed different diets did not display altered fasting blood glucose levels. These results suggest that dietary regimens are extremely important for individuals with Smith-Magenis syndrome and that food high in fat and carbohydrates may exacerbate obesity outcomes.

  12. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes

    Science.gov (United States)

    Doco-Fenzy, Martine; Leroy, Camille; Schneider, Anouck; Petit, Florence; Delrue, Marie-Ange; Andrieux, Joris; Perrin-Sabourin, Laurence; Landais, Emilie; Aboura, Azzedine; Puechberty, Jacques; Girard, Manon; Tournaire, Magali; Sanchez, Elodie; Rooryck, Caroline; Ameil, Agnès; Goossens, Michel; Jonveaux, Philippe; Lefort, Geneviève; Taine, Laurence; Cailley, Dorothée; Gaillard, Dominique; Leheup, Bruno; Sarda, Pierre; Geneviève, David

    2014-01-01

    Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader–Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion. PMID:24129437

  13. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes.

    Science.gov (United States)

    Doco-Fenzy, Martine; Leroy, Camille; Schneider, Anouck; Petit, Florence; Delrue, Marie-Ange; Andrieux, Joris; Perrin-Sabourin, Laurence; Landais, Emilie; Aboura, Azzedine; Puechberty, Jacques; Girard, Manon; Tournaire, Magali; Sanchez, Elodie; Rooryck, Caroline; Ameil, Agnès; Goossens, Michel; Jonveaux, Philippe; Lefort, Geneviève; Taine, Laurence; Cailley, Dorothée; Gaillard, Dominique; Leheup, Bruno; Sarda, Pierre; Geneviève, David

    2014-04-01

    Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader-Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion.

  14. Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants.

    Directory of Open Access Journals (Sweden)

    Clara Serra-Juhé

    2017-05-01

    Full Text Available Obesity is a multifactorial disorder with high heritability (50-75%, which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs, have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in 3 standard deviations above the mean at <3 years of age using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls with the validated CNVs and rare sequence variants (RSVs detected by targeted resequencing of selected CNV genes (n = 14, and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358. In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7 and the X-linked gastrin-peptide receptor (GRPR, all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

  15. Early Onset Werner Syndrome

    Directory of Open Access Journals (Sweden)

    Berna İmge Aydoğan

    2015-09-01

    Full Text Available Werner syndrome (WS is a rare autosomal recessive adult-onset progeroid disorder characterized by the early onset of aged-appearance and age-related metabolic disorders. Symptoms of premature aging usually first develop in the second-third decades of life. We report a 27-year-old female who was admitted to our clinic at the age of eighteen with hyperglycemia. She was diagnosed with diabetes and type 4 dyslipidemia at the age of seven. In her family history, her parents were first cousins and she had three healthy brothers. On her first physical examination; she had bird-like face appearance, global hair loss, beaked nose, short stature and she was overweight. She had global hair loss with gray and thin hair. Hoarseness of voice and hyperkeratosis of skin were observed. She had bilateral cataracts and moderate sensorineural hearing loss. On psychiatric examination, borderline mental retardation was detected. She had severe insulin resistance and hypertriglyceridemia despite levothyroxine, gemfibrozil, omega-3 and intensive insulin treatment. Routine lipid apheresis was performed to lower the triglyceride levels reaching 5256 mg/dL. She also had focal segmental glomerulosclerosis, hepatosteatosis, osteoporosis and epilepsy. Disease was accompanied by several congenital deformities, such as Rathke’s cleft cyst, angiomyolipoma and femoral neck hypoplasia. WS is a rare genetic disorder characterized by multiple endocrine manifestations as well as soft tissue changes. We present a case of early disturbances that were diagnosed before typical clinical signs and symptoms. We propose that WS should be kept in mind when type 2 diabetes and hyperlipidemia are diagnosed early in childhood. Turk Jem 2015; 19: 99-104

  16. Early-Onset Dementia

    DEFF Research Database (Denmark)

    Konijnenberg, Elles; Fereshtehnejad, Seyed-Mohammad; Kate, Mara Ten;

    2017-01-01

    BACKGROUND: Early-onset dementia (EOD) is a rare condition, with an often atypical clinical presentation, and it may therefore be challenging to diagnose. Specialized memory clinics vary in the type of patients seen, diagnostic procedures applied, and the pharmacological treatment given. The aim...... of this study was to investigate quality-of-care indicators in subjects with EOD from 3 tertiary memory clinics in 3 European countries. METHODS: We included 1325 newly diagnosed EOD patients, ages 65 years or younger, between January 1, 2007 and December 31, 2013, from the Danish Dementia Registry...... (Rigshospitalet, Copenhagen), the Swedish Dementia Registry ("SveDem", Karolinska University Hospital, Stockholm), and the Amsterdam Dementia Cohort (VU University Medical Center). RESULTS: The frequency of EOD among all dementia patients was significantly lower in Copenhagen (410, 20%) and Stockholm (284, 21...

  17. Alanine aminotransferase elevation in obese infants and children: a marker of early onset non alcoholic Fatty liver disease.

    Science.gov (United States)

    Engelmann, Guido; Hoffmann, Georg Friedrich; Grulich-Henn, Juergen; Teufel, Ulrike

    2014-04-01

    Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. In a prospective study 224 healthy, overweight or obese children aged 1 - 12 years were examined. Body Mass Index-Standard Deviation Score, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transpeptidase were measured. Elevated alanine aminotransferase was observed in 29% of children. 26 % of obese and 30 % of overweight children had liver enzyme elevations. Obese children had significantly higher alanine aminotransferase levels than overweight children (0.9 vs. 0.7 times the Upper Limit of Normal; P = 0.04). Elevation of liver enzymes appears in 29 % obese children in a tertiary care centre. Absolute alanine aminotransferase levels are significantly higher in obese than in overweight children. Even obese children with normal liver enzymes show signs of fatty liver disease as demonstrated by liver enzymes at the upper limit of normal.

  18. Intracellular Retention of Human Melanocortin-4 Receptor:A Molecular Mechanism Underlying Early-onset Obesity in F261S Pedigree of Chinese

    Institute of Scientific and Technical Information of China (English)

    QI-CHEN FANG; WEI-PING JIA; SHU-BING CAI; XIN-YU SHAO; RONG ZHANG; CONG-RONG WANG; YU-QIAN BAO; KUN-SAN XIANG

    2008-01-01

    To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocortin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation. Methods F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to α-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls. Results The α-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the EC value compared with the wild-type receptor (P<0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls. Conclusions The decreased response to α-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.

  19. Alanine Aminotransferase Elevation in Obese Infants and Children: A Marker of Early Onset Non Alcoholic Fatty Liver Disease

    OpenAIRE

    Engelmann, Guido; Hoffmann, Georg Friedrich; Grulich-Henn, Juergen; Teufel, Ulrike

    2014-01-01

    Background: Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. Objectives: We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. Patients and Methods: In a prospective study 224 h...

  20. The Pilot Study on Early-onset Obesity of Children%儿童早发性肥胖的探讨研究

    Institute of Scientific and Technical Information of China (English)

    姚金苹; 王晓莉; 朱文丽; 魏乾伟; 韩丽娜; 李艳辉

    2012-01-01

      目的探讨界定儿童早发性肥胖的年龄.方法采用北京市西城区体检的811名4~6岁学龄前儿童的队列资料,分析早期月龄的体质量对学龄前期体质量的影响,同时计算超重或肥胖的持续时间作为另一个指标.结果学龄前儿童肥胖检出率为7.6%、超重为17.9%;儿童在月龄为3、5、8、12、24、36和48时出现超重的儿童其在学龄前期更容易出现超重(P<0.05,OR 值在2.5到55.8之间),同样在这些时期出现肥胖的儿童学龄前期也更容易出现肥胖(P<0.05,OR 值在3.1到104.8之间).3月龄和24月龄开始的肥胖持续两年的比例最高,均为26.1%.结论对24个月龄作为“早发性肥胖”的最早月龄进行进一步探讨.%  Objective  Try to define the age of the children with early-onset obesity. Methods  Analysis the influence of the weight in the early month on the weight in preschool with the cohort data of 811 children aged 4~6 years, who had accepted physical check regularly after birth, and calculated another indicator the duration of overweight and obesity at the same time. Results The prevalence of obesity and overweight in 4~6 years children in Xicheng District of Beijing were 7.6% and 17.9% respectively; The children with overweight at the age of 3, 5, 8, 12, 24, 36 and 48 months were more possible to overweight at the age of preschool(P<0.05,OR value from 2.5 to 55.8),and the obesity was the same, too(P<0.05,OR value from 3.1 to 104.8). The highest proportion of continuous obesity which last 2 years were onset at 3 months and 24 months, both were 26.1%.Conclusion The twenty-fourth month as the earliest age for "early-onset obesity"could be further investigation.

  1. Genetic variance in the spinocerebellar ataxia type 2 (ATXN2 gene in children with severe early onset obesity.

    Directory of Open Access Journals (Sweden)

    Karla P Figueroa

    Full Text Available BACKGROUND: Expansion of a CAG repeat in the coding region of exon 1 in the ATXN2 gene located in human chromosome 12q24.1 causes the neurodegenerative disease spinocerebellar ataxia type 2 (SCA2. In contrast to other polyglutamine (polyQ disorders, the SCA2 repeat is not highly polymorphic in central European (CEU controls with Q22 representing 90% of alleles, and Q23 contributing between 5-7% of alleles. Recently, the ATXN2 CAG repeat has been identified as a target of adaptive selection in the CEU population. Mouse lines deficient for atxn2 develop marked hyperphagia and obesity raising the possibility that loss-of-function mutations in the ATXN2 gene may be related to energy balance in humans. Some linkage studies of obesity related phenotypes such as antipsychotic induced weight gain have reported significant lod scores on chromosome 12q24. We tested the hypothesis that rare loss-of-function ATXN2 variants cause obesity analogous to rare mutations in the leptin, leptin receptor and MC4R genes. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the coding region of ATXN2 including intron-exon boundaries in 92 severely obese children with a body mass index (BMI >3.2 standard deviations above age- and gender-adjusted means. We confirmed five previously identified single nucleotide polymorphisms (SNPs and three new SNPs resulting in two synonymous substitutions and one intronic polymorphism. Alleles encoding >Q22 were overrepresented in our sample of obese children and contributed 15% of alleles in children identified by their parents as white. SNP rs695872 closely flanking the CAG repeat showed a greatly increased frequency of C/C homozygotes and G/C heterozygotes compared with reported frequencies in the CEU population. CONCLUSIONS/SIGNIFICANCE: Although we did not identify variants leading to novel amino acid substitutions, nonsense or frameshift mutations, this study warrants further examination of variation in the ATXN2 gene in obesity and

  2. Early onset sebaceous carcinoma

    Directory of Open Access Journals (Sweden)

    Kaltreider Sara A

    2011-09-01

    Full Text Available Abstract Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.

  3. A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity.

    Science.gov (United States)

    Mencarelli, Monica; Zulian, Alessandra; Cancello, Raffaella; Alberti, Luisella; Gilardini, Luisa; Di Blasio, Anna Maria; Invitti, Cecilia

    2012-12-01

    Rare mutations in several genes have a critical role in the control of homeostatic mechanisms such as food-intake, energy balance and glucose metabolism. In this study, we performed a mutational screening in a 58-year-old woman presenting early-onset type 2 diabetes and central obesity. The entire coding regions of MC4R, MC3R, HNF1A, GCK and POMC (pro-opiomelanocortin) genes were analyzed by direct sequencing. A new missense mutation was identified within the POMC gene signal peptide sequence, resulting in a heterozygous substitution of an arginine for a glycine at codon 15 (p.A15G) that was excluded in 300 healthy normal weight controls. The mutation segregated in the family and was associated with overweight, type 2 diabetes, hypertension and coronary heart disease in the carriers. Functional studies demonstrated that POMC protein was not detectable in β-TC3 cells transfected with A15G-POMC vector as well as in their culture media, despite POMC mRNA levels were comparable for amount and stability to those of wild-type-transfected cells. In silico RNA folding prediction indicated that the mutation gives rise to a different RNA secondary structure, suggesting that it might affect translation and protein synthesis. To the best of our knowledge, this is the first report addressing the functional consequences of a mutation in the signal peptide of POMC. These findings further support the hypothesis that POMC-derived peptides might have a role in the control of peripheral glucose metabolism and suggest that disruption of central POMC secretion might represent an additional link between type 2 diabetes and obesity.

  4. The development of youth-onset severe obesity in urban US girls

    Directory of Open Access Journals (Sweden)

    Kathleen M. McTigue

    2015-12-01

    Conclusions: Youth-onset severe obesity warrants particular concern in urban girls due to high prevalence and an increasing secular prevalence trend. Late childhood and early adolescence may represent a key developmental window for prevention and treatment, but is too late to prevent youth-onset severe obesity entirely.

  5. Early prevention of obesity

    Directory of Open Access Journals (Sweden)

    Claudio Maffeis

    2014-06-01

    Full Text Available Childhood obesity is the metabolic disorder with the highest prevalence in both children and adults. Urgency to treat and prevent childhood obesity is based on the clear evidence that obesity tends to track from childhood to adulthood, is associated to morbidity also in childhood and to long-term mortality. Early life, i.e., intrauterine life and the first two years, is a sensitive window for prevention. Anatomical and functional maturation of the hypothalamic structures devoted to regulating energy intake and expenditure and body size mainly occurs in the first 1,000 days of life. Therefore, factors affecting the foetal exposition to maternal metabolic environment and early postnatal nutrition are crucial in modulating the definition of the metabolic programming processes in the brain. Maternal diseases, mainly malnutrition for defect or excess, obesity and diabetes, placental disorders and dysfunctions, maternal use of alcohol and drugs, smoking, affect long term metabolic programming of the foetus with lifelong consequences. Similarly, early nutrition contributes to complete the long-term metabolic regulating framework initiated in the uterus. Breastfeeding, adequate weaning, attention to portion size and diet composition are potential tools for reducing the obesity risk later in childhood. Longitudinal randomized controlled studies are needed for exploring the efficacy of obesity prevention strategies initiated after conception.Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  6. Genetics Home Reference: early-onset glaucoma

    Science.gov (United States)

    ... Home Health Conditions early-onset glaucoma early-onset glaucoma Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Glaucoma is a group of eye disorders in which ...

  7. Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups.

    Science.gov (United States)

    Scherag, André; Dina, Christian; Hinney, Anke; Vatin, Vincent; Scherag, Susann; Vogel, Carla I G; Müller, Timo D; Grallert, Harald; Wichmann, H-Erich; Balkau, Beverley; Heude, Barbara; Jarvelin, Marjo-Riitta; Hartikainen, Anna-Liisa; Levy-Marchal, Claire; Weill, Jacques; Delplanque, Jérôme; Körner, Antje; Kiess, Wieland; Kovacs, Peter; Rayner, Nigel W; Prokopenko, Inga; McCarthy, Mark I; Schäfer, Helmut; Jarick, Ivonne; Boeing, Heiner; Fisher, Eva; Reinehr, Thomas; Heinrich, Joachim; Rzehak, Peter; Berdel, Dietrich; Borte, Michael; Biebermann, Heike; Krude, Heiko; Rosskopf, Dieter; Rimmbach, Christian; Rief, Winfried; Fromme, Tobias; Klingenspor, Martin; Schürmann, Annette; Schulz, Nadja; Nöthen, Markus M; Mühleisen, Thomas W; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Boes, Tanja; Illig, Thomas; Froguel, Philippe; Hebebrand, Johannes; Meyre, David

    2010-04-22

    Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85x10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84x10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at approximately 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree

  8. Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups.

    Directory of Open Access Journals (Sweden)

    André Scherag

    2010-04-01

    Full Text Available Meta-analyses of population-based genome-wide association studies (GWAS in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions generalized to (i the population level and (ii to adults by genotyping another 31,182 individuals (GENERALIZATION step. Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85x10(-8 in the DISCOVERY step and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene and MSRA (methionine sulfoxide reductase A gene; p = 4.84x10(-7, the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at approximately 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial

  9. Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

    Science.gov (United States)

    Scherag, André; Dina, Christian; Hinney, Anke; Vatin, Vincent; Scherag, Susann; Vogel, Carla I. G.; Müller, Timo D.; Grallert, Harald; Wichmann, H.-Erich; Balkau, Beverley; Heude, Barbara; Jarvelin, Marjo-Riitta; Hartikainen, Anna-Liisa; Levy-Marchal, Claire; Weill, Jacques; Delplanque, Jérôme; Körner, Antje; Kiess, Wieland; Kovacs, Peter; Rayner, Nigel W.; Prokopenko, Inga; McCarthy, Mark I.; Schäfer, Helmut; Jarick, Ivonne; Boeing, Heiner; Fisher, Eva; Reinehr, Thomas; Heinrich, Joachim; Rzehak, Peter; Berdel, Dietrich; Borte, Michael; Biebermann, Heike; Krude, Heiko; Rosskopf, Dieter; Rimmbach, Christian; Rief, Winfried; Fromme, Tobias; Klingenspor, Martin; Schürmann, Annette; Schulz, Nadja; Nöthen, Markus M.; Mühleisen, Thomas W.; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Boes, Tanja; Illig, Thomas; Froguel, Philippe; Hebebrand, Johannes; Meyre, David

    2010-01-01

    Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85×10−8 in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84×10−7), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at ∼1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between

  10. Early-Onset Neonatal Sepsis

    Science.gov (United States)

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  11. Early- versus Late-Onset Systemic Sclerosis

    Science.gov (United States)

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  12. Obesity and late-onset hypogonadism.

    Science.gov (United States)

    Corona, G; Vignozzi, L; Sforza, A; Mannucci, E; Maggi, M

    2015-12-15

    Obesity and male hypogonadism (HG) are often associated, as demonstrated in all cross-sectional studies. Prospective studies have indicated that i) having HG at baseline increases the risk of visceral obesity (and metabolic syndrome) and that ii) obesity induces incident HG. Hence, there is a bidirectional relationship between the two conditions. This is the main topic of this review, along with some pathogenic considerations. Meta-analysis of intervention studies indicates that treating obesity is a very efficient treatment for obesity-induced HG. The mechanism by which obesity induces HG has not yet been completely understood, but dietary-induced hypothalamic inflammation, along with a decreased GnRH release, is plausible. Among patients seeking medical care for obesity, the proportion of HG is relatively high. The prevalence of obesity among patients referring for sexual dysfunction is also elevated. Hence, in symptomatic, obese, hypogonadal subjects, testosterone supplementation (TS) can be considered. Whereas long-term uncontrolled register studies suggest that TS could decrease weight, analysis of controlled studies only support a parallel increase in lean mass and decrease in fat mass, with a resulting null effect on weight. Considering that T induces an increase in muscle mass, it is conceivable that the amount of activity obese people can undertake after TS will increase, allowing a closer adherence to physical exercise programs. Some studies, here meta-analyzed, support this concept.

  13. Early life origins of obesity.

    Science.gov (United States)

    Newnham, John P; Pennell, Craig E; Lye, Stephen J; Rampono, Jonathan; Challis, John R G

    2009-06-01

    There is increasing evidence that obesity has its origins in early life. Predisposition is based on interactions between the genome and environmental influences acting through epigenetic modifications. Individuals most at risk are those whose ancestral line has made a rapid transition from a traditional to a Westernized style of life. The process involves not only metabolism, but also behavior. As a result, those people who are most at risk of obesity may be those least likely to respond to educational programs based on lifestyle modification. Understanding the mechanisms and pathways that underpin the early origins of obesity is vital if we are to make progress in addressing this major problem of modern life.

  14. Disruption of hypothalamic leptin signaling in mice leads to early-onset obesity, but physiological adaptations in mature animals stabilize adiposity levels.

    Science.gov (United States)

    Ring, Laurence E; Zeltser, Lori M

    2010-08-01

    Distinct populations of leptin-sensing neurons in the hypothalamus, midbrain, and brainstem contribute to the regulation of energy homeostasis. To assess the requirement for leptin signaling in the hypothalamus, we crossed mice with a floxed leptin receptor allele (Leprfl) to mice transgenic for Nkx2.1-Cre, which drives Cre expression in the hypothalamus and not in more caudal brain regions, generating LeprNkx2.1KO mice. From weaning, LeprNkx2.1KO mice exhibited phenotypes similar to those observed in mice with global loss of leptin signaling (Leprdb/db mice), including increased weight gain and adiposity, hyperphagia, cold intolerance, and insulin resistance. However, after 8 weeks of age, LeprNkx2.1KO mice maintained stable adiposity levels, whereas the body fat percentage of Leprdb/db animals continued to escalate. The divergence in the adiposity phenotypes of Leprdb/db and LeprNkx2.1KO mice with age was concomitant with increased rates of linear growth and energy expenditure in LeprNkx2.1KO mice. These data suggest that remaining leptin signals in LeprNkx2.1KO mice mediate physiological adaptations that prevent the escalation of the adiposity phenotype in adult mice. The persistence of severe adiposity in LeprNkx2.1KO mice, however, suggests that compensatory actions of circuits regulating growth and energy expenditure are not sufficient to reverse obesity established at an early age.

  15. Early onset (childhood) monogenic neuropathies.

    Science.gov (United States)

    Landrieu, Pierre; Baets, Jonathan

    2013-01-01

    Hereditary neuropathies (HN) with onset in childhood are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission and, in selected cases, pathological findings. Especially relevant to pediatrics are the items "secondary" versus "primary" neuropathy, "syndromic versus nonsyndromic," and "period of life." Different combinations of these parameters frequently point toward specific monogenic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first concern in pediatrics. As a rule, metabolic diseases include additional, orienting symptoms or signs, and their biochemical diagnosis is based on logical algorithms. Primary, motor sensory are the most frequent HN and are dominated by demyelinating autosomal dominant (AD) forms (CMT1). Other forms include demyelinating autosomal recessive (AR) forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Peripheral motor neuron disorders are dominated by AR SMN-linked spinal muscular atrophies. (Distal) hereditary motor neuropathies represent 40 genes with various biological functions have been found to be responsible for primary HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait, and some for various types of transmission.

  16. Early Onset Inflammation in Pre-Insulin-Resistant Diet-Induced Obese Rats Does Not Affect the Vasoreactivity of Isolated Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Raun, Kirsten; Boonen, Harrie C M;

    2012-01-01

    Background: Obesity is an increasing burden affecting developed and emerging societies since it is associated with an increased risk of diabetes and consequent cardiovascular complications. Increasing evidence points towards a pivotal role of inflammation in the etiology of vascular dysfunction...

  17. Early-onset Lafora body disease

    Science.gov (United States)

    Turnbull, Julie; Girard, Jean-Marie; Lohi, Hannes; Chan, Elayne M.; Wang, Peixiang; Tiberia, Erica; Omer, Salah; Ahmed, Mushtaq; Bennett, Christopher; Chakrabarty, Aruna; Tyagi, Atul; Liu, Yan; Pencea, Nela; Zhao, XiaoChu; Scherer, Stephen W.; Ackerley, Cameron A.

    2012-01-01

    The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht–Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and

  18. Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study.

    Science.gov (United States)

    Giannini, Cosimo; Weiss, Ram; Cali, Anna; Bonadonna, Riccardo; Santoro, Nicola; Pierpont, Bridget; Shaw, Melissa; Caprio, Sonia

    2012-03-01

    We sought to determine whether obese adolescents with high-"normal" 2-h post-oral glucose tolerance test glucose levels display defects in insulin secretion and sensitivity associated with future development of impaired glucose tolerance (IGT). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and insulin secretion by applying mathematical modeling during the hyperglycemic clamp in 60 normal glucose tolerance (NGT) obese adolescents, divided into three groups based on the 2-h glucose values (DI) decreased across NGT categories, while no difference was observed between the highest NGT and IGT subjects. Age and (C)DI were the best predictors of 2-h glucose after two years. Across rising categories of normal 2-h glucose levels, NGT obese adolescents exhibit significant impairment of β-cell function relative to insulin sensitivity associated with the development of IGT.

  19. Early Onset Charcot-Marie-Tooth Disease

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-06-01

    Full Text Available The clinical signs and genetic analysis of early-onset Charcot-Marie-Tooth disease (CMT in a 2-year-old boy and members of his family are reported from the Academic Medical Center, Amsterdam, and Sophia Children’s Hospital, Rotterdam, the Netherlands.

  20. Risk assessment in neonatal early onset sepsis.

    Science.gov (United States)

    Mukhopadhyay, Sagori; Puopolo, Karen M

    2012-12-01

    The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Unusual early-onset Huntingtons disease.

    Science.gov (United States)

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  2. Nonsurgical Management of Early-onset Scoliosis.

    Science.gov (United States)

    Thorsness, Robert J; Faust, John R; Behrend, Caleb J; Sanders, James O

    2015-09-01

    Early-onset scoliosis is potentially fatal if left untreated. Although surgical management with growing instrumentation may be necessary, this is not a panacea and is associated with high complication rates. Recent evidence has demonstrated that nonsurgical treatment can be an effective early management strategy in delaying or even precluding the need for surgery, especially surgery with growing instrumentation. The goal of both nonsurgical and surgical management is to control or correct the spinal curve to allow appropriate pulmonary development while delaying definitive fusion until an appropriate skeletal age. Although more commonly used to delay surgery, serial cast correction using the Cotrel and Morel elongation-derotation-flexion technique may result in complete correction in patients with infantile idiopathic scoliosis and smaller curve magnitudes.

  3. Ethics dilemmas of early detection of obesity

    DEFF Research Database (Denmark)

    Vallgårda, Signild

    2016-01-01

    Aim: To discuss the ethics dilemmas of the early detection of overweight and obesity. Methods: Analysis of the ethical aspects of early detection. Results: The early detection of overweight and obesity entails a number of ethical dilemmas because it may both be helpful and harmful. It may help...

  4. Obesity and Cytokines in Childhood-Onset Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Nailú Angélica Sinicato

    2014-01-01

    Full Text Available Background. In systemic lupus erythematosus (SLE, atherosclerosis is attributed to traditional and lupus related risk factors, including metabolic syndrome (MetS, obesity, and inflammation. Objective. To evaluate the association between obesity, measures of body fat content, serum tumor necrosis factor alpha (TNF-α, and interleukin (IL-6 and -10 levels in childhood-onset SLE (cSLE. Methods. We screened consecutive cSLE patients followed up in the Pediatric Rheumatology Outpatient Clinic of the State University of Campinas. cSLE patients were assessed for disease and damage. Obesity was definite as body mass index (BMI ≥30 kg/m2. Serum TNF-α, IL-6, and IL-10 levels were measured by ELISA. Dual-energy X-ray absorptiometry was used to determine total fat mass, lean mass, and percent of body fat. Results. We included 52 cSLE patients and 52 controls. cSLE patients had higher serum TNF-α  (P=0.004, IL-6 (P=0.002, and IL-10 (P<0.001 levels compared to controls. We observed higher serum TNF-α  (P=0.036 levels in cSLE patients with obesity. An association between serum TNF-α levels and body fat percent (P=0.046 and total fat mass on trunk region (P=0.035 was observed. Conclusion. Serum TNF-α levels were associated with obesity and body fat content in cSLE. Our finding suggests that obesity may contribute to the increase of serum TNF-α levels in cSLE.

  5. Early-onset scoliosis: current treatment.

    Science.gov (United States)

    Cunin, V

    2015-02-01

    Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with

  6. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    Science.gov (United States)

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

  7. Association of Obesity with Onset of Puberty and Sex Hormones in Chinese Girls: A 4-Year Longitudinal Study.

    Directory of Open Access Journals (Sweden)

    Lingling Zhai

    Full Text Available To examine the influence of childhood obesity on the early onset of puberty and sex hormones in girls.Healthy girls with different percentages of body fat at baseline (40 obese, 40 normal, and 40 lean were recruited from three elementary schools in Shenyang, China. These girls (mean age 8.5 years were also matched by height, school grade, Tanner stage, and family economic status at baseline. Anthropometry, puberty characteristics, and sex hormone concentrations were measured at baseline and at each follow-up visit. The generalized estimating equation model and analysis of variance for repeated measures using a generalized linear model were used to determine the differences in puberty characteristics and sex hormones among three groups.Over 4 years, mean age of breast II onset was earlier among obese girls (8.8 years than normal girls (9.2 years and lean girls (9.3 years. The prevalence (% of early-maturation in the obese, normal, and lean groups was 25.9%, 11.1%, and 7.4%, respectively. Obesity was associated with an increased risk for breast stage II (year 2: RR, 6.3; 95% CI, 1.9-21.1 and year 3: RR, 6.9; 95% CI, 0.8-60.1. None of the girls experienced menarche in the first year; however, by the fourth year 50.0% of obese girls had menarche onset, which was higher than normal weight (27.5% and lean girls (8.1%. The mean estradiol level increased with age in the obese, normal, and lean groups. The mean estradiol concentration was higher in obese girls than in normal and lean girls throughout the 4-year period (P<0.05.Childhood obesity contributes to early onset of puberty and elevated levels of estradiol in girls.

  8. [Early onset scoliosis. What are the options?].

    Science.gov (United States)

    Farrington, D M; Tatay-Díaz, A

    2013-01-01

    The prognosis of children with progressive early onset scoliosis has improved considerably due to recent advances in surgical and non-surgical techniques and the understanding of the importance of preserving the thoracic space. Improvements in existing techniques and development of new methods have considerably improved the management of this condition. Derotational casting can be considered in children with documented progression of a <60° curve without previous surgical treatment. Both single and dual growing rods are effective, but the latter seem to offer better results. Hybrid constructs may be a better option in children who require a low-profile proximal anchor. The vertical expandable prosthetic titanium rib (VEPTR(®)) appears to be beneficial for patients with congenital scoliosis and fused ribs, and thoracic Insufficiency Syndrome. Children with medical comorbidities who may not tolerate repeated lengthenings should be considered for Shilla or Luque Trolley technique. Growth modulation using shape memory alloy staples or other tethers seem promising for mild curves, although more research is required to define their precise indications. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  9. Clinical characteristics of early- and late-onset gout

    Science.gov (United States)

    Zhang, Bingqing; Fang, Weigang; Zeng, Xuejun; Zhang, Yun; Ma, Ya; Sheng, Feng; Zhang, Xinlei

    2016-01-01

    Abstract A retrospective cross-sectional study using data from an outpatient clinic in China was conducted to investigate the clinical features of early-onset gout patients. All patients diagnosed with gout were asked about clinical characteristics of their gout and comorbid diseases. Patients presenting with acute flares were asked about common triggers before the flare. “Early-onset” gout was defined as onset of gout before 40 years and “late-onset” as onset ≥40 years. Major joint involvement, flare frequency before presentation, the cumulative number of involved joints, proportions of tophi complications at presentation, flare triggers, as well as any metabolic, cardiovascular, cerebrovascular, and renal comorbidities, were compared between the 2 groups. A total of 778 gout patients were enrolled in this study, including 449 (57.7%) in the early-onset group and 329 (42.3%) in the late-onset group. Compared with the late-onset gout patients, the early-onset gout patients had a higher proportion of ankle/mid-foot involvement (62.8% vs 48.2%, P gout patients had fewer metabolic, cardiovascular, cerebrovascular, or renal complications. Early- and late-onset gout patients had different clinical features. Early-onset seems to be influenced more by lifestyle, while late-onset patients have more complications because of comorbidities. PMID:27893683

  10. Obesity, islet cell autoimmunity, and cardiovascular risk factors in youth at onset of type 1 autoimmune diabetes.

    Science.gov (United States)

    Cedillo, Maribel; Libman, Ingrid M; Arena, Vincent C; Zhou, Lei; Trucco, Massimo; Ize-Ludlow, Diego; Pietropaolo, Massimo; Becker, Dorothy J

    2015-01-01

    The current increase in childhood type 1 diabetes (T1D) and obesity has led to two conflicting hypotheses and conflicting reports regarding the effects of overweight on initiation and spreading of islet cell autoimmunity vs earlier clinical manifestation of preexisting autoimmune β-cell damage driven by excess weight. The objective of the study was to address the question of whether the degree of β-cell autoimmunity and age are related to overweight at diabetes onset in a large cohort of T1D youth. This was a prospective cross-sectional study of youth with autoimmune T1D consecutively recruited at diabetes onset. The study was conducted at a regional academic pediatric diabetes center. Two hundred sixty-three consecutive children younger than 19 years at onset of T1D participated in the study. Relationships between body mass index and central obesity (waist circumference and waist to height ratio) and antigen spreading (islet cell autoantibody number), age, and cardiovascular (CVD) risk factors examined at onset and/or 3 months after the diagnosis were measured. There were no significant associations between number of autoantibodies with measures of adiposity. Age relationships revealed that a greater proportion of those with central obesity (21%) were in the youngest age group (0-4 y) compared with those without central obesity (6%) (P = .001). PATIENTS with central obesity had increased CVD risk factors and higher onset C-peptide levels (P obesity accelerates progression of autoantibody spreading once autoimmunity, marked by standard islet cell autoantibody assays, is present. Central obesity was present in almost one-third of the subjects and was associated with early CVD risk markers already at onset.

  11. Attention Deficit Hyperactivity Disorder Symptoms Mediate Early-Onset Smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized c

  12. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized c

  13. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)

    2008-01-01

    textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,

  14. Early childhood obesity prevention policies

    National Research Council Canada - National Science Library

    Birch, Leann L; Burns, Annina Catherine; Parker, Lynn

    2011-01-01

    Reviews factors related to overweight and obese children from birth to age 5, with a focus on nutrition, physical activity, and sedentary behavior, and recommends policies that can alter children's...

  15. Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, autonomic dysregulation and neuroendocrine tumor syndrome with a homogenous enlargement of the pituitary gland: a case report.

    Science.gov (United States)

    Aljabban, Lama; Kassab, Lina; Bakoura, Nour Alhuda; Alsalka, Mohammad Fayez; Maksoud, Ismaeil

    2016-11-22

    Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome is a rare pediatric disorder with a variable sequence of clinical presentations, undefined etiology, and high risk of mortality. Our patient presented an unusual course of the disease accompanied by a homogenous mild enlargement of her pituitary gland with an intact pituitary-endocrine axis which, to the best of our knowledge, represents a new finding in rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome. We present a documented case of a 4 years and 8-month-old Syrian Arabic girl with a distinctive course of signs and symptoms of rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome accompanied by mature ganglioneuroma in her chest, a homogenous mild enlargement of her pituitary gland, generalized cortical brain atrophy, and seizures. Three months after her first marked symptoms were noted she had a sudden progression of severe respiratory distress that ended with her death. The findings of this case could increase our understanding of the pathogenetic mechanisms of rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation, and place more emphases on pediatricians to consider rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome whenever early rapid onset of obesity, associated with any malfunction, is observed in children. This knowledge could be lifesaving for children with rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome.

  16. Severe early onset ethylmalonic encephalopathy with West syndrome.

    Science.gov (United States)

    Papetti, Laura; Garone, Giacomo; Schettini, Livia; Giordano, Carla; Nicita, Francesco; Papoff, Paola; Zeviani, Massimo; Leuzzi, Vincenzo; Spalice, Alberto

    2015-12-01

    Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome.

  17. Ethics dilemmas of early detection of obesity

    DEFF Research Database (Denmark)

    Vallgårda, Signild

    2016-01-01

    Aim: To discuss the ethics dilemmas of the early detection of overweight and obesity. Methods: Analysis of the ethical aspects of early detection. Results: The early detection of overweight and obesity entails a number of ethical dilemmas because it may both be helpful and harmful. It may help...... people to lead a healthier life and non-detection could be considered neglectful. It may, however, cause anxiety, interfere with people’s integrity, focus only on individual causes and responsibilities, cause stigmatization and have adverse effects by inducing weight gain. Conclusions: Documentation...

  18. COMPARATIVE STUDY OF MATERNAL AND PERINATAL OUTCOME IN EARLY ONSET AND LATE ONSET PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Sreedevi Atluri

    2017-01-01

    Full Text Available BACKGROUND Preeclampsia is the leading cause of maternal and perinatal morbidity and mortality worldwide, the exact aetiology of which is still unknown. The concept of early and late pre-eclampsia depending on gestational age at onset is more modern and is widely accepted that these two entities have different aetiologies and should be considered as different forms of the disease. Even though the presenting features overlap, these two entities of preeclampsia differ by biochemical markers, maternal and foetal outcomes. Aim of the Study- This study compares early-onset preeclampsia and late-onset preeclampsia with respect to their clinical presentation, laboratory parameters, management options, maternal and foetal outcomes which gives us an idea that these two preeclampsia subtypes have different pathological processes and a need for varied clinical approach to prevent adverse outcomes. METHODS This is a prospective comparative study conducted in JSS Hospital, Mysore from November, 2014 to June, 2016. All Antenatal cases (both booked and unbooked with gestational age ≥20 weeks between 18 yrs. and 40 yrs. of age diagnosed as preeclampsia as per the inclusion and exclusion criteria attending the outpatient department or admitted were selected and divided in to two groups, early onset preeclampsia (EOP group if gestational age at onset of preeclampsia is before 34 weeks and late onset preeclampsia if gestational age at onset is at 34 weeks or later were observed until delivery and early postpartum period and babies till early neonatal period. RESULTS A total of 158 patients at >20 weeks of gestation with preeclampsia were enrolled for this study. Early-onset Preeclampsia (EOP and Late-onset Preeclampsia (LOP had 75 and 83 pre eclamptic women respectively. Early onset group had severe clinical picture with deranged laboratory findings (Thrombocytopenia, altered liver enzymes, lactic dehydrogenase (LDH levels, urea and creatinine levels compared to

  19. DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease

    NARCIS (Netherlands)

    Olgiati, Simone; Quadri, Marialuisa; Fang, Mingyan; Rood, Janneke P. M. A.; Saute, Jonas A.; Chien, Hsin Fen; Bouwkamp, Christian G.; Graafland, Josja; Minneboo, Michelle; Breedveld, Guido J.; Zhang, Jianguo; Verheijen, Frans W.; Boon, Agnita J. W.; Kievit, Anneke J. A.; Jardim, Laura Bannach; Mandemakers, Wim; Barbosa, Egberto Reis; Rieder, Carlos R. M.; Leenders, Klaus L.; Wang, Jun; Bonifati, Vincenzo

    ObjectiveDNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age MethodsThe DNAJC6 open reading frame was analyzed in 274 patients with early-onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity

  20. Lost human capital from early-onset chronic depression.

    Science.gov (United States)

    Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

    2000-06-01

    Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

  1. Blood-Based Biomarkers of Early-Onset Breast Cancer

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0214 TITLE: Blood -based biomarkers of early-onset breast cancer PRINCIPAL INVESTIGATOR: Nasim Ahmadiyeh...DATES COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE Blood -based biomarkers of early-onset breast cancer 5a. CONTRACT NUMBER W81XWH-13-1...While the normal breast is the ideal tissue in which to study this phenomenon, gene expression profiling of blood lymphocytes has been successfully

  2. DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease.

    Science.gov (United States)

    Olgiati, Simone; Quadri, Marialuisa; Fang, Mingyan; Rood, Janneke P M A; Saute, Jonas A; Chien, Hsin Fen; Bouwkamp, Christian G; Graafland, Josja; Minneboo, Michelle; Breedveld, Guido J; Zhang, Jianguo; Verheijen, Frans W; Boon, Agnita J W; Kievit, Anneke J A; Jardim, Laura Bannach; Mandemakers, Wim; Barbosa, Egberto Reis; Rieder, Carlos R M; Leenders, Klaus L; Wang, Jun; Bonifati, Vincenzo

    2016-02-01

    DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within ∼10 years from onset). Here, for the first time, we report DNAJC6 mutations in early-onset Parkinson's disease (PD). The DNAJC6 open reading frame was analyzed in 274 patients with early-onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity mapping, linkage analysis, whole-exome sequencing, and protein studies. We identified two families with different novel homozygous DNAJC6 mutations segregating with PD. In each family, the DNAJC6 mutation was flanked by long runs of homozygosity within highest linkage peaks. Exome sequencing did not detect additional pathogenic variants within the linkage regions. In both families, patients showed severely decreased steady-state levels of the auxilin protein in fibroblasts. We also identified a sporadic patient carrying two rare noncoding DNAJC6 variants possibly effecting RNA splicing. All these cases fulfilled the criteria for a clinical diagnosis of early-onset PD, had symptoms onset in the third-to-fifth decade, and slow disease progression. Response to dopaminergic therapies was prominent, but, in some patients, limited by psychiatric side effects. The phenotype overlaps that of other monogenic forms of early-onset PD. Our findings delineate a novel form of hereditary early-onset PD. Screening of DNAJC6 is warranted in all patients with early-onset PD compatible with autosomal recessive inheritance. Our data provide further evidence for the involvement of synaptic vesicles endocytosis and trafficking in PD pathogenesis. © 2016 American Neurological Association.

  3. Pulmonary dysfunction in obese early adolescents

    Directory of Open Access Journals (Sweden)

    Bambang Supriyatno

    2010-08-01

    Full Text Available Aim Obesity leads to various complications, including pulmonary dysfunction. Studies on pulmonary function of obese children are limited and the results are controversial. This study was aimed to determine proportion of pulmonary dysfunction on early adolescents with obesity and to evaluate correlation between obesity degree with pulmonary dysfunction degree.Methods A cross-sectional study was conducted at the Department of Child Health, Medical School, University of Indonesia, from November 2007 to December 2008. Subjects were 10 to 12 year-old adolescents with obesity. Subjects underwent pulmonary function test (PFT to assess FEV1/FVC, FEV1, FVC, V50, and V25.Results 110 subjects fulfilled study criteria, 83 (75.5% were male and 27 (24.5% were female with median BMI 26.7 (22.6-54.7 kg/m2; 92 subjects (83.6% were superobese. History of asthma and allergic rhinitis were found in 32 (29.1% and 46 (41.8% subjects, respectively. 64 (58.2% subjects had abnormal PFT results consisting of restrictive type in 28 (25.5% subjects, obstructive in 3 (2.7%, and combined type in 33 (30%. Mean FEV1, FVC, V50, and V25 values were below normal, while mean FEV1/FVC ratio was normal. There was no statistically significant correlation between BMI and PFT parameters. No significant correlation was found between degree of obesity and the severity of pulmonary dysfunction.Conclusions Pulmonary dysfunction occurs in 58.2% obese early adolescents. The most common abnormality was combined type (30%, followed by restrictive (25.5%, and obstructive type (2.7%. There was no correlation between BMI and pulmonary function test parameters. (Med J Indones 2010;19:179-84Key words: early adolescents, obesity, pulmonary function test

  4. Early-onset colorectal cancer: a sporadic or inherited disease?

    Science.gov (United States)

    Stigliano, Vittoria; Sanchez-Mete, Lupe; Martayan, Aline; Anti, Marcello

    2014-09-21

    Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a "sporadic" subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.

  5. Adolescent-Onset Depression: Are Obesity and Inflammation Developmental Mechanisms or Outcomes?

    Science.gov (United States)

    Byrne, Michelle L; O'Brien-Simpson, Neil M; Mitchell, Sarah A; Allen, Nicholas B

    2015-12-01

    Depression often has its first onset during adolescence and is associated with obesity. Furthermore, inflammatory processes have been implicated in both depression and obesity, although research amongst adolescents is limited. This review explores associations between depression and obesity, depression and inflammation, and obesity and inflammation from a developmental perspective. The temporal relations between these factors are examined to explore whether obesity and elevated inflammation act as either risk factors for, or outcomes of, adolescent-onset depression. Sex differences in these processes are also summarized. We propose a model whereby increases in sex hormones during puberty increase risk for depression for females, which can lead to obesity, which in turn increases levels of inflammation. Importantly, this model suggests that inflammation and obesity are outcomes of adolescent depression, rather than initial contributing causes. Further research on biological and psychosocial effects of sex hormones is needed, as is longitudinal research with children and adolescents.

  6. Brain structure abnormalities in early-onset and adolescent-onset conduct disorder.

    Science.gov (United States)

    Fairchild, Graeme; Passamonti, Luca; Hurford, Georgina; Hagan, Cindy C; von dem Hagen, Elisabeth A H; van Goozen, Stephanie H M; Goodyer, Ian M; Calder, Andrew J

    2011-06-01

    The developmental taxonomic theory proposes that neurodevelopmental factors play a critical role in the etiology of early-onset conduct disorder, whereas adolescent-onset conduct disorder arises as a result of social mimicry of deviant peers. Recent studies have challenged this theory by demonstrating that adolescents with both early- and adolescent-onset forms of conduct disorder show impaired emotional learning and abnormal neural activation during facial expression processing. The present study extends this work by investigating brain structure in both subtypes of conduct disorder. Voxel-based morphometry was used to compare gray matter volumes in four regions of interest (amygdala, insula, anterior cingulate, and orbitofrontal cortex) in male adolescents with early-onset (N=36) or adolescent-onset (N=27) conduct disorder and in healthy comparison subjects (N=27). Whole-brain structural analyses were also performed. The combined conduct disorder group displayed gray matter volume reductions in the bilateral amygdala, extending into the insula, relative to healthy comparison subjects. Separate comparisons between healthy subjects and each conduct disorder subgroup revealed lower amygdala volume in both subgroups and reduced right insula volume in the adolescent-onset subgroup. Regression analyses within the conduct disorder subjects alone demonstrated a negative correlation between conduct disorder symptoms and right insula volume. The results demonstrate that gray matter volume reductions in brain regions involved in processing socioemotional stimuli are associated with conduct disorder, regardless of age of onset. Brain structural abnormalities may contribute to the emergence of adolescent-onset as well as early-onset conduct disorder.

  7. Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

    Science.gov (United States)

    Bloor, Ian D; Sébert, Sylvain P; Saroha, Vivek; Gardner, David S; Keisler, Duane H; Budge, Helen; Symonds, Michael E; Mahajan, Ravi P

    2013-10-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

  8. Markers of neurodevelopmental impairments in early-onset psychosis

    Directory of Open Access Journals (Sweden)

    Petruzzelli MG

    2015-07-01

    Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy Background: The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods: A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results: Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001, learning difficulties (P=0.04, enuresis (P=0.0008, a lower intelligence quotient (P<0.001, and subtle motor impairments (P=0.005 than control subjects. Conclusion: We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

  9. Psychological and Behavioral Risk Factors for Obesity Onset in Adolescent Girls: A Prospective Study

    Science.gov (United States)

    Stice, Eric; Presnell, Katherine; Shaw, Heather; Rohde, Paul

    2005-01-01

    Because little is known about risk factors for obesity, the authors tested whether certain psychological and behavioral variables predicted future onset of obesity. The authors used data from a prospective study of 496 adolescent girls who completed a baseline assessment at age 11-15 years and 4 annual follow-ups. Self-reported dietary restraint,…

  10. Psychological and Behavioral Risk Factors for Obesity Onset in Adolescent Girls: A Prospective Study

    Science.gov (United States)

    Stice, Eric; Presnell, Katherine; Shaw, Heather; Rohde, Paul

    2005-01-01

    Because little is known about risk factors for obesity, the authors tested whether certain psychological and behavioral variables predicted future onset of obesity. The authors used data from a prospective study of 496 adolescent girls who completed a baseline assessment at age 11-15 years and 4 annual follow-ups. Self-reported dietary restraint,…

  11. Diagnosis of Late Stage, Early Onset, Small Fiber Polyneuropathy

    Science.gov (United States)

    2016-10-01

    additionally discovered SFPN that affects adolescents and adults [2]. This early-onset SFPN usually begins in adolescence or early adulthood but can...promote early diagnosis. What was the impact on other disciplines? Nothing to report. What was the impact on technology transfer? Nothing to report...What was the impact on society beyond science and technology ? As described above, Veterans’ health and, by extension, public health will be

  12. Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep

    OpenAIRE

    Bloor, Ian D.; Sébert, Sylvain P.; Saroha, Vivek; Gardner, David S.; Keisler, Duane H.; Budge, Helen; Symonds, Michael E.; Mahajan, Ravi P.

    2013-01-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissu...

  13. Obesity's Effects on the Onset of Functional Impairment among Older Adults

    Science.gov (United States)

    Jenkins, Kristi Rahrig

    2004-01-01

    Purpose: This study has two purposes. First, it determines if there is a relationship between body weight and the onset of functional impairment across time among this sample of older adults. More specifically, it examines if obese older adults are more likely to experience the onset of functional impairment. Second, it explores how health…

  14. Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis.

    Science.gov (United States)

    McWilliams, Robert R; Maisonneuve, Patrick; Bamlet, William R; Petersen, Gloria M; Li, Donghui; Risch, Harvey A; Yu, Herbert; Fontham, Elizabeth T H; Luckett, Brian; Bosetti, Cristina; Negri, Eva; La Vecchia, Carlo; Talamini, Renato; Bueno de Mesquita, H Bas; Bracci, Paige; Gallinger, Steven; Neale, Rachel E; Lowenfels, Albert B

    2016-02-01

    While pancreatic cancer (PC) most often affects older adults, to date, there has been no comprehensive assessment of risk factors among PC patients younger than 60 years. We defined early-onset PC (EOPC) and very-early-onset PC (VEOPC) as diagnosis of PC in patients younger than 60 and 45 years, respectively. We pooled data from 8 case-control studies, including 1954 patients with EOPC and 3278 age- and sex-matched control subjects. Logistic regression analysis was performed to identify associations with EOPC and VEOPC. Family history of PC, diabetes mellitus, smoking, obesity, and pancreatitis were associated with EOPC. Alcohol use equal to or greater than 26 g daily also was associated with increased risk of EOPC (odds ratio, 1.49; 95% confidence interval, 1.21-1.84), and there appeared to be a dose- and age-dependent effect of alcohol on risk. The point estimate for risk of VEOPC was an odds ratio of 2.18 (95% confidence interval, 1.17-4.09). The established risk factors for PC, including smoking, diabetes, family history of PC, and obesity, also apply to EOPC. Alcohol intake appeared to have an age-dependent effect; the strongest association was with VEOPC.

  15. Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    Hui Yu; Li-Fang Xie; Kang Chen; Gang-Yi Yang; Xiao-Yan Xing; Jia-Jun Zhao; Tian-Pei Hong

    2016-01-01

    Background:Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly;however,the age at diagnosis has gradually reduced in recent years.Although the incidence of young-onset T2DM is increasing,it is still not fully clear the onset characteristics and risk factors of early-onset T2DM.The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.Methods:This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China.A total of 1545 patients with T2DM with an age at onset of<40 years were included,and the control group consisted of subjects aged <40 years with normal blood glucose level.Results:In patients with young-onset T2DM,the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%,respectively.Most of the patients were obese,followed irregular diet pattern and sedentary lifestyle,had life or work pressure,and had a family history of diabetes mellitus.Compared with subjects with normal blood glucose level,logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99,95% confidence interval [CI] 42.37-4714.87),family history of diabetes mellitus (OR 23.46,CI14.47-38.03),dyslipidemia (OR 2.65,CI 1.54-4.56),diastolic blood pressure (OR 1.02,CI 1.00-1.04),and body mass index (OR 0.95,CI 0.92-0.99) are independent factors for early-onset T2DM.Conclusions:We observed that abdominal obesity,family history of diabetes mellitus,and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM.It is,therefore,necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.

  16. Differences between early and late onset adult depression

    DEFF Research Database (Denmark)

    Drachmann Bukh, Jens; Bock, Camilla; Vinberg, Maj

    2011-01-01

    episode depression were systematically recruited. Characteristics including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, family history, and treatment outcome were assessed by structured interviews and compared by chi-square tests for categorical data...... prevalence of co-morbid personality disorders, higher levels of neuroticism, and a lower prevalence of stressful life events preceding onset compared to patients with later age-of-onset. There were no differences in severity of the depressive episode, treatment outcome or family loading of psychiatric......, t-tests for continuous parametric data and Mann-Whitney U-test for continuous nonparametric data. Logistic and multiple regression analyses were used to adjust the analyses for potentially confounding variables. Results: Patients with early onset of depression were characterised by a higher...

  17. Early Onset Marfan Syndrome: Atypical Clinical Presentation of Two Cases

    Directory of Open Access Journals (Sweden)

    Ozyurt Abdullah

    2015-06-01

    Full Text Available Early onset Marfan Syndrome (eoMFS is a rare, severe form of Marfan Syndrome (MFS. The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system.

  18. Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

    Science.gov (United States)

    Danner, Stephanie; Fristad, Mary A.; Arnold, L. Eugene; Youngstrom, Eric A.; Birmaher, Boris; Horwitz, Sarah M.; Demeter, Christine; Findling, Robert L.; Kowatch, Robert A.

    2009-01-01

    Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current…

  19. Early-Onset Psychosis in Youth with Intellectual Disability

    Science.gov (United States)

    Friedlander, R. I.; Donnelly, T.

    2004-01-01

    Accurate diagnosis of psychotic disorders may be very difficult in youth with intellectual disabilities. The authors reviewed the assessment, treatment and follow-up of 21 youths with ID referred because of early onset of psychotic symptoms. Just over one half of the patients had a diagnosis of schizophrenia or schizo-affective disorder. One third…

  20. Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

    Science.gov (United States)

    ... called sarcomeres . Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of this protein's most ... CMD Salih congenital muscular dystrophy Salih myopathy titinopathy & early-onset myopathy with ...

  1. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to

  2. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

    Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

  3. Early-onset androgenetic alopecia and endocrine disruptors

    Directory of Open Access Journals (Sweden)

    M. Guarrera

    2011-01-01

    Full Text Available Androgenetic alopecia (AGA is the most common acquired non scarring alopecia in humans caused by androgen hormones in the setting of a genetic predisposition. Usually AGA starts after puberty, but recently it has been observed also in adolescents. Their mean age was 13 years with a slight prevalence in males. The premature AGA may be caused by environmental, alimentary (meat and milk or cosmetics overexposure to sexual hormones or to endocrine disrupters (EDs. EDs are "exogenous substances that interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body causing adverse effects to human health" and they are able bind to the steroid hormone receptors. Early onset AGA may be linked to the well known phenomenon of early puberty caused in some cases by hormones contained in food or by environmental chemicals. Therefore it is likely that the EDs may play a role also in the pathogenesis of early-onset AGA.

  4. Intraspinal anomalies in early-onset idiopathic scoliosis.

    Science.gov (United States)

    Pereira, E A C; Oxenham, M; Lam, K S

    2017-06-01

    In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

  5. Does early-onset multiple sclerosis differ from adult-onset form in Iranian people

    Directory of Open Access Journals (Sweden)

    Fereshteh Ashtari

    2010-01-01

    Full Text Available Background: Few studies have attempted to delineate the clinical profile of multiple Sclerosis (MS among people of Asia. This study sought to identify the characteristics of early-onset Multiple Sclerosis (EOMS comparison to adult-onset form (AOMS in Isfahan, IRAN. Methods: This prospective study was conducted on 104 youths with multiple sclerosis beginning before the age of 16 years and 123 patients with adult-onset multiple sclerosis. Patients were observed for a mean period of 5 years. The common presenting symptoms, MRI finding, course of disease and disability score were compared between the two groups. Results: The mean onset age of disease in youths and adults were 14 ± 1.9 and 27.7 ± 8.06 years, respectively. Female/male ratio was 4.47:1 in EOMS and 3.92:1 in AOMS, this ratio was 7:1 in early childhood MS (≤ 10 year. The most common presenting symptom was optic neuritis in the EOMS group and paresthesia in AOMS. Optic neuritis was common in AOMS too, but brainstem/cerebellar signs were more common in EOMS than AOMS. Seizure occurred more frequently in EOMS than in the AOMS group (12.6% vs. 1.6%, respectively, p < 0.001. MRI showed that brainstem plaques were more prevalent in the EOMS compared with the AOMS group. Conclusions: It was concluded that early-onset MS does not significantly differ from adult form in terms of major clinical manifestation and course of disease, however Seizure is more common in EOMS, and brainstem and cerebellar symptoms as presenting symptom are more common.

  6. Obesity in Early Pregnancy May Raise Child's Risk of Epilepsy

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_164428.html Obesity in Early Pregnancy May Raise Child's Risk of ... researchers said. "This means more severe grades of obesity correspond to increasingly higher risk," said study co- ...

  7. Early onset of treatment effects with oral risperidone

    Directory of Open Access Journals (Sweden)

    Naber Dieter

    2007-01-01

    Full Text Available Abstract Background The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. Methods In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. Results Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. Conclusion Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration.

  8. Inflammation profile of four early onset Crohn patients.

    Science.gov (United States)

    Marcuzzi, Annalisa; Girardelli, Martina; Bianco, Anna Monica; Martelossi, Stefano; Magnolato, Andrea; Tommasini, Alberto; Crovella, Sergio

    2012-02-10

    Crohn disease (CD) is a multifactorial disorder affecting mainly young adults. Sometimes, however, it can present in the first year of life (Early onset Crohn disease (EOCD)) showing an unpredictable course and can often be more severe than at older ages. Some cases have been associated to an underlying primary immunodeficiency such as IL10R deficiency. We studied the functional response to IL-10 and the genotype of IL-10 receptor in four patients with early onset crohn-like colitis. We found an IL10R variant, which may be associated with a decreased response to the cytokine in one patient. Further studies to determine its pathogenic effect should be performed. In addition IL-10 mediated inhibition of LPS-induced TNFα expression was measured in patient's monocytes.

  9. Risk Assessment in Neonatal Early-Onset Sepsis

    Science.gov (United States)

    Mukhopadhyay, Sagori; Puopolo, Karen M.

    2013-01-01

    The incidence of neonatal early-onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early-onset sepsis remains a potentially fatal condition, particularly among very low-birth weight infants. Clinical signs of neonatal infection are non-specific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk, and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures. PMID:23177799

  10. Familial early onset sarcoidosis with bone cysts and erosions

    Energy Technology Data Exchange (ETDEWEB)

    Blank, Norbert; Max, Regina; Lorenz, Hanns-Martin [University of Heidelberg, Department of Internal Medicine V, Division of Rheumatology, Heidelberg (Germany); Autschbach, Frank [University of Heidelberg, Department of Pathology, Heidelberg (Germany); Libicher, Martin [University of Cologne, Department of Radiology, Cologne (Germany)

    2007-09-15

    Early onset sarcoidosis is a granulomatous disease which is characterized by synovitis, polyarthritis, skin and eye involvement. We report the skeletal features of one patient with a family history and clinical symptoms suggestive of early onset sarcoidosis (EOS) which was confirmed by skin biopsy. Radiographs reveal postarthritic deformities of the MCP joints, contractures, a coarsened trabecular pattern at the PIP joints and small bone cysts resembling osteitis cystoides multiplex. Similar lesions were described in radiographs of the older sister and an uncle of our patient. This is the first report demonstrating bone cysts and erosions which could be a diagnostic feature in this rare disease and may help to differentiate other rheumatoid disorders. (orig.)

  11. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    Science.gov (United States)

    Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy.

  12. Stiff-person syndrome with early onset in infancy

    Directory of Open Access Journals (Sweden)

    S. A. Malmberg

    2015-01-01

    Full Text Available The case of stiff-person syndrome with benign course in 16-years old patient is presented. The initial clinical signs of the disease were observed in infancy with retarded development of motor functions and skeleton muscle lumps. The diagnosis was made using generally accepted clinical and electromyographical criteria. Aspects of differential diagnosis, pathogenesis and clinical course polymorphism in early-onset cases of the disease are discussed.

  13. Walking strategies in subjects with congenital or early onset strabismus

    OpenAIRE

    Irene eAprile; Maurizio eFerrarin; Luca ePadua; Enrica eDi Sipio; Chiara eSimbolotti; Sergio ePetroni; Costanza eTredici; Anna eDickmann

    2014-01-01

    Introduction: In congenital strabismus, sensory adaptations occur hampering the correct development of normal binocular vision. The aim of this study is to investigate if patients with congenital or early onset exotropic or esotropic strabismus adopt different walking strategies with respect to healthy subjects. Our hypothesis is that the abnormal binocular cooperation, occurring in patients with exotropic or esotropic strabismus, could influence neurosensorial adaptation of the gait pattern....

  14. Case of early childhood-onset narcolepsy with cataplexy: comparison with a monozygotic co-twin.

    Science.gov (United States)

    Ito, Hiromichi; Mori, Kenji; Mori, Tatsuo; Goji, Aya; Kagami, Shoji

    2014-10-01

    We describe here a rare case of early childhood-onset (5 years of age) narcolepsy. This case was interesting because of the ability to compare the patient's symptoms to the condition of her healthy monozygotic co-twin sister. The only environmental difference between the co-twins was head injury, which may be associated with the presence of narcolepsy. The co-twin was extroverted, sociable, reliable, and dexterous. In contrast, the patient could be described as introverted, gentle, honest and persevering, but was weak at conversation, assessment of a situation, memory, planning, activity (she was inactive), a sense of time, understanding of an analog clock, operating efficiency, and physical education (due to obesity). The sisters showed the same degree of appetite and dexterity with their fingers. Narcolepsy is often under-recognized or underdiagnosed, especially when the onset occurs in childhood. When we observe preschoolers with excessive daytime sleepiness, we should consider the possibility of narcolepsy with cataplexy.

  15. Outcome and risk factors of early onset severe preeclampsia

    Institute of Scientific and Technical Information of China (English)

    GONG Yun-hui; JIA Jin; L(U) Dong-hao; DAI Li; BAI Yi; ZHOU Rong

    2012-01-01

    Background Early onset severe preeclampsia is a specific type of severe preeclampsia,which causes high morbidity and mortality of both mothers and fetus.This study aimed to investigate the clinical definition,features,treatment,outcome and risk factors of early onset severe preaclampsia in Chinese women.üMethods Four hundred and thirteen women with severe preeclampsia from June 2006 to June 2009 were divided into three groups according to the gestational age at the onset of preeclampsia as follows:group A (less than 32 weeks,73 cases),group B (between 32 and 34 weeks,71 cases),and group C (greater than 34 weeks,269 cases).The demographic characteristics of the subjects,complications,delivery modes and outcome of pregnancy were analyzed retrospectively.üResults The systolic blood pressure at admission and the incidence of severe complications were significantly lower in group C than those in groups A and B,prolonged gestational weeks and days of hospitalization were significantly shorter in group C than those in groups A and B.Liver and kidney dysfunction,pleural and peritoneal effusion,placental abruption and postpartum hemorrhage were more likely to occur in group A compared with the other two groups.Twenty-four-hour urine protein levels at admission,intrauterine fetal death and days of hospitalization were risk factors that affected complications of severe preeclampsia.Gestational week at admission and delivery week were also risk factors that affected perinatal outcome.Conclusions Early onset severe preeclampsia should be defined as occurring before 34 weeks,and it is featured by more maternal complications and a worse perinatal prognosis compared with that defined as occurring after 34 weeks.Independent risk factors should be used to tailor the optimized individual treatment plan,to balance both maternal and neonatal safety.

  16. Cyclophosphamide for Rapid-Onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome

    OpenAIRE

    Paz-Priel, Ido; Cooke, David W.; Chen, Allen R

    2010-01-01

    Patients with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor syndrome have poor long-term outcomes. We report a patient who was treated successfully with high-dose cyclophosphamide immunoablation. This experience offers a novel therapeutic approach and an indirect insight into the underlying pathogenesis of this syndrome.

  17. Analysis of clinical characteristics and perinatal outcomes in pre-pregnancy obesity patients with early-onset preeclampsia%孕前肥胖的早发型子痫前期患者临床特点与围产结局分析

    Institute of Scientific and Technical Information of China (English)

    吴璠; 华绍芳; 李月琴

    2016-01-01

    Objective To explore clinical characteristics and the perinatal effects of multiple systems in pre-pregnancy obesity patients with early-onset preeclampsia. Methods A total of 111 cases with early-onset preeclampsia in our Inpatient Obstetric Department were reviewed in this study. According to pre-pregnancy body mass index (BMI), patients were divided into normal before pregnancy group (BMI<28 kg/m2, n=56) and obese before pregnancy group (BMI≥28 kg/m2, n=55) . The body weight, BMI, weight gain during pregnancy, risk factors, clinical features, and clinical features of neonatal index were compared between two groups. The correlation between maternal and neonatal indexes and glucose and lipid indexes were compared. Results Obese before pregnancy was more prone to blood concentration and disorders of lipid metabolism. The serum levels of lipid, glycosylated hemoglobin (HbA1c), hematocrit, platelet and fibrinogen were significantly higher in obese before pregnancy group than than those of normal group. The induced neonatal acidosis and other organ damage, newborn Apgar score, pH, glucose were significantly lower in obese before pregnancy group than those of normal group. The residual alkali (BE), lactic acid (LAC), creatine kinase (CK) and creatine kinase (CKMB) were higher in obese before pregnancy group than those of normal before pregnancy group. Correlation analysis showed that maternal low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), three acyl glycerol (TG) and HbA 1c were negatively correlated with neonatal Apgar score and pH, and which were positively correlated with neonatal LAC and CKMB. Both differences were significant (P<0.05 or P<0.01). Conclusion The dyslipidaemia in early onset preeclampsia in obesity patients before pregnancy is closely related with maternal and perinatal outcomes.%目的:探讨孕前肥胖的早发型子痫前期患者临床特点及对围产儿多系统的影响。方法回顾分析我院产科住院

  18. New function for an old enzyme: NEP deficient mice develop late-onset obesity.

    Directory of Open Access Journals (Sweden)

    Matthias Becker

    Full Text Available BACKGROUND: According to the World Health Organization (WHO there is a pandemic of obesity with approximately 300 million people being obese. Typically, human obesity has a polygenetic causation. Neutral endopeptidase (NEP, also known as neprilysin, is considered to be one of the key enzymes in the metabolism of many active peptide hormones. METHODOLOGY/PRINCIPAL FINDINGS: An incidental observation in NEP-deficient mice was a late-onset excessive gain in body weight exclusively from a ubiquitous accumulation of fat tissue. In accord with polygenetic human obesity, mice were characterized by deregulation of lipid metabolism, higher blood glucose levels, with impaired glucose tolerance. The key role of NEP in determining body mass was confirmed by the use of the NEP inhibitor candoxatril in wild-type mice that increased body weight due to increased food intake. This is a peripheral and not a central NEP action on the switch for appetite control, since candoxatril cannot cross the blood-brain barrier. Furthermore, we demonstrated that inhibition of NEP in mice with cachexia delayed rapid body weight loss. Thus, lack in NEP activity, genetically or pharmacologically, leads to a gain in body fat. CONCLUSIONS/SIGNIFICANCE: In the present study, we have identified NEP to be a crucial player in the development of obesity. NEP-deficient mice start to become obese under a normocaloric diet in an age of 6-7 months and thus are an ideal model for the typical human late-onset obesity. Therefore, the described obesity model is an ideal tool for research on development, molecular mechanisms, diagnosis, and therapy of the pandemic obesity.

  19. Early causes of child obesity and implications for prevention

    OpenAIRE

    Cole, T J

    2007-01-01

    Child obesity is becoming a serious public health concern, and major research effort is being devoted both to understand its aetiology and to improve the effectiveness of prevention strategies. Early growth patterns, both prenatally and postnatally, are emerging as important markers of later obesity risk, with rapid neonatal weight gain a clear risk factor for later obesity and metabolic syndrome. Thus, in two distinct senses child obesity is a growing problem. The paper summarises current ev...

  20. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, William Frans Christian; Raabjerg Christensen, A M

    2007-01-01

    , delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed...... that schizophrenia patients (n = 15) had significantly larger lateral ventricles as compared to controls. Duration and dose of antipsychotics correlated negatively with global gray matter volume in minimally medicated patients (n = 18). CONCLUSION: Findings of white matter changes and enlarged lateral ventricles...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis....

  1. [46-OR] : Early and late onset preeclampsia versus small for gestational age risks in subsequent pregnancies

    NARCIS (Netherlands)

    Bernardes, Thomas P; Mol, Ben W; Ravelli, Anita C; van den Berg, Paul P; Stolk, Ronald P; Groen, Henk

    OBJECTIVES: Current literature suggests that early and late onset preeclampsia should be treated as distinct entities and that early onset preeclampsia shares pathophysiology aspects with intrauterine growth restriction. Our objective was to investigate whether 5th percentile small for gestational

  2. Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

    Science.gov (United States)

    ... myopathy with early-onset Paget disease and frontotemporal dementia Enable Javascript to view the expand/collapse boxes. ... myopathy with early-onset Paget disease and frontotemporal dementia ( IBMPFD ) is a condition that can affect the ...

  3. Successful Scene Encoding in Presymptomatic Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Quiroz, Yakeel T; Willment, Kim Celone; Castrillon, Gabriel; Muniz, Martha; Lopera, Francisco; Budson, Andrew; Stern, Chantal E

    2015-01-01

    Brain regions critical to episodic memory are altered during the preclinical stages of Alzheimer's disease (AD). However, reliable means of identifying cognitively-normal individuals at higher risk to develop AD have not been established. To examine whether functional MRI can detect early functional changes associated with scene encoding in a group of presymptomatic presenilin-1 (PSEN1) E280A mutation carriers. Participants were 39 young, cognitively-normal individuals from an autosomal dominant early-onset AD kindred, located in Antioquia, Colombia. Participants performed a functional MRI scene encoding task and a post-scan subsequent memory test. PSEN1 mutation carriers exhibited hyperactivation within medial temporal lobe regions (hippocampus,parahippocampal formation) during successful scene encoding compared to age-matched non-carriers. Hyperactivation in medial temporal lobe regions during scene encoding is seen in individuals genetically-determined to develop AD years before their clinical onset. Our findings will guide future research with the ultimate goal of using functional neuroimaging in the early detection of preclinical AD.

  4. Early Onset of Selective Serotonin Reuptake Inhibitor Antidepressant Action

    Science.gov (United States)

    Taylor, Matthew J.; Freemantle, Nick; Geddes, John R.; Bhagwagar, Zubin

    2008-01-01

    Context: Selective serotonin reuptake inhibitors (SSRIs) are often described as having a delayed onset of effect in the treatment of depression. However, some trials have reported clinical improvement as early as the first week of treatment. Objective: To test the alternative hypotheses of delayed vs early onset of antidepressant action with SSRIs in patients with unipolar depression. Data Sources: Trials identified by searching CENTRAL, The Cochrane Collaboration database of controlled trials (2005), and the reference lists of identified trials and other systematic reviews. Study Selection: Randomized controlled trials of SSRIs vs placebo for the treatment of unipolar depression in adults that reported outcomes for at least 2 time points in the first 4 weeks of treatment (50 trials from >500 citations identified). Trials were excluded if limited to participants older than 65 years or specific comorbidities. Data Extraction: Data were extracted on trial design, participant characteristics, and outcomes by a single reviewer. Data Synthesis: Pooled estimates of treatment effect on depressive symptom rating scales were calculated for weeks 1 through 6 of treatment. In the primary analysis, the pattern of response seen was tested against alternative models of onset of response. The primary analysis incorporated data from 28 randomized controlled trials (n=5872). A model of early treatment response best fit the experimental data. Treatment with SSRIs rather than placebo was associated with clinical improvement by the end of the first week of use. A secondary analysis indicated an increased chance of achieving a 50% reduction in Hamilton Depression Rating Scale scores by 1 week (relative risk, 1.64; 95% confidence interval, 1.2-2.25) with SSRI treatment compared with placebo. Conclusions: Treatment with SSRIs is associated with symptomatic improvement in depression by the end of the first week of use, and the improvement continues at a decreasing rate for at least 6

  5. Early-onset anorexia nervosa in girls with Asperger syndrome

    Directory of Open Access Journals (Sweden)

    Dudova I

    2015-07-01

    Full Text Available Iva Dudova, Jana Kocourkova, Jiri Koutek Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Eating disorders frequently occur in conjunction with autism spectrum disorders, posing diagnostic and therapeutic difficulties. The comorbidity of anorexia nervosa and Asperger syndrome is a significant clinical complication and has been associated with a poorer prognosis. The authors are presenting the cases of an eleven-year-old girl and a five-and-a-half-year-old girl with comorbid eating disorders and Asperger syndrome. Keywords: eating disorders, early-onset anorexia nervosa, autism spectrum disorders, Asperger syndrome, diagnostics, therapy

  6. Early-onset sarcoidosis mimicking refractory cutaneous histiocytosis.

    Science.gov (United States)

    Ohga, Shouichi; Ichino, Kiyomi; Urabe, Kazunori; Ishimura, Masataka; Takada, Hidetoshi; Nishikomori, Ryuta; Furue, Masutaka; Hara, Toshiro

    2008-03-01

    A 10-year-old female was diagnosed as having early-onset sarcoidosis (EOS) after a prolonged skin disease. A granuloma emerged on the face at age 2 and massive lesions extended to the rest of the body. Repeated biopsies indicated histiocytic proliferation. At age 7, fever, disseminated macular eruptions, and multinucleated giant cells in the bone marrow prompted vinblastine and prednisolone therapy. Five months after stopping therapy, hypercalcemic crisis occurred along with fever, cytopenias, and interferon-gamma-nemia indicating a macrophage activation syndrome. A biopsy of nodules confirmed the diagnosis of sarcoidosis. The atypical EOS should be differentiated from histiocytosis.

  7. Early onset neonatal sepsis: diagnostic dilemmas and practical management.

    Science.gov (United States)

    Bedford Russell, A R; Kumar, R

    2015-07-01

    Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Susceptibility genetic variants associated with early-onset colorectal cancer.

    Science.gov (United States)

    Giráldez, María Dolores; López-Dóriga, Adriana; Bujanda, Luis; Abulí, Anna; Bessa, Xavier; Fernández-Rozadilla, Ceres; Muñoz, Jenifer; Cuatrecasas, Miriam; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Piqué, Josep M; Carracedo, Angel; Ruiz-Ponte, Clara; Cosme, Angel; Enríquez-Navascués, José María; Moreno, Victor; Andreu, Montserrat; Castells, Antoni; Balaguer, Francesc; Castellví-Bel, Sergi

    2012-03-01

    Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies.

  9. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

    Directory of Open Access Journals (Sweden)

    Alexander Strom

    Full Text Available Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE-infected female cynomolgus monkeys (Macaca fascicularis. The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c. infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001 which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  10. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

    Science.gov (United States)

    Strom, Alexander; Yutzy, Barbara; Kruip, Carina; Ooms, Mark; Schloot, Nanette C; Roden, Michael; Scott, Fraser W; Loewer, Johannes; Holznagel, Edgar

    2014-01-01

    Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  11. Obesity and onset of depression among U.S. middle-aged and older adults.

    Science.gov (United States)

    Xiang, Xiaoling; An, Ruopeng

    2015-03-01

    This paper aims to examine the relationship between obesity and onset of depression among U.S. middle-aged and older adults. Data came from 1994 to 2010 waves of the Health and Retirement Study. Study sample consisted of 6514 community-dwelling adults born between 1931 and 1941 who were free of clinically relevant depressive symptoms in 1994. Body mass index (BMI) was calculated from self-reported height/weight. Body weight status was classified into normal weight (18.5kg/m(2)≤BMIobesity (BMI≥30kg/m(2)). A score of ≥3 on the 8-item Center for Epidemiologic Studies Depression Scale was used to define clinically relevant depressive symptoms. Kaplan-Meier estimator and time-dependent Cox proportional hazards model were performed to examine the association between body weight status and onset of clinically relevant depressive symptoms. Unhealthy body weight was associated future onset of depression. Compared with their normal weight counterparts, overweight and obese participants were 13% (hazard ratio [HR]=1.13, 95% confidence interval [CI]=1.04-1.23) and 9% (HR=1.09, 95% CI=1.01-1.18) more likely to have onset of clinically relevant depressive symptoms during the 16years of follow-up, respectively. The relationship between obesity and depression onset appeared stronger among females and non-Hispanic whites than their male and racial/ethnic minority counterparts. Health care providers should be aware of the potential risk for depression among obese older adults. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Premature adrenarche: novel lessons from early onset androgen excess.

    Science.gov (United States)

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

    2011-08-01

    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  13. Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

    Science.gov (United States)

    Smeets-Janssen, M M J; Meesters, P D; Comijs, H C; Eikelenboom, P; Smit, J H; de Haan, L; Beekman, A T F; Stek, M L

    2013-11-01

    Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2)  = 0.2). These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Early onset of fesoterodine efficacy in subjects with overactive bladder.

    Science.gov (United States)

    Goldman, Howard B; Morrow, Jon D; Gong, Jason; Tseng, Li-Jung; Schneider, Tim

    2011-02-01

    To assess the onset of efficacy of fesoterodine 4 mg once daily on overactive bladder (OAB) symptoms after 1 week of treatment. This was a prespecified analysis of data collected during the first week of a 12-week, open-label, single-arm, flexible-dose study of fesoterodine. Eligible subjects were adult men and women (aged ≥ 18 years) who reported urinary frequency (eight or more micturitions per 24 h) and urgency (three or more episodes per 24 h) in 5-day bladder diaries at baseline, and dissatisfaction with previous tolterodine or tolterodine extended-release treatment received within 2 years of screening. All subjects received fesoterodine 4 mg once daily during the first 4 weeks of treatment (with an optional dose increase to fesoterodine 8 mg after week 4). Early onset of efficacy of fesoterodine 4 mg was assessed based on changes from baseline to week 1 in variables recorded in 5-day bladder diaries, including total micturitions, urgency episodes, urgency urinary incontinence (UUI) episodes and nocturnal micturitions. Urgency and severe urgency episodes were defined as those rated ≥ 3 and ≥ 4, respectively, on the five-point Urinary Sensation Scale (USS) (1 = no urgency, 5 = UUI); frequency-urgency sum (a combined measure of micturition frequency and urgency) was defined as the sum of all USS ratings. All bladder diary variables, including total and nocturnal micturitions, UUI episodes, urgency episodes, severe urgency episodes and frequency-urgency sum per 24 h, were significantly improved (all P fesoterodine 4 mg compared to baseline. The diary-dry rate at week 1 (i.e. subjects with at least one UUI episode at baseline who subsequently reported no UUI episodes on week 1 diary) was 38%. In this open-label study of subjects with OAB who had been previously treated and dissatisfied with tolterodine, fesoterodine 4 mg showed a rapid onset of efficacy at 1 week. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

  15. Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

    Science.gov (United States)

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

    2008-01-01

    Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

  16. Early-onset Pseudoexfoliation Syndrome following Multiple Intraocular Procedures

    Directory of Open Access Journals (Sweden)

    Heydar Amini

    2012-01-01

    Full Text Available Purpose: To present early-onset ocular manifestations of pseudoexfoliation syndrome in young patients who had undergone multiple intraocular procedures. Methods: This is an observational case series, introducing four cases with histories of multiple intraocular procedures for glaucoma. Results: All reported cases demonstrated typical manifestations of pseudoexfoliation unilaterally in the eye that had undergone multiple surgeries. The diagnosis of pseudoexfoliation was made prior to the age of 50 in all subjects and the earliest manifestation was at the age of 18 in a case with primary congenital glaucoma Conclusion: The role of multiple surgical procedures, in addition to genetic predisposition, should be further investigated as a possible inciting factor predisposing to pseudoexfoliation in younger individuals.

  17. Predictors of survival in severe, early onset COPD.

    Science.gov (United States)

    Hersh, Craig P; DeMeo, Dawn L; Al-Ansari, Essam; Carey, Vincent J; Reilly, John J; Ginns, Leo C; Silverman, Edwin K

    2004-11-01

    Multiple risk factors for mortality in patients with COPD have been described, but most studies have involved older, primarily male subjects. The purpose of this study was to determine the mortality rate and predictors of survival in subjects with severe, early onset COPD. The cohort of 139 probands in the Boston Early-Onset COPD Study was recruited from lung transplant and general pulmonary clinics between September 1994 and July 2002. Subjects were < 53 years old, had an FEV(1) of < 40% of predicted, did not have severe alpha(1)-antitrypsin deficiency, and had not undergone lung transplantation. The initial evaluation included a standardized respiratory questionnaire, spirometry, and a blood sample. A follow-up telephone interview was conducted between May and December 2002. Subjects were young (mean age at enrollment, 47.9 years) and had severe airflow obstruction (mean baseline FEV(1), 19.4% predicted). A total of 72.7% of the subjects were women (p < 0.0001 [comparison to equal gender distribution]). The median estimated survival time was 7.0 years from the time of study enrollment, determined by the Kaplan-Meier method. The majority of deaths were due to cardiorespiratory illness. In a multivariable Cox proportional hazards model, adjusting for age, gender, and baseline FEV(1), lifetime cigarette consumption (hazard ratio [HR], 1.20 [per 10 pack-years]; 95% confidence interval [CI], 1.02 to 1.40) and recent smoking status (HR, 2.50; 95% CI, 1.03 to 6.05) were both significant predictors of mortality. In this cohort, recent smoking status predicted increased mortality independent of the effects of lifetime smoking intensity. Smoking cessation may confer a survival benefit even among patients with very severe COPD.

  18. Incidence of early-onset dementia in Mar del Plata.

    Science.gov (United States)

    Sanchez Abraham, M; Scharovsky, D; Romano, L M; Ayala, M; Aleman, A; Sottano, E; Etchepareborda, I; Colla Machado, C; García, M I; Gonorazky, S E

    2015-03-01

    Early-onset dementia (EOD) is defined as dementia with onset before the age of 65 years. EOD is increasingly recognised as an important clinical and social problem with devastating consequences for patients and caregivers. Determine the annual crude incidence rate and the specific incidence rates by sex and age in patients with EOD, and the standardised rate using the last national census of the population of Argentina (NCPA), from 2010. Hospital Privado de Comunidad, Mar del Plata, Argentina, attends a closed population and is the sole healthcare provider for 17 614 people. Using the database pertaining to the Geriatric Care department, we identified all patients diagnosed with EOD between 1 January, 2005 and 31 December, 2011. EOD was defined as dementia diagnosed in patients younger than 65. The study period yielded 14 patients diagnosed with EOD out of a total of 287 patients evaluated for memory concerns. The crude annual incidence of EOD was 11 per 100 000/year (CI 95%: 6.25-19.1): 17 per 100 000 (CI 95%: 7.2-33.1) in men and 8 per 100 000 (CI 95%: 3.4-17.2) in women. We observed a statistically significant increase when comparing incidence rates between patients aged 21 to <55 years and ≥ 55 to <65 years (3 vs 22 per 100 000, P=.0014). The rate adjusted by NCPA census data was 5.8 cases of EOD habitants/year. This study, conducted in a closed population, yielded an EOD incidence rate of 11 per 100 000 inhabitants/year. To the best of our knowledge, this is the first prospective epidemiological study in Argentina and in Latin America. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  19. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12 ye

  20. Adult-onset obesity reveals prenatal programming of glucose-insulin sensitivity in male sheep nutrient restricted during late gestation.

    Directory of Open Access Journals (Sweden)

    Philip Rhodes

    Full Text Available BACKGROUND: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. METHODS/PRINCIPAL FINDINGS: Pregnant sheep received adequate (1.0M; CE, n = 6 or energy restricted (0.7M diet during early (1-65 days; LEE, n = 6 or late (65-128 days; LEL, n = 7 gestation (term approximately 147 days. Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT and body composition determination by dual energy x-ray absorptiometry (DXA. All animals were then exposed to an obesogenic environment for 6-7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were 'lean' (1.5 years. Obesity revealed generalised metabolic 'inflexibility' and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulin(AUC (from 133 to 341 [s.e.d. 26] ng.ml(-1.120 mins during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] ng.ml(-1 and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16] ng.ml(-1; LEL male vs. CE male, respectively. Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. CONCLUSIONS: This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and 'reveals' programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young

  1. Late-onset systemic lupus erythematosus in Northwestern Spain: differences with early-onset systemic lupus erythematosus and literature review.

    Science.gov (United States)

    Alonso, M D; Martinez-Vazquez, F; de Teran, T Diaz; Miranda-Filloy, J A; Dierssen, T; Blanco, R; Gonzalez-Juanatey, C; Llorca, J; Gonzalez-Gay, M A

    2012-09-01

    To further investigate into the epidaemiology of systemic lupus erythematosus (SLE) in Southern Europe, we have assessed the incidence, clinical spectrum and survival of patients diagnosed with late-onset SLE (age ≥ 50 years) according to the 1982 American College of Rheumatology (ACR) classification criteria at the single hospital for a well-defined population of Lugo, Northwestern (NW) Spain. Between January 1987 and December 2006, 51 (39.3%) of the 150 patients diagnosed as having SLE fulfilled definitions for late-onset SLE. The predominance of women among late-onset SLE (4:1) was reduced when compared with that observed in early-onset SLE (7:1). However, the incidence of late-onset SLE was significantly higher in women (4.2 [95% confidence interval (CI): 3.1-5.6] per 100,000 population) than in men (1.3 [95% CI: 0.6-2.2] per 100,000 population) (p < 0.001). As observed in early-onset SLE, the most frequent clinical manifestation in patients with late-onset SLE was arthritis (71.2%). Renal disease was less common in late-onset SLE (13.5%) than in early-onset SLE (26.4%); p = 0.07). In contrast, secondary Sjögren syndrome was more commonly found in the older age-group (27.1% versus 12.1%; p = 0.03). A non-significantly increased incidence of serositis was also observed in late-onset SLE patients (33.9% versus 22.0%; p = 0.13). Hypocomplementaemia (72.9% versus 91.2%) and positive results for anti-DNA and anti-Sm (49.2% and 6.8% versus 68.1% and 23.1, respectively) were significantly less common in late-onset SLE patients than in early-onset SLE. The probability of survival was reduced in late-onset SLE (p < 0.001). With respect to this, the 10-year and 15-year survival probability were 74.9 % and 63.3% in the late-onset SLE group and 96.3% and 91.0% in patients with early-onset SLE, respectively. In conclusion, our results confirm that in NW Spain SLE is not uncommon in individuals 50 years and older. In keeping with earlier studies

  2. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders.

    Science.gov (United States)

    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita

    2012-01-01

    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose regulation, Lipid metabolism and nerve signaling. Emphasis is laid on BCHE's diverse functions whose impediment affects the above mentioned metabolic pathways. Insilco techniques were employed to analyze the sequence, structural and functional similarities of the two proteins. A point mutation is focused which is common to both BCHE and Neuroligin. The mutation occurs at the homologous position in both the proteins making them deficient. This affects the three metabolic pathways leading to the respective disorders. The work describes the pathway that describes the role of BCHE in the onset of obesity mediated diabetes. The pathway further explains the association between Diabetes, Obesity and neurological disturbances.

  3. Early Onset Alzheimer’s Disease and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Marco Antonio Meraz-Ríos

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia in elderly adults. It is estimated that 10% of the world’s population aged more than 60–65 years could currently be affected by AD, and that in the next 20 years, there could be more than 30 million people affected by this pathology. One of the great challenges in this regard is that AD is not just a scientific problem; it is associated with major psychosocial and ethical dilemmas and has a negative impact on national economies. The neurodegenerative process that occurs in AD involves a specific nervous cell dysfunction, which leads to neuronal death. Mutations in APP, PS1, and PS2 genes are causes for early onset AD. Several animal models have demonstrated that alterations in these proteins are able to induce oxidative damage, which in turn favors the development of AD. This paper provides a review of many, although not all, of the mutations present in patients with familial Alzheimer’s disease and the association between some of these mutations with both oxidative damage and the development of the pathology.

  4. Maternal inheritance in recurrent early-onset depression.

    Science.gov (United States)

    Bergemann, Eric R; Boles, Richard G

    2010-02-01

    Major depressive disorder (MDD) is believed to have a genetic factor in its pathogenesis. On the basis of studies in MDD showing brain energy depletion and maternal inheritance in some families, we hypothesize that some of the genetic factor is likely maternally inherited on the mitochondrial DNA (mtDNA). Six hundred and seventy-two pedigrees from the Genetics of Recurrent Early-Onset Depression project were analyzed for matrilineal/nonmatrilineal pairs. Pairs were constructed to control for sex, age and autosomal gene contribution (e.g. maternal vs. paternal aunts). Individuals with and without any mood disorder were tallied and compared across five different pairs. Matrilineal relatives (with the same mtDNA sequence as the proband) were significantly more likely to suffer from a mood disorder than were nonmatrilineal relatives (with another mtDNA sequence; odds ratio 2.0, 95% confidence interval: 1.5-2.6, P = 3 x 10(-6)). Our data show a modest maternal bias in the susceptibility towards the development of depression, suggesting that predisposing genetic factors likely reside on the mtDNA. Thus, our data strengthen the hypothesis that energy metabolism may be involved in the pathogenesis of depression.

  5. Psychosocial impact of early onset dementia among caregivers

    Directory of Open Access Journals (Sweden)

    Nathália R. S. Kimura

    2015-12-01

    Full Text Available Introduction: There is growing recognition of early onset dementia (EOD as a significant clinical and social problem because of its effects on physical and mental health of people with dementia (PWD and their caregivers. Objective: To analyze the psychosocial impact of EOD in family caregivers. Methods: The study design was qualitative. Nine EOD caregivers (7 women were recruited at a service for Alzheimer's disease and assessed using semi-structured interviews. Interpretative phenomenological analysis was used to analyze caregivers' reports. Results: Five themes emerged from the narratives: psychological and emotional impact; physical impact; financial and professional impact; social impact and need for support services. The majority of the caregivers of people with EOD perceived their emotional wellbeing as poor or extremely poor. Carers reported poor physical health, which tends to be longer-lasting than mental health problems. Two caregivers had to retire after the disclosure of the dementia diagnosis, and seven reduced their work loads because they had to look after PWD. Preserving the abilities of PWD is essential to maintain their self-esteem, dignity and sense of utility. For the caregivers, interventions and stimulating activities make PWD feel worthwhile and contribute to improving life. Conclusion: The caregivers of people with EOD assume the role of caregiver prematurely and need to balance this activity with other responsibilities. There is a need for more studies of EOD in order to improve understanding of the impact of this disease and to enable development of adequate services for PWD and their caregivers.

  6. HLA region excluded by linkage analyses of early onset periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Sun, C.; Wang, S.; Lopez, N.

    1994-09-01

    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.

  7. Early-onset arthritis in retired National Football League players.

    Science.gov (United States)

    Golightly, Yvonne M; Marshall, Stephen W; Callahan, Leigh F; Guskiewicz, Kevin

    2009-09-01

    Injury has been identified as a potential risk factor for osteoarthritis. However, no previous study has addressed playing-career injuries and subsequent osteoarthritis in a large sample of former athletes. The purpose of this study was to describe the prevalence and determinants of arthritis and osteoarthritis in retired professional football players. Self-reported arthritis prevalence and retrospectively-recalled injury history were examined in a cross-sectional survey of 2,538 retired football players. Football players reported a high incidence of injury from their professional playing days (52.8% reported knee injuries, 74.1% reported ligament/tendon injuries, and 14.2% reported anterior cruciate ligament tears). For those under 60 years, 40.6% of retired NFL players reported arthritis, compared with 11.7% of U.S. males (prevalence ratio = 3.5, 95% CI: 3.3 to 3.7). Within the retired NFL player cohort, osteoarthritis was more prevalent in those with a history of knee injury (prevalence ratio = 1.7, 95% CI: 1.5 to 1.9) and ligament/tendon injury (prevalence ratio = 1.6, 95% CI: 1.4 to 1.9). In males under the age of 60, arthritis is over 3 times more prevalent in retired NFL players than in the general U.S. population. This excess of early-onset arthritis may be due to the high incidence of injury in football.

  8. Neuronal correlates of facial emotion discrimination in early onset schizophrenia.

    Science.gov (United States)

    Seiferth, Nina Y; Pauly, Katharina; Kellermann, Thilo; Shah, N Jon; Ott, Gudrun; Herpertz-Dahlmann, Beate; Kircher, Tilo; Schneider, Frank; Habel, Ute

    2009-01-01

    Emotion discrimination deficits represent a well-established finding in schizophrenia. Although imaging studies addressed the cerebral dysfunctions underlying emotion perception in adult patients, the question of trait vs state characteristics is still unresolved. The investigation of juvenile patients offers the advantage of studying schizophrenia at an age where influences of illness course and long-term medication are minimized. This may enable a more detailed characterization of emotion discrimination impairments and their cerebral correlates with respect to their appearance and exact nature. A total of 12 juvenile patients with early onset schizophrenia and matched healthy juveniles participated in this study. fMRI data were acquired during an emotion discrimination task consisting of standardized photographs of faces displaying happy, sad, angry, fearful, or neutral facial expression. Similar to findings in adult patients, juvenile patients exhibited reduced performance specificity whereas sensitivity was unaffected. Independent of the valence, their processing of emotional faces was associated with hypoactivations in both fusiform gyri and in the left inferior occipital gyrus. In addition, hyperactivations in patients were found in the right cuneus common to happy, angry, and fearful faces. Further, most distinct changes were present in juvenile patients when processing sad faces. These results point to a dysfunction in cerebral circuits relevant for emotion processing already prominent in adolescent schizophrenia patients. Regions affected by a decrease in activation are related to visual and face processing, similar to deficits reported in adult patients. These changes are accompanied by hyperactivations in areas related to emotion regulation and attribution, possibly reflecting compensatory mechanisms.

  9. Gestational length affects neurocognition in early-onset schizophrenia.

    Science.gov (United States)

    Teigset, Charlotte M; Mohn, Christine; Rund, Bjørn Rishovd

    2016-10-30

    Obstetric complications (OC) have been linked to an increased risk for schizophrenia in offspring, especially in early-onset schizophrenia (EOS). Extensive cognitive deficits occur in EOS, although no study has yet to investigate the relationship between OC and cognition in EOS. This study aims to examine the frequency of OC in EOS compared to controls, and also investigates the relationship between OC and neurocognitive dysfunction in the two groups. Nineteen EOS patients and 53 healthy controls were tested with the MATRICS Consensus Cognitive Battery (MCCB), and the cognitive measures were combined with OC data from the Norwegian Birth Registry. The results indicated no group differences in OC in EOS and healthy controls, but a shorter gestational length in the EOS group led to significant decreases in the overall neurocognitive composite score, and in processing speed. This suggests that the poorer neuropsychological performances commonly found in EOS may be partly attributable to the length of gestation. The worsened neurocognitive functioning did not appear among controls, so gestational length had a different impact on the two groups. Our findings indicated that a shorter gestational length did not increase the risk for developing EOS, but did significantly affect the cognitive difficulties in this group.

  10. Early-Onset Friedreich's Ataxia With Oculomotor Apraxia

    Directory of Open Access Journals (Sweden)

    Amene Saghazadeh

    2017-02-01

    Full Text Available Friedreich’s ataxia (FRDA is a rare autosomal recessive spinocerebellar ataxia which in the majority of cases is associated with a GAA-trinucleotide repeat expansion in the first intron of Frataxin gene located on chromosome 9. The clinical features include progressive gait and limb ataxia, cerebellar dysarthria, neuropathy, optic atrophy, and loss of vibration and proprioception. Ataxia with ocular motor apraxia type 1 (AOA1 is another autosomal recessive cerebellar ataxia which is associated with oculomotor apraxia, hypoalbuminaemia, and hypercholesterolemia. Here we describe two siblings (13- and 10-year-old display overlapping clinical features of both early-onset FRDA and AOA1. Almost all of laboratory test (including urinary analysis/culture, biochemistry, peripheral blood smear, C-reactive protein level, erythrocyte sedimentation rate-1h results were within the normal range for both patients. Due to the normal laboratory test results; we concluded that the diagnosis was more likely to be FRDA than AOA1. Therefore, neurologists should bear in mind that clinical presentations of FRDA may vary widely from the classical phenotype of gait and limb ataxia to atypical manifestations such as oculomotor apraxia.

  11. Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.

    Science.gov (United States)

    Miyake, Noriko; Fukai, Ryoko; Ohba, Chihiro; Chihara, Takahiro; Miura, Masayuki; Shimizu, Hiroshi; Kakita, Akiyoshi; Imagawa, Eri; Shiina, Masaaki; Ogata, Kazuhiro; Okuno-Yuguchi, Jiu; Fueki, Noboru; Ogiso, Yoshifumi; Suzumura, Hiroshi; Watabe, Yoshiyuki; Imataka, George; Leong, Huey Yin; Fattal-Valevski, Aviva; Kramer, Uri; Miyatake, Satoko; Kato, Mitsuhiro; Okamoto, Nobuhiko; Sato, Yoshinori; Mitsuhashi, Satomi; Nishino, Ichizo; Kaneko, Naofumi; Nishiyama, Akira; Tamura, Tomohiko; Mizuguchi, Takeshi; Nakashima, Mitsuko; Tanaka, Fumiaki; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-10-06

    We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Pretreatment Cardiometabolic Status in Youth With Early-Onset Psychosis

    DEFF Research Database (Denmark)

    Jensen, Karsten G; Correll, Christoph U; Rudå, Ditte

    2017-01-01

    : Comparing 113 youths with FEP (age ± SD = 15.74 ± 1.36 years, males = 30.1%, schizophrenia-spectrum disorders = 92.9%, antipsychotic-naive: n = 57) to 60 controls, patients had higher waist circumference (WC) z scores (1.13 ± 1.65 vs 0.42 ± 1.27, P = .018), cholesterol (4.10 ± 0.71 vs 3.79 ± 0.49 mmol/L, P...... percentile. Hypercholesterolemia (34.0% vs 12.5%, P = .015) was more frequent in patients, while decreased high-density lipoprotein cholesterol was more frequent in controls (32.5% vs 19.0%, P = .032). Family history of type 2 diabetes mellitus was associated with increased body mass index (BMI) z score (P...... exposure was not associated with increased cardiometabolic risk. Early age at onset predicted increased BMI and WC z scores, while diagnosis of schizophrenia and higher Clinical Global Impression-Severity score were associated with increased blood lipids. CONCLUSIONS: Youths with FEP had significantly...

  13. Sex-specific cognitive abnormalities in early-onset psychosis

    Directory of Open Access Journals (Sweden)

    Miguel Ruiz-Veguilla

    Full Text Available Objectives: Brain maturation differs depending on the area of the brain and sex. Girls show an earlier peak in maturation of the prefrontal cortex. Although differences between adult females and males with schizophrenia have been widely studied, there has been less research in girls and boys with psychosis. The purpose of this study was to examine differences in verbal and visual memory, verbal working memory, auditory attention, processing speed, and cognitive flexibility between boys and girls. Methods: We compared a group of 80 boys and girls with first-episode psychosis to a group of controls. Results: We found interactions between group and sex in verbal working memory (p = 0.04 and auditory attention (p = 0.01. The female controls showed better working memory (p = 0.01 and auditory attention (p = 0.001 than males. However, we did not find any sex differences in working memory (p = 0.91 or auditory attention (p = 0.93 in the psychosis group. Conclusions: These results are consistent with the presence of sex-modulated cognitive profiles at first presentation of early-onset psychosis.

  14. Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension.

    Science.gov (United States)

    Veerbeek, Jan H W; Hermes, Wietske; Breimer, Anath Y; van Rijn, Bas B; Koenen, Steven V; Mol, Ben W; Franx, Arie; de Groot, Christianne J M; Koster, Maria P H

    2015-03-01

    Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been investigated whether these differences in CVD risk factors are already present at postpartum cardiovascular screening. We evaluated postpartum differences in CVD risk factors in 3 subgroups of patients with a history of hypertensive pregnancy. We compared the prevalence of common CVD risk factors postpartum among 448 women with previous early-onset preeclampsia, 76 women with previous late-onset preeclampsia, and 224 women with previous pregnancy-induced hypertension. Women with previous early-onset preeclampsia were compared with women with late-onset preeclampsia and pregnancy-induced hypertension and had significantly higher fasting blood glucose (5.29 versus 4.80 and 4.83 mmol/L), insulin (9.12 versus 6.31 and 6.7 uIU/L), triglycerides (1.32 versus 1.02 and 0.97 mmol/L), and total cholesterol (5.14 versus 4.73 and 4.73 mmol/L). Almost half of the early-onset preeclampsia women had developed hypertension, as opposed to 39% and 25% of women in the pregnancy-induced hypertension and late-onset preeclampsia groups, respectively. Our data show differences in the prevalence of common modifiable CVD risk factors postpartum and suggest that prevention strategies should be stratified according to severity and gestational age of onset for the hypertensive disorders of pregnancy.

  15. Racial and ethnic differences in obesity and overweight as predictors of the onset of functional impairment.

    Science.gov (United States)

    Wei, Liang; Wu, Bei

    2014-01-01

    To examine racial and ethnic differences in the effects of body mass index (BMI) on the onset of functional impairment over 10 years of follow-up. Longitudinal analyses of a cohort from a nationally representative survey of community-dwelling American adults. Six waves (1996-2006) of the Health and Retirement Study (HRS). Two groups of HRS participants aged 50 and older without functional impairment at baseline (1996): 5,884 with no mobility difficulty and 8,484 with no activity of daily living (ADL) difficulty. Mobility difficulty was a composite measure of difficulty walking several blocks, walking one block, climbing several flights of stairs, and climbing one flight of stairs. ADL difficulty was measured as difficulty in dressing, bathing or showering, eating, and getting in and out of bed without help. The association between baseline BMI and risk of developing functional impairment was estimated using generalized estimating equation models. Overweight and obesity were significant predictors of functional impairment. Overweight and obese Hispanics were 41% and 91% more likely, respectively, to develop ADL disability than whites in the same BMI categories. Overweight and severely obese blacks were also more likely than their white counterparts to develop ADL disability. Risk of developing ADL difficulty was higher for Hispanics than for blacks in the obese category. No significant differences in onset of mobility difficulty were found between racial or ethnic groups within any BMI category. Blacks and Hispanics were at higher risk than whites of ADL but not mobility impairment. In addition to weight control, prevention efforts should promote exercise to reduce functional impairment, especially for blacks and Hispanics, who are at higher risk. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

  16. Racial/Ethnic Differences in Obesity and Overweight as Predictors of the Onset of Functional Impairment

    Science.gov (United States)

    Wei, Liang; Wu, Bei

    2014-01-01

    Objectives To examine racial/ethnic differences in the effects of body mass index (BMI) on the onset of functional impairment over 10 years of follow-up. Design Longitudinal analyses of a cohort from a nationally representative survey of community-dwelling American adults. Setting Six waves (1996-2006) of US Health and Retirement Study (HRS). Participants Two groups of HRS participants aged ≥50 without functional impairment at baseline (1996): 5,884 with no mobility difficulty, and 8,484 with no Activities of Daily Living (ADLs) difficulty. Measurements Mobility difficulty was a composite measure of difficulty in walking several blocks, walking one block, climbing several flights of stairs, and climbing one floor of stairs. ADL difficulty was measured by difficulty in dressing, bathing or showing, eating, and getting in or out of bed without help. The association between the baseline BMI categories and risk to develop functional impairment was estimated using generalized estimating equations (GEE) models. Results Overweight and obesity were significant predictors for functional impairment. Compared to the Whites in the same overweight and obese categories, Hispanics were 41% and 91% more likely to develop ADL disability. Blacks in the overweight and severely obese categories were also more likely than their White counterparts to develop ADL disability. Risk of developing ADL difficulty was higher for Hispanics than for Blacks in the obese category. For onset of mobility difficulty, no significant differences were found across racial/ethnic groups within any BMI Category. Conclusion Blacks and Hispanics were at higher risk than Whites for ADL but not mobility impairment. In addition to weight control, prevention efforts should promote exercise to reduce functional impairment, especially for Blacks and Hispanics, who are at higher risk. PMID:24384026

  17. Early Onset Squamous Cell Carcinoma In A Case Of Lichen Planus

    Directory of Open Access Journals (Sweden)

    Singh Shri Nath

    1998-01-01

    Full Text Available Lichen planus, which is a very common condition, is being presented. However, the uncommon feature in this cases is its early onset and equally early development of squamous cell carcinoma on a lesion on the right thigh.

  18. Nutrient Intakes in Early Life and Risk of Obesity.

    Science.gov (United States)

    Rolland-Cachera, Marie Françoise; Akrout, Mouna; Péneau, Sandrine

    2016-06-06

    There is increasing evidence that environmental factors in early life predict later health. The early adiposity rebound recorded in most obese subjects suggests that factors promoting body fat development have operated in the first years of life. Birth weight, growth velocity and body mass index (BMI) trajectories seem to be highly sensitive to the environmental conditions present during pregnancy and in early life ("The first 1000 days"). Particularly, nutritional exposure can have a long-term effect on health in adulthood. The high protein-low fat diet often recorded in young children may have contributed to the rapid rise of childhood obesity prevalence during the last decades. Metabolic programming by early nutrition could explain the development of later obesity and adult diseases.

  19. Nutrient Intakes in Early Life and Risk of Obesity

    Directory of Open Access Journals (Sweden)

    Marie Françoise Rolland-Cachera

    2016-06-01

    Full Text Available There is increasing evidence that environmental factors in early life predict later health. The early adiposity rebound recorded in most obese subjects suggests that factors promoting body fat development have operated in the first years of life. Birth weight, growth velocity and body mass index (BMI trajectories seem to be highly sensitive to the environmental conditions present during pregnancy and in early life (“The first 1000 days”. Particularly, nutritional exposure can have a long-term effect on health in adulthood. The high protein-low fat diet often recorded in young children may have contributed to the rapid rise of childhood obesity prevalence during the last decades. Metabolic programming by early nutrition could explain the development of later obesity and adult diseases.

  20. Evidence for apolipoprotein E {epsilon}4 association in early-onset Alzheimer`s patients with late-onset relatives

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Tur, J.; Delacourte, A.; Chartier-Harlin, M.C. [INSERM, Rouen (France)] [and others

    1995-12-18

    Recently several reports have extended the apolipoprotein E (APOE) {epsilon}4 association found in late-onset Alzheimer`s disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset {<=}60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE {epsilon}A allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that, for an individual, bearing at least one {epsilon}4 allele increases both the risk of AD before age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases. 19 refs., 3 tabs.

  1. DNAJC6 Mutations Associated with Early-Onset Parkinson's Disease

    NARCIS (Netherlands)

    S. Olgiati (Simone); M. Quadri (Marialuisa); M. Fang (Mingyan); J.P.M.A. Rood (Janneke P.M.A.); J.A. Saute (Jonas A.); H.F. Chien (Hsin Fen); C.G. Bouwkamp (Christian); J. Graafland (Josja); M. Minneboo (Michelle); G.J. Breedveld (Guido J.); J. Zhang (Jianguo); F.W. Verheijen (Frans W.); A.J.W. Boon (Agnita J.W.); A.J.A. Kievit (Anneke J.A.); L.B. Jardim (L.); W.J. Mandemakers (Wim); E.R. Barbosa (Egberto Reis); C.R.M. Rieder (Carlos); K.L. Leenders (Klaus L.); J. Wang (Jinxia); V. Bonifati (Vincenzo)

    2016-01-01

    markdownabstract_Objective_ DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within ∼10 years from onset). Here, for the

  2. Clinical features and gene analysis in Korean patients with early-onset Parkinson disease.

    Science.gov (United States)

    Chung, Eun Joo; Ki, Chang-Seok; Lee, Won Yong; Kim, In-Suk; Kim, Ji-Youn

    2006-08-01

    Systematic analysis of clinical features and gene mutations has not been performed in Korean patients with early-onset Parkinson disease (PD). To investigate the clinical characteristics and genetic background of Korean patients with early-onset PD. Clinical and genetic study. University hospital. Ninety-four patients with early-onset PD (mean +/- SD age at onset, 39.8 +/- 7.3 years) of 1100 patients with PD. Analysis of clinical characteristics and mutation analysis of the parkin and PTEN-induced kinase (PINK1) genes by direct sequencing and gene-dosage analysis using the multiplex ligation-dependent probe amplification technique. The correlation between age at onset and clinical characteristics and the clinical features of patients with onset before age 30 years vs patients with onset after age 30 years. Because age at onset was younger, levodopa-induced dyskinesia and off-dystonia were more frequently observed (P=.008). Patients affected before age 30 years showed more frequent levodopa-induced dyskinesia and off-dystonia (P=.002). We identified 3 patients (5%) with parkin gene mutations but none with the PINK1 mutation. Earlier onset of levodopa-induced dyskinesia and off-dystonia were characteristic features of early-onset PD, especially before an onset age of 30 years. However, parkin gene mutations were less frequent in these patients than in Japanese groups reported elsewhere.

  3. Strong family history and early onset of schizophrenia: about 2 families in Northern Nigeria

    OpenAIRE

    Nuhu, Folorunsho Tajudeen; Eseigbe, Edwin Ehi; Issa, Baba Awoye; Gomina, Michael Omeiza

    2016-01-01

    Schizophrenia is a highly heritable psychotic disorder and high genetic loading is associated with early onset of the disease. The outcome of schizophrenia has also been linked with the age of onset as well as the presence of family history of the disease. Therefore families with patients with early onset Schizophrenia are subpopulations for genetic studies. We present 2 families with heavy genetic loading who have adolescents with schizophrenia.

  4. Strong family history and early onset of schizophrenia: about 2 families in Northern Nigeria.

    Science.gov (United States)

    Nuhu, Folorunsho Tajudeen; Eseigbe, Edwin Ehi; Issa, Baba Awoye; Gomina, Michael Omeiza

    2016-01-01

    Schizophrenia is a highly heritable psychotic disorder and high genetic loading is associated with early onset of the disease. The outcome of schizophrenia has also been linked with the age of onset as well as the presence of family history of the disease. Therefore families with patients with early onset Schizophrenia are subpopulations for genetic studies. We present 2 families with heavy genetic loading who have adolescents with schizophrenia.

  5. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

    Science.gov (United States)

    McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

    2007-01-01

    Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

  6. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  7. Rare variants in GJA5 are associated with early-onset lone atrial fibrillation

    DEFF Research Database (Denmark)

    Christophersen, Ingrid E; Holmegard, Haya N; Jabbari, Javad;

    2013-01-01

    Genetic factors are believed to be important in early-onset lone atrial fibrillation (AF). The gene GJA5 encodes the gap-junction protein Cx40, which together with Cx43 is responsible for the electrical coupling of the atrial cardiomyocytes. The regulatory single nucleotide polymorphism rs10465885...... in GJA5 was recently associated with early-onset lone AF (...

  8. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  9. Follow up of intima-media thickness after severe early-onset preeclampsia

    NARCIS (Netherlands)

    Blaauw, Judith; Souwer, Esteban T D; Coffeng, Sophie M; Smit, Andries J; van Doormaal, Jasper J; Faas, Marijke M; van Pampus, Maria G

    2014-01-01

    OBJECTIVE: Early-onset preeclampsia is associated with premature cardiovascular disease. We previously demonstrated that femoral intima-media thickness (IMT) and markers of cardiovascular disease were increased in women 1 year after early-onset preeclampsia. The current study measured (progression o

  10. Children with Very Early Onset Obsessive-Compulsive Disorder: Clinical Features and Treatment Outcome

    Science.gov (United States)

    Nakatani, Eriko; Krebs, Georgina; Micali, Nadia; Turner, Cynthia; Heyman, Isobel; Mataix-Cols, David

    2011-01-01

    Background: There is emerging evidence that early onset obsessive-compulsive disorder (OCD) may be a phenomenologically distinct subtype of the disorder. Previous research has shown that individuals who report an early onset display greater severity and persistence of symptoms, and they may be less responsive to treatment. To date, this question…

  11. Early-onset preeclampsia : Constitutional factors and consequences for future pregnancy outcome and cardiovascular health

    NARCIS (Netherlands)

    van Rijn, B.B.

    2008-01-01

    In this thesis, maternal constitutional factors related to long-term cardiovascular health and subsequent pregnancy outcome in women with early-onset preeclampsia is addressed. Aims of the thesis: To evaluate subsequent pregnancy outcome in women with a first pregnancy complicated by early-onset

  12. [46-OR] : Early and late onset preeclampsia versus small for gestational age risks in subsequent pregnancies

    NARCIS (Netherlands)

    Bernardes, Thomas P; Mol, Ben W; Ravelli, Anita C; van den Berg, Paul P; Stolk, Ronald P; Groen, Henk

    2015-01-01

    OBJECTIVES: Current literature suggests that early and late onset preeclampsia should be treated as distinct entities and that early onset preeclampsia shares pathophysiology aspects with intrauterine growth restriction. Our objective was to investigate whether 5th percentile small for gestational a

  13. Internalizing and Externalizing Behaviors as Predictors of Sexual Onset in Early Adolescence

    Science.gov (United States)

    Boislard, Marie-Aude P.; Dussault, Frédéric; Brendgen, Mara; Vitaro, Frank

    2013-01-01

    This study had three goals: (a) assessing the predictive association of externalizing and internalizing behaviors during childhood with sexual onset during early adolescence; (b) examining the interactive link of externalizing and internalizing behaviors with early sexual onset; and (c) investigating the moderating effect of gender in this…

  14. Association analysis of the tyrosine hydroxylase gene polymorphisms with early-onset schizophrenia in Chinese population

    Institute of Scientific and Technical Information of China (English)

    吕钦谕

    2014-01-01

    Objective To investigate the relationship between the tyrosine hydroxylase(TH)gene and early-onset schizophrenia in Chinese Han population.Methods To tag single nucleotide polymorphisms(tag SNPs)rs2070762,rs6356 and rs11042978 in the TH gene were genotyped in 315 early-onset schizophrenics(188 male patients,127 female patients)and 391 controls subjects

  15. Early-onset preeclampsia : Constitutional factors and consequences for future pregnancy outcome and cardiovascular health

    NARCIS (Netherlands)

    van Rijn, B.B.

    2008-01-01

    In this thesis, maternal constitutional factors related to long-term cardiovascular health and subsequent pregnancy outcome in women with early-onset preeclampsia is addressed. Aims of the thesis: To evaluate subsequent pregnancy outcome in women with a first pregnancy complicated by early-onset pre

  16. Parental and Child Characteristics Related to Early-Onset Disordered Eating

    DEFF Research Database (Denmark)

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia

    2015-01-01

    characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies...

  17. Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

    Science.gov (United States)

    Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

    2009-01-01

    Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

  18. Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

    Science.gov (United States)

    Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

    2009-01-01

    Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

  19. Early life obesity and chronic kidney disease in later life.

    Science.gov (United States)

    Yim, Hyung Eun; Yoo, Kee Hwan

    2015-08-01

    The prevalence of chronic kidney disease (CKD) has increased considerably with a parallel rise in the prevalence of obesity. It is now recognized that early life nutrition has life-long effects on the susceptibility of an individual to develop obesity, diabetes, cardiovascular disease and CKD. The kidney can be programmed by a number of intrauterine and neonatal insults. Low birth weight (LBW) is one of the most identifiable markers of a suboptimal prenatal environment, and the important intrarenal factors sensitive to programming events include decreased nephron number and altered control of the renin-angiotensin system (RAS). LBW complicated by accelerated catch-up growth is associated with an increased risk of obesity, hypertension and CKD in later life. High birth weight and exposure to maternal diabetes or obesity can enhance the risk for developing CKD in later life. Rapid postnatal growth per se may also contribute to the subsequent development of obesity and CKD regardless of birth weight and prenatal nutrition. Although the mechanisms of renal risks due to early life nutritional programming remain largely unknown, experimental and clinical studies suggest the burdening role of early life obesity in longstanding cardiovascular and renal diseases.

  20. Early onset scoliosis: the value of serial risser casts.

    Science.gov (United States)

    Waldron, Sean R; Poe-Kochert, Connie; Son-Hing, Jochen P; Thompson, George H

    2013-12-01

    Treatment of early onset scoliosis (EOS) is challenging. In many cases, bracing will not be effective and growing rod surgery may be inappropriate. Serial, Risser casts may be an effective intermediate method of treatment. We studied 20 consecutive patients with EOS who received serial Risser casts under general anesthesia between 1999 and 2011. Analyses included diagnosis, sex, age at initial cast application, major curve severity, initial curve correction, curve magnitude at the time of treatment change or latest follow-up for those still in casts, number of casts per patient, the type of subsequent treatment, and any complications. There were 8 patients with idiopathic scoliosis, 6 patients with neuromuscular scoliosis, 5 patients with syndromic scoliosis, and 1 patient with skeletal dysplasia. Fifteen patients were female and 5 were male. The mean age at first cast was 3.8±2.3 years (range, 1 to 8 y), and the mean major curve magnitude was 74±18 degrees (range, 40 to 118 degrees). After initial cast application, the major curve measured 46±14 degrees (range, 25 to 79 degrees). At treatment change or latest follow-up for those still in casts, the major curve measured 53±24 degrees (range, 13 to 112 degrees). The mean time in casts was 16.9±9.1 months (range, 4 to 35 mo). The mean number of casts per patient was 4.7±2.2 casts (range, 1 to 9 casts). At the time of this study, 7 patients had undergone growing rod surgery, 6 patients were still undergoing casting, 5 returned to bracing, and 2 have been lost to follow-up. Four patients had minor complications: 2 patients each with superficial skin irritation and cast intolerance. Serial Risser casting is a safe and effective intermediate treatment for EOS. It can stabilize relatively large curves in young children and allows the child to reach a more suitable age for other forms of treatment, such as growing rods. Level IV; case series.

  1. Walking strategies in subjects with congenital or early onset strabismus

    Directory of Open Access Journals (Sweden)

    Irene eAprile

    2014-07-01

    Full Text Available Introduction. In congenital strabismus, sensory adaptations occur hampering the correct development of normal binocular vision. The aim of this study is to investigate if patients with congenital or early onset exotropic or esotropic strabismus adopt different walking strategies with respect to healthy subjects. Our hypothesis is that the abnormal binocular cooperation, occurring in patients with exotropic or esotropic strabismus, could influence neurosensorial adaptation of the gait pattern. Materials and Methods. Twenty-five patients were enrolled:19 with esotropic (ESO and 6 with exotropic strabismus (EXO. All patients underwent a ophthalmological and orthoptic evaluation. Biomechanical data were collected using a stereophotogrammetric system and a force platform. Twenty-seven age-matched healthy subjects (HS were used as controls. Results. The comparison between patients with ESO and patients with EXO strabismus showed that the maximal power at the knee and at the ankle was lower in EXO group (p<0.01 and p<0.05 respectively. The step width was statistically different between ESO and EXO groups (p<0.01, lower in patients with ESO and higher in patients with EXO strabismus when compared with HS (though not statistically significant. The deviation angle values showed a relationship with the step width (at the near fixation p<0.05 and with the maximal power at the knee and at the ankle (at the far fixation for the knee p<0.001 and for the ankle p<0.05; at the near fixation for the knee p<0.05: in the patients with EXO the increased angle deviation is related to larger step width and to lower power at the knee and at the ankle. In the patients with ESO strabismus this relationship is less robust. Discussion. Patients with EXO and ESO strabismus adopt different strategies to compensate their walking difficulties, and these strategies are likely due to an expanded visual field in patients with EXO and to a reduced visual field in patients with ESO

  2. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice

    OpenAIRE

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Åke

    2005-01-01

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5α-androstane-3β, 17β-diol (3βAdiol). 3βAdiol is estrogenic in ERα or ERβ positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1–/– mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous...

  3. A randomised controlled trial for overweight and obese parents to prevent childhood obesity - Early STOPP (STockholm Obesity Prevention Program

    Directory of Open Access Journals (Sweden)

    Cao Yingting

    2011-05-01

    Full Text Available Abstract Background Overweight and obesity have a dramatic negative impact on children's health not only during the childhood but also throughout the adult life. Preventing the development of obesity in children is therefore a world-wide health priority. There is an obvious urge for sustainable and evidenced-based interventions that are suitable for families with young children, especially for families with overweight or obese parents. We have developed a prevention program, Early STOPP, combating multiple obesity-promoting behaviors such unbalanced diet, physical inactivity and disturbed sleeping patterns. We also aim to evaluate the effectiveness of the early childhood obesity prevention in a well-characterized population of overweight or obese parents. This protocol outlines methods for the recruitment phase of the study. Design and methods This randomized controlled trial (RCT targets overweight and/or obese parents with infants, recruited from the Child Health Care Centers (CHCC within the Stockholm area. The intervention starts when infants are one year of age and continues until they are six and is regularly delivered by a trained coach (dietitian, physiotherapist or a nurse. The key aspects of Early STOPP family intervention are based on Swedish recommendations for CHCC, which include advices on healthy food choices and eating patterns, increasing physical activity/reducing sedentary behavior and regulating sleeping patterns. Discussion The Early STOPP trial design addresses weaknesses of previous research by recruiting from a well-characterized population, defining a feasible, theory-based intervention and assessing multiple measurements to validate and interpret the program effectiveness. The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge, this longitudinal RCT is the first attempt to demonstrate whether an early, long-term, targeted health promotion program focusing on healthy

  4. Association of FTO Polymorphisms with Early Age of Obesity in Obese Italian Subjects

    Directory of Open Access Journals (Sweden)

    Federica Sentinelli

    2012-01-01

    Aims of our study are to investigate: (1 the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI and obesity-related parameters in a large cohort (n=752 of Italian obese subjects; (2 the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P<0.043 and rs9930506 (P<0.029 with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI+1.4 kg/m2 per G allele. We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population.

  5. Origin of cardiovascular risk in overweight preschool children: a cohort study of cardiometabolic risk factors at the onset of obesity.

    Science.gov (United States)

    Shashaj, Blegina; Bedogni, Giorgio; Graziani, Maria P; Tozzi, Alberto E; DiCorpo, Maria L; Morano, Donatella; Tacconi, Ludovica; Veronelli, Patrizio; Contoli, Benedetta; Manco, Melania

    2014-10-01

    To date, the relationship among adiposity, insulin resistance, and cardiovascular risk factors at the onset of overweight or obesity has been unexplored. To assess whether insulin resistance and metabolic abnormalities are detectable at the onset of obesity and to unravel the interplay among adiposity, insulin resistance, and other such abnormalities. The Origin of Cardiovascular Risk in Overweight Preschool Children cohort study aimed to evaluate at the onset of obesity in preschool children the prevalence of metabolic abnormalities, including hypertension, dyslipidemia, impaired carbohydrate metabolism, and nonalcoholic fatty liver disease. Between July 1, 2011, and July 30, 2012, in the Rome municipality, 13 family pediatricians enrolled healthy children (age range, 2.0-5.8 years) in the study during their routine practice of growth monitoring. Clinical medical records of 5729 children were reviewed; 597 children manifested new-onset overweight or obesity as their body mass index changed from normal weight to overweight or obesity in the previous 12 months according to the International Obesity Task Force classification. Of them, 219 were studied. Patients with new-onset overweight or obesity underwent clinical laboratory testing, including oral glucose tolerance test, and ultrasonographic investigations of fatty liver and intimal medial thickness of the common carotid arteries, subcutaneous adipose tissue, and visceral adipose tissue. The homeostatic assessment model algorithm-insulin resistance was calculated. Among the entire population (n = 5729), overweight increased from 7.0% at 2.0 years to 16.9% at 5.8 years, with corresponding figures of 1.1% to 2.9% for obesity. In total, 597 overweight or obese children (10.4%) were identified, and 219 of them (36.7%) were studied. Among the latter, 86 patients (39.3%) had at least 1 metabolic abnormality. Hypertension was diagnosed in 29 patients (13.2%), dyslipidemia in 55 patients (25.1%), impaired fasting

  6. Epigenetics, obesity and early-life cadmium or lead exposure.

    Science.gov (United States)

    Park, Sarah S; Skaar, David A; Jirtle, Randy L; Hoyo, Cathrine

    2017-01-01

    Obesity is a complex and multifactorial disease, which likely comprises multiple subtypes. Emerging data have linked chemical exposures to obesity. As organismal response to environmental exposures includes altered gene expression, identifying the regulatory epigenetic changes involved would be key to understanding the path from exposure to phenotype and provide new tools for exposure detection and risk assessment. In this report, we summarize published data linking early-life exposure to the heavy metals, cadmium and lead, to obesity. We also discuss potential mechanisms, as well as the need for complete coverage in epigenetic screening to fully identify alterations. The keys to understanding how metal exposure contributes to obesity are improved assessment of exposure and comprehensive establishment of epigenetic profiles that may serve as markers for exposures.

  7. Dissecting Allele Architecture of Early Onset IBD Using High-Density Genotyping.

    Directory of Open Access Journals (Sweden)

    David J Cutler

    Full Text Available The inflammatory bowel diseases (IBD are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent.We performed a fine mapping association study of early onset IBD using high-density Immunochip genotyping on 1008 pediatric-onset IBD cases (801 Crohn's disease; 121 ulcerative colitis and 86 IBD undetermined and 1633 healthy controls. Of the 158 SNP genotypes obtained (out of the 163 identified in adult onset, this study replicated 4% (5 SNPs out of 136 of the SNPs identified in the Crohn's disease (CD cases and 0.8% (1 SNP out of 128 in the ulcerative colitis (UC cases. Replicated SNPs implicated the well known NOD2 and IL23R. The point estimate for the odds ratio (ORs for NOD2 was above and outside the confidence intervals reported in adult onset. A polygenic liability score weakly predicted the age of onset for a larger collection of CD cases (p< 0.03, R2= 0.007, but not for the smaller number of UC cases.The allelic architecture of common susceptibility variants for early onset IBD is similar to that of adult onset. This immunochip genotyping study failed to identify additional common variants that may explain the distinct phenotype that characterize early onset IBD. A comprehensive dissection of genetic loci is necessary to further characterize the genetic architecture of early onset IBD.

  8. Working memory and FDG-PET dissociate early and late onset Alzheimer disease patients.

    Science.gov (United States)

    Kalpouzos, Grégoria; Eustache, Francis; de la Sayette, Vincent; Viader, Fausto; Chételat, Gaël; Desgranges, Béatrice

    2005-05-01

    The aims of this study were to determine the influence of the onset of Alzheimer's disease (AD) on 1) memory and cerebral glucose metabolism, 2) the relationships between cognitive performance and cerebral glucose metabolism. Brain metabolism was measured by 18FDG-PET in 12 early onset AD patients (age 65), with comparable mean MMSE scores. Working memory, semantic memory and episodic memory were assessed. Cognitivo-metabolic correlations (CMC) and complementary interregional correlations were performed in order to identify specific neurocognitive processes within each group. Both AD groups performed poorly on all tasks, except digit span in the late onset group. The early onset group performed more poorly than the late onset one on both the digit span and Brown-Peterson Paradigm (BPP) tasks. Temporo-parietal hypometabolism was found in both groups, the left hemisphere being more affected than the right, especially in the early onset patients, who also showed specific left frontal hypometabolism. For the BPP task, the CMC principally involved left frontal areas in the early onset group, and the cerebellum in the late onset one. For the digit span task, they involved cerebellar and occipital regions in the latter. Regarding the digit span, the occipital and cerebellar involvement may have reflected an effective compensatory mechanism in the late onset patients, while high left supramarginal gyrus hypometabolism in the early onset patients may have explained their failure in this task. In the BPP task, the lower performance of the early onset group may have been due to a frontal lobe dysfunction, as suggested by 1) the hypometabolism of this region, 2) the CMC results, 3) the interregional correlations, which indicated greater disruption of the antero- posterior loop.

  9. Family functioning and obesity risk behaviors: implications for early obesity intervention.

    Science.gov (United States)

    Wen, Li Ming; Simpson, Judy M; Baur, Louise A; Rissel, Chris; Flood, Victoria M

    2011-06-01

    Family functioning is found to be associated with overweight and obesity in childhood, but its association with maternal obesity risk behaviors is not clear. This study aimed to investigate whether family functioning is associated with maternal obesity risk behaviors and to inform the development of early obesity interventions. A total of 408 first-time mothers at 24-34 weeks of pregnancy were included in the study. They participated in the Healthy Beginnings Trial (HBT) conducted in southwest Sydney, Australia in 2008. An analysis of cross-sectional baseline data was conducted using ordinal logistic regression modeling. Key measures were assessed using the McMaster Family Assessment Device, and self-reported obesity risk behaviors including excessive consumption of soft drinks, fast food, and excessive small screen time. The study found that 30% of the study population had a family functioning score ≥2, indicating unhealthy family functioning. About one-third (36%) of the mothers had more than one obesity risk behavior. Mothers with a family functioning score ≥2 were more likely to have more than one obesity risk behavior (47% vs. 32%, P family functioning score ≥2 increased from 22% to 29% to 39% as the number of maternal obesity risk behaviors increased from 0 to 1 to 2 or more, giving an adjusted proportional odds ratio (AOR) of 2.0 (95% confidence interval (CI) 1.3-3.0, P = 0.001). Family functioning is independently associated with the number of maternal obesity risk behaviors after allowing for the effects of maternal age and education. Overweight and obesity interventions should consider addressing family functioning.

  10. Factors Associated with Early Platelet Activation in Obese Children

    Science.gov (United States)

    García, Anel Gómez; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Aguilar, Cleto Alvarez

    2014-01-01

    Objective To investigate the factors associated with platelet activation in obese children. Design Cross-sectional study. Setting Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:−0.215; t:−2.819; P=0.006). Conclusions Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. PMID:24415745

  11. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    Science.gov (United States)

    2015-04-01

    a potential modulator of Abeta toxicity), and NOTCH4 (a presenilin pathway gene). Exome chip results identified variants in MICA encoding the HLA-A...and 2+ Non-white Hispanic families, including the AD-relevant HLA-A (associated with earlier AD age-at-onset), CHST15 (a potential modulator or Abeta

  12. Early Onset Optic Neuritis Following Measles-Rubella Vaccination

    Directory of Open Access Journals (Sweden)

    Siamak Moradian

    2008-12-01

    Full Text Available

    PURPOSE: To report two cases of optic neuritis with onset less than 24 hours following measles-rubella (MR vaccination. CASE REPORT: Two teenage patients developed acute optic neuritis 6 to 7 hours after MR booster vaccination. The first patient demonstrated bilateral papillitis and severe visual loss but improved significantly with pulse intravenous steroid therapy with methylprednisolone 500 mg/day. The second patient had unilateral retrobulbar optic neuritis and demonstrated excellent visual recovery without intervention. CONCLUSION: Acute optic neuritis is a rare complication of MR vaccination and may occur early after immunization.

  1. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    Science.gov (United States)

    2017-04-01

    focus toward identification of Alzheimer disease (AD) risk genes over the past five years has been testing the common disease common variant (CDCV...hypothesis through the use of genome-wide association studies (GWAS) in late onset Alzheimer disease (LOAD). While common variation clearly plays a role...12-25 4 INTRODUCTION: The primary focus in the identification of Alzheimer disease (AD) risk genes has focused on the common disease

  2. DYT1 MUTATIONS AMONGST EARLY ONSET PRIMARY DYSTONIA PATIENTS IN CHINA

    Institute of Scientific and Technical Information of China (English)

    Jing-fang Yang; Jian-yu Li; Yong-jie Li; Tao Wu; Yan-li Zhang; Biao Chen

    2008-01-01

    Objective To investigate the frequency of GAG deletion in the DYTI gene among early onset primary dystonia patients in China. Mothods Thirteen patients with early onset primary torsion dystonia were screened for mutation in exon 5 of the DYT1 gene using denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing, and the results were confirmed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Resuits The GAG deletion mutation which results in Glu302del in exon 5 of the DYTI gene was found in 5 pa-tients. The detecting results were consistent between with DHPLC and PCR-RFLP. We did not fred any other mutations in the DYT1 gene.Conclusions The GAG deletion in the DYT1 gene is common amongst early onset primary torsion dystonia pa-tients in China. The frequency of DYT1 mutation is not significantly different between European and Asian patients with early onset primary dystonia.

  3. Early-Onset, Regular Cannabis Use Is Linked to IQ Decline

    Science.gov (United States)

    ... Is Linked to IQ Decline Early-Onset, Regular Cannabis Use Is Linked to IQ Decline Email Facebook ... that cannabis use may harm the developing brain. Cannabis Use Correlates With Cognitive Decline The study participants ...

  4. QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease

    National Research Council Canada - National Science Library

    Guarani, Virginia; Jardel, Claude; Chrétien, Dominique; Lombès, Anne; Bénit, Paule; Labasse, Clémence; Lacène, Emmanuelle; Bourillon, Agnès; Imbard, Apolline; Benoist, Jean-François; Dorboz, Imen; Gilleron, Mylène; Goetzman, Eric S; Gaignard, Pauline; Slama, Abdelhamid; Elmaleh-Bergès, Monique; Romero, Norma B; Rustin, Pierre; Ogier de Baulny, Hélène; Paulo, Joao A; Harper, J Wade; Schiff, Manuel

    2016-01-01

    ... (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy with liver disease, including defects in respiratory chain...

  5. Diet induced weight loss accelerates onset of negative alliesthesia in obese women

    Directory of Open Access Journals (Sweden)

    Frankham Patrick

    2005-10-01

    Full Text Available Abstract Background The physiological and behavioral responses to hypocaloric diet are to increase energy intake to defend a steady body weight. We utilized the method of "negative alliesthesia" for measuring the hedonic reponse to sweet stimulus before (Initial session and 3 months after entering a weight loss program. The negative alliesthesia test is known by physiologists but few clinical data exist. It is based on the observation that repeated pleasant gustatory stimuli turn into unpleasantness in the process of alliesthesia. At first visit participants repeatedly ingested sweet stimuli until they found them unpleasant and rated quantitatively on a linear analogue scale their hedonic experience. This procedure was repeated every 3 min until participants felt displeasure to end the session. The same protocol was followed after three months of following a weight loss diet. Dieting energy intake was from 1400 – 2000 kcal/d for 8 wk. Energy composition was 50% carb:25% prot: 25% lipid. After 8 wk caloric intake increased by 50 kcal/wk, to reach daily intake of 1800 – 2400 kcal/d. Energy composition was 50% carb:22% prot: 27% lipid. We report results on the effect of slow weight loss on negative alliesthesia in ten obese female participants enrolled in a commercial diet program based on Canada's Food Guide (Mincavi®. Results Results showed that diet lowered the mean BMI (Initial session 36.8 +/- 1.8 vs. 3 mo 34.9 +/- 1.8 kg/m2. At 3 mo the onset of negative alliesthesia, time to abandon experimental session, was shortened (Initial session 33 vs. 3 mo 24 min. The same trend was observed in the time to reach indifference (Initial session 21.9 +/- 3.8 vs. 3 mo 16.2 +/-2.4 min. There was no observed difference in maximum (Initial session +79.5 +/- 11.7; 3 mo +94.5 +/- 9.9 mm and minimum (Initial session -90.0 +/- 14.4; 3 mo -106 +/- 11.1 mm hedonic rating. Conclusion Earlier onset of negative alliesthesia, as seen in our participants, is not

  6. High Throughput Sequencing of Germline and Tumor from Men With Early-Onset Metastatic Prostate Cancer

    Science.gov (United States)

    2014-10-01

    challenge, Dr. Tomlins has continued to develop state of the art technologies to use formalin-fixed paraffin-embedded (FFPE) prostate cancer specimens...men with early-onset, metastatic prostate cancer PRINCIPAL INVESTIGATOR: Kathleen A. Cooney, M.D. CONTRACTING ORGANIZATION...High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-13-1-0371 5c

  7. Sarcopenic obesity and risk of new onset depressive symptoms in older adults: English Longitudinal Study of Ageing.

    Science.gov (United States)

    Hamer, M; Batty, G D; Kivimaki, M

    2015-12-01

    We examined the role of sarcopenic obesity as a risk factor for new-onset depressive symptoms over 6-year follow-up in a large sample of older adults. The sample comprised 3862 community dwelling participants (1779 men, 2083 women; mean age 64.6±8.3 years) without depressive symptoms at baseline, recruited from the English Longitudinal Study of Ageing. At baseline and 4-year follow-up, handgrip strength (kg) of the dominant hand was assessed using a hand-held dynamometer, as a measure of sarcopenia. The outcome was new onset depressive symptoms at 6-year follow-up, defined as a score of ⩾4 on the 8-item Centre of Epidemiological Studies Depression scale. Sarcopenic obesity was defined as obese individuals (body mass index ⩾30 kg m(-)(2)) in the lowest tertile of sex-specific grip strength (obese adults in the lowest tertile of handgrip strength (odds ratio (OR), 1.79, 95% confidence interval (CI), 1.10, 2.89) compared with non-obese individuals with high handgrip strength. Participants who were obese at baseline and had a decrease of more than 1 s.d. in grip strength over 4-year follow-up were at greatest risk of depressive symptoms (OR=1.97, 95% CI, 1.22, 3.17) compared with non-obese with stable grip strength. A reduction in grip strength was associated with higher risk of depressive symptoms in obese participants only, suggesting that sarcopenic obesity is a risk factor for depressive symptoms.

  8. Thin mother, obese child? A review of early risk factors for obesity in offspring.

    Science.gov (United States)

    Tabibzadeh, Pantea; Mewes, Ricarda

    2016-09-01

    The huge percentages of persons with obesity in many countries constitute a public health crisis. The severe consequences of obesity for physical health and emotional wellbeing already emerge in childhood. Therefore, the acknowledgment of early risk factors is essential to provide recommendations for prevention strategies. This review outlines the current state of research concerning early risk factors for obesity, that is, factors that even contribute to later obesity of the offspring during gestation. In this regard, this review specifically addresses the link between restricted eating behavior of the mother and obesity in her offspring. We systematically searched for articles in PsychINFO, PsychINDEX, MEDLINE, PubMed, MEDPILOT, and Web of Science, and we identified additional studies in bibliographies. Although some risk factors (e.g., short period of breastfeeding, gestational diabetes, and high maternal BMI) have a vast evidence base, others (e.g., restricted eating behavior and second-hand smoking) are insufficiently studied. Physical activity and diet programs in pregnancy can reduce not only the occurrence of gestational diabetes, but also the risk of inappropriate weight gain. As smoking during pregnancy and inappropriate eating behavior are associated with lower education, psychoeducation, for instance in sex education classes, could be easily conceivable.

  9. The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation

    Directory of Open Access Journals (Sweden)

    K.A. Sagar

    2015-12-01

    Full Text Available Marijuana (MJ use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24 and late onset (age 16 or later; n = 26, and 34 healthy control participants (HCs. All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

  10. 1:4 matched case-control study on influential factor of early onset neonatal sepsis.

    Science.gov (United States)

    Jiang, Z; Ye, G-Y

    2013-09-01

    Bacteria, funghi, viruses and protozoa can lead to neonatal sepsis. Neonatal sepsis is the leading cause of infectious disease onset and death in many neonates. To explore the major risk factors of early-onset neonatal sepsis and provide a scientific basis for strategies of early-onset neonatal sepsis prevention. A 1:4 matched case-control study was adopted and 147 cases of early-onset neonatal sepsis were enrolled. Conditional logistic regression model was used to analyze the univariate and multivariate data to estimate the odds ratio (OR) and the 95% confidence interval (95% CI). Univariate analysis shows that the impact factors on the occurrence of early-onset neonatal sepsis include the following: Maternal age > 35, mother having fixed occupation, mother of urban residence, abnormal fetal position, fetal times, parity, caesarean section, premature rupture of membranes, amniotic fluid volume abnormalities, pregnancy-induced hypertension, placental abnormalities, fetal distress, newborn gender, low birth weight infants, neonatal Apgar scoring at one and five minutes, neonatal jaundice, wet lung, anemia, IVH, and premature infant. Multivariate logistic regression analysis showed that maternal age > 35 (OR = 4.835, OR 95% CI = 1.170-19.981), cesarean section (OR = 0.103, OR 95% CI = 0.041-0.258), premature rupture of membranes (OR = 0.207, OR 95% CI = 0.078-0.547), premature infants (OR = 0.059, OR 95% CI = 0.010-0.329) and newborn jaundice (OR = 0.092, OR 95% CI = 0.021-0.404) were the factors of early-onset neonatal sepsis. Early-onset neonatal sepsis could be affected by multi-factors, and targeted prevention may reduce the incidence of early-onset neonatal sepsis rates.

  11. Are early-onset cannabis smokers at an increased risk of depression spells?

    Science.gov (United States)

    Fairman, Brian J; Anthony, James C

    2012-04-01

    A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both pcannabis smokers did not statistically differ from one another. Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Exercise and Early-Onset Alzheimer’s Disease: Theoretical Considerations

    Directory of Open Access Journals (Sweden)

    Astrid M. Hooghiemstra

    2012-04-01

    Full Text Available Background/Aims: Although studies show a negative relationship between physical activity and the risk for cognitive impairment and late-onset Alzheimer’s disease, studies concerning early-onset Alzheimer’s disease (EOAD are lacking. This review aims to justify the value of exercise interventions in EOAD by providing theoretical considerations that include neurobiological processes. Methods: A literature search on key words related to early-onset dementia, exercise, imaging, neurobiological mechanisms, and cognitive reserve was performed. Results/Conclusion: Brain regions and neurobiological processes contributing to the positive effects of exercise are affected in EOAD and, thus, provide theoretical support for exercise interventions in EOAD. Finally, we present the design of a randomized controlled trial currently being conducted in early-onset dementia patients.

  13. A systematic review of the long-term outcome of early onset schizophrenia

    DEFF Research Database (Denmark)

    Clemmensen, Lars; Vernal, Ditte Lammers; Steinhausen, Hans-Christoph

    2012-01-01

    of onset in these studies was 10 years, small to moderate for more unfavourable outcomes in males, and small to large for worse outcomes in studies including patients diagnosed before 1970. CONCLUSIONS: In contrast to the adult manifestation, the early manifestation of schizophrenia in childhood......ABSTRACT: BACKGROUND: The current review analyzes the long-term outcome and prognosis of early onset schizophrenia based on previously published studies onset schizophrenia based on previously published studies in 1980. METHODS: A systematic search of articles published in the English......-language literature after 1980 identified a total of 21 studies, which included 716 patients who were either suffering from early onset schizophrenia (EOS) or both EOS and other psychotic disorders (MIX). The authors of the current review scored the outcome as either "good," "moderate," or "poor." The mean age...

  14. A case of early-onset radiation retinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Yoko; Den, Seika; Shimizu, Kazuhiro; Ikeda, Tsunehiko [Osaka Medical Coll., Takatsuki (Japan)

    2001-12-01

    We encountered a 27-year-old male early caused by radiation retinopathy five months after radiotherapy (51 Gy) for astrocytoma. The retinopathy was the proliferative retinopathy, with several dot and blot hemorrhages, hard and soft exudate, increased capillary permeability, macula edema and avasucular areas. So it was treated with panretial photocoagulation like diabetic retinopathy. Now hemorrhage, exudate, edema and avascular areas were improved. Photocoagulation treatment is effective to stop the progression of radiation retinopathy. Radiation retinopathy is sometimes early caused, therefore long-term follow up is recommended on starting radiotherapy. (author)

  15. Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers

    Science.gov (United States)

    Hartz, Sarah M.; Short, Susan E.; Saccone, Nancy L.; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H.; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Guđbjartsson, Daniel; Hansel, Nadia N.; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Hum, Sc; Rosenberger, Albert; Scheet, Paul; Shaffer, John R.; Teumer, Alexander; Thompson, John R.; Vink, Jacqueline M.; Vogelzangs, Nicole; Wenzlaff, Angela S.; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H.; Balmforth, Anthony J.; Baumeister, Sebastian E.; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W.; Boyd, Heather A.; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M.; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S.; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M.; Hayward, Caroline; Heikkilä, Kauko; Lic, Phil; Hewitt, John K.; Hottenga, Jouke Jan; Jensen, Majken K.; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J.; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M.; Mathias, Rasika A.; McNeil, Daniel W.; Medland, Sarah E.; Montgomery, Grant W.; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M.; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I.; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J.; Francks, Clyde; Gejman, Pablo V.; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S.; Lehtimäki, Terho; Levinson, Douglas F.; Marazita, Mary L.; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D.; Murray, Jeffrey C.; Nöthen, Markus M.; Penninx, Brenda W.; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J.; Sanders, Alan R.; Schwartz, Ann G.; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E.; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H.-Erich; Amos, Christopher I.; Breslau, Naomi; Cannon, Dale S.; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O.; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G.; Stevens, Victoria L.; Stitzel, Jerry A.; Weiss, Robert B.; Kraft, Peter; Bierut, Laura J.

    2012-01-01

    Context Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources Primary data. Study Selection Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Data Extraction Uniform statistical analysis scripts were run locally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36–1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21–1.33, n = 19 505) (P = .01). Conclusion These results highlight an increased genetic vulnerability to smoking in early-onset smokers. PMID:22868939

  16. The impact of obesity on LADG for early gastric cancer.

    Science.gov (United States)

    Kim, Ki-Han; Kim, Min-Chan; Jung, Ghap-Joong; Kim, Hyung-Ho

    2006-01-01

    Laparoscopy-assisted distal gastrectomy (LADG) has become a viable alternative treatment for patients suffering with early gastric cancer. Surgeons have long thought that obesity might increase the rate of intraoperative or postoperative complications. We set out to clarify the effect that obesity has on performing LADG for the treatment of early gastric cancer. We retrospectively reviewed 97 patients who had undergone LADG for early gastric cancer between May 1998 and March 2004. We measured the degree of obesity by using the body mass index (BMI; kg/m(2)), and we compared the surgical outcomes between the normal BMI group (BMI or = 23 kg/m(2)). We further subdivided the patients into four groups: normal BMI males and normal BMI females, and high BMI males and high BMI females, and we analyzed them in terms of operation times, numbers of retrieved lymph nodes, and rates of postoperative complications. There were no significant differences between the normal and high BMI groups in terms of the patients' characteristics, surgical outcomes, postoperative courses, postoperative complications, and operation times. There were no statistically significant differences in the number of retrieved lymph nodes or in the rate of postoperative complications among the four groups (P = 0.5030 and P = 0.3489, respectively). However, there was a statistically significant difference in operation times among the four groups (P = 0.004). Specifically, the males in the high BMI group required a longer operation time than did the females with a normal BMI (P = 0.006) and the females with a high BMI (P = 0.019). For LADG in patients with early gastric cancer, obesity may affect the operation time, and men with high BMI require a longer operation time than do women with normal or high BMI.

  17. Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

    Science.gov (United States)

    Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

    2016-01-01

    This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

  18. Preliminary findings demonstrating latent effects of early adolescent marijuana use onset on cortical architecture

    Directory of Open Access Journals (Sweden)

    Francesca M. Filbey

    2015-12-01

    Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

  19. Late- versus early-onset geriatric depression in a memory research center

    Directory of Open Access Journals (Sweden)

    Carol Dillon

    2009-10-01

    Full Text Available Carol Dillon1, Ricardo F Allegri2, Cecilia M Serrano1, Mónica Iturry1, Pablo Salgado1, Frank B Glaser1, Fernando E Taragano21Memory Research Center, Department of Neurology, Hospital General Abel Zubizarreta, GCBA Buenos Aires, Argentina; 2Department of Neuropsychology (SIREN, CEMIC University, Buenos Aires, ArgentinaObjective: To contrast early-onset (<60 years and late-onset (>60 years depression in geriatric patients by evaluating differences in cognition, vascular comorbidity and sociological risk factors. Both patient groups were compared with normal subjects.Materials and methods: We recruited 76 patients with depressive symptoms (37 late onset and 39 early onset and 17 normal controls matched by age and educational level. All subjects were assessed using a semistructured neuropsychiatric interview and an extensive neuropsychological battery. Vascular and sociological risk factors were also evaluated.Results: We found a significant variation in performance between depressive patients and normal controls in most cognitive functions, especially memory (P < 0.0001, semantic fluency (P < 0.0001, verbal fluency, and digit-symbol (P < 0.0001. Late-onset depression patients scored lower and exhibited more severe impairment in memory domains than early-onset depression patients (P < 0.05. Cholesterol levels and marital status were significantly (P < 0.05 different between the depressive groups. Both depressed groups (early- and lateonset were more inactive than controls (P < 0.05; odds ratio: 6.02.Conclusion: Geriatric depression may be a manifestation of brain degeneration, and the initial symptom of a dementia. It is important to consider this in the treatment of patients that exhibit late-onset depressive symptoms.Keywords: early- and late-onset depression, geriatrics, cognition

  20. Early-Onset Chronic Inflammatory Disease Associated with Maternal Microchimerism

    Directory of Open Access Journals (Sweden)

    Tomoaki Ishikawa

    2012-01-01

    Full Text Available Maternal microchimerism (mMc refers to the presence of a small population of cells originating from the mother. Whether mMc leads to autoimmune responses in children remains controversial. We describe here an 11-year-old boy with persistent fever and elevated levels of C-reactive protein from infancy onward. During infancy, the patient presented with high fever, skin rashes, and hepatic dysfunction. Careful examination including a liver biopsy failed to reveal the cause. At 4 years old, petechiae developed associated with thrombocytopenia and positive anti-dsDNA autoantibodies. Steroid pulse therapy was effective, but the effect of low-dose prednisone was insufficient. At age 9, an extensive differential diagnosis was considered especially for infantile onset autoinflammatory disorders but failed to make a definitive diagnosis. On admission, the patient exhibited short stature, hepatosplenomegaly, generalized superficial lymphadenopathy, and rashes. Laboratory findings revealed anemia, elevated levels of inflammation markers, and hypergammaglobulinemia. Serum complement levels were normal. Serum levels of IL-6 and B-cell activating factor were elevated. Viral infections were not identified. Although HLA typing revealed no noninherited maternal antigens in lymphocytes, female cells were demonstrated in the patient’s skin and lymph nodes, suggesting that maternal microchimerism might be involved in the pathogenesis of fever without source in infants.

  1. Early Onset of Laying and Bumblefoot Favor Keel Bone Fractures

    Directory of Open Access Journals (Sweden)

    Sabine G. Gebhardt-Henrich

    2015-11-01

    Full Text Available Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely.

  2. Early Onset of Laying and Bumblefoot Favor Keel Bone Fractures.

    Science.gov (United States)

    Gebhardt-Henrich, Sabine G; Fröhlich, Ernst K F

    2015-11-27

    Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely.

  3. Early-onset gastric cancer: Learning lessons from the young

    OpenAIRE

    Milne, A. N.; Offerhaus, G J A

    2010-01-01

    There is by no means a clear-cut pattern of mutations contributing to gastric cancers, and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer, such as Helicobacter pylori infection, diet, ageing and other environmental factors. Tumours are unquestionably riddled with genetic changes yet we are faced with an unsolvable puzzle with respect to a temporal relationship. It is postulated that inherited genetic factors may be more important in early-on...

  4. The role of temperament in the relationship between early onset of tobacco and cannabis use: The TRAILS study

    NARCIS (Netherlands)

    Creemers, H.E.; Korhonen, T.; Kaprio, J; Vollebergh, W.A.M.; Ormel, J.; Verhulst, F.C.; Huizink, A.C.

    2009-01-01

    Background: While temperamental characteristics have been related to the onset of cannabis use, it is not clear at what point(s) along the trajectory from early onset of tobacco use (EOT) to early onset of cannabis use (EOC) these characteristics exert their impact. This study examined if (1) temper

  5. The role of temperament in the relationship between early onset of tobacco and cannabis use : The TRAILS study

    NARCIS (Netherlands)

    Creemers, Hanneke E.; Korhonen, Tellervo; Kaprio, Jaakko; Vollebergh, Wilma A. M.; Ormel, Johan; Verhulst, Frank C.; Huizink, Anja C.

    2009-01-01

    Background: While temperamental characteristics have been related to the onset of cannabis use, it is not clear at what point(s) along the trajectory from early onset of tobacco use (EOT) to early onset of cannabis use (EOC) these characteristics exert their impact. This study examined if (1) temper

  6. Differences between early and late-onset Alzheimer's disease in neuropsychological tests.

    Directory of Open Access Journals (Sweden)

    Francisca eSá

    2012-05-01

    Full Text Available Although patients with Alzheimer disease (AD share clinical and histological features regardless of age of onset, the hypothesis that early-onset AD constitutes a distinct subgroup prevails. Some authors suggest that early attention or language impairment constitute patterns of differentiation in terms of neuropsychological profile. However, investigations are not consensual in terms of cognitive domains affected in each group.Aim: To investigate whether there is early neuropsychological difference between two types of AD using the conventional dividing line of 65 years.Methods: We evaluated the results obtained in the Mini-Mental State Examination (MMSE and in a comprehensive neuropsychological battery – Battery of Lisbon for the Assessment of Dementia (BLAD, at a Dementia clinic in the University Hospital of Coimbra and a Memory Clinic. Consecutive patients with a clinical probable diagnosis of mild to moderate AD, using standard criteria (DSMIV and NINCDS-ADRDA, were selected. Statistical analysis was performed using Qui-square and U-Mann-Whitney, for categorical and non-categorical variables.Results: The sample included 280 patients: 109 with early-onset AD and 171 with a late-onset form. Groups were comparable in gender, education, severity of disease and MMSE. In BLAD, the early onset group had lower scores in Naming (p=0,025, Right-Left Orientation (p=0,029 and Praxis (p=0,001, and better performances in Orientation (p=0,001 and Visual Memory (p=0,022. After application of Bonferroni correction for multiple comparisons only Praxis and Orientation could differentiate the two groups.Discussion: The results are suggestive of dissociated profiles between early and late-onset AD. Younger patients have a major impairment in Praxis and a tendency for a great impairment in neocortical temporal functions. Late-onset form had a tendency for worse performances in Visual Memory and Orientation, suggesting a more localized disease to the limbic

  7. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

    Directory of Open Access Journals (Sweden)

    Rafaela Torres Portugal Leite

    2015-01-01

    Full Text Available Introduction. Bipolar disorder (BD implies risk of suicide. The age at onset (AAO of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

  8. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

    Science.gov (United States)

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

  9. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

    Science.gov (United States)

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; Souza, Fábio Gomes de Matos e

    2015-01-01

    Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear. PMID:26097750

  10. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts.

    Science.gov (United States)

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; de Matos E Souza, Fábio Gomes

    2015-01-01

    Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words "bipolar disorder," "suicide attempts," "cannabis," "marijuana," "early age at onset," and "early onset." Results. The following percentages in bipolar patients were found: suicide attempts 3.6-42%; suicide attempts and substance use 5-60%; suicide attempts and cannabis use 15-42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

  11. Early Liver Transplantation for Neonatal-Onset Methylmalonic Acidemia.

    Science.gov (United States)

    Spada, Marco; Calvo, Pier Luigi; Brunati, Andrea; Peruzzi, Licia; Dell'Olio, Dominic; Romagnoli, Renato; Porta, Francesco

    2015-07-01

    With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalamin-unresponsive methylmalonyl-CoA mutase (MCM) deficiency is characterized by the persistent risk of recurrent life-threatening decompensation episodes with metabolic acidosis, hyperammonemia, and coma. Liver transplant has been proposed as an alternative treatment and anecdotally attempted in the last 2 decades with inconsistent results. Most criticisms of this approach have been directed at the continuing risk of neurologic and renal damage after transplant. Here, we report the perioperative and postoperative clinical and biochemical outcomes of 2 patients with severe MCM deficiency who underwent early liver transplant. In both cases, liver transplant allowed prevention of decompensation episodes, normalization of dietary protein intake, and a marked improvement of quality of life. No serious complications have been observed at 12 years' and 2 years' follow-up, respectively, except for mild kidney function impairment in the older patient. On the basis of our experience, we strongly suggest that liver transplant should be offered as a therapeutic option for children with cobalamin-unresponsive MCM deficiency at an early stage of the disease.

  12. Association between rs9930506 polymorphism of the fat mass & obesity-associated (FTO) gene & onset of obesity in Polish adults.

    Science.gov (United States)

    Wrzosek, Malgorzata; Zakrzewska, Anna; Ruczko, Lech; Jabłonowska-Lietz, Beata; Nowicka, Grażyna

    2016-03-01

    The fat mass and obesity-associated (FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults. The study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism. It was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes. This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.

  13. PREVALENCE AND SUSCEPTIBILITY PATTERN OF E. COLI IN LOW BIRTH WEIGHT NEONATES OF EARLY ONSET SEPSIS

    Directory of Open Access Journals (Sweden)

    R. Singh et al.

    2011-12-01

    Full Text Available Neonatal sepsis is one of the commonest cause of neonatal mortality in the developing world which can be classified into early onset sepsis (EOS which occurs in the first 7 days of life and late onset sepsis (LOS which occurs ≥7 days of life. E. coli has been reported to be one of the significant and most common nosocomial pathogen which may cause septicemia, pneumonia and meningitis in the newborn. Most of the antibiotics which have been used extensively as life saving are rendered useless because of the emergence of resistant strains of bacterias. Therefore for determining the prevalence and antimicrobial susceptibility pattern of E. coli which is responsible for EOS and LOS and to establish the relationship with birth weight, a total of 229 blood samples were obtained from the neonates admitted to neonatal intensive care unit (NICU who showed the clinical signs and symptoms of neonatal sepsis and sent for culture and sensitivity. Out of these 229, 102 showed the positive culture, among which early onset sepsis was found in 80 neonates while late onset sepsis was diagnosed in 22 neonates. The most frequent pathogen isolated from positive blood culture was E. coli (66.66% and it was also the most common pathogen in low birth weight and preterm neonates of both early (59 cases- 57.84% and late-onset (9 cases- 8.82% sepsis and the incidence was found higher in early onset sepsis. The isolate was completely resistant to vancomycin and the resistance was higher for monotherapy of semi-synthetic penicillin group of antibiotics than their combination therapy with sulbactum. Imepenam and gatifloxacin showed the highest sensitivity (100%, followed by Piperacillin - tazobactum and ciprofloxacin, however the frequency of resistance was more common in low birth weight neonates of early onset sepsis.

  14. Early onset primary pulmonary cryptococcosis in a renal transplant patient

    Directory of Open Access Journals (Sweden)

    Tarai B

    2010-01-01

    Full Text Available We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB. Broncho-alveolar fluid (BAL shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold in serum and was negative in cerebrospinal fluid (CSF. The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.

  15. Pantoea species causing early onset neonatal sepsis: a case report.

    Science.gov (United States)

    Tiwari, Shreekant; Beriha, Siba Shankar

    2015-09-04

    Pantoea agglomerans is a plant pathogen which very rarely causes an opportunistic infection. Human beings are usually infected by thorn prick injuries or by contaminated parenteral fluids. Pantoea agglomerans has been reported as a cause of neonatal sepsis very rarely and to the best of our knowledge this is the first reported case from India. A 4-day-old Asian baby boy from the rural area of Odisha, India, was admitted to our neonatal intensive care unit when he presented with fever, tachypnea and chest retraction. Pantoea species were isolated from his blood culture. He was treated successfully with meropenem administered intravenously and other supportive measures. Early detection and proper management may cause a favorable outcome.

  16. "Greenlight study": a controlled trial of low-literacy, early childhood obesity prevention

    National Research Council Canada - National Science Library

    Sanders, Lee M; Perrin, Eliana M; Yin, H Shonna; Bronaugh, Andrea; Rothman, Russell L

    2014-01-01

    ..., are at increased risk of developing obesity. The objective of the Greenlight Intervention Study is to assess the effectiveness of a low-literacy, primary-care intervention on the reduction of early childhood obesity...

  17. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    Science.gov (United States)

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.

  18. Loss of Nfkb1 leads to early onset aging.

    Science.gov (United States)

    Bernal, Giovanna M; Wahlstrom, Joshua S; Crawley, Clayton D; Cahill, Kirk E; Pytel, Peter; Liang, Hua; Kang, Shijun; Weichselbaum, Ralph R; Yamini, Bakhtiar

    2014-11-01

    NF-κB is a major regulator of age-dependent gene expression and the p50/NF-κB1 subunit is an integral modulator of NF-κB signaling. Here, we examined Nfkb1-/- mice to investigate the relationship between this subunit and aging. Although Nfkb1-/- mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes. In addition, aged Nfkb1-/- animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+. In vitro, serially passaged primary Nfkb1-/- MEFs have more senescent cells than comparable Nfkb1+/+ MEFs. Also, Nfkb1-/- MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1-/- animals compared to Nfkb1+/+. Finally, in wildtype animals a substantial decrease in p50 DNA binding is seen in aged tissue compared to young. Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence. Moreover, loss of p50 DNA binding is a prominent feature of aged mice relative to young. These findings support the strong link between the NF-κB pathway and mammalian aging.

  19. Early-Life Toxic Insults and Onset of Sporadic Neurodegenerative Diseases-an Overview of Experimental Studies.

    Science.gov (United States)

    Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma

    2016-01-01

    The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies.

  20. The role of SCL2A1 in Early Onset and Childhood Absence Epilepsies

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    Introduction: Early onset absence epilepsy (EOAE) constitutes an idiopathic generalized epilepsy syndrome with typical absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter of the blood-brain barrier (GLUT-1), account for approximately 10% of EOAE......>C) leading to an amino acid exchange (336Leu>Val), the family history was unremarkable. The other EOAE patient with a very early onset of a severe epilepsy phenotype and movement disorder had a base exchange at position c.1189C>T causing a stop codon (p.Q397X) in exon 9. Familial GTCS were reported in his...

  1. Hybrid Model for Early Onset Prediction of Driver Fatigue with Observable Cues

    Directory of Open Access Journals (Sweden)

    Mingheng Zhang

    2014-01-01

    Full Text Available This paper presents a hybrid model for early onset prediction of driver fatigue, which is the major reason of severe traffic accidents. The proposed method divides the prediction problem into three stages, that is, SVM-based model for predicting the early onset driver fatigue state, GA-based model for optimizing the parameters in the SVM, and PCA-based model for reducing the dimensionality of the complex features datasets. The model and algorithm are illustrated with driving experiment data and comparison results also show that the hybrid method can generally provide a better performance for driver fatigue state prediction.

  2. Clinical characteristics of early- and late-onset gout: A cross-sectional observational study from a Chinese gout clinic.

    Science.gov (United States)

    Zhang, Bingqing; Fang, Weigang; Zeng, Xuejun; Zhang, Yun; Ma, Ya; Sheng, Feng; Zhang, Xinlei

    2016-11-01

    A retrospective cross-sectional study using data from an outpatient clinic in China was conducted to investigate the clinical features of early-onset gout patients.All patients diagnosed with gout were asked about clinical characteristics of their gout and comorbid diseases. Patients presenting with acute flares were asked about common triggers before the flare. "Early-onset" gout was defined as onset of gout before 40 years and "late-onset" as onset ≥40 years. Major joint involvement, flare frequency before presentation, the cumulative number of involved joints, proportions of tophi complications at presentation, flare triggers, as well as any metabolic, cardiovascular, cerebrovascular, and renal comorbidities, were compared between the 2 groups.A total of 778 gout patients were enrolled in this study, including 449 (57.7%) in the early-onset group and 329 (42.3%) in the late-onset group. Compared with the late-onset gout patients, the early-onset gout patients had a higher proportion of ankle/mid-foot involvement (62.8% vs 48.2%, P gout patients had fewer metabolic, cardiovascular, cerebrovascular, or renal complications.Early- and late-onset gout patients had different clinical features. Early-onset seems to be influenced more by lifestyle, while late-onset patients have more complications because of comorbidities.

  3. Perbedaan Berat Lahir Bayi Pasien Preeklampsia Berat / Eklampsia Early dan Late Onset di RSUP Dr. M. Djamil Padang

    Directory of Open Access Journals (Sweden)

    Rizka Amelia

    2016-01-01

    Full Text Available AbstrakPreeklampsia dan eklampsia tidak hanya berdampak bagi ibu, tetapi juga terhadap janin yang dikandungnya, seperti hambatan pertumbuhan janin intrauterin yang dapat dilihat dari berat lahir bayi tersebut. Ibu dengan preeklampsia berat/ eklampsia early onset cenderung melahirkan bayi dengan berat lahir Kecil untuk Masa Kehamilan (KMK, sementara yang  late onset cenderung melahirkan bayi dengan berat lahir Sesuai untuk Masa Kehamilan (SMK atau bahkan Besar untuk Masa Kehamilan (BMK. Tujuannya penelitian ini adalah menentukan perbedaan berat lahir bayi pasien preeklampsia berat/ eklampsia early dan late onset. Penelitian ini dilaksanakan dari Oktober 2012 sampai Juli 2013 di bagian Rekam Medik RSUP Dr. M. Djamil Padang. Jenis penelitian yang digunakan adalah observasional analitik dengan desain cross sectional. Hasil penelitian menunjukkan bahwa angka kejadian preeklampsia berat/ eklampsia early onset adalah 26,1% dan yang late onset sebanyak 73,9%. Bayi KMK lebih banyak dilahirkan oleh ibu preeklampsia berat/ eklampsia early onset (16,67% dibandingkan dengan yang  late onset (7,35%. Setelah dilakukan analisis melalui uji chi-square, disimpulkan bahwa tidak ada perbedaan berat lahir bayi antara pasien preeklampsia berat/eklampsia early dan late onset secara signifikan (p>0,05.Kata kunci: preeklampsia berat/eklampsia early onset, preeklampsia berat/eklampsia late onset, berat lahir bayi AbstractPreeclampsia and eclampsia are not only effect to mother, but also influent to the fetus, such as intrauterine fetal growth retardation  which can be seen as baby's birth weight. Mothers with early onset severe preeclampsia / eclampsia tend to give birth small for gestational age  babies, while the late onset tend to give birth normal birth weight or large for gestational age babies. The objective of this study was to determine the differentiation between baby's birth weight of early and late onset severe preeclampsia/ eclampsia. The research was

  4. Raynaud's syndrome: comparison of late and early onset forms using hand perfusion scintigraphy.

    Science.gov (United States)

    Csiki, Z; Galuska, L; Garai, I; Szabó, N; Varga, J; András, Cs; Zeher, M

    2006-09-01

    Primary Raynaud's disease is generally a disease of younger females; however, there are cases where symptoms present over the age of 40. These cases are described as late onset. In our current prospective study we compared the characteristics of early and late onset types of primary Raynaud's in 127 patients. In addition to the collection of medical records, we performed capillary-microscopy and hand perfusion scintigraphy using Tc-99 m DTPA to evaluate the microcirculation of each patient's fingers. Regarding the spectrum of the capillary-microscopic findings, we did not find any significant difference between the early and late onset forms. However, in hand perfusion examinations done using Tc-99 m DTPA, we measured a significantly lower finger/palm ratio (FPR) in the early onset group of patients. We also observed a correlation between the duration of the disease and the FPR, as well as between the age and FPR. Longer disease duration resulted in a significantly lower FPR. On the basis of our results, we believe that late onset Raynaud's should be treated as a separate entity. Due to its different characteristics found on examination and follow-up of our patients, functional hand perfusion examination should be recommended independently of the age-related characteristics of the disease.

  5. Maternal obesity in early pregnancy and subsequent pregnancy outcome in a Nigerian population.

    Science.gov (United States)

    Ezeanochie, M C; Ande, A B; Olagbuji, B N

    2011-12-01

    Despite a rising prevalence worldwide, there is limited data on pregnancy outcome among African women with prepregnancy or early pregnancy obesity. This was a case-control study to determine the prevalence of maternal obesity in early pregnancy and compare the subsequent pregnancy outcome between 201 women with obesity and 201 non-obese controls in a University Teaching Hospital in Nigeria. The prevalence of obesity in early pregnancy was 9.63%. Obesity was significantly associated with advanced maternal age and parity > or =1. It was also a risk factor for pregnancy induced hypertension, admissions during pregnancy, caesarean delivery and associated with 5th minute apgar score Obesity in early pregnancy is a risk factor for adverse pregnancy outcome among pregnant Nigerian women. This information should be utilised by physicians to improve the outcome of pregnancy and promote safe motherhood.

  6. Managing early childhood obesity in the primary care setting: a behavior modification approach.

    Science.gov (United States)

    Drohan, Samantha H

    2002-01-01

    The purpose of this article is to encourage primary care pediatric nurses to begin behavioral-based obesity treatment efforts as early as the preschool years. By examining the critical periods for obesity development and how the formation of food and activity behaviors interacts with those critical periods during the preschool years, the value of initiating early obesity treatment will be highlighted. Furthermore, the theory of behavior modification is presented and core principles are applied to early childhood weight management efforts.

  7. Candidate colorectal cancer predisposing gene variants in Chinese early-onset and familial cases

    NARCIS (Netherlands)

    Zhang, J.X.; Fu, L.; Voer, R.M. de; Hahn, M.M.; Jin, P.; Lv, C.X.; Verwiel, E.T.; Ligtenberg, M.J.L.; Hoogerbrugge, N.; Kuiper, R.P.; Sheng, J.Q.; Geurts van Kessel, A.H.M.

    2015-01-01

    AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer (CRC) predisposing genes in early-onset or familial CRC cases. METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with non-polyposis CRC

  8. Genetic correlates of early accelerated infant growth associated with juvenile-onset type 1 diabetes

    NARCIS (Netherlands)

    Kharagjitsingh, A.V.; de Ridder, M.A.J.; Alizadeh, B.Z.; Veeze, H.J.; Bruining, G.J.; Roep, B.O.; Koeleman, Bobby P.C.

    2012-01-01

    Objective: We previously showed that accelerated growth predisposing to development of childhood-onset type 1 diabetes (T1D) is restricted to the first year after birth. We assessed whether this phenomenon of increased early growth is associated with variants of two genes, insulin-like growth factor

  9. Assessing early-onset hallucinations in the touch-screen generation.

    Science.gov (United States)

    Demeulemeester, Morgane; Kochman, Fréderic; Fligans, Benjamin; Tabet, Ahmed J; Thomas, Pierre; Jardri, Renaud

    2015-03-01

    The increasing development of apps for digital devices provides an opportunity for new instruments to assess hallucinations in young individuals. Here we present the Multisensory HAllucinations Scale for Children (MHASC), dedicated to assessing complex early-onset hallucinations. The MHASC will soon be translated into multilanguage versions with the support of the International Consortium of Hallucination Research. Royal College of Psychiatrists.

  10. Early onset of cannabis use: Does personality modify the relation with changes in perceived parental involvement?

    NARCIS (Netherlands)

    Creemers, Hanneke E.; Buil, J. Marieke; van Lier, Pot A. C.; Keijsers, Loes; Meeus, W.H.J.; Koot, Hans M.; Huizink, Anja C.

    2015-01-01

    Background The present study examined (1) the association between changes in perceived parental control and support from age 13 to 15 and early onset of cannabis use (before age 16), and (2) whether personality modifies the association between a decline in perceived parental control and support and

  11. Early Onset Ageing and Service Preparation in People with Intellectual Disabilities: Institutional Managers' Perspective

    Science.gov (United States)

    Lin, Jin-Ding; Wu, Chia-Ling; Lin, Pei-Ying; Lin, Lan-Ping; Chu, Cordia M.

    2011-01-01

    Although longevity among older adults with intellectual disabilities is increasing, there is limited information on their premature aging related health characteristics and how it may change with increasing age. The present paper provides information of the institutional manager's perception on early onset aging and service preparation for this…

  12. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

    NARCIS (Netherlands)

    A.N.A. Milne; R. Carvalho; F.M. Morsink; A.R. Musler; W.W.J. de Leng; A. Ristimaki; G.J.A. Offerhaus

    2006-01-01

    Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (<= 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in g

  13. Early-onset periodontitis in Morocco is associated with the highly leukotoxic clone of Actinobacillus actinomycetemcomitans

    DEFF Research Database (Denmark)

    Haubek, Dorte; Ennibi, O.-K.; Poulsen, Knud

    2001-01-01

    A particular clone (JP2) of Actinobacillus actinomycetemcomitans with increased leukotoxin production has been isolated from individuals with early-onset periodontitis (EOP). The aim of this study was to determine the frequency of carriers of this clone and its association with EOP in Moroccan...

  14. Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

    Science.gov (United States)

    Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

    2011-01-01

    Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

  15. Apolipoprotein E genotype and association between smoking and early onset Alzheimer's disease.

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); P. de Knijff (Peter); M. Cruts (Marc); A. Wehnert (Anita); L.M. Havekes; C. van Broeckhoven (Christine); A. Hofman (Albert)

    1995-01-01

    textabstractOBJECTIVE--To investigate the hypothesis that differential survival between smokers and non-smokers leading to a decrease in the frequency of the e4 allele of the apolipoprotein E gene may explain the inverse relation between smoking history and early onset Alzheimer's disease. DESIGN--A

  16. [A study on early-onset group "B" streptococcal neonatal infection].

    Science.gov (United States)

    Vacheva, R; Todorova, M; Decheva, A; Yarakova, N; Kraleva, I; Takova, Ts; Dimitrova, N; Dobreva, A

    2012-01-01

    The results achieved with 80% reduction in the incidence of early-onset neonatal group B streptococcal (GBS) sepsis following the implementation of the preliminary (1996, 2002) and subsequently the revised (2010) guidelines for intrapartum antibiotic prophylaxis imposed the discussion on a large scale of the updated:--algorithms for GBS screening (35-37 weeks of gestation) with the recommended dosage of penicillin-G for intrapartum antibiotic prophylaxis for women having normal labor and delivery;--algorithms for GBS screening and intrapartum antibiotic prophylaxis for women with preterm labor (PPROM) or premature rupture of membranes (PROM);--intrapartum antibiotic prophylaxis regimens for women with penicillin allergy;--algorithm for management of newborns with respect to risk of early-onset GBS disease. The present study is aimed at studying the distribution of the early-onset GBS disease in our country based on the data of leading obstetrics & gynecology clinics and wards. The aim is to diferrentiate clinically the cases and investigate the influence of the known risk factors on the part of the mother. A special accent is put over the microbiological diagnostics of cases in view of CDC expanded recommendations on the laboratory methods for identification of GBS. As a final conclusion the necessity for introduction of an official registration of the early- and late-onset GBS disease in the country is emphasized.

  17. Clinical features and mortality in patients with early-onset Alzheimer's disease.

    NARCIS (Netherlands)

    W.N. Samson; C.M. van Duijn (Cock); W.C.J. Hop (Wim); A. Hofman (Albert)

    1996-01-01

    textabstractIn a population-based study of 198 patients with probable early-onset Alzheimer's disease (AD), we studied the occurrence of extrapyramidal signs (tremors and rigidity), myoclonus, psychosis and seizures, as well as their predictive value for mortality. The presence of tremors was signif

  18. Assessing Age of Onset Effects in (Early) Child L2 Acquisition

    Science.gov (United States)

    Unsworth, Sharon

    2013-01-01

    This study compares the development of three different types of bilingual/second language children in their acquisition of gender-marking on adjectives in Dutch to investigate whether there is evidence for age-of-onset effects in early childhood as proposed by Meisel (2009). The three groups of children are: simultaneous bilingual children,…

  19. DYT1 mutations in early onset primary torsion dystonia and Parkinson disease patients in Chinese populations.

    Science.gov (United States)

    Yang, Jing-Fang; Wu, Tao; Li, Jian-Yu; Li, Yong-Jie; Zhang, Yan-Li; Chan, Piu

    2009-01-30

    Torsion dystonia is an autosomal dominant movement disorder characterized by involuntary, repetitive muscle contractions and twisted postures. The most severe early onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. Moreover, dystonia and Parkinson disease share the common feature of reduced dopamine neurotransmission in the striatum, so we assumed that mutations in the DYT1 gene might have the same role in cases of early onset primary torsion dystonia (EOPTD) and early onset Parkinson disease (EOPD) that present dystonia. In this present study, 17 patients with EOPTD, 221 patients with EOPD and 164 control subjects were screened for mutations of the DYT1 gene by denaturing high performance liquid chromatography (DHPLC), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing. Our results showed that the GAG deletion was identified in 7 EOPTD patients, which results in Glu302del of DYT1 gene. No mutations were found in EOPD patients and control subjects. By carefully reviewing the available literature on studies of sporadic, non-Ashkenazi Jewish populations, the results showed that the prevalence rate of DYT1 mutation was not significantly different (p=0.267) between European (27.3%) and Asian (22.2%) patients with early onset primary torsion dystonia.

  20. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, Rick; Lawerman, Tjitske F.; Kuiper, Marieke J; Lunsing, Roelineke J; Burger, Huibert; Sival, Deborah A

    AIM: To determine whether ataxia rating scales are reliable disease biomarkers for early onset ataxia (EOA). METHOD: In 40 patients clinically identified with EOA (28 males, 12 females; mean age 15y 3mo [range 5-34y]), we determined interobserver and intraobserver agreement (interclass correlation

  1. Assessment of speech in early-onset ataxia : a pilot study

    NARCIS (Netherlands)

    Kuiper, Marieke J.; Brandsma, Rick; Lawerman, T.F.; Lunsing, Roelineke J.; Keegstra, Anne L.; Burger, Huibert; De Koning, Tom J.; Tijssen, Marina A. J.; Sival, Deborah A.

    2014-01-01

    AIM: The aim of the study was to determine whether paediatric ataxia speech subscores are reliably applicable for international early-onset ataxia (EOA) databases. If so, we reasoned that ataxia speech subscores should be associated with ataxia scores and involve high interobserver agreement,

  2. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, Rick; Lawerman, Tjitske F.; Kuiper, Marieke J.; Lunsing, Roelineke J.; Burger, Huibert; Sival, Deborah A.

    AIM To determine whether ataxia rating scales are reliable disease biomarkers for early onset ataxia (EOA). METHOD In 40 patients clinically identified with EOA (28 males, 12 females; mean age 15y 3mo [range 5-34y]), we determined interobserver and intraobserver agreement (interclass correlation

  3. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, R.; Lawerman, T. F.; Kuiper, M. J.; Geffen, van Joke; Lunsing, I. J.; Burger, H.; de Koning, T. J.; de Vries, J. J.; de Koning-Tijssen, M. A. J.; Sival, D. A.

    Objective: To determine observer-agreement and discriminantvalidity of ataxia rating scales.Background: In children and young adults, Early Onset Ataxia(EOA) is frequently concurrent with other Movement Disorders,resulting in moderate inter-observer agreement among MovementDisorder professionals. To

  4. Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

    Science.gov (United States)

    Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

    2012-01-01

    Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

  5. Genetic correlates of early accelerated infant growth associated with juvenile-onset type 1 diabetes

    NARCIS (Netherlands)

    Kharagjitsingh, Av; de Ridder, Maj; Alizadeh, Bz; Veeze, Hj; Bruining, Gj; Roep, Bo; Koeleman, Bobby Pc

    2012-01-01

    OBJECTIVE: We previously showed that accelerated growth predisposing to development of childhood-onset type 1 diabetes (T1D) is restricted to the first year after birth. We assessed whether this phenomenon of increased early growth is associated with variants of two genes, insulin-like growth factor

  6. Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

    Science.gov (United States)

    Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

    2011-01-01

    Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

  7. Guiding of serum procalcitonin-guided antibiotic in elderly early-onset stroke-associated pneumonia

    Institute of Scientific and Technical Information of China (English)

    龙威

    2013-01-01

    Objective To evaluate the effects of serum procalcitonin (PCT) -guided antibiotic therapy in elderly patients with early-onset stroke-associated pneumonia (EOP) .Methods Totally 179 eligible elderly patients with EOP were randomly devided into 2 groups:standard therapy

  8. Developmental Trends and L1 Effects in Early L2 Learners' Onset Cluster Production

    Science.gov (United States)

    Tessier, Anne-Michelle; Duncan, Tamara Sorenson; Paradis, Johanne

    2013-01-01

    This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…

  9. Early-onset periodontitis in Morocco is associated with the highly leukotoxic clone of Actinobacillus actinomycetemcomitans

    DEFF Research Database (Denmark)

    Haubek, Dorte; Ennibi, O.-K.; Poulsen, Knud

    2001-01-01

    A particular clone (JP2) of Actinobacillus actinomycetemcomitans with increased leukotoxin production has been isolated from individuals with early-onset periodontitis (EOP). The aim of this study was to determine the frequency of carriers of this clone and its association with EOP in Moroccan...

  10. The nigrostriatal dopaminergic system in familial early onset parkinsonism with parkin mutations

    NARCIS (Netherlands)

    Portman, AT; Giladi, N; Leenders, KL; Maguire, P; Veenma-van der Duin, L; Swart, J; Pruim, J; Simon, ES; Hassin-Baer, S; Korczyn, AD

    2001-01-01

    Nigrostriatal dopaminergic function and cerebral energy metabolism were measured with PET in two brothers with early-onset parkinsonism caused by mutation of the parkin gene. Energy metabolism did not differ, but the nigrostriatal dopaminergic pattern was clearly different than that of sporadic PD.

  11. Early onset vulvar Lichen Sclerosus in premenopausal women and oral contraceptives.

    Science.gov (United States)

    Günthert, Andreas R; Faber, Melanie; Knappe, Gabriele; Hellriegel, Simin; Emons, Günter

    2008-03-01

    For vulvar Lichen sclerosus (LS) immunological factors, genetic predisposition, and decreased 5 alpha-reductase activity have been discussed as aetiological factors. During the last decade an increase of LS in young women has been suspected. Aim of this study was to evaluate data of premenopausal women with early onset LS to find potential risk factors focussing on the use of oral contraceptives. We retrospectively analyzed the data of 40 premenopausal patients with early onset LS regarding use of oral contraceptives (OCPs), and first occurrence of LS. To compare these data in a case-control study we analyzed a matched control group of 110 healthy women. All our LS patients were using OCPs compared to 73 women (66.4%) in the control group. OCPs with anti-androgenic activity (chlormadinone acetate, cyproterone acetate, dienogest, and drospirenone) were used by 28 (70%) of the LS patients and by 35 (47.9%) of the 73 women using OCPs in the control group. Thus, the odds ratio for early onset LS for women using anti-androgenic OCPs was 2.53 (95% CI: 1.12-5.75). Our data suggest that disturbance of the androgen dependent growth of the vulvar skin by OCPs and especially by OCPs with anti-androgenic properties might trigger the early onset of LS in a subgroup of susceptible young women.

  12. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, R.; Lawerman, T. F.; Kuiper, M. J.; Geffen, van Joke; Lunsing, I. J.; Burger, H.; de Koning, T. J.; de Vries, J. J.; de Koning-Tijssen, M. A. J.; Sival, D. A.

    2015-01-01

    Objective: To determine observer-agreement and discriminantvalidity of ataxia rating scales.Background: In children and young adults, Early Onset Ataxia(EOA) is frequently concurrent with other Movement Disorders,resulting in moderate inter-observer agreement among MovementDisorder professionals. To

  13. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, Rick; Lawerman, Tjitske F; Kuiper, Marieke J; Lunsing, Roelineke J; Burger, Huibert; Sival, Deborah A

    2016-01-01

    AIM: To determine whether ataxia rating scales are reliable disease biomarkers for early onset ataxia (EOA). METHOD: In 40 patients clinically identified with EOA (28 males, 12 females; mean age 15y 3mo [range 5-34y]), we determined interobserver and intraobserver agreement (interclass correlation c

  14. Visual orientation in hospitalized boys with early onset conduct disorder and borderline intellectual functioning

    NARCIS (Netherlands)

    van der Meere, Jacob; Börger, Norbert; Pirila, Silja

    2012-01-01

    The aim of the present study is to investigate visual orientation in hospitalized boys with severe early onset conduct disorder and borderline intellectual functioning. It is tested whether boys with the dual diagnosis have a stronger action-oriented response style to visual-cued go signals than the

  15. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized

  16. Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

    Science.gov (United States)

    Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

    2012-01-01

    Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

  17. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia

  18. Visual orientation in hospitalized boys with early onset conduct disorder and borderline intellectual functioning

    NARCIS (Netherlands)

    van der Meere, Jacob; Börger, Norbert; Pirila, Silja

    2012-01-01

    The aim of the present study is to investigate visual orientation in hospitalized boys with severe early onset conduct disorder and borderline intellectual functioning. It is tested whether boys with the dual diagnosis have a stronger action-oriented response style to visual-cued go signals than the

  19. Assessment of speech in early-onset ataxia : a pilot study

    NARCIS (Netherlands)

    Kuiper, Marieke J.; Brandsma, Rick; Lawerman, T.F.; Lunsing, Roelineke J.; Keegstra, Anne L.; Burger, Huibert; De Koning, Tom J.; Tijssen, Marina A. J.; Sival, Deborah A.

    2014-01-01

    AIM: The aim of the study was to determine whether paediatric ataxia speech subscores are reliably applicable for international early-onset ataxia (EOA) databases. If so, we reasoned that ataxia speech subscores should be associated with ataxia scores and involve high interobserver agreement, includ

  20. Obesity and early cessation of breastfeeding in Denmark

    DEFF Research Database (Denmark)

    Kronborg, Hanne; Væth, Michael; Rasmussen, Kathleen M.

    2013-01-01

    Background: Obesity is associated with early cessation of breastfeeding. Breastfeeding is multi-factorial and several factors contribute to this association. Our aim was to investigate to what extent socio-demographic and psychosocial characteristics, parity and prenatal conditions could explain...... the association between high BMI and early cessation of breastfeeding Methods: We used data from a randomized trial of 1597 Danish mothers of singleton infants. Self-reported Maternal postnatal weight and height were available from 1375 (86 %). High BMI was defined as body mass index ≥32 kg/m2 at ~ 17 d after...... delivery. Outcome was cessation of exclusive breastfeeding by 17 wk postpartum used in proportional hazards regression models. Results: In the unadjusted analysis mothers with high postpartum BMI compared to other mothers had a significantly higher rate of cessation of exclusive breastfeeding, and were...

  1. Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON

    Directory of Open Access Journals (Sweden)

    Hooghiemstra Astrid M

    2012-08-01

    Full Text Available Abstract Background Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. Methods/Design One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study, after three months (end of the exercise program and after six months (follow-up. Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. Discussion The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. Trial registration The present study is registered

  2. Early-onset neonatal group B streptococcus sepsis following national risk-based prevention guidelines.

    Science.gov (United States)

    Darlow, Brian A; Voss, Lesley; Lennon, Diana R; Grimwood, Keith

    2016-02-01

    Neonatal infection with group B streptococcus (GBS) is an important cause of infant mortality. Intrapartum antibiotics reduce early-onset GBS sepsis, but recommendations vary as to whether they should be offered following antenatal screening or based on risk factors alone. We aimed to determine the incidence of early-onset GBS sepsis in New Zealand five years after the publication of national risk-based GBS prevention guidelines. Prospective surveillance of early-onset GBS sepsis (defined as infection in the first 48 h of life) was undertaken between April 2009 and March 2011 through the auspices of the New Zealand Paediatric Surveillance Unit as part of a survey of infection presenting in the first week of life. There were 29 cases of confirmed early-onset GBS sepsis, including one case of meningitis, giving an incidence rate of 0.23 per 1000 (95% CI 0.16-0.33) live births. Three infants (10.3%) died. In 16 cases (55%), a maternal risk factor qualifying the mother for intrapartum antibiotics was present, but only five (31%) received this intervention. A retrospective review of the major hospital laboratory databases for this period identified two additional cases. A secondary sensitivity analysis taking account of these cases provided an estimated national incidence of 0.26 (95% CI 0.18-0.37) per 1000 live births. Ten years after a similar survey and five years after promoting a single, risk-based prevention protocol nationally, the incidence of early-onset GBS disease in New Zealand has more than halved, but opportunities remain to further reduce the rate. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  3. Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Directory of Open Access Journals (Sweden)

    Yi-Chu Liao

    Full Text Available Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive.Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability.GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.

  4. Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Liao, Yi-Chu; Liu, Yo-Tsen; Tsai, Pei-Chien; Chang, Chia-Ching; Huang, Yen-Hua; Soong, Bing-Wen; Lee, Yi-Chung

    2015-01-01

    Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT) type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive. Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability. GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.

  5. Premorbid risk factors for major depressive disorder: are they associated with early onset and recurrent course?

    Science.gov (United States)

    Wilson, Sylia; Vaidyanathan, Uma; Miller, Michael B; McGue, Matt; Iacono, William G

    2014-11-01

    Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age 11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual single nucleotide polymorphism based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset.

  6. Blood Culture Proven Early Onset Sepsis and Late Onset Sepsis in Very-Low-Birth-Weight Infants in Korea.

    Science.gov (United States)

    Lee, Soon Min; Chang, Meayoung; Kim, Ki-Soo

    2015-10-01

    Neonatal sepsis remains one of the most important causes of death and co-morbidity in very-low-birth-weight (VLBW) infants. The aim of this study was to determine the current incidences of early-onset sepsis (EOS) and late-onset sepsis (LOS), the distribution of pathogens, and the impact of infection on co-morbidities in VLBW infants. We analyzed the data including sepsis episode from 2,386 VLBW infants enrolled in Korean Neonatal Network from January 2013 to June 2014. We defined EOS as a positive blood culture occurring between birth and 7 days of life and LOS after 7 days of life. Sepsis was found in 21.1% of VLBW infants. The risk of sepsis was inversely related to birth weight and gestational age. EOS was found in only 3.6% of VLBW infants, however the mortality rate was as high as 34.1%. EOS was associated with the increased odds for bronchopulmonary dysplasia and intraventricular hemorrhage. The vast majority of EOS was caused by Gram-positive organisms, particularly coagulase-negative staphylococci (30.6%). LOS developed in 19.4% of VLBW infants with a 16.1% mortality rate. Pathogens in LOS were dominated by coagulase-negative staphylococci (38.3%). Twenty-five percent and fifty percent of first LOS episode occurred after 12 days and 20 days from birth, respectively. Younger and smaller VLBW infants showed the earlier occurrence day for the 25% of first LOS episode. This study provides a recent nationwide epidemiology of sepsis in VLBW infants in Korea. Based on this study, successful strategies to reduce infections would improve survival and reduce morbidity.

  7. Characteristics of familial aggregation in early-onset Alzheimer`s disease: Evidence of subgroups

    Energy Technology Data Exchange (ETDEWEB)

    Campion, D. [INSERM, Paris (France); Martinez, M.; Babron, M.C. [and others

    1995-06-19

    Characteristics of familial aggregation of Alzheimer`s Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer`s disease. 58 refs., 5 figs., 2 tabs.

  8. Neuropsychology test and P300 detection characteristics analysis in early-onset Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    黄静

    2014-01-01

    Objective To investigate the clinical and cognitive characteristics of early-onset Parkinson’s disease(EOPD).Methods Two hundred and forty-two Parkinson’s disease(PD)patients were divided into EOPD(≤50 year-old,n=76)and late-onset Parkinson’s disease(LOPD;>50 year-old,n=1 66)according to their age.The age,disease duration,family history and other general clinical features were compared between EOPD and LOPD groups.Global and various aspects of cognitive dysfunction were

  9. Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis.

    Directory of Open Access Journals (Sweden)

    J Casey Olson

    Full Text Available Early onset deformity of the spine and chest wall (initiated <8 years of age is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old. Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old. Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8. Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55° had decreased body weight (89%, right (59% and left (86% lung mass, right (74% and left (69% radial alveolar count, right lung volume at total lung capacity (60%, and forced vital capacity (75%. Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may

  10. Predictors of onset of psychosis in patients with Parkinson's disease: Who gets it early?

    Science.gov (United States)

    Lenka, Abhishek; George, Lija; Arumugham, Shyam Sundar; Hegde, Shantala; Reddy, Venkateswara; Kamble, Nitish; Yadav, Ravi; Pal, Pramod Kumar

    2017-09-14

    Psychosis is one of the common non-motor symptoms of PD, which substantially worsens the quality of life. Hence, it is important to identify factors that are associated with early onset of psychosis in PD. In order to identify those factors, the current study aims to compare various demographic and clinical features of PD patients with early and late onset psychosis. In this prospective case-control study, 51 consecutive patients with PD having psychosis (PDP) were recruited. Median of the latency of onset of psychotic symptoms from the onset of motor symptoms was calculated (5.5 years) and after doing a median split, the cohort of PDP was divided into early onset PDP (EOP, n = 25) and late onset PDP (LOP, n = 26). Both the groups were compared for several demographic and clinical characteristics. Compared to those with LOP, patients with EOP had poor scores on frontal assessment battery (13.8 ± 2.0 vs 15.3 ± 1.8, p = 0.007), more frequently had Rapid Eye movement sleep Behavior Disorder (RBD) (80% vs 46.2%, p = 0.02), Postural Instability with Gait Difficulty (PIGD) phenotype (72% vs 26.9%, p = 0.002), and excessive daytime sleepiness (Epworth Sleepiness Scale: 8.04 ± 3.7 vs 3.9 ± 3.1). Patients with LOP were older (63.4 ± 7.0 years vs 56.5 ± 8.1 years, p = 0.002) and had higher Levodopa equivalent dose/day (LEDD: 819.1 ± 365.8 vs 608.5 ± 356.3, p = 0.04) compared to those with EOP. Presence of RBD, excessive daytime sleepiness, frontal lobe dysfunction, and PIGD phenotype of PD may be associated with early onset of psychosis in PD. Higher LEDD may not trigger early occurrence of psychosis in PD. Copyright © 2017. Published by Elsevier Ltd.

  11. Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations.

    Science.gov (United States)

    Milh, Mathieu; Villeneuve, Nathalie; Chouchane, Mondher; Kaminska, Anna; Laroche, Cécile; Barthez, Marie Anne; Gitiaux, Cyril; Bartoli, Céline; Borges-Correia, Ana; Cacciagli, Pierre; Mignon-Ravix, Cécile; Cuberos, Hélène; Chabrol, Brigitte; Villard, Laurent

    2011-10-01

    STXBP1 (MUNC18-1) mutations have been associated with various types of epilepsies, mostly beginning early in life. To refine the phenotype associated with STXBP1 aberrations in early onset epileptic syndromes, we studied this gene in a cohort of patients with early onset epileptic encephalopathy. STXBP1 was screened in a multicenter cohort of 52 patients with early onset epilepsy (first seizure observed before the age of 3 months), no cortical malformation on brain magnetic resonance imaging (MRI), and negative metabolic screening. Three groups of patients could be distinguished in this cohort: (1) Ohtahara syndromes (n = 38); (2) early myoclonic encephalopathies (n = 7); and (3) early onset epileptic encephalopathies that did not match any familiar syndrome (n = 7). None of the patients displayed any cortical malformation on brain MRI and all were screened through multiple video-electroencephalography (EEG) recordings for a time period spanning from birth to their sixth postnatal month. Subsequently, patients had standard EEG or video-EEG recordings. We found five novel STXBP1 mutations in patients for whom video-EEG recordings could be sampled from the beginning of the disease. All patients with a mutation displayed Ohtahara syndrome, since most early seizures could be classified as epileptic spasms and since the silent EEG periods were on average shorter than bursts. However, each patient in addition displayed a particular clinical and EEG feature: In two patients, early seizures were clonic, with very early EEG studies exhibiting relatively low amplitude bursts of activity before progressing into a typical suppression-burst pattern, whereas the three other patients displayed epileptic spasms associated with typical suppression-burst patterns starting from the early recordings. Epilepsy dramatically improved after 6 months and finally disappeared before the end of the first year of life for four patients; the remaining one patient had few seizures until 18

  12. The many faces of asthma in obesity.

    Science.gov (United States)

    Sideleva, O; Dixon, A E

    2014-03-01

    Obesity is a major risk factor for the development of asthma, and causes severe, uncontrolled disease that responds poorly to therapy. The obese state alters early onset allergic asthma, and leads to the development of a novel form of late onset asthma secondary to obesity. The presentation of early onset allergic asthma is altered through effects on immune function. Factors such as mechanical loading, effects of adipokines on airways, altered diet, insulin resistance and altered metabolism of nitric oxide likely all contribute to increased airway reactivity in obesity, causing late onset asthma in obesity. Obesity also alters responses to environmental factors such as ozone and particulate matter. Focused studies to understand the importance of these factors in the pathogenesis of airway disease in obesity will be essential to develop therapies to intervene in this new epidemic of airway disease.

  13. An analysis of expectant management in women with early-onset preeclampsia in China.

    Science.gov (United States)

    Chen, Q; Shen, F; Gao, Y F; Zhao, M

    2015-06-01

    Preeclampsia is a pregnancy-specific disorder and a leading cause of morbidity and mortality in both women and fetus. Although women with early severe preeclampsia are generally considered to require expedious delivery, expectant management may benefit for pregnancy prolongation. We performed a retrospective analysis of expectant management in early-onset preeclampsia, with or without fetal grow restriction (FGR) over a 6-year period, to investigate whether these women benefit from expectant management. Data including clinical parameters and liver and renal function from 186 nulliparous women with early-onset preeclampsia were analysed. In women with early-onset preeclampsia, 76.8% were delivered after 48 h and the median pregnancy prolongation was 8 days, whereas 23.2% were delivered within 48 h. There was no difference in maternal parameters, liver or renal functions between women in these two groups, regardless of the severity of preeclampsia. However, the stillbirth number was higher in preeclamptic women delivered after 48 h compared with those delivered within 48 h. Our study demonstrates that the decision for immediate delivery or expectant management was not associated with clinical parameter or laboratory biomarker of liver and renal function. However, the risk of stillbirth should still be taken into consideration when making the decision for immediate delivery or expectant management in the clinic.

  14. Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

    Science.gov (United States)

    Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

    2017-03-16

    To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Modified areal cartography in auditory cortex following early- and late-onset deafness.

    Science.gov (United States)

    Wong, Carmen; Chabot, Nicole; Kok, Melanie A; Lomber, Stephen G

    2014-07-01

    Cross-modal plasticity following peripheral sensory loss enables deprived cortex to provide enhanced abilities in remaining sensory systems. These functional adaptations have been demonstrated in cat auditory cortex following early-onset deafness in electrophysiological and psychophysical studies. However, little information is available concerning any accompanying structural compensations. To examine the influence of sound experience on areal cartography, auditory cytoarchitecture was examined in hearing cats, early-deaf cats, and cats with late-onset deafness. Cats were deafened shortly after hearing onset or in adulthood. Cerebral cytoarchitecture was revealed immunohistochemically using SMI-32, a monoclonal antibody used to distinguish auditory areas in many species. Auditory areas were delineated in coronal sections and their volumes measured. Staining profiles observed in hearing cats were conserved in early- and late-deaf cats. In all deaf cats, dorsal auditory areas were the most mutable. Early-deaf cats showed further modifications, with significant expansions in second auditory cortex and ventral auditory field. Borders between dorsal auditory areas and adjacent visual and somatosensory areas were shifted ventrally, suggesting expanded visual and somatosensory cortical representation. Overall, this study shows the influence of acoustic experience in cortical development, and suggests that the age of auditory deprivation may significantly affect auditory areal cartography. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Perbedaan Rerata Kadar Soluble Fms-Like Tyrosine Kinase-1 (Sflt-1 Serum pada Penderita Early Onset, Late Onset Preeklampsia Berat / Eklampsia dan Kehamilan Normal

    Directory of Open Access Journals (Sweden)

    Laila Rahmi

    2016-01-01

    Full Text Available AbstrakPreeklampsia merupakan sumber utama morbiditas dan mortalitas ibu di seluruh dunia. Kegagalan pengaturan dan ketidakseimbangan agen vasoaktif proangiogenik dan antiangiogenik plasenta, soluble fms-like tyrosine kinase-1 (sFlt-1, vascular endothelial growth factor (VEGF dan placental growth factor (PlGF memainkan peran penting dalam patogenesis preeklampsia. Tujuan penelitian ini adalah menentukan perbedaan rerata kadar sFlt-1 serum pada penderita early onset, late onset preeklampsia berat/ eklampsia dan kehamilan normal. Penelitian dilakukan di RSUP Dr. M. Djamil, RS TK. III dr. Reksodiwiryo dan Laboratorium Biologi Molekuler Fakultas Kedokteran Universitas Andalas Padang dari Februari sampai  Desember 2014 dengan desain cross sectional. Subjek berjumlah 84 orang, terdiri dari tiga kelompok, yaitu kelompok early onset preeklampsia berat/ eklampsia, late onset preeklampsia berat/ eklampsia, dan kehamilan normal sebagai kelompok kontrol yang diambil dengan teknik consecutive sampling. Darah dikumpulkan dari subjek penelitian dengan cara intravena kemudian diukur dengan metode ELISA. Rerata kadar sFlt-1 pada kelompok early onset, late onset preeklampsia berat/ eklampsia dan kehamilan normal secara berturut-turut adalah 4,69±0,96 ng/ml, 2,39±0,57 ng/ml, dan 1,23±0,42 ng/ml. Perbedaan ini sangat signifikan dengan uji statistik ANOVA (p<0,05 dan uji Post Hoc Test Multiple Comparisons. Kesimpulan penelitian adalah terdapat perbedaan yang sangat signifikan antara kadar sFlt-1 serum pada kelompok early onset preeklampsia berat/ eklampsia, late onset preeklampsia berat/ eklampsia dan kehamilan normal.Kata kunci: sFlt-1, antiangiogenik, preeklampsia berat/ eklampsia, kehamilan normal AbstractPreeclampsia is a major cause maternal morbidity and mortality in the world. Failure regulation and imbalance of vasoactive agents and antiangiogenic proangiogenik placenta, soluble fms-like tyrosine kinase-1 (sFlt-1, vascular endothelial growth factor

  17. Early onset otitis media: risk factors and effects on the outcome of chronic suppurative otitis media.

    Science.gov (United States)

    Lasisi, Akeem O; Olayemi, Oladapo; Irabor, Achiaka E

    2008-07-01

    The onset of early otitis media (EOM), in the first few months of life has been reported to predict later chronic otitis media (CSOM), although the prevalence rates are increasing little is known about specific risk factors. In this survey we examined the hypothesis that higher risk factors is associated with the development of OM within 1 year compared to later onset and early onset otitis media (OM) has potential for negative outcome of CSOM. This is a survey of the age at onset of otorrhoea and associated risk factors in children with CSOM, in five sites spread in two sub-urban cities in two states in Nigeria. Questionnaires were administered on the informants followed by examination of the children. EOM was seen in 136/189 (70%) with CSOM, the age range was 1-150 months, mean of 59.25 (SD = 44.55). Of the 85 CSOM subjects with hearing loss, EOM accounted for 49 (57.7%) while 36 (42.4%) was later onset, On multivariate analysis (OR = 0.276, CI = 0.133-0.572, P = 0.001) revealing EOM was significant in the development of hearing loss however there was no correlation with the frequency of attack of otorrhoea (OR = 1.025, CI = 0.88-1.19, P = 0.75). Low socioeconomic status seen in 110/136 EOM (P = 0.000), allergy (P = 0.030) and number of people >10 in household (OR = 4.13, CI = 1.81-9.39, P = 0.001) constituted the significant risk for EOM compared to later onset. Bottlefeeding, adenoiditis/adenoid hypertrophy, indoor cooking and upper respiratory infection were not found to have statistical significance in early onset OM compared to later onset OM. This study found correlation between EOM and hearing loss and identified allergy, low social status and chronic exposure to overcrowding through increased number of children in the household significant risk factors for future research focus. This may help in controlling the prevalence of hearing loss accompanying CSOM.

  18. Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Karas, Giorgos [Vrije Universiteit Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Scheltens, Philip; Jones, Bethany [Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Department of Clinical Neurology, Amsterdam (Netherlands); Rombouts, Serge [Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Department of Clinical Physics and Informatics, Amsterdam (Netherlands); Schijndel, Ronald van [Vrije Universiteit Medical Center, Image Analysis Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Department of Clinical Physics and Informatics, Amsterdam (Netherlands); Klein, Martin [Vrije Universiteit Medical Center, Department of Medical Psychology, Amsterdam (Netherlands); Flier, Wiesje van der [Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Vrenken, Hugo [Vrije Universiteit Medical Center, Image Analysis Center, Amsterdam (Netherlands); Barkhof, Frederik [Vrije Universiteit Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Image Analysis Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands)

    2007-12-15

    Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans. We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex. The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning. Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset. (orig.)

  19. Genetic risk factors for myocardial infarction more clearly manifest for early age of first onset.

    Science.gov (United States)

    Titov, Boris V; Osmak, German J; Matveeva, Natalia A; Kukava, Nino G; Shakhnovich, Roman M; Favorov, Alexander V; Ruda, Mikhail Ya; Favorova, Olga O

    2017-07-06

    Epidemiological genetics established that heritability in determining the risk of myocardial infarction (MI) is substantially greater when MI occurs early in life. However, the genetic architecture of early-onset and late-onset MI was not compared. We analyzed genotype frequencies of SNPs in/near 20 genes whose protein products are involved in the pathogenesis of atherosclerosis in two groups of Russian patients with MI: the first group included patients with age of first MI onset <60 years (N = 230) and the second group with onset ≥60 years (N = 174). The control group of corresponding ethnicity consisted of 193 unrelated volunteers without cardiovascular diseases (93 individuals were over 60 years). We found that in the group of patients with age of onset <60 years, SNPs FGB rs1800788*T, TGFB1 rs1982073*T/T, ENOS rs2070744*C and CRP rs1130864*T/T were associated with risk of MI, whereas in patients with age of onset ≥60 years, only TGFB1 rs1982073*T/T was associated with risk of MI. Using APSampler software, we found composite markers associated with MI only in patients with early onset: FGB rs1800788*T + TGFB1 rs1982073*T; FGB rs1800788*T + LPL rs328*C + IL4 rs2243250*C; FGB rs1800788*T + ENOS rs2070744*C (Fisher p values of 1.4 × 10(-6) to 2.2 × 10(-5); the permutation p values of 1.1 × 10(-5) to 3.0 × 10(-4); ORs = 2.67-2.54). Alleles included in the combinations were associated with MI less significantly and with lower ORs than the combinations themselves. The result showed a substantially greater contribution of the genetic component in the development of MI if it occurs early in life, and demonstrated the usefulness of genetic testing for young people.

  20. Early formula feeding practices and their potential contribution to later obesity risk

    LENUS (Irish Health Repository)

    Tarrant, R C

    2013-01-02

    Background and Aims: Early feeding practices, including early introduction to solid foods and overfeeding, are known risk factors for childhood obesity. This study aimed to assess maternal formula feeding practices and infant formula feeding patterns, factors that are known to potentially contribute to later obesity risk. \\r\

  1. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders

    OpenAIRE

    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita

    2012-01-01

    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose r...

  2. MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Martin Weygandt

    2015-01-01

    Full Text Available Currently, it is unclear whether pediatric multiple sclerosis (PMS is a pathoetiologically homogeneous disease phenotype due to clinical and epidemiological differences between early and late onset PMS (EOPMS and LOPMS. Consequently, the question was raised whether diagnostic guidelines need to be complemented by specific EOPMS markers. To search for such markers, we analyzed cerebral MRI images acquired with standard protocols using computer-based classification techniques. Specifically, we applied classification algorithms to gray (GM and white matter (WM tissue probability parameters of small brain regions derived from T2-weighted MRI images of EOPMS patients (onset <12 years, LOPMS patients (onset ≥12 years, and healthy controls (HC. This was done for PMS subgroups matched for disease duration and participant age independently. As expected, maximal diagnostic information for distinguishing PMS patients and HC was found in a periventricular WM area containing lesions (87.1% accuracy, p < 2.2 × 10−5. MRI-based biomarkers specific for EOPMS were identified in prefrontal cortex. Specifically, a coordinate in middle frontal gyrus contained maximal diagnostic information (77.3%, p = 1.8 × 10−4. Taken together, we were able to identify biomarkers reflecting pathognomonic processes specific for MS patients with very early onset. Especially GM involvement in the separation between PMS subgroups suggests that conventional MRI contains a richer set of diagnostically informative features than previously assumed.

  3. A common genetic background could explain early-onset Crohn's disease.

    Science.gov (United States)

    Bianco, Anna Monica; Zanin, Valentina; Girardelli, Martina; Magnolato, Andrea; Martelossi, Stefano; Martellossi, Stefano; Tommasini, Alberto; Marcuzzi, Annalisa; Crovella, Sergio

    2012-04-01

    Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

  4. Early onset pneumonia following pulmonary contusion: the case of Stonewall Jackson.

    Science.gov (United States)

    Lively, Mathew W

    2012-03-01

    Confederate Lieutenant General Thomas J. "Stonewall" Jackson was wounded by his own men at the Battle of Chancellorsville during the American Civil War. While being removed from the field, Jackson fell from the litter and struck the right side of his chest on a large stone or stump. Four days following the amputation of his left arm, Jackson developed pneumonia in his right lung. His treating physicians believed the infection developed secondary to a pulmonary contusion that occurred when he fell from the litter. Pulmonary contusions are an independent risk factor in the development of post-traumatic pneumonia and an infection that occurs within 72 to 96 hours of injury is termed an early onset pneumonia. The nature and timing of Stonewall Jackson's illness following his wounding is consistent with the modem diagnosis of early onset pneumonia following chest trauma.

  5. Cortisol and ACTH levels in drug-naive adolescents with first-episode early onset schizophrenia.

    Science.gov (United States)

    Şimşek, Şeref; Gençoğlan, Salih; Yüksel, Tuğba; Aktaş, Hüseyin

    2017-03-01

    The aim of this study was to investigate serum levels of cortisol and adrenocorticotropic hormone in adolescents with first-episode early onset schizophrenia. A total of 23 adolescent patients, who did not receive prior therapy and who were diagnosed with psychosis according to DSM-IV, were included. Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, Positive and Negative Symptom Scale, and Clinical Global Impression Scale were conducted with the participants. No significant differences were found between the patients and the control subjects in serum cortisol and adrenocorticotropic hormone levels (P > .05). Our study's findings do not support the hypothesis of increased hypothalamic-pituitary-adrenal axis activity in first-episode early onset schizophrenia.

  6. A novel early onset phenotype in a zebrafish model of merosin deficient congenital muscular dystrophy

    Science.gov (United States)

    Smith, Sarah J.; Wang, Jeffrey C.; Gupta, Vandana A.; Dowling, James J.

    2017-01-01

    Merosin deficient congenital muscular dystrophy (MDC1A) is a severe neuromuscular disorder with onset in infancy that is associated with severe morbidities (particularly wheelchair dependence) and early mortality. It is caused by recessive mutations in the LAMA2 gene that encodes a subunit of the extracellular matrix protein laminin 211. At present, there are no treatments for this disabling disease. The zebrafish has emerged as a powerful model system for the identification of novel therapies. However, drug discovery in the zebrafish is largely dependent on the identification of phenotypes suitable for chemical screening. Our goal in this study was to elucidate novel, early onset abnormalities in the candyfloss (caf) zebrafish, a model of MDC1A. We uncovered and characterize abnormalities in spontaneous coiling, the earliest motor movement in the zebrafish, as a fully penetrant change specific to caf mutants that is ideal for future drug testing. PMID:28241031

  7. Variants of early-onset restrictive eating disturbances in middle childhood

    OpenAIRE

    Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

    2016-01-01

    Objective: This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Method: Using the EDY-Q, a total of 1444 children aged 8-13 years were screened in elementary schools in Switzerland v...

  8. Does Diagnostic Classification of Early-Onset Psychosis Change over Follow-Up?

    Science.gov (United States)

    Fraguas, David; de Castro, Maria J.; Medina, Oscar; Parellada, Mara; Moreno, Dolores; Graell, Montserrat; Merchan-Naranjo, Jessica; Arango, Celso

    2008-01-01

    Objective: To examine the diagnostic stability and the functional outcome of patients with early-onset psychosis (EOP) over a 2-year follow-up period. Methods: A total of 24 patients (18 males (75%) and 6 females (25%), mean age [plus or minus] SD: 15.7 [plus or minus] 1.6 years) with a first episode of EOP formed the sample. Psychotic symptoms…

  9. CYP450 polymorphisms as risk factors for early-onset lung cancer: gender-specific differences.

    Science.gov (United States)

    Timofeeva, Maria N; Kropp, Silke; Sauter, Wiebke; Beckmann, Lars; Rosenberger, Albert; Illig, Thomas; Jäger, Birgit; Mittelstrass, Kirstin; Dienemann, Hendrik; Bartsch, Helmut; Bickeböller, Heike; Chang-Claude, Jenny C; Risch, Angela; Wichmann, Heinz-Erich

    2009-07-01

    Cytochrome P450 (CYP) enzymes, involved in metabolism of tobacco carcinogens, are also involved in estrogen metabolism and many are regulated by estrogens. These genes may thus be of relevance to gender-specific differences in lung cancer risk, particularly in early-onset lung cancer, where a high proportion of women is observed. We conducted a case-control study to investigate genetic polymorphisms in cytochromes that might modify the risk of developing early-onset lung cancer. In total, 638 Caucasian patients under the age of 51 with primary lung cancer and 1300 cancer-free control individuals, matched by age and sex, were included in this analysis. Thirteen polymorphisms in the CYP1A1, CYP1B1, CYP2A13, CYP3A4 and CYP3A5 genes were analyzed. No significant association was found for any of the analyzed polymorphisms and lung cancer risk overall. However, among women, a significantly increased risk of early-onset lung cancer was observed for carriers of the minor allele of CYP1B1 SNP rs1056836 [odds ratio (OR) 1.97; 95% confidence interval (CI) 1.32-2.94; P lung cancer risk was observed in the group of women carriers of the minor allele of CYP2A13 SNP rs1709084 (OR 1.64; 95% CI 1.00-2.70; P = 0.05). The effect of these two polymorphisms was shown to be modified by smoking. Haplotype analysis was performed for CYP1B1 and CYP2A13. No differences between cases and controls were observed for both genes (P = 0.63 and P = 0.42 for CYP1B1 and CYP2A13, respectively). Our results suggest that the CYP1B1 and the CYP2A13 genotypes may contribute to individual susceptibility to early-onset lung cancer in women.

  10. Executive Abilities as Reflected by Clock Hand Placement: Frontotemporal Dementia Versus Early-Onset Alzheimer Disease.

    Science.gov (United States)

    Barrows, Robin J; Barsuglia, Joseph; Paholpak, Pongsatorn; Eknoyan, Donald; Sabodash, Valeriy; Lee, Grace J; Mendez, Mario F

    2015-12-01

    The clock-drawing test (CDT) is widely used in clinical practice to diagnose and distinguish patients with dementia. It remains unclear, however, whether the CDT can distinguish among the early-onset dementias. Accordingly, we examined the ability of both quantitative and qualitative CDT analyses to distinguish behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer disease (eAD), the 2 most common neurodegenerative dementias with onset <65 years of age. We hypothesized that executive aspects of the CDT would discriminate between these 2 disorders. The study compared 15 patients with bvFTD and 16 patients with eAD on the CDT using 2 different scales and correlated the findings with neuropsychological testing and magnetic resonance imaging. The total CDT scores did not discriminate bvFTD and eAD; however, specific analysis of executive hand placement items successfully distinguished the groups, with eAD exhibiting greater errors than bvFTD. The performance on those executive hand placement items correlated with measures of naming as well as visuospatial and executive function. On tensor-based morphometry of the magnetic resonance images, executive hand placement correlated with right frontal volume. These findings suggest that lower performance on executive hand placement items occurs with involvement of the right dorsolateral frontal-parietal network for executive control in eAD, a network disproportionately affected in AD of early onset. Rather than the total performance on the clock task, the analysis of specific errors, such as executive hand placement, may be useful for early differentiation of eAD, bvFTD, and other conditions.

  11. Risk for Early-Onset Schizophrenia Assessed via Gray-Matter Distributions

    OpenAIRE

    Christensen, James D.

    2005-01-01

    Automated image analysis algorithms were used to measure regional gray matter volumes in children with early-onset schizophrenia. Logistic regression analysis of gray matter volumes within Brodman areas was used to test the ability to predict whether a subject was normal or schizophrenic. The ROC area-under-the-curve was 0.84 ± 0.15 across the 10 cross validation groups indicating good discrimination between schizophrenic and normal subjects.

  12. Risk for early-onset schizophrenia assessed via gray-matter distributions.

    Science.gov (United States)

    Christensen, James D

    2005-01-01

    Automated image analysis algorithms were used to measure regional gray matter volumes in children with early-onset schizophrenia. Logistic regression analysis of gray matter volumes within Brodman areas was used to test the ability to predict whether a subject was normal or schizophrenic. The ROC area-under-the-curve was 0.84 +/- 0.15 across the 10 cross validation groups indicating good discrimination between schizophrenic and normal subjects.

  13. Gender-related differences in severe, early-onset chronic obstructive pulmonary disease.

    Science.gov (United States)

    Silverman, E K; Weiss, S T; Drazen, J M; Chapman, H A; Carey, V; Campbell, E J; Denish, P; Silverman, R A; Celedon, J C; Reilly, J J; Ginns, L C; Speizer, F E

    2000-12-01

    Men have higher prevalence rates of chronic obstructive pulmonary disease (COPD) than women, which has been attributed to the historically higher rates of cigarette smoking in males. However, the increased rates of cigarette smoking in females within the last several decades have been associated with steadily increasing rates of COPD in women. As part of a study of the genetics of severe, early-onset COPD, we assembled a group of 84 probands with severe, early-onset COPD (without severe alpha(1)-antitrypsin deficiency) and 348 of their first-degree relatives. We found a markedly elevated prevalence (71.4%) of females among the early-onset COPD probands. Among the entire group of first-degree relatives of early-onset COPD probands, univariate analysis demonstrated similar spirometric values and bronchodilator responsiveness in males and females; however, among current or ex-smokers, female first-degree relatives had significantly lower FEV(1)/ FVC (81.4 +/- 17.2% in females versus 87.0 +/- 12.9% in males, p = 0.009) and significantly greater bronchodilator responsiveness (expressed as percentage of baseline FEV(1)) (7.7 +/- 9.4% pred in females versus 4.1 +/- 6.4% pred in males, p = 0.002). Female smoking first-degree relatives were significantly more likely to demonstrate profound reductions in FEV(1) (< 40% pred) than male smoking first-degree relatives (p = 0. 03). Multivariate analysis, performed with generalized estimating equations, demonstrated that current or ex-smoking female first-degree relatives had significantly greater risk of FEV(1) < 80% pred (OR 1.91, 95% CI 1.03- 3.54), FEV(1) < 40% pred (OR 3.56, 95% CI 1.08-11.71), and bronchodilator response greater than 10% of baseline FEV(1) (OR 4.74, 95% CI 1.91-11.75). These results suggest that women may be more susceptible to the development of severe COPD.

  14. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

    Science.gov (United States)

    Flanagan, Sarah E; Haapaniemi, Emma; Russell, Mark A; Caswell, Richard; Lango Allen, Hana; De Franco, Elisa; McDonald, Timothy J; Rajala, Hanna; Ramelius, Anita; Barton, John; Heiskanen, Kaarina; Heiskanen-Kosma, Tarja; Kajosaari, Merja; Murphy, Nuala P; Milenkovic, Tatjana; Seppänen, Mikko; Lernmark, Åke; Mustjoki, Satu; Otonkoski, Timo; Kere, Juha; Morgan, Noel G; Ellard, Sian; Hattersley, Andrew T

    2014-08-01

    Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.

  15. Expectant management of early-onset severe preeclampsia. Literature review and treatment protocol

    Directory of Open Access Journals (Sweden)

    César Augusto Rendón

    2013-12-01

    Full Text Available The main goal of expectant management in women with severe preeclampsia (PE remote from term is to improve neonatal outcome, without compromising maternal health. Studies suggest that expectant management in early-onset preeclampsia may be associated with decreased neonatal morbidity, but also conclude that further studies are needed to assess maternal safety. The aim of this review is to assess the current issue evidence regarding the management of severe preeclampsia remote from term.

  16. Association between Interleukin-10 gene polymorphisms and risk of early-onset preeclampsia.

    Science.gov (United States)

    Song, Limeng; Zhong, Mei

    2015-01-01

    We conducted a case-control study to investigate the role of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) polymorphisms in the development of early-onset preeclampsia. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the polymorphisms of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872). The genotype distributions of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) confirmed with HWE in the controls, and the P value for HWE was 0.41, 0.38 and 0.26, respectively. The results of the multivariate logistic regression analysis revealed that the association of individuals expressing the CC genotype and AC+CC of IL-10 -592A/C (rs1800872) with a significantly increased risk of early-onset preeclampsia in co-dominant and dominant models, compared to the AA genotype; the OR (95% CI) for these individuals was determined to be 2.09 (1.12-3.90) and 1.66 (1.03-2.71), respectively. In the recessive model, we found that CC genotype of IL-10 -592A/C (rs1800872) was associated with the increased risk of early-onset preeclampsia when compared with AA+AC genotype (OR = 1.67; 95% CI = 1.01-2.92). In conclusion, our study has indicated that IL-10 -592A/C (rs1800872) polymorphism was associated with an increased risk of early-onset preeclampsia in a Chinese population.

  17. Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.

    Science.gov (United States)

    Mayoral, María; Merchán-Naranjo, Jessica; Rapado, Marta; Leiva, Marta; Moreno, Carmen; Giráldez, Marisa; Arango, Celso; Parellada, Mara

    2010-11-01

    The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls. NSS were assessed by means of the Neurological Evaluation Scale in a sample of 29 patients with Asperger syndrome (mean age = 12.86 ± 2.58 years), 30 patients with first-episode early-onset psychoses (mean age 14.17 ± 1.02 years) and 30 healthy controls (mean age 12.33 ± 2.69 years). Significant group differences were found between Asperger syndrome patients and healthy controls both in all the Neurological Evaluation Scale subscales and in the Neurological Evaluation Scale total score. There were no significant differences between both groups of patients in any of the Neurological Evaluation Scale scores. NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses. © 2010 Blackwell Publishing Asia Pty Ltd.

  18. Maternal and feto-placental phenotypes of early-onset severe preeclampsia.

    Science.gov (United States)

    Pilliod, Rachel A; Feinberg, Bruce B; Burwick, Richard M

    2016-01-01

    To characterize maternal and feto-placental phenotypes of severe preeclampsia that trigger early-onset delivery. A retrospective cohort review of pregnant women receiving care from 2000 to 2010. Subjects with early-onset severe preeclampsia delivering between 20 and 32 weeks were identified excluding multiple gestations or major anomalies. We defined indications for delivery as maternal (i.e. severe headache or abnormal laboratory parameters), feto-placental (i.e. non-reassuring tracing) or mixed (i.e. both maternal and feto-placental factors). To characterize the groups, demographic, clinical, laboratory, ultrasound and pathology data were abstracted. Statistical analysis was conducted. We identified 164 subjects meeting inclusion criteria. Indications for delivery were maternal (57.3%), feto-placental (29.9%) or mixed (12.8%). Compared to neonates delivered for maternal indications, birthweight was significantly lower among neonates delivered for feto-placental or mixed indications (p feto-placental factors (p = 0.02). Women delivered for maternal indications had more significant lab abnormalities than women delivered for feto-placental or mixed indications. In attempting to classify early-onset severe preeclampsia by delivery indication, we found patterns to suggest that feto-placental and maternal phenotypes of disease may have distinct pathophysiologic underpinnings.

  19. Beyond mice: Emerging and transdisciplinary models for the study of early-onset myopathies.

    Science.gov (United States)

    Jagla, Krzysztof; Kalman, Benoit; Boudou, Thomas; Hénon, Sylvie; Batonnet-Pichon, Sabrina

    2017-04-01

    The use of the adapted models to decipher patho-physiological mechanisms of human diseases is always a great challenge. This is of particular importance for early-onset myopathies, in which pathological mutations often impact not only on muscle structure and function but also on developmental processes. Mice are currently the main animal model used to study neuromuscular disorders including the early-onset myopathies. However strategies based on simple animal models and on transdisciplinary approaches exploring mechanical muscle cell properties emerge as attractive, non-exclusive alternatives. These new ways provide valuable opportunities to improve our knowledge on how mechanical, biochemical, and genetic/epigenetic cues modulate the formation, organization and function of muscle tissues. Here we provide an overview of how single cell and micro-tissue engineering in parallel to non-mammalian, Drosophila and zebrafish models could contribute to filling gaps in our understanding of pathogenic mechanisms underlying early-onset myopathies. We also discuss their potential impact on designing new diagnostic and therapeutic strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Reduced life expectancy seen in hereditary diseases which predispose to early-onset tumors

    Directory of Open Access Journals (Sweden)

    Evans DGR

    2013-07-01

    Full Text Available D Gareth R Evans,1 Sarah Louise Ingham21Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester Foundation Trust, St Mary's Hospital, Manchester, UK; 2Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UKAbstract: There are several hereditary diseases that are a predisposition to early-onset tumors. These include syndromic conditions like neurofibromatosis 1 and 2, von Hippel–Lindau syndrome, Gorlin syndrome, multiple endocrine neoplasia, and familial adenomatous polyposis; and conditions which are usually not possible to diagnose clinically in a single individual, such as Lynch syndrome and BRCA1/2. Understanding of the mortality in hereditary cancer predisposing diseases is important for developing effective disease treatment programs. A number of studies have been undertaken to investigate the genetic predictors, prevalence and incidence, and treatment outcomes of these diseases; however, the majority examine only the most common of these diseases (eg, neurofibromatosis or BRCA, or look into postoperative survival. The mortality of individuals who are diagnosed with one of these hereditary diseases remains an area for investigation. This review is the first to attempt identification of studies investigating life expectancy in hereditary diseases which predispose to early-onset tumors.Keywords: mortality, survival, life expectancy, early-onset, tumors

  1. Prediction of early-onset asthma in genetically at-risk children.

    Science.gov (United States)

    Mrazek, D A; Klinnert, M; Mrazek, P J; Brower, A; McCormick, D; Rubin, B; Ikle, D; Kastner, W; Larsen, G; Harbeck, R; Jones, J

    1999-02-01

    The W.T. Grant Foundation Asthma Risk Study was designed to prospectively examine children who were considered at a genetically increased risk for the development of asthma. The respective contributions of 11 potential risk factors, both environmental and biological, were assessed in order to determine their relative roles in affecting the early onset of asthma. This is a report of an inception cohort of children born to asthmatic mothers and followed for a 3-year period. All 150 families were recruited from the general community and living within 2 h of the National Jewish Center for Immunology and Respiratory Medicine (Denver, CO). Mothers in the index risk sample had been previously diagnosed with asthma and were recruited during their pregnancy through physician referrals and media solicitation. The index sample of 150 families was 92% Caucasian and predominantly middle class. The mean age of mothers was 29.3 years, and of fathers, 31.1 years. The main outcome was the determination of the early onset of asthma and its association with quantified risk factors. By age 3 years, 14 of the 150 children had developed asthma. Frequent illness, IgE levels at age 6 months, parenting difficulties, and early eczema were significantly associated with the onset of asthma (P = 0.003, P = 0.006, P = 0.01, and P = 0.03, respectively). Only frequent illness, elevated serum IgE levels, and parenting difficulties entered a predictive model where they were independently related to the development of asthma.

  2. Early impact basins and the onset of plate tectonics. Ph.D. Thesis - Maryland Univ.

    Science.gov (United States)

    Frey, H.

    1977-01-01

    The fundamental crustal dichotomy of the Earth (high and low density crust) was established nearly 4 billion years ago. Therefore, subductable crust was concentrated at the surface of the Earth very early in its history, making possible an early onset for plate tectonics. Simple thermal history calculations spanning 1 billion years show that the basin forming impact thins the lithosphere by at least 25%, and increases the sublithosphere thermal gradients by roughly 20%. The corresponding increase in convective heat transport, combined with the highly fractured nature of the thinned basin lithosphere, suggest that lithospheric breakup or rifting occurred shortly after the formation of the basins. Conditions appropriate for early rifting persisted from some 100,000,000 years following impact. We suggest a very early stage of high temperature, fast spreading "microplate" tectonics, originating before 3.5 billion years ago, and gradually stabilizing over the Archaean into more modern large plate or Wilson Cycle tectonics.

  3. The treatment of asthma in obesity.

    Science.gov (United States)

    Dixon, Anne

    2012-06-01

    The world is facing an unprecedented epidemic of obesity. This epidemic has led to major changes in the epidemiology of common diseases such as asthma. Obesity is a major risk factor for new-onset asthma. This article will discuss the role of mechanical and metabolic factors, as well as obesity-related comorbidities, in both causing airway disease and also affecting response to therapy in obese asthmatics. Asthma in obese individuals probably includes a spectrum of disease with at least two distinct phenotypes: early-onset allergic disease complicated by obesity and late-onset disease developing in the setting of obesity. Both phenotypes are distinct from asthma in lean individuals. Treatment of asthma in obesity needs to consider altered response to controller therapy, and the fact that mechanical factors, metabolic inflammation and other comorbidities are probably contributing to airway disease. Future studies should focus on the development of therapies specifically tailored towards the treatment of asthma in obesity.

  4. Plasma proteome profiles predict diet-induced metabolic syndrome and the early onset of metabolic syndrome in a pig model

    NARCIS (Netherlands)

    Pas, te M.F.W.; Koopmans, S.J.; Kruijt, L.; Smits, M.A.

    2013-01-01

    Obesity and related diabetes are important health threatening multifactorial metabolic diseases and it has been suggested that 25 % of all diabetic patients are unaware of their patho-physiological condition. Feeding behavior is often associated with the onset of the metabolic syndrome. We have deve

  5. Combined Effect of TLR2 Gene Polymorphism and Early Life Stress on the Age at Onset of Bipolar Disorders

    OpenAIRE

    José Oliveira; Bruno Etain; Mohamed Lajnef; Nora Hamdani; Meriem Bennabi; Djaouida Bengoufa; Aparna Sundaresh; Arij Ben Chaabane; Frank Bellivier; Chantal Henry; Jean-Pierre Kahn; Dominique Charron; Rajagopal Krishnamoorthy; Marion Leboyer; Ryad Tamouza

    2015-01-01

    Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential in...

  6. Long term functioning in early onset psychosis: Two years prospective follow-up study

    Directory of Open Access Journals (Sweden)

    Taha Ghada RA

    2011-07-01

    Full Text Available Abstract Background There were few studies on the outcome of schizophrenia in developing countries. Whether the outcome is similar to or different from developed world is still a point for research. The main aim of the current study was to know if patients with early onset non affective psychosis can behave and function properly after few years from start of the illness or not. Other aims included investigation of possible predictors and associated factors with remission and outcome. Method The study prospectively investigated a group of 56 patients with onset of psychosis during childhood or adolescence. Diagnosis made according to DSM-IV criteria and included; schizophrenia, psychotic disorder not otherwise specified and acute psychosis. Severity of psychosis was measured by PANSS. Measures of the outcome included; remission criteria of Andreasen et al 2005, the children's global assessment scale and educational level. Results Analysis of data was done for only 37 patients. Thirty patients diagnosed as schizophrenia and 7 with Psychotic disorder not otherwise specified. Mean duration of follow up was 38.4 +/- 16.9 months. At the end of the study, 6 patients (16.2% had one episode, 23(62.1% had multiple episodes and 8 (21.6% continuous course. Nineteen patients (51.4% achieved full remission, and only 11(29.7% achieved their average educational level for their age. Twenty seven percent of the sample had good outcome and 24.3% had poor outcome. Factors associated with non remission and poor outcome included gradual onset, low IQ, poor premorbid adjustment, negative symptoms at onset of the illness and poor adherence to drugs. Moreover, there was tendency of negative symptoms at illness start to predict poor outcome. Conclusion Some patients with early onset non affective psychosis can behave and function properly after few years from the start of the illness. Although remission is a difficult target in childhood psychosis, it is still achievable.

  7. Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Svati H Shah

    2009-01-01

    Full Text Available Neuropeptide Y (NPY is a strong candidate gene for coronary artery disease (CAD. We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families, we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004 in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72, family-based association of this block with CAD (p = 0.02, and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05, showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09; and (b GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02. A promoter SNP (rs16147 within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04. To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03. Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

  8. Early Adiposity Rebound and Obesity in Children with Congenital Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Shou-Yen Chen

    2013-04-01

    Conclusion: Children with CHT have a higher risk of obesity due to earlier age of AR. We recommend that supervision and intervention on weight control should be provided to prevent the occurrence of obesity later.

  9. Simultaneous POMC gene transfer to hypothalamus and brainstem increases physical activity, lipolysis and reduces adult-onset obesity.

    Science.gov (United States)

    Zhang, Yi; Rodrigues, Enda; Li, Gang; Gao, Yongxin; King, Michael; Carter, Christy S; Tumer, Nihal; Cheng, Kit-Yan; Scarpace, Philip J

    2011-04-01

    Pro-opiomelanocortin (POMC) neurons are identified in two brain sites, the arcuate nucleus of the hypothalamus and nucleus of the solitary tract (NTS) in brainstem. Earlier pharmacological and POMC gene transfer studies demonstrate that melanocortin activation in either site alone improves insulin sensitivity and reduces obesity. The present study, for the first time, investigated the long-term efficacy of POMC gene transfer concurrently into both sites in the regulation of energy metabolism in aged F344xBN rats bearing adult-onset obesity. Pair feeding was included to reveal food-independent POMC impact on energy expenditure. We introduced adeno-associated virus encoding either POMC or green fluorescence protein to the two brain areas in 22-month-old rats, then recorded food intake and body weight, assessed oxygen consumption, serum leptin, insulin and glucose, tested voluntary wheel running, analysed POMC expression, and examined fat metabolism in brown and white adipose tissues. POMC mRNA was significantly increased in both the hypothalamus and NTS region at termination. Relative to pair feeding, POMC caused sustained weight reduction and additional fat loss, lowered fasting insulin and glucose, and augmented white fat hormone-sensitive lipase activity and brown fat uncoupling protein 1 level. By wheel running assessment, the POMC animals ran twice the distance as the Control or pair-fed rats. Thus, the dual-site POMC treatment ameliorated adult-onset obesity effectively, involving a moderate hypophagia lasting ∼60 days, enhanced lipolysis and thermogenesis, and increased physical activity in the form of voluntary wheel running. The latter finding provides a clue for countering age-related decline in physical activity. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

  10. Tumor necrosis factor-alpha and interleukin-6 in early-onset neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Prambudi Rukmono

    2016-05-01

    Full Text Available Background Neonatal sepsis remains a major cause of mortality and morbidity in newborns. Early-onset neonatal sepsis occurs in infants under the age of 72 hours, while late-onset neonatal sepsis occurs in infants over the age of 72 hours and may be due to nosocomial infection. Diagnosing neonatal sepsis is a challenge, as its clinical symptoms are not clear. Corroborating tests include routine blood, C-reactive protein (CRP, serology, tumor necrosis factor-alpha (TNF-α, and interleukin-6 (IL-6 examinations.Objective To compare the TNF-α and IL-6 levels in patients with proven and unproven early-onset neonatal sepsis (EONSMethods This case-control study was done in the Perinatology Unit, Abdul Moeloek Hospital, Lampung. Subjects were under the age of 72 hours with risk factors and clinical symptoms of sepsis. They underwent routine blood tests and blood cultures. Infants with positive cultures were considered to have proven sepsis (26 subjects and infants with negative blood cultures were considered to have unproven sepsis (26 subjects. All subjects underwent serological examinations of TNF-α and IL-6.Results There were no differences in the basic characteristics of subjects between the two groups. Levels of TNF-α in the sepsis group were significantly higher than in the unproven group [(28.30 vs. 10.96 pg/mL, respectively (P=0.001]. Furthermore, Il-6 was significantly higher in the proven sepsis group than in the unproven sepsis group [(28.3 vs. 9.69 pg/mL, respectively (P=0.006].Conclusion Levels of TNF-alpha and IL-6 are significantly higher in infants with proven than unproven early-onset neonatal sepsis.

  11. Early- versus Late-Onset Fetal Growth Restriction Differentially Affects the Development of the Fetal Sheep Brain.

    Science.gov (United States)

    Alves de Alencar Rocha, Anna Karynna; Allison, Beth J; Yawno, Tamara; Polglase, Graeme R; Sutherland, Amy E; Malhotra, Atul; Jenkin, Graham; Castillo-Melendez, Margie; Miller, Suzanne L

    2017-01-01

    Fetal growth restriction (FGR) is a common complication of pregnancy, principally caused by suboptimal placental function, and is associated with high rates of perinatal mortality and morbidity. Clinical studies suggest that the time of onset of placental insufficiency is an important contributor towards the neurodevelopmental impairments that are evident in children who had FGR. It is however currently unknown how early-onset and late-onset FGR differentially affect brain development. The aim of this study was to examine neuropathology in early-onset and late-onset FGR fetal sheep and to determine whether they differentially alter brain development. We induced placental insufficiency and FGR via single umbilical artery ligation at either 88 days (early-onset) or 105 days (late-onset) of fetal sheep gestation (term is approx. 147 days), reflecting a period of rapid white matter brain development. Fetal blood samples were collected for the first 10 days after surgery, and all fetuses were sacrificed at 125 days' gestation for brain collection and subsequent histopathology. Our results show that early-onset FGR fetuses became progressively hypoxic over the first 10 days after onset of placental insufficiency, whereas late-onset FGR fetuses were significantly hypoxic compared to controls from day 1 after onset of placental insufficiency (SaO2 46.7 ± 7.4 vs. 65.7 ± 3.9%, respectively, p = 0.03). Compared to control brains, early-onset FGR brains showed widespread white matter injury, with a reduction in both CNPase-positive and MBP-positive density of staining in the periventricular white matter (PVWM), subcortical white matter, intragyral white matter (IGWM), subventricular zone (SVZ), and external capsule (p development that principally mediates altered brain development associated with FGR. © 2017 S. Karger AG, Basel.

  12. Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Justin Chapman

    Full Text Available BACKGROUND: Insulin resistance is manifested in muscle, adipose tissue, and liver and is associated with adipose tissue inflammation. The cellular components and mechanisms that regulate the onset of diet-induced insulin resistance are not clearly defined. METHODOLOGY AND PRINCIPAL FINDINGS: We initially observed osteopontin (OPN mRNA over-expression in adipose tissue of obese, insulin resistant humans and rats which was normalized by thiazolidinedione (TZD treatment in both species. OPN regulates inflammation and is implicated in pathogenic maladies resulting from chronic obesity. Thus, we tested the hypothesis that OPN is involved in the early development of insulin resistance using a 2-4 week high fat diet (HFD model. OPN KO mice fed HFD for 2 weeks were completely protected from the severe skeletal muscle, liver and adipose tissue insulin resistance that developed in wild type (WT controls, as determined by hyperinsulinemic euglycemic clamp and acute insulin-stimulation studies. Although two-week HFD did not alter body weight or plasma free fatty acids and cytokines in either strain, HFD-induced hyperleptinemia, increased adipose tissue inflammation (macrophages and cytokines, and adipocyte hypertrophy were significant in WT mice and blunted or absent in OPN KO mice. Adipose tissue OPN protein isoform expression was significantly altered in 2- and 4-week HFD-fed WT mice but total OPN protein was unchanged. OPN KO bone marrow stromal cells were more osteogenic and less adipogenic than WT cells in vitro. Interestingly, the two differentiation pathways were inversely affected by HFD in WT cells in vitro. CONCLUSIONS: The OPN KO phenotypes we report reflect protection from insulin resistance that is associated with changes in adipocyte biology and adipose tissue inflammatory status. OPN is a key component in the development of HFD-induced insulin resistance.

  13. Familial liability, obstetric complications and childhood development abnormalities in early onset schizophrenia: a case control study

    Directory of Open Access Journals (Sweden)

    Lucarelli Elisabetta

    2011-04-01

    Full Text Available Abstract Background Genetic and environmental risk factors and gene-environment interactions are linked to higher likelihood of developing schizophrenia in accordance with the neurodevelopmental model of disease; little is known about risk factors and early development in early-onset schizophrenia (EOS and very early-onset schizophrenia (VEOS. Methods We present a case-control study of a sample of 21 patients with EOS/VEOS and a control group of 21 patients with migraine, recruited from the Child Neuropsychiatry Unit, Department of Neurologic and Psychiatric Science, University of Bari, Italy. The aim was to assess the statistical association between VEOS/EOS and family history for psychiatric disorders, obstetric complications and childhood developmental abnormalities using 2 × 2 tables and a Chi Squared or Fisher test. Results The results show a statistical association between EOS/VEOS and schizophrenia and related disorders (P = 0.02 and personality disorders (P = 0.003 in relatives, and between EOS/VEOS and developmental abnormalities of early relational skills (P = 0.008 and learning (P = 0.04; there is not a statistically relevant difference between cases and controls (P > 0.05 for any obstetric complications (pre, peri and postpartum. Conclusions This study confirms the significant role of familial liability but not of obstetric complications in the pathogenesis of VEOS/EOS; the association between childhood developmental abnormalities and EOS/VEOS supports the neurodevelopmental model of disease.

  14. PSEN1 and PRNP gene mutations: co-occurrence makes onset very early in a family with FTD phenotype.

    Science.gov (United States)

    Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Geracitano, Silvana; Cola, Rosanna; Puccio, Gianfranco; Curcio, Sabrina A M; Frangipane, Francesca; Mirabelli, Maria; Clodomiro, Alessandra; Di Lorenzo, Raffaele; Smirne, Nicoletta; Maletta, Raffaele; Iapaolo, David; Bruni, Amalia C

    2011-01-01

    Prion protein (PRNP) gene mutations have recently been associated with clinical pictures resembling Frontotemporal dementia (FTD). We describe a novel seven extra-repeat insertional mutation in the PRNP gene in a family affected by early-onset autosomal dominant FTD previously reported as caused by a PSEN1 mutation in which there was inconsistency between clinical picture and genotype. Both mutations were pathogenic and showed a variable penetrance when present separately; when occurring together, the onset was very early, within the third decade of life. Genetic screening of the PRNP gene becomes of major importance in early onset autosomal dominant dementia.

  15. Early Cannabis Use and Estimated Risk of Later Onset of Depression Spells : Epidemiologic Evidence From the Population-based World Health Organization World Mental Health Survey Initiative

    NARCIS (Netherlands)

    de Graaf, Ron; Radovanovic, Mirjana; van Laar, Margriet; Fairman, Brian; Degenhardt, Louisa; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; de Girolamo, Giovanni; Fayyad, John; Gureje, Oye; Maria Haro, Josep; Huang, Yueqin; Kostychenko, Stanislav; Lepine, Jean-Pierre; Matschinger, Herbert; Medina Mora, Maria Elena; Neumark, Yehuda; Ormel, Johan; Posada-Villa, Jose; Stein, Dan J.; Tachimori, Hisateru; Wells, J. Elisabeth; Anthony, James C.

    2010-01-01

    Early-onset cannabis use is widespread in many countries and might cause later onset of depression. Sound epidemiologic data across countries are missing. The authors estimated the suspected causal association that links early-onset (age <17 years) cannabis use with later-onset (age >= 17 years) ris

  16. Early Cannabis Use and Estimated Risk of Later Onset of Depression Spells : Epidemiologic Evidence From the Population-based World Health Organization World Mental Health Survey Initiative

    NARCIS (Netherlands)

    de Graaf, Ron; Radovanovic, Mirjana; van Laar, Margriet; Fairman, Brian; Degenhardt, Louisa; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; de Girolamo, Giovanni; Fayyad, John; Gureje, Oye; Maria Haro, Josep; Huang, Yueqin; Kostychenko, Stanislav; Lepine, Jean-Pierre; Matschinger, Herbert; Medina Mora, Maria Elena; Neumark, Yehuda; Ormel, Johan; Posada-Villa, Jose; Stein, Dan J.; Tachimori, Hisateru; Wells, J. Elisabeth; Anthony, James C.

    2010-01-01

    Early-onset cannabis use is widespread in many countries and might cause later onset of depression. Sound epidemiologic data across countries are missing. The authors estimated the suspected causal association that links early-onset (age <17 years) cannabis use with later-onset (age >= 17 years) ris

  17. Identifying anomalously early spring onsets in the CESM large ensemble project

    Science.gov (United States)

    Labe, Zachary; Ault, Toby; Zurita-Milla, Raul

    2016-08-01

    Seasonal transitions from winter to spring impact a wide variety of ecological and physical systems. While the effects of early springs across North America are widely documented, changes in their frequency and likelihood under the combined influences of climate change and natural variability are poorly understood. Extremely early springs, such as March 2012, can lead to severe economical losses and agricultural damage when these are followed by hard freeze events. Here we use the new Community Earth System Model Large Ensemble project and Extended Spring Indices to simulate historical and future spring onsets across the United States and in the particular the Great Lakes region. We found a marked increase in the frequency of March 2012-like springs by midcentury in addition to an overall trend towards earlier spring onsets, which nearly doubles that of observational records. However, changes in the date of last freeze do not occur at the same rate, therefore, causing a potential increase in the threat of plant tissue damage. Although large-scale climate modes, such as the Pacific Decadal Oscillation, have previously dominated decadal to multidecadal spring onset trends, our results indicate a decreased role in natural climate variability and hence a greater forced response by the end of the century for modulating trends. Without a major reduction in greenhouse gas emissions, our study suggests that years like 2012 in the US could become normal by mid-century.

  18. Early-onset Alzheimer’s Disease: Nonamnestic Subtypes and Type 2 AD

    Science.gov (United States)

    Mendez, Mario F.

    2012-01-01

    Patients with Alzheimer’s disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ~4–5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer’s research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22–64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein E ε4 (APOE ε4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. PMID:23178565

  19. Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

    Science.gov (United States)

    Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G

    2013-06-01

    The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

  20. An insight into early onset of scoliosis: new update information - a review.

    Science.gov (United States)

    Alsiddiky, A M

    2015-08-01

    Early-onset scoliosis is an onerous challenge to physicians. These patients are young with significant remaining growth potential. Thus, patients are likely to develop progressive deformities, cosmetic disfigurement and cardiopulmonary consequences warrant early intervention in many cases. The purpose of this review is to provide the readers with brief description of the disease, therapeutic modalities available and their indications and use. Publications and abstracts related to EOS in the last decade were carried out and synthesized into a review "an insight into early onset of scoliosis." A comprehensive understanding of the scoliosis, its impact on the thoracic development may guide in treatment, which is often required at a young age in these children to prevent irreversible pulmonary insufficiency. Current treatment techniques are based on multiple factors may include non-surgical strategies, such as Derotational body cast or brace in younger patients with curve treatment of spinal deformity should be considered when nonoperative measures are failed to arrest curve progression. Growing rods have been the mainstay treatment of early-onset scoliosis which require repeated surgeries for distraction and are associated with exponential increase in complications. The vertical expandable prosthetic titanium rib may be beneficial for those patients with congenital scoliosis and fused ribs and thoracic insufficiency syndrome. Shilla technique is an alternative to growing rods that avoids the morbidity of repeated lengthening. Growth modulation using staples or tethers shows promise for milder curvatures, but further follow-up is needed to define their use. Although new technologies have improved the treatment of children with EOS but it continues to be challenging with high complication rates.

  1. Recognising early onset neonatal sepsis: an essential step in appropriate antimicrobial use.

    Science.gov (United States)

    van Herk, Wendy; Stocker, Martin; van Rossum, Annemarie M C

    2016-07-05

    Early diagnosis and timely treatment of early onset neonatal sepsis (EOS) are essential to prevent life threatening complications. Subtle, nonspecific clinical presentation and low predictive values of biomarkers complicate early diagnosis. This uncertainty commonly results in unnecessary and prolonged empiric antibiotic treatment. Annually, approximately 395,000 neonates (7.9% of live term births) are treated for suspected EOS in the European Union, while the incidence of proven EOS varies between 0.01 and 0.53 per 1000 live births. Adherence to guidelines for the management of suspicion of EOS is poor. Pragmatic approaches to minimise overtreatment in neonates with suspected EOS, using combined stratified risk algorithms, based on maternal and perinatal risk factors, clinical characteristics of the neonate and sequential biomarkers are promising. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  2. Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

    Science.gov (United States)

    Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

    2013-12-01

    Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

  3. Allergy to dust mites may contribute to early onset and severity of alopecia areata.

    Science.gov (United States)

    Li, S F; Zhang, X T; Qi, S L; Ye, Y T; Cao, H; Yang, Y Q; McElwee, K J; Zhang, X

    2015-03-01

    A higher risk of allergic diseases such as rhinitis, asthma and atopic eczema (atopic dermatitis) has been reported for patients with alopecia areata (AA) compared with the general population, but the significance of this is still largely unclear. To determine whether serum total or specific IgE play a role in the onset and severity of AA. We tested 461 serum samples from 351 patients with AA and 110 healthy controls (HC) for total IgE (tIgE) and specific IgE (sIgE) by ImmunoCAP-100 or in vitro test (IVT). The absolute value of tIgE was higher in patients with AA than in normal controls (P 120 IU/mL) detected in patients with AA (29.3%) was similar to that of HC (21.8%). Prevalences of raised sIgE against various allergens detected by ImmunoCAP-100 showed that Dermatophagoides pteronyssinus (Der p; 31.1%) and Dermatophagoides farinae (Der f; 29.0%) were the most common allergens. Similar results were found by IVT, with the most common response being against Der p/Der f (29.0%). However, the prevalences of tIgE and sIgE against dust mites (Der p and Der f) in patients with early-onset AA and severe AA were significantly higher than those with late-onset AA and mild AA (P = 0.02, P = 0.02 vs. P = 0.03 and P = 0.001, respectively). Notably, the increases in tIgE and sIgE were independent of atopy history. Allergy to dust mites may have an effect on the immune response in AA, and may contribute to its early onset and severity in patients of Chinese origin. © 2014 British Association of Dermatologists.

  4. Amyloid imaging with [(18)F]florbetapir in geriatric depression: early-onset versus late-onset.

    Science.gov (United States)

    Tateno, Amane; Sakayori, Takeshi; Higuchi, Makoto; Suhara, Tetsuya; Ishihara, Keiichi; Kumita, Shinichiro; Suzuki, Hidenori; Okubo, Yoshiro

    2015-07-01

    We examined patients with mild cognitive impairment (MCI) with a history of geriatric depression (GD) and healthy controls (HC) to evaluate the effect of beta-amyloid (Aβ) pathology on the pathology of GD by using [(18)F]florbetapir PET. Thirty-three elderly patients (76.7 ± 4.2 years) and 22 healthy controls (HC; 72.0 ± 4.5 years, average ± SD) were examined by [(18)F]florbetapir positron emission tomography (PET) to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI to determine the degree of atrophy, by Mini-Mental State Examination for cognitive functions, and by Geriatric Depression Scale for the severity of depression, and by Clinical Dementia Rating for activity of daily living (ADL). The cut-off value of 1.08 for SUVR was defined as Aβ-positive. Of the patients and HC, 39.4% and 27.3%, respectively, were beta-amyloid-positive. The onset age of GD was significantly correlated with SUVR (r = 0.44, p depression and ADL, and brain atrophy. GD + Aβ had significantly older average ± SD age at onset of GD (73.6 ± 7.1 versus 58.7 ± 17.8, p < 0.01) and significantly shorter average ± SD time between onset of GD and PET scan day (3.1 ± 5.2 years versus 18.1 ± 18.6 years, p < 0.001) than GD-Aβ. Our results showed that the rate of Aβ positivity was higher in late-onset GD and that onset-age was associated with SUVR, suggesting that the later the onset of GD, the more Aβ pathology affected its onset. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Prophylactic fenbendazole therapy does not affect the incidence and onset of type 1 diabetes in non-obese diabetic mice.

    Science.gov (United States)

    Franke, Deanna D H; Shirwan, Haval

    2006-03-01

    Fenbendazole (FBZ) is a common, highly efficacious broad-spectrum anthelmintic drug used to treat and limit rodent pinworm infections. However, the effect of its prophylactic use on the immune response of rodents is largely undefined. The non-obese diabetic (NOD) mouse is a model commonly used to study type 1 diabetes (T1D). Parasitic infections will inhibit diabetes development in NOD mice; thus, in the presence of contamination, prophylactic treatment with anthelmintics must be considered to maintain experimental research. Herein, we investigated the prophylactic use of FBZ in NOD mice to determine its effect on the incidence and onset of diabetes, lymphocyte sub-populations and T cell proliferative responses. NOD mice were separated into control and treatment groups. The treatment group received a diet containing FBZ. Animals were monitored for the incidence and onset of T1D. At matched time points, diabetic and non-diabetic mice were killed and splenic lymphocytes analyzed for various cell sub-populations and mitogen-induced proliferative responses using flow cytometry. Treated and control mice were monitored >23 weeks with no detectable effects on the incidence or onset of diabetes. Moreover, no significant differences were detected in lymphocyte sub-populations and mitogen-induced CD4(+) and CD8(+) proliferative responses between control and treatment groups. These results suggest that prophylactic FBZ treatment does not significantly alter the incidence or onset of diabetes in NOD mice. The prophylactic use of FBZ, therefore, presents a viable approach for the prevention of pinworm infection in precious experimental animals with substantial scientific and economic benefits.

  6. Early and late onset depression in young and middle aged adults : Differential symptomatology, characteristics and risk factors?

    NARCIS (Netherlands)

    Korten, Nicole C. M.; Comijs, Hannie C.; Lamers, Femke; Penninx, Brenda W. J. H.

    2012-01-01

    Background: Early onset depression (EOD) and late onset depression (LOD) may be different phenomena. In this study, differences between EOD and LOD in symptomatology, psychiatric characteristics and psychosocial/somatic factors were examined. Methods: Baseline data were from 1104 participants with a

  7. Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth

    DEFF Research Database (Denmark)

    Mortensen, Preben Bo; Nørgaard-Pedersen, Bent; Waltoft, Berit Lindum

    2007-01-01

    of infection and other schizophrenia-like disorders or affective disorders. CONCLUSIONS: Our study supports an association between Toxoplasma gondii and early-onset schizophrenia. Further studies are needed to establish if the association is causal and if it generalizes to cases with onset after age 18...

  8. Toxoplasma gondii as a Risk Factor for Early-Onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth

    DEFF Research Database (Denmark)

    Mortensen, Preben Bo; Nørgaard-Pedersen, Bent; Waltoft, Berit Lindum

    2006-01-01

    of infection and other schizophrenia-like disorders or affective disorders. CONCLUSIONS: Our study supports an association between T gondii and early-onset schizophrenia. Further studies are needed to establish if the association is causal and if it generalizes to cases with onset after age 18....

  9. Early diet, insulin-like growth factor-1, growth and later obesity.

    Science.gov (United States)

    Michaelsen, Kim F; Larnkjaer, Anni; Molgaard, Christian

    2013-01-01

    There is increasing evidence that factors in early life are important for the risk of developing overweight and obesity later in childhood. Among the postnatal factors, breastfeeding and complementary feeding are especially interesting because the pattern of these two factors can be changed. Breastfeeding has been shown to reduce the risk of later obesity, although the effect is not substantial. Complementary feeding also seems to play a role. There is some evidence that a high protein intake is associated with a higher risk of obesity later in childhood, whereas a high fat intake during the complementary feeding period does not seem to be a risk factor for later obesity. Thus, the dietary pattern during this period is different from the pattern seen in older children and adults where a high fat intake is associated with a higher risk of obesity and a high protein intake in some studies seems to protect against obesity. A few studies have also suggested that early introduction of complementary foods (before age 4 months) is associated with an increased risk of later obesity. A high weight gain during early life, especially the first 6 months, is associated with a higher risk of developing obesity. However, some studies suggest that weight gain during the 6- to 12-month age period, when complementary feeding is introduced, is not associated with later obesity. Insulin-like growth factor-1 (IGF-1) values and body composition both play a role in the complex pattern between early diet and later obesity, but our present knowledge about how these factors are influenced by diet during infancy is limited. Future studies should include longitudinal data on IGF-1 and body composition during infancy to improve our understanding of how diet in early life can play a role in prevention of later obesity. Copyright © 2013 S. Karger AG, Basel.

  10. Mutation analysis of ATP13A2 in early-onset parkinsonism patients

    Institute of Scientific and Technical Information of China (English)

    Yuping Ning; Hiroyuki Tomiyama; Yuanzhe Li; Manabu Funayama; Hiroyo Yoshino; Shigeto Sato; Yoshikuni Mizuno; Nobutaka Hattori

    2008-01-01

    BACKGROUND: A recent study has found that ATP13A2 is the causative gene for PARK9-linked autosomal recessive early-onset parkinsonism, described previously in Jordanian and Chilean families (Kufor-Rakeb syndrome). OBJECTIVE: To screen eastern Asian patients with early-onset parkinsonism for mutations in ATP13A2 and to describe positron emission tomography (PET) findings of PARK9-linked parkinsonism.DESIGN, TIME AND SETTING: In total, 117 patients were selected from the Department of Neurology, Juntendo University, from February 2003 to October 2006, for this molecular genetics and case-control study.PARTICIPANTS: The patients with parkinsonism consist of two cohorts. Ninety four patients with onset age of less than 30 years were selected for the first cohort. They included 49 males and 44 females, comprising 73 Japanese, 9 Korean, 8 Taiwanese, and 4 Mainland Chinese. Eleven patients had parkinsonism complicated with dementia, 15 patients had family histories of parkinsonism (including 2 families), and 5 patients were from consanguineous parents (including one family). The second cohort of 23 patients was composed of patients with consanguineous parents (n = 15) or who had affected siblings (n = 6) or both (n = 2), but the age at onset ranged from 30 to 50 years.METHODS: In 117 patients with parkinsonism, direct sequencing of ATP13A2 exons 13, 16, and 26, in which mutations had been reported previously, were performed. Sequencing was also performed in all 29 exons, including splice sites, in 28 probands who showed homozygosity at the PARK9 locus by haplotype analysis. Mutation analysis was also performed in 150 normal people. Linkage analysis was performed on all 3 parkinsonism families using short tandem repeat markers flanking the PARK9 locus. For patients who had ATP13A2 mutation, we performed brain MRI and 18F-dopa PET scans.MAIN OUTCOME MEASURES: ATP13A2 DNA sequence, 18F-dopa PET scan and brain MRI findings.RESULTS: A novel F182L mutation in a consanguineous

  11. Committee Opinion Summary No. 638: First-Trimester Risk Assessment for Early-Onset Preeclampsia.

    Science.gov (United States)

    2015-09-01

    Hypertensive disorders with adverse sequelae (including preterm birth, maternal morbidity and mortality, and long-term risk of maternal cardiovascular disease) complicate 5-10% of pregnancies. Early identification of pregnant women at risk of developing early-onset preeclampsia would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease. In practice, however, the effectiveness of such triage would be hindered by the low positive predictive value for early-onset preeclampsia reported in the literature. In spite of the modest predictive value of first-trimester preeclampsia risk assessment and the lack of data demonstrating improved clinical outcomes, commercial tests are being marketed for the prediction of preeclampsia in the first trimester. Taking a detailed medical history to evaluate for risk factors is currently the best and only recommended screening approach for preeclampsia; it should remain the method of screening for preeclampsia until studies show that aspirin or other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests.

  12. Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Dandan Tan

    Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

  13. The Role of Pancreatic Stone Protein in Diagnosis of Early Onset Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    Anwar A. Rass

    2016-01-01

    Full Text Available Introduction. Early diagnosis and treatment of neonatal sepsis may help decrease neonatal mortality. Aim of the Study. To evaluate the role of pancreatic stone protein as a marker for early onset neonatal sepsis. Methods. A hospital-based prospective study was conducted on 104 (52 uninfected and 52 infected neonates admitted to the Neonatal Intensive Care Unit (NICU of Zagazig University hospitals during the period from April 2014 to April 2015. All newborns were subjected to full history taking, careful neonatal assessment, blood, C-reactive protein (CRP, and serum pancreatic stone protein. Results. Serum PSP levels were significantly higher in the infected group than in the uninfected group. At a cutoff level of PSP 12.96 ng/mL, the sensitivity was 96.2%, the specificity was 88.5%, positive predictive value was 95.8%, negative predictive value was 89.3%, and area under the curve was 0.87. A significant positive correlation between CRP and PSP was found in infected group. Conclusion. The high negative predictive value of PSP (89.3% indicates that the serum PSP level is a good marker for diagnosis of early onset neonatal sepsis and can be used to limit hospital stay and antibiotic use in neonates treated for suspected sepsis.

  14. Early-Onset Scoliosis: A Review of History, Current Treatment, and Future Directions.

    Science.gov (United States)

    Yang, Scott; Andras, Lindsay M; Redding, Gregory J; Skaggs, David L

    2016-01-01

    Early-onset scoliosis (EOS) is defined as curvature of the spine in children >10° with onset before age 10 years. Young children with EOS are at risk for impaired pulmonary function because of the high risk of progressive spinal deformity and thoracic constraints during a critical time of lung development. The treatment of EOS is very challenging because the population is inhomogeneous, often medically complex, and often needs multiple surgeries. In the past, early spinal fusion was performed in children with severe progressive EOS, which corrected scoliosis but limited spine and thoracic growth and resulted in poor pulmonary outcomes. The current goal in treatment of EOS is to maximize growth of the spine and thorax by controlling the spinal deformity, with the aim of promoting normal lung development and pulmonary function. Bracing and casting may improve on the natural history of progression of spinal deformity and are often used to delay surgical intervention or in some cases obviate surgery. Recent advances in surgical implants and techniques have led to the development of growth-friendly implants, which have replaced early spine fusion as the surgical treatment of choice. Treatment with growth-friendly implants usually requires multiple surgeries and is associated with frequent complications. However, growth-friendly spine surgery has been shown to correct spinal deformity while allowing growth of the spine and subsequently lung growth.

  15. The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

    Science.gov (United States)

    Wan, Ji-Peng; Wang, Hong; Li, Chang-Zhong; Zhao, Han; You, Li; Shi, Dong-Hong; Sun, Xiu-Hua; Lv, Hong; Wang, Fei; Wen, Ze-Qing; Wang, Xie-Tong; Chen, Zi-Jiang

    2014-11-01

    Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. © The Author(s) 2014.

  16. The dramatic effects of Galantamine in a patient with early-onset Alzheimer's disease.

    Science.gov (United States)

    Dev, Harveer; Agius, Mark; Zaman, Rashid

    2010-06-01

    We discuss the case of a 51 year old former mid-wife presented to the NHS Luton and Bedfordshire psychiatric services with a 2 year history of increasing forgetfulness with significant impairment to her daily function. She was diagnosed with non-familial early-onset Alzheimer's Disease (EOAD) and started on 8mg daily of the acetylcholinesterase inhibitor Galantamine. The information for this study was gathered from patient notes, consultant, collateral and personal accounts. Periodic outpatient consultations at the NHS Luton and Bedfordshire psychiatric services were used to monitor Mrs LF's global, functional and behavioral progress. These were supplemented with the mini mental state examination (MMSE) at each outpatient appointment. The graph of MMSE scores illustrates severe decline in scores, followed eventually by increase in score to sustained improvement while continuing on galantamine. Functionally, this lady has successfully negotiated a divorce, moved into her own accommodation, began travelling on holidays, including abroad, with friends, and has now embarked on a new relationship. Whilst only being a single case study, this demonstrates the significant benefits which are attainable with Galantamine in EOAD. The extent of this improvement may be a result of individual variation, or perhaps a greater efficacy for this drug in the subset of 'early-onset' AD patients, which has long been thought to share the same mechanism as traditional AD. The responsiveness to Galantamine in this patient may suggest an alternative mechanism of Early Onset Alzheimer's Disease to typical Alzheimer's Disease in the over 65's. The case raises interesting questions as to whether EOAD should be considered distinct to typical (over 65's) AD, given the greater than expected response to Galantamine.

  17. Identification of inherited genetic variations influencing prognosis in early-onset breast cancer.

    Science.gov (United States)

    Rafiq, Sajjad; Tapper, William; Collins, Andrew; Khan, Sofia; Politopoulos, Ioannis; Gerty, Sue; Blomqvist, Carl; Couch, Fergus J; Nevanlinna, Heli; Liu, Jianjun; Eccles, Diana

    2013-03-15

    Genome-Wide Association Studies (GWAS) have begun to investigate associations between inherited genetic variations and breast cancer prognosis. Here, we report our findings from a GWAS conducted in 536 patients with early-onset breast cancer aged 40 or less at diagnosis and with a mean follow-up period of 4.1 years (SD = 1.96). Patients were selected from the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer. A Bonferroni correction for multiple testing determined that a P value of 1.0 × 10(-7) was a statistically significant association signal. Following quality control, we identified 487,496 single nucleotide polymorphisms (SNP) for association tests in stage 1. In stage 2, 35 SNPs with the most significant associations were genotyped in 1,516 independent cases from the same early-onset cohort. In stage 2, 11 SNPs remained associated in the same direction (P ≤ 0.05). Fixed effects meta-analysis models identified one SNP associated at close to genome wide level of significance 556 kb upstream of the ARRDC3 locus [HR = 1.61; 95% confidence interval (CI), 1.33-1.96; P = 9.5 × 10(-7)]. Four further associations at or close to the PBX1, RORα, NTN1, and SYT6 loci also came close to genome-wide significance levels (P = 10(-6)). In the first ever GWAS for the identification of SNPs associated with prognosis in patients with early-onset breast cancer, we report a SNP upstream of the ARRDC3 locus as potentially associated with prognosis (median follow-up time for genotypes: CC = 4 years, CT = 3 years, and TT = 2.7 years; Wilcoxon rank-sum test CC vs. CT, P = 4 × 10(-4) and CT vs. TT, P = 0.76). Four further loci may also be associated with prognosis.

  18. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie

    2015-01-01

    Partnering early childhood education and care (ECEC) and the home together may be more effective in combating obesogenic risk factors in preschool children. Thus, an evaluation of ECEC obesity prevention interventions with a parental component was conducted, exploring parental engagement and its effect on obesity and healthy lifestyle outcomes. A…

  19. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie

    2015-01-01

    Partnering early childhood education and care (ECEC) and the home together may be more effective in combating obesogenic risk factors in preschool children. Thus, an evaluation of ECEC obesity prevention interventions with a parental component was conducted, exploring parental engagement and its effect on obesity and healthy lifestyle outcomes. A…

  20. Early Maternal Employment and Childhood Obesity among Economically Disadvantaged Families in the USA

    Science.gov (United States)

    Coley, Rebekah Levine; Lombardi, Caitlin McPherran

    2012-01-01

    Research indicates a link between maternal employment and children's risk of obesity, but little prior work has addressed maternal employment during children's infancy. This study examined the timing and intensity of early maternal employment and associations with children's later overweight and obesity in a sample of low-income families in…

  1. Early Maternal Employment and Childhood Obesity among Economically Disadvantaged Families in the USA

    Science.gov (United States)

    Coley, Rebekah Levine; Lombardi, Caitlin McPherran

    2012-01-01

    Research indicates a link between maternal employment and children's risk of obesity, but little prior work has addressed maternal employment during children's infancy. This study examined the timing and intensity of early maternal employment and associations with children's later overweight and obesity in a sample of low-income families in…

  2. ATP13A2 variants in early-onset Parkinson's disease patients and controls

    DEFF Research Database (Denmark)

    Djarmati, Ana; Hagenah, Johann; Reetz, Kathrin

    2009-01-01

    Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exons...... of the ATP13A2 coding region in 112 patients with early-onset PD (EOPD; origin and of 55 controls. We identified four carriers (3.6%) of novel single heterozygous ATP13A2 missense changes that were absent in controls. Interestingly, the carrier of one of these variants...

  3. Functional and Radiographic Outcomes Following Growth-Sparing Management of Early-Onset Scoliosis.

    Science.gov (United States)

    Johnston, Charles E; Tran, Dong-Phuong; McClung, Anna

    2017-06-21

    In this study, we sought to evaluate radiographic, functional, and quality-of-life outcomes of patients who have completed growth-sparing management of early-onset scoliosis. This prospective study involved patients with early-onset scoliosis who underwent growth-sparing treatment and either "final" fusion or observation for ≥2 years since the last lengthening procedure. Demographics, radiographic parameters, pulmonary function test (PFT) values, and scores of patient-reported assessments (Early-Onset Scoliosis Questionnaire [EOSQ] and Scoliosis Research Society [SRS]-30) were obtained. At the most recent follow-up, patients performed 2 additional functional outcome tests: step-activity monitoring and a treadmill exercise-tolerance test. Twelve patients were evaluated as "graduates" of growth-sparing management of early-onset scoliosis (mean of 37 months since the most recent surgery). The major scoliosis curve measurement averaged 88° before treatment and 47° at the most recent follow-up. T1-S1 height increased from a mean of 22.3 cm to 34.7 cm and T1-T12 height, from 13.3 to 22.3 cm. At the most recent follow-up, the mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) as a percentage of the predicted volume were 52.1% and 55.3%, respectively, and were essentially unchanged from the earliest PFT that patients could perform (FEV1 = 53.8% of predicted and FVC = 53.5% of predicted). There was no difference between graduates and controls with respect to activity time or total steps in step-activity monitoring, and in the exercise-tolerance test, graduates walked at the same speed but at a higher heart rate and at a significantly higher (p scoliosis appears to be spine elongation and maintenance of pulmonary function at a level that is no less than the percentage of normal at initial presentation. Functional testing and patient-reported outcomes at a mean of 3 years from the last surgery suggest that activity levels were generally equal

  4. Using hip measures to avoid misdiagnosing early rapid onset osteoarthritis for osteonecrosis.

    Science.gov (United States)

    Nelson, Fred R T; Bhandarkar, Varun S; Woods, Tammy A

    2014-06-01

    In the early phases, subchondral insufficiency fractures and rapidly destructive osteoarthritis of the hip are often mistaken for osteonecrosis of the hip. Three hip measures were used comparing combined subchondral insufficiency fractures and rapidly destructive 18 osteoarthritis patients to 18 osteonecrosis patients. Due to the rarity of these conditions there was no statistical power. Initial diagnoses for the osteoarthritis patients were recorded. The osteoarthritis group had significantly higher means for Tönnis angle (P osteoarthritis. Using hip measures will reduce the misdiagnosis of rapid onset osteoarthritis of the hip for osteonecrosis.

  5. Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

    Science.gov (United States)

    Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

    2017-08-22

    To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

  6. Approach to early-onset colorectal cancer:Clinicopathological,familial,molecular and immunohistochemical characteristics

    Institute of Scientific and Technical Information of China (English)

    Jose; Perea; Edurne; Alvaro; Yolanda; Rodríguez; Cristina; Gravalos; Eva; Sánchez-Tomé; Barbara; Rivera; Francisco; Colina; Pablo; Carbonell; Rogelio; González-Sarmiento; Manuel; Hidalgo; Miguel; Urioste

    2010-01-01

    AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study w...

  7. Early-onset type 2 diabetes in a Mexican survey. Results from the National Health and Nutrition Survey 2006

    OpenAIRE

    Aída Jiménez-Corona; Rosalba Rojas; Francisco J Gómez-Pérez; Aguilar-Salinas, Carlos A

    2010-01-01

    OBJECTIVE: To describe the characteristics of patients with type 2 diabetes diagnosed before age 40 (early-onset type 2 diabetes) identified in a nation-wide, population-based study. MATERIALS AND METHODS: The survey was done in Mexico during 2006. Medical history, anthropometric and biochemical measurements were obtained in every subject. RESULTS: Cases diagnosed before (n=181) and after age 40 (n=659) were included. Early-onset type 2 diabetes was present in 13.1% of the previously diagnose...

  8. Mapping the Progression of Atrophy in Early- and Late-Onset Alzheimer's Disease.

    Science.gov (United States)

    Migliaccio, Raffaella; Agosta, Federica; Possin, Katherine L; Canu, Elisa; Filippi, Massimo; Rabinovici, Gil D; Rosen, Howard J; Miller, Bruce L; Gorno-Tempini, Maria Luisa

    2015-01-01

    The term early-onset Alzheimer's disease (EOAD) identifies patients who meet criteria for AD, but show onset of symptoms before the age of 65. We map progression of gray matter atrophy in EOAD patients compared to late-onset AD (LOAD). T1-weighted MRI scans were obtained at diagnosis and one-year follow-up from 15 EOAD, 10 LOAD, and 38 age-matched controls. Voxel-based and tensor-based morphometry were used, respectively, to assess the baseline and progression of atrophy. At baseline, EOAD patients already showed a widespread atrophy in temporal, parietal, occipital, and frontal cortices. After one year, EOAD had atrophy progression in medial temporal and medial parietal cortices. At baseline, LOAD patients showed atrophy in the medial temporal regions only, and, after one year, an extensive pattern of atrophy progression in the same neocortical cortices of EOAD. Although atrophy mainly involved different lateral neocortical or medial temporal hubs at baseline, it eventually progressed along the same brain default-network regions in both groups. The cortical region showing a significant progression in both groups was the medial precuneus/posterior cingulate.

  9. Early- and late-onset Alzheimer disease: Are they the same entity?

    Science.gov (United States)

    Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

    2015-11-03

    Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Early Versus Late Onset of Cannabis Use: Differences in Striatal Response to Cannabis Cues

    Science.gov (United States)

    Wetherill, Reagan R.; Hager, Nathan; Jagannathan, Kanchana; Mashhoon, Yasmin; Pater, Heather; Childress, Anna Rose; Franklin, Teresa R.

    2017-01-01

    Addiction theories posit that addiction is the result of a progressive transition from voluntary to habitual, compulsive drug use—changes that have been linked, in animals, to a shift from ventral to dorsal striatal control over drug-seeking behavior. Thus, we hypothesized that early-onset (EOs) cannabis users versus late-onset (LOs) cannabis users might exhibit, respectively, greater dorsal versus ventral striatal response to drug cues. We used functional magnetic resonance imaging and an event-related blood oxygen level-dependent backward-masking task to evaluate striatal responses to backward-masked cannabis cues (vs. neutral cues) in EOs (cannabis use patterns. Direct comparisons revealed that EOs showed greater response to cannabis cues in the dorsal striatum than LOs (p 50 voxels). Within-group analyses revealed that EOs showed greater neural response to cannabis cues in the dorsal striatum, whereas LOs exhibited greater neural response to cannabis cues in the ventral striatum. Although cross-sectional, these findings are consistent with recent addiction theories suggesting a progressive shift from ventral to dorsal striatal control over drug-seeking behavior and highlight the importance of age of onset of cannabis use on the brain and cognition.

  11. Cardiovascular Disease Risk Factors After Early-Onset Preeclampsia, Late-Onset Preeclampsia, and Pregnancy-Induced Hypertension

    NARCIS (Netherlands)

    Veerbeek, Jan H. W.; Hermes, Wietske; Breimer, Anath Y.; van Rijn, Bas B.; Koenen, Steven V.; Mol, Ben W.; Franx, Arie; de Groot, Christianne J. M.; Koster, Maria P. H.; Koster, M.P.H. (Wendy)

    2015-01-01

    Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been investi

  12. Design and methods for evaluating an early childhood obesity prevention program in the childcare center setting

    National Research Council Canada - National Science Library

    Natale, Ruby; Scott, Stephanie Hapeman; Messiah, Sarah E; Schrack, Maria Mesa; Uhlhorn, Susan B; Delamater, Alan

    2013-01-01

    .... Presently, approximately 70 percent of children in the United States are currently enrolled in early childcare facilities, making this an ideal setting to implement and evaluate childhood obesity prevention efforts...

  13. Weight and weight gain during early infancy predict childhood obesity

    DEFF Research Database (Denmark)

    Andersen, Lise Geisler; Holst, Claus; Michaelsen, Kim F.

    2012-01-01

    Infant weight and weight gain are positively associated with later obesity, but whether there is a particular critical time during infancy remains uncertain.......Infant weight and weight gain are positively associated with later obesity, but whether there is a particular critical time during infancy remains uncertain....

  14. Stop Obesity Early (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2016-11-17

    Nearly one in 10 children who enter kindergarten are obese. This podcast discusses the risks associated with childhood and adulthood obesity, as well as the importance of exercise and proper nutrition.  Created: 11/17/2016 by MMWR.   Date Released: 11/17/2016.

  15. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    Science.gov (United States)

    Lee, Soo Min; Nguyen, Dara; Anand, Marie; Kant, Ritu; Köhncke, Clemens; Lisewski, Ulrike; Roepke, Torsten K.; Hu, Zhaoyang; Abbott, Geoffrey W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2─/─ mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis. PMID:26984260

  16. A case of probable non-familial early onset Alzheimer dementia in a Hispanic male

    Directory of Open Access Journals (Sweden)

    Corey Ephrussi

    2012-07-01

    Full Text Available Background: Early onset Alzheimer's type dementia (EOAD is usually familial and associated with mutations in the Presenilin-1 (PSEN1, Presenilin-2 (PSEN2 or amyloid precursor protein (APP genes. It is rarely reported in patients of Hispanic descent. Case report: A 49-year-old Hispanic male developed significant cognitive impairment over a 4-year period. PET scan showed diminished metabolic activity in the posterior parietal/temporal lobes. Genetic testing revealed the presence of a PSEN1 gene mutation. Conclusion: Disparities in health care may account for an under-recognition of EOAD in the Hispanic population. Clinicians should test for EOAD in all patients with appropriate symptomatology, regardless of ethnicity. Early recognition and enrollment in clinical trials is vital to enhancing our understanding of the natural history and treatment of this condition.

  17. The Usefulness of Biological and Neuroimaging Markers for the Diagnosis of Early-Onset Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Alessandro Padovani

    2011-01-01

    Full Text Available The recent proposed criteria for Alzheimer's Disease (AD have strongly claimed the usefulness of biological and neuroimaging markers for early identification AD. Cerebrospinal fluid (CSF Tau/Abeta ratio, hippocampal atrophy, posterior cingulate, and neocortical associative area hypometabolism, or amyloid burden evaluated by PiB compound, held the premises to increase diagnostic accuracy in the preclinical disease stages. Despite many efforts to identify subjects at risk of developing AD, less attention has been paid to presenile AD diagnosis. A few data are already available in early onset AD, mainly obtained in cases of monogenic disorder. In this paper, we discuss the current literature on the role of biological and neuroimaging markers in presenile AD.

  18. Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13.

    Science.gov (United States)

    Minassian, Natali A; Lin, Meng-Chin A; Papazian, Diane M

    2012-04-01

    Mutations in Kv3.3 cause spinocerebellar ataxia type 13 (SCA13). Depending on the causative mutation, SCA13 is either a neurodevelopmental disorder that is evident in infancy or a progressive neurodegenerative disease that emerges during adulthood. Previous studies did not clarify the relationship between these distinct clinical phenotypes and the effects of SCA13 mutations on Kv3.3 function. The F448L mutation alters channel gating and causes early-onset SCA13. R420H and R423H suppress Kv3 current amplitude by a dominant negative mechanism. However, R420H results in the adult form of the disease whereas R423H produces the early-onset, neurodevelopmental form with significant clinical overlap with F448L. Since individuals with SCA13 have one wild type and one mutant allele of the Kv3.3 gene, we analysed the properties of tetrameric channels formed by mixtures of wild type and mutant subunits. We report that one R420H subunit and at least one R423H subunit can co-assemble with the wild type protein to form active channels. The functional properties of channels containing R420H and wild type subunits strongly resemble those of wild type alone. In contrast, channels containing R423H and wild type subunits show significantly altered gating, including a hyperpolarized shift in the voltage dependence of activation, slower activation, and modestly slower deactivation. Notably, these effects resemble the modified gating seen in channels containing a mixture of F448L and wild type subunits, although the F448L subunit slows deactivation more dramatically than the R423H subunit. Our results suggest that the clinical severity of R423H reflects its dual dominant negative and dominant gain of function effects. However, as shown by R420H, reducing current amplitude without altering gating does not result in infant onset disease. Therefore, our data strongly suggest that changes in Kv3.3 gating contribute significantly to an early age of onset in SCA13.

  19. 2014 CODEPEH recommendations: Early detection of late onset deafness, audiological diagnosis, hearing aid fitting and early intervention.

    Science.gov (United States)

    Núñez-Batalla, Faustino; Jáudenes-Casaubón, Carmen; Sequí-Canet, Jose Miguel; Vivanco-Allende, Ana; Zubicaray-Ugarteche, Jose

    2016-01-01

    The latest scientific literature considers early diagnosis of deafness as the key element to define the educational and inclusive prognosis of the deaf child, because it allows taking advantage of the critical period of development (0-4 years). Highly significant differences exist between deaf people who have been stimulated early and those who have received late or improper intervention. Early identification of late-onset disorders requires special attention and knowledge on the part of every childcare professional. Programs and additional actions beyond neonatal screening should be designed and planed to ensure that every child with a significant hearing loss is detected early. For this purpose, the CODEPEH would like to highlight the need for continuous monitoring of children's auditory health. Consequently, CODEPEH has drafted the recommendations included in the present document. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  20. A polymorphism in the human agouti-related protein is associated with late-onset obesity.

    Science.gov (United States)

    Argyropoulos, George; Rankinen, Tuomo; Neufeld, Doni R; Rice, Treva; Province, Michael A; Leon, Arthur S; Skinner, James S; Wilmore, Jack H; Rao, D C; Bouchard, Claude

    2002-09-01

    The mouse agouti-related protein (AGRP) is a powerful appetite effector that results in hyperphagia and the development of obesity when administered intracerebroventricularly or when overexpressed in transgenic mice. Animal studies have also shown that exogenous administration of AGRP predisposes toward hedonic intake of high fat and high sucrose diets. The human ortholog (hAGRP) maps on chromosome 16q22 and has similar physiological properties, as tested in animal models. A polymorphism was identified in the third exon of hAGRP, c.199G-->A, that resulted in a nonconservative amino acid substitution, Ala(67)Thr. Computational analysis of the protein showed significant differences in the coils of the two polymorphic isoforms of the protein. Human studies showed no genotype effects in individuals with a mean age of 25 yr. However, the G/G genotype was significantly associated with fatness and abdominal adiposity in the parental population with a mean age of 53 yr. The c.199G-->A polymorphism in hAGRP could, therefore, play a role in the development of human obesity in an age-dependent fashion.

  1. Menkes disease – An important cause of early onset refractory seizures

    Directory of Open Access Journals (Sweden)

    Puneet Jain

    2014-01-01

    Full Text Available Context: Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities. Aims: We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute. Setting/Design: The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported. Statistical analysis used: Descriptive statistics were used. Results: During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4, myoclonic (2 and tonic seizures (1. The electroencephalographic abnormalities included hypsarrythmia (2 and multifocal epileptiform discharges (3. The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels. Conclusions: Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis.

  2. GATA2 is associated with familial early-onset coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Jessica J Connelly

    2006-08-01

    Full Text Available The transcription factor GATA2 plays an essential role in the establishment and maintenance of adult hematopoiesis. It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelial cells and smooth muscle cells. We have shown that GATA2 expression is predictive of location within the thoracic aorta; location is suggested to be a surrogate for disease susceptibility. The GATA2 gene maps beneath the Chromosome 3q linkage peak from our family-based sample set (GENECARD study of early-onset coronary artery disease. Given these observations, we investigated the relationship of several known and novel polymorphisms within GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significant association of two of these single nucleotide polymorphisms in an independent case-control sample set that was phenotypically similar to the GENECARD families. These observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary artery disease inheritance.

  3. Validity of hematologic parameters in identification of early and late onset neonatal infection.

    Science.gov (United States)

    Varsha; Rusia, Usha; Sikka, Meera; Faridi, M M A; Madan, Nishi

    2003-10-01

    This study was designed to evaluate the utility of hematological parameters and C-reactive protein (CRP) to formulate a sepsis screen to detect sepsis in early and late onset infection. Hundred and fifty neonates clinically suspected of bacterial infection, based on risk factors and/or clinical features were selected for the study. Blood was collected by venipuncture at the time of admission in all neonates. A total leukocyte count (TLC), differential leukocyte count (DLC), its derivatives [Total neutrophil count (TNC or T), ratio of immature to total neutrophil count (I/T), ratio of immature to mature neutrophil count (I/M)] and CRP were obtained. TLC = 10x10(9)/L, TNC = 8x10(9)/L, I/T = 0.16, I/M = 0.25 and CRP = 0.6 mg/dl were found to be good parameters in detection of sepsis. During the first three days of life leukopenia, neutropenia, elevated I/T ratio, elevated I/M ratio and CRP were good diagnostic aids while after 3 days of life CRP was the best single test. This emphasizes use of multiple indicators for detection of sepsis. Using these parameters a sepsis screen was formulated which detected >90% of proven early and late onset sepsis suggesting that other neonates with positive sepsis screen but blood culture negativity may have been truly infected.

  4. Submersion and early-onset acute respiratory distress syndrome: a case report.

    Science.gov (United States)

    Diamond, Wayde; MacDonald, Russell D

    2011-01-01

    Drowning is a common cause of accidental death, particularly in younger people, and acute respiratory failure is common in these patients. This case report describes a healthy 18-year-old man who suffered a cardiorespiratory arrest due to submersion while swimming in a freshwater lake. First-responder cardiopulmonary resuscitation and defibrillation using an automated external defibrillator resulted in a return of spontaneous circulation. The patient was evacuated to a tertiary care center by a rotor-wing air medical crew. The crew experienced difficulties in oxygenating and ventilating the patient because of early-onset acute respiratory distress syndrome (ARDS). This case report describes the pathophysiology and prehospital management of a patient with suspected early-onset ARDS secondary to drowning. This case report is unique because it describes the oxygenation and ventilation difficulties encountered in managing this patient in the transport setting, and possible strategies to deal with these difficulties. Finally, this case report highlights the prehospital bypass decision-making process for patients requiring specialized medical care.

  5. Candidate predisposing germline copy number variants in early onset colorectal cancer patients.

    Science.gov (United States)

    Brea-Fernandez, A J; Fernandez-Rozadilla, C; Alvarez-Barona, M; Azuara, D; Ginesta, M M; Clofent, J; de Castro, L; Gonzalez, D; Andreu, M; Bessa, X; Llor, X; Xicola, R; Jover, R; Castells, A; Castellvi-Bel, S; Capella, G; Carracedo, A; Ruiz-Ponte, C

    2017-05-01

    A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter. We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis. These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

  6. A Survey on Current Practice of Management of Early Onset Neonatal Sepsis.

    Science.gov (United States)

    Dey, A C; Hossain, M I; Afroze, S; Dey, S K; Mannan, M A; Shahidullah, M

    2016-04-01

    It was a survey type of cross sectional study where the participants were from different teaching/referral hospital across the country and was done to gather information regarding current practice of management of neonatal sepsis among paediatricians and neonatologists and was conducted on the spot during a national conference of Bangladesh Perinatal Society in December 2013. Specialists in neonatology, paediatrics, and some other disciplines working in different institutes across the country were requested to respond. Out of 150 physicians, 92 (61.33%) were neonatologists. Physicians suspected early onset neonatal sepsis (EONS) when there is history suggestive of prolonged rupture of membrane (74.77%), prolonged labour (9.33%), chorioamnionitis (7.33%) and maternal fever (2%). Clinical sepsis is found commonly (53.33%) which is later proved by laboratory evidences such as Hb%, TC, DC PBF (peripheral blood film), C-reactive protein, chest X-ray etc. Injection Ampicillin and Gentamycin are still the first choice of antibiotics (61.3%). Preferred route was intravenous (95.3%). Antibiotics were given for 7-10 days by most of the physicians (48.77%). However there is lack of uniformity among the participants in regard to taking decision about antibiotics, the choice of first line and the subsequent options of antibiotics. So, neonatal sepsis is the most important cause of neonatal mortality in the community. Therefore a standard protocolized approach for diagnosis and management of Early Onset Neonatal Sepsis may prove critical which is currently not in practice uniformly.

  7. [Knowledge of Andalusian pediatricians and parents about early-onset tooth decay].

    Science.gov (United States)

    González, E; Pérez-Hinojosa, S; Alarcón, J A; Peñalver, M A

    2015-01-01

    To determine the level of knowledge of pediatricians and parents from Andalucía (southern Spain) about early-onset tooth decay, and to assess if pediatricians provide information to parents about pediatric oral care and visits to the pediatric dentist. A random sample of 113 pediatricians and 112 parents with children under 3 years of age received an anonymous questionnaire comprising 14 items for pediatricians and 16 items for parents, grouped into five blocks: visits to the dentist, oral hygiene, caries, nutritional habits, and treatment of caries. The chi-squared test was used to assess differences between groups. Pediatricians showed deficiencies in their knowledge about visits to the dentist and treatment of caries, however their level of knowledge on oral hygiene, tooth decay and nutritional habits were adequate. Parents showed a low level of knowledge in all aspects of the study, mainly about the treatment of tooth decay. There were no significant differences between pediatricians and parents in the knowledge about visits to the dentist, however pediatricians had more knowledge than the parents about hygiene, tooth decay, nutritional habits and treatment (Ptooth decay, and provide more information to parents about the oral care and the possibility of visiting a pediatric dentist. Parents have a very low level of knowledge about early-onset tooth decay, and particularly about treatment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  8. Androgen receptor CAG polymorphism and sporadic and early-onset prostate cancer among Mexican men.

    Science.gov (United States)

    Gómez, Rocío; Torres-Sánchez, Luisa; Camacho-Mejorado, Rafael; Burguete-García, Ana I; Vázquez-Salas, Ruth Argelia; Martínez-Nava, Gabriela A; Santana, Carla; Noris, Gino

    2016-09-01

    A short CAG repeat length in the gene encoding for the androgen receptor (AR) has been associated with prostate cancer (PC) risk and aggressiveness. In Latino men, information on this association is scarce. Hence, the aim of this study was to evaluate this association in Mexican males. Using fragment analysis by capillary electrophoresis, we determined the number of CAG repeats-(CAG)n-in AR gene from 158 incident PC cases and 326 age-matched healthy controls (±5 years), residing in Mexico City, Mexico. According to Gleason scale and age at diagnosis, cases were classified as high (⩾7) and low grade (CAG repeat length than controls (18.6±2.2 vs 19.5±2.5; P=0.02). Lower number of CAG repeats (CAG)⩽19 were associated with a greater risk for early-onset PC (odds ratio: 2.31; 95% confidence interval: 1.14-4.69). CAG repeat length could increase the risk for sporadic and early-onset PC. The best cutoff point for identifying at-risk subjects was (CAG)19. However, further studies are necessary to replicate our findings in subjects with a family history of PC and also to evaluate the association between CAG repeats length and disease progression.

  9. Early-onset facioscapulohumeral muscular dystrophy - significance of pelvic extensors in sagittal spinal imbalance.

    Science.gov (United States)

    Lee, Choon Sung; Kang, Suk Jung; Hwang, Chang Ju; Lee, Sung-Woo; Ahn, Young-Joon; Kim, Yung-Tae; Lee, Dong-Ho; Lee, Mi Young

    2009-11-01

    Although facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited myopathy, cases of infantile or early-childhood onset have rarely been reported. The purpose of this study was to describe a case of early-onset FSHD with lumbar hyperlordosis, which shows the significance of the dynamic component of sagittal spinal imbalance. An 11-year-old girl presented with progressive gait disturbance and lumbar hyperlordosis. The motor power of her pelvic extensor muscles was grade 3. Pelvic tilt and hip flexion were markedly increased as determined by gait analysis. The most important factor in the development of hyperlordosis is the weakness of the pelvic extensor muscles, and the results of gait analysis exquisitely explain the pathophysiology. The patient stands with her spine hyperextended to maintain upright posture by a compensatory mechanism of relatively strong back extensor muscles. Corrective surgery for lumbar hyperlordosis was not considered because it could have eliminated the compensatory lumbar hyperextension, thus making the spine of the patient stoop forward through her hip joint during walking by the weakness of her pelvic extensor muscles. This FSHD case is an impressive example of a patient showing the concept that weak pelvic extensor muscles cannot keep the spine upright and balanced.

  10. Very Early-Onset Inflammatory Manifestations of X-Linked Chronic Granulomatous Disease

    Directory of Open Access Journals (Sweden)

    Roxane Labrosse

    2017-09-01

    Full Text Available Chronic granulomatous disease (CGD is a rare primary immune deficiency caused by mutations in genes coding for components of the nicotinamide adenine dinucleotide phosphate oxidase, characterized by severe and recurrent bacterial and fungal infections, together with inflammatory complications. Dysregulation of inflammatory responses are often present in this disease and may lead to granulomatous lesions, most often affecting the gastrointestinal (GI and urinary tracts. Treatment of inflammatory complications usually includes corticosteroids, whereas antimicrobial prophylaxis is used for infection prevention. Curative treatment of both infectious susceptibility and inflammatory disease can be achieved by hematopoietic stem cell transplantation. We report herein three patients with the same mutation of the CYBB gene who presented with very early-onset and severe GI manifestations of X-linked CGD. The most severely affected patient had evidence of antenatal inflammatory involvement of the GI and urinary tracts. Extreme hyperleukocytosis with eosinophilia and high inflammatory markers were observed in all three patients. A Mycobacterium avium lung infection and an unidentified fungal lung infection occurred in two patients both during their first year of life, which is indicative of the severity of the disease. All three patients underwent bone marrow transplantation and recovered fully from their initial symptoms. To our knowledge, these are the first reports of patients with such an early-onset and severe inflammatory manifestations of CGD.

  11. Relationship between renal histology and plasma antithrombin III activity in women with early onset preeclampsia.

    Science.gov (United States)

    Weiner, C P; Bonsib, S M

    1990-04-01

    Renal biopsy was performed in 12 women with the clinical diagnosis of severe, early-onset preeclampsia at the time of cesarean delivery for the express purpose of aiding future counseling on the risk of recurrence. The mean gestation at delivery was 30 +/- 3 weeks. The mean birthweight was 1090 +/- 505 gm. Four women (33%) were multiparous. Antithrombin III activity was determined immediately prior to delivery unrelated to clinical care and as part of other protocols. The biopsy was performed without difficulty in each, although the sample was inadequate in one patient. The clinical diagnosis of preeclampsia was confirmed in nine (82%). However, three of the nine had underlying renal disease, as did the two women without histologic evidence of preeclampsia (42% of the total). Correlations between laboratory parameters with the histopathologic diagnoses were sought. Neither uric acid, creatinine, blood urea nitrogen, platelet count, or 24-hour urinary protein measurements aided the differentiation of the various subgroups. Antithrombin III activity in women with biopsy-supported preeclampsia (77% +/- 12%) was significantly lower than that in women without histologic evidence of preeclampsia (116% +/- 8%). Antithrombin III activity correctly predicted biopsy findings in at least 9 of 11 (82%). These preliminary findings confirm the high frequency of underlying disease in women with early-onset preeclampsia. Although low antithrombin III activity does not differentiate between "pure" preeclampsia and superimposed disease, a normal antithrombin III activity is reassuring and more consistent with a nonpreeclamptic renal complication than with preeclampsia.

  12. Effects of nicotine chewing gum on UPDRS score and P300 in early-onset parkinsonism.

    Science.gov (United States)

    Mitsuoka, Takako; Kaseda, Yumiko; Yamashita, Hiroshi; Kohriyama, Tatsuo; Kawakami, Hideshi; Nakamura, Shigenobu; Yamamura, Yasuhiro

    2002-03-01

    It has been reported that nicotine shows some beneficial effects on Parkinson's disease. The purpose of the present study is to assess the therapeutic effects of nicotine chewing gum in patients with early-onset parkinsonism (EOP). The subjects were 8 patients with early-onset parkinsonism (male/female = 4/4, mean age; 51.3 years). Four out of 8 patients had a history of smoking (smokers). To estimate the effects of nicotine gum, the scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and auditory event-related potentials (ERPs) were studied before and after taking nicotine gum in the EOP patients. In smokers, UPDRS scores improved by more than 10% and the P300 latency of auditory ERPs was shortened by more than 30 msec. In contrast, nicotine had no remarkable effects on UPDRS scores or auditory ERPs in non-smokers. We suggest that nicotine chewing gum may be a possible choice for the treatment of patients with EOP, especially when they are smokers.

  13. [Early identification of impaired renal function in obese children with non-alcoholic fatty liver disease].

    Science.gov (United States)

    Lin, Hu; Fu, Junfen; Chen, Xuefeng; Huang, Ke; Wu, Wei; Liang, Li

    2013-07-01

    To early assess the impaired renal function in the obese children with non-alcoholic fatty liver disease (NAFLD) and to identify the relationship between NAFLD and impairment of renal function. Three hundred and eighty-six obese children were enrolled and divided into NAFLD group and simple obesity group (control) according to the diagnostic criteria. Clinical biochemical parameters and early impaired renal functions were evaluated and compared. Among all patients 234 obese children aged over 10 y were subdivided into 3 groups: NAFLD combined with metabolic syndrome (NAFLD+MS) group, NAFLD group and simple obesity group (control), and the above indexes were compared among 3 groups. The urinary microalbumin levels in NAFLD, NAFLD+MS (>10y) and NAFLD groups (>10y) were significantly higher than those in controls. Additionally, the positive correlations of urinary microalbumin with systolic pressure, triglyceride and 2h-postprandial blood glucose were found. There is early renal dysfunction in children with NAFLD and those accompanied with MS, which may be associated with hypertension and glucose-lipid metabolic disorder. The results indicate that NAFLD is not only an early sign of early impaired renal function but also an early stage of chronic kidney disease (CKD) in obese children.

  14. Hepatocyte nuclear factor 1-alpha mutation in normal glucose-tolerant subjects and early-onset type 2 diabetic patients.

    Science.gov (United States)

    Lim, Dong Mee; Huh, Nam; Park, Keun Yong

    2008-12-01

    The prevalence of diabetes in Korea is reported to be approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are rare in Korea. A diagnostic technique for autosomal dominant MODY is being actively sought. In this regard, we used a DNA chip to investigate the frequency of mutations of the MODY3 gene (hepatocyte nuclear factor-1alpha) in Korean patients with early-onset type 2 diabetes. The genomic DNA of 30 normal individuals [age, 24.9+/-8.6 years] and 25 patients with early-onset type 2 diabetes (age, 27+/-5.9 years) was extracted, and the MODY3 gene was amplified. The amplified DNA was hybridized onto a MODY3 chip, which has oligonucleotides of 15-25 bases, representing wild-type and mutant MODY3 sequences in both forward and reverse orientations, immobilized on its surface. Among the normal subjects, there was no mutation of MODY3. Among those with early-onset type 2 diabetes, there was one case of MODY3 mutation. Our results indicate that MODY3 mutations are not rare in Korean early-onset type 2 diabetes patients in Korea and suggest that MODY3 mutations in patients with early-onset type 2 diabetes need to be further evaluated.

  15. 'Abhorreas pinguedinem': Fat and obesity in early modern medicine (c. 1500-1750).

    Science.gov (United States)

    Stolberg, Michael

    2012-06-01

    Contrary to a widely held belief, the medicalization of obesity is not a recent development. Obesity was extensively discussed in leading early modern medical textbooks, as well as in dozens of seventeenth- and eighteenth-century dissertations. Drawing upon ancient and medieval writings, these works discussed the negative impact of obesity upon health and linked it with premature death. Obesity was particularly associated with apoplexy, paralysis, asthma and putrid fevers, and a range of therapeutic options was proposed. This paper offers a first survey of the medical understanding of the causes, effects and treatment of obesity in the early modern period. It examines the driving forces behind the physicians' interest and traces the apparently rather limited response to their claims among the general public. Comparing early modern accounts of obesity with the views and stereotypes prevailing today, it notes the impact of changing medical, moral and aesthetic considerations and identifies, among other things, a shift in the early modern period from concepts of pathological compression to images of the obese body as lax and boundless. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Neurosecretory protein GL stimulates food intake, de novo lipogenesis, and onset of obesity.

    Science.gov (United States)

    Iwakoshi-Ukena, Eiko; Shikano, Kenshiro; Kondo, Kunihiro; Taniuchi, Shusuke; Furumitsu, Megumi; Ochi, Yuta; Sasaki, Tsutomu; Okamoto, Shiki; Bentley, George E; Kriegsfeld, Lance J; Minokoshi, Yasuhiko; Ukena, Kazuyoshi

    2017-08-11

    Mechanisms underlying the central regulation of food intake and fat accumulation are not fully understood. We found that neurosecretory protein GL (NPGL), a newly-identified neuropeptide, increased food intake and white adipose tissue (WAT) in rats. NPGL-precursor gene overexpression in the hypothalamus caused increases in food intake, WAT, body mass, and circulating insulin when fed a high calorie diet. Intracerebroventricular administration of NPGL induced de novo lipogenesis in WAT, increased insulin, and it selectively induced carbohydrate intake. Neutralizing antibody administration decreased the size of lipid droplets in WAT. Npgl mRNA expression was upregulated by fasting and low insulin levels. Additionally, NPGL-producing cells were responsive to insulin. These results point to NPGL as a novel neuronal regulator that drives food intake and fat deposition through de novo lipogenesis and acts to maintain steady-state fat level in concert with insulin. Dysregulation of NPGL may be a root cause of obesity.

  17. Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity.

    Science.gov (United States)

    Den Hartigh, Laura J; Omer, Mohamed; Goodspeed, Leela; Wang, Shari; Wietecha, Tomasz; O'Brien, Kevin D; Han, Chang Yeop

    2017-03-01

    Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary adipocytes differentiated from mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding. These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions, such as insulin resistance. © 2016 American Heart Association, Inc.

  18. Voxel-based structural magnetic resonance imaging (MRI study of patients with early onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Suzuki Katsuaki

    2008-12-01

    Full Text Available Abstract Background Investigation into the whole brain morphology of early onset schizophrenia (EOS to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity. Methods A total of 18 EOS patients (onset under 16 years and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM software package was employed to explore alterations of the regional grey (GM and white matter (WM volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS. Results EOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region, and negatively correlated with WM in the brain stem (pons and in the bilateral cerebellum (hemisphere region. Conclusion Our findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons, within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas

  19. Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.

    Science.gov (United States)

    Dobbs, Kerry; Domínguez Conde, Cecilia; Zhang, Shen-Ying; Parolini, Silvia; Audry, Magali; Chou, Janet; Haapaniemi, Emma; Keles, Sevgi; Bilic, Ivan; Okada, Satoshi; Massaad, Michel J; Rounioja, Samuli; Alwahadneh, Adel M; Serwas, Nina K; Capuder, Kelly; Çiftçi, Ergin; Felgentreff, Kerstin; Ohsumi, Toshiro K; Pedergnana, Vincent; Boisson, Bertrand; Haskoloğlu, Şule; Ensari, Arzu; Schuster, Michael; Moretta, Alessandro; Itan, Yuval; Patrizi, Ornella; Rozenberg, Flore; Lebon, Pierre; Saarela, Janna; Knip, Mikael; Petrovski, Slavé; Goldstein, David B; Parrott, Roberta E; Savas, Berna; Schambach, Axel; Tabellini, Giovanna; Bock, Christoph; Chatila, Talal A; Comeau, Anne Marie; Geha, Raif S; Abel, Laurent; Buckley, Rebecca H; İkincioğulları, Aydan; Al-Herz, Waleed; Helminen, Merja; Doğu, Figen; Casanova, Jean-Laurent; Boztuğ, Kaan; Notarangelo, Luigi D

    2015-06-18

    Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that are present are quantitatively or functionally deficient. Impaired humoral immunity is also common. Patients have severe infections, autoimmunity, or both. The specific molecular, cellular, and clinical features of many types of combined immunodeficiencies remain unknown. Methods We performed genetic and cellular immunologic studies involving five unrelated children with early-onset invasive bacterial and viral infections, lymphopenia, and defective T-cell, B-cell, and natural killer (NK)-cell responses. Two patients died early in childhood; after allogeneic hematopoietic stem-cell transplantation, the other three had normalization of T-cell function and clinical improvement. Results We identified biallelic mutations in the dedicator of cytokinesis 2 gene (DOCK2) in these five patients. RAC1 activation was impaired in the T cells. Chemokine-induced migration and actin polymerization were defective in the T cells, B cells, and NK cells. NK-cell degranulation was also affected. Interferon-α and interferon-λ production by peripheral-blood mononuclear cells was diminished after viral infection. Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a new mendelian disorder with pleiotropic defects of hematopoietic and nonhematopoietic immunity. Children with clinical features of combined immunodeficiencies, especially with early-onset, invasive infections, may have this condition. (Supported by the National Institutes of Health and others.).

  20. Risk factors for adverse fetal outcomes among women with early- versus late-onset intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Jin, Jin; Pan, Shi-lei; Huang, Li-ping; Yu, Yan-hong; Zhong, Mei; Zhang, Guo-wei

    2015-03-01

    To determine risk factors for adverse fetal outcomes (AFOs) among women with intrahepatic cholestasis of pregnancy (ICP) on the basis of time of onset. In a retrospective analysis, data were obtained for all women with ICP admitted to two centers in Guangzhou, China, between February 1, 1993, and January 31, 2014. Patients were divided into group A (early-onset ICP) and group B (late-onset ICP), and were further divided on the basis of severity. The frequency of AFOs was assessed. Among 371 eligible women, 57 (15.4%) were in group A and 314 (84.6%) in group B. AFOs affected 20 (35.1%) women in group A and 67 (21.3%) in group B (P=0.024), and 12 (54.5%) of 22 women in group A and 21 (29.6%) of 71 in group B with severe ICP (P=0.032). Independent risk factors for AFO in group A were increased levels of serum bile acid (P=0.016) and alkaline phosphatase (P=0.004). Independent risk factors in group B were increased levels of alkaline phosphatase (P<0.001) and gamma-glutamyl transpeptidase (P=0.001). Early-onset ICP is associated with a higher frequency of AFO than is late-onset ICP, especially in severe disease. The risk factors differ between early-onset and late-onset ICP. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Early diet, insulin-like growth factor-1, growth and later obesity

    DEFF Research Database (Denmark)

    Michaelsen, Kim F; Larnkjær, Anni; Mølgaard, Christian

    2013-01-01

    . However, some studies suggest that weight gain during the 6- to 12-month age period, when complementary feeding is introduced, is not associated with later obesity. Insulin-like growth factor-1 (IGF-1) values and body composition both play a role in the complex pattern between early diet and later obesity......, but our present knowledge about how these factors are influenced by diet during infancy is limited. Future studies should include longitudinal data on IGF-1 and body composition during infancy to improve our understanding of how diet in early life can play a role in prevention of later obesity.......There is increasing evidence that factors in early life are important for the risk of developing overweight and obesity later in childhood. Among the postnatal factors, breastfeeding and complementary feeding are especially interesting because the pattern of these two factors can be changed...

  2. Reduced Expression of FOXP3 and Regulatory T-Cell Function in Severe Forms of Early-onset Autoimmune Enteropathy

    NARCIS (Netherlands)

    Moes, Nicolette; Rieux-Laucat, Frederic; Begue, Bernadette; Verdier, Julien; Neven, Benedicte; Patey, Natacha; Torgerson, Troy T.; Picard, Capucine; Stolzenberg, Marie-Claude; Ruemmele, Corinne; Rings, Edmond Hhm; Casanova, Jean-Laurent; Piloquet, Hugues; Biver, Armand; Breton, Anne; Ochs, Hans D.; Hermine, Olivier; Fischer, Alain; Goulet, Olivier; Cerf-Bensussan, Nadine; Ruemmele, Frank M.

    BACKGROUND & AIMS: Little is known about the pathophysiology of early onset forms of autoimmune enteropathy (AIE). AIE has been associated with mutations in FOXP3-a transcription factor that controls regulatory T-cell development and function. We analyzed the molecular basis of neonatal or early

  3. Ultrasonographic assessment of cervical length in pregnancies scheduled for a cesarean delivery: prediction of early spontaneous onset of labor.

    Science.gov (United States)

    Rizzo, Giuseppe; Aiello, Elisa; Pietrolucci, Maria Elena; Arduini, Domenico

    2016-10-01

    To investigate whether the cervical length measured by transvaginal ultrasound at 35 to 36 weeks of gestation is predictive of spontaneous early onset of labor in pregnancies scheduled for elective cesarean section (CS). This was a prospective observational study on 167 women scheduled for elective CS at 39 weeks of gestation. The cervical length was measured ultrasonographycally at 35 to 36 weeks of gestation and the pregnancies characteristics were recorded. The presence or absence of spontaneous onset of labor before the time scheduled for elective CS was related to cervical length and pregnancies characteristics. Of the 167 pregnancies enrolled, 25 (14.97%) underwent early spontaneous onset of labor before the time scheduled for the elective CS. The cervical length was significantly shorter in these women when compared with those delivering with an elective CS (21 vs. 30 mm z=5.49 Ponset of labor in univariate analysis (P=0.01). Multivariate logistic regression analysis showed that cervical length (adjusted odds ratio 1.40; 95% confidence interval (CI) 1.22-1.61; P≤0.0001) was the only predictor for the early onset of labor. The area under the receiver-operating characteristics curve for the prediction of early onset of labor was 0.844 (95% CI 0.738-0.950) for cervical length as test variable. Kaplan-Meier analysis demonstrated that a cervical length onset of labor in pregnancies scheduled for CS and may be useful in individualizing the gestational age for elective CS.

  4. Alcohol use in motion pictures and its relation with early-onset teen drinking.

    Science.gov (United States)

    Sargent, James D; Wills, Thomas A; Stoolmiller, Mike; Gibson, Jennifer; Gibbons, Frederick X

    2006-01-01

    Little is known about the impact of viewing depictions of alcohol in entertainment media on adolescent drinking behavior. Our aims were to assess drinking in a sample of popular contemporary movies and to examine the association of movie alcohol exposure with early-onset drinking in an adolescent sample. We conducted a school-based cross-sectional survey (N=4655) with longitudinal follow-up of never-drinkers (N=2406) involving adolescents ages 10-14 years and recruited from 15 New Hampshire and Vermont schools. Screen depictions of alcohol use were timed for each of 601 popular contemporary movies. Each adolescent was asked if he/she had seen a unique list of 50 movie titles, randomly selected from the larger pool. Movie alcohol use was summed for movies the adolescent had seen, adjusted to reflect exposure to the larger pool and modeled as a continuous variable. Ninety-two percent of the movies in the sample depicted drinking; median screen time for movie alcohol use was 2.5 minutes (interquartile range [IQR]: 0.9-5.0 minutes). Median exposure to movie alcohol use from the 601 movies was 8.6 hours (IQR: 4.6-13.5 hours). Overall 23.1% of the cross-sectional sample had tried alcohol, and 14.8% of initial nondrinkers had tried alcohol at the follow-up assessment. We found statistical evidence to support a curvilinear association between higher exposure to movie alcohol use and increased risk of prevalent and incident alcohol use, with a statistically significant linear and quadratic effect, and suggesting a higher dose-effect relationship at lower movie alcohol exposure levels compared to higher levels. The linear and the quadratic associations remained strong and significant in cross-sectional and prospective models after controlling for sociodemographics (grade in school, school, gender, parent education), personality characteristics of the adolescent (sensation seeking, rebelliousness, self-esteem), school performance, parenting style, and smoking experimentation

  5. A systematic review of the long-term outcome of early onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Clemmensen Lars

    2012-09-01

    Full Text Available Abstract Background The current review analyzes the long-term outcome and prognosis of early onset schizophrenia based on previously published studies in 1980. Methods A systematic search of articles published in the English-language literature after 1980 identified a total of 21 studies, which included 716 patients who were either suffering from early onset schizophrenia (EOS or both EOS and other psychotic disorders (MIX. The authors of the current review scored the outcome as either “good,” “moderate,” or “poor.” The mean age of onset in these studies was Results In general, the outcome in studies with EOS is worse than the outcome in MIX studies. Only 15.4% of the patients in EOS studies versus 19.6% of the patients in MIX studies experienced a “good” outcome. In contrast, 24.5% of the patients in EOS studies versus 33.6% in MIX studies experienced a “moderate” outcome, and 60.1% in EOS studies versus 46.8% in MIX studies experienced a “poor” outcome. The authors identified various significant effects on outcome. In EOS, the findings were significantly affected by sample attrition, indicating that in studies with a high dropout rate, fewer patients experienced a “moderate” outcome, and more patients experienced a “poor” outcome; however, the effect sizes were small. Furthermore, the effects were also small and more favourable for specific functioning measures, as opposed to more global measures, small to moderate in terms of worse outcomes for follow-up periods >10 years, small to moderate for more unfavourable outcomes in males, and small to large for worse outcomes in studies including patients diagnosed before 1970. Conclusions In contrast to the adult manifestation, the early manifestation of schizophrenia in childhood and adolescence still carries a particularly poor prognosis. According to these aggregated data analyses, longer follow-up periods, male sex, and patients having been diagnosed before 1970

  6. Heart rate and blood pressure control in obesity - how to detect early dysregulation?

    Science.gov (United States)

    Javorka, Michal; Turianikova, Zuzana; Tonhajzerova, Ingrid; Lazarova, Zuzana; Czippelova, Barbora; Javorka, Kamil

    2016-09-01

    Obesity is accompanied by many severe complications including various cardiovascular disorders. An impairment of cardiovascular control by autonomic nervous system could be one of the possible links between obesity and cardiovascular complications development. The aim of this study was to compare spontaneous heart rate and systolic blood pressure oscillations reflecting cardiovascular autonomic control of young obese subjects with normal control subjects by linear and nonlinear methods and to find sensitive markers of early autonomic dysregulation. Continuous recordings of beat-to-beat systolic blood pressure and RR intervals from ECG were obtained from 40 obese subjects (25 female, age 14·2 [13·1-16·1] (median [interquartile range]) years) and gender and age matched non-obese control subjects. In addition to linear measures (time and frequency domain), we performed recurrence quantification analysis (RQA) and multiscale entropy analysis for both signals. While no significant differences in heart rate and systolic blood pressure dynamics were detected by linear measures and MSE, analysis of recurrence plots from RR intervals time series showed significant differences - indices trapping time and maximal length of vertical from RQA were significantly higher in obese compared to control group. We conclude that heart rate and blood pressure control by autonomic nervous system in young obese subjects is relatively well preserved. However, novel RQA-related measures are able to detect early subtle abnormalities in cardiac autonomic control in obese subjects indicating decreased signal complexity. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  7. Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease

    Science.gov (United States)

    Xiao, Yuan; Wang, Xin-Qiong; Yu, Yi; Guo, Yan; Xu, Xu; Gong, Ling; Zhou, Tong; Li, Xiao-Qin; Xu, Chun-Di

    2016-01-01

    AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease (VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients. METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing (NGS) based on an Illumina-Miseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10RA, IL-10RB, NOD2, FUT2, IL23R, GPR35, GPR65, TNFSF15, and ADAM30. The Sanger sequencing was used to verify the variations detected in NGS. RESULTS: Out of the 13 pediatric patients, ten were diagnosed with Crohn’s disease, and three diagnosed with ulcerative colitis. Mutations in IL-10RA and IL-10RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10RA and FUT2 polymorphisms, and two patients had IL-10RB and FUT2 polymorphisms. Gene variations were not found in the rest four patients. Children with mutations had lower percentile body weight (1.0% vs 27.5%, P = 0.002) and hemoglobin (87.4 g/L vs 108.5 g/L, P = 0.040) when compared with children without mutations. Although the age of onset was earlier, height was shorter, and the response to treatment was poorer in the mutation group, there was no significant difference in these factors between groups. CONCLUSION: IL-10RA and IL-10RB mutations are common in Chinese children with VEO-IBD. Patients with mutations have an earlier disease onset, lower body weight and hemoglobin, and poorer prognosis. PMID:27350736

  8. Adaptive behavior and later school achievement in children with early-onset epilepsy.

    Science.gov (United States)

    Berg, Anne T; Caplan, Rochelle; Baca, Christine B; Vickrey, Barbara G

    2013-07-01

    To determine whether early measures of adaptive behavior are predictive of later school difficulties and achievement in otherwise neurotypical (unimpaired) children with onset of epilepsy during the preschool years. In a prospective cohort study, parents completed the Vineland Adaptive Behavior Scales (VABS) for children who were aged 5 years or less at epilepsy diagnosis. Eight to 9 years later, the children were assessed using the Wechsler Intelligence Scales for Children (WISC), the Wide Range Achievement Test (WRAT), and the Child Behavior Checklist (CBCL). Associations of VABS scores with later WRAT and CBCL scores were tested. A total of 108 neurotypical children (64 males, 44 females; mean age at testing 11 y 11 mo, SD 2 y) were studied. After adjustment for IQ and other factors, there was an increase of 0.15 points (95% confidence interval [CI] 0.03-0.27 points; p=0.03) and 0.14 points (95% CI 0.0-0.28 points; p=0.05) in WRAT reading and spelling scores for each 1-point increment in the VABS communication score. Corresponding numbers for the VABS socialization score were 0.20 (95% CI 0.08-0.32; p=0.005) and 0.17 (95% CI 0.05-0.29; p=0.005). In neurotypical preschool children with epilepsy, early social and communication scores predict later school performance. These findings raise questions about opportunities for early identification and intervention for children at greatest risk. © 2013 Mac Keith Press.

  9. Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis.

    Science.gov (United States)

    Khaertynov, Kh S; Boichuk, S V; Khaiboullina, S F; Anokhin, V A; Andreeva, A A; Lombardi, V C; Satrutdinov, M A; Agafonova, E A; Rizvanov, A A

    2017-01-01

    Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS), as well as those with early onset of sepsis (EOS), had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted.

  10. Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    Kh. S. Khaertynov

    2017-01-01

    Full Text Available Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS, as well as those with early onset of sepsis (EOS, had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted.

  11. Frequency of LRRK2 mutations in early- and late-onset Parkinson disease.

    Science.gov (United States)

    Clark, L N; Wang, Y; Karlins, E; Saito, L; Mejia-Santana, H; Harris, J; Louis, E D; Cote, L J; Andrews, H; Fahn, S; Waters, C; Ford, B; Frucht, S; Ottman, R; Marder, K

    2006-11-28

    To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD). We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the 50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.

  12. Case-control study of severe pre-eclampsia of early onset.

    Science.gov (United States)

    Moore, M P; Redman, C W

    1983-08-27

    Twenty four women with severe pre-eclampsia diagnosed before 34 weeks' gestation were compared with 48 randomly selected controls matched for age and parity. Subjects were studied in the puerperium using a questionnaire, clinical examination, and review of case records. A history of infertility, headaches (particularly migraine), pre-eclampsia in a previous pregnancy, or a raised serum alpha-fetoprotein concentration at the time of screening for neural tube defect in the index pregnancy were all identified as significant risk factors in the pre-eclamptic women. Maternal age, a history of chronic hypertension or renal disease, or excessive maternal weight were not significantly associated with pre-eclampsia. Almost all the infants of pre-eclamptic women showed retarded growth: 18 were below the 10th centile and only one weighed more than the 25th centile. Four babies died. These observations indicate that pre-eclampsia of early onset may differ from the late onset disease not only in its very high perinatal morbidity and mortality but in its distinctive maternal risk factors.

  13. Home visitation programs: An untapped opportunity for the delivery of early childhood obesity prevention

    Science.gov (United States)

    Salvy, Sarah-Jeanne; de la Haye, Kayla; Galama, Titus; Goran, Michael I.

    2016-01-01

    Background Extant obesity efforts have had limited impact among low-income underserved children, in part because of limitations inherent to existing programs: 1) short duration and low intensity; 2) late timing of implementation, when children are already overweight or obese; 3) intervention delivery limiting their accessibility and sustainability; and 4) failure to address barriers such as a lack of culturally competent services, poverty and housing instability, which interfere with healthy lifestyle changes. Objective This concept paper proposes an innovative model of obesity prevention implemented in infancy and sustained throughout early childhood to address the limitations of current obesity prevention efforts. Specifically, we propose to integrate sustained, weekly, in-home obesity prevention as part of the services already delivered by ongoing Home Visitation Programs, which currently do not target obesity prevention. Conclusion The home visiting structure represents an ideal model for impactful obesity prevention as home visitation programs: (1) already provide comprehensive services to diverse low-income infants and families who are most at risk for obesity and poor health due to socio-economic and structural conditions; (2) services are initiated in infancy and sustained throughout critical developmental periods for the formation of healthy/unhealthy behaviors; and (3) have been in place for more than 40 years, with a widespread presence across the United States and nationwide, which is critical for the scalability and sustainability of obesity prevention. PMID:27911984

  14. A Community-Based Intervention to Prevent Obesity Beginning at Birth among American Indian Children: Study Design and Rationale for the PTOTS Study

    Science.gov (United States)

    Karanja, Njeri; Aickin, Mikel; Lutz, Tam; Mist, Scott; Jobe, Jared B.; Maupome, Gerardo; Ritenbaugh, Cheryl

    2012-01-01

    Eating and physical activity behaviors associated with adult obesity have early antecedents, yet few studies have focused on obesity prevention interventions targeting very young children. Efforts to prevent obesity beginning at birth seem particularly important in populations at risk for early-onset obesity. National estimates indicate that…

  15. A Community-Based Intervention to Prevent Obesity Beginning at Birth among American Indian Children: Study Design and Rationale for the PTOTS Study

    Science.gov (United States)

    Karanja, Njeri; Aickin, Mikel; Lutz, Tam; Mist, Scott; Jobe, Jared B.; Maupome, Gerardo; Ritenbaugh, Cheryl

    2012-01-01

    Eating and physical activity behaviors associated with adult obesity have early antecedents, yet few studies have focused on obesity prevention interventions targeting very young children. Efforts to prevent obesity beginning at birth seem particularly important in populations at risk for early-onset obesity. National estimates indicate that…

  16. Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Cristino de Albuquerque

    2015-01-01

    Full Text Available The spinocerebellar ataxias (SCA are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7 is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

  17. Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias.

    Science.gov (United States)

    Albuquerque, Marcus Vinicius Cristino de; Pedroso, José Luiz; Braga Neto, Pedro; Barsottini, Orlando Graziani Povoas

    2015-01-01

    The spinocerebellar ataxias (SCA) are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7) is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

  18. Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Viaña, John Noel M; Bittlinger, Merlin; Gilbert, Frederic

    2017-01-01

    Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimer's disease, with several recruiting participants early-onset Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

  19. [Identifying different susceptibility loci associated with early onset diabetes and cardiovascular disease in Mexican families].

    Science.gov (United States)

    Canizales-Quinteros, Samuel; Huertas-Vázquez, Adriana; Riba-Ramírez, Laura; Monroy-Guzmán, Adriana; Domínguez-López, Aarón; Romero-Hidalgo, Sandra; Aguilar-Salinas, Carlos; Rodríguez-Torres, Maribel; Ramírez-Jiménez, Salvador; Tusié-Luna, María Teresa

    2005-01-01

    Coronary artery disease and diabetes mellitus are among the primary mortality and morbidity causes in Mexico. Genetic factors play a fundamental role in the development of these entities. In the past few years due to the recognition and study of families with monogenic forms of diabetes and dislipidemias associated with development of atherosclerosis, several genes and loci have been associated with these conditions through genetic linkage studies. These studies have provided evidence of the genetic heterogeneity that exists and the type of genes involved in different ethnic groups. The study of Mexican families with early-onset diabetes and combined familial hyperlipidemia showed the participation of different genetic loci associated with these conditions in the Mexican population. These findings show the value of gene mapping strategies in the identification of the genetic component in these entities in our population.

  20. Time perspective and early-onset substance use: a model based on stress-coping theory.

    Science.gov (United States)

    Wills, T A; Sandy, J M; Yaeger, A M

    2001-06-01

    This research tested the relation of time perspective to early-onset substance use (tobacco, alcohol, and marijuana) with a sample of 454 elementary school students with a mean age of 11.8 years. An adaptation of the Zimbardo Time Perspective Inventory (P. G. Zimbardo & J. N. Boyd, 1999) was administered with measures derived from stress-coping theory. Independent effects showed future orientation inversely related to substance use and present orientation positively related to substance use. Structural modeling analysis indicated that the relation of time perspective measures to substance use was indirect, mediated through behavioral coping and anger coping. Proximal factors for substance use were negative affect, peer substance use, and resistance efficacy. Results are discussed with respect to epigenetic models and the role of executive functions in self-control ability.

  1. Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia.

    Science.gov (United States)

    Sokolenko, Anna P; Rozanov, Maxim E; Mitiushkina, Natalia V; Sherina, Natalia Yu; Iyevleva, Aglaya G; Chekmariova, Elena V; Buslov, Konstantin G; Shilov, Evgeny S; Togo, Alexandr V; Bit-Sava, Elena M; Voskresenskiy, Dmitry A; Chagunava, Oleg L; Devilee, Peter; Cornelisse, Cees; Semiglazov, Vladimir F; Imyanitov, Evgeny N

    2007-01-01

    Previous studies indicate that founder mutations may play a noticeable role in breast cancer (BC) predisposition in Russia. Here we performed a systematic analysis of eight recurrent mutations in 302 BC cases (St.-Petersburg, Russia), which were selected due to the presence of clinical indicators of hereditary disease (bilaterality and/or early onset (A in 2 (0.7%), and BRCA1 185delAG, BRCA2 6174delT and NBS1 657del5 in 1 (0.3%) patient each. No cases with BRCA1 300T>G (C61G) mutation was identified. The obtained data suggest that a significant fraction of hereditary BC cases in Russia can be diagnosed using only a limited number of simple PCR tests.

  2. Role of Early Onset Neutropenia in Development of Candidemia in Premature Infants.

    Science.gov (United States)

    Ramy, Nermin; Hashim, Mohamed; Abou Hussein, Heba; Sawires, Happy; Gaafar, Maha; El Maghraby, Ayat

    2017-04-24

    The aim of the study was to assess the effect of early-onset neutropenia (EON) on the development of candidemia in premature infants and evaluate other risk factors. This prospective study was carried out in a neonatal intensive care unit of Cairo University Hospital. Fifty neutropenic premature infants were matched to 50 non-neutropenics. Subjects were then regrouped into candidemics and non-candidemics to study other risk factors such as central venous catheters, mechanical ventilation, parenteral nutrition, drugs as corticosteroids and others. Candidemia was assessed by Bactec and then seminested polymerase chain reaction for culture negatives. Candidemia developed in 28 neutropenic preterms and in 8 non-neutropenics (odds ratio  = 6.68, 95% confidence interval = 2.61-17.1, p  candidemia in multivariate regression analysis included EON, mechanical ventilation and steroid therapy. EON is an independent risk factor for candidemia in premature infants.

  3. Severe agitation in severe early-onset Alzheimer’s disease resolves with ECT

    Directory of Open Access Journals (Sweden)

    Aksay SS

    2014-11-01

    Full Text Available Suna Su Aksay, Lucrezia Hausner, Lutz Frölich, Alexander Sartorius Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Abstract: Dementia-related behavioral disturbances are mostly treated with antipsychotics; however, the observed beneficial effects are modest and the risk of serious adverse effects high. We report the case of a 57-year-old woman with severe early-onset Alzheimer’s disease and severe agitation, whom we treated with electroconvulsive therapy (ECT. A significant clinical improvement was achieved over eight ECT sessions, which were tolerated well without cognitive worsening, and lasted approximately 3 months. Our case demonstrates the safe and effective use of ECT in pharmacotherapy-resistant severe agitation in Alzheimer’s disease. The risk–benefit profile of ECT for dementia-related agitation should be further investigated in clinical trials. Keywords: dementia, electroconvulsive therapy, cognition, emotional distress, disinhibition.

  4. A Case Report on Juvenile Neuromyelitis Optica: Early Onset, Long Remission Period, and Atypical Treatment Response.

    Science.gov (United States)

    Elpers, Christiane; Gross, Catharina C; Fiedler, Barbara; Meuth, Sven G; Kurlemann, Gerhard

    2015-08-01

    Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the central nervous system and preferentially targets the optic nerves and spinal cord. NMO is rare in children and clinical course of the disease is highly variable as described in studies. Here, we present a case report of a young girl presenting with a rare course of pediatric NMO with an early disease onset at the age of 12 years, a relapse free interval of 4 years, evidence of NMO immunoglobulin G (IgG) and an unusual response against immunosuppressive therapy. The aim of this report is to highlight the potentially long remission period between relapses complicating proper diagnosis despite well defined diagnostic criteria. In addition, we want to encourage the use of rituximab in pediatric NMO, although larger cohorts are warranted to establish B cell depleting therapies in juvenile NMO.

  5. Ultrasound control of magnet growing rod distraction in early onset scoliosis.

    Science.gov (United States)

    Pérez Cervera, T; Lirola Criado, J F; Farrington Rueda, D M

    2016-01-01

    The growing rod technique is currently one of the most common procedures used in the management of early onset scoliosis. However, in order to preserve spine growth and control the deformity it requires frequent surgeries to distract the rods. Magnetically driven growing rods have recently been introduced with same treatment goal, but without the inconvenience of repeated surgical distractions. One of the limitations of this technical advance is an increase in radiation exposure due to the increase in distraction frequency compared to conventional growing rods. An improvement of the original technique is presented, proposing a solution to the inconvenience of multiple radiation exposure using ultrasound technology to control the distraction process of magnetically driven growing rods.

  6. Combined targeted treatment in early onset epilepsy associated with tuberous sclerosis

    Directory of Open Access Journals (Sweden)

    Romina Moavero

    2016-01-01

    Full Text Available Tuberous sclerosis is associated with epilepsy in up to 85% of cases, and in 2/3, the onset is within the first year of life. An early antiepileptic treatment is crucial to minimize the consequences of epilepsy on cognition and behavior. We present a case report of a child with tuberous sclerosis who presented with infantile spasms at the age of 6 months, immediately treated with vigabatrin. Because of the presence of a subependymal giant cell astrocytoma, he also received everolimus since 18 months of age. We might wonder if an earlier treatment could have produced a better outcome; in fact, despite a targeted combined treatment, he continues to suffer from sporadic focal motor seizures, and at the age of 40 months, he presents severe developmental delay with autism-like behavior.

  7. Apathy and depressive mood in nursing home patients with early-onset dementia.

    Science.gov (United States)

    Leontjevas, Ruslan; van Hooren, Susan; Waterink, Wim; Mulders, Ans

    2009-01-01

    The study explored whether apathy and depressive mood symptoms (DMS) are related to cognitive and functional features of dementia in 63 nursing home (NH) residents with early-onset dementia (EOD). All EOD residents from one NH (n = 41) and a random sample from another NH were assessed for depressive symptoms (Montgomery Asberg Depression Rating Scale [MADRS]), apathy (Neuropsychiatric Inventory [NPI]), global cognitive functions (Mini-Mental State Examination [MMSE]), activities of daily living (ADL, Minimum Data Set-Resident Assessment Instrument [MDS-RAI]), and overall dementia severity (Global Deterioration Scale [GDS]). DMS were not associated with apathy and dementia severity. Regression analyses adjusted for age, gender, the type of dementia, and DMS revealed that dementia severity measures accounted, respectively, for 14% (ADL), 13% (GDS), and 9% (MMSE) of the variance in apathy. In line with previous research in older patients, the higher apathy scores were associated with more cognitive and functional problems in EOD.

  8. Management of early onset neonatal sepsis differs in the north and south of Scandinavia

    DEFF Research Database (Denmark)

    Drageset, Martin; Fjalstad, Jon Widding; Mortensen, Sven

    2017-01-01

    AIM: This study compared the management and outcomes of early-onset neonatal sepsis (EONS) in two tertiary neonatal units in Denmark and Norway. METHODS: We retrospectively studied all infants diagnosed with EONS between April 2010 and March 2013 and managed at Odense University Hospital, Denmark...... was the most frequently detected pathogen in 11 cases (31%), followed by Group B streptococci in nine (26%) and Escherichia coli in six (17%). In 85% of the 238 cases the empiric therapy comprised gentamicin and a beta-lactam, namely ampicillin in Denmark and benzylpenicillin in Norway. Patients with positive...... blood cultures had higher C-reactive protein levels than patients with negative blood cultures and higher sepsis-attributable mortality. Lumbar punctures were performed more frequently in Denmark. CONCLUSION: There were marginal differences in the management of EONS between units in Denmark and Norway...

  9. Aberrant high-frequency desynchronization of cerebellar cortices in early-onset psychosis.

    Science.gov (United States)

    Wilson, Tony W; Slason, Erin; Hernandez, Olivia O; Asherin, Ryan; Reite, Martin L; Teale, Peter D; Rojas, Donald C

    2009-10-30

    Sensorimotor integration deficits are routinely observed in both schizophreniform and mood-disordered psychoses. Neurobiological theories of schizophrenia and related psychoses have proposed that aberrations in large-scale cortico-thalamic-cerebellar-thalamic-cortical loops may underlie integration abnormalities, and that such dysfunctional connectivity may be central to the pathophysiology. In this study, we utilized a basic mechanoreception task to probe cortical-cerebellar circuitry in early-onset psychosis. Ten adolescents with psychosis and 10 controls completed unilateral tactile stimulation of the right and left index finger, as whole-head magnetoencephalography (MEG) data were acquired. MEG data were imaged in the frequency domain, using spatial filtering, and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise analyses of group and task effects using statistical parametric mapping. Our results indicated bilateral ERD activation of cerebellar regions and postcentral gyri in both groups during stimulation of either hand. Interestingly, during left finger stimulations, adolescents with psychosis exhibited greater alpha and gamma ERD activity in right cerebellar cortices relative to controls. Subjects with psychosis also showed greater ERD in bilateral cerebellum and the right postcentral gyrus during right finger stimulation, and these differences were statistically stronger for higher frequency bins. Lastly, controls exhibited greater alpha ERS of the right postcentral gyrus during right finger stimulation. These findings provide new data on the neurodevelopmental trajectory of basic mechanoreception in adolescents, and also indicate aberrant cerebellar functioning in early-onset psychoses, especially in the right cerebellum, which may be the crucial dysfunctional node in cortico-thalamic-cerebellar-thalamic-cortical circuits.

  10. Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation

    Directory of Open Access Journals (Sweden)

    Schneider Peter

    2010-07-01

    Full Text Available Abstract Background and aims There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN. Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones. Methods 3-9 years (mean 5.2 ± 1.7 after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC and bone mineral density (BMD as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA. In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I. Results The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m2, resumption of menses. Clinical improvement was correlated with BMC and BMD accrual (χ2 = 5.62/χ2 = 6.65, p = 0.06 / p = 0.036. The duration of amenorrhea had a negative correlation with BMD (r = -.362; p th percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters. Conclusions Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN.

  11. Epileptic spasms and early-onset photosensitive epilepsy in Patau syndrome: An EEG study.

    Science.gov (United States)

    Spagnoli, Carlotta; Kugathasan, Umaiyal; Brittain, Helen; Boyd, Stewart G

    2015-08-01

    Patau syndrome, trisomy 13, is the third commonest autosomal trisomy. It is associated with a 25-50% prevalence of epilepsy, but detailed electroclinical descriptions are rare. The occurrence of early-onset photosensitivity has recently been reported in single patients. We collected electroclinical data on 8 infants (age range from 2 months to 3 years and 9 months, median: 17 months) with Patau syndrome referred for an EEG in our Clinical Neurophysiology Department between 1991 and 2011. All EEGs, case-notes, cytogenetic diagnosis and neuroimaging when available were reviewed; data on the occurrence of seizures, epileptiform discharges, photoparoxysmal response and their characteristics in terms of positive frequencies, latencies, grade and duration were noted and analysed. Two patients had been previously diagnosed with epilepsy (one with tonic spasms and one with multiple seizure types). We found 3 patients with photosensitive myoclonic epilepsy (37.5%), and one with non-photosensitive myoclonic epilepsy. We also recorded non-epileptic myoclonic jerks in one patient known to suffer from epileptic spasms. Among photosensitive patients we found self-limited, Waltz's grade 2-4, spike-wave/polyspike-wave discharges in low, medium and high frequency ranges in two patients and in the high frequency range in the third patient, with latencies and duration from less than 1s to a maximum of 9s. In our cohort of Patau syndrome patients, we found a high prevalence of spasms and photic-induced myoclonic jerks. Photosensitivity shows an unusual early age of onset. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. Early-onset neonatal sepsis in Dhaka, Bangladesh: risk associated with maternal bacterial colonisation and chorioamnionitis.

    Science.gov (United States)

    Chan, Grace J; Baqui, Abdullah H; Modak, Joyanta K; Murillo-Chaves, Adriana; Mahmud, Abdullah A; Boyd, Theonia K; Black, Robert E; Saha, Samir K

    2013-09-01

    To estimate the risk of early-onset neonatal sepsis among newborns of mothers with chorioamnionitis and/or bacterial colonisation in Dhaka. We conducted a cohort study at a maternity centre following 600 mother-newborn pairs. Women with a positive bacterial vaginal culture or positive Group B streptococcus (GBS) rectal culture during labour were classified as colonised. Women with placental histopathology demonstrating signs of maternal or foetal inflammation were classified as having chorioamnionitis. Newborns were followed over the first 7 days of life. The primary outcome measure was physician or community health worker diagnosis of neonatal sepsis following modified World Health Organization Integrated Management of Childhood Illnesses criteria. Survival analysis was conducted with non-parametric, parametric and semiparametric models. Of the 600 mother-newborn pairs, 12.8% of newborns were diagnosed with early-onset sepsis. Five hundred and forty-three women had both colonisation and chorioamnionitis data, 55.4% of mothers were non-exposed, 31.7% were only colonised and 12.9% had chorioamnionitis regardless of colonisation status. After adjusting for birthweight, sex, maternal characteristics and wealth, newborns of only colonised mothers developed sepsis 63% faster and had a 71% higher risk of developing sepsis than their non-exposed counterparts (RT = 0.37, 95% CI 0.14-1.03; RH = 1.71, 95% CI 1.00-2.94). Newborns of mothers with chorioamnionitis developed sepsis 74% faster and had a 111% higher risk of developing sepsis (RT = 0.26, 95% CI 0.07-0.94; RH = 2.11, 95% CI 1.06-4.21). Newborns born to mothers with colonisation or chorioamnionitis developed sepsis faster and were at higher risk of developing sepsis in Dhaka. © 2013 John Wiley & Sons Ltd.

  13. Typical and atypical appearance of early-onset Alzheimer's disease: A clinical, neuroimaging and neuropathological study.

    Science.gov (United States)

    Kawakatsu, Shinobu; Kobayashi, Ryota; Hayashi, Hiroshi

    2017-04-01

    The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia. We reported MRI, single-photon emission CT and neuropathological findings in six representative cases. We also described a "left temporal variant" of AD presenting with transcortical cortical sensory aphasia, which has not been reported previously and is another subtype of the posterior variant of AD. We found a significant correlation between regional cerebral blood flow and counts of NFTs in the cerebral cortices. An atypical presentation with focal neuropsychological symptoms roughly correlated with the density of NFTs in the cerebral cortex and more directly related to spongiform changes in the superficial layers of these areas. In contrast, the distribution of amyloid depositions was diffuse and did not necessarily correlate with focal neuropsychological symptoms. Braak staging or ABC score is not necessarily appropriate to evaluate atypical AD, and instead, spongiform changes in addition to tau pathology in the association cortices better explain the diversity of atypical AD. Interestingly, another patient with a posterior variant of AD had a novel type of atypical plaque, which we referred to as "lucent plaque". They were recognizable with HE staining in the circumference and dystrophic neurites were abundant with Gallyas-Braak staining. These plaques demonstrated intense immunoreactivity to both tau AT-8 and amyloid β (Aβ), suggesting a peculiar coexistence pattern of amyloid and tau in these plaques. Clinicopathological studies

  14. Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications.

    Science.gov (United States)

    Monroy-Jaramillo, Nancy; Guerrero-Camacho, Jorge Luis; Rodríguez-Violante, Mayela; Boll-Woehrlen, Marie-Catherine; Yescas-Gómez, Petra; Alonso-Vilatela, María Elisa; López-López, Marisol

    2014-04-01

    Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed.

  15. Epidemiology of early-onset dementia: a review of the literature

    Science.gov (United States)

    Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

    2013-01-01

    Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

  16. Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease.

    Science.gov (United States)

    Silverman, Edwin K; Palmer, Lyle J; Mosley, Jonathan D; Barth, Matthew; Senter, Jody M; Brown, Alison; Drazen, Jeffrey M; Kwiatkowski, David J; Chapman, Harold A; Campbell, Edward J; Province, Michael A; Rao, D C; Reilly, John J; Ginns, Leo C; Speizer, Frank E; Weiss, Scott T

    2002-05-01

    Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction; airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC). To identify genetic determinants of quantitative spirometric phenotypes, an autosomal 10-cM genomewide scan of short tandem repeat (STR) polymorphic markers was performed in 72 pedigrees (585 individuals) ascertained through probands with severe early-onset COPD. Multipoint variance-component linkage analysis (using SOLAR) was performed for quantitative phenotypes, including FEV(1), FVC, and FEV(1)/FVC. In the initial genomewide scan, significant evidence for linkage to FEV(1)/FVC was demonstrated on chromosome 2q (LOD score 4.12 at 222 cM). Suggestive evidence was found for linkage to FEV(1)/FVC on chromosomes 1 (LOD score 1.92 at 120 cM) and 17 (LOD score 2.03 at 67 cM) and to FVC on chromosome 1 (LOD score 2.05 at 13 cM). The highest LOD score for FEV(1) in the initial genomewide scan was 1.53, on chromosome 12, at 36 cM. After inclusion of 12 additional STR markers on chromosome 12p, which had been previously genotyped in this population, suggestive evidence for linkage of FEV(1) (LOD score 2.43 at 37 cM) to this region was demonstrated. These observations provide both significant evidence for an early-onset COPD-susceptibility locus on chromosome 2 and suggestive evidence for linkage of spirometry-related phenotypes to several other genomic regions. The significant linkage of FEV(1)/FVC to chromosome 2q could reflect one or more genes influencing the development of airflow obstruction or dysanapsis.

  17. Managing the Risk for Early Onset Osteoporosis in Long-Duration Astronauts Due to Spaceflight

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

    Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition

  18. Comparison of Passive Microwave-Derived Early Melt Onset Records on Arctic Sea Ice

    Science.gov (United States)

    Bliss, Angela C.; Miller, Jeffrey A.; Meier, Walter N.

    2017-01-01

    Two long records of melt onset (MO) on Arctic sea ice from passive microwave brightness temperatures (Tbs) obtained by a series of satellite-borne instruments are compared. The Passive Microwave (PMW) method and Advanced Horizontal Range Algorithm (AHRA) detect the increase in emissivity that occurs when liquid water develops around snow grains at the onset of early melting on sea ice. The timing of MO on Arctic sea ice influences the amount of solar radiation absorbed by the ice-ocean system throughout the melt season by reducing surface albedos in the early spring. This work presents a thorough comparison of these two methods for the time series of MO dates from 1979through 2012. The methods are first compared using the published data as a baseline comparison of the publically available data products. A second comparison is performed on adjusted MO dates we produced to remove known differences in inter-sensor calibration of Tbs and masking techniques used to develop the original MO date products. These adjustments result in a more consistent set of input Tbs for the algorithms. Tests of significance indicate that the trends in the time series of annual mean MO dates for the PMW and AHRA are statistically different for the majority of the Arctic Ocean including the Laptev, E. Siberian, Chukchi, Beaufort, and central Arctic regions with mean differences as large as 38.3 days in the Barents Sea. Trend agreement improves for our more consistent MO dates for nearly all regions. Mean differences remain large, primarily due to differing sensitivity of in-algorithm thresholds and larger uncertainties in thin-ice regions.

  19. Early Determinants of Obesity: Genetic, Epigenetic, and In Utero Influences

    Directory of Open Access Journals (Sweden)

    Kyung E. Rhee

    2012-01-01

    Full Text Available There is an emerging body of work indicating that genes, epigenetics, and the in utero environment can impact whether or not a child is obese. While certain genes have been identified that increase one’s risk for becoming obese, other factors such as excess gestational weight gain, gestational diabetes mellitus, and smoking can also influence this risk. Understanding these influences can help to inform which behaviors and exposures should be targeted if we are to decrease the prevalence of obesity. By helping parents and young children change certain behaviors and exposures during critical time periods, we may be able to alter or modify one’s genetic predisposition. However, further research is needed to determine which efforts are effective at decreasing the incidence of obesity and to develop new methods of prevention. In this paper, we will discuss how genes, epigenetics, and in utero influences affect the development of obesity. We will then discuss current efforts to alter these influences and suggest future directions for this work.

  20. Parental and Early Childhood Influences on Adolescent Obesity: A Longitudinal Study

    Science.gov (United States)

    Chivers, Paola; Parker, Helen; Bulsara, Max; Beilin, Lawrence; Hands, Beth

    2012-01-01

    The influence of parental and early childhood factors on adolescent obesity was investigated using a longitudinal model of body mass index (BMI) from birth to 14 years. Trajectories of BMI using linear mixed model (LMM) analysis were used to investigate the influence of early parental and childhood factors on BMI at 14 years in the Raine birth…

  1. Early onset APOE E4-negative Alzheimer's disease patients show faster cognitive decline on non-memory domains.

    Science.gov (United States)

    Smits, Lieke L; Pijnenburg, Yolande A L; van der Vlies, Annelies E; Koedam, Esther L G E; Bouwman, Femke H; Reuling, Ilona E W; Scheltens, Philip; van der Flier, Wiesje M

    2015-07-01

    Age at onset and APOE E4-genotype have been shown to influence clinical manifestation of Alzheimer's disease (AD). We investigated rate of decline in specific cognitive domains according to age at onset and APOE E4-genotype in patients with AD. 199 patients with probable AD underwent at least two annual neuropsychological assessments. Patients were classified according to age-at-onset (≤ 65 years vs >65 years) and APOE genotype (positive vs negative). The neuropsychological test battery compromised tests for memory, language, attention, executive and visuo-spatial functioning. For each domain compound z-scores were calculated, based on the baseline performance of patients. Average duration of follow-up was 1.5 ± 1 years. We used linear mixed models (LMM) to estimate effects of age, APOE and age⁎APOE on cognitive decline over time. At baseline, patients were 65 ± 8 years, 98(49%) were female and MMSE was 22 ± 4. LMM showed that early onset patients declined faster on executive functioning (β ± SE:-0.09 ± 0.06) than late onset patients, but age was not related to decline in the other cognitive domains. APOE E4 negative patients declined faster on language than APOE E4 positive patients (β ± SE:-0.1 ± 0.06). When we took age and APOE genotype into account simultaneously, we found that compared to late onset-E4 positive patients, early onset-E4 negative patients declined faster on language (β ± SE:-0.36 ± 0.1), attention (β ± SE:-0.42 ± 0.1), executive (β ± SE:-0.41 ± 0.1) and visuo-spatial functioning (β ± SE:-0.43 ± 0.1). Late onset-E4 negative and early onset-E4 positive patients showed intermediate rates of decline. We found no differences in decline on memory. We found that patients who develop AD despite absence of the two most important risk factors, show steepest cognitive decline on non-memory cognitive domains. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  2. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

    Directory of Open Access Journals (Sweden)

    Eniko Nagy

    Full Text Available Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD, a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC, using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice. Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het" dams that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het dams, T/I pups initially gained weight similarly to wild type (WT pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and

  3. Family History of Skin Cancer is Associated with Early-Onset Basal Cell Carcinoma Independent of MC1R Genotype

    Science.gov (United States)

    Berlin, Nicholas L.; Cartmel, Brenda; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.; Ferrucci, Leah M.

    2015-01-01

    Background As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual’s risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin-1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). Materials and Methods Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale Dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. Results A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80–3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74–3.35). Conclusions Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90–7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC. PMID:26381319

  4. Early life origins of obesity: role of hypothalamic programming.

    Science.gov (United States)

    Bouret, Sebastien G

    2009-03-01

    The incidence of obesity is increasing at an alarming rate and this worldwide epidemic represents an ominous predictor of increases in diseases such as type 2 diabetes and metabolic syndrome. Epidemiological and animals studies suggest that maternal obesity and alterations in postnatal nutrition are associated with increased risks for obesity, hypertension, and type 2 diabetes in the offspring. Furthermore, there is also growing appreciation that developmental programming of neuroendocrine systems by the perinatal environment represents a possible cause for these diseases. This review article provides a synthesis of recent evidence concerning the actions of perinatal hormones and nutrition in programming the development and organization of hypothalamic circuits that regulate body weight and energy balance. Particular attention is given to the neurodevelopmental actions of insulin and leptin.

  5. Early metabolic improvement following bariatric surgery in morbidly obese adolescents.

    Science.gov (United States)

    Teeple, E A; Teich, S; Schuster, D P; Michalsky, M P

    2012-01-01

    Bariatric surgery results in durable weight loss and improved comorbidities. The objectives of this study were to examine the efficacy of gastric bypass in reducing comorbid burden and improving metabolic status among morbidly obese adolescents. The medical records of 15 gastric bypass patients were retrospectively reviewed. Changes in metabolic markers were determined at baseline, 1 and 2 years post-operatively. Comparative analysis demonstrated significant improvement in weight, BMI, insulin, HbA1C, C-peptide, %B, %S, IR, cholesterol, percentile cholesterol, TG, percentile TG, HDL, percentile HDL, LDL, percentile LDL, and VLDL. Results support bariatric surgery as a treatment for morbidly obese adolescents with comorbidities.

  6. ANALYSIS OF CLINICO - RADIOLOGICAL OUTCOME OF POSTERIOR INSTRUMENTATION IN EARLY ONSET POTT’S PARAPARESIS: A RETROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Jayant

    2015-02-01

    Full Text Available BACKGROUND: The preferred modality of surgical intervention in thoraco - lumbar spinal tuberculosis has been controversial . The aim is to evaluate the role of isolated posterior instrumentation without anterior instrumentation and without anterior or posterior bone grafting in cases of early onset pott’s paraparesis . MATERIAL AND METHODS: 22 patients with early onset Pott’s Par aparesis have been treated surgically by posterior instrumentation ( P edicular screws with rods with posterior decompression with paraspinal abscess drainage as a single stage procedure under chemotherapy cover . Patients have been followed for minimum of 18 months . RESULTS: Inter - body fusion has been noticed in all patients in follow - up . The mean kyphotic angle of 28 ° has been improved to mean kyphotic angle of 5 . 4° in immediate post - operative period . CONCLUSION: Isolated posterior stabilization seems to be adequate for clinical and radiological improvement in early onset pott’s paraparesis with maintenance of acceptable kyphotic angle .

  7. Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

    Energy Technology Data Exchange (ETDEWEB)

    Das, Suvarthi [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kumar, Ashutosh [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Seth, Ratanesh Kumar [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Tokar, Erik J. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Kadiiska, Maria B. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Waalkes, Michael P. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Mason, Ronald P. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Chatterjee, Saurabh, E-mail: schatt@mailbox.sc.edu [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States)

    2013-06-15

    Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates

  8. Is genetic testing of value in predicting and treating obesity?

    Science.gov (United States)

    Ng, Maggie C Y; Bowden, Donald W

    2013-01-01

    Obesity is a multifactorial disease resulting from the interaction between genetic factors and lifestyle. Identification of rare genetic variations with strong effects on obesity has been useful in diagnosing and designing personalized therapy for early-onset or syndromic obesity. However, common variants identified in recent genome-wide association studies have limited clinical value.

  9. Is Genetic Testing of Value in Predicting and Treating Obesity?

    OpenAIRE

    Ng, Maggie C.Y.; Bowden, Donald W.

    2013-01-01

    Obesity is a multifactorial disease resulting from the interaction between genetic factors and lifestyle. Identification of rare genetic variations with strong effects on obesity has been useful in diagnosing and designing personalized therapy for early-onset or syndromic obesity. However, common variants identified in recent genome-wide association studies have limited clinical value.

  10. Myeloperoxidase Is an Early Biomarker of Inflammation and Cardiovascular Risk in Prepubertal Obese Children

    OpenAIRE

    Olza, Josune; Aguilera, Concepcion M.; Gil-Campos, Mercedes; Leis, Rosaura; Bueno, Gloria; Martínez-Jiménez, Maria D.; Valle, Miguel; Cañete, Ramon; Tojo, Rafael; Moreno, Luis A.; Gil, Angel

    2012-01-01

    OBJECTIVE Obesity is associated with a state of chronic low-grade inflammation. Myeloperoxidase (MPO) plays an important role in the initiation and progression of acute and chronic inflammatory diseases, such as cardiovascular disease (CVD). The objectives of the current study were to evaluate plasma MPO levels in prepubertal obese children and to determine whether MPO could be an early biomarker of inflammation and CVD risk. RESEARCH DESIGN AND METHODS In a prospective multicenter case-contr...

  11. Influence of obesity on early surgical outcomes of laparoscopic-assisted gastrectomy in gastric cancer.

    Science.gov (United States)

    Kim, Min Gyu; Yook, Jeong Hwan; Kim, Kap Choong; Kim, Tae Hwan; Kim, Hee Sung; Kim, Beom Su; Kim, Byung Sik

    2011-06-01

    The aim of this study is to estimate the impact of obesity on surgical outcomes of laparoscopic-assisted gastrectomy for gastric cancer. Between January 2005 and January 2010, 1100 consecutive patients who underwent laparoscopic-assisted distal gastrectomy for gastric cancer were reviewed to evaluate the impact of obesity. The patients were classified into 3 groups according to the World Health Organization classification, as normal weight [body mass index (BMI) 18.5 to 24.9 kg/m], overweight (BMI 25 to 29.9 kg/m), and obese patients (BMI ≥30 kg/m). The postoperative complication rates for normal weight, overweight, and obese patients were 5.7%, 10.0%, 15.4%, respectively. Overweight and obese patients had a significantly prolonged operation time, increased intraoperative blood loss, prolonged first flatus, day of commencement of soft diet, increased number of administration of analgesics, and prolonged hospital stay. Overweight and obesity were associated with poor early surgical outcomes of laparoscopic-assisted gastrectomy. This study suggested that greater cautions and improved surgical techniques were required to improve early surgical outcomes of laparoscopic-assisted gastrectomy for overweight and obese patients.

  12. Cortical gamma generators suggest abnormal auditory circuitry in early-onset psychosis.

    Science.gov (United States)

    Wilson, Tony W; Hernandez, Olivia O; Asherin, Ryan M; Teale, Peter D; Reite, Martin L; Rojas, Donald C

    2008-02-01

    Neurobiological theories of schizophrenia and related psychoses have increasingly emphasized impaired neuronal coordination (i.e., dysfunctional connectivity) as central to the pathophysiology. Although neuroimaging evidence has mostly corroborated these accounts, the basic mechanism(s) of reduced functional connectivity remains elusive. In this study, we examine the developmental trajectory and underlying mechanism(s) of dysfunctional connectivity by using gamma oscillatory power as an index of local and long-range circuit integrity. An early-onset psychosis group and a matched cohort of typically developing adolescents listened to monaurally presented click-trains, as whole-head magnetoencephalography data were acquired. Consistent with previous work, gamma-band power was significantly higher in right auditory cortices across groups and conditions. However, patients exhibited significantly reduced overall gamma power relative to controls, and showed a reduced ear-of-stimulation effect indicating that ipsi- versus contralateral presentation had less impact on hemispheric power. Gamma-frequency oscillations are thought to be dependent on gamma-aminobutyric acidergic interneuronal networks, thus these patients' impairment in generating and/or maintaining such activity may indicate that local circuit integrity is at least partially compromised early in the disease process. In addition, patients also showed abnormality in long-range networks (i.e., ear-of-stimulation effects) potentially suggesting that multiple stages along auditory pathways contribute to connectivity aberrations found in patients with psychosis.

  13. Early onset of industrial-era warming across the oceans and continents.

    Science.gov (United States)

    Abram, Nerilie J; McGregor, Helen V; Tierney, Jessica E; Evans, Michael N; McKay, Nicholas P; Kaufman, Darrell S

    2016-08-25

    The evolution of industrial-era warming across the continents and oceans provides a context for future climate change and is important for determining climate sensitivity and the processes that control regional warming. Here we use post-ad 1500 palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-nineteenth century and was nearly synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests that greenhouse forcing of industrial-era warming commenced as early as the mid-nineteenth century and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change and that, in some regions, about 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial values, even when taking natural variability into account.

  14. Early onset of industrial-era warming across the oceans and continents

    Science.gov (United States)

    2016-08-01

    The evolution of industrial-era warming across the continents and oceans provides a context for future climate change and is important for determining climate sensitivity and the processes that control regional warming. Here we use post-AD 1500 palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-nineteenth century and was nearly synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests that greenhouse forcing of industrial-era warming commenced as early as the mid-nineteenth century and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change and that, in some regions, about 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial values, even when taking natural variability into account.

  15. Early onset polymyalgia rheumatica: two rare cases under age of 50

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jinyoung [Yonsei University College of Medicine, Department of Rehabilitation Medicine, Gangnam Severance Hospital, Rehabilitation Institute of Neuromuscular Disease, Seoul (Korea, Republic of); Sung, Duk Hyun [Samsung Medical Center, Department of Physical and Rehabilitation Medicine, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul (Korea, Republic of)

    2017-06-15

    Polymyalgia rheumatica (PMR) is almost an exclusive disease of adults over the age of 50, and only a few cases have been reported. Two 46-year-old females visited our locomotor pain clinic with multiple joint pain with increased acute phase reactants. Rheumatologic markers, and HLA-B27 were checked. Serum protein electrophoresis and serum immunofixation electrophoresis, imaging studies including plane image, sonography, and magnetic resonance image was done. {sup 18}F-Fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed characteristic findings of PMR, without evidences of sacroiliitis. Since PMR can develop in mid 40s, a high index of suspicion is necessary in younger patients presenting the bilateral pain in shoulders, hips, and back, with elevated acute phase reactants. Furthermore, in addition to the previous case reports, FDG-PET/CT is helpful in making early differential diagnosis of PMR in patients under the age of 50. Here we present two cases of PMR onset in the mid-40s emphasizing the importance of diagnostic imaging for early differential diagnosis in PMR. (orig.)

  16. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions

    Science.gov (United States)

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-01-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70–80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. PMID:28689169

  17. A Study on Apolipoprotein E Polymorphism in Early Onset of Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    朱铁兵; 杨志健; 钱卫冲; 王连生; 马根山; 马文珠

    2003-01-01

    Objective:To assess the relationship between apolipoprotein E( apoE) polymorphism and early anset of Coronary heart disease(CHD) and the effect of apoE on lipids and lipoproteins in Chinese healthy subjects.Methods:Sixty-eight cases(CHD1) aged less than 55y,136 cases(CHD2) aged more than 65y with CHD and 136 healthy subjects were enrolled and their plamsma levels of triglyceride(TG),total cholesterol(TC) and high density lipoprotein cholesterol(HDL-C) were determined.The apoE genotypes were identified by polymerase chain reaction-restriction fragment lengths polymorphism.Results:apoE3/4 genotype and E4 allele frequency in CHD1 were higher than those in CHD2 and healthy subjects and no difference was found between CHD2 and healthy subjects.Meanwhile the plasma levels of TC and low density lipoprotein cholesterol(LDL-C) were higher in CHD2 than in either CHD1 or healthy subjects.Each apoE isoprotein has variable TC and LDL-C levels characterized by E2(E2/2+E2/3)early onset of CHD.

  18. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions.

    Science.gov (United States)

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-09-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Proatherogenic Lipid Profile in Early Childhood: Association with Weight Status at 4 Years and Parental Obesity.

    Science.gov (United States)

    Riaño-Galán, Isolina; Fernández-Somoano, Ana; Rodríguez-Dehli, Cristina; Valvi, Damaskini; Vrijheid, Martine; Tardón, Adonina

    2017-08-01

    To determine lipid profiles in early childhood and evaluate their association with weight status at 4 years of age. Additionally, we evaluated whether the risk of overweight or having an altered lipid profile was associated with parental weight status. Five hundred eighty two mothers and their 4-year-old children from 2 Spanish population-based cohorts were studied. Weight status in children at 4 years of age was classified as overweight or obese using the International Obesity Task Force criteria. Plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were determined in children and lipid ratios were calculated. A proatherogenic lipid profile was defined as having the 3 lipid ratios in the third tertile. A total of 12.9% of children were overweight and 6.4% were obese. Weight status at 4 years of age was related to maternal prepregnancy body mass index, paternal body mass index, gestational diabetes, and birth weight, but not with other sociodemographic characteristics of the mother. We found no association with gestational age, sex of the child, or breastfeeding. The risk of overweight/obesity was increased 4.17-fold if mothers were overweight/obese (95% CI 1.76-9.88) and 5.1-fold (95% CI 2.50-10.40) if both parents were overweight/obese. There were 133 children (22.8%) with a proatherogenic lipid profile. The risk of a proatherogenic lipid profile was increased 2.44-fold (95% CI 1.54-3.86) if they were overweight/obese at 4 years of age and 2-fold if the father was overweight/obese (95% CI 1.22-3.35). Four-year-old overweight/obese children have higher lipid risk profiles. Offspring of overweight/obese parents have an increased risk for obesity and a proatherogenic lipid profile. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Urinary podocalyxin, the novel biomarker for detecting early renal change in obesity.

    Science.gov (United States)

    Suwanpen, Chayanut; Nouanthong, Phonethipsavanh; Jaruvongvanich, Veeravich; Pongpirul, Krit; Pongpirul, Wannarat Amornnimit; Leelahavanichkul, Asada; Kanjanabuch, Talerngsak

    2016-02-01

    The prevalence of obesity is increasing during the past decade along with obesity-related glomerulopathy (ORG), glomeruli injury due to the obesity. The major pathogenesis of ORG is the shedding of podocytes from the glomerular cell barrier into urine. Podocalyxin (PCX), a main surface antigen of podocyte, correlates well with glomerulosclerosis progression and glomerular injury severity, and might be a potential biomarker for early renal alteration in obesity. In addition, vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA) also play a role in promoting glomerulosclerosis. The aim of this study was to explore whether obese subjects without other diseases excrete more PCX-positive (PCX+) cells than non-obese individuals, in comparison with urine protein-creatinine ratio (UPCR) and glomerular filtration rate (GFR) as traditional renal markers. Moreover, the effect of body mass index (BMI) on urinary VEGF, PCX or α-SMA positive cells was also investigated. Forty-eight obese and 13 non-obese adults were included. Exfoliated cells from fresh first void morning urine were harvested, stained with PCX, VEGF, and α-SMA antibody, and quantified by flow cytometry. Correlation between interested urinary biomarkers (cells positive for PCX, VEGF plus PCX and α-SMA), UPCR and GFR with BMI and metabolic risk factors were analyzed. Obese patients had significantly higher PCX+ cells than non-obese [0.62 (0.00-13.13) vs. 0.15 (0.00-0.72) cells/ml × mg cr, p Obese subjects without other diseases and with normal UPCR and GFR showed evidence of renal alteration through the detection of a higher number of PCX+ cells. Increasing BMI also resulted in higher number of PCX+ cells.

  2. A study on early-onset neonatal group B streptococcal infection, Bulgaria, 2007-2011.

    Science.gov (United States)

    Todorova-Christova, M; Vacheva, R; Decheva, A; Nikolov, A; Slancheva, B; Stoichkova, D; Christova, E; Shopova, E; Hitrova, S; Masseva, A; Yarakova, N; Kraleva, I; Takova, T S; Dimitrova, N; Dobreva, A

    2014-09-01

    This study examines neonatal group B streptococcal (GBS) colonization and its relation to early-onset GBS disease (EOGBSD), based upon the experience of leading obstetrics and gynecology centers in Bulgaria. The objectives of the study were to update neonatal colonization rates and to assess relationships between clinically differentiated cases (culture-proven GBS newborns) and risk factors inherent to the infant and mother, using a computerized file. The neonatal GBS colonization rate ranged from 5.48 to 12.19 per 1000 live births. Maternal-fetal infection (MFI, a provisional clinical diagnosis in culture-proven colonized infants with initial signs of infection that is usually overcome with antibiotic treatment) and/or intrapartum asphyxia (IA) have been demonstrated as the most frequent clinical manifestations, with significant correlations for the primary diagnosis, but not affirmative for the final diagnosis at discharge, resulting from adequate treatment of neonates. MFI and IA were significantly related to prematurity, and reciprocally, prematurity was associated with the risk of MFI, indirectly suggesting that preterm birth or PPROM (preterm premature rupture of membranes, an obstetric indication associated with early labor and delivery, one of the major causes of preterm birth) is a substantial risk factor for EOGBSD. The regression analysis indicated that in the case of a newborn with MFI, a birth weight 593.58 g lower than the birth weight of an infant without this diagnosis might be expected. Testing the inverse relationship, i.e., the way birth weight influences a certain diagnosis (logistic regression) established the presence of a relationship between birth weight categories (degree of prematurity) and the diagnosis of MFI. The proportions and odds ratios, converted into probabilities that a baby would develop MFI, indicate the particularly high risk for newborns with extremely low and very low birth weight: extremely low birth weight (≤1000 g), the

  3. Early-life influences on obesity: From preconception to adolescence

    Science.gov (United States)

    The double burden of under- and overnutrition profoundly affects human health globally. According to the World Health Organization, obesity and diabetes rates have almost doubled worldwide since 1980, and, in 2011, more than 40 million children under 5 years of age were overweight. Ecologic factors,...

  4. Obesity Prevention in Early Adolescence: Student, Parent, and Teacher Views

    Science.gov (United States)

    Power, Thomas G.; Bindler, Ruth C.; Goetz, Summer; Daratha, Kenneth B.

    2010-01-01

    Background: Obesity is a significant health problem among today's youth; however, most school-based prevention programs in this area have had limited success. Focus groups were conducted with seventh- to eighth-grade students, parents, and teachers to provide insight into the development of a comprehensive program for the prevention of adolescent…

  5. Machine Learning Techniques for Prediction of Early Childhood Obesity.

    Science.gov (United States)

    Dugan, T M; Mukhopadhyay, S; Carroll, A; Downs, S

    2015-01-01

    This paper aims to predict childhood obesity after age two, using only data collected prior to the second birthday by a clinical decision support system called CHICA. Analyses of six different machine learning methods: RandomTree, RandomForest, J48, ID3, Naïve Bayes, and Bayes trained on CHICA data show that an accurate, sensitive model can be created. Of the methods analyzed, the ID3 model trained on the CHICA dataset proved the best overall performance with accuracy of 85% and sensitivity of 89%. Additionally, the ID3 model had a positive predictive value of 84% and a negative predictive value of 88%. The structure of the tree also gives insight into the strongest predictors of future obesity in children. Many of the strongest predictors seen in the ID3 modeling of the CHICA dataset have been independently validated in the literature as correlated with obesity, thereby supporting the validity of the model. This study demonstrated that data from a production clinical decision support system can be used to build an accurate machine learning model to predict obesity in children after age two.

  6. Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis.

    Science.gov (United States)

    Silverman, E K; Chapman, H A; Drazen, J M; Weiss, S T; Rosner, B; Campbell, E J; O'DONNELL, W J; Reilly, J J; Ginns, L; Mentzer, S; Wain, J; Speizer, F E

    1998-06-01

    Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-1-antitrypsin deficiency, could be demonstrated. First- degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.

  7. BRCA mutations, molecular markers, and clinical variables in early-onset breast cancer: a population-based study.

    Science.gov (United States)

    Musolino, Antonino; Bella, Maria A; Bortesi, Beatrice; Michiara, Maria; Naldi, Nadia; Zanelli, Paola; Capelletti, Marzia; Pezzuolo, Debora; Camisa, Roberta; Savi, Mario; Neri, Tauro M; Ardizzoni, Andrea

    2007-06-01

    Early age at onset is generally considered an indicator of genetic susceptibility to breast cancer. To address both the proportion of early-onset breast cancer associated with BRCA-1 or BRCA-2 germline mutation and the contribution of germline mutations to the clinical features and outcome of these tumors, we analyzed molecular status and clinical variables of a population-based sample of 66 Italian women diagnosed with breast cancer before the age of 40 who were unselected for family history. BRCA mutations were screened by automated sequencing of the entire BRCA-1 and BRCA-2 coding regions and splice junctions. Twenty-eight late-onset (over 45 years), sporadic, breast cancers were designated as "control group" for comparisons with early-onset cases. BRCA mutations (10 BRCA-1 and 6 BRCA-2) were detected in 15 (22.7%) out of 66 tested patients. The combination of ER, PR, HER-2/neu negativity and p53 positivity was significantly more frequent in BRCA-1 positive tumors than in BRCA-2 positive and non-BRCA tumors (P=0.03). Taken collectively, BRCA-positive tumors correlated with high histologic grade and ER negativity compared with non-BRCA and sporadic tumors (P=0.05 and 0.003, respectively). There were no significant differences between BRCA-associated breast cancers (BABC) and non-BABC in relapse-free, event-free, and overall survival. Our data confirm that the combination of age at onset and tumor phenotype can provide an efficient model for identifying individuals with a high probability of carrying BRCA mutations and support the hypothesis that breast cancer in BRCA carriers is qualitatively distinct from other early-onset breast cancers and from late-onset, sporadic, breast carcinomas. Further studies on incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.

  8. The effect of obesity on recurrence pattern in early breast cancer patients.

    Science.gov (United States)

    Yazici, Ozan; Aksoy, Sercan; Sendur, Mehmet An; Babacan, Taner; Ozdemir, Nuriye; Ozisik, Yavuz; Zengin, Nurullah; Altundag, Kadri

    2015-01-01

    Obesity is a well known risk factor for breast cancer recurrence and poor prognosis. We studied the effect of body mass index (BMI) on recurrence pattern in early breast cancer patients. This retrospective cross-sectional study analyzed the data of 2731 early stage breast cancer patients. Patients who had metastatic disease at the time of diagnosis and with unknown BMI values were excluded from study (N=276). Patients were classified into three BMI categories: normal body weight, overweight, and obese. The recurrent/metastatic sites of patients were grouped in 8 categories: local, contralateral, lymph node, bone, lung, liver, brain and others. The association between first relapse site of early breast cancer patients and BMI categories were evaluated. The median patient age was 48 years (range 18-92). The median follow up time was 40 months (range 1-284). During follow-up, 469 (17.1%) patients developed recurrence and/or metastasis. Of 2455 total patients, 853 (34.6%) were classified as having normal weight, 898 (36.2%) were overweighted and 704 (29.2%) were obese. In the whole patient group no relation between metastatic sites and BMI groups was noticed. The first primary metastatic sites were also not associated with BMI groups in pre and postmenopausal subpopulations. In obese patients, disease free survival (DFS) was shorter compared to normal weighted patients, but the difference was not significant. There was no significant difference between site-specific DFS in relation to BMI categorization. Obese and overweighted patients had significantly shorter overall survival (OS) compared to the normal-weight group (p=0.003). Although obesity had no effect on recurrence pattern of early breast cancer patients, obese early breast cancer patients had shorter OS compared to their normal-weight counterparts.

  9. Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity

    NARCIS (Netherlands)

    Arnoldussen, I.A.C.; Zerbi, V.; Wiesmann, M.; Noordman, R.H.J.; Bolijn, S.; Mutsaers, M.P.C.; Dederen, P.J.W.C.; Kleemann, R.; Kooistra, T.; Tol, E.A.F. van; Gross, G.; Schoemaker, M.H.; Wieling, P.Y.; Kilian, A.

    2016-01-01

    orldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid

  10. Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity

    NARCIS (Netherlands)

    Arnoldussen, I.A.C.; Zerbi, V.; Wiesmann, M.; Noordman, R.H.J.; Bolijn, S.; Mutsaers, M.P.C.; Dederen, P.J.W.C.; Kleemann, R.; Kooistra, T.; Tol, E.A.F. van; Gross, G.; Schoemaker, M.H.; Wieling, P.Y.; Kilian, A.

    2016-01-01

    orldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid

  11. Adaptive behavior and later school achievement in children with early-onset epilepsy

    Science.gov (United States)

    Berg, Anne T; Caplan, Rochelle; Baca, Christine B; Vickrey, Barbara G

    2013-01-01

    Aim To determine whether early measures of adaptive behavior are predictive of later school difficulties and achievement in otherwise neurotypical (unimpaired) children with onset of epilepsy during the pre-school years. Method In a prospective cohort study, parents completed the Vineland Adaptive Behavior Scales (VABS) for children who were aged 5 years or less at epilepsy diagnosis. Eight to nine years later, the children were assessed using the Wechsler Intelligence Scales for Children (WISC), the Wide Range Achievement Test (WRAT), and the Child Behavior Checklist (CBCL). Associations of VABS scores with later WRAT and CBCL scores were tested. Results A total of 108 neurotypical children (64 males, 44 females; mean age at testing 11y 11mo, SD 2y) were studied. After adjustment for IQ and other factors, there was an increase of 0.15 points (95% confidence interval [CI] 0.03–0.27 points; p=0.03) and 0.14 points (95% CI 0.0–0.28 points; p=0.05) in WRAT reading and spelling scores for each 1-point increment in the VABS communication score. Corresponding numbers for the VABS socialization score were 0.20 (95% CI 0.08–0.32; p=0. 005) and 0.17 (95% CI 0.05–0.29; p=0.005). Conclusion In neurotypical preschool children with epilepsy, early social and communication scores predict later school performance. These findings raise questions about opportunities for early identification and intervention for children at greatest risk. PMID:23534842

  12. Matrix metalloproteinase 1 (MMP1) is associated with early-onset lung cancer.

    Science.gov (United States)

    Sauter, Wiebke; Rosenberger, Albert; Beckmann, Lars; Kropp, Silke; Mittelstrass, Kirstin; Timofeeva, Maria; Wölke, Gabi; Steinwachs, Angelika; Scheiner, Daniela; Meese, Eckart; Sybrecht, Gerhard; Kronenberg, Florian; Dienemann, Hendrik; Chang-Claude, Jenny; Illig, Thomas; Wichmann, Heinz-Erich; Bickeböller, Heike; Risch, Angela

    2008-05-01

    Matrix metalloproteinases (MMP) play a key role in the breakdown of extracellular matrix and in inflammatory processes. MMP1 is the most highly expressed interstitial collagenase degrading fibrillar collagens. Overexpression of MMP1 has been shown in tumor tissues and has been suggested to be associated with tumor invasion and metastasis. Nine haplotype tagging and additional two intronic single nucleotide polymorphisms (SNP) of MMP1 were genotyped in a case control sample, consisting of 635 lung cancer cases with onset of disease below 51 years of age and 1,300 age- and sex-matched cancer-free controls. Two regions of linkage disequilibrium (LD) of MMP1 could be observed: a region of low LD comprising the 5' region including the promoter and a region of high LD starting from exon 1 to the end of the gene and including the 3' flanking region. Several SNPs were identified to be individually significantly associated with risk of early-onset lung cancer. The most significant effect was seen for rs1938901 (P = 0.0089), rs193008 (P = 0.0108), and rs996999 (P = 0.0459). For rs996999, significance vanished after correction for multiple testing. For each of these SNPs, the major allele was associated with an increase in risk with an odds ratio between 1.2 and 1.3 (95% confidence interval, 1.0-1.5). The haplotype analysis supported these findings, especially for subgroups with high smoking intensity. In summary, we identified MMP1 to be associated with an increased risk for lung cancer, which was modified by smoking.

  13. Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Sand Jette C

    2007-07-01

    Full Text Available Abstract Background X-linked Charcot-Marie Tooth (CMT is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions. Methods We describe two novel mutations in the connexin32 gene in two Norwegian families. Results Family 1 had a c.225delG (R75fsX83 which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands. The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25–49 m/s. Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals. Conclusion The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode.

  14. Early- and late-onset psoriasis: a cross-sectional clinical and immunocytochemical investigation.

    Science.gov (United States)

    Theodorakopoulou, E; Yiu, Z Z N; Bundy, C; Chularojanamontri, L; Gittins, M; Jamieson, L A; Motta, L; Warren, R B; Griffiths, C E M

    2016-11-01

    There is accumulating evidence that early-onset psoriasis (EOP; presenting at or before 40 years of age) and late-onset psoriasis (LOP; presenting after 40 years of age) are different diseases. We aimed to identify potential clinical and immunocytochemical differences between EOP and LOP. We assessed immunocytochemistry in involved (PP) skin and uninvolved skin (n = 31) and demographics, psoriasis phenotype and psychological parameters (n = 340) in a cross-sectional study. Immunocytochemistry revealed (17 EOP, 14 LOP) a greater lymphocytic infiltrate in PP skin of EOP compared with LOP (P = 0·03), with a higher epidermal CD4(+) : CD8(+) ratio in LOP (1·3) compared with EOP (0·5) (P = 0·002). In 340 patients with psoriasis (278 EOP, 62 LOP), we found an association with a positive first or second degree family history of psoriasis [62·0% vs. 35·6%, adjusted odds ratio (OR) 8·32, 95% confidence interval (CI) 1·90-36·52] and a higher likelihood of having parents with EOP (adjusted OR 10·34, 95% CI 1·32-81·83) in the EOP group. Patients with EOP were more likely to have received biological therapy (13·3% EOP vs. 3·5% LOP, P = 0·042), while patients with LOP had a higher likelihood of having type 2 diabetes (adjusted OR 3·43, 95% CI 1·004-11·691) and autoimmune thyroiditis (adjusted OR 5·05, 95% CI 1·62-15·7). Patients with LOP also had greater anxiety than patients with EOP (mean Hospital Anxiety and Depression Scale-A score LOP 8 ± 5, EOP 5 ± 5; P = 0·006). Our findings provide further evidence for the difference between EOP and LOP. © 2016 British Association of Dermatologists.

  15. Maternal obesity in early pregnancy and risk of adverse outcomes.

    Directory of Open Access Journals (Sweden)

    Inmaculada Bautista-Castaño

    Full Text Available OBJECTIVES: To assess the role of the health consequences of maternal overweight and obesity at the start of pregnancy on gestational pathologies, delivery and newborn characteristics. METHODS: A cohort of pregnant women (n = 6.558 having delivered at the Maternal & Child University Hospital of Gran Canaria (HUMIGC in 2008 has been studied. Outcomes were compared using multivariate analyses controlling for confounding variables. RESULTS: Compared to normoweight, overweight and obese women have greater risks of gestational diabetes mellitus (RR = 2.13 (95% CI: 1.52-2.98 and (RR = 2.85 (95% CI: 2.01-4.04, gestational hypertension (RR = 2.01 (95% CI: 1.27-3.19 and (RR = 4.79 (95% CI: 3.13-7.32 and preeclampsia (RR = 3.16 (95% CI: 1.12-8.91 and (RR = 8.80 (95% CI: 3.46-22.40. Obese women have also more frequently oligodramnios (RR = 2.02 (95% CI: 1.25-3.27, polyhydramnios. (RR = 1.76 (95% CI: 1.03-2.99, tearing (RR = 1.24 (95% CI: 1.05-1.46 and a lower risk of induced deliveries (RR = 0.83 (95% CI: 0.72-0.95. Both groups have more frequently caesarean section (RR = 1.36 (95% CI: 1.14-1.63 and (RR = 1.84 (95% CI: 1.53-2.22 and manual placenta extraction (RR = 1.65 (95% CI: 1.28-2.11 and (RR = 1.77 (95% CI: 1.35-2.33. Newborns from overweight and obese women have higher weight (p<0.001 and a greater risk of being macrosomic (RR = 2.00 (95% CI: 1.56-2.56 and (RR = 2.74 (95% CI: 2.12-3.54. Finally, neonates from obese mother have a higher risk of being admitted to special care units (RR = 1.34 (95% CI: 1.01-1.77. Apgar 1 min was significantly higher in newborns from normoweight mothers: 8.65 (95% CI: 8.62-8.69 than from overweight: 8.56 (95% CI: 8.50-8.61 or obese mothers: 8.48 (95% CI: 8.41-8.54. CONCLUSION: Obesity and overweight status at the beginning of pregnancy increase the adverse outcomes of the pregnancy. It is important to promote the normalization of bodyweight in those

  16. Mutations in MODY Genes Are not Common Cause of Early-Onset Type 2 Diabetes in Mexican Families

    Directory of Open Access Journals (Sweden)

    Bravo-Ríos LE

    2005-05-01

    Full Text Available CONTEXT: Maturity-onset diabetes of the young (MODY is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes. OBJECTIVE: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance. PATIENTS: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied. DESIGN: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines. MAIN OUTCOME MEASURES: MODY gene mutation screening and P379H mutant protein transactivation assay. RESULTS: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter. CONCLUSIONS: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.

  17. Obesity and depression in adolescence and beyond: reciprocal risks.

    Science.gov (United States)

    Marmorstein, N R; Iacono, W G; Legrand, L

    2014-07-01

    Obesity and major depressive disorder (MDD) are associated, but evidence about how they relate over time is conflicting. The goal of this study was to examine prospective associations between depression and obesity from early adolescence through early adulthood. Participants were drawn from a statewide, community-based, Minnesota sample. MDD and obesity with onsets by early adolescence (by age 14), late adolescence (between 14 and 20) and early adulthood (ages 20-24) were assessed via structured interview (depression) and study-measured height and weight. Cross-sectional results indicated that depression and obesity with onsets by early adolescence were concurrently associated, but the same was not true later in development. Prospective results indicated that depression by early adolescence predicted the onset of obesity (odds ratio (OR)=3.76, confidence interval =1.33-10.59) during late adolescence among female individuals. Obesity that developed during late adolescence predicted the onset of depression (OR=5.89, confidence interval=2.31-15.01) during early adulthood among female individuals. For girls, adolescence is a high-risk period for the development of this comorbidity, with the nature of the risk varying over the course of adolescence. Early adolescent-onset depression is associated with elevated risk of later onset obesity, and obesity, particularly in late adolescence, is associated with increased odds of later depression. Further investigation into the mechanisms of these effects and the reasons for the observed gender and developmental differences is needed. Prevention programs focused on early-onset cases of depression and adolescent-onset cases of obesity, particularly among female individuals, may help in reducing risk for this form of comorbidity.

  18. Relationship between obesity and early failure of total knee prostheses

    Directory of Open Access Journals (Sweden)

    De Palma Rossana

    2009-03-01

    Full Text Available Abstract Background Obesity is a risk factor for knee arthritis. Total knee arthroplasty is the definitive surgical treatment of this disease. Therefore, a high percentage of subjects treated are overweight. Since 2000 in the Emilia-Romagna Region the Register of Orthopedic Prosthetic Implantology, RIPO, has recorded data of all the primary and revision operations performed on the knee; height and weight of patients at the time of surgery have also been recorded. Methods To understand how overweight and obesity affect the outcome of knee arthroplasty, a population of subjects treated with cemented total knee arthroplasty between 2000 and 2005 was studied. 9735 knee prostheses were implanted in 8892 patients; 18.9% of the patients were normal weight, 48.2% were overweight (25 40. Mean and range of follow-up were respectively 3.1 and 1.5–6 yrs. Implant failure was defined as the exchange of at least one component for whatever reason. Results In normal weight patients there were 36 failures out of 1840 implants (1.96%, in overweight patients there were 87 out of 4692 (1.85%, in obese 59 out of 3031 (1.94%, and in morbidly obese there were 4 out of 172 (2.3%. The mean time to failure for each class was 1.57, 1.48, 1.60, 1.77 yrs. Cox regression analyses showed that the risk of implant failure was not influenced by BMI, absolute body weight, or sex. Conversely, an increased failure risk was observed in mobile meniscus prostheses in comparison with those with a fixed meniscus (Rate Ratio 1.88; an increased failure risk was also related to age (Rate Ratio 1.05 per year. These results were also confirmed when considering septic loosening as the end-point. There were no differences in the rate of perioperative complications and death in the 4 classes of BMI. Conclusion In conclusion, cemented knee prostheses, implanted in patients with arthritis do not have significantly different rates of survival or perioperative complications in obese subjects

  19. Nutrition in pregnancy and early childhood and associations with obesity in developing countries.

    Science.gov (United States)

    Yang, Zhenyu; Huffman, Sandra L

    2013-01-01

    Concerns about the increasing rates of obesity in developing countries have led many policy makers to question the impacts of maternal and early child nutrition on risk of later obesity. The purposes of the review are to summarise the studies on the associations between nutrition during pregnancy and infant feeding practices with later obesity from childhood through adulthood and to identify potential ways for preventing obesity in developing countries. As few studies were identified in developing countries, key studies in developed countries were included in the review. Poor prenatal dietary intakes of energy, protein and micronutrients were shown to be associated with increased risk of adult obesity in offspring. Female offspring seem to be more vulnerable than male offspring when their mothers receive insufficient energy during pregnancy. By influencing birthweight, optimal prenatal nutrition might reduce the risk of obesity in adults. While normal birthweights (2500-3999 g) were associated with higher body mass index (BMI) as adults, they generally were associated with higher fat-free mass and lower fat mass compared with low birthweights (obesity in adults. Breastfeeding and timely introduction of complementary foods were shown to protect against obesity later in life in observational studies. High-protein intake during early childhood however was associated with higher body fat mass and obesity in adulthood. In developed countries, increased weight gain during the first 2 years of life was associated with a higher BMI in adulthood. However, recent studies in developing countries showed that higher BMI was more related to greater lean body mass than fat mass. It appears that increased length at 2 years of age was positively associated with height, weight and fat-free mass, and was only weakly associated with fat mass. The protective associations between breastfeeding and obesity may differ in developing countries compared to developed countries because many

  20. Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Simon, Ronald; Feuerbach, Lars;

    2013-01-01

    comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS......Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued...... gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity...

  1. Neuropsychological deficits in the prodromal phase and course of an early-onset schizophrenia. A case report.

    Science.gov (United States)

    Puetz, Vanessa; Günther, Thomas; Kahraman-Lanzerath, Berrak; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2014-05-01

    Although clear advances have been achieved in the study of early-onset schizophrenia (EOS), little is known to date about premorbid and prodromal neuropsychological functioning in EOS. Here, we report on a case of an adolescent male with EOS who underwent neuropsychological testing before and after illness onset. Marked cognitive deficits in the domains of attention, set-shifting, and verbal memory were present both pre-onset and during the course of schizophrenia, though only deficits in verbal memory persisted after illness-onset and antipsychotic treatment. The findings of this case study suggest that impairments in the verbal memory domain are particularly prominent symptoms of cognitive impairment in prodromal EOS and persist in the course of the disorder, which further demonstrates the difficult clinical situation of adequate schooling opportunities for adolescent patients with EOS.

  2. The impact of obesity on early mortality after coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    Čemerlić-Ađić Nada

    2014-01-01

    Full Text Available Background/Aim. It had been suggested that elevated body mass index (BMI is a beneficial and preventive factor when it comes to the outcome for patients undergoing coronary artery bypass grafting (CABG. At the same time, obesity is strongly associated with coronary artery disease development. The aim of this study was to determine the significance of the obesity paradox in patients referred for CABG and to examine if a relationship exists between obesity and early coronary surgery outcome. Methods. This study comparised 791 patients who had undergone isolated CABG over one year period (year 2010. The average age of patients was 62.33 ± 8.12 years and involved 568 (71.8% male and 223 (28.2% female patients, while the mean logistic EuroSCORE was 3.42%. The patients were categorized into three distinct groups based on their BMI: I - BMI 30 kg/m2. Regression analysis was conducted to determine whether BMI was an independent predictor of early mortality after CABG. Results. The majority of the cohort could be categorized as overweight (49% or obese (30%. There was no association between BMI and gender (p = 0.398. The overall early mortality was 2.15% (1.85% in the group I, 2.06% in the group II and 2.51% in the group III; p = 0.869. Univariate analysis showed that obesity cannot be regarded as an independent risk factor for early mortality following CABG (odds ratio 1.021, 95% confidence interval 0.910-1.145, p = 0.724. Duration of in-hospital period following the surgery was comparable within the BMI groups (p = 0.502. Conclusion. Compared to non-obese patients, overweight and obese individuals have similar early mortality rate following CABG. This study can substantiate the presence of obesity paradox only in terms that elevated BMI patients have comparable outcome with non-obese. Further research is needed to delineate potential underlying mechanisms that set off obesity to protective factor for coronary surgery.

  3. Early-onset and robust amyloid pathology in a new homozygous mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Antje Willuweit

    Full Text Available BACKGROUND: Transgenic mice expressing mutated amyloid precursor protein (APP and presenilin (PS-1 or -2 have been successfully used to model cerebral beta-amyloidosis, one of the characteristic hallmarks of Alzheimer's disease (AD pathology. However, the use of many transgenic lines is limited by premature death, low breeding efficiencies and late onset and high inter-animal variability of the pathology, creating a need for improved animal models. Here we describe the detailed characterization of a new homozygous double-transgenic mouse line that addresses most of these issues. METHODOLOGY/PRINCIPAL FINDINGS: The transgenic mouse line (ARTE10 was generated by co-integration of two transgenes carrying the K670N/M671L mutated amyloid precursor protein (APP(swe and the M146V mutated presenilin 1 (PS1 both under control of a neuron-specific promoter. Mice, hemi- as well as homozygous for both transgenes, are viable and fertile with good breeding capabilities and a low rate of premature death. They develop robust AD-like cerebral beta-amyloid plaque pathology with glial inflammation, signs of neuritic dystrophy and cerebral amyloid angiopathy. Using our novel image analysis algorithm for semi-automatic quantification of plaque burden, we demonstrate an early onset and progressive plaque deposition starting at 3 months of age in homozygous mice with low inter-animal variability and 100%-penetrance of the phenotype. The plaques are readily detected in vivo by PiB, the standard human PET tracer for AD. In addition, ARTE10 mice display early loss of synaptic markers and age-related cognitive deficits. By applying a gamma-secretase inhibitor we show a dose dependent reduction of soluble amyloid beta levels in the brain. CONCLUSIONS: ARTE10 mice develop a cerebral beta-amyloidosis closely resembling the beta-amyloid-related aspects of human AD neuropathology. Unifying several advantages of previous transgenic models, this line particularly qualifies for

  4. Preliminary analysis of immune activation in early onset type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Julia D. Rempel

    2013-08-01

    Full Text Available Introduction. First Nations and other Aboriginal children are disproportionately affected by cardiometabolic diseases, including type 2 diabetes (T2D. In T2D, the disruption of insulin signalling can be driven by pro-inflammatory immunity. Pro-inflammatory responses can be fueled by toll-like receptors (TLR on immune cells such as peripheral blood mononuclear cells (PBMC, a white blood cell population. TLR4 can bind to lipids from bacteria and food sources activating PBMC to produce cytokines tumour necrosis factor (TNF-α and interleukin (IL-1β. These cytokines can interfere with insulin signalling. Here, we seek to understand how TLR4 activation may be involved in early onset T2D. We hypothesized that immune cells from youth with T2D (n=8 would be more reactive upon TLR4 stimulation relative to cells from age and body mass index (BMI-matched controls without T2D (n=8. Methods. Serum samples were assayed for adipokines (adiponectin and leptin, as well as cytokines. Freshly isolated PBMC were examined for immune reactivity upon culture with TLR4 ligands bacterial lipopolysaccharide (LPS, 2 and 0.2 ng/ml and the fatty acid palmitate (200 µM. Culture supernatants were evaluated for the amount of TNF-α and IL-1β produced by PBMC. Results. Youth with T2D displayed lower median serum adiponectin levels compared to controls (395 vs. 904 ng/ml, p<0.05. PBMC isolated from youth with and without T2D produced similar levels of TNF-α and IL-1β after exposure to the higher LPS concentration. However, at the low LPS dose the T2D cohort exhibited enhanced IL-1β synthesis relative to the control cohort. Additionally, exposure to palmitate resulted in greater IL-1β synthesis in PBMCs isolated from youth with T2D versus controls (p<0.05. These differences in cytokine production corresponded to greater monocyte activation in the T2D cohort. Conclusion. These preliminary results suggest that cellular immune responses are exaggerated in T2D, particularly

  5. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

    Science.gov (United States)

    Oláhová, Monika; Hardy, Steven A; Hall, Julie; Yarham, John W; Haack, Tobias B; Wilson, William C; Alston, Charlotte L; He, Langping; Aznauryan, Erik; Brown, Ruth M; Brown, Garry K; Morris, Andrew A M; Mundy, Helen; Broomfield, Alex; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Moeslinger, Dorothea; Koch, Johannes; Stettner, Georg M; Bonnen, Penelope E; Prokisch, Holger; Lightowlers, Robert N; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M A; Taylor, Robert W

    2015-12-01

    Mitochondrial Complex IV [cytochrome c oxidase (COX)] deficiency is one of the most common respiratory chain defects in humans. The clinical phenotypes associated with COX deficiency include liver disease, cardiomyopathy and Leigh syndrome, a neurodegenerative disorder characterized by bilateral high signal lesions in the brainstem and basal ganglia. COX deficiency can result from mutations affecting many different mitochondrial proteins. The French-Canadian variant of COX-deficient Leigh syndrome is unique to the Saguenay-Lac-Saint-Jean region of Québec and is caused by a founder mutation in the LRPPRC gene. This encodes the leucine-rich pentatricopeptide repeat domain protein (LRPPRC), which is involved in post-transcriptional regulation of mitochondrial gene expression. Here, we present the clinical and molecular characterization of novel, recessive LRPPRC gene mutations, identified using whole exome and candidate gene sequencing. The 10 patients come from seven unrelated families of UK-Caucasian, UK-Pakistani, UK-Indian, Turkish and Iraqi origin. They resemble the French-Canadian Leigh syndrome patients in having intermittent severe lactic acidosis and early-onset neurodevelopmental problems with episodes of deterioration. In addition, many of our patients have had neonatal cardiomyopathy or congenital malformations, most commonly affecting the heart and the brain. All patients who were tested had isolated COX deficiency in skeletal muscle. Functional characterization of patients' fibroblasts and skeletal muscle homogenates showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits. We also identified a Complex I assembly defect in skeletal muscle, indicating different roles for LRPPRC in post-transcriptional regulation of mitochondrial mRNAs between tissues. Patient fibroblasts showed decreased steady-state levels

  6. [Epigenetics and obesity].

    Science.gov (United States)

    Casanello, Paola; Krause, Bernardo J; Castro-Rodríguez, José A; Uauy, Ricardo

    Current evidence supports the notion that exposure to various environmental conditions in early life may induce permanent changes in the epigenome that persist throughout the life-course. This article focuses on early changes associated with obesity in adult life. A review is presented on the factors that induce changes in whole genome (DNA) methylation in early life that are associated with adult onset obesity and related disorders. In contrast, reversal of epigenetic changes associated with weight loss in obese subjects has not been demonstrated. This contrasts with well-established associations found between obesity related DNA methylation patterns at birth and adult onset obesity and diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity and assess the effects of interventions in early life that may delay or prevent obesity in early life. This might contribute to lower the obesity-related burden of death and disability at the population level. The available evidence indicates that epigenetic marks are in fact modifiable, based on modifications in the intrauterine environment and changes in food intake, physical activity and dietary patterns patterns during pregnancy and early years of adult life. This offers the opportunity to intervene before conception, during pregnancy, infancy, childhood, and also in later life. There must be documentation on the best preventive actions in terms of diet and physical activity that will modify or revert the adverse epigenetic markers, thus preventing obesity and diabetes in suceptible individuals and populations. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Relationship between obesity and early failure of total knee prostheses

    OpenAIRE

    Bordini, B.; Stea, S.; Cremonini, S.; Viceconti, M.; Palma, R.; Toni, A.

    2009-01-01

    Abstract Background Obesity is a risk factor for knee arthritis. Total knee arthroplasty is the definitive surgical treatment of this disease. Therefore, a high percentage of subjects treated are overweight. Since 2000 in the Emilia-Romagna Region the Register of Orthopedic Prosthetic Implantology, RIPO, has recorded data of all the primary and revision operations performed on the knee; height and weight of patients at the time of surgery have also been recorded. Methods To understand how ove...

  8. Circulating MicroRNAs as Novel Diagnostic Biomarkers for Very Early-onset (≤40 years) Coronary Artery Disease

    Institute of Scientific and Technical Information of China (English)

    DU Ying; SUN Jing; DONG Qian; LIU Geng; LI JianJun; YANG Sheng Hua; LI Sha; CUI ChuanJue; ZHANG Yan; ZHUChengGang; GUO YuanLin; WU NaQiong; GAO Ying

    2016-01-01

    ObjectiveVery early-onset coronary artery disease (CAD) is a great challengein cardiovascular medicine throughout the world, especially regarding its early diagnosis. This study explored whether circulating microRNAs (miRNAs) could be used as potential biomarkers for patients with very early-onset CAD. MethodsWe performed an initial screening of miRNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age- and sex-matched normal controls. For further confirmation, we prospectively examined the miRNAs selected from 40 patientswithvery early-onset CAD and 40 angiography-normal controls. ResultsA total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysisof the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p exhibited significantly decreased expression in patients compared with that in controls (P<0.05).The areas under the receiver operating characteristic curve for these miRNAs were 0.824 (95% CI, 0.731-0.917;P<0.001), 0.758 (95%CI, 0.651-0.864;P<0.001), 0.753 (95% CI, 0.643-0.863;P<0.001), and 0.782 (95% CI, 0.680-0.884;P<0.001), respectively, in the validation set. ConclusionTo our knowledge, this isan advanced study to report about four serum miRNAs (miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p) that could be used as novel biomarkers for the diagnosis of very early-onset CAD.

  9. Developmental Origins of Common Disease: Epigenetic Contributions to Obesity.

    Science.gov (United States)

    Kappil, Maya; Wright, Robert O; Sanders, Alison P

    2016-08-31

    The perinatal period is a window of susceptibility for later life disease. Recent epigenetic findings are beginning to increase our understanding of the molecular mechanisms that may contribute to the programming of obesity. This review summarizes recent evidence that supports the role of epigenetically mediated early life programming in the later onset of obesity. Establishing such links between environmental exposures and modifiable molecular changes ultimately holds promise to inform interventional efforts toward alleviating the environmentally mediated onset of obesity.

  10. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  11. Physical activity, sedentary behaviour and energy balance in the preschool child: opportunities for early obesity prevention.

    Science.gov (United States)

    Reilly, John J

    2008-08-01

    Prevalence of obesity in preschool children has increased dramatically in recent years. The preschool years (age 3-6 years) have been regarded as critical for the programming of energy balance, via the concept of early 'adiposity rebound'. Children who undergo early adiposity rebound are at increased risk of later obesity. Recent evidence suggests that associations between timing of adiposity rebound and later obesity may not reflect programming, but might denote that 'obesogenic' growth trajectories are often established by the preschool period. Studies of objectively-measured physical activity and sedentary behaviour in preschool children show that levels of physical activity are typically low and sedentary behaviour high. The review of evidence presented here is supportive of the hypothesis that physical activity is protective against obesity in the preschool period, and that sedentary behaviour, particularly television viewing, is obesogenic. Definitive evidence on dose-response relationships between physical activity, sedentary behaviour and obesity remain unclear. Dose-response evidence could be obtained fairly readily by intervention and longitudinal observational studies that use accelerometry in preschool children. The generalisability of much of the evidence base is limited and there is a need for research on the influence of physical activity and sedentary behaviour in the preschool years in the aetiology of obesity in the developing world.

  12. Effects of maternal obesity on early and long-term outcomes for offspring

    Directory of Open Access Journals (Sweden)

    Stirrat LI

    2014-03-01

    Full Text Available Laura I Stirrat,1,2 Rebecca M Reynolds2,3 1Medical Research Council Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK; 2Tommy's Centre for Maternal and Fetal Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK; 3Endocrinology Unit, University/British Heart Foundation Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK Abstract: The prevalence of maternal obesity has increased significantly in recent years, and obesity is currently the most common comorbidity of pregnancy. Pregnancies of obese women are often defined as "high-risk" for the purposes of clinical care, with many well documented risks to the mother and developing baby. Maternal physiology and metabolism is dysregulated in the context of obesity, which may contribute to some of the adverse outcomes during pregnancy. Furthermore, maternal obesity has been hypothesized to cause harmful effects for the developing baby through "early life programming." This review will examine evidence from human studies for outcomes of offspring from obese women during pregnancy, during labor, during the neonatal period, and later in life. Keywords: pregnancy, short-term, physiology, metabolism, early life programming, neonatal complications, adverse intrauterine environment

  13. Early life factors associated with adult onset systemic lupus erythematosus (SLE in women

    Directory of Open Access Journals (Sweden)

    Christine Gibson Parks

    2016-03-01

    Full Text Available Background: Exposure early in life can influence adult disease and immunity, but the role of early life exposures in risk of SLE is not established.Methods: Women in a national cohort (ages 35-74 provided data on perinatal, maternal and sociodemographic factors, longest residence to age 14 and residential farm history of at least 12 months to age 18. Cases (N=124 reported SLE diagnosed age 16 years or older with use of disease modifying anti-rheumatic drugs. Non-cases (N=50,465 did not report lupus. Odds ratios (OR and 95% confidence intervals (CI were estimated by logistic regression adjusting for age and race/ethnicity. Results: SLE was associated with low birthweight (data on 84 cases and 36,477 non-cases; 4 weeks early vs. full-term; OR=3.4; 95%CI 1.6, 7.4. Considering longest childhood residence to age 14, SLE was associated with more frequent pesticide use (e.g., at least monthly OR=2.3; 95%CI 1.3, 4.1. SLE was associated with having an early and extended childhood farm residence (i.e., prenatal/maternal farm exposure and longest childhood farm residence; OR=1.8; 95%CI 1.1, 3.0 versus neither. In those with a childhood-only farm residence of 12+ months, agricultural pesticide use was associated with SLE, with the strongest associations for direct personal exposures. Conclusions: The association of SLE with premature birth is consistent with studies in other populations, and with an observed association with low birthweight. The associations of SLE with childhood exposure to residential and agricultural pesticides warrant further study.INTRODUCTIONSystemic lupus erythematosus (SLE is an autoimmune disease characterized by immune reactivity to multiple nuclear components and inflammation, resulting in diverse clinical features and multiple organ involvement. The causes of SLE are generally not known. Racial disparities and increased familial risk suggest a genetic predisposition. It is believed that environmental factors may contribute to

  14. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

    Directory of Open Access Journals (Sweden)

    José Oliveira

    Full Text Available Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD, particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2 and 4 (TLR4, major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified, genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02. Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

  15. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

    Science.gov (United States)

    Oliveira, José; Etain, Bruno; Lajnef, Mohamed; Hamdani, Nora; Bennabi, Meriem; Bengoufa, Djaouida; Sundaresh, Aparna; Chaabane, Arij Ben; Bellivier, Frank; Henry, Chantal; Kahn, Jean-Pierre; Charron, Dominique; Krishnamoorthy, Rajagopal; Leboyer, Marion; Tamouza, Ryad

    2015-01-01

    Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

  16. Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

    Science.gov (United States)

    Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

    2016-06-01

    It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases.

  17. Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

    NARCIS (Netherlands)

    Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M. M.; Olinga, Peter

    2014-01-01

    Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for

  18. Prevalidation of liver slices as a model for the early onset of liver fibrosis to test anti-fibrotic drugs

    NARCIS (Netherlands)

    Westra, Inge; Groothuis, Genoveva; Olinga, Peter

    2011-01-01

    Liver fibrosis is the progressive accumulation of connective tissue that affects the normal function of the liver and will eventually lead to liver cirrhosis. The aim of this study is to prevalidate precision-cut liver slices (PCLS) as an in vitro model to investigate the early onset of liver fibros

  19. Components of Negative Affect as Moderators of the Relationship between Early Drinking Onset and Binge-Drinking Behavior

    Science.gov (United States)

    McNamara, Robert S.; Swaim, Randall C.; Rosen, Lee A.

    2010-01-01

    This study examines the moderating effects of negative affect on the relationship between early drinking onset and binge-drinking behavior. Six hundred and thirty-five eleventh- and twelfth-grade students completed the American Drug and Alcohol Survey and reported on a variety of measures, including items assessing anxiety, anger, depression, age…

  20. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    Science.gov (United States)

    Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

  1. Slow identification of facial happiness in early adolescence predicts onset of depression during 8 years of follow-up

    NARCIS (Netherlands)

    Vrijen, Charlotte; Hartman, Catharina A.; Oldehinkel, Albertine J.

    2016-01-01

    Adolescent onset depression places a high burden on those who suffer from it, and is difficult to treat. An improved understanding of mechanisms underlying susceptibility to adolescent depression may be useful in early detection and as target in treatment. Facial emotion identification bias has been

  2. The Northern Ireland Early Onset Psychosis Study: Phenomenology and Co-Morbidity in the First 25 Cases

    Science.gov (United States)

    Fulton, Karen; Short, Mary; Harvey-Smith, Diane; Rushe, Teresa M.; Mulholland, Ciaran

    2008-01-01

    Diagnosing psychotic disorders in young people is difficult. High rates of co-morbidity may be one reason for this difficulty, but it may also be the case that current diagnostic categories are not the most useful when approaching the care of young people with psychotic symptoms. The Northern Ireland Early Onset Psychosis Study is the first study…

  3. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    Science.gov (United States)

    Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

  4. Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation

    DEFF Research Database (Denmark)

    Nielsen, Jonas Bille; Bentzen, Bo Hjorth; Olesen, Morten Salling;

    2014-01-01

    Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Disturbances in cardiac potassium conductance are considered as one of the disease mechanisms in AF. We aimed to investigate if mutations in potassium-channel β-subunits KCNE2 and KCNE3 are associated with early-onset lone AF. ...

  5. A Novel TTBK2 De Novo Mutation in a Danish Family with Early-Onset Spinocerebellar Ataxia

    DEFF Research Database (Denmark)

    Lindquist, Suzanne Granhøj; Møller, Lisbeth Birk; Dali, Christine I.

    2017-01-01

    examined. Exome sequencing was performed and a "movement disorders" gene panel consisting of approximately 200 genes was used for filtering, while Sanger sequencing was used for subsequent testing for the mutation in the family. Onset of symptoms in affected family members was in early childhood. A novel...

  6. Association analysis of the brain-derived neurotrophic factor gene polymorphisms with early-onset schizophrenia in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    易正辉

    2012-01-01

    Objective To investigate the relationship between the brain-derived neurotrophic factor (BDNF) gene Tag SNPs(rs 11030101 and rs6265) and early-onset schizophrenia in the Chinese Han population. Methods The tag single nucleotide polymorphisms (tag SNPs) rs11030101 and rs6265 in the BDNF gene were genotyped

  7. Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD.

    Science.gov (United States)

    Celedon, J C; Speizer, F E; Drazen, J M; Weiss, S T; Campbell, E J; Carey, V J; Reilly, J J; Ginns, L; Silverman, E K

    1999-11-01

    Bronchodilator responsiveness has been associated with a subsequent accelerated decline in forced expiratory volume in one second (FEV1). Therefore, bronchodilator responsiveness and total serum immunoglobulin E(IgE) levels were assessed in 184 adult first-degree relatives of probands with severe early-onset chronic obstructive pulmonary disease (COPD) and a control group. Greater bronchodilator responsiveness was found among current smokers or exsmokers who were first-degree relatives of early-onset COPD probands than in currently or exsmoking controls, expressed as increase in FEV1 as a percentage of baseline (5.8+/-8.1 versus 2.9+/-5.1%, p<0.01), absolute increase in FEV1 from baseline (120+/-130 versus 60+/-110 mL, p<0.05), and increase in FEV1 as a percentage of the predicted value (3.6:4.1 versus 2.2+/-3.9%, p<0.05). However, elevated total serum IgE levels were not found in first-degree relatives of early-onset COPD probands compared with control subjects. The increased bronchodilator responsiveness among currently smoking/exsmoking first-degree relatives of early-onset COPD probands suggests that these individuals may have enhanced susceptibility to the detrimental effects of cigarette smoking.

  8. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    Science.gov (United States)

    Nieto, Rebeca Garcia; Castellanos, F. Xavier

    2011-01-01

    Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric…

  9. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease

    NARCIS (Netherlands)

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T; Zaal, Kristien; Chandrasekharappa, Settara C; P Hanson, Eric; Yu, Zhen; Mullikin, James C; Hasni, Sarfaraz A; Wertz, Ingrid E; Ombrello, Amanda K; Stone, Deborah L; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K; Leavis, Helen L; van Royen, Annet; Sibley, Cailin; Batu, Ezgi D; Gül, Ahmet; Siegel, Richard M; Boehm, Manfred; Milner, Joshua D; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M; Kastner, Daniel L; Aksentijevich, Ivona

    2015-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflamma

  10. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    Science.gov (United States)

    Nieto, Rebeca Garcia; Castellanos, F. Xavier

    2011-01-01

    Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric…

  11. "I Need a Cigarette"--The Effects of Cigarette Smoking on Depression and Anxiety of Youth with Early Onset Schizophrenia

    Science.gov (United States)

    Chen, Ya-Ling; Rittner, Barbara; Maguin, Eugene; Dziadaszek, Shannon

    2017-01-01

    The aim of this research was to examine effects of cigarette smoking on depression and anxiety among children and adolescents (youth) with early onset schizophrenia and/or psychosis. Data were obtained from the national evaluation of the Comprehensive Community Mental Health Services for Children and Their Families Program (CMHS Program). Cubic…

  12. Two novel mutations in the GDAP1 and PRX genes in early onset Charcot-Marie-Tooth syndrome.

    Science.gov (United States)

    Auer-Grumbach, M; Fischer, C; Papić, L; John, E; Plecko, B; Bittner, R E; Bernert, G; Pieber, T R; Miltenberger, G; Schwarz, R; Windpassinger, C; Grill, F; Timmerman, V; Speicher, M R; Janecke, A R

    2008-02-01

    Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested.

  13. Involvement of lysosomal dysfunction in autophagosome accumulation and early pathologies in adipose tissue of obese mice.

    Science.gov (United States)

    Mizunoe, Yuhei; Sudo, Yuka; Okita, Naoyuki; Hiraoka, Hidenori; Mikami, Kentaro; Narahara, Tomohiro; Negishi, Arisa; Yoshida, Miki; Higashibata, Rikako; Watanabe, Shukoh; Kaneko, Hiroki; Natori, Daiki; Furuichi, Takuma; Yasukawa, Hiromine; Kobayashi, Masaki; Higami, Yoshikazu

    2017-04-03

    Whether obesity accelerates or suppresses autophagy in adipose tissue is still debatable. To clarify dysregulation of autophagy and its role in pathologies of obese adipose tissue, we focused on lysosomal function, protease maturation and activity, both in vivo and in vitro. First, we showed that autophagosome formation was accelerated, but autophagic clearance was impaired in obese adipose tissue. We also found protein and activity levels of CTSL (cathepsin L) were suppressed in obese adipose tissue, while the activity of CTSB (cathepsin B) was significantly enhanced. Moreover, cellular senescence and inflammasomes were activated in obese adipose tissue. In 3T3L1 adipocytes, downregulation of CTSL deteriorated autophagic clearance, upregulated expression of CTSB, promoted cellular senescence and activated inflammasomes. Upregulation of CTSB promoted additional activation of inflammasomes. Therefore, we suggest lysosomal dysfunction observed in obese adipose tissue leads to lower autophagic clearance, resulting in autophagosome accumulation. Simultaneously, lysosomal abnormalities, including deteriorated CTSL function and compensatory activation of CTSB, caused cellular senescence and inflammasome activation. Our findings strongly suggest lysosomal dysfunction is involved in early pathologies of obese adipose tissue.

  14. Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status.

    Science.gov (United States)

    da Luz, Felipe Q; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A; Swinbourne, Jessica; da Silva, Dhiordan C; da S Oliveira, Margareth

    2017-02-28

    Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants-53 with morbid obesity and 58 of normal weight-were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight.

  15. Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status

    Science.gov (United States)

    da Luz, Felipe Q.; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A.; Swinbourne, Jessica; da Silva, Dhiordan C.; da S. Oliveira, Margareth

    2017-01-01

    Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants—53 with morbid obesity and 58 of normal weight—were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight. PMID:28264484

  16. Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats.

    Science.gov (United States)

    Llarena, Marta; Andrade, Fernando; Hasnaoui, Mounia; Portillo, María P; Pérez-Matute, Patricia; Arbones-Mainar, Jose M; Hijona, Elizabeth; Villanueva-Millán, María Jesús; Aguirre, Leixuri; Carpéné, Christian; Aldámiz-Echevarría, Luis

    2016-09-01

    Obesity-associated nephropathy is considered to be a leading cause of end-stage renal disease. Resveratrol supplementation represents a promising therapy to attenuate kidney injury, but the poor solubility and limited bioavailability of this polyphenol limits its use in dietary intervention. Piceatannol, a resveratrol analogue, has been suggested as a better option. In this study, we aimed to provide evidence of a preventive action of piceatannol in very early stages of obesity-associated nephropathy. Thirty obese Zucker rats were divided into three experimental groups: one control and two groups orally treated for 6 weeks with 15 and 45 mg piceatannol/kg body weight/day. Enzyme-linked immunosorbent assays (ELISA) were used to determine renal and urinary kidney injury molecule-1 (Kim-1), renal fibrosis markers (transforming growth factor β1 and fibronectin) and renal sirtuin-1 protein. Oxidative stress was assessed in the kidney by measuring lipid peroxidation and nitrosative stress (thiobarbituric acid reactive substrates and 3-nitrotyrosine levels, respectively) together with the activity of the antioxidant enzyme superoxide dismutase. Renal fatty acids profile analysis was performed by thin-layer and gas chromatography. Piceatannol-treated rats displayed lower levels of urinary and renal Kim-1. Renal fibrosis biomarkers and lipid peroxidation exhibited a tendency to decrease in the piceatannol-treated groups. Piceatannol treatment did not modify superoxide dismutase activity or sirtuin-1 protein levels, while it seemed to increase the levels of polyunsaturated and omega-6 polyunsaturated fatty acids in the kidneys. Our findings suggest a mild renoprotective effect of piceatannol in obese Zucker rats and the need of intervention at early stages of renal damage.

  17. Early Onset of Industrial-Era Warming Across the Oceans and Continents

    Science.gov (United States)

    Abram, N.; McGregor, H. V.; Tierney, J. E.; Evans, M. N.; McKay, N.; Kaufman, D. S.; Pages 2k Consortium*, T.

    2016-12-01

    The evolution of industrial-era warming provides critical context for future climate change, and has fundamental importance for determining climate sensitivity and the processes that control regional warming. Palaeoclimate data from the Common Era - a period when natural and anthropogenic climate forcings are reasonably well constrained - provide valuable perspectives on anthropogenic greenhouse warming, but have focused mainly on the Northern Hemisphere using records derived primarily from terrestrial settings. Given the importance of the oceans in determining the pace and regional structure of climate changes, it is essential to extend our palaeoclimate assessments to determine how regional-scale warming developed in the oceans and over land during the Industrial Era. Here we use post-1500CE palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-19th Century, and was near-synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests greenhouse forcing of industrial-era warming commenced as early as the mid-19th Century, and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change, and in some regions 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial variability. *PAGES 2k Consortium authors are: Kaustubh Thirumalai, Belen Martrat, Hugues Goosse, Steven J. Phipps, Eric J. Steig, K. Halimeda Kilbourne, Casey P. Saenger, Jens Zinke, Guillaume Leduc, Jason A. Addison, P. Graham Mortyn, Marit-Solveig Seidenkrantz, Marie-Alexandrine Sicre, Kandasamy Selvaraj, Helena L. Filipsson, Raphael

  18. [Cord blood procalcitonin in the assessment of early-onset neonatal sepsis].

    Science.gov (United States)

    Oria de Rueda Salguero, Olivia; Beceiro Mosquera, José; Barrionuevo González, Marta; Ripalda Crespo, María Jesús; Olivas López de Soria, Cristina

    2017-08-01

    Early diagnosis of early-onset neonatal sepsis (EONS) is essential to reduce morbidity and mortality. Procalcitonin (PCT) in cord blood could provide a diagnosis of infected patients from birth. To study the usefulness and safety of a procedure for the evaluation of newborns at risk of EONS, based on the determination of PCT in cord blood. Neonates with infectious risk factors, born in our hospital from October 2013 to January 2015 were included. They were processed according to an algorithm based on the values of cord blood procalcitonin (< 0.6ng/ml versus ≥0.6ng/ml). They were later classified as proved infection, probable, or no infection. Of the 2,519 infants born in the study period, 136 met inclusion criteria. None of 120 cases with PCT<0.6ng/ml in cord blood developed EONS (100% negative predictive value). On the other hand, of the 16 cases with PCT ≥0.6ng/ml, 10 were proven or probably infected (62.5% positive predictive value). The sensitivity of the PCT against infection was 100%, with a specificity of 95.2% (area under the receiver operator curve 0.969). The incidence of infection in the study group was 7.4%, and 26.1% in cases with maternal chorioamnionitis. 21 newborn (15.4%) received antibiotic therapy. The studied protocol has shown to be effective and safe to differentiate between patients with increased risk of developing an EONS, in those where the diagnostic and therapeutic approach was more interventionist, versus those with less likelihood of sepsis, who would benefit from a more conservative management. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Placental Nkx2-5 and target gene expression in early-onset and severe preeclampsia.

    Science.gov (United States)

    Rivers, Elena R; Horton, Anthony J; Hawk, Angela F; Favre, Elizabeth G; Senf, Katherine M; Nietert, Paul J; Chang, Eugene Y; Foley, Ann C; Robinson, Christopher J; Lee, Kyu-Ho

    2014-11-01

    Preeclampsia (PE) affects 2-8% of pregnancies worldwide and is a significant source of maternal and neonatal morbidity and mortality. However, the mechanisms underlying PE are poorly understood and major questions regarding etiology and risk factors remain to be addressed. Our objective was to examine whether abnormal expression of the cardiovascular developmental transcription factor, Nkx2-5, was associated with early onset and severe preeclampsia (EOSPE). Using qPCR and immunohistochemical assay, we examined expression of Nkx2-5 and target gene expression in EOSPE and control placental tissue. We tested resulting mechanistic hypotheses in cultured cells using shRNA knockdown, qPCR, and western blot. Nkx2-5 is highly expressed in racially disparate fashion (Caucasians > African Americans) in a subset of early EOSPE placentae. Nkx2-5 mRNA expression is highly correlated (Caucasians > African Americans) to mRNA expression of the preeclampsia marker sFlt-1, and of the Nkx2-5 target and RNA splicing factor, Sam68. Knockdown of Sam68 expression in cultured cells significantly impacts sFlt-1 mRNA isoform generation in vitro, supporting a mechanistic hypothesis that Nkx2-5 impacts EOSPE severity in a subset of patients via upregulation of Sam68 to increase sFlt-1 expression. Expression of additional Nkx2-5 targets potentially regulating metabolic stress response is also elevated in a racially disparate fashion in EOSPE. Expression of Nkx2-5 and its target genes may directly influence the genesis and racially disparate severity, and define a mechanistically distinct subclass of EOSPE.

  20. Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis.

    Science.gov (United States)

    Cizmeci, Mehmet Nevzat; Kara, Semra; Kanburoglu, Mehmet Kenan; Simavli, Serap; Duvan, Candan Iltemur; Tatli, Mustafa Mansur

    2014-03-01

    Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism's access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min-max: 118.1-8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis. Copyright © 2013 Elsevier Ltd. All rights reserved.