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Sample records for early onset obesity

  1. Biologically inactive leptin and early-onset extreme obesity.

    PubMed

    Wabitsch, Martin; Funcke, Jan-Bernd; Lennerz, Belinda; Kuhnle-Krahl, Ursula; Lahr, Georgia; Debatin, Klaus-Michael; Vatter, Petra; Gierschik, Peter; Moepps, Barbara; Fischer-Posovszky, Pamela

    2015-01-01

    Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss. PMID:25551525

  2. Bone Characteristics and Their Determinants in Adolescents and Young Adults with Early-Onset Severe Obesity.

    PubMed

    Viljakainen, H T; Valta, H; Lipsanen-Nyman, M; Saukkonen, T; Kajantie, E; Andersson, S; Mäkitie, O

    2015-10-01

    Childhood obesity is associated with compromised bone health. We studied bone characteristics and their determinants in obese young adults. The study included 68 subjects with early-onset severe obesity and 73 normal-weight controls. Data on physical activity (PA), diet and smoking were collected. Bone characteristics were measured using peripheral QCT. The obese and control subjects were similar in age (mean 19.6 ± 2.6 years) and height but BMIs differed (39.7 and 22.6 kg/m(2)). A clustering of unhealthy lifestyles was marked: Obese subjects reported less supervised PA in childhood, adolescence and currently (p < 0.03) and were more likely to smoke (p = 0.005), and had a lower healthy eating index (HEI) (p = 0.007) but similar alcohol consumption compared with controls. In obese women, all crude bone characteristics were higher than in controls; in men, the differences were smaller. Associations of lifestyle factors with bone characteristics were tested using partial correlations. Independently of BMI, supervised PA in adolescence and alcohol consumption were related positively to bone characteristics in both groups. HEI associated positively with bone characteristics only in controls, while smoking was a positive determinant of bone characteristics only in obese subjects. The multivariate model showed that the contribution of lifestyle factors to bone characteristics was minimal compared with BMI. Early-onset obesity is accompanied by poor dietary quality, sedentary lifestyle, and more frequent smoking, but the overall contribution of these lifestyle factors to bone strength is limited. Bone strength is more likely to be compromised in men and in unloaded bone sites in subjects with early-onset severe obesity. The impact of obesity-related endocrine changes on bone characteristics need to be evaluated in future studies. PMID:26139232

  3. Early onset of puberty in an obese boy with Klinefelter syndrome

    PubMed Central

    Cho, Byoung-Wook; Kwon, Seung-Eun; Kim, Soon-Ki; Lee, Taek; Han, Jee-Young

    2016-01-01

    Klinefelter syndrome (KS) is one of the most common disease entities characterized by X-chromosomal aberration causing the primary hypogonadism in adult men. Patients with KS seem to be typically characterized by tall, slender bodies with delayed puberty and hypergonadotropic hypogonadism. However, it has been known that they have a broad spectrum of phenotype ranging from almost normal external appearances to typical phenotype. Only 25% KS Patients are ever diagnosed because KS remains unrecognized. Also, boys with KS have an onset of pubertal development within the normal range, not delayed onset of puberty. Adolescents with KS are generally diagnosed as having the lack of pubertal progress. Early detection of KS can be difficult without awareness. We report an unusual case of early onset of puberty in obese boy with KS who presented with a unilateral non-hormone secreting testicular teratoma. PMID:27104178

  4. Early onset of puberty in an obese boy with Klinefelter syndrome.

    PubMed

    Cho, Byoung-Wook; Kwon, Seung-Eun; Kim, Soon-Ki; Lee, Taek; Han, Jee-Young; Lee, Ji-Eun

    2016-03-01

    Klinefelter syndrome (KS) is one of the most common disease entities characterized by X-chromosomal aberration causing the primary hypogonadism in adult men. Patients with KS seem to be typically characterized by tall, slender bodies with delayed puberty and hypergonadotropic hypogonadism. However, it has been known that they have a broad spectrum of phenotype ranging from almost normal external appearances to typical phenotype. Only 25% KS Patients are ever diagnosed because KS remains unrecognized. Also, boys with KS have an onset of pubertal development within the normal range, not delayed onset of puberty. Adolescents with KS are generally diagnosed as having the lack of pubertal progress. Early detection of KS can be difficult without awareness. We report an unusual case of early onset of puberty in obese boy with KS who presented with a unilateral non-hormone secreting testicular teratoma. PMID:27104178

  5. Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice.

    PubMed

    Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

    2016-01-01

    Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

  6. Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

    PubMed Central

    Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

    2016-01-01

    Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

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

    PubMed

    Alaimo, Joseph T; Hahn, Natalie C; Hahn, Natalie H; Mullegama, Sureni V; Elsea, Sarah H

    2014-01-01

    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. PMID:25127133

  8. Early-Onset Alzheimer's

    MedlinePlus

    MENU Return to Web version Early-Onset Alzheimer’s What is early-onset Alzheimer’s disease? Early-onset Alzheimer’s disease is when Alzheimer’s affects a person younger than 65 years of age. People ...

  9. Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in Finland

    PubMed Central

    Armenio, Miriam; Pekkinen, Minna; Pettersson, Maria; Valta, Helena; Lipsanen-Nyman, Marita; Mäkitie, Outi; Lindstrand, Anna

    2015-01-01

    Background The salivary α-amylase locus (AMY1) is located in a highly polymorphic multi allelic copy number variable chromosomal region. A recent report identified an association between AMY1 copy numbers and BMI in common obesity. The present study investigated the relationship between AMY1 copy number, BMI and serum amylase in childhood-onset obesity. Patients Sixty-one subjects with a history of childhood-onset obesity (mean age 19.1 years, 54% males) and 71 matched controls (19.8 yrs, 45% males) were included. All anthropometric measures were greater in the obese; their mean BMI was 40 kg/m2 (range 25-62 kg/m2) compared with 23 kg/m2 in the controls (15-32 kg/m2). Results Mean AMY1 copy numbers did not differ between the obese and control subjects, but gender differences were observed; obese men showed the highest and obese women the lowest number of AMY1 copies (p=0.045). Further, only in affected females, AMY1 copy number correlated significantly with whole body fat percent (r=-0.512, p=0.013) and BMI (r=-0.416, p=0.025). Finally, a clear linear association between AMY1 copy number and serum salivary amylase was observed in all subgroups but again differences existed between obese males and females. Conclusions In conclusion, our findings suggest that AMY1 copy number differences play a role in childhood-onset obesity but the effect differs between males and females. Further studies in larger cohorts are needed to confirm these observations. PMID:26132294

  10. The juvenile-onset, adolescent-onset and adult-onset obese.

    PubMed

    Garn, S M; Sullivan, T V; Hawthorne, V M

    1991-02-01

    As shown in more than 8000 proband-parent pairs derived from a total-community sample and followed in longitudinal fashion, the 5-year incidence of obesity (new cases per 5-year period) approximates 8 percent for the juvenile-onset, adolescent-onset and adult-onset obese alike. Parents of juvenile-onset (ages 5-9), adolescent-onset (10-19) and adult-onset obese (20-39) tend to be of above-average fatness level, +0.25Z scores, overall, regardless of the age at onset of obesity in their progeny. Except for the parents of the juvenile-onset obese, educational level of the parents tends to be below average for the sample as a whole. These new data acquired in longitudinal context and explored in retrospective-prospective fashion do not substantiate the notion that different onset ages of obesity indicate separate etiologies and different family constellations. PMID:2040547

  11. Binge eating onset in obese patients with binge eating disorder.

    PubMed

    Marcus, M D; Moulton, M M; Greeno, C G

    1995-01-01

    In this study we examined whether obese women with binge eating disorder (BED) reporting earlier onset binge eating differed from those with later onset binge eating on salient clinical parameters. Subjects were 112 women who sought treatment for BED. Subjects with early (< or = age 18) and later onset (> age 18) did not differ in age, weight, body mass index, or severity of binge eating. Participants were interviewed using the Eating Disorder Examination (EDE) and the Structured Clinical Interview for DSM-III-R, and completed a weight and diet history questionnaire. Early-onset binge eaters were more likely than those with later-onset to binge-eat before dieting, to have early onset of obesity and dieting, to have longer binge-free periods, and more paternal obesity and binge eating. Early-onset binge eaters also reported more eating-disorders psychopathology, and they were more likely to report a lifetime history of bulimia nervosa and DSM-III-R mood disorder. These data suggest that there are marked differences among BED patients presenting for treatment. Further research is needed to determine whether these differences reflect a different etiology or have implications for treatment. PMID:8820527

  12. Onset Age of Obesity and Variables of Personality and Biography.

    ERIC Educational Resources Information Center

    Steinberg, Carol

    Three hypotheses derived from Hilde Bruch's formulations regarding onset differences among the obese were tested. In Bruch's theory, adult-onset, or reactive, obesity is a result of psychological trauma; the individual uses eating as a defense against anxiety and depression. Child-onset, or developmental, obesity results from a mixture of…

  13. A new patient with a terminal de novo 2p25.3 deletion of 1.9 Mb associated with early-onset of obesity, intellectual disabilities and hyperkinetic disorder

    PubMed Central

    2014-01-01

    Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH analysis, have been reported in about 18 patients sharing common clinical features represented by early-onset obesity/ overweightness associated with intellectual disabilities (ID) and behavioural troubles. This observations led to hypothesize that 2p subtelomeric deletion should be associated with syndromic obesity and MYT1L became the main candidate gene for ID and obesity since it is deleted or disrupted in all hitherto published cases. Here we described a 2p25.3 de novo terminal deletion of 1.9 Mb, of paternal origin, detected by array-CGH analysis in a girl of 4.4 years with a distinctive phenotype consisting of early-onset of obesity associated with moderate ID, and hyperkinetic disorder. The deletion disrupted MYT1L and encompassed five other OMIM genes, ACP1, TMEM18, SNTG2, TPO, and PXDN. Here, we discuss the combined functional effects of additional haploinsufficient genes, that may concur with heterozygous deletion of MYT1L, in the aetiology for syndromic obesity associated with 2p25.5 subtelomeric deletion. PMID:25126114

  14. Early-Onset Neonatal Sepsis

    PubMed Central

    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

  15. Obesity and late-onset hypogonadism.

    PubMed

    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. PMID:26143633

  16. Predictors of Early Alcohol Drinking Onset

    ERIC Educational Resources Information Center

    Dooley, David; Prause, JoAnn

    2007-01-01

    Early alcohol drinking onset (ADO) has been implicated as a cause of adult alcohol disorder inviting interventions that target the causes of ADO. This study explores the precursors of early ADO using variables measured before drinking onset, reaching back to the mothers of the respondents. The sample consists of children of the women respondents…

  17. Epidemiology of early-onset schizophrenia.

    PubMed

    Häfner, H; Nowotny, B

    1995-01-01

    A total of 232 (84%) first episodes of schizophrenia from our epidemiologically defined ABC sample (Age, Beginning and Course) were retrospectively assessed with regard to the onset and early course of the disorder. In a follow-up study a representative subgroup (n = 133) was prospectively examined in five cross sections over 3 years from first admission on. Population-based incidence rates for 5-year age groups comprising a range of < 10 - < 60 years were calculated on the basis of two definitions of onset: first sign of disorder and first psychotic symptom. In 40% of adult patients who had been admitted with a first schizophrenic episode after age 20 years the prodromal phase, in 11% the psychotic prephase, began before that age. This demonstrates that schizophrenia often begins in an age period in which the social and cognitive development and brain maturation are still unfinished. Early-onset schizophrenias (< or = 20 years) were compared with a medium-onset group (21 - < 35 years) and a late-onset group (35 - < 60 years) with regard to age and type of onset, early symptom-related course, social development and social course. The number of schizophrenia-specific positive and negative syndromes in early-onset schizophrenia is comparable to that of higher age groups. However, neurotic syndromes, emotional disorders and conduct disorders are most frequent in younger patients, especially in young men. Paranoid syndromes seem to prevail in late-onset schizophrenia, whereas less differentiated positive syndromes, such as delusional mood, are more frequent in the youngest age group. An earlier onset of schizophrenia has more severe social consequences than onset in adults, because it interrupts the cognitive and social development at an earlier stage. The worse social course of schizophrenia in men compared with women cannot be related to a more severe symptomatology, but to the earlier age at onset and the impairment or stagnation of social ascent at an earlier stage

  18. Early Childhood Obesity is Associated with Compromised Cerebellar Development

    PubMed Central

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS — a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric MRI images. Individuals with PWS (n=16) and EMO (n=12) had smaller cerebellar volumes than a control group of 15 siblings (p=0.02 control vs. EMO; p=0.0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 ± 25; EMO 81 ± 19; and Controls 112 ± 13 (p<0.0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development. PMID:19437203

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

    PubMed Central

    McTigue, Kathleen M.; Stepp, Stephanie D.; Moore, Charity G.; Cohen, Elan D.; Hipwell, Alison E.; Loeber, Rolf; Kuller, Lewis H.

    2015-01-01

    Objective To understand the incidence and persistence of severe obesity (≥1.2× 95th BMI percentile-for-age) in girls across the transition to adolescence, and map developmental trajectories of adolescent severe obesity in a high-risk sample. Methods We examined ten years of prospectively collected data from a population sample of urban girls (n=2,226; 53% African American, aged 7–10 in 2003–2004). We determined severe obesity prevalence and incidence by age. Logistic regression evaluated for secular trend in the association between age and severe obesity prevalence. Unconditional latent growth curve models (LGCMs) compared BMI development through the adolescence transition between girls with severe obesity versus healthy BMI. Results Severe obesity prevalence was 8.3% at age 7–10 and 10.1% at age 16–19 (white: 5.9%; African American: 13.2%; p<0.001). Age-specific prevalence increased more rapidly among the latest-born, versus earliest-born, girls (p=0.034). Incidence was 1.3% to 2.4% annually. When we compared 12–15 year-old girls with severe obesity versus healthy BMI, average body weight was already distinct 5 years earlier (16.5 kg versus 25.7 kg; p<0.001) and the BMI difference between groups increased annually. LCGMs between ages 7–10 and 11–14 indicated an increase of 3.32 kg/m2 in the healthy-BMI group and 8.50 kg/m2 in the severe obesity group, a 2.6-fold difference. 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. PMID:26509122

  20. Cognitive dysfunction in early onset parkinsonism.

    PubMed

    Tsai, C H; Lu, C S; Hua, M S; Lo, W L; Lo, S K

    1994-01-01

    Cognitive functions of 24 patients with early onset parkinsonism (age of onset before 40 years) and 24 controls were investigated by a battery of neuropsychological tests. Patients were shown to be impaired in performance IQ (PIQ), conceptual ability and regulation behavior, memory, visuospatial perception, and manual dexterity. Patients were also shown to have a higher Zung Depression score. However, analysis of the testing scores appeared to indicate that only a small portion of poor performance on neuropsychological tests are depression related. The results demonstrated that patients with early onset parkinsonism, in whom the factor of aging is not as important, still show cognitive dysfunction and suggested that Parkinson's disease itself can cause cognitive impairment. PMID:8178636

  1. [Brain imaging in early onset anorexia].

    PubMed

    Bargiacchi, A

    2014-05-01

    Structural and functional brain alterations in the structures involved in taste processing, emotions regulation and the reward system have been described in anorexia nervosa. The neurodevelopmental origin of this disorder has been recently discussed. In this article, brain-imaging data in early onset anorexia nervosa will be recalled and the relationship between clinical symptoms, normal brain maturation and brain imaging data in adolescents and adults will be discussed. PMID:24726667

  2. Elevated Reward Region Responsivity Predicts Future Substance Use Onset But Not Overweight/Obesity Onset

    PubMed Central

    Stice, Eric; Yokum, Sonja; Burger, Kyle S.

    2013-01-01

    Background We tested the hypotheses that adolescents who show elevated reward region responsivity are at increased risk for initial onset of overweight/obesity and substance use, which is important because there have been no such prospective tests of the reward surfeit model of these motivated behaviors. Methods One hundred sixty-two adolescents (mean age = 15.3 ± 1.06 years) with healthy weights (mean body mass index = 20.8 ± 1.90) completed functional magnetic resonance imaging paradigms that assessed neural activation in response to receipt and anticipated receipt of palatable food and monetary reward; body fat and substance use were assessed at baseline and 1-year follow-up. Results Elevated caudate (r = .31, p < .001) and putamen (r = .28, p < .001) response to monetary reward predicted substance use onset over 1-year follow-up, but reward circuitry responsivity did not predict future overweight/obesity onset. Adolescents who reported substance use versus abstinence at baseline also showed less caudate (r = –.31, p < .001) response to monetary reward. Discussion Results show that hyper-responsivity of reward circuitry increases risk for future substance use onset, providing novel support for the reward surfeit model. Results also imply that even a limited substance use history was associated with reduced reward region responsivity, extending results from studies that compared substance-dependent individuals with healthy control subjects and suggesting that substance use downregulates reward circuitry. However, aberrant reward region responsivity did not predict initial unhealthy weight gain. PMID:23312561

  3. Nonsurgical Management of Early-onset Scoliosis.

    PubMed

    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. PMID:26306805

  4. Obesity in Childhood Cancer Survivors: Call for Early Weight Management.

    PubMed

    Zhang, Fang Fang; Parsons, Susan K

    2015-09-01

    A high prevalence of obesity and cardiometabolic conditions has been increasingly recognized in childhood cancer survivors. In particular, survivors of pediatric acute lymphoblastic leukemia have been found to be at risk of becoming overweight or obese early in treatment, with increases in weight maintained throughout treatment and beyond. Nutrition plays an important role in the etiology of obesity and cardiometabolic conditions and is among the few modifiable factors that can prevent or delay the early onset of these chronic conditions. However, nutritional intake in childhood cancer survivors has not been adequately examined and the evidence is built on data from small cohorts of survivors. In addition, the long-term impact of cancer diagnosis and treatment on survivors' nutritional intake as well as how survivors' nutritional intake is associated with chronic health conditions have not been well quantified in large-scale studies. Promoting family-based healthy lifestyles, preferably at a sensitive window of unhealthy weight gain, is a priority for preventing the early onset of obesity and cardiometabolic conditions in childhood cancer survivors. PMID:26374183

  5. Obstetric Outcome in Early and Late Onset Gestational Diabetes Mellitus.

    PubMed

    Easmin, S; Chowdhury, T A; Islam, M R; Beg, A; Jahan, M K; Latif, T; Dhar, S; Alam, M N; Akhter, M

    2015-07-01

    Obstetric outcome in early onset and late onset GDM was compared in a prospective study conducted at the Department of Obstetrics & Gynecology in BIRDEM, Dhaka, Bangladesh. A total 120 pregnant women were recruited purposively for the study in which 60 were early onset GDM and 60 were late onset GDM during study period of January 2008 to December 2009. Patients were followed up in different periods of gestation, during delivery and early postpartum period & findings were compared between two groups. BMI & family history of diabetes were significantly higher in early GDM group (p<0.05). Evidence of increased glycaemia was observed in early GDM group & difference of glycaemic status was statistically significant (p<0.05). Insulin was needed in 85% of early onset GDM and 55% in late onset GDM. There was also significant difference (p<0.05). In this study, 23.3% of early onset GDM group developed pre-eclampsia while in late onset GDM it was 10% and was statistically significant (p<0.05). Regarding intrapartum & postpartum complications - perineal tear, PPH wound infection, puerperal sepsis were more in early onset than late onset GDM group with no significant difference. Regarding foetal outcome, 8.3% early GDM group delivered asphyxiated baby in comparison to 3.3% in late GDM group. Twenty percent (20%) of early onset GDM group had to admit their babies in neonatal unit while in late onset group it was 5%. There was significant difference between two groups (p<0.05). Neonatal hypoglycaemia was also statistically significantly (p<0.05) higher in early GDM group. Neonatal hyper-bilirubinaemia, RDS, perinatal death was more in early onset GDM subjects. Early onset GDM subjects are high risk subgroup & have significant deleterious effect on maternal and perinatal outcome than late GDM groups. PMID:26329938

  6. Early-onset scoliosis: current treatment.

    PubMed

    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

  7. Early onset of lithium-associated hypothyroidism.

    PubMed Central

    Vincent, A; Baruch, P; Vincent, P

    1993-01-01

    In general practice, psychiatrists are confronted with the difficulty of structuring a rational design for the early detection of hypothyroidism. To determine the period during which a patient receiving lithium is most at risk of developing hypothyroidism, a retrospective study was conducted on the records of 154 patients at two general hospital lithium clinics from January 1980 to August 1991. Forty-two cases of hypothyroidism (clinical hypothyroidism and/or abnormally elevated levels of TSH) were detected. A significant difference was found between the onset of hypothyroidism and age (older patients developed more thyroid dysfunction), but no significant differences were found between thyroid abnormality and sex or diagnostic category and menopausal status, although trends were observed for the two former variables. This longitudinal study is the first to describe an outline of thyroid functioning in terms of the duration of treatment. Lithium-associated hypothyroidism develops most often during the first two years. Of the 42 cases of hypothyroidism, 16 were diagnosed within six months (38%), 23 within the first year (55%), and 31 two years (74%). Since thyroid functioning is an important parameter in the course of affective disorders, its close and frequent monitoring is mandatory during the first two years of treatment. PMID:8461286

  8. Early onset Alzheimer's disease and oxidative stress.

    PubMed

    Meraz-Ríos, Marco Antonio; Franco-Bocanegra, Diana; Toral Rios, Danira; Campos-Peña, Victoria

    2014-01-01

    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. PMID:24669286

  9. Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Rovet, Joanne F.; And Others

    1988-01-01

    Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

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

    PubMed

    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. PMID:25666100

  11. Genetics Home Reference: early-onset glaucoma

    MedlinePlus

    ... Glaucoma Genetic Testing Registry (2 links) Glaucoma, congenital Primary open angle glaucoma juvenile onset 1 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (2 links) ...

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

    PubMed

    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. PMID:23885012

  13. Co-Occurring Problems of Early Onset Persistent, Childhood Limited, and Adolescent Onset Conduct Problem Youth

    ERIC Educational Resources Information Center

    Barker, Edward D.; Oliver, Bonamy R.; Maughan, Barbara

    2010-01-01

    Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

  14. Impulsivity in Juvenile Delinquency: Differences among Early-Onset, Late-Onset, and Non-Offenders

    ERIC Educational Resources Information Center

    Carroll, Annemaree; Hemingway, Francene; Bower, Julie; Ashman, Adrian; Houghton, Stephen; Durkin, Kevin

    2006-01-01

    The present research investigated differences in levels of impulsivity among early-onset, late-onset, and non-offending adolescents. 129 adolescents (114 males, 15 females), of whom 86 were institutionalised (M age = 15.52 years) and 43 were regular school students (M age = 15.40 years) participated. Each participant completed the Adapted…

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

    ERIC Educational Resources Information Center

    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,…

  16. The short-term consequences of early onset cannabis use.

    PubMed

    Fergusson, D M; Lynskey, M T; Horwood, L J

    1996-08-01

    The associations between early onset (prior to 15 years of age) cannabis use and rates of mental health or adjustment problems during the period from 15 to 16 years of age were studied in a New Zealand birth cohort. Early onset cannabis users were at increased risks of later substance use behaviors, conduct/oppositional disorders, juvenile offending, severe truancy, school dropout, anxiety, depression, and suicidal ideation. Early cannabis users had odds of these outcomes ranging from 2.7 to 30.8 times higher than the odds for those who did not use cannabis prior to age 15. Most of the elevated risks of early onset users were explained by the fact that they were a high-risk groups of adolescents characterized by family disadvantages, early adjustment problems, and high affiliations with substance-using or delinquent peers. Nonetheless, even after adjustment for a wide range of confounding factors, early onset users had increased risks of later cannabis use. It is concluded that while most of the elevated risks of early onset users were explained by social, family, and individual characteristics of this group, early onset users were at increased risks of later cannabis use. PMID:8886945

  17. [Early assessment of overweight for preventing obesity].

    PubMed

    Négre, Véronique

    2015-12-01

    The overweight child should be detected as soon as possible to avoid the occurrence of a more severe obesity, source of early complications. Thus, it is essential to carefully follow the BMI curve in all children with particular attention to the age of the early adiposity rebound (between 1 and 5 years). Early rebound indicates predisposition, and represents a risk factor for later obesity. The announcement is not harmless and should avoid unnecessary judging or blaming the family outside rare situations of abuse. Overweight results from an energy imbalance favored by many risk factors often entangled. These predisposing factors are specific to the child (especially genetic and epigenetic origin) and environmental. Among these environmental factors, those occurring during pregnancy and the nutritional education (too permissive or too restrictive) represent targets for primary prevention. PMID:26979017

  18. Differences Between Early and Late Onset Adult Depression

    PubMed Central

    Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj; Gether, Ulrik; Kessing, Lars Vedel

    2011-01-01

    Background: It is unclear, whether age-of-onset identifies subgroups of depression. Aim: To assess the clinical presentation of depression with onset in the early adult age (18-30 years) as compared to depression with later onset (31-70 years). Method: A total number of 301 patients with first 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, 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 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 illness. Conclusion: Early adult onset of depression is associated with co-morbid personality deviances, whereas late onset is associated with environmental risk factors. PMID:21866230

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

    ERIC Educational Resources Information Center

    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…

  20. Early-onset Parkinson's disease and depression.

    PubMed

    Bertucci Filho, Délcio; Teive, Hélio A G; Werneck, Lineu C

    2007-03-01

    Patients with Parkinsons disease (PD) in whom symptoms start before the age of 45 years (EOPD) present different clinical characteristics from those with the late-onset form of the disease. The incidence of depression is believed to be greater in patients with EOPD than with the late-onset form of the disease, although there is no risk factor or marker for depression in patients with PD. We studied 45 patients with EOPD to define the frequency of depression and to identify possible differences between the groups with and without depression. Depression was diagnosed in 16 (35.5%) of the patients, a higher incidence than in the population at large but similar to the figure for late-onset Parkinson disease; 8 (50%) of the patients had mild depression, 4 (25%) moderate depression and 4 (25%) were in remission. There was no relationship between depression and any of the clinical characteristics of the disease, although the EOPD patients with depression presented earlier levodopa-related complications and were more affected on the Hoehn-Yahr, UPDRS and Schwab-England scales. PMID:17420818

  1. A comparative study of 470 cases of early-onset and late-onset schizophrenia.

    PubMed

    Howard, R; Castle, D; Wessely, S; Murray, R

    1993-09-01

    The presence or absence of 22 schizophrenic symptoms was recorded with the age at onset of illness in 470 patients with non-affective, non-organic psychoses. Positive and negative formal thought disorder, affective symptoms, inappropriate affect, delusions of grandiosity or passivity, primary delusions other than delusional perception, and thought insertion and withdrawal were all more common in early-onset cases (age at onset 44 years or less; n = 336). Persecutory delusions with and without hallucinations, organised delusions, and third-person, running commentary and accusatory or abusive auditory hallucinations were all more common in late-onset cases (age at onset 45 years or more; n = 134). There was no difference between cases of early and late onset in the prevalence of delusions of reference, bizarre delusions, delusional perception, or lack of insight. We conclude that although there are clinical similarities between cases of schizophrenia with early and late onset, there are sufficient differences between them to suggest that they are not phenotypically homogeneous. PMID:8401965

  2. Preventing Obesity Across Generations: Evidence for Early Life Intervention.

    PubMed

    Haire-Joshu, Debra; Tabak, Rachel

    2016-03-18

    To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life. PMID:26989828

  3. Chorioamnionitis and Culture-Confirmed Early-onset Neonatal Infections

    PubMed Central

    Wortham, Jonathan M.; Hansen, Nellie I.; Schrag, Stephanie J.; Hale, Ellen; Van Meurs, Krisa; Sánchez, Pablo J.; Cantey, Joseph B.; Faix, Roger; Poindexter, Brenda; Goldberg, Ronald; Bizzarro, Matthew; Frantz, Ivan; Das, Abhik; Benitz, William E.; Shane, Andi L.; Higgins, Rosemary; Stoll, Barbara J.

    2016-01-01

    Background Current guidelines for prevention of neonatal group B Streptococcal (GBS) disease recommend diagnostic evaluations and empiric antibiotic therapy for well-appearing, chorioamnionitis-exposed newborns. Some clinicians question these recommendations, citing the decline in early-onset GBS disease rates since widespread intrapartum antibiotic prophylaxis (IAP) implementation and potential antibiotic risks. We aimed to determine whether chorioamnionitis-exposed newborns with culture-confirmed early-onset infections can be asymptomatic at birth. Methods Multicenter, prospective surveillance for early-onset neonatal infections was conducted 2006–2009. Early-onset infection was defined as isolation of a pathogen from blood or cerebrospinal fluid collected ≤72 hours after birth. Maternal chorioamnionitis was defined by clinical diagnosis in the medical record or histologic diagnosis by placental pathology. Hospital records of newborns with early-onset infections born to mothers with chorioamnionitis were reviewed retrospectively to determine symptom onset. Results Early-onset infections were diagnosed in 389 of 396,586 live births, including 232 (60%) chorioamnionitis-exposed newborns. Records for 229 were reviewed; 29 (13%) had no documented symptoms within 6 hours of birth, including 21 (9%) who remained asymptomatic at 72 hours. IAP exposure did not differ significantly between asymptomatic and symptomatic infants (76% vs. 69%, p=0.52). Assuming complete guideline implementation, we estimated 60 to 1400 newborns would receive diagnostic evaluations and antibiotics for each infected, asymptomatic newborn, depending on chorioamnionitis prevalence. Conclusions Some infants born to mothers with chorioamnionitis may have no signs of sepsis at birth despite having culture-confirmed infections. Implementation of current clinical guidelines may result in early diagnosis, but large numbers of uninfected asymptomatic infants would be treated. PMID:26719293

  4. Early onset esophageal adenocarcinoma: a distinct molecular entity?

    PubMed Central

    van Nistelrooij, Anna M.J.; van Marion, Ronald; Biermann, Katharina; Spaander, Manon C.W.; van Lanschot, J. Jan B.; Wijnhoven, Bas P.L.; Dinjens, Winand N.M.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is typically diagnosed in elderly with a median age of 68 years. The incidence of EAC has been rising over the last decades, also among young adults. The aim of the study was to investigate whether early onset EAC is a distinct molecular entity. To identify early onset EACs, the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA) was searched. Twenty-eight tumors of patients aged ≤40 years were selected and matched with 27 tumors of patients aged ≥68 years. DNA was isolated from surgically resected specimen and sequenced on the Ion Torrent Personal Genome Machine with the Ion AmpliSeq Cancer Panel. No differences in mutational load between early onset and conventional EACs were observed (P=0.196). The most frequently mutated genes were TP53 (73%) and P16 (16%). Additional mutations in early onset EACs occurred exclusively in: APC, CDH1, CTNNB1, FGFR2, and STK11. In the conventional EACs additional mutations were exclusively identified in: ABL1, FBXW7, GNA11, GNAS, KRAS, MET, SMAD4, and VHL. Additional mutations besides TP53 and P16 seem to occur in different genes related to cell fate pathways for early onset EACs, while the additional mutations in conventional EACs are related to survival pathways. PMID:26973859

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

    PubMed Central

    Yu, Hui; Xie, Li-Fang; Chen, Kang; Yang, Gang-Yi; Xing, Xiao-Yan; Zhao, Jia-Jun; Hong, Tian-Pei; Shan, Zhong-Yan; Li, Hong-Mei; Chen, Bing; Tang, Xu-Lei; Qi, Ling; Yang, Jing; Fang, Yuan; Li, Ting; Wang, Shuang-Shuang; Liang, Xue; Yin, Ya-Qi; Mu, Yi-Ming

    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, CI 14.47–38.03), 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. PMID:26996471

  6. Antibiotics in early life and obesity

    PubMed Central

    Cox, Laura M.; Blaser, Martin J.

    2015-01-01

    The intestinal microbiota can influence host metabolism. When given early in life, agents that disrupt microbiota composition and consequently its metabolic activity, can influence body mass of the host by either promoting weight gain or stunting growth, which is consistent with effects of the microbiota on development. In this Perspective, we posit that microbiota disruptions in early-life can have long-lasting effects on body weight in adulthood. Furthermore, we examine the dichotomy between antibiotic-induced repressed or promoted growth and review the experimental and epidemiological evidence that supports these phenotypes. Considering the characteristics of the gut microbiota in early life as a distinct dimension of human growth and development, as well as comprehending its susceptibility to perturbation, will allow for increased understanding of human physiology and could lead to development of interventions to stem current epidemic diseases, such as obesity and types 1 and 2 diabetes mellitus. PMID:25488483

  7. Early and Late Onset Sepsis in Late Preterm Infants

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Cotten, C. Michael; Clark, Reese H.; Benjamin, Daniel K.; Smith, P. Brian

    2009-01-01

    Background Preterm birth is increasing worldwide, and late preterm births, which comprise more than 70% of all preterm births, account for much of the increase. Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants. Methods This is an observational cohort study of infants < 121 days of age (119,130 infants less than or equal to 3 days of life and 106,142 infants between 4 and 120 days of life) with estimated gestational age at birth between 34 and 36 weeks, admitted to 248 neonatal intensive care units in the United States between 1996 and 2007. Results During the study period, the cumulative incidence of early and late onset sepsis was 4.42 and 6.30 episodes per 1000 admissions, respectively. Gram-positive organisms caused the majority of early and late onset sepsis episodes. Infants with early onset sepsis caused by Gram-negative rods and infants with late onset sepsis were more likely to die than their peers with sterile blood cultures (OR 4.39, 95% CI 1.71–11.23, P=0.002; and OR 3.37, 95% CI 2.35–4.84, P<0.001, respectively). Conclusion Late preterm infants demonstrate specific infection rates, pathogen distribution, and mortality associated with early and late onset sepsis. The results of this study are generalizable to late preterm infants admitted to the special care nursery or neonatal intensive care unit. PMID:19953725

  8. Characterization of Early Partial Seizure Onset: Frequency, Complexity and Entropy

    PubMed Central

    Jouny, Christophe C.; Bergey, Gregory K.

    2011-01-01

    Objective A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Methods Eighteen different measures including power in frequency bands up to 300Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from forty-five patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). Results GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Conclusions Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Significance Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. PMID:21872526

  9. TERT Core Promotor Mutations in Early-Onset Bladder Cancer

    PubMed Central

    Giedl, Johannes; Rogler, Anja; Wild, Andreas; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Rümmele, Petra; Hurst, Carolyn; Knowles, Margaret; Hartmann, Arndt; Zinnall, Ulrike; Stoehr, Robert

    2016-01-01

    Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients. PMID:27313781

  10. TERT Core Promotor Mutations in Early-Onset Bladder Cancer.

    PubMed

    Giedl, Johannes; Rogler, Anja; Wild, Andreas; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Rümmele, Petra; Hurst, Carolyn; Knowles, Margaret; Hartmann, Arndt; Zinnall, Ulrike; Stoehr, Robert

    2016-01-01

    Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55.6% and 82.8% described so far, and are independent of stage and grade. Since limited data on molecular alterations of early-onset bladder tumors exists, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hotspot regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57.6% vs. 84.8%, p<0.001). Among the early-onset cohort cases younger than the cohort's median age of 39 years at disease onset showed a significantly reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67.5%; p=0.012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients. PMID:27313781

  11. Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

    PubMed Central

    Sheng, Ke; Fang, Weidong; Zhu, Yingcheng; Shuai, Guangying; Zou, Dezhi; Su, Meilan; Han, Yu; Cheng, Oumei

    2016-01-01

    HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset. PMID:27462265

  12. [Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

    PubMed

    Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

    2016-07-01

    Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described. PMID:27346312

  13. Early onset marfan syndrome: Atypical clinical presentation of two cases

    PubMed Central

    Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

    2015-01-01

    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. PMID:26929908

  14. Early-Onset Psychosis in Youth with Intellectual Disability

    ERIC Educational Resources Information Center

    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…

  15. Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

    ERIC Educational Resources Information Center

    Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

    2010-01-01

    Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

  16. GRIN1 Mutations in Early-Onset Epileptic Encephalopathy.

    PubMed

    Chen, Wenjuan; Yuan, Hongjie

    2015-06-01

    Investigators from Yokohama City University and other medical centers in Israel and Japan reported mutations on N-methyl-D-aspartate (NMDA) receptors subunit GRIN1 (GluN1) identified in patients with nonsyndromic intellectual disability and early-onset epileptic encephalopathy. PMID:26933583

  17. Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

    ERIC Educational Resources Information Center

    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…

  18. [A case of early-onset COPD with recurrent pneumothorax].

    PubMed

    Terashima, Takeshi; Matsuzaki, Tatsu; Ogawa, Rika; Naitou, Asuka; Morishita, Tetsuo; Ishizaka, Akitoshi

    2009-02-01

    Early-onset chronic obstructive pulmonary disease (COPD) is designated as onset under age 50. We report a case of early-onset COPD with recurrent pneumothorax. A 29-year-old woman visited our hospital with productive cough and dyspnea on exertion. CT scan of the chest demonstrated severe panlobular emphysema. A pulmonary function test showed a reduction in FEV1.0 (41% of the predicted value). A diagnosis of severe COPD was made. Her symptoms and pulmonary function improved after the treatment of inhaled corticosteroid, long-acting beta2-agonist, and anti-cholinergic drugs. She had pneumothorax at least 8 times in the right lung. The level of alpha1-antitrypsin was normal. On the basis of the characteristics of the appearance of the chest X-ray and CT scan, the possibility of bronchiolitis obliterans, lymphoangioleiomyomatosis or Langerhans cell histiocytosis was thought to be low. We considered that several factors, such as high susceptibility, pulmonary infection during her childhood, bronchial asthma, malnutrition, smoking history from an early age, and long-term passive exposure to cigarette smoke may have contributed to the development of early-onset COPD in the present case. PMID:19260533

  19. Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

    ERIC Educational Resources Information Center

    McIntosh, David E.; Trotter, Jeffrey S.

    2006-01-01

    Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

  20. GPR39, a receptor of the ghrelin receptor family, plays a role in the regulation of glucose homeostasis in a mouse model of early onset diet-induced obesity.

    PubMed

    Verhulst, P J; Lintermans, A; Janssen, S; Loeckx, D; Himmelreich, U; Buyse, J; Tack, J; Depoortere, I

    2011-06-01

    GPR39, which may function as a Zn(2+) sensor, is a member of the G protein-coupled receptor family that also includes the receptor for the hunger hormone ghrelin. The down-regulation of GPR39 mRNA in adipose tissue of obese type 2 diabetic patients suggests that GPR39 may contribute to the pathogenesis of the disease. The present study aimed to investigate the role of GPR39 in the regulation of energy balance and glucose homeostasis in wild-type (GPR39(+/+) ) and GPR39 knockout mice (GPR39(-/-) ) with obesity-related type 2 diabetes. GPR39 mRNA levels in adipose tissue of fasted GPR39(+/+) mice fed a high-fat diet (HFD) for 30 weeks were reduced and correlated positively with blood glucose levels. Body weight, fat percentage and energy intake were increased in the HFD group but did not differ between both genotypes. Within the HFD group, blood glucose levels were lower in GPR39(-/-) than in GPR39(+/+) mice, despite significant reductions in prandial plasma insulin levels. The latter may not be a result of changes in β-cell hyperplasia because immunohistochemical staining of pancreata of mice on a HFD showed no differences between genotypes. The lower blood glucose levels may involve alterations in insulin sensitivity as revealed by glucose tolerance tests and respiratory quotient measurements that showed a preference of obese GPR39(-/-) mice for the use of carbohydrates as metabolic fuel. The increase in plasma ghrelin levels in GPR39(-/-) mice fed a HFD may contribute to the alterations in glucose homeostasis, whereas changes in gastric emptying or intestinal Zn(2+) absorption are not involved. The results obtained in the present study suggest that GPR39 plays a role in the pathogenesis of obesity-related type 2 diabetes by affecting the regulation of glucose homeostasis. PMID:21470317

  1. Neonatal Septicemia in Nepal: Early-Onset versus Late-Onset

    PubMed Central

    Ansari, Shamshul; Nepal, Hari Prasad; Gautam, Rajendra; Shrestha, Sony; Neopane, Puja; Chapagain, Moti Lal

    2015-01-01

    Introduction. Neonatal septicemia is defined as infection in the first 28 days of life. Early-onset neonatal septicemia and late-onset neonatal septicemia are defined as illnesses appearing from birth to three days and from four to twenty-eight days postnatally, respectively. Methods. In this cross-sectional study, blood samples from the suspected infants were collected and processed in the bacteriology laboratory. The growth was identified by standard microbiological protocol and the antibiotic sensitivity testing was carried out by modified Kirby-Bauer disk diffusion method. Results. Among total suspected cases, the septicemia was confirmed in 116 (12.6%) neonates. Early-onset septicemia (EOS) was observed in 82 infants and late-onset septicemia (LOS) in 34 infants. Coagulase-negative staphylococcus (CoNS) (46.6%) was the predominant Gram-positive organism isolated from EOS as well as from LOS cases followed by Staphylococcus aureus (14.6%). Acinetobacter species (9.5%) was the predominant Gram-negative organism followed by Klebsiella pneumoniae (7.7%). Conclusions. The result of our study reveals that the CoNS, Staphylococcus aureus, Acinetobacter spp., and Klebsiella pneumoniae are the most common etiological agents of neonatal septicemia. In particular, since rate of CoNS causing sepsis is alarming, prompting concern to curb the excess burden of CoNS infection is necessary. PMID:26649057

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

    PubMed Central

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

    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. PMID:25897226

  3. Depression in patients with early versus late onset of Parkinson's disease.

    PubMed

    Starkstein, S E; Berthier, M L; Bolduc, P L; Preziosi, T J; Robinson, R G

    1989-11-01

    We examined correlates of depression in patients whose onset of Parkinson's disease (PD) began before age 55 (early-onset group) compared with patients whose onset was after age 55 (late-onset group). The early-onset group showed a significantly higher frequency of depression than the late-onset group. When both groups were matched for duration of the disease, the early-onset group still showed a significantly higher frequency of depression, whereas tremor, akinesia, and rigidity were significantly more severe in the late-onset group. A stepwise regression analysis showed that in the early-onset group, depression scores were significantly correlated with scores of cognitive impairment and duration of the disease, while in the late-onset group, depression scores were significantly correlated with impairments in activities of daily living. These data suggest that depression in patients with early-onset PD may have a different etiology than in patients with late-onset PD. PMID:2812320

  4. Early-onset dementias: diagnostic and etiological considerations

    PubMed Central

    2013-01-01

    This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect. PMID:24565469

  5. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism.

    PubMed

    Schrag, Anette; Schott, Jonathan M

    2006-04-01

    In this review we discuss the epidemiological, clinical, and genetic characteristics of early-onset parkinsonism, defined as parkinsonism starting before age 40 (sometimes 50) years. Juvenile parkinsonism is very rare and is the result of various secondary or genetic causes. In patients with onset at or above age 21 years, secondary causes require exclusion but are rare; most cases with a fairly pure parkinsonian syndrome (eg, young-onset Parkinson's disease; YOPD) are due to typical Lewy-body Parkinson's disease or, less commonly, genetic causes. In comparison with patients with late-onset disease, most patients with YOPD progress more slowly in terms of motor features and have a longer disease course with preservation of cognitive function, but typically develop motor fluctuations and dyskinesias earlier. Patients with YOPD generally experience a greater effect in their lives than those with late onset, with poorer social adjustment, higher rates of depression, and lower quality of life. Management of YOPD must therefore aim to maintain occupational, social, and daily functioning, while delaying or ameliorating motor complications of treatment, providing psychological support, and, where possible, preventing psychiatric complications including depression. PMID:16545752

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

    PubMed

    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 (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 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. PMID:22235025

  7. Obesity in Childhood Cancer Survivors: Call for Early Weight Management123

    PubMed Central

    Zhang, Fang Fang; Parsons, Susan K

    2015-01-01

    A high prevalence of obesity and cardiometabolic conditions has been increasingly recognized in childhood cancer survivors. In particular, survivors of pediatric acute lymphoblastic leukemia have been found to be at risk of becoming overweight or obese early in treatment, with increases in weight maintained throughout treatment and beyond. Nutrition plays an important role in the etiology of obesity and cardiometabolic conditions and is among the few modifiable factors that can prevent or delay the early onset of these chronic conditions. However, nutritional intake in childhood cancer survivors has not been adequately examined and the evidence is built on data from small cohorts of survivors. In addition, the long-term impact of cancer diagnosis and treatment on survivors’ nutritional intake as well as how survivors’ nutritional intake is associated with chronic health conditions have not been well quantified in large-scale studies. Promoting family-based healthy lifestyles, preferably at a sensitive window of unhealthy weight gain, is a priority for preventing the early onset of obesity and cardiometabolic conditions in childhood cancer survivors. PMID:26374183

  8. Childhood Risk Factors for Early-Onset Drinking*

    PubMed Central

    Donovan, John E.; Molina, Brooke S. G.

    2011-01-01

    Objective: There is relatively little research on the childhood antecedent predictors of early-onset alcohol use. This study examined an array of psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory as potential antecedent risk factors for the initiation of alcohol use at age 14 or younger. Method: A sample of 452 children (238 girls) ages 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random-digit dialing procedures. Children and parents were interviewed using computer-assisted interviews. Logistic regression analyses were used to examine the age-10 univariate and multivariate predictors of the initiation of alcohol use by age 14 or younger. Results: Twenty-five percent of the sample reported having more than a sip or a taste of alcohol in their life by age 14. Sex, race, and age cohort did not relate to early drinking status. Children with two parents were less likely to initiate drinking early. Early initiation of drinking related significantly to an array of antecedent risk factors (personality, social environment, and behavioral) assessed at age 10 that reflect psychosocial proneness for problem behavior. In the multivariate model, the variables most predictive of early-onset drinking were having a single parent, sipping or tasting alcohol by age 10, having parents who also started drinking at an early age, and parental drinking frequency. Conclusions: Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to engage in problem behavior as measured by Problem Behavior Theory and having a family environment conducive to alcohol use. PMID:21906502

  9. Early Onset of Selective Serotonin Reuptake Inhibitor Antidepressant Action

    PubMed Central

    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

  10. Latin America: native populations affected by early onset periodontal disease.

    PubMed

    Nowzari, Hessam; Botero, Javier Enrique

    2011-06-01

    Millions of individuals are affected by early onset periodontal disease in Latin America, a continent that includes more than 20 countries. The decision-makers claim that the disease is not commonly encountered. In 2009, 280,919 authorized immigrants were registered in the United States versus 5,460,000 unauthorized (2,600,000 in California). The objective of the present article is to raise awareness about the high prevalence of the disease among Latin Americans and the good prognosis of preventive measures associated with minimal financial cost. PMID:21823496

  11. Tumor Microsatellite Instability in Early Onset Gastric Cancer

    PubMed Central

    Bacani, Julinor; Zwingerman, Rhonda; Di Nicola, Nando; Spencer, Samantha; Wegrynowski, Trish; Mitchell, Kyle; Hay, Kazuko; Redston, Mark; Holowaty, Eric; Huntsman, David; Pollett, Aaron; Riddell, Robert; Gallinger, Steven

    2005-01-01

    Gastric cancer (GC) remains a leading cause of cancer mortality worldwide. Genetic factors are implicated, including DNA mismatch repair (MMR) deficiency manifested as tumor microsatellite instability (MSI). However, a standardized panel of markers and a definition of low-versus-high level MSI in GC are lacking. We examined a population-based cohort of early onset (≤50 yrs) gastric cancer. We identified 211 cases of early onset gastric cancer in Central-East Ontario from 1989 to 1993, with archival material available for 139 cases. Testing included a six-mononucleotide marker panel and a three-MMR immunohistochemical panel. Overall, 30% (41 of 139) of GC were MSI+, with allelic shifts at one to eight markers. An unexpected discordance between the BAT-25, BAT-26, and BAT-40 markers was observed in the MSI+ cases. Six cases showing multiple loci instability (≥3 markers MSI+/MSI-high) demonstrated MMR protein deficiency. Three novel hMLH1 mutations (two germline frameshift and one somatic nonsense) were also found. The only significant clinicopathological associations were increased tumor size in MSI+ cases (P = 0.04) and Lauren histotype (P = 0.006) and tumor grade (P = 0.007) in MSI-high cases. Tumor size, location, depth, nodal status, and Ming subtype were significant prognostic variables. Therefore, we propose a new definition of high-level MSI based on unifying characteristics of instability of more than or equal to three of six mononucleotide markers and loss of MMR protein expression. PMID:16237216

  12. Continuation of Gradual Weight Gain Necessary for the Onset of Puberty May Be Responsible for Obesity Later in Life

    PubMed Central

    Lehrer, Steven

    2016-01-01

    A continuation of the gradual weight gain necessary for the onset of puberty may be responsible for obesity later in life. Hypothetically, a group of brain nuclei form components of a single pubertal clock mechanism that drives pre-pubertal weight gain and governs the onset of puberty and fertility. No mechanism evolved to shut off pre-pubertal and pubertal weight and body fat gain after puberty. The weight gain continues unabated throughout life. A better understanding of the mechanism of puberty and pre-pubertal weight gain could provide new insights into obesity and diseases associated with obesity such as type 2 diabetes, dyslipidemia, hypertension, heart disease, depression, etc. PMID:26562472

  13. Glucose Metabolic Brain Networks in Early-Onset vs. Late-Onset Alzheimer's Disease

    PubMed Central

    Chung, Jinyong; Yoo, Kwangsun; Kim, Eunjoo; Na, Duk L.; Jeong, Yong

    2016-01-01

    Objective: Early-onset Alzheimer's disease (EAD) shows distinct features from late-onset Alzheimer's disease (LAD). To explore the characteristics of EAD, clinical, neuropsychological, and functional imaging studies have been conducted. However, differences between EAD and LAD are not clear, especially in terms of brain connectivity and networks. In this study, we investigated the differences in metabolic connectivity between EAD and LAD by adopting graph theory measures. Methods: We analyzed 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images to investigate the distinct features of metabolic connectivity between EAD and LAD. Using metabolic connectivity and graph theory analysis, metabolic network differences between LAD and EAD were explored. Results: Results showed the decreased connectivity centered in the cingulate gyri and occipital regions in EAD, whereas decreased connectivity in the occipital and temporal regions as well as increased connectivity in the supplementary motor area were observed in LAD when compared with age-matched control groups. Global efficiency and clustering coefficients were decreased in EAD but not in LAD. EAD showed progressive network deterioration as a function of disease severity and clinical dementia rating (CDR) scores, mainly in terms of connectivity between the cingulate gyri and occipital regions. Global efficiency and clustering coefficients were also decreased along with disease severity. Conclusion: These results indicate that EAD and LAD have distinguished features in terms of metabolic connectivity, with EAD demonstrating more extensive and progressive deterioration. PMID:27445800

  14. Cerebral Cell Renewal in Adult Mice Controls the Onset of Obesity

    PubMed Central

    Gouazé, Alexandra; Brenachot, Xavier; Rigault, Caroline; Krezymon, Alice; Rauch, Camille; Nédélec, Emmanuelle; Lemoine, Aleth; Gascuel, Jean; Bauer, Sylvian; Pénicaud, Luc; Benani, Alexandre

    2013-01-01

    The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance. PMID:23967273

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

    ERIC Educational Resources Information Center

    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. The onset of galactic winds in early-type galaxies

    NASA Technical Reports Server (NTRS)

    Forman, W.; Jones, C.; Tucker, W.; David, L. P.

    1990-01-01

    Researchers report on a program using Einstein x ray observations of the x ray spectra and surface brightness profiles (or extents) of a large sample of early-type (elliptical and SO) galaxies for which the goal is to determine the critical optical luminosity for which galactic winds are important. For galaxies in which the x ray emission is dominated by hydrostatic coronae, the x ray spectra will be relatively soft (characterized by a temperature of approx. 10 to the 7th power K), while for galaxies with a galactic wind, the emission will be dominated by the spectrally harder discrete sources (since the x ray emission from the wind is essentially negligible). In this new sample of 180 galaxies, there are 28 early type galaxies with sufficient counts to obtain a spectrum with the Einstein Image Proportional Counter (IPC). This sample more than doubles the total number of early-type galaxies in earlier compilations (Forman, Jones, and Tucker 1985; Canizares et al. 1987). The new spectral observations will help determine the critical optical luminosity for the onset of galactic winds which is important for understanding the chemical evolution of galaxies and of the intergalactic medium. The implications of galactic winds for the heavy element enrichment and energy content of the intracluster medium are discussed.

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

    PubMed

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

    2016-01-01

    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. PMID:27275827

  18. Nutrient Intakes in Early Life and Risk of Obesity

    PubMed Central

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

    2016-01-01

    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. PMID:27275827

  19. The unique experience of spouses in early-onset dementia.

    PubMed

    Ducharme, Francine; Kergoat, Marie-Jeanne; Antoine, Pascal; Pasquier, Florence; Coulombe, Renée

    2013-09-01

    To date, few studies have examined the experience of spouse caregivers living with a person with early-onset dementia. Moreover, few support resources are offered to these family caregivers and fewer are still tailored to their unique trajectory. The aim of this qualitative study was to document the lived experience of spouse caregivers of young patients in order to inform the development of professional support tailored to their reality. A sample of 12 spouses of persons diagnosed with dementia before the age of 65 participated in semistructured interviews. Six themes emerged from their caregiver trajectories, namely, difficulty managing behavioral and psychological symptoms, long quest for diagnosis, nondisclosure to others and denial of diagnosis, grief for loss of spouse and midlife projects, difficulty juggling unexpected role and daily life responsibilities, and difficulty planning for future. Results open up innovative avenues for the development of interventions geared to facilitating role transition for these spouse caregivers. PMID:23823140

  20. Molecular genetics of early-onset Alzheimer's disease revisited.

    PubMed

    Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

    2016-06-01

    As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. PMID:27016693

  1. The Relationship between Asthma and Obesity in Urban Early Adolescents

    PubMed Central

    Jay, Melanie; Wijetunga, N. Ari; Stepney, Cesalie; Dorsey, Karen; Chua, Danica Marie

    2012-01-01

    Asthma and obesity, which have reached epidemic proportions, impact urban youth to a great extent. Findings are inconsistent regarding their relationship; no studies have considered asthma management. We explored the association of obesity and asthma-related morbidity, asthma-related health care utilization, and asthma management in urban adolescents with uncontrolled asthma. We classified 373 early adolescents (mean age=12.8 years; 82% Hispanic or Black) from New York City public middle schools into 4 weight categories: normal (body mass index [BMI]<85th percentile); overweight (85th percentile≤BMI<95th percentile); obese (95th percentile≤BMI<97th percentile); and very obese (BMI≥97th percentile). We compared sample obesity prevalence to national estimates, and tested whether weight categories predicted caregiver reported asthma outcomes, adjusting for age and race/ethnicity. Obesity prevalence was 37%, with 28% of the sample being very obese; both rates were significantly higher than national estimates. We found no significant differences in asthma-related health care utilization or asthma management between weight categories, and a few differences in asthma-related morbidity. Relative to normal weight and obese youth, overweight youth had higher odds of never having any days with asthma-related activity limitations. They also had higher odds of never having asthma-related school absences compared with obese youth. Overweight youth with asthma-related activity limitations had more days with limitations compared with normal weight youth. Overweight, but not obese youth, missed more school due to asthma than normal weight youth. Overweight and obesity prevalence was very high in urban, Hispanic, and Black adolescents with uncontrolled asthma, but not strongly associated with asthma-related morbidity, asthma-related health care utilization, or asthma management practices. PMID:22970423

  2. Clinical Characteristics and Prognostic Factors in Early-Onset Alopecia Totalis and Alopecia Universalis

    PubMed Central

    Cho, Hyun Hee; Jo, Seong Jin; Paik, Seung Hwan; Jeon, Hye Chan; Kim, Kyu Han; Eun, Hee Chul

    2012-01-01

    Alopecia totalis (AT) and alopecia universalis (AU), severe forms of alopecia areata (AA), show distinguishable clinical characteristics from those of patch AA. In this study, we investigated the clinical characteristics of AT/AU according to the onset age. Based on the onset age around adolescence (< or ≥ 13 yr), 108 patients were classified in an early-onset group and the other 179 patients in a late-onset group. We found that more patients in the early-onset group had a family history of AA, nail dystrophy, and history of atopic dermatitis than those in the late-onset group. These clinical differences were more prominent in patients with AU than in those with AT. In addition, significantly more patients with concomitant medical disorders, especially allergic diseases were found in the early-onset group (45.8%) than in the late-onset group (31.2%). All treatment modalities failed to show any association with the present hair condition of patients. In the early-onset group, patients with AU or a family history of AA showed worse prognosis, whereas this trend was not observed in the late-onset group. Systemic evaluations might be needed in early-onset patients due to the higher incidence of comorbid diseases. It is suggested that patients with AU or family history of AA make worse progress in the early-onset group than in the late-onset group. PMID:22787378

  3. Making a Difference in Early Childhood Obesity

    ERIC Educational Resources Information Center

    Huber, Dan

    2009-01-01

    News reports calling attention to the steady increase in the number of overweight adults have become an accepted part of our media landscape. Worse still, warnings continue that more and more young children, like the adults who care for them, are carrying too much weight. Unfortunately, this bad news about our growing obesity problem isn't just…

  4. Clinical features associated with an early onset in chronic tic disorders.

    PubMed

    Richer, Francois; Daghfal, Roula; Rouleau, Guy A; Lespérance, Paul; Chouinard, Sylvain

    2015-12-30

    In chronic tic disorders such as Tourette syndrome (TS), tics often appear between 4 and 8 years but they can also appear in early childhood, a period in which symptom expression may be affected by early brain development. The present study examined whether symptom expression in early-onset TS was distinct from that observed in TS with a later onset. We compared the clinical characteristics in children with TS who developed tics before age 4 or after age 6. Early-onset TS was significantly associated with an increased rate of stuttering and other speech disfluencies as well as an increased rate of oppositional defiant disorder, symptoms that often appear before age 4. Early-onset TS was also linked to maternal transmission of tics. Early-onset TS was not significantly associated with tic severity, obsessive-compulsive behavior or attention-deficit hyperactivity disorder. The results suggest that an early onset affects symptom expression in tic disorders. PMID:26596364

  5. Early trauma, dissociation, and late onset in the eating disorders.

    PubMed

    Tobin, D L; Molteni, A L; Elin, M R

    1995-04-01

    Although the majority of patients with anorexia nervosa and bulimia nervosa develop these disorders in their teens and 20s, some patients develop an eating disorder in their 30s, 40s, or 50s. We present a subgroup of patients with the following pattern of symptoms and historical detail: (1) severe sexual and physical abuse by family members; (2) relatively good premorbid professional and marital adjustment (considering later difficulties) though characterized by (3) hypomania, binge eating, and morbid obesity. A pronounced shift in eating behaviors follows (4) medical trauma (e.g., injury, cancer, surgery) that occurs after age 30, interrupts previous hypomanic adaptation, and leads to severe restriction, purging, and dramatic weight loss (e.g., 100 lb). Although only one patient met full criteria for anorexia nervosa, weight loss and starvation were serious enough to provoke further medical crises in all patients. Finally, (5) during both weight loss and weight restoration patients demonstrated significant dissociative disturbance, including dissociated mood and personality states (i.e., multiple personality disorder), self-destructive behavioral episodes repeating early trauma, and avoidance of food as a way to manage PTSD symptoms. PMID:7773268

  6. Gender effects on brain changes in early-onset psychosis.

    PubMed

    Rapado-Castro, Marta; Bartholomeusz, Cali F; Castro-Fornieles, Josefina; González-Pinto, Ana; Otero, Soraya; Baeza, Inmaculada; Moreno, Carmen; Graell, Montserrat; Janssen, Joost; Bargalló, Nuria; Pantelis, Christos; Desco, Manuel; Arango, Celso

    2015-10-01

    Progressive loss of cortical gray matter (GM) and increase of cerebrospinal fluid (CSF) have been reported in early-onset psychosis (EOP). EOP typically begins during adolescence, a time when developmental brain trajectories differ by gender. This study aimed to determine gender differences in progression of brain changes in this population. A sample of 61 (21 females) adolescents with a first psychotic episode and a matched sample of 70 (23 females) controls underwent both baseline and 2-year follow-up anatomical brain imaging assessments. Regional GM and CSF volumes were obtained using automated methods based on the Talairach's proportional grid system. At baseline, only male patients showed a clear pattern of alterations in the frontal lobe relative to controls (smaller GM and larger CSF volumes). However, parallel longitudinal changes for male and female patients relative to controls were observed, resulting in a common pattern of brain changes across both genders: rate of left frontal lobe GM volume loss was larger in male (-3.8%) and female patients (-4.2%) than in controls (-0.7% males; -0.4% females). The reverse was found for the CSF volume in the left frontal lobe. While the GM and CSF volumes of females with EOP appear to be within the normal range at initial illness onset, our results point to a similar trajectory of increased/accelerated brain changes in both male and female patients with EOP. The pattern of progression of brain changes in psychosis appears to be independent of gender or structural alterations on appearance of psychotic symptoms. PMID:25589436

  7. Pregnancy and early onset pauciarticular juvenile chronic arthritis

    PubMed Central

    Musiej-Nowakowska, E.; Ploski, R.

    1999-01-01

    OBJECTIVES—To study interaction of early onset pauciarticular juvenile chronic arthritis (EOP-JCA) and pregnancy in the Polish population, in particular to confirm the ameliorating effect of pregnancy on disease activity reported by others and to analyse the factors that govern the occurrence of postpartum flare, with emphasis on the potential role of breast feeding.
METHODS—The reproductive outcome and disease status in 39 adult women with history of EOP- JCA was examined by means of a questionnaire and an interview. In all patients the disease onset occurred before the 6th birthday, 19 had persistent pauciarticular JCA (PeEOP-JCA) and 20 had extended pauciarticular JCA (ExEOP-JCA).
RESULTS—23 women had at least one successful pregnancy, seven had unsuccessful pregnancies but all of them had also one or more successful pregnancies. Among those who have never been pregnant (n=16) there was a higher frequency of eye disease and ExEOP-JCA compared with the rest of the group. In almost all cases pregnancy was associated with remission of disease activity, however a postpartum flare appeared after 22 pregnancies (52%). The flares were more frequent in women who had an active disease before pregnancy, had a flare after a previous pregnancy and/or were breast feeding.
CONCLUSIONS—In EOP-JCA patients pregnancy generally has a good outcome and induces amelioration of disease activity. After delivery, however, a flare of disease often appears, especially in women who were breast feeding, had a postparum flare previously or had an active disease before pregnancy. The pattern of interaction between disease and pregnancy found in EOP-JCA makes EOP-JCA similar in this respect to RA, but different from systemic lupus erythematosus and ankylosing spondylitis.

 PMID:10419865

  8. Gaze holding deficits discriminate early from late onset cerebellar degeneration.

    PubMed

    Tarnutzer, Alexander A; Weber, K P; Schuknecht, B; Straumann, D; Marti, S; Bertolini, G

    2015-08-01

    The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined

  9. A new childhood asthma phenotype: obese with early menarche.

    PubMed

    Castro-Rodriguez, Jose A

    2016-03-01

    Three concomitant phenomena occur in the later years of childhood: increases in the incidence of asthma, obesity and early menarche. This article is an overview of the current epidemiologic, basic, genetic and epigenetic evidence about this relationship. As a consequence we propose that obese girls who have an early menarche (≤ 11 years of age) constitute a new asthma phenotype in childhood. Future studies need to be carried out in order to find the best control and treatment of this new asthma phenotype. PMID:26644272

  10. [EARLY MOTHER-CHILD BONDING FACTORS ASSOCIATED WITH CHILDREN OBESITY].

    PubMed

    Vargas Martínez, Gabriela; Cruzat Mandich, Claudia; Díaz Castrillón, Fernanda; Moore Infante, Catalina; Ulloa Jiménez, Valentina

    2015-01-01

    The aim of this study is to describe the experience of a group of mothers with obese children, regarding how early bond affects the relationship that both have with food and this, in turn, impacts on childhood obesity. The present study has a qualitative, exploratory and descriptive design. The sample consists of five chilean women between 22 and 39 years old, with obese children between 2 and 4 years old. In-depth interviews were carried out and open coding strategy was used as method of analysis. Results show a tendency of mothers to establish insecure attachment relations, difficulties of tuning and expression of affection, and a predominance of a permissive parenting style around food. This has important implications for prevention and treatment of obesity, focusing on the attachment bond between mother and child. PMID:26545652

  11. Endocrine and Metabolic Biomarkers Predicting Early Childhood Obesity Risk.

    PubMed

    Socha, Piotr; Hellmuth, Christian; Gruszfeld, Dariusz; Demmelmair, Hans; Rzehak, Peter; Grote, Veit; Weber, Martina; Escribano, Joaquin; Closa-Monasterolo, Ricardo; Dain, Elena; Langhendries, Jean-Paul; Riva, Enrica; Verduci, Elvira; Koletzko, Berthold

    2016-01-01

    There is growing evidence of long-term effects of early dietary intervention in infancy on later obesity risk. Many studies showed reduced risk of obesity with breastfeeding in infancy, which could be related to the reduced protein intake with human milk compared to infant formula. In a randomized controlled trial (Childhood Obesity Project), we were able to show that infant formula with reduced protein content results in lower BMI both at 2 and 6 years. These effects seem to be mediated mainly by branched-chain amino acids which stimulate the insulin-like growth factor (IGF)-1 axis and insulin release. In this trial, we also showed an influence of high-protein diet on larger kidney size, which seems to be partly explained by a significant effect of free IGF-1 on kidney volume. The IGF-1 axis was shown to regulate early growth, adipose tissue differentiation and early adipogenesis in animals and in humans. Leptin and adiponectin can also be regarded as important endocrine regulators of obesity. These markers were tested in observational studies. Leptin seems to be closely correlated with BMI but changes in adiponectin require further exploration. Still, there is a lack of good data or some results are contradictory to indicate the role of either leptin or adiponectin in infancy for determining later obesity risk. PMID:27088335

  12. Risk for obesity in adolescence starts in early childhood

    PubMed Central

    Shankaran, S; Bann, C; Das, A; Lester, B; Bada, H; Bauer, CR; La Gasse, L; Higgins, RD

    2013-01-01

    Objective The objective of this study was to assess the predictive value of body mass index (BMI) at earlier ages on risk of overweight/obesity at age of 11 years. Study Design This is a longitudinal study of 907 children from birth to age of 11 years. Predictors include BMI at earlier ages and outcome is overweight/obesity status at age of 11 years. Analyses were adjusted for covariates known to affect BMI. Result At 11 years, 17% were overweight and 25% were obese. Children whose BMI was measured as ≥85th percentile once at preschool age had a twofold risk for overweight/obesity at 11 years of age. Risk increased by 11-fold if a child's BMI measured was noted more than once during this age. During early elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity at 11 years was fivefold and increased by 72-fold if noted more than two times. During late elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity was 26-fold and increased by 351-fold if noted more than two times. Risk of overweight/obesity at 11 years was noted with higher maternal prepregnancy weight, higher birth weight, female gender and increased television viewing. Conclusion Children in higher BMI categories at young ages have a higher risk of overweight/obesity at 11 years of age. Effect size was greater for measurements taken closer to 11 years of age. Pediatricians need to identify children at-risk for adolescent obesity and initiate counseling and intervention at earlier ages. PMID:21415836

  13. Early onset of ghrelin production in a marsupial.

    PubMed

    Menzies, Brandon R; Shaw, Geoff; Fletcher, Terry P; Renfree, Marilyn B

    2009-02-27

    Ghrelin regulates appetite in mammals and can stimulate growth hormone (GH) release from the pituitary. In rats and humans, ghrelin cells appear in the stomach during late fetal life. Nevertheless, the role of ghrelin in early mammalian development is not well understood. Marsupials deliver highly altricial young that weigh less than 1g so they must feed and digest milk at a comparatively immature stage of development. Since they complete their growth and differentiation while in the pouch, they are accessible models in which to determine the time course of ghrelin production during development. We examined the distribution of gastric ghrelin cells, plasma ghrelin concentrations and pituitary expression of the ghrelin receptor (ghsr-1alpha) and GH in the tammar wallaby, Macropus eugenii. There were ghrelin immunopositive cells in the developing mesenchyme of the stomach from day 10 post partum (pp) to day 150pp. Subsequently ghrelin protein in the fore-stomach declined and was absent by day 250pp but remained in the gastric cells of the hind-stomach. Ghrelin was detected in the developing pancreas from day 10pp but was absent by day 150pp and in the adult. Pituitary ghsr-1alpha expression and plasma concentrations of ghrelin increased significantly up to day 70-120pp while GH expression was also elevated, declining with GH to reach adult levels by day 180pp. These results demonstrate an early onset of gastric ghrelin expression in the tammar in concert with a functional stomach at a relatively earlier stage than that of developmentally more mature eutherian young. PMID:19026714

  14. Early-onset sensorineural hearing loss in Lassa fever.

    PubMed

    Ibekwe, T S; Okokhere, P O; Asogun, D; Blackie, F F; Nwegbu, M M; Wahab, K W; Omilabu, S A; Akpede, G O

    2011-02-01

    Lassa fever (LF) is a viral hemorrhagic disease which affects one-fourth to two million people annually with the fatality rate of about 10,000. It is associated with sensorineural hearing loss (SNHL) usually at the convalescent stage. Recently, cases of SNHL at the acute phase have been reported. This study was done to further investigate the incidence and features of SNHL in acute phase of LF. It is a prospective case-control study of LF patients seen with acute SNHL conducted between July 2007 and April 2009 at Irrua Specialist Teaching Hospital Nigeria. The diagnosis of acute LF was based on the clinical features and detection of IgM antibodies and/or positive Lassa virus-specific reverse transcriptase-polymerase chain reaction using primers S36+ and LVS 339 while SNHL was diagnosed clinically and confirmed with PTA and speech discrimination tests. Patients with other acute febrile illnesses were used as control. Statistical analysis was done using SPSS version 11 and Fisher's exact test while level of significance was set at p < 0.05. Out of the 37 confirmed cases of LF, 5 (13.5%) and none (0%) of the control developed early-onset SNHL (p = 0.03). Forty percent of the cases studied had negative IgM. The audiograms showed involvement at all frequency groups with pure tone average 65-85 dB and the speech discrimination 20-40%. The overall case fatality rate was 27.0%, and for early SNHL cases 60.0% (p > 0.05). The incidence of SNHL in LF infection is about 13.5% and could be a reflection of a worse disease process. There is possibility of direct viral invasion aside immunological reaction as a causative mechanism. PMID:20809263

  15. Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring.

    PubMed

    Fainberg, H P; Sharkey, D; Sebert, S; Wilson, V; Pope, M; Budge, H; Symonds, M E

    2013-01-01

    Reduced maternal food intake between early-to-mid gestation results in tissue-specific adaptations in the offspring following juvenile-onset obesity that are indicative of insulin resistance. The aim of the present study was to establish the extent to which renal ectopic lipid accumulation, as opposed to other markers of renal stress, such as iron deposition and apoptosis, is enhanced in obese offspring born to mothers nutrient restricted (NR) throughout early fetal kidney development. Pregnant sheep were fed either 100% (control) or NR (i.e. fed 50% of their total metabolisable energy requirement from 30-80 days gestation and 100% at all other times). At weaning, offspring were made obese and, at approximately 1 year, kidneys were sampled. Triglyceride content, HIF-1α gene expression and the protein abundance of the outer-membrane transporter voltage-dependent anion-selective channel protein (VDAC)-I on the kidney cortex were increased in obese offspring born to NR mothers compared with those born to controls, which exhibited increased iron accumulation within the tubular epithelial cells and increased gene expression of the death receptor Fas. In conclusion, suboptimal maternal nutrition coincident with early fetal kidney development results in enhanced renal lipid deposition following juvenile obesity and could accelerate the onset of the adverse metabolic, rather than cardiovascular, symptoms accompanying the metabolic syndrome. PMID:22951182

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

    SciTech Connect

    Perez-Tur, J.; Delacourte, A.; Chartier-Harlin, M.C.

    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.

  17. Distributional Cues and the Onset Bias in Early Word Segmentation

    ERIC Educational Resources Information Center

    Babineau, Mireille; Shi, Rushen

    2014-01-01

    In previous infant studies on statistics-based word segmentation, the unit of statistical computation was always aligned with the syllabic edge, which had a consonant onset. The current study addressed whether the learning system imposes a constraint that favors word forms beginning with a consonant onset over those beginning with an onsetless…

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

    ERIC Educational Resources Information Center

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  1. Family Functioning and Early Onset of Sexual Intercourse in Latino Adolescents

    ERIC Educational Resources Information Center

    Velez-Pastrana, Maria C.; Gonzalez-Rodriguez, Rafael A.; Borges-Hernandez, Adalisse

    2005-01-01

    The purpose of this study was to identify factors associated with early onset of sexual intercourse. Within an ecological system's conceptual framework, familial factors associated with early onset of sexual activity were identified in a sample of 425 adolescents from San Juan metro area schools. Measures included questions about sexual activity,…

  2. Child and Adolescent (Early Onset) Schizophrenia: A Review in Light of DSM-III-R.

    ERIC Educational Resources Information Center

    Werry, John S.

    1992-01-01

    This review of studies of early onset schizophrenia examines the nosological similarity between adult and early onset schizophrenia, differential diagnosis, treatment, and the extent to which children and adolescents diagnosed as having schizophrenia using adult criteria have the characteristic adult correlates. The paper discusses gender…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed Central

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

    2015-01-01

    Background: 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. Methods: 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 (<35.3 kg men; <19.6 kg women). Results: Using a multivariable logistic regression model, the risk of depressive symptoms was greatest in 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. Conclusions: 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. PMID:26122029

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

    PubMed Central

    Frankham, Patrick; Gosselin, Caroline; Cabanac, Michel

    2005-01-01

    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 consistent with previous

  7. Neuropsychological profile in early Parkinson's disease: Comparison between patients with right side onset versus left side onset of motor symptoms

    PubMed Central

    Adwani, Sikandar; Yadav, Ravi; Kumar, Keshav; Chandra, S. R.; Pal, Pramod Kumar

    2016-01-01

    Aims: Though impaired cognition in Parkinson's disease (PD) is well known, data in early PD is sparse. This study was designed to assess the cognitive profile in patients with early PD (motor symptoms <5 years and Hoehn and Yahr stage <2), and to compare the cognitive profile between these patients with right versus left side onset of motor symptoms. Materials and Methods: National Institute of National Health and Neurosciences (NIMHANS) neuropsychological battery was used to assess the cognitive profile in 50 patients with early PD and compared with 50 age-, education-, and gender-matched healthy controls. Within the PD group, the cognitive profile was also compared between patients with right side onset motor symptoms (RPD) versus those with left side onset (LPD). The neuropsychological tests assessed the executive functions, memory, attention, visuospatial functions, and psychomotor speed. Results: Among the 50 patients, 25 each were RPD and LPD. The two subgroups were matched for age, gender, education, age at disease onset, disease duration, and degree of motor disability. There was no significant difference between the groups on Hoehn and Yahr staging or Unified Parkinson Disease Rating Scale (UPDRS) motor score. Patients with early PD performed significantly worse in the tasks involving memory, executive functions, and attention compared to controls. However, there was no difference in the cognitive profile between RPD and LPD subgroups. Conclusions: Patients with early PD have cognitive dysfunction with predominant involvement of frontal and temporal lobes. Side of onset of motor symptoms probably does not have significant role in future development or profile of cognitive dysfunction in PD. PMID:27011633

  8. Early childhood obesity prevention in low-income, urban communities.

    PubMed

    Dawson-McClure, Spring; Brotman, Laurie Miller; Theise, Rachelle; Palamar, Joseph J; Kamboukos, Dimitra; Barajas, R Gabriela; Calzada, Esther J

    2014-01-01

    Given the disproportionately high rates of obesity-related morbidity among low-income, ethnic minority youth, obesity prevention in this population is critical. Prior efforts to curb childhood obesity have had limited public health impact. The present study evaluates an innovative approach to obesity prevention by promoting foundational parenting and child behavioral regulation. This pre-post intervention study evaluated an enhanced version of ParentCorps with 91 families of pre-Kindergarten students in low-income, urban communities. Assessments included tests of knowledge and parent report. Consistent with findings from two randomized controlled trials of ParentCorps, parent knowledge and use of foundational parenting practices increased and child behavior problems decreased. Child nutrition knowledge and physical activity increased and television watching decreased; for boys, sleep problems decreased. Comparable benefits occurred for children at high risk for obesity based on child dysregulation, child overweight, and parent overweight. Results support a "whole child," family-centered approach to health promotion in early childhood. PMID:24702665

  9. Early dropout predictive factors in obesity treatment

    PubMed Central

    Michelini, Ilaria; Falchi, Anna Giulia; Grecchi, Ilaria; Montagna, Elisabetta; De Silvestri, Annalisa; Tinelli, Carmine

    2014-01-01

    Diet attrition and failure of long term treatment are very frequent in obese patients. This study aimed to identify pre-treatment variables determining dropout and to customise the characteristics of those most likely to abandon the program before treatment, thus making it possible to modify the therapy to increase compliance. A total of 146 outpatients were consecutively enrolled; 73 patients followed a prescriptive diet while 73 followed a novel brief group Cognitive Behavioural Treatment (CBT) in addition to prescriptive diet. The two interventions lasted for six months. Anthropometric, demographic, psychological parameters and feeding behaviour were assessed, the last two with the Italian instrument VCAO Ansisa; than, a semi-structured interview was performed on motivation to lose weight. To identify the baseline dropout risk factors among these parameters, univariate and multivariate logistic models were used. Comparison of the results in the two different treatments showed a higher attrition rate in CBT group, despite no statistically significant difference between the two treatment arms (P = 0.127). Dropout patients did not differ significantly from those who did not dropout with regards to sex, age, Body Mass Index (BMI), history of cycling, education, work and marriage. Regardless of weight loss, the most important factor that determines the dropout appears to be a high level of stress revealed by General Health Questionnaire-28 items (GHQ-28) score within VCAO test. The identification of hindering factors during the assessment is fundamental to reduce the dropout risk. For subjects at risk, it would be useful to dedicate a stress management program before beginning a dietary restriction. PMID:24611111

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

    PubMed Central

    Aprile, Irene; Ferrarin, Maurizio; Padua, Luca; Di Sipio, Enrica; Simbolotti, Chiara; Petroni, Sergio; Tredici, Costanza; Dickmann, Anna

    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. Materials and Methods: Twenty-five patients were enrolled: 19 with esotropic (ESO) and 6 with exotropic strabismus (EXO). All patients underwent an 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 binocular visual field in patients with EXO and to a reduced visual field in

  11. Model mice for 15q11-13 duplication syndrome exhibit late-onset obesity and altered lipid metabolism.

    PubMed

    Kishimoto, Rui; Tamada, Kota; Liu, Xiaoxi; Okubo, Hiroko; Ise, Satoko; Ohta, Hisashi; Ruf, Sandra; Nakatani, Jin; Kohno, Nobuoki; Spitz, François; Takumi, Toru

    2015-08-15

    Copy number variations on human chromosome 15q11-q13 have been implicated in several neurodevelopmental disorders. A paternal loss or duplication of the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region confers a risk of obesity, although the mechanism remains a mystery due to a lack of an animal model that accurately recreates the obesity phenotype. We performed detailed analyses of mice with duplication of PWS/AS locus (6 Mb) generated by chromosome engineering and found that animals with a paternal duplication of this region (patDp/+) show late-onset obesity, high sensitivity for high-fat diet, high levels of blood leptin and insulin without an increase in food intake. We show that prior to becoming obese, young patDp/+ mice already had enlarged white adipocytes. Transcriptome analysis of adipose tissue revealed an up-regulation of Secreted frizzled-related protein 5 (Sfrp5), known to promote adipogenesis. We additionally generated a new mouse model of paternal duplication focusing on a 3 Mb region (3 Mb patDp/+) within the PWS/AS locus. These mice recapitulate the obese phenotypes including expansion of visceral adipose tissue. Our results suggest paternally expressed genes in PWS/AS locus play a significant role for the obesity and identify new potential targets for future research and treatment of obesity. PMID:26002101

  12. Astrocyte Leptin Receptor (ObR) and Leptin Transport in Adult-Onset Obese Mice

    PubMed Central

    Pan, Weihong; Hsuchou, Hung; He, Yi; Sakharkar, Amul; Cain, Courtney; Yu, Chuanhui; Kastin, Abba J.

    2008-01-01

    The agouti viable yellow (Avy) spontaneous mutation generates an unusual mouse phenotype of agouti-colored coat and adult-onset obesity with metabolic syndrome. Persistent production of agouti signaling protein in Avy mice antagonizes melanocortin receptors in the hypothalamus. To determine how this disruption of neuroendocrine circuits affects leptin transport across the blood-brain barrier (BBB), we measured leptin influx in Avy and B6 control mice after the development of obesity, hyperleptinemia, and increased adiposity. After iv bolus injection, 125I-leptin crossed the BBB significantly faster in young (2 month old) B6 mice than in young Avy mice or in older (8 month old) mice of either strain. This difference was not observed by in situ brain perfusion studies, indicating the cause being circulating factors, such as elevated leptin levels or soluble receptors. Thus, Avy mice showed peripheral leptin resistance. ObRa, the main transporting receptor for leptin at the BBB, showed no change in mRNA expression in the cerebral microvessels between the age-matched (2 month old) Avy and B6 mice. Higher ObRb mRNA was seen in the Avy microvasculature with unknown significance. Immunofluorescent staining unexpectedly revealed that many of the ObR(+) cells were astrocytes and that the Avy mice showed significantly more ObR(+) astrocytes in the hypothalamus than the B6 mice. Although leptin permeation from the circulation was slower in the Avy mice, the increased ObR expression in astrocytes and increased ObRb mRNA in microvessels suggest the possibility of heightened central nervous system sensitivity to circulating leptin. PMID:18292187

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

    PubMed Central

    Prahalad, Sampath; Walters, Thomas; Guthery, Stephen L.; Dubinsky, Marla; Baldassano, Robert; Crandall, Wallace V.; Rosh, Joel; Markowitz, James; Stephens, Michael; Kellermayer, Richard; Pfefferkorn, Marian; Heyman, Melvin B.; LeLeiko, Neal; Mack, David; Moulton, Dedrick; Kappelman, Michael D.; Kumar, Archana; Prince, Jarod; Bose, Promita; Mondal, Kajari; Ramachandran, Dhanya; Bohnsack, John F.; Griffiths, Anne M.; Haberman, Yael; Essers, Jonah; Thompson, Susan D.; Aronow, Bruce; Keljo, David J.; Hyams, Jeffrey S.; Denson, Lee A.; Kugathasan, Subra

    2015-01-01

    Background 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. Methods 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. Conclusions 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. PMID:26098103

  14. Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D.

    PubMed

    Nguyen, K Hoa; Ande, Sudharsana R; Mishra, Suresh

    2016-01-29

    The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both, obesity-related abnormalities and m-PHB. Collectively, this data provides a proof-of-concept that obesity-associated abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D and reveals PHB as a potential susceptibility gene for T1D. PMID:26766792

  15. Pure Word Deafness in a Patient with Early-Onset Alzheimer's Disease: An Unusual Presentation

    PubMed Central

    Kim, Sook Hui; Suh, Mee Kyung; Seo, Sang Won; Chin, Juhee; Han, Seol-Heui

    2011-01-01

    Background and Purpose The occurrence of PWD in neurodegenerative disease is very rare, and this is the first report of it being related to early-onset AD. We describe a patient with early-onset Alzheimer's disease (AD) who presented with pure word deafness (PWD). Case Report The patient had experienced PWD for 2 years, followed by other cognitive deficits suggestive of parietotemporal dysfunction. Brain imaging including 18FDG-PET and [11C] PIB-PET supported the diagnosis of AD. Conclusions Our case highlights the clinical variability that characterizes early-onset AD. PMID:22259620

  16. Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

    PubMed Central

    Arango, Celso

    2014-01-01

    Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

  17. Differential neurodevelopmental trajectories in patients with early-onset bipolar and schizophrenia disorders.

    PubMed

    Arango, Celso; Fraguas, David; Parellada, Mara

    2014-03-01

    Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

  18. Alcohol Abuse and the Elderly: Comparison of Early & Late-Life Onset.

    ERIC Educational Resources Information Center

    Schonfeld, Lawrence; And Others

    Two types of elderly alcohol abusers are described. Early onset or long-term alcohol abusers are abusers with long-standing behavioral problems considered well known to the social service delivery system. Late-life onset elderly alcohol abusers are those whose drinking problems began in the later years, after age 50, often in response to stresses…

  19. Global and Temporal Cortical Folding in Patients with Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Penttila, Jani; Paillere-Martinot, Marie-Laure; Martinot, Jean-Luc; Mangin, Jean-Francois; Burke, Lisa; Corrigall, Richard; Frangou, Sophia; Cachia, Arnaud

    2008-01-01

    Disturbances in the temporal lobes and alterations in cortical folding in adult on-set schizophrenia are studied using magnetic resonance T1 images of 51 patients. The study showed that patients with early on-set schizophrenia had lower global sulcal indices in both hemispheres and the left collateral sulcus has a lower sulcal index irrespective…

  20. White Matter Abnormalities in Early-Onset Schizophrenia: A Voxel-Based Diffusion Tensor Imaging Study

    ERIC Educational Resources Information Center

    Kumra, Sanjiv; Ashtari, Manzar; Cervellione, Kelly L.; Henderson, Inika; Kester, Hana; Roofeh, David; Wu, Jinghui; Clarke, Tana; Thaden, Emily; Kane, John M.; Rhinewine, Joseph; Lencz, Todd; Diamond, Alan; Ardekani, Babak A.; Szeszko, Philip R.

    2005-01-01

    Objective: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). Method: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and…

  1. Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

    ERIC Educational Resources Information Center

    Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

    2005-01-01

    Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

  2. What controls early or late onset of tropical North Atlantic hurricane season?

    NASA Astrophysics Data System (ADS)

    Zuo, Heng; Li, Tim; Liu, Jia; Peng, Melinda

    2016-06-01

    The occurrence of first hurricane in early summer signifies the onset of an active Atlantic hurricane season. The interannual variation of this hurricane onset date is examined for the period 1979-2013. It is found that the onset date has a marked interannual variation. The standard deviation of the interannual variation of the onset day is 17.5 days, with the climatological mean onset happening on July 23. A diagnosis of tropical cyclone (TC) genesis potential index (GPI) indicates that the major difference between an early and a late onset group lies in the maximum potential intensity (MPI). A further diagnosis of the MPI shows that it is primarily controlled by the local SST anomaly (SSTA). Besides the SSTA, vertical shear and mid-tropospheric relative humidity anomalies also contribute significantly to the GPI difference between the early and late onset groups. It is found that the anomalous warm (cold) SST over the tropical Atlantic, while uncorrelated with the Niño3 index, persists from the preceding winter to concurrent summer in the early (late) onset group. The net surface heat flux anomaly always tends to damp the SSTA, which suggests that ocean dynamics may play a role in maintaining the SSTA in the tropical Atlantic. The SSTA pattern with a maximum center in northeastern tropical Atlantic appears responsible for generating the observed wind and moisture anomalies over the main TC development region. A further study is needed to understand the initiation mechanism of the SSTA in the Atlantic.

  3. Evidence for three loci modifying age-at-onset of Alzheimer's disease in early-onset PSEN2 families.

    PubMed

    Marchani, Elizabeth E; Bird, Thomas D; Steinbart, Ellen J; Rosenthal, Elisabeth; Yu, Chang-En; Schellenberg, Gerard D; Wijsman, Ellen M

    2010-07-01

    Families with early-onset Alzheimer's disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of linkage between age-at-onset and chromosome 1q23.3 (P < 0.001) when analysis included all families, and to chromosomes 1q23.3 (P < 0.001), 17p13.2 (P = 0.0002), 7q33 (P = 0.017), and 11p14.2 (P = 0.017) in a single large pedigree. Simultaneous analysis of these four chromosomes maintained strong evidence of linkage to chromosomes 1q23.3 and 17p13.2 when all families were analyzed, and to chromosomes 1q23.3, 7q33, and 17p13.2 within the same single pedigree. Inclusion of major gene covariates proved essential to detect these linkage signals, as all linkage signals dissipated when PSEN2 and APOE were excluded from the model. The four chromosomal regions with evidence of linkage all coincide with previous linkage signals, associated SNPs, and/or candidate genes identified in independent AD study populations. This study establishes several candidate regions for further analysis and is consistent with an oligogenic model of AD risk and age-at-onset. More generally, this study also demonstrates the value of searching for modifier loci in existing datasets previously used to identify primary causal variants for complex disease traits. PMID:20333730

  4. Distributional cues and the onset bias in early word segmentation.

    PubMed

    Babineau, Mireille; Shi, Rushen

    2014-12-01

    In previous infant studies on statistics-based word segmentation, the unit of statistical computation was always aligned with the syllabic edge, which had a consonant onset. The current study addressed whether the learning system imposes a constraint that favors word forms beginning with a consonant onset over those beginning with an onsetless sub-syllable, by examining infants' segmentation of vowel-initial non-words in French liaison. French-learning 20- and 24-month-old infants (N = 64) were familiarized with sentences containing variable liaison consonants preceding the same vowel-initial non-word (e.g., /n/onche, /z/onche, /r/onche, /t/onche), such that the distributional cues supported the sub-syllabic target (e.g., onche). After familiarization, we tested sub-syllabic statistical segmentation by presenting the vowel-initial target (e.g., onche) versus another non-familiarized vowel-initial word (e.g., èque). Another group of infants was tested with a consonant-initial mis-segmentation of the target (e.g., zonche) versus another non-familiarized consonant-initial word (e.g., zèque). Results showed that 20-month-olds failed to segment the vowel-initial targets, but they mis-segmented the targets as consonant-initial, indicating that the onset bias dominated over sub-syllabic statistics for word segmentation at this age. Twenty-four-month-olds showed ambiguous interpretations (i.e., both vowel-initial segmentation and consonant-initial mis-segmentation), suggesting that the use of statistics to segment sub-syllabic words was emerging while the onset bias continued to have an impact. PMID:25437756

  5. Clinical patterns and outcome of early-onset inflammatory bowel disease.

    PubMed

    Ledder, Oren; Catto-Smith, Anthony G; Oliver, Mark R; Alex, George; Cameron, Donald J S; Hardikar, Winita

    2014-11-01

    We sought to determine whether extremely-early-onset childhood inflammatory bowel disease (age <6 years; 20 ulcerative colitis [UC], 8 Crohn disease [CD], 2 indeterminate, sequentially diagnosed) was clinically more severe than in older children (6-17 years; 19 UC, 39 CD, 2 indeterminate). Early-onset UC was marked by less abdominal pain at presentation, but an aggressive course with a significant reduction in weight-for-age, increased use of immunosuppressants, and more surgery. Children with early-onset CD were more likely to have bloody stools at presentation and an isolated colitis. This study supports the suggestion that inflammatory bowel disease phenotype differs in early-onset disease. PMID:24979317

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

    PubMed

    Sagar, K A; Dahlgren, M K; Gönenç, A; Racine, M T; Dreman, M W; Gruber, S A

    2015-12-01

    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. PMID:25936584

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

    PubMed Central

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

    2016-01-01

    Background & objectives: 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. Methods: 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. Results: 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. Interpretation & conclusions: This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults. PMID:27241640

  8. Distinguishing the early-onset/persistent and adolescence-onset antisocial behavior types: from birth to 16 years.

    PubMed

    Aguilar, B; Sroufe, L A; Egeland, B; Carlson, E

    2000-01-01

    Moffitt's theory regarding two types of adolescent antisocial behavior was investigated using a prospective, longitudinal study of normal and abnormal development in a primarily low socioeconomic status, ethnically diverse sample. Results supported the presence of an early-onset/persistent (EOP) group and an adolescence-onset (AO) group. Groups were most reliably and significantly distinguished by indices of socioemotional history within the first 3 years, but no significant differences were found on early measures of temperament or neuropsychological functioning. EOPs scored significantly lower than other groups on measures of neuropsychological functioning only during late childhood and adolescence, suggesting that the declines in verbal functioning that have been so reliably found in this and other samples of early-starting antisocial adolescents are progressive and consequent to adverse experience. In adolescence, AOs were significantly more likely to report high levels of internalizing symptoms and life stress, suggesting that AO antisocial behavior is not a benign phenomenon. Implications of these findings for etiologic theories of adolescent antisocial behavior are discussed. PMID:10847620

  9. Early Microbe Contact and Obesity Risk: Evidence Of Causality?

    PubMed

    Isolauri, Erika; Salminen, Seppo; Rautava, Samuli

    2016-07-01

    The industrialized societies worldwide are in the middle of epidemics of diet-related chronic diseases, obesity being the common denominator. Lately, these conditions have been linked with a distinct microbiota composition in affected individuals different from that of healthy individuals. In particular, dysbiosis during critical stages of development induces lasting alterations in the immune and metabolic phenotype. The compositional development of the gut microbiota, again, is highly sensitive to environmental influences such as maternal health and nutrition, the mode of delivery, early feeding and antibiotic use. Shifts in the microbiota by high-energy diet increase energy extraction and storage, provoke a low-grade inflammatory response and impair gut barrier function, and, consequently, result in obesity and metabolic disease. A lower abundance of butyrate-producing bacteria and lower overall richness of bacteria has been associated with increased metabolic disease risk in humans. Recent reports suggest that Akkermansia type bacteria or butyrate producing microbes may have anti-inflammatory potential and enhance intestinal barrier function, which may both alleviate obesity and related metabolic complications. Thus we are not directly what we eat or our mother eats, but what our microbiota eat and how the collective composition of the microbiome is modified by the diet. On this basis, altering the intestinal microecosystem may be taken as a key target to attain prophylactic or therapeutic effects in metabolic and inflammatory conditions. Tools for such modulation include specific probiotic bacteria and potentially also non-digestible carbohydrate components able to modify microbiota composition and activity. PMID:27380597

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

    PubMed Central

    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

  11. Depression and Anxiety Symptoms: Onset, Developmental Course and Risk Factors during Early Childhood

    ERIC Educational Resources Information Center

    Cote, Sylvana M.; Boivin, Michel; Liu, Xuecheng; Nagin, Daniel S.; Zoccolillo, Mark; Tremblay, Richard E.

    2009-01-01

    Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS). Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically…

  12. Predictors of Early-Onset Permanent Hearing Loss in Malnourished Infants in Sub-Saharan Africa

    ERIC Educational Resources Information Center

    Olusanya, Bolajoko O.

    2011-01-01

    The objective of this study was to determine the predictors of early-onset permanent hearing loss (EPHL) among undernourished infants in a low-income country where routine screening for developmental disabilities in early childhood is currently unattainable. All infants attending four community-based clinics for routine immunization who met the…

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

    ERIC Educational Resources Information Center

    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…

  14. Early-onset colorectal cancer: A separate subset of colorectal cancer

    PubMed Central

    Silla, Irene Osorio; Rueda, Daniel; Rodríguez, Yolanda; García, Juan Luis; de la Cruz Vigo, Felipe; Perea, José

    2014-01-01

    Colorectal cancer (CRC) has a great impact on the world population. With increasing frequency, CRC is described according to the presenting phenotype, based on its molecular characteristics. Classification of CRC tumors according to their genetic and/or epigenetic alterations is not only important for establishing the molecular bases of the disease, but also for predicting patient outcomes and developing more individualized treatments. Early-onset CRC is a heterogeneous disease, with a strong familial component, although the disease is sporadic in an important proportion of cases. Different molecular alterations appear to contribute to the apparent heterogeneity of the early-onset population and subgroups can be distinguished with distinct histopathologic and familial characteristics. Moreover, compared with late-onset CRC, there are characteristics that suggest that early-onset CRC may have a different molecular basis. The purpose of this review was to analyze the current state of knowledge about early-onset CRC with respect to clinicopathologic, familial and molecular features. Together, these features make it increasingly clear that this subset of CRC may be a separate disease, although it has much in common with late-onset CRC. PMID:25516639

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

    PubMed

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

    2015-01-01

    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. PMID:26633520

  16. Prevention of Early-onset Neonatal Group B Streptococcal Disease

    PubMed Central

    Marió, M. J. Soto; Valenzuela, I; Vásquez, A. E; Illanes, S. E

    2013-01-01

    Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is an opportunistic pathogen that colonizes the gastrointestinal and genitourinary tracts of up to 50% of healthy adults and newborns; it is responsible for significant morbidity and mortality. Early detection can be used to establish the use of antibiotic prophylaxis to significantly reduce neonatal sepsis. This article reviews methods of detection and prevention of GBS infection in the neonate. PMID:24358406

  17. Early-onset hypoparathyroidism and chronic keratitis revealing APECED.

    PubMed

    Mezgueldi, Ellia; Bertholet-Thomas, Aurélia; Milazzo, Solange; Morris, Michael; Bacchetta, Justine; Fabien, Nicole; Cochat, Pierre; Weetman, Anthony P; Kemp, Elizabeth Helen; Belot, Alexandre

    2015-10-01

    Early diagnosis of potentially life-threatening autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is crucial, but is often delayed due to the clinical heterogeneity of the disorder. Even in the absence of the classic disease triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency, a diagnosis of APECED should be considered in children who have hypoparathyroidism and chronic keratitis, with a past medical history showing a mild and transient Candida infection. PMID:26509012

  18. Collaborating for impact: a multilevel early childhood obesity prevention initiative.

    PubMed

    Agrawal, Tara; Hoffman, Jessica A; Ahl, Marilyn; Bhaumik, Urmi; Healey, Christine; Carter, Sonia; Dickerson, Deborah; Nethersole, Shari; Griffin, Daphne; Castaneda-Sceppa, Carmen

    2012-01-01

    This article presents Healthy Kids, Healthy Futures, a multilevel initiative in Boston, Massachusetts, which brings major institutions' missions and resources together to address early childhood obesity prevention. Programming is designed to facilitate healthy eating and physical activity in preschool children's home, school, and community environments by engaging parents and early childhood educators in the places where they live, learn, and play. This article describes how established interventions were implemented in a novel setting to engage the parents of children attending Head Start and staff, and presents pilot data from the first 2 years of the initiative. Healthy Kids, Healthy Futures is a feasible initiative, which has shown concrete, positive results that can be replicated. PMID:22617410

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

    PubMed Central

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

    2015-01-01

    Simple Summary Numerous studies have documented a high prevalence of keel bone fractures in laying hens. 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. About 62% of the hens had broken keel bones at depopulation. More new fractures occurred during the time when laying rates were highest. Hens with broken keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. All birds with bumblefoot on both feet had a fracture at depopulation. Abstract 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. PMID:26633520

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

    PubMed

    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. PMID:26097750

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

    PubMed Central

    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

  2. Genome-Wide Association Scan for Variants Associated with Early-Onset Prostate Cancer

    PubMed Central

    Lange, Ethan M.; Johnson, Anna M.; Wang, Yunfei; Zuhlke, Kimberly A.; Lu, Yurong; Ribado, Jessica V.; Keele, Gregory R.; Li, Jin; Duan, Qing; Li, Ge; Gao, Zhengrong; Li, Yun; Xu, Jianfeng; Isaacs, William B.; Zheng, Siqun; Cooney, Kathleen A.

    2014-01-01

    Prostate cancer is the most common non-skin cancer and the second leading cause of cancer related mortality for men in the United States. There is strong empirical and epidemiological evidence supporting a stronger role of genetics in early-onset prostate cancer. We performed a genome-wide association scan for early-onset prostate cancer. Novel aspects of this study include the focus on early-onset disease (defined as men with prostate cancer diagnosed before age 56 years) and use of publically available control genotype data from previous genome-wide association studies. We found genome-wide significant (p<5×10−8) evidence for variants at 8q24 and 11p15 and strong supportive evidence for a number of previously reported loci. We found little evidence for individual or systematic inflated association findings resulting from using public controls, demonstrating the utility of using public control data in large-scale genetic association studies of common variants. Taken together, these results demonstrate the importance of established common genetic variants for early-onset prostate cancer and the power of including early-onset prostate cancer cases in genetic association studies. PMID:24740154

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

    PubMed Central

    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

  4. Early Onset Neonatal Septicaemia Caused by Pantoea agglomerans

    PubMed Central

    Sengupta, Mallika; Das, Niloy Kumar; Guchhait, Partha; Misra, Saheli

    2016-01-01

    Pantoea agglomerans is an opportunistic pathogen causing infection in the immunocompromised patients. It is a plant pathogen and a rare human pathogen causing neonatal sepsis, joint infection, urinary tract infection and bloodstream infections. Neonatal Gram negative septicaemia may have an unusual presentation of subtle generalised neonatal seizures without any other cardinal features of sepsis. An appropriate diagnosis is therefore the key to proper management. P. agglomerans being an unusual cause of neonatal sepsis should be diagnosed early with proper antibiogram for clinical cure. Here, we report a case of neonatal sepsis caused by P. agglomerans in a tertiary care hospital in Eastern India. PMID:27437219

  5. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice.

    PubMed

    Schneeberger, Marc; Everard, Amandine; Gómez-Valadés, Alicia G; Matamoros, Sébastien; Ramírez, Sara; Delzenne, Nathalie M; Gomis, Ramon; Claret, Marc; Cani, Patrice D

    2015-01-01

    Recent evidence indicates that the gut microbiota plays a key role in the pathophysiology of obesity. Indeed, diet-induced obesity (DIO) has been associated to substantial changes in gut microbiota composition in rodent models. In the context of obesity, enhanced adiposity is accompanied by low-grade inflammation of this tissue but the exact link with gut microbial community remains unknown. In this report, we studied the consequences of high-fat diet (HFD) administration on metabolic parameters and gut microbiota composition over different periods of time. We found that Akkermansia muciniphila abundance was strongly and negatively affected by age and HFD feeding and to a lower extend Bilophila wadsworthia was the only taxa following an opposite trend. Different approaches, including multifactorial analysis, showed that these changes in Akkermansia muciniphila were robustly correlated with the expression of lipid metabolism and inflammation markers in adipose tissue, as well as several circulating parameters (i.e., glucose, insulin, triglycerides, leptin) from DIO mice. Thus, our data shows the existence of a link between gut Akkermansia muciniphila abundance and adipose tissue homeostasis on the onset of obesity, thus reinforcing the beneficial role of this bacterium on metabolism. PMID:26563823

  6. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice

    PubMed Central

    Schneeberger, Marc; Everard, Amandine; Gómez-Valadés, Alicia G.; Matamoros, Sébastien; Ramírez, Sara; Delzenne, Nathalie M.; Gomis, Ramon; Claret, Marc; Cani, Patrice D.

    2015-01-01

    Recent evidence indicates that the gut microbiota plays a key role in the pathophysiology of obesity. Indeed, diet-induced obesity (DIO) has been associated to substantial changes in gut microbiota composition in rodent models. In the context of obesity, enhanced adiposity is accompanied by low-grade inflammation of this tissue but the exact link with gut microbial community remains unknown. In this report, we studied the consequences of high-fat diet (HFD) administration on metabolic parameters and gut microbiota composition over different periods of time. We found that Akkermansia muciniphila abundance was strongly and negatively affected by age and HFD feeding and to a lower extend Bilophila wadsworthia was the only taxa following an opposite trend. Different approaches, including multifactorial analysis, showed that these changes in Akkermansia muciniphila were robustly correlated with the expression of lipid metabolism and inflammation markers in adipose tissue, as well as several circulating parameters (i.e., glucose, insulin, triglycerides, leptin) from DIO mice. Thus, our data shows the existence of a link between gut Akkermansia muciniphila abundance and adipose tissue homeostasis on the onset of obesity, thus reinforcing the beneficial role of this bacterium on metabolism. PMID:26563823

  7. Development of a Model of Early-Onset IgA Nephropathy

    PubMed Central

    Okazaki, Keiko; Suzuki, Yusuke; Otsuji, Mareki; Suzuki, Hitoshi; Kihara, Masao; Kajiyama, Tadahiro; Hashimoto, Azusa; Nishimura, Hiroyuki; Brown, Rhubell; Hall, Stacy; Novak, Jan; Izui, Shozo; Hirose, Sachiko

    2012-01-01

    ddY mice spontaneously develop IgA nephropathy (IgAN) with a variable age of disease onset. Establishing a model with early-onset IgAN could aid the investigation of mechanisms that underlie the pathogenesis of this disease. On the basis of histologic grading in serial biopsies, we previously classified ddY mice into early-onset, late-onset, and quiescent groups. Here, we selectively mated mice with the early-onset phenotype for >20 generations and established “grouped ddY” mice that develop IgAN within 8 weeks of age. Similar to human IgAN, the prognosis was worse for male mice than females. These mice homogeneously retained genotypes of four marker loci previously associated with the early-onset phenotype, confirming a close association of these loci with early-onset IgAN in ddY mice. Grouped ddY mice comprised two sublines, however, which had distinct genotypes at a susceptibility locus for high serum IgA levels, which maps within the Ig heavy-chain gene complex. The subline bearing the Igh-2a IgA allotype had a more rapid course of fatal disease and lower oligosaccharide content, suggesting that aberrant IgA glycosylation may promote the progression of murine IgAN. Taken together, these data indicate that grouped ddY mice may be a useful model for the identification of susceptibility genes and the underlying molecular mechanisms involved in the pathogenesis of human IgAN. PMID:22797187

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

    PubMed Central

    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 estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3βAdiol, CYP7B1 performs two major tasks: (i) it allows 3βAdiol to have growth inhibitory effects through ERβ and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3βAdiol. When CYP7B1 is inactivated, 3βAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen. PMID:15710898

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

    PubMed

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

    2005-02-22

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta 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 estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen. PMID:15710898

  10. Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

    PubMed Central

    2011-01-01

    Background Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology. PMID:21320302

  11. Amyloid beta protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer's disease.

    PubMed

    Nakamura, T; Shoji, M; Harigaya, Y; Watanabe, M; Hosoda, K; Cheung, T T; Shaffer, L M; Golde, T E; Younkin, L H; Younkin, S G

    1994-12-01

    The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD. PMID:7998778

  12. Loss of Nfkb1 leads to early onset aging

    PubMed Central

    Crawley, Clayton D.; Cahill, Kirk E.; Pytel, Peter; Liang, Hua; Kang, Shijun; Weichselbaum, Ralph R.; Yamini, Bakhtiar

    2014-01-01

    NF-(B is a major regulator of age-dependent gene expression and the p50/NF-(B1 subunit is an integral modulator of NF-(B 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-(B pathway and mammalian aging. PMID:25553648

  13. Classifying onset durations of early VLF events: Scattered field analysis and new insights

    NASA Astrophysics Data System (ADS)

    Kotovsky, D. A.; Moore, R. C.

    2015-08-01

    The physical processes responsible for a variety of early VLF scattering events have not yet been satisfactorily identified. Properly categorizing the early VLF event type is imperative to understand the causative physical processes involved. In this paper, the onset durations of 26 exceptionally high signal-to-noise ratio early VLF scattering events are analyzed, using scattered fields to classify events. New observations of events that exhibit "slow" amplitude changes, but "fast" scattered field changes are presented, which call into question previous analyses of early/slow events. We separately identify and analyze three early VLF events that definitively exhibit slow scattered field behavior. Additionally, we identify a significant number of events which have onset durations between the current definitions of fast and slow. Four events are observed which unambiguously exhibit a rapid initial rotation of the scattered field phasor during the first few seconds of the recovery stage. Possible physical mechanisms are discussed.

  14. Matters of Size: Obesity as a Diversity Issue in the Field of Early Childhood.

    ERIC Educational Resources Information Center

    Jalongo, Mary Renck

    1999-01-01

    Notes that obesity is the primary reason for peer rejection in America; examines effects of obesity on wellness, self-esteem, peer relationships, and social status of children/families and early childhood teachers. Suggests that early childhood educators: (1) educate all stakeholders about nutrition and body size issues; (2) speak out against…

  15. Anaesthetists' experiences with the early labour epidural recommendation for obese parturients: a qualitative study.

    PubMed

    Va, Eley; Lk, Callaway; Aaj, van Zundert; J, Lipman; C, Gallois

    2016-09-01

    Caring for obese pregnant women presents challenges for all medical professionals. Despite a lack of supporting evidence, expert opinion and international guidelines suggest early labour epidural insertion for obese women. Anecdotally this is not supported by all anaesthetists. This qualitative study explored the experiences of anaesthetists regarding early epidural analgesia in obese parturients, to answer the research question: Are anaesthetists consistent in how they apply early epidural analgesia in obese parturients? Personal in-depth interviews with 42 specialist anaesthetists working in south-east Queensland, Australia, were completed between February and April, 2015. Leximancer™ text analysis software applied a validated algorithm to the data to identify themes and concepts. The major themes were explored by the first author to answer the research question. Three major themes were identified: the demands associated with caring for obese women; concern regarding the anaesthetic technique used in obese women; and the importance of communication with obstetric staff. Disagreement regarding interpretation and application of early epidural analgesia was identified within this group of anaesthetists. These anaesthetists were inconsistent in how they interpreted and applied early epidural analgesia for obese parturients, with some questioning the validity of the practice. The combination of uncertainty, urgency and technical difficulty presented by obese parturients provoked anxiety in these clinicians, particularly the anticipation of unplanned general anaesthesia. Consistent anaesthetic practice could improve the implementation of early epidural analgesia in obese parturients. PMID:27608347

  16. Surgical treatment of early onset scoliosis in neurofibromatosis.

    PubMed

    Greggi, Tiziana; Martikos, Konstantinos

    2012-01-01

    Case series report of twenty-three patients, aged between 4 and 11 years, were surgically treated at the Authors' Spine Surgery Division in the past 15 years. Mean follow-up is 5 years (range, 18 months to 15 years). Mean age at the time of surgical procedure was 9.1 years (range, 4 years to 11 years). Average scoliosis was 48° (range, 38° to 82°) and skeletal maturity according to Risser sign was 0 in all of the patients. Patients were divided into 2 Groups according to the surgical procedure adopted. Posterior only instrumentation was performed in 16 patients that presented with a thoracic kyphosis lower than 50° (Group A), in the remaining 7 patients showing thoracic kyphosis exceeding 50°, combined anterior and posterior instrumented arthrodesis was performed (Group B). One patient, belonging to Group A, was instrumented with growing rod without fusion. Average correction of scoliosis was 60%, overall complication rate 24% and major 7%. Crankshaft phenomenon was observed in 21% (Group A): in these cases, anterior arthrodesis was performed after a mean 15-month from first surgical procedure. Fusion failure was observed in 1 (Group B) patient who underwent revision of posterior instrumentation. Clinical and radiographic evaluation at F-up showed good outcome in terms of deformity progression and quality of life. Early and aggressive surgery is the most effective management for dystrophic curves in neurofibromatosis has been proven to be. Our experience confirms the need for spinal stabilization even in pediatric age in rapidly progressive spinal deformities. PMID:22744522

  17. Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: a European early-onset dementia consortium study.

    PubMed

    Cuyvers, Elise; van der Zee, Julie; Bettens, Karolien; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; Robberecht, Caroline; Dillen, Lubina; Merlin, Céline; Geerts, Nathalie; Graff, Caroline; Thonberg, Håkan; Chiang, Huei-Hsin; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Nacmias, Benedetta; Sorbi, Sandro; Sanchez-Valle, Raquel; Lladó, Albert; Gelpi, Ellen; Almeida, Maria Rosário; Santana, Isabel; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Matěj, Radoslav; Rohan, Zdenek; Ruiz, Agustín; Frisoni, Giovanni B; Fabrizi, Gian Maria; Vandenberghe, Rik; De Deyn, Peter P; Van Broeckhoven, Christine; Sleegers, Kristel

    2015-05-01

    Meta-analysis of existing genome-wide association studies on Alzheimer's disease (AD) showed subgenome-wide association of an intronic variant in the sequestosome 1 (SQSTM1) gene with AD. We performed targeted resequencing of SQSTM1 in Flanders-Belgian AD patients selected to be enriched for a genetic background (n = 435) and geographically matched nonaffected individuals (n = 872) to investigate the role of both common and rare SQSTM1 variants. Results were extended to the European early-onset dementia cohorts (926 early-onset Alzheimer's disease [EOAD] patients and 1476 nonaffected individuals). Of the 61 detected exonic variants in SQSTM1, the majority were rare (n = 57). Rare variant (minor allele frequency <0.01) burden analysis did not reveal an increased frequency of rare variants in EOAD patients in any of the separate study populations nor when meta-analyzing all cohorts. Common variants p.D292= and p.R312= showed nominal association with AD (odds ratiop.D292= = 1.11 [95% confidence interval = 1-1.22], p = 0.04), only when including the Flanders-Belgian cohort in the meta-analysis. We cannot exclude a role of SQSTM1 genetic variability in late-onset AD, but our data indicate that SQSTM1 does not play a major role in the etiology of EOAD. PMID:25796131

  18. Early hepatic insult in the offspring of obese maternal mice.

    PubMed

    Bringhenti, Isabele; Ornellas, Fernanda; Martins, Marcela Anjos; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2015-02-01

    We hypothesized that the maternal obesity initiates metabolic disorders associated with oxidative stress in the liver of offspring since early life. Mouse's mothers were assigned into 2 groups according to the diet offered (n = 10 per group): standard chow (SC) or high-fat diet (HF). The results revealed that HF offspring had an increase in body mass at day 10 (+25%, P < .05) and in glucose levels (+25%, P < .0001). Hepatic triacylglycerol was increased in HF offspring at day 1 and day 10 compared with SC offspring (+30%, P < .01 and +40%, P < .01) as was hepatic steatosis (+110%, P < .001; +145%, P < .0001). Fatty acid synthase was increased in HF offspring at day 1 (+450%, P < .01) and peroxisome proliferator activator receptor-γ was elevated at day 1 and day 10 (+140%, P < .01; +2741%, P < .01). Peroxisome proliferator activator receptor-α was diminished in HF offspring at day 10 compared with SC offspring (-100%, P < .01). Moreover, carnitine palmitoyl-CoA transferase-1 was decreased in HF offspring at day 1 and day 10 (-80%, P < .01; -60%, P < .05). In the HF offspring (compared with the SC offspring), the catalase and the superoxide dismutase were significantly lower in both days 1 and 10 (P < .05). In 10-day-old offspring, glutathione peroxidase 1 and glutathione reductase were lower in HF offspring than in SC offspring (P < .0001). Our findings suggest that the maternal obesity in mice induces an early oxidative dysfunction coupled with hepatic steatosis and might contribute to progressive liver injury later in life. PMID:25582085

  19. Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder

    PubMed Central

    Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

    2015-01-01

    Objectives Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. Methods DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset with the definition of first manic or depressive episode at age ≤ 19 years (versus adult-onset cases at age > 19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Results Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). Conclusions These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. PMID:26528762

  20. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  1. Reconceptualizing Early- and Late-Onset: A Life Course Analysis of Older Heroin Users

    PubMed Central

    Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.

    2013-01-01

    Purpose Our knowledge regarding older users of illicit drugs is limited despite their increasing numbers. In this paper we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods Qualitative data were collected from 29 older heroin users. Life course analysis focused on the users’ experiences across the life span. Results The findings suggest that those aging-into heroin use (late-onset) are disadvantaged compared to those who are maturing-in (early-onset) except in areas of health. Implications We propose that conceptualizing the use of heroin and other illicit drugs among older adults based on their life course trajectory will provide insights for social and health services, including drug treatment. PMID:18981280

  2. Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study

    PubMed Central

    Margari, Francesco; Presicci, Anna; Petruzzelli, Maria Giuseppina; Ventura, Patrizia; Di Cuonzo, Franca; Palma, Michele; Margari, Lucia

    2008-01-01

    Although schizophrenia has been diagnosed in children, this group of disorders has received too little attention in the clinical and research literature. Preliminary data suggest that early onset schizophrenia (EOS) and very early onset schizophrenia (VEOS) tend to have a worse outcome than adult onset schizophrenia, and seem to be related to a greater familial vulnerability, due to genetic, psychosocial, and environmental factors. Recently, advanced neuroimaging techniques have revealed structural and functional brain abnormalities in some cerebral areas. This paper reports on a case diagnosed as VEOS, with premorbid year-long psychopathological history. The patient showed atypical proton magnetic resonance spectroscopy findings, and normal brain and spine computer tomography and brain magnetic resonance images. PMID:19043525

  3. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature.

    PubMed

    Chew, H B; Ngu, L H; Keng, W T

    2011-01-01

    A rare syndrome of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) has been recently described. We report the first patient with this syndrome in Southeast Asia and review reported cases to date. Our patient was good health with normal development until the age of 2. He then developed hyperphagic obesity, hypersomnolence, seizures, alveolar hypoventilation, central hypothyroidism, sodium and water dysregulation, gastrointestinal dysmotility, strabismus, disordered temperature and irregular heart rate, altered sweating, delayed puberty, mental retardation and recurrent respiratory tract infections. The cardiomyopathy with heart failure and abnormal cerebral spinal fluid (CSF) neurotransmitter analysis present in our patient have not been reported previously. Tumours of the sympathetic nervous system are known to be associated with this syndrome but had not been found in our patient at the time of reporting. We highlight the difficulty of achieving the diagnosis of ROHHAD syndrome and its overlap with other well-established disease entities. The mortality and morbidity resulting from the high incidence of cardiorespiratory arrest may be prevented by early ventilatory support. PMID:22715259

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

    PubMed

    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. PMID:23390859

  5. The Effects of Childhood ADHD Symptoms on Early-Onset Substance Use: A Swedish Twin Study

    ERIC Educational Resources Information Center

    Chang, Zheng; Lichtenstein, Paul; Larsson, Henrik

    2012-01-01

    Research has documented that children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of substance use problems. Few studies, however, have focused on early-onset substance use. This study therefore investigated how the two symptom dimensions of ADHD (hyperactivity/impulsivity and inattention) are…

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

    ERIC Educational Resources Information Center

    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…

  7. A recurrent fibrillin-1 mutation in severe early onset Marfan syndrome

    PubMed Central

    Sureka, Dimple; Stheneur, Chantal; Odent, Sylvie; Arno, Gavin; Murphy, Daniel; Bernstein, Jonathan A.

    2014-01-01

    The recurrent substitution of isoleucine for threonine at codon 1048 (I1048T) substitution has been linked to severe, early onset Marfan syndrome, however, the existence of strong genotype-phenotype associations in Marfan syndrome (MFS) is not widely agreed upon. Our aim is to substantiate the association between the I1048T substitution and a severe clinical presentation to facilitate care planning and genetic counseling. We review the clinical findings from seven cases of early-onset MFS with a recurrent I1048T substitution. The presented findings include those from one newly diagnosed case, significant new detail from three additional cases, and a review of published findings in three cases. All seven individuals with the I1048T substitution had mitral insufficiency, arachnodactyly and characteristic facies consistent with early-onset MFS. Our findings support the existence of a genotype-phenotype correlation between the I1048T substitution and early-onset MFS. Recognition of this relationship has implications for genetic counseling and clinical care. Additionally, exploration of how the I1048T substitution results in a severe phenotype may lead to further insight into the pathophysiology of MFS.

  8. Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

    ERIC Educational Resources Information Center

    Frazier, Jean A.; Giuliano, Anthony J.; Johnson, Jacqueline L.; Yakutis, Lauren; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.; Hooper, Stephen R.

    2012-01-01

    Objective: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method: Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated…

  9. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

    ERIC Educational Resources Information Center

    Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

    2007-01-01

    Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

  10. Early- Versus Late-Onset Prosthetic Mesh Infection: More than Time Alone.

    PubMed

    Kong, Wencheng; Wang, Jian; Mao, Qi; Ren, Lele; Zhang, Shaoyi; Yao, Danhua; Guo, Mingxiao; Li, Yousheng

    2015-12-01

    Prosthetic mesh used for ventral incisional hernia makes hernia repair surgery simple, effective, and safe. The mesh infection is a formidable complication and bimodal distribution. The differences between early- and late-onset are unknown. This is a cohort study of patients undergoing ventral incisional hernia (VIH) repair from January 2003 to September 2013. Data of specific risk variables were collected from electronic medical record systems in Jinling Hospital. And, the quality of lives was evaluated by WHO Quality of Life-BREF. A total of 102 VIH repair patients were analyzed and followed including the noninfection group and early- and late-onset group. There were significant differences between the early- and late-onset group in clinical manifestation, descriptive analysis of the study population, and postoperative quality of lives. These differences might imply the different pathophysiologic process of early- and late-onset mesh infection. Permanent prosthetic mesh should be used with caution, and the study of intraperitoneal onlay mesh is still needed in long-term follow-up. PMID:27011528

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

    ERIC Educational Resources Information Center

    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…

  12. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

    PubMed

    Gargett, C E; Schwab, K E; Brosens, J J; Puttemans, P; Benagiano, G; Brosens, I

    2014-07-01

    The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition. PMID:24674992

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

    ERIC Educational Resources Information Center

    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,…

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

    ERIC Educational Resources Information Center

    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),…

  15. Psychosocial Interventions for Children with Early-Onset Bipolar Spectrum Disorder

    ERIC Educational Resources Information Center

    Lofthouse, Nicholas; Fristad, Mary A.

    2004-01-01

    Once considered virtually nonexistent, bipolar disorder in children has recently received a great deal of attention from mental health professionals and the general public. This paper provides a current review of literature pertaining to the psychosocial treatment of children with early-onset bipolar spectrum disorder (EOBPSD). Commencing with…

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

    ERIC Educational Resources Information Center

    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…

  17. Enhanced Visual Speech Perception in Individuals with Early-Onset Hearing Impairment

    ERIC Educational Resources Information Center

    Auer, Edward T., Jr.; Bernstein, Lynne E.

    2007-01-01

    Purpose: L. E. Bernstein, M. E. Demorest, and P. E. Tucker (2000) demonstrated enhanced speechreading accuracy in participants with early-onset hearing loss compared with hearing participants. Here, the authors test the generalization of Bernstein et al.'s (2000) result by testing 2 new large samples of participants. The authors also investigated…

  18. Maturation, Peer Context, and Indigenous Girls' Early-Onset Substance Use

    ERIC Educational Resources Information Center

    Walls, Melissa L.; Whitbeck, Les B.

    2011-01-01

    This article examines a biosocial model of the impact of puberty on indigenous girls' early-onset substance use by considering the potential mediating role of peer context (i.e., mixed-sex peer groups and substance use prototypes) on the puberty and substance use relationship. Data include responses from 360 girls of a common indigenous cultural…

  19. Early-onset neutropenia induced by rituximab in a patient with lupus nephritis and hemolytic anemia.

    PubMed

    Arroyo-Ávila, Mariangelí; Fred-Jiménez, Ruth M; Vilá, Luis M

    2015-01-01

    Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 10(9)/L) after the second weekly rituximab infusion (375 mg/m(2) weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections. PMID:25767732

  20. Early-Onset Neutropenia Induced by Rituximab in a Patient with Lupus Nephritis and Hemolytic Anemia

    PubMed Central

    Arroyo-Ávila, Mariangelí; Fred-Jiménez, Ruth M.; Vilá, Luis M.

    2015-01-01

    Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several complications of systemic lupus erythematosus (SLE) including nephritis, cerebritis, and hematological disorders. Neutropenia is among the adverse events associated with rituximab; this usually occurs several weeks after therapy. However, early-onset neutropenia has been reported only in a few cases. Herein, we describe a 36-year-old Hispanic SLE woman who developed severe early-onset neutropenia (0.3 × 109/L) after the second weekly rituximab infusion (375 mg/m2 weekly × 4) given for nephritis and hemolytic anemia. She also had early-onset thrombocytopenia after rituximab therapy. Both hematological disorders resolved 12 days after the fourth and final dose. This case, together with few others, suggests that early-onset neutropenia may occur during rituximab therapy. Even though rituximab-induced neutropenia seems to be transient, it may predispose SLE patients to severe complications such as infections. PMID:25767732

  1. Reconceptualizing Early and Late Onset: A Life Course Analysis of Older Heroin Users

    ERIC Educational Resources Information Center

    Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.

    2008-01-01

    Purpose: Researchers' knowledge regarding older users of illicit drugs is limited despite the increasing numbers of users. In this article, we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods: We collected qualitative data from…

  2. Exploring the genetic basis of early-onset chronic kidney disease.

    PubMed

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-03-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of CKD in adults. In the USA the most common diagnostic groups of renal disease that manifest before the age of 25 years are congenital anomalies of the kidneys and urinary tract, steroid-resistant nephrotic syndrome, chronic glomerulonephritis and renal cystic ciliopathies, which together encompass >70% of early-onset CKD diagnoses. Findings from the past decade suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. Developments in high-throughput sequencing in the past few years has rendered identification of causative mutations in this high number of genes feasible. Use of genetic analyses in patients with early onset-CKD will provide patients and their families with a molecular genetic diagnosis, generate new insights into disease mechanisms, facilitate aetiology-based classifications of patient cohorts for clinical studies, and might have consequences for personalized approaches to the prevention and treatment of CKD. In this Review, we discuss the implications of next-generation sequencing in clinical genetic diagnostics and the discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and the therapeutic implications of these findings. PMID:26750453

  3. Prelabor cesarean delivery and early-onset acute childhood leukemia risk.

    PubMed

    Thomopoulos, Thomas P; Skalkidou, Alkistis; Dessypris, Nick; Chrousos, George; Karalexi, Maria A; Karavasilis, Theodoros G; Baka, Margarita; Hatzipantelis, Emmanuel; Kourti, Maria; Polychronopoulou, Sophia; Sidi, Vasiliki; Stiakaki, Eftichia; Moschovi, Maria; Loutradis, Dimitrios; Petridou, Eleni Th

    2016-03-01

    The long-term impact of cesarean delivery (CD) on the health of the offspring is being explored methodically. We sought to investigate the effect of birth by (a) prelabor and (b) during-labor CD on the risk of early-onset (≤3 years) acute lymphoblastic leukemia (ALL), specifically of its prevailing precursor B (B-ALL) subtype. A total of 1099 incident cases of ALL (957 B-ALL), 131 of acute myeloid leukemia (AML), and their 1 : 1 age-matched and sex-matched controls, derived from the Nationwide Registry for Childhood Hematological Malignancies (1996-2013), were analyzed using multivariate regression models. A null association was found between prelabor and/or during labor CD and either ALL (B-ALL) or AML in the 0-14 age range. By contrast, birth by CD increased significantly the risk of early-onset ALL [odds ratioCD (ORCD)=1.57, 95% confidence interval (CI): 1.10-2.24] mainly on account of prelabor CD (ORprelaborCD=1.66, 95% CI: 1.13-2.43). The respective figures were even higher for the early-onset precursor B-ALL (ORCD=1.66, 95% CI: 1.15-2.40 and ORprelaborCD=1.79, 95% CI: 1.21-2.66), whereas no association emerged for early-onset AML. Prelabor CD, which deprives exposure of the fetus/infant to the presumably beneficial effect of stress hormones released in both vaginal labor and during labor CD, was associated exclusively with an increased risk of early-onset ALL, particularly the precursor B-ALL subtype. If confirmed, these adverse long-term outcomes of CD may point to re-evaluation of prelabor CD practices and prompt scientific discussion on the best ways to simulate the effects of vaginal delivery, such as a precesarean induction of labor. PMID:25793919

  4. Exome sequencing identified null mutations in LOXL3 associated with early-onset high myopia

    PubMed Central

    Li, Jiali; Gao, Bei; Xiao, Xueshan; Li, Shiqiang; Jia, Xiaoyun; Sun, Wenmin; Guo, Xiangming

    2016-01-01

    Purpose To identify null mutations in novel genes associated with early-onset high myopia using whole exome sequencing. Methods Null mutations, including homozygous and compound heterozygous truncations, were selected from whole exome sequencing data for 298 probands with early-onset high myopia. These data were compared with those of 507 probands with other forms of eye diseases. Null mutations specific to early-onset high myopia were considered potential candidates. Candidate mutations were confirmed with Sanger sequencing and were subsequently evaluated in available family members and 480 healthy controls. Results A homozygous frameshift mutation (c.39dup; p.L14Afs*21) and a compound heterozygous frameshift mutation (c.39dup; p.L14Afs*21 and c.594delG; p.Q199Kfs*35) in LOXL3 were separately identified in two of the 298 probands with early-onset high myopia. These mutations were confirmed with Sanger sequencing and were not detected in 1,974 alleles of the controls from the same region (507 individuals with other conditions and 480 healthy control individuals). These two probands were singleton cases, and their parents had only heterozygous mutations. A homozygous missense mutation in LOXL3 was recently reported in a consanguineous family with Stickler syndrome. Conclusions Our results suggest that null mutations in LOXL3 are likely associated with autosomal recessive early-onset high myopia. LOXL3 is a potential candidate gene for high myopia, but this possibility should be confirmed in additional studies. LOXL3 null mutations in human beings are not lethal, providing a phenotype contrary to that in mice. PMID:26957899

  5. Early-onset and late-onset Alzheimer's disease are associated with distinct patterns of memory impairment.

    PubMed

    Joubert, Sven; Gour, Natalina; Guedj, Eric; Didic, Mira; Guériot, Claude; Koric, Lejla; Ranjeva, Jean-Philippe; Felician, Olivier; Guye, Maxime; Ceccaldi, Mathieu

    2016-01-01

    The goal of this study was to investigate the specific patterns of memory breakdown in patients suffering from early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Twenty EOAD patients, twenty LOAD patients, twenty matched younger controls, and twenty matched older controls participated in this study. All participants underwent a detailed neuropsychological assessment, an MRI scan, an FDG-PET scan, and AD patients had biomarkers as supporting evidence of both amyloïdopathy and neuronal injury. Results of the neuropsychological assessment showed that both EOAD and LOAD groups were impaired in the domains of memory, executive functions, language, praxis, and visuoconstructional abilities, when compared to their respective control groups. EOAD and LOAD groups, however, showed distinct patterns of memory impairment. Even though both groups were similarly affected on measures of episodic, short term and working memory, in contrast semantic memory was significantly more impaired in LOAD than in EOAD patients. The EOAD group was not more affected than the LOAD group in any memory domain. EOAD patients, however, showed significantly poorer performance in other cognitive domains including executive functions and visuoconstructional abilities. A more detailed analysis of the pattern of semantic memory performance among patient groups revealed that the LOAD was more profoundly impaired, in tasks of both spontaneous recall and semantic recognition. Voxel-Based Morphometry (VBM) analyses showed that impaired semantic performance in patients was associated with reduced gray matter volume in the anterior temporal lobe (ATL) region, while PET-FDG analyses revealed that poorer semantic performance was associated with greater hypometabolism in the left temporoparietal region, both areas reflecting key regions of the semantic network. Results of this study indicate that EOAD and LOAD patients present with distinct patterns of memory impairment, and that

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

    PubMed Central

    Lee, Soon Min; Chang, Meayoung

    2015-01-01

    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. PMID:26566360

  7. A Pilot Study of Parent Mentors for Early Childhood Obesity.

    PubMed

    Foster, Byron A; Aquino, Christian A; Gil, Mario; Gelfond, Jonathan A L; Hale, Daniel E

    2016-01-01

    Objective. To assess the feasibility of a parent mentor model of intervention for early childhood obesity using positive deviance-based methods to inform the intervention. Methods. In this pilot, randomized clinical trial, parent-child dyads (age: 2-5) with children whose body mass index (BMI) was ≥95th percentile were randomized to parent mentor intervention or community health worker comparison. The child's height and weight were measured at baseline, after the six-month intervention, and six months after the intervention. Feasibility outcomes were recruitment, participation, and retention. The primary clinical outcome was BMI z-score change. Results. Sixty participants were enrolled, and forty-eight completed the six-month intervention. At baseline, the BMI z-score in the parent mentor group was 2.63 (SD = 0.65) and in the community health worker group it was 2.61 (SD = 0.89). For change in BMI z-score over time, there was no difference by randomization group at the end of the intervention: -0.02 (95% CI: -0.26, 0.22). At the end of the intervention, the BMI z-score for the parent mentor group was 2.48 (SD = 0.58) and for the community health worker group it was 2.45 (SD = 0.91), both reduced from baseline, p < 0.001. Conclusion. The model of a parent mentor clinical trial is feasible, and both randomized groups experienced small, sustained effects on adiposity in an obese, Hispanic population. PMID:27379182

  8. A Pilot Study of Parent Mentors for Early Childhood Obesity

    PubMed Central

    Foster, Byron A.; Aquino, Christian A.; Gil, Mario; Gelfond, Jonathan A. L.; Hale, Daniel E.

    2016-01-01

    Objective. To assess the feasibility of a parent mentor model of intervention for early childhood obesity using positive deviance-based methods to inform the intervention. Methods. In this pilot, randomized clinical trial, parent-child dyads (age: 2–5) with children whose body mass index (BMI) was ≥95th percentile were randomized to parent mentor intervention or community health worker comparison. The child's height and weight were measured at baseline, after the six-month intervention, and six months after the intervention. Feasibility outcomes were recruitment, participation, and retention. The primary clinical outcome was BMI z-score change. Results. Sixty participants were enrolled, and forty-eight completed the six-month intervention. At baseline, the BMI z-score in the parent mentor group was 2.63 (SD = 0.65) and in the community health worker group it was 2.61 (SD = 0.89). For change in BMI z-score over time, there was no difference by randomization group at the end of the intervention: −0.02 (95% CI: −0.26, 0.22). At the end of the intervention, the BMI z-score for the parent mentor group was 2.48 (SD = 0.58) and for the community health worker group it was 2.45 (SD = 0.91), both reduced from baseline, p < 0.001. Conclusion. The model of a parent mentor clinical trial is feasible, and both randomized groups experienced small, sustained effects on adiposity in an obese, Hispanic population. PMID:27379182

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

    PubMed

    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. PMID:25422974

  10. Premorbid Risk Factors for Major Depressive Disorder: Are They Associated With Early Onset and Recurrent Course?

    PubMed Central

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

    2014-01-01

    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 SNP-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. PMID:25422974

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

    PubMed Central

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

    2015-01-01

    Background 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. Methodology and Principal Findings 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. Conclusion 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. PMID:26244500

  12. Successful Management of New-Onset Diabetes Mellitus and Obesity With the Use of Laparoscopic Sleeve Gastrectomy After Kidney Transplantation-A Case Report.

    PubMed

    Chen, J-H; Lee, C-H; Chang, C-M; Yin, W-Y

    2016-04-01

    In kidney transplantation, obesity is associated with poorer graft survival and patient survival. Bariatric surgery may provide benefit for these patients, not only by inducing weight loss, but also via reduction of diabetes. We report a case of morbid obesity, poorly controlled new-onset diabetes mellitus, and gout after kidney transplantation that was treated with laparoscopic sleeve gastrectomy 3 years after kidney transplantation. After 1 year of follow-up, 76% excessive body weight loss was attained. No complications were noted. The operation also provided total remission of diabetes and gout as well as good graft survival. Based on our experience, laparoscopic sleeve gastrectomy may be a feasible treatment for obese patients after renal transplantation to help resolve obesity and control new-onset diabetes. However, the timing of operation and the long-term potential for graft and patient survivals with this operation require further study. PMID:27234772

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

    SciTech Connect

    Campion, D.; Martinez, M.; Babron, M.C.

    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.

  14. Next steps in obesity prevention: altering early life systems to support healthy parents, infants, and toddlers.

    PubMed

    Nader, Philip R; Huang, Terry T-K; Gahagan, Sheila; Kumanyika, Shiriki; Hammond, Ross A; Christoffel, Katherine Kaufer

    2012-06-01

    There is an urgent need for effective, sustainable child obesity prevention strategies. Progress toward this goal requires strengthening current approaches to add a component that addresses pregnancy onward. Altering early-life systems that promote intergenerational transmission of obesity holds promise for interrupting the continuing cycle of the obesity epidemic. A 2011 Institute of Medicine (IOM) report emphasizes the need for interventions early in life to prevent obesity. A 2010 IOM report called for addressing gaps in existing obesity research evidence by using a systems perspective, simultaneously addressing interacting obesity promoting factors in multiple sectors and at multiple societal levels. A review of evidence from basic science, prevention, and systems research supports an approach that (1) begins at the earliest stages of development, and (2) uses a systems framework to simultaneously implement health behavior and environmental changes in communities. PMID:22799545

  15. Complement Split Products in Amniotic Fluid in Pregnancies Subsequently Developing Early-Onset Preeclampsia

    PubMed Central

    Banadakoppa, Manu; Vidaeff, Alex C.; Yallampalli, Uma; Ramin, Susan M.; Belfort, Michael A.; Yallampalli, Chandra

    2015-01-01

    Objective. To determine the second-trimester amniotic fluid concentrations of complement split products in pregnancies subsequently affected by early-onset preeclampsia. Study Design. Cohort of 731 women with singleton pregnancies undergoing second-trimester genetic amniocentesis followed up to delivery and analyzed as a nested case-control study. Cases of preeclampsia developing before 34 weeks' gestation (n = 15) were compared with 47 uncomplicated term controls. Amniotic fluid collected at amniocentesis was tested for complement split products Bb, C4a, C3a, and C5a. Results. Women who developed early-onset preeclampsia as compared with the term pregnant controls had significantly higher (P = 0.04) median amniotic fluid C3a levels (318.7 ng/mL versus 254.5 ng/mL). Median amniotic fluid Bb levels were also significantly higher (P = 0.03) in preeclamptic women than in normal pregnant women (1127 ng/mL versus 749 ng/mL). Median levels of C4a and C5a were not significantly different between the groups. Conclusion. Our data suggest that complement activation in early pregnancy is associated with early-onset preeclampsia. We believe this to be the first prospective study to link complement activation in amniotic fluid in early pregnancy and later development of preeclampsia. Our findings provide evidence that immune dysregulation may precede the clinical manifestations of preeclampsia and that the alternative complement pathway is principally involved. PMID:26556948

  16. DRD3 variation associates with early-onset heroin dependence, but not specific personality traits.

    PubMed

    Kuo, Shin-Chang; Yeh, Yi-Wei; Chen, Chun-Yen; Huang, Chang-Chih; Chang, Hsin-An; Yen, Che-Hung; Ho, Pei-Shen; Liang, Chih-Sung; Chou, Han-Wei; Lu, Ru-Band; Huang, San-Yuan

    2014-06-01

    Dopamine D3 receptor-mediated pathways are involved in the mechanism of addiction, and genetic factors play a role in the vulnerability to heroin dependence. The aim of this study was to examine whether the corresponding gene, DRD3, is associated with the development of heroin dependence and specific personality traits in HD patients. Eight polymorphisms in DRD3 were analyzed in 1067 unrelated Han Chinese subjects (566 heroin dependence patients and 501 controls). All participants were screened using the same assessment tool and all patients met the criteria for heroin dependence. A Tridimensional Personality Questionnaire was used to assess personality traits in 276 heroin dependence patients. In addition, heroin dependence patients were divided into 4 clinical subgroups based on age-of-onset and family history of substance abuse, to reduce the clinical heterogeneity. The rs6280 and rs9825563 variants showed association with the development of early-onset heroin dependence. The GTA haplotype frequency in the block (rs324029, rs6280, rs9825563) was significantly associated with early-onset heroin dependence (p=0.003). However, these significant associations were weaker after Bonferroni's correction. In addition, these DRD3 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. DRD3 is possibly a genetic factor in the development of early-onset heroin dependence, but is not associated with specific personality traits in these patients among the Han Chinese population. PMID:24398431

  17. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

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

    PubMed Central

    Olson, J. Casey; Takahashi, Ayuko; Glotzbecker, Michael P.; Snyder, Brian D.

    2015-01-01

    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 also have

  19. Potential clinical translation of juvenile rodent inactivity models to study the onset of childhood obesity.

    PubMed

    Roberts, Michael D; Company, Joseph M; Brown, Jacob D; Toedebusch, Ryan G; Padilla, Jaume; Jenkins, Nathan T; Laughlin, M Harold; Booth, Frank W

    2012-08-01

    According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2-19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6-11 yr old fail to obtain the recommended 60 min/day of physical activity and 92% of adolescents fail to achieve this goal [Troiano et al. Med Sci Sports Exerc. 40, 2008]. Nonetheless, invasive mechanistic studies in children linking diminished physical activity with metabolic maladies are lacking for obvious ethical reasons. The rodent wheel lock (WL) model was adopted by our laboratory and others to study how different organ systems of juvenile rats respond to a cessation of daily physical activity. Our WL model houses rats in cages equipped with voluntary running wheels starting at 28 days of age. After a certain period of voluntary running (3 to 6 wk), the wheels are locked, thus preventing the rats' primary source of physical activity. The studies discussed herein suggest that obesity-associated maladies including skeletal muscle insulin resistance, hypothalamic leptin resistance, fatty acid oxidation impairments in skeletal muscle and adipose tissue, nonalcoholic fatty liver disease, and endothelial dysfunction are initiated in juvenile animals that are restrained from voluntary exercise via WL. The use of the juvenile rodent WL or other inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity. PMID:22696577

  20. Early Maternal Employment and Childhood Obesity among Economically Disadvantaged Families in the USA

    ERIC Educational Resources Information Center

    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. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    ERIC Educational Resources Information Center

    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…

  2. Altered brain development in an early-onset murine model of Alzheimer's disease.

    PubMed

    Allemang-Grand, R; Scholz, J; Ellegood, J; Cahill, L S; Laliberté, C; Fraser, P E; Josselyn, S A; Sled, J G; Lerch, J P

    2015-02-01

    Murine models of Alzheimer's disease (AD) have been used to draw associations between atrophy of neural tissue and underlying pathology. In this study, the early-onset TgCRND8 mouse model of AD and littermate controls were scanned longitudinally with in vivo manganese-enhanced MRI (MEMRI) before and after the onset of amyloid plaque deposition at 12 weeks of age. Separate cohorts of mice were scanned at 1 week (ex vivo imaging) and 4 weeks (MEMRI) of age to investigate early life alterations in the brain. Contrary to our expectations, differences in neuroanatomy were found in early post-natal life, preceding plaque deposition by as much as 11 weeks. Many of these differences remained at all imaging time points, suggesting that they were programmed early in life and were unaffected by the onset of pathology. Furthermore, rather than showing atrophy, many regions of the TgCRND8 brain grew at a faster rate compared to controls. These regions contained the greatest density of amyloid plaques and reactive astrocytes. Our findings suggest that pathological processes as well as an alteration in brain development influence the TgCRND8 neuroanatomy throughout the lifespan. PMID:25311279

  3. Obesity

    MedlinePlus

    Morbid obesity; Fat - obese ... is because the body stores unused calories as fat. Obesity can be caused by: Eating more food ... use your BMI to estimate how much body fat you have. Your waist measurement is another way ...

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

    PubMed

    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. PMID:26695168

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

    PubMed Central

    Evans, D Gareth R; Ingham, Sarah Louise

    2013-01-01

    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. PMID:23935382

  6. Weighing Evidence from Mendelian Randomization-Early-Life Obesity as a Causal Factor in Multiple Sclerosis?

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2016-06-01

    In this Perspective, Alberto Ascherio and Kassandra Munger discuss the implications of Richards and colleagues' study exploring the role of early-life obesity in risk of multiple sclerosis. PMID:27351631

  7. Association between serum soluble tumor necrosis factor-α receptors and early childhood obesity.

    PubMed

    Ouyang, Shengrong; Li, Wei; Liu, Zhuo; Li, Yuanyuan; Li, Sen; Wu, Jianxin

    2016-06-30

    This study aimed to characterize the inflammatory cytokine profiles and further validate the significantly different cytokines in the serum obtained from obese children aged 36-48 months. Four obese children and four lean controls were randomly selected for inflammatory cytokine array assay, in which two cytokines [soluble tumor necrosis factor-α receptors (sTNFRs) 1 and 2] were found to be significantly different. Both cytokines (sTNFR1 and sTNFR2) were then further validated through enzyme-linked immunosorbent assay (ELISA) in 61 obese children and 52 lean children. ELISA results revealed that serum sTNFR1 level in obese children significantly increased (p = 0.003), whereas sTNFR2 did not change significantly (p = 0.069). Stratified analysis by gender showed that only obese girls presented increased sTNFR1 (p = 0.005) and sTNFR2 (p = 0.049) levels. We conclude that serum sTNFR1 is elevated in early childhood obesity. Moreover, serum sTNFR1 and sTNFR2 are associated with obese girls but not obese boys, thereby suggesting that serum sTNFRs in early childhood obesity may be sex related. PMID:27040725

  8. Advanced magnetic resonance neuroimaging in bulbar and limb onset early amyotrophic lateral sclerosis

    PubMed Central

    Vora, Maulik; Kumar, Suresh; Sharma, Sanjiv; Sharma, Sudhir; Makhaik, Sushma; Sood, R. G.

    2016-01-01

    Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal and most common motor neuron disease, caused by progressive loss of motor neurons. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopic (MRS) studies detect pathological changes in neuronal fibers in vivo. We evaluated the role of DTI and MRS in early course of the disease, which may prove beneficial in the early diagnosis and better management. Materials and Methods: Twenty-one patients with ALS and 13 age-matched controls received 1.5T DTI and three-dimensional multi-voxel MRS. Fractional anisotropy (FA), apparent diffusion coefficient, N-acetyl aspartate (NAA)/Creatine (Cr), and NAA/Choline (Ch) ratios were analyzed in various regions of the brain and compared with healthy controls. ALS patients were classified as definite, possible, and probable category, and patients were also studied in limb versus bulbar onset. Results: Decreased FA and increase mean diffusivity values in regions of corticospinal tract (CST) and corpus callosum (CC) was consistent finding in definite and probable disease category (P < 0.05). In possible disease, CC involvement was not significant. NAA/Cr and NAA/Ch ratios were lower in CC and regions of CST. However, in possible disease, CC involvement was not significant, while regions of CST were showing significant reduction in NAA/Cr and NAA/Ch ratios (P < 0.05). Conclusion: DTI and MRS detect changes associated with ALS even in the early phase of the disease. Bulbar onset and limb onset ALS patients show different pattern of involvement. Extramotor involvement suggested by CC involvement is a feature seen in bulbar onset patient and can suggest poor outcome in such patients. The present findings may be helpful for designing further studies in the direction of more early diagnosis of disease and its management. PMID:26933355

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

    ERIC Educational Resources Information Center

    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…

  10. Homozygous partial genomic triplication of the parkin gene in early-onset parkinsonism.

    PubMed

    Mata, Ignacio F; Alvarez, Victoria; Coto, Eliecer; Blazquez, Marta; Guisasola, Luis M; Salvador, Carlos; Kachergus, Jennifer M; Lincoln, Sarah J; Farrer, Matthew

    2005-06-01

    Autosomal recessive mutations in the parkin gene are the predominant cause of familial, early-onset parkinsonism; missense mutations involving one or a few nucleotides, exonic deletions and duplications have been described. Here we report a family with two affected brothers. Direct sequencing of parkin did not detect mutations, but semi-quantitative analysis identified a novel exonic rearrangement of exons 2-4. Both patients were homozygous for unique genomic triplications of the parkin gene. PMID:15862897

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

    PubMed Central

    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. PMID:26617906

  12. Early onset life-threatening myelosuppression after low dose of intravesical thiotepa

    PubMed Central

    Agnelli, Giancarlo; Gresele, Paolo; de Cunto, Maria; del Favero, Albano

    1982-01-01

    Intravesical instillation of thiotepa is a popular treatment for localized bladder carcinoma. The drug can enter the systemic circulation, and such absorption may be enhanced by extensive tumour infiltration or by a recent tumour resection. A case is reported of early onset life-threatening pancytopenia following an unusually low dose of the drug in a patient who had undergone a recent tumour resection. PMID:6812036

  13. Intestinal deletion of leptin signaling alters activity of nutrient transporters and delayed the onset of obesity in mice.

    PubMed

    Tavernier, Annabelle; Cavin, Jean-Baptiste; Le Gall, Maude; Ducroc, Robert; Denis, Raphaël G P; Cluzeaud, Françoise; Guilmeau, Sandra; Sakar, Yassine; Barbot, Laurence; Kapel, Nathalie; Le Beyec, Johanne; Joly, Francisca; Chua, Streamson; Luquet, Serge; Bado, Andre

    2014-09-01

    The importance of B-isoform of leptin receptor (LEPR-B) signaling in the hypothalamus, pancreas, or liver has been well characterized, but in the intestine, a unique site of entry for dietary nutrition into the body, it has been relatively ignored. To address this question, we characterized a mouse model deficient for LEPR-B specifically in intestinal epithelial cells (IECs). (IEC)LEPR-B-knockout (KO) and wild-type (WT) mice were generated by Cre-Lox strategy and fed a normal or high-fat diet (HFD). The analyses of the animals involved histology and immunohistochemistry of intestinal mucosa, indirect calorimetric measurements, whole-body composition, and expression and activities of nutrient transporters. (IEC)LEPR-B-KO mice exhibited a 2-fold increase in length of jejunal villi and have normal growth on a normal diet but were less susceptible (P<0.01) to HFD-induced obesity. No differences occurred in energy intake and expenditure between (IEC)LEPR-B-WT and -KO mice, but (IEC)LEPR-B-KO mice fed an HFD showed increased excreted fats (P<0.05). Activities of the Na(+)/glucose cotransporter SGLT-1 and GLUT2 were unaffected in LEPR-B-KO jejunum, while GLUT5-mediated fructose transport and PepT1-mediated peptide transport were substantially reduced (P<0.01). These data demonstrate that intestinal LEPR-B signaling is important for the onset of diet-induced obesity. They suggest that intestinal LEPR-B could be a potential per os target for prevention against obesity. PMID:24928195

  14. 2014 CODEPEH recommendations: Early detection of late onset deafness, audiological diagnosis, hearing aid fitting and early intervention.

    PubMed

    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. PMID:26443498

  15. Iowa Gambling Task in patients with early-onset Parkinson's disease: strategy analysis.

    PubMed

    Gescheidt, Tomáš; Czekóová, Kristína; Urbánek, Tomáš; Mareček, Radek; Mikl, Michal; Kubíková, Radka; Telecká, Sabina; Andrlová, Hana; Husárová, Ivica; Bareš, Martin

    2012-12-01

    The aim of our study was to analyse decision making in early-onset Parkinson's disease (PD) patients performing the Iowa Gambling Task (IGT). We compared 19 patients with early-onset PD (≤ 45 years) on dopaminergic medication (no evidence of depression, dementia, executive dysfunction according to the Tower of London test and the Stroop test, or pathological gambling) with 20 age-matched controls. A computer version of the IGT was employed. The PD patients achieved slightly lower IGT scores than the control group. A detailed analysis based on 'shift frequencies' between the individual decks showed that the patients tended to change their preferences for the decks more frequently, with a higher preference for the 'disadvantageous' deck B. Control subjects seemed to develop a more effective strategy. These differences could be caused by the poorer ability of the patients to develop any strategy at all. We observed changes in decision making during IGT performance in patients with early-onset PD, although they had no executive dysfunction as measured by established neuropsychological tests. The more detailed analysis employed in the present study could lead to a more accurate study of IGT performance and application of IGT in clinical practice. PMID:22526761

  16. Modeling early-onset post-ischemic seizures in aging mice

    PubMed Central

    Wu, Chiping; Wang, Justin; Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H; McDonald, Robert; Zhang, Liang

    2016-01-01

    Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16–20 month-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6–8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals. PMID:25943585

  17. Early-onset osteoarthritis of mouse temporomandibular joint induced by partial discectomy

    PubMed Central

    Xu, L.; Polur, I.; Lim, C.; Servais, J. M.; Dobeck, J.; Li, Y.; Olsen, B. R.

    2010-01-01

    Summary Objective The objective of this study is to characterize mouse temporomandibular joint (TMJ) following partial discectomy, since there is no documentation of whether or not partial discectomy can induce early-onset osteoarthritis (OA) in mouse TMJ. Methods Partial discs of TMJ in mice were removed by microsurgery. Histology was performed to characterize articular cartilages from the TMJ of mice. The morphology of the articular cartilages was evaluated using a modified Mankin scoring system. Immunohistostaining was carried out to examine the expression of discoidin domain receptor 2 (Ddr2), a type II collagen receptor, matrix metalloproteinase 13 (Mmp-13), and Mmp-derived type II collagen fragments in the articular cartilage of condyles from the mouse TMJ. Results Articular cartilage degeneration was seen in the mouse TMJ post discectomy, including increased proteoglycan staining in the extracellular matrix at 4 weeks, the appearance of chondrocyte clusters at 8 weeks, reduced proteoglycan staining and fibrillation at 12 weeks and the loss of articular cartilage at 16 weeks. Increased immunostaining for Ddr2, Mmp-13, and Mmp-derived type II collagen fragments was detected. Conclusion Results indicate that partial discectomy induces early-onset OA in mouse TMJ and that increased expression of Mmp-13, likely due to the elevated expression of Ddr2, may be one of the factors responsible for the early-onset OA in mouse TMJ. PMID:19230720

  18. Early factors leading to later obesity: interactions of the microbiome, epigenome, and nutrition.

    PubMed

    Chang, Lilly; Neu, Josef

    2015-05-01

    Obesity is a major public health problem in the United States and many other countries. Childhood obesity rates have risen extensively over the last several decades with the numbers continuing to rise. Obese and overweight children are at high risk of becoming overweight adolescents and adults. The causes are multifactorial and are affected by various genetic, behavioral, and environmental factors. This review aims to discuss a previously under-recognized antecedent of obesity and related chronic metabolic diseases such as heart disease and diabetes. Specifically, we highlight the relationship of the microbial ecology of the gastrointestinal tract during early development and the consequent effects on metabolism, epigenetics, and inflammatory responses that can subsequently result in metabolic syndrome. Although studies in this area are just beginning, this area of research is rapidly expanding and may lead to early life interventions that may have significant impacts in the prevention of obesity. PMID:26043042

  19. Group size, cage shelf level, and emotionality in non-obese diabetic mice: impact on onset and incidence of IDDM.

    PubMed

    Ader, D N; Johnson, S B; Huang, S W; Riley, W J

    1991-01-01

    We hypothesized that differential housing, shown to influence emotionality and health in infectious and neoplastic disease, would influence onset/incidence of diabetes in an autoimmune animal model of insulin-dependent diabetes mellitus (IDDM). Non-obese diabetic mice were assigned to same-sex groups of one, five, or eight animals/cage, counterbalanced across shelf level by sex and group. During weekly urine glucose testing, presence of behaviors indicating emotional arousal was recorded. Sex, group, and shelf level affected emotionality: males, animals housed alone, and those on the top of the rack exhibited higher emotionality. Emotionality and shelf level predicted IDDM in females only. Delayed onset of IDDM was associated with high emotionality and with being housed on the top of the rack. Group size had no significant effect on IDDM. Emotionality may be a mediating factor in animals genetically predisposed to develop IDDM. This variable and cage shelf level should be incorporated into the design of studies in which IDDM is the outcome. PMID:1882012

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

    NASA Technical Reports Server (NTRS)

    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.

  1. Delineation of Early and Later Adult Onset Depression by Diffusion Tensor Imaging

    PubMed Central

    Yu, Hongjun; Nie, Binbin; Li, Na; Luo, Chunrong; Li, Haijun; Liu, Fang; Bai, Yan; Shan, Baoci; Xu, Lin; Xu, Xiufeng

    2014-01-01

    Background Due to a lack of evidence, there is no consistent age of onset to define early onset (EO) versus later onset (LO) major depressive disorder (MDD). Fractional anisotropy (FA), derived from diffusion tensor imaging (DTI), has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry, abnormalities of which might facilitate the delineation of EO versus LO MDD. Method In this study, 61 pairs of untreated, non-elderly, first-episode MDD patients and healthy controls (HCs) aged 18–45 years old received DTI scans. The voxel-based analysis method (VBM), classification analysis, using the Statistical Package for the Social Sciences (SPSS), and regression analyses were used to determine abnormal FA clusters and their correlations with age of onset and clinical symptoms. Results Classification analysis suggested in the best model that there were two subgroups of MDD patients, delineated by an age of onset of 30 years old, by which MDD patients could be divided into EO (18–29 years old) and LO (30–45 years old) groups. LO MDD was characterized by decreased FA, especially in the white matter (WM) of the fronto-occipital fasciculus and posterior limb of internal capsule, with a negative correlation with the severity of depressive symptoms; in marked contrast, EO MDD showed increased FA, especially in the WM of the corpus callosum, corticospinal midbrain and inferior fronto-occipital fasciculus, while FA of the WM near the midbrain had a positive correlation with the severity of depressive symptoms. Conclusion Specific abnormalities of the brain circuitry in EO vs. LO MDD were delineated by an age of onset of 30 years old, as demonstrated by distinct abnormal FA clusters with opposite correlations with clinical symptoms. This DTI study supported the evidence of an exact age for the delineation of MDD, which could have broad multidisciplinary importance. Trial Registration ClinicalTrials.gov NCT00703742 PMID:25393297

  2. Mental development and growth in children with chronic liver disease of early and late onset.

    PubMed

    Stewart, S M; Uauy, R; Kennard, B D; Waller, D A; Benser, M; Andrews, W S

    1988-08-01

    Comparison was made of the mental function and physical growth of 21 children in whom liver disease occurred in the first year of life with 15 patients with late (17 months of age to 12 years of age) manifestation of liver disease. Ages (mean +/- SD) at testing for the two groups was 8 +/- 3 years for the early group and 11 +/- 5 years for the late group. Wechsler verbal, performance, and full-scale IQ scores were lower for the early group (range of mean scores: early, 85 to 86 v late, 96 to 103). Growth measures were significantly different in the two groups. Means +/- SD (percentage of standard) were: length for early group, 92 +/- 9; for late, 99 +/- 7; and head circumference for early, 98 +/- 4; for late, 101 +/- 2. The groups were similar in severity of liver disease and acute nutritional status, however. Patients with intellectual impairment had a longer duration of illness, poor nutritional status, and vitamin E deficiency; 82% of impaired patients were in the early group. The data suggest that liver disease during early life has pernicious effects on intellectual function and linear growth. Careful monitoring of nutritional status of children with early-onset liver disease and aggressive nutritional support beginning at the time of diagnosis may help reduce delays in growth and mental development. PMID:3399290

  3. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood. PMID:24434909

  4. Early-Onset Type 2 Diabetes Impairs Skeletal Acquisition in the Male TALLYHO/JngJ Mouse

    PubMed Central

    Van Vliet, M.; Motyl, K.; Karim, L.; Brooks, D. J.; Louis, L.; Conlon, C.; Rosen, C. J.; Bouxsein, M. L.

    2014-01-01

    Type 2 diabetes (T2D) incidence in adolescents is rising and may interfere with peak bone mass acquisition. We tested the effects of early-onset T2D on bone mass, microarchitecture, and strength in the TALLYHO/JngJ mouse, which develops T2D by 8 weeks of age. We assessed metabolism and skeletal acquisition in male TALLYHO/JngJ and SWR/J controls (n = 8–10/group) from 4 weeks to 8 and 17 weeks of age. Tallyho mice were obese; had an approximately 2-fold higher leptin and percentage body fat; and had lower bone mineral density vs SWR at all time points (P < .03 for all). Tallyho had severe deficits in distal femur trabecular bone volume fraction (−54%), trabecular number (−27%), and connectivity density (−82%) (P < .01 for all). Bone formation was higher in Tallyho mice at 8 weeks but lower by 17 weeks of age vs SWR despite similar numbers of osteoblasts. Bone marrow adiposity was 7- to 50-fold higher in Tallyho vs SWR. In vitro, primary bone marrow stromal cell differentiation into osteoblast and adipocyte lineages was similar in SWR and Tallyho, suggesting skeletal deficits were not due to intrinsic defects in Tallyho bone-forming cells. These data suggest the Tallyho mouse might be a useful model to study the skeletal effects of adolescent T2D. PMID:25051433

  5. CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas

    PubMed Central

    Riant, F.; Bergametti, F.; Fournier, H.-D.; Chapon, F.; Michalak-Provost, S.; Cecillon, M.; Lejeune, P.; Hosseini, H.; Choe, C.; Orth, M.; Bernreuther, C.; Boulday, G.; Denier, C.; Labauge, P.; Tournier-Lasserve, E.

    2013-01-01

    Mutations of CCM3/PDCD10 cause 10-15% of hereditary cerebral cavernous malformations. The phenotypic characterization of CCM3-mutated patients has been hampered by the limited number of patients harboring a mutation in this gene. This is the first report on molecular and clinical features of a large cohort of CCM3 patients. Molecular screening for point mutations and deletions was used to identify 54 CCM3-mutated index patients. Age at referral and clinical onset, type of inaugural events and presence of extra-axial lesions were investigated in these 54 index patients and 22 of their mutated relatives. Mean age at clinical onset was 23.0 ± 16 years. Clinical onset occurred before 10 years in 26% of the patients, and cerebral hemorrhage was the initial presentation in 72% of these patients. Multiple extra-axial, dural-based lesions were detected in 7 unrelated patients. These lesions proved to be meningiomas in 3 patients who underwent neurosurgery and pathological examination. This ‘multiple meningiomas’ phenotype is not associated with a specific CCM3 mutation. Hence, CCM3 mutations are associated with a high risk of early-onset cerebral hemorrhage and with the presence of multiple meningiomas. PMID:23801932

  6. Herlyn-Werner-Wunderlich syndrome: An "early" onset case report and review of Literature.

    PubMed

    Angotti, R; Molinaro, F; Bulotta, A L; Bindi, E; Cerchia, E; Sica, M; Messina, M

    2015-01-01

    Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital mullerian anomaly consisting of uterus didelphys, hemivaginal septum, and unilateral renal agenesis [1,2]. Most authors reported cases of Herlyn-Werner-Wunderlich syndrome with prepuberal or postpuberal onset with cyclical abdominal pain and a vaginal mass (3-8). Only six cases are reported in Literature with early onset of this syndrome under 5 years (9-14). Our case is about 3 years old girl, with all the features of this syndrome who came to our attention for lower abdominal mass. The aim of this article is to share our experience and focus the attention on the importance of high level of suspicion of HWWS in neonatal period to early diagnosis and treatment. The possible early presentation of this syndrome should be suspected in all neonates (females) with renal agenesia confirmed postnatally or with prenatal diagnosis. It is common, in fact, an error of evaluation with planning of removal of mass, that can damage patients in term of chance for a successful reproductive outcome. For all these reasons, our team consider HWWS as differential diagnosis in newborn with prenatal ultrasonography of a cystic mass behind the urinary bladder in the absence of a kidney and plan a pelvic ultrasound (with aim to identify an uterus, normal or dydhelfus, and presence or absence of pelvic mass), an examination under anesthesia and cystoscopy and vaginoscopy, if it is necessary. A high level of suspicion, indeed, is the key to early diagnosis. PMID:25932973

  7. Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy.

    PubMed

    Gürsoy, Semra; Erçal, Derya

    2016-03-01

    Epileptic encephalopathies are characterized by recurrent clinical seizures and prominent interictal epileptiform discharges seen during the early infantile period. Although epileptic encephalopathies are mostly associated with structural brain defects and inherited metabolic disorders, pathogenic gene mutations may also be involved in the development of epileptic encephalopathies even when no clear genetic inheritance patterns or consanguinity exist. The most common epileptic encephalopathies are Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome and Dravet syndrome, which are usually unresponsive to traditional antiepileptic medication. Many of the diagnoses describe the phenotype of these electroclinical syndromes, but not the underlying causes. To date, approximately 265 genes have been defined in epilepsy and several genes including STXBP1, ARX, SLC25A22, KCNQ2, CDKL5, SCN1A, and PCDH19 have been found to be associated with early-onset epileptic encephalopathies. In this review, we aimed to present a diagnostic approach to primary genetic causes of early-onset epileptic encephalopathies. PMID:26271793

  8. Early onset West syndrome with cerebral hypomyelination and reduced cerebral white matter.

    PubMed

    Tohyama, Jun; Akasaka, Noriyuki; Osaka, Hitoshi; Maegaki, Yoshihiro; Kato, Mitsuhiro; Saito, Naka; Yamashita, Sumimasa; Ohno, Kousaku

    2008-05-01

    Numerous numbers of pre-, peri- and postnatal damages cause West syndrome in early infancy, however, etiology in many cases are not still elucidated despite intensive biochemical and neuroradiologic investigations. We described four patients having early onset epileptic encephalopathy with severe hypomyelination and reduction in cerebral white matter. The clinical symptoms of these patients are impaired visual attention, acquired microcephaly, spastic tetraplegia, profound psychomotor delay and infantile spasms since early infancy. All patients had striking hypomyelination of cerebrum, reduced volume of white matter and cortical atrophy on MRI. Serial MRI investigations in three patients showed absence of myelination of the white matter. On EEG, one patient revealed suppression-burst and other three had hypsarrhythmia. Despite having intractable seizures, no patient showed deterioration of neurological development. The group of these findings is mimicking to clinical manifestations of 3-phosphoglycerate dehydrogenase deficiency, and has some overlap with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) like syndrome, however it is not compatible with these two conditions. The findings observed in our patients can be regarded as a new clinical condition associated with early onset West syndrome. PMID:18065176

  9. Heart rate and blood pressure control in obesity - how to detect early dysregulation?

    PubMed

    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. PMID:25684329

  10. Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q

    SciTech Connect

    Baldwin, C.T.; Farrer, L.A.; Adair, R.; Dharmavaram, R.; Jimenez, S.; Anderson, L.

    1995-03-01

    Calcium pyrophosphate-deposition disease (CPDD), also called {open_quotes}chondrocalcinosis{close_quotes} or {open_quotes}pseudogout{close_quotes}, is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2nd and 5th decades of life. In this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. 29 refs., 2 figs., 1 tab.

  11. The TRIB3 Q84R Polymorphism and Risk of Early-Onset Type 2 Diabetes

    PubMed Central

    Prudente, Sabrina; Scarpelli, Daniela; Chandalia, Manisha; Zhang, Yuan-Yuan; Morini, Eleonora; Del Guerra, Silvia; Perticone, Francesco; Li, Rong; Powers, Christine; Andreozzi, Francesco; Marchetti, Piero; Dallapiccola, Bruno; Abate, Nicola; Doria, Alessandro; Sesti, Giorgio; Trischitta, Vincenzo

    2009-01-01

    Context: The prevalence of type 2 diabetes (T2D), particularly among young adults, has been rising steadily during the past 2 decades. T2D, especially in its early-onset subtype, is under genetic control. TRIB3 inhibits insulin-stimulated Akt phosphorylation and subsequent insulin action. A TRIB3 gain-of-function polymorphism, Q84R (rs2295490), impairs insulin signaling. Objective: The objective of the study was to verify the association of TRIB3 Q84R with: 1) T2D, either subtyped or not according to age at diagnosis (early-onset, <45 yr, or ≥ 45 yr); 2) insulin secretion and sensitivity in nondiabetic individuals; or 3) in vitro insulin secretion from isolated human islets. Design: Four different case-control samples comprising a total of 5469 whites were examined. Insulinogenic and insulin sensitivity indexes and their interplay (disposition index) were assessed in 645 nondiabetic individuals at oral glucose tolerance test, glucose (16.7 mmol/liter)-induced in vitro insulin secretion was assessed in islets isolated from 54 nondiabetic donors. Results: In the whole sample, the R84 variant was nominally associated with T2D (odds ratio 1.17, 95% confidence interval 1.00–1.36, P = 0.04). When stratifying according to age of diabetes onset, R84 carriers had an increased risk of early-onset T2D (odds ratio 1.32, 95% confidence interval 1.10–1.58, P = 0.002). Among 645 nondiabetic subjects, R84 carriers had higher glucose levels (P = 0.005) and lower insulinogenic (P = 0.03) and disposition index (P = 0.02) during the oral glucose tolerance test. R84 islets were more likely to display relatively low glucose-stimulated insulin release (P = 0.04). Conclusions: The TRIB3 R84 variant is associated with early-onset T2D in whites. Alteration in the insulin secretion/insulin sensitivity interplay appears to underlie this association. PMID:18984671

  12. Disparities in Early Transitions to Obesity in Contemporary Multi-Ethnic U.S. Populations

    PubMed Central

    Avery, Christy L.; Holliday, Katelyn M.; Chakladar, Sujatro; Engeda, Joseph C.; Hardy, Shakia T.; Reis, Jared P.; Schreiner, Pamela J.; Shay, Christina M.; Daviglus, Martha L.; Heiss, Gerardo; Lin, Dan Yu; Zeng, Donglin

    2016-01-01

    Background Few studies have examined weight transitions in contemporary multi-ethnic populations spanning early childhood through adulthood despite the ability of such research to inform obesity prevention, control, and disparities reduction. Methods and Results We characterized the ages at which African American, Caucasian, and Mexican American populations transitioned to overweight and obesity using contemporary and nationally representative cross-sectional National Health and Nutrition Examination Survey data (n = 21,220; aged 2–80 years). Age-, sex-, and race/ethnic-specific one-year net transition probabilities between body mass index-classified normal weight, overweight, and obesity were estimated using calibrated and validated Markov-type models that accommodated complex sampling. At age two, the obesity prevalence ranged from 7.3% in Caucasian males to 16.1% in Mexican American males. For all populations, estimated one-year overweight to obesity net transition probabilities peaked at age two and were highest for Mexican American males and African American females, for whom a net 12.3% (95% CI: 7.6%-17.0%) and 11.9% (95% CI: 8.5%-15.3%) of the overweight populations transitioned to obesity by age three, respectively. However, extrapolation to the 2010 U.S. population demonstrated that Mexican American males were the only population for whom net increases in obesity peaked during early childhood; age-specific net increases in obesity were approximately constant through the second decade of life for African Americans and Mexican American females and peaked at age 20 for Caucasians. Conclusions African American and Mexican American populations shoulder elevated rates of many obesity-associated chronic diseases and disparities in early transitions to obesity could further increase these inequalities if left unaddressed. PMID:27348868

  13. A Community-Based Intervention to Prevent Obesity Beginning at Birth among American Indian Children: Study Design and Rationale for the PTOTS Study

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    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 <50 degrees. Surgical 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. PMID:26241527

  15. Early childhood healthy and obese weight status: potentially protective benefits of breastfeeding and delaying solid foods.

    PubMed

    Moss, Brian G; Yeaton, William H

    2014-07-01

    The aim of this study was to assess the relationship between breastfeeding and postponing introduction to solid food (SF) on children's obesity and healthy weight status (WS), at 2 and 4 years. Drawing upon a nationally representative sample of children from the Early Childhood Longitudinal Study-Birth Cohort, we estimated the magnitude of the relationship between children's WS and early feeding practices. Contingency tables and multinomial logistic regression were used to analyze obese and healthy WS for breastfed and never breastfed children and examine three timing categories for SF introduction. With both percentages and odds, breastfeeding and delaying introduction to SF until 4 months were associated with lower obesity rates and higher, healthy WS rates (typically 5-10%). Analyses of feeding practice combinations revealed that when children were not breastfed, obesity odds decreased when SF introduction was postponed until 4 months. Obesity odds were further reduced when SF delay was combined with breastfeeding. Consistent increases in healthy WS were also observed. Benefits were stable across both follow-up periods. Breastfeeding and delaying complementary foods yielded consistently and substantially lower likelihood of obesity and greater probability of healthy WS. Health policies targeting early feeding practices represent promising interventions to decrease preschool obesity and promote healthy WS. PMID:24057991

  16. Genotype-phenotype correlates in Taiwanese patients with early-onset recessive Parkinsonism.

    PubMed

    Lee, Ming-Jen; Mata, Ignacio F; Lin, Chin-Hsien; Tzen, Kai-Yuan; Lincoln, Sarah J; Bounds, Rebecca; Lockhart, Paul J; Hulihan, Mary M; Farrer, Matthew J; Wu, Ruey-Meei

    2009-01-15

    We screened for mutations in the PARKIN, DJ-1, and PINK1 genes in a Taiwanese cohort (68 probands; 58 sporadic and 10 familial) with early-onset parkinsonism (EOP, onset <50 years of age). We identified 9 patients harboring mutations in PARKIN (three compound heterozygous and six single heterozygous carriers), 3 patients with heterozygous PINK1 mutations (including two novel substitutions M341I and P209A), and no DJ-1 mutations. Our frequencies of PARKIN (two allele mutation, 4.4%; single allele, 8.8%) and PINK1 (single heterozygous, 4.4%) mutations in Taiwanese-Chinese are similar to those in Caucasian and other Asian EOP patients. Although the role of heterozygosity of recessive genes in EOP remains to be resolved, molecular analysis and functional imaging will play a decisive role in differential diagnosis and determined therapeutic strategy. PMID:19006224

  17. Comparison of Clock Test Deficits Between Elderly Patients With Early and Late Onset Depression.

    PubMed

    Klein, Lisa; Saur, Ralf; Müller, Stephan; Leyhe, Thomas

    2015-12-01

    To compare clock test deficits in elderly patients with early onset depression (EOD) and late onset depression (LOD), we assessed 32 elderly healthy controls (HCs), 26 patients with EOD, and 27 patients with LOD with the clock drawing test (CDT), clock setting test, clock reading test, and the Tübingen Clock Questionnaire testing semantic memory about clock times. There was no significant difference in depression severity between patients with EOD and LOD. Patients with LOD had significantly lower scores on the CDT than patients with EOD and HCs. Semantic memory impairment concerning minute hand functionality was highly correlated with CDT performance and was significantly different between the EOD and the LOD groups. It can be suggested that significant differences in cognitive impairment severity between patients with EOD and LOD can be detected with CDT. Semantic memory impairment concerning minute hand functionality might affect CDT test results in elderly patients with depression. PMID:26047634

  18. A novel PIGA mutation in a family with X-linked, early-onset epileptic encephalopathy.

    PubMed

    Kim, Young Ok; Yang, Jae Hyuk; Park, Chungoo; Kim, Seul Kee; Kim, Myeong-Kyu; Shin, Myung-Geun; Woo, Young Jong

    2016-09-01

    Early-onset epileptic encephalopathies (EOEEs) are severe and intractable infantile-onset epilepsies with progressive intellectual disability and other associated neurologic comorbidities. Whole-exome sequencing (WES) was recently used to determine the causative gene mutations in individuals with unclassified EOEEs. The present study used WES to determine the causative variant in a family with X-linked, EOEE. One potential variant (c. 427A>G, NM_002641.3; p.Lys143Glu, NP_002632.1) of the gene encoding phosphatidylinositol glycan biosynthesis class A protein (PIGA; PIGA) was found, which was verified by Sanger sequencing. The functional effect of this PIGA mutation was assessed by the surface expression levels of glycosylphosphatidylinositol-anchored proteins on blood cells: CD16 on red blood cells was significantly decreased in the proband (by 11.0%) and his mother (by 15.6%). This is the second report of a less-severe form of PIGA deficiency. PMID:26923721

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

    PubMed

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

    2016-07-01

    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. PMID:27222092

  20. Early Life Factors Influencing the Risk of Obesity

    PubMed Central

    2015-01-01

    The obesity epidemic is a worldwide problem. Factors predisposing to obesity include genetics, race, socioeconomic conditions, birth by cesarean section, and perinatal antibiotic use. High protein (HP) content in infant formulas has been identified as a potential culprit predisposing to rapid weight gain in the first few months of life and leading to later obesity. In a large multicountry study the effects of lower protein (LP) formula (1.77 and 2.2 g protein/100 kcal, before and after the 5th month, respectively) were compared to those of higher protein (2.9 and 4.4 g protein/100 kcal, respectively). Results indicated that at 24 months, the weight-for-length z score of infants in the LP formula group was 0.20 (0.06, 0.34) lower than that of the HP group and was similar to that of the breastfed reference group. The authors concluded that a HP content of infant formula is associated with higher weight in the first 2 years of life but has no effect on length. LP intake in infancy might diminish the later risk of overweight and obesity. At 6 years of age HP children had a significantly higher body mass index (by 0.51; 95% confidence interval [CI], 0.13-0.90; p=0.009) and a 2.43 (95% CI, 1.12-5.27; p=0.024) fold greater risk of becoming obese than those who received the LP. In conclusion, several factors may influence development of metabolic syndrome and obesity. Breastfeeding should always be encouraged. An overall reduction of protein intake in formula non breastfed infants seems to be an additional way to prevent obesity. PMID:26770895

  1. Risk factors of early onset of MS in women in reproductive age period: survival analysis approach.

    PubMed

    Mohammadbeigi, Abolfazl; Kazemitabaee, Maryamsadat; Etemadifar, Masoud

    2016-08-01

    The incidence of multiple sclerosis (MS) has doubled in over the last decades in women, whereas it has been almost unchanged in men. The purpose of this study was to investigate the risk factors of early onset multiple sclerosis in women during reproductive years. A retrospective longitudinal study conducted on 200 women aged 15 to 50 years with MS, registered by the MS Society in Isfahan. Data gathering was fulfilled by standard questionnaire including variables about reproductive period, demographic characteristics, and history of diseases. Kaplan-Mayer with log-rank test and Cox regression models were used in predicting of the age of effective factors in onset of MS. P values less than 0.05 were considered statistically significant. The mean age of studied women was 31.77 ± 8.13 years and the mean and median age of onset the symptoms of MS was 26.79 ± 7.77 and 26 years, respectively. Based on the cox results occurring menarche at 15 years and higher increase the risk of MS 2.8-fold than those their menarche occurred at 12 years and lower (HR: 2.81, 95 % CI; 1.58-4.98).In addition, having only one pregnancy is related to higher risk of MS than other parities and increase the risk of MS 4.5-fold comparing to without parities. Age of menarche and parity numbers was the most important reproductive factors of MS in women. Nevertheless, history of autoimmune diseases, animal bite, childhood disease, family history of MS, regional area (tropical), and living in rural area were not related to early onset of MS. PMID:26790684

  2. Integrating Biological and Social Processes in Relation to Early-Onset Persistent Aggression in Boys and Girls.

    ERIC Educational Resources Information Center

    Brennan, Patricia A.; Hall, Jason; Bor, William; Najman, Jake M.; Williams, Gail

    2003-01-01

    Examined longitudinally the relationship between biological and social risk factors and aggressive behavior patterns among high-risk Australian adolescents in three groups: early-onset persistent aggression, adolescent-onset aggression, and nonaggressive behavior groups. Findings revealed that the interaction of biological and social risk factors…

  3. Internalizing and externalizing psychopathology as predictors of cannabis use disorder onset during adolescence and early adulthood.

    PubMed

    Farmer, Richard F; Seeley, John R; Kosty, Derek B; Gau, Jeff M; Duncan, Susan C; Lynskey, Michael T; Lewinsohn, Peter M

    2015-09-01

    Risk-related liabilities associated with the development of cannabis use disorders (CUDs) during adolescence and early adulthood are thought to be established well before the emergence of the index episode. In this study, internalizing and externalizing psychopathology from earlier developmental periods were evaluated as risk factors for CUDs during adolescence and early adulthood. Participants (N = 816) completed 4 diagnostic assessments between the ages 16 and 30, during which current and past CUDs were assessed as well as a full range of psychiatric disorders associated with internalizing and externalizing psychopathology domains. In unadjusted and adjusted time-to-event analyses, externalizing but not internalizing psychopathology from proximal developmental periods predicted subsequent CUD onset. A large proportion of adolescent and early adult cases, however, did not manifest any externalizing or internalizing psychopathology during developmental periods before CUD onset. Findings are consistent with the emerging view that externalizing disorders from proximal developmental periods are robust risk factors for CUDs. Although the identification of externalizing liabilities may aid in the identification of individuals at risk for embarking on developmental pathways that culminate in CUDs, such liabilities are an incomplete indication of overall risk. PMID:25799438

  4. Early-onset alopecia and amyotrophic lateral sclerosis: a cohort study.

    PubMed

    Fondell, Elinor; Fitzgerald, Kathryn C; Falcone, Guido J; O'Reilly, Eilis J; Ascherio, Alberto

    2013-10-01

    A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 46-81 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (1992-2008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk = 2.74, 95% confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (Ptrend = 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation. PMID:23942216

  5. Successful scene encoding in presymptomatic early-onset Alzheimer’s disease

    PubMed Central

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

    2016-01-01

    Background 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. Objective To examine whether fMRI can detect early functional changes associated with scene encoding in a group of presymptomatic Presenilin-1 (PSEN1) E280A mutation carriers. Methods Participants were 39 young, cognitively-normal individuals from an autosomal dominant early-onset AD kindred, located in Antioquia, Colombia. Participants performed an fMRI scene encoding task and a post-scan subsequent memory test. Results PSEN1 mutation carriers exhibited hyperactivation within medial temporal lobe regions during successful scene encoding (hippocampal formation, parahippocampal gyrus) compared to age-matched non-carriers. Conclusion 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. PMID:26401774

  6. Internalizing and Externalizing Psychopathology as Predictors of Cannabis Use Disorder Onset during Adolescence and Early Adulthood

    PubMed Central

    Farmer, Richard F.; Seeley, John R.; Kosty, Derek B.; Gau, Jeff M.; Duncan, Susan C.; Lynskey, Michael T.; Lewinsohn, Peter M.

    2015-01-01

    Risk-related liabilities associated with the development of cannabis use disorders (CUDs) during adolescence and early adulthood are thought to be established well before the emergence of the index episode. In this study, internalizing and externalizing psychopathology from earlier developmental periods were evaluated as risk factors for CUDs during adolescence and early adulthood. Participants (N = 816) completed four diagnostic assessments between the ages 16 and 30, during which current and past CUDs were assessed as well as a full range of psychiatric disorders associated with internalizing and externalizing psychopathology domains. In unadjusted and adjusted time-to-event analyses, externalizing but not internalizing psychopathology from proximal developmental periods predicted subsequent CUD onset. A large proportion of adolescent and early adult cases, however, did not manifest any externalizing or internalizing psychopathology during developmental periods prior to CUD onset. Findings are consistent with the emerging view that externalizing disorders from proximal developmental periods are robust risk factors for CUDs. Although the identification of externalizing liabilities may aid in the identification of individuals at risk for embarking on developmental pathways that culminate in CUDs, such liabilities are an incomplete indication of overall risk. PMID:25799438

  7. The Burden of Invasive Early-Onset Neonatal Sepsis in the United States, 2005–2008

    PubMed Central

    Weston, Emily J.; Pondo, Tracy; Lewis, Melissa M.; Martell-Cleary, Pat; Morin, Craig; Jewell, Brenda; Daily, Pam; Apostol, Mirasol; Petit, Sue; Farley, Monica; Lynfield, Ruth; Reingold, Art; Hansen, Nellie I.; Stoll, Barbara J.; Shane, Andi L.; Zell, Elizabeth; Schrag, Stephanie J.

    2011-01-01

    Background Sepsis in the first 3 days of life is a leading cause of morbidity and mortality among infants. Group B Streptococcus (GBS), historically the primary cause of early-onset sepsis, has declined through widespread use of intrapartum chemoprophylaxis. We estimated the national burden of invasive early-onset sepsis (EOS) cases and deaths in the era of GBS prevention. Methods Population-based surveillance for invasive EOS was conducted in 4 of CDC’s Active Bacterial Core surveillance (ABCs) sites from 2005–2008. We calculated incidence using state and national live birth files. Estimates of the national number of cases and deaths were calculated, standardizing by race and gestational age. Results ABCs identified 658 cases of EOS; 72 (10.9%) were fatal. Overall incidence remained stable during the three years (2005:0.77 cases/1,000 live births; 2008:0.76 cases/1,000 live births). GBS (~38%) was the most commonly reported pathogen followed by Escherichia coli (~24%). Black preterm infants had the highest incidence (5.14 cases/1,000 live births) and case fatality (24.4%). Non-black term infants had the lowest incidence (0.40 cases/1,000 live births) and case fatality (1.6%). The estimated national annual burden of EOS was approximately 3,320 cases (95% CI: 3,060–3,580) including 390 deaths (95% CI: 300–490). Among preterm infants, 1,570 cases (95% CI: 1,400–1,770; 47.3% of the overall) and 360 deaths (95% CI: 280–460; 92.3% of the overall) occurred annually. Conclusions The burden of invasive early-onset sepsis remains substantial in the era of GBS prevention and disproportionately affects preterm and black infants. Identification of strategies to prevent preterm births is needed to reduce the neonatal sepsis burden. PMID:21654548

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

    PubMed Central

    Zhang, Jun-Xiao; Fu, Lei; de Voer, Richarda M; Hahn, Marc-Manuel; Jin, Peng; Lv, Chen-Xi; Verwiel, Eugène TP; Ligtenberg, Marjolijn JL; Hoogerbrugge, Nicoline; Kuiper, Roland P; Sheng, Jian-Qiu; Geurts van Kessel, Ad

    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 diagnosed at ≤ 40 years of age, or from multiple affected CRC families with at least 1 first-degree relative diagnosed with CRC at ≤ 55 years of age. Genomic DNA from blood was enriched for exome sequences using the SureSelect Human All Exon Kit, version 2 (Agilent Technologies) and sequencing was performed on an Illumina HiSeq 2000 platform. Data were processed through an analytical pipeline to search for rare germline variants in known or novel CRC predisposing genes. RESULTS: In total, 32 germline variants in 23 genes were identified and confirmed by Sanger sequencing. In 6 of the 21 families (29%), we identified 7 mutations in 3 known CRC predisposing genes including MLH1 (5 patients), MSH2 (1 patient), and MUTYH (biallelic, 1 patient), five of which were reported as pathogenic. In the remaining 15 families, we identified 20 rare and novel potentially deleterious variants in 19 genes, six of which were truncating mutations. One previously unreported variant identified in a conserved region of EIF2AK4 (p.Glu738_Asp739insArgArg) was found to represent a local Chinese variant, which was significantly enriched in our early-onset CRC patient cohort compared to a control cohort of 100 healthy Chinese individuals scored negative by colonoscopy (33.3% vs 7%, P < 0.001). CONCLUSION: Whole-exome sequencing of early-onset or familial CRC cases serves as an efficient method to identify known and potential pathogenic variants in established and novel candidate CRC predisposing genes. PMID:25892863

  9. Internet-Delivered, Family-Based Treatment for Early-Onset OCD: A Preliminary Case Series

    PubMed Central

    Comer, Jonathan S.; Furr, Jami M.; Cooper-Vince, Christine E.; Kerns, Caroline E.; Chan, Priscilla T.; Edson, Aubrey L.; Khanna, Muniya; Franklin, Martin E.; Garcia, Abbe M.; Freeman, Jennifer B.

    2014-01-01

    Given the burdens of early-onset obsessive-compulsive disorder (OCD), limitations in the broad availability and accessibility of evidence-based care for affected youth present serious public health concerns. The growing potential for technological innovations to transform care for the most traditionally remote and underserved families holds enormous promise. This article presents the rationale, key considerations, and a preliminary case series for a promising behavioral telehealth innovation in the evidence-based treatment of early-onset OCD. We developed an Internet-based format for the delivery of family-based treatment for early-onset OCD directly to families in their homes, regardless of their geographic proximity to a mental health facility. Videoteleconferencing (VTC) methods were used to deliver real-time cognitive-behavioral therapy centering on exposure and response prevention to affected families. Participants in the preliminary case series included 5 children between the ages of 4 and 8 (MAge = 6.5) who received the Internet-delivered treatment format. All youth completed a full treatment course, all showed OCD symptom improvements and global severity improvements from pre- to posttreatment, all showed at least partial diagnostic response, and 60% no longer met diagnostic criteria for OCD at posttreatment. No participants got worse, and all mothers characterized the quality of services received as “excellent.” The present work adds to a growing literature supporting the potential of VTC and related computer technology for meaningfully expanding the reach of supported treatments for OCD and lays the foundation for subsequent controlled evaluations to evaluate matters of efficacy and engagement relative to standard in-office evidence-based care. PMID:24295036

  10. Common and Rare Variant Analysis in Early-Onset Bipolar Disorder Vulnerability

    PubMed Central

    Jamain, Stéphane; Cichon, Sven; Etain, Bruno; Mühleisen, Thomas W.; Georgi, Alexander; Zidane, Nora; Chevallier, Lucie; Deshommes, Jasmine; Nicolas, Aude; Henrion, Annabelle; Degenhardt, Franziska; Mattheisen, Manuel; Priebe, Lutz; Mathieu, Flavie; Kahn, Jean-Pierre; Henry, Chantal; Boland, Anne; Zelenika, Diana; Gut, Ivo; Heath, Simon; Lathrop, Mark; Maier, Wolfgang; Albus, Margot; Rietschel, Marcella; Schulze, Thomas G.; McMahon, Francis J.; Kelsoe, John R.; Hamshere, Marian; Craddock, Nicholas; Nöthen, Markus M.; Bellivier, Frank; Leboyer, Marion

    2014-01-01

    Bipolar disorder is one of the most common and devastating psychiatric disorders whose mechanisms remain largely unknown. Despite a strong genetic contribution demonstrated by twin and adoption studies, a polygenic background influences this multifactorial and heterogeneous psychiatric disorder. To identify susceptibility genes on a severe and more familial sub-form of the disease, we conducted a genome-wide association study focused on 211 patients of French origin with an early age at onset and 1,719 controls, and then replicated our data on a German sample of 159 patients with early-onset bipolar disorder and 998 controls. Replication study and subsequent meta-analysis revealed two genes encoding proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We performed additional replication studies in two datasets from the WTCCC (764 patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436 controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the WTCCC sample. In addition, we identified in the French cohort one affected individual with a deletion at the PLCXD3 locus and another one carrying a missense variation in PLCXD3 (p.R93H), both supporting a role of the phosphatidylinositol pathway in early-onset bipolar disorder vulnerability. Although the current nominally significant findings should be interpreted with caution and need replication in independent cohorts, this study supports the strategy to combine genetic approaches to determine the molecular mechanisms underlying bipolar disorder. PMID:25111785

  11. A Unified Hypothesis of Early- and Late-Onset Alzheimer’s Disease Pathogenesis

    PubMed Central

    Atwood, Craig S.; Bowen, Richard L.

    2016-01-01

    Early-onset familial Alzheimer’s disease (EOFAD) and late-onset sporadic AD (LOSAD) both follow a similar pathological and biochemical course that includes: neuron and synapse loss and dysfunction, microvascular damage, microgliosis, extracellular amyloid-β deposition (Aβ), and the deposition of phosphorylated tau protein in the form of intracellular neurofibrillary tangles in affected brain regions. Any mechanistic explanation of AD must accommodate these biochemical and neuropathological features for both forms of the disease. Cell cycle abnormalities represent another major biochemical and neuropathological feature common to both EOFAD and LOSAD, and 1) appear very early in the disease process, prior to the appearance of plaques and tangles, and 2) explain the biochemical (e.g., tau phosphorylation), neuropathological (e.g., neuron hypertrophy) and cognitive changes observed in EOFAD and LOSAD. Since neurogenesis after the formation of a memory is sufficient to induce forgetting, any stimulus that promotes cell cycle re-entry will be a negative event for memory. In this insight paper, we propose that aberrant re-entry of terminally differentiated, post-mitotic neurons into the cell cycle is a common pathway that explains both early and late-onset forms of AD. In the case of EOFAD, mutations in APP, PSEN1, and PSEN2 that alter AβPP and Notch processing drive reactivation of the cell cycle, while in LOSAD, age-related reproductive endocrine dyscrasia that upregulates mitogenic TNF signaling, AβPP processing toward the amyloidogenic pathway and tau phosphorylation drives reactivation of the cell cycle. Inhibition of cell cycle reentry of post-mitotic neurons may be a useful therapeutic strategy to prevent or halt disease progression. PMID:26402752

  12. Common and rare variant analysis in early-onset bipolar disorder vulnerability.

    PubMed

    Jamain, Stéphane; Cichon, Sven; Etain, Bruno; Mühleisen, Thomas W; Georgi, Alexander; Zidane, Nora; Chevallier, Lucie; Deshommes, Jasmine; Nicolas, Aude; Henrion, Annabelle; Degenhardt, Franziska; Mattheisen, Manuel; Priebe, Lutz; Mathieu, Flavie; Kahn, Jean-Pierre; Henry, Chantal; Boland, Anne; Zelenika, Diana; Gut, Ivo; Heath, Simon; Lathrop, Mark; Maier, Wolfgang; Albus, Margot; Rietschel, Marcella; Schulze, Thomas G; McMahon, Francis J; Kelsoe, John R; Hamshere, Marian; Craddock, Nicholas; Nöthen, Markus M; Bellivier, Frank; Leboyer, Marion

    2014-01-01

    Bipolar disorder is one of the most common and devastating psychiatric disorders whose mechanisms remain largely unknown. Despite a strong genetic contribution demonstrated by twin and adoption studies, a polygenic background influences this multifactorial and heterogeneous psychiatric disorder. To identify susceptibility genes on a severe and more familial sub-form of the disease, we conducted a genome-wide association study focused on 211 patients of French origin with an early age at onset and 1,719 controls, and then replicated our data on a German sample of 159 patients with early-onset bipolar disorder and 998 controls. Replication study and subsequent meta-analysis revealed two genes encoding proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We performed additional replication studies in two datasets from the WTCCC (764 patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436 controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the WTCCC sample. In addition, we identified in the French cohort one affected individual with a deletion at the PLCXD3 locus and another one carrying a missense variation in PLCXD3 (p.R93H), both supporting a role of the phosphatidylinositol pathway in early-onset bipolar disorder vulnerability. Although the current nominally significant findings should be interpreted with caution and need replication in independent cohorts, this study supports the strategy to combine genetic approaches to determine the molecular mechanisms underlying bipolar disorder. PMID:25111785

  13. Early infancy – a critical period for development of obesity

    PubMed Central

    Gillman, M. W.

    2015-01-01

    Abundant epidemiologic evidence from the developed world now shows that more rapid weight gain during the first half of infancy predicts later obesity and cardio-metabolic risk. In countries in transition in which stunting is still prevalent, distinguishing the effects of gain in weight from linear growth remains a challenge. Moreover very few studies to date have incorporated body composition measures during infancy, which is key to understanding determinants of infant weight gain that also predict later obesity. In addition to infant feeding type potential determinants include the perinarai endocrine milieu. Animal and emerging human data raise the possibility chat ensuring adequate leptin exposure to the growing fetus may regulate energy balance as the infant grows. Understanding these pathways as well as examining the balance between cardiovascular and cognitive effects in both term and preterm infants will point the way toward effective interventions to alter infant growth to prevent later obesity. PMID:25141932

  14. Parental and Early Childhood Influences on Adolescent Obesity: A Longitudinal Study

    ERIC Educational Resources Information Center

    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…

  15. Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

    SciTech Connect

    Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar; Tokar, Erik J.; Kadiiska, Maria B.; Waalkes, Michael P.; Mason, Ronald P.; Chatterjee, Saurabh

    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 protein

  16. Very early onset trichotillomania presenting with recurrent trichobezoar: conventional wisdom questioned.

    PubMed

    Menon, Vikas; Shaik, Subahani; Mohan, Pazhanivel

    2015-01-01

    Trichotillomania (TTM), a disorder characterized by compulsive hair pulling, is undergoing a conceptual and nosological re-evaluation. Little long-term information is available about this condition when it strikes in early childhood. Trichobezoar, an ingestional foreign body lodged in the gastrointestinal tract composed of swallowed hair, is usually associated with underlying psychiatric and emotional disturbances. In this report, we describe a young girl who had her symptom onset at the age of 3, but presented again after more than a decade with recurrent symptomatic large trichobezoars needing surgical removal both times. Her clinical course and presentation challenged contemporary understanding of TTM. PMID:25878449

  17. A Novel Presenilin 1 Mutation in Early-Onset Alzheimer's Disease With Prominent Frontal Features.

    PubMed

    Nygaard, Haakon B; Lippa, Carol F; Mehdi, Djekidel; Baehring, Joachim M

    2014-08-01

    Familial Alzheimer's disease (AD) is a rare disorder involving known autosomal dominant mutations in the amyloid precursor protein and presenilin (PSEN) 1 and 2. Here, we present a case of early-onset AD with prominent frontal features associated with a novel deletion of codon 40 in the PSEN1 gene. Serial brain magnetic resonance imaging and(18)F florbetapir imaging show prominent involvement of the frontal lobes, corresponding with the clinical presentation. This case report illustrates a possible link between a novel PSEN1 mutation and frontal variant AD. PMID:24463146

  18. Offset layered closure reduces deep wound infection in early-onset scoliosis surgery.

    PubMed

    Grzywna, Alexandra M; Miller, Patricia E; Glotzbecker, Michael P; Emans, John B

    2016-07-01

    Deep wound infection is a common complication in early-onset scoliosis (EOS) surgery. Soft tissue technique has received less attention as a means to reduce infection. A retrospective review of 1170 EOS surgeries (single surgeon, institution) investigated the impact of offset layered closure (OLC) and soft tissue awareness. The introduction of OLC reduced deep infection from 3.0% in 99 surgeries to 0.37% in 1071. Logistic regression confirmed that OLC led to significantly lower odds of infection (P=0.007). This deep infection rate (0.37%) is more typical of elective surgery, providing a more optimistic view of infection in EOS surgery than generally reported. PMID:27196268

  19. Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

    PubMed Central

    Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

    2015-01-01

    IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological

  20. S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia

    PubMed Central

    Everett, Thomas R; Wilkinson, Ian B; Mahendru, Amita A; McEniery, Carmel M; Garner, Stephen F; Goodall, Alison H; Lees, Christoph C

    2014-01-01

    Aims To determine the effects of in vivo S-nitrosoglutathione (GSNO) infusion on cardiovascular function, platelet function, proteinuria and biomarker parameters in early-onset pre-eclampsia. Methods We performed an open-label dose-ranging study of GSNO in early-onset pre-eclampsia. Six women underwent GSNO infusion whilst receiving standard therapy. The dose of GSNO was increased incrementally to 100 μg min−1 whilst maintaining blood pressure of >140/80 mmHg. Aortic augmentation index, aortic pulse wave velocity, blood pressure and maternal–fetal Doppler parameters were measured at each dose. Platelet P-selectin, protein-to-creatinine ratio and soluble anti-angiogenic factors were measured pre- and postinfusion. Results Augmentation index fell at 30 μg min−1 S-nitrosoglutathione (−6%, 95% confidence interval 0.6 to 13%), a dose that did not affect blood pressure. Platelet P-selectin expression was reduced [mean (interquartile range), 6.3 (4.9–7.6) vs. 4.1 (3.1–5.7)% positive, P = 0.03]. Soluble endoglin levels showed borderline reduction (P = 0.06). There was a borderline significant change in pre-to-postinfusion protein-to-creatinine ratio [mean (interquartile range), 0.37 (0.09–0.82) vs. 0.23 (0.07–0.49) g mmol−1, P = 0.06]. Maternal uterine and fetal Doppler pulsatility indices were unchanged. Conclusions In early-onset pre-eclampsia, GSNO reduces augmentation index, a biomarker of small vessel tone and pulse wave reflection, prior to affecting blood pressure. Proteinuria and platelet activation are improved at doses that affect blood pressure minimally. These effects of GSNO may be of therapeutic potential in pre-eclampsia, a condition for which no specific treatment exists. Clinical studies of GSNO in early-onset pre-eclampsia will determine whether these findings translate to improvement in maternal and/or fetal outcome. PMID:24627995

  1. Early-life influences on obesity: from preconception to adolescence

    PubMed Central

    Wahlqvist, Mark L.; Krawetz, Stephen A.; Rizzo, Nico S.; Dominguez-Bello, Maria Gloria; Szymanski, Linda M.; Barkin, Shari; Yatkine, Ann; Waterland, Robert A.; Mennella, Julie A.; Desai, Mina; Ross, Michael G.; Krebs, Nancy F.; Young, Bridget E.; Wardle, Jane; Wrann, Christiane D.; Kral, John G.

    2015-01-01

    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 less than 5 years of age were overweight. Ecologic factors, parental genetics and fitness, and the intrauterine environment significantly influence the likelihood of offspring developing the dysmetabolic diathesis of obesity. This report examines effects of these factors, including preconception, intrauterine and postnatal energy balance affecting programming of transgenerational transmission, and development of chronic diseases later in life—in particular, diabesity and its comorbidities. PMID:26037603

  2. Early-life influences on obesity: from preconception to adolescence.

    PubMed

    Wahlqvist, Mark L; Krawetz, Stephen A; Rizzo, Nico S; Dominguez-Bello, Maria Gloria; Szymanski, Linda M; Barkin, Shari; Yatkine, Ann; Waterland, Robert A; Mennella, Julie A; Desai, Mina; Ross, Michael G; Krebs, Nancy F; Young, Bridget E; Wardle, Jane; Wrann, Christiane D; Kral, John G

    2015-07-01

    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, parental genetics and fitness, and the intrauterine environment significantly influence the likelihood of offspring developing the dysmetabolic diathesis of obesity. This report examines the effects of these factors, including preconception, intrauterine and postnatal energy balance affecting programming of transgenerational transmission, and development of chronic diseases later in life-in particular, diabesity and its comorbidities. PMID:26037603

  3. Relationship between obesity and early failure of total knee prostheses

    PubMed Central

    Bordini, Barbara; Stea, Susanna; Cremonini, Sara; Viceconti, Marco; De Palma, Rossana; Toni, Aldo

    2009-01-01

    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 < Body Mass Index <= 30), 31.1% were obese (30 < BMI <= 40), and 1.8% were morbidly obese (BMI > 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

  4. Obesity

    MedlinePlus

    Obesity means having too much body fat. It is different from being overweight, which means weighing too ... what's considered healthy for his or her height. Obesity occurs over time when you eat more calories ...

  5. Genomewide Significant Linkage to Recurrent, Early-Onset Major Depressive Disorder on Chromosome 15q

    PubMed Central

    Holmans, Peter; Zubenko, George S.; Crowe, Raymond R.; DePaulo Jr., J. Raymond; Scheftner, William A.; Weissman, Myrna M.; Zubenko, Wendy N.; Boutelle, Sandra; Murphy-Eberenz, Kathleen; MacKinnon, Dean; McInnis, Melvin G.; Marta, Diana H.; Adams, Philip; Knowles, James A.; Gladis, Madeleine; Thomas, Jo; Chellis, Jennifer; Miller, Erin; Levinson, Douglas F.

    2004-01-01

    A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs (555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers (mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Zlr statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Zlr=4.14, equivalent LOD = 3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD. PMID:15108123

  6. MAPPING THE PROGRESSION OF ATROPHY IN EARLY AND LATE ONSET ALZHEIMER’S DISEASE

    PubMed Central

    Migliaccio, R; Agosta, F; Possin, KL; Canu, E; Filippi, M; Rabinovici, GD; Rosen, HJ; Miller, BL; Gorno-Tempini, ML

    2015-01-01

    The term early age-of-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 (GM) 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. PMID:25737041

  7. Association of M235T variant of the angiotensinogen gene with familial hypertension of early onset.

    PubMed

    Schmidt, S; Sharma, A M; Zilch, O; Beige, J; Walla-Friedel, M; Ganten, D; Distler, A; Ritz, E

    1995-01-01

    A higher frequency of a variant of the angiotensinogen gene characterized by a transition in exon 2 causing a replacement of methionine by threonine (M235T) has recently been found in hypertensive individuals, but not all authors were able to confirm this observation. We examined (i) 219 patients with primary hypertension, (ii) 92 normotensive controls (spouses), and (iii) a sample of the general population (blood donors, n = 139). Analysis of genomic DNA was performed by PCR amplification and alleles were separated on agarose gels. In the general population and in normotensive spouses the respective frequencies of the T and M alleles were: general population: M = 0.6, T = 0.4; normotensive spouses: M = 0.59, T = 0.41. A significantly higher frequency of the 235T allele was found in hypertensive individuals with a family history of hypertension and an onset of hypertension before 50 years of age (spouses: 0.41 versus HT with age of onset < or = 50 years and family history of HT: 0.56; P = 0.01 by chi 2). In conclusion, the present study confirms the observation of a higher frequency of the 235T allele of the angiotensinogen gene in hypertension and identifies individuals with family history and early onset of hypertension as individuals at risk. PMID:7478115

  8. Sunbed use during adolescence and early adulthood is associated with increased risk of early-onset melanoma

    PubMed Central

    Cust, Anne E; Armstrong, Bruce K; Goumas, Chris; Jenkins, Mark A; Schmid, Helen; Hopper, John L; Kefford, Richard F; Giles, Graham G; Aitken, Joanne F; Mann, Graham J

    2010-01-01

    Sunbed use is associated with increased risk of melanoma. Younger people might be more susceptible to the carcinogenic effects of ultraviolet radiation. We investigated the association between sunbed use and risk of early-onset cutaneous malignant melanoma. From the Australian Melanoma Family Study, a multi-centre, population-based, case-control-family study, we analysed data for 604 cases diagnosed between ages 18 and 39 years and 479 controls. Data were collected by interview. Associations were estimated as odds ratios (ORs) using unconditional logistic regression, adjusting for age, sex, city, education, family history, skin colour, usual skin response to sunlight, and sun exposure. Compared with having never used a sunbed, the OR for melanoma associated with ever-use was 1.41 (95% confidence interval (CI) 1.01-1.96), and 2.01 (95% CI 1.22-3.31) for more than 10 lifetime sessions (Ptrend 0.01 with cumulative use). The association was stronger for earlier age at first use (Ptrend 0.02). The association was also stronger for melanoma diagnosed when aged 18-29 years (OR for more than 10 lifetime sessions = 6.57, 95% CI 1.41-30.49) than for melanoma diagnosed when 30-39 years (OR 1.60, 95% CI 0.92-2.77; Pinteraction 0.01). Among those who had ever used a sunbed and were diagnosed between 18-29 years of age, three quarters (76%) of melanomas were attributable to sunbed use. Sunbed use is associated with increased risk of early-onset melanoma, with risk increasing with greater use, an earlier age at first use and for earlier onset disease. PMID:20669232

  9. Obesity Prevention in Early Adolescence: Student, Parent, and Teacher Views

    ERIC Educational Resources Information Center

    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…

  10. Early-life influences on obesity: From preconception to adolescence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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,...

  11. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    PubMed Central

    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

  12. Early onset ovarian hyperstimulation syndrome despite use of segmentation approach and ovarian hyperstimulation syndrome prophylaxis

    PubMed Central

    Mahajan, Nalini; Gupta, Shalu; Sharma, Shilpa; Rani, Kumkum; Naidu, Padmaja; Arora, Puneet R.

    2015-01-01

    We report a case of early onset severe ovarian hyperstimulation syndrome (OHSS) presenting with oliguria in an antagonist cycle triggered with GnRH agonist and a freeze-all approach. Prophylactic measures in the form of GnRH antagonist, cabergolin and plasma expanders were given after oocyte retrieval. Twenty-four hours after oocyte retrieval patient developed oliguria and moderate ascites. She was managed in ICU with albumin and diuretics. She responded to conservative management and did not require paracentesis. Severe OHSS can occur in PCOS patients even after using a segmented approach i.e. GnRH agonist trigger with a ‘freeze all’ policy. Patients at risk of OHSS should be closely monitored following ovum pickup even when an agonist trigger has been given, for early detection and management. PMID:26752860

  13. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia.

    PubMed

    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

  14. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    PubMed

    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. PMID:26358864

  15. Generation of a novel mouse model that recapitulates early and adult onset glycogenosis type IV.

    PubMed

    Akman, H Orhan; Sheiko, Tatiana; Tay, Stacey K H; Finegold, Milton J; Dimauro, Salvatore; Craigen, William J

    2011-11-15

    Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen branching enzyme (GBE). The diagnostic feature of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age of disease onset. Absence of enzyme activity is lethal in utero or in infancy affecting primarily muscle and liver. However, residual enzyme activity (5-20%) leads to juvenile or adult onset of a disorder that primarily affects muscle as well as central and peripheral nervous system. Here, we describe two mouse models of GSD IV that reflect this spectrum of disease. Homologous recombination was used to insert flippase recognition target recombination sites around exon 7 of the Gbe1 gene and a phosphoglycerate kinase-Neomycin cassette within intron 7, leading to a reduced synthesis of GBE. Mice bearing this mutation (Gbe1(neo/neo)) exhibit a phenotype similar to juvenile onset GSD IV, with wide spread accumulation of PG. Meanwhile, FLPe-mediated homozygous deletion of exon 7 completely eliminated GBE activity (Gbe1(-/-)), leading to a phenotype of lethal early onset GSD IV, with significant in utero accumulation of PG. Adult mice with residual GBE exhibit progressive neuromuscular dysfunction and die prematurely. Differently from muscle, PG in liver is a degradable source of glucose and readily depleted by fasting, emphasizing that there are structural and regulatory differences in glycogen metabolism among tissues. Both mouse models recapitulate typical histological and physiological features of two human variants of branching enzyme deficiency. PMID:21856731

  16. Early Onset Prion Disease from Octarepeat Expansion Correlates with Copper Binding Properties

    PubMed Central

    Stevens, Daniel J.; Walter, Eric D.; Rodríguez, Abel; Draper, David; Davies, Paul; Brown, David R.; Millhauser, Glenn L.

    2009-01-01

    Insertional mutations leading to expansion of the octarepeat domain of the prion protein (PrP) are directly linked to prion disease. While normal PrP has four PHGGGWGQ octapeptide segments in its flexible N-terminal domain, expanded forms may have up to nine additional octapeptide inserts. The type of prion disease segregates with the degree of expansion. With up to four extra octarepeats, the average onset age is above 60 years, whereas five to nine extra octarepeats results in an average onset age between 30 and 40 years, a difference of almost three decades. In wild-type PrP, the octarepeat domain takes up copper (Cu2+) and is considered essential for in vivo function. Work from our lab demonstrates that the copper coordination mode depends on the precise ratio of Cu2+ to protein. At low Cu2+ levels, coordination involves histidine side chains from adjacent octarepeats, whereas at high levels each repeat takes up a single copper ion through interactions with the histidine side chain and neighboring backbone amides. Here we use both octarepeat constructs and recombinant PrP to examine how copper coordination modes are influenced by octarepeat expansion. We find that there is little change in affinity or coordination mode populations for octarepeat domains with up to seven segments (three inserts). However, domains with eight or nine total repeats (four or five inserts) become energetically arrested in the multi-histidine coordination mode, as dictated by higher copper uptake capacity and also by increased binding affinity. We next pooled all published cases of human prion disease resulting from octarepeat expansion and find remarkable agreement between the sudden length-dependent change in copper coordination and onset age. Together, these findings suggest that either loss of PrP copper-dependent function or loss of copper-mediated protection against PrP polymerization makes a significant contribution to early onset prion disease. PMID:19381258

  17. Altered PDE10A expression detectable early before symptomatic onset in Huntington's disease.

    PubMed

    Niccolini, Flavia; Haider, Salman; Reis Marques, Tiago; Muhlert, Nils; Tziortzi, Andri C; Searle, Graham E; Natesan, Sridhar; Piccini, Paola; Kapur, Shitij; Rabiner, Eugenii A; Gunn, Roger N; Tabrizi, Sarah J; Politis, Marios

    2015-10-01

    There is an urgent need for early biomarkers and novel disease-modifying therapies in Huntington's disease. Huntington's disease pathology involves the toxic effect of mutant huntingtin primarily in striatal medium spiny neurons, which highly express phosphodiesterase 10A (PDE10A). PDE10A hydrolyses cAMP/cGMP signalling cascades, thus having a key role in the regulation of striatal output, and in promoting neuronal survival. PDE10A could be a key therapeutic target in Huntington's disease. Here, we used combined positron emission tomography (PET) and multimodal magnetic resonance imaging to assess PDE10A expression in vivo in a unique cohort of 12 early premanifest Huntington's disease gene carriers with a mean estimated 90% probability of 25 years before the predicted onset of clinical symptoms. We show bidirectional changes in PDE10A expression in premanifest Huntington's disease gene carriers, which are associated with the probability of symptomatic onset. PDE10A expression in early premanifest Huntington's disease was decreased in striatum and pallidum and increased in motor thalamic nuclei, compared to a group of matched healthy controls. Connectivity-based analysis revealed prominent PDE10A decreases confined in the sensorimotor-striatum and in striatonigral and striatopallidal projecting segments. The ratio between higher PDE10A expression in motor thalamic nuclei and lower PDE10A expression in striatopallidal projecting striatum was the strongest correlate with higher probability of symptomatic conversion in early premanifest Huntington's disease gene carriers. Our findings demonstrate in vivo, a novel and earliest pathophysiological mechanism underlying Huntington's disease with direct implications for the development of new pharmacological treatments, which can promote neuronal survival and improve outcome in Huntington's disease gene carriers. PMID:26198591

  18. Predictors of outcome in early-onset psychosis: a systematic review

    PubMed Central

    Díaz-Caneja, Covadonga M; Pina-Camacho, Laura; Rodríguez-Quiroga, Alberto; Fraguas, David; Parellada, Mara; Arango, Celso

    2015-01-01

    Given the global burden of psychotic disorders, the identification of patients with early-onset psychosis (EOP; that is, onset before the age of 18) at higher risk of adverse outcome should be a priority. A systematic search of Pubmed, Embase, and PsycInfo (1980 through August 2014) was performed to identify longitudinal observational studies assessing correlates and/or predictors of clinical, functional, cognitive, and biological outcomes in EOP. Seventy-five studies were included in the review. Using multivariate models, the most replicated predictors of worse clinical, functional, cognitive, and biological outcomes in EOP were premorbid difficulties and symptom severity (especially of negative symptoms) at baseline. Longer duration of untreated psychosis (DUP) predicted worse clinical, functional, and cognitive outcomes. Higher risk of attempting suicide was predicted by greater severity of psychotic illness and of depressive symptoms at the first episode of psychosis. Age at onset and sex were not found to be relevant predictors of outcome in most multivariate models, whereas studies using bivariate analyses yielded inconsistent results. Lower intelligence quotient at baseline predicted lower insight at follow-up, worse functional outcomes, and a diagnostic outcome of schizophrenia. Biological predictors of outcome in EOP have been little studied and have not been replicated. Lower levels of antioxidants at baseline predicted greater brain volume changes and worse cognitive functioning at follow-up, whereas neuroimaging markers such as regional cortical thickness and gray matter volume at baseline predicted remission and better insight at follow-up, respectively. EOP patients with poorer premorbid adjustment and prominent negative symptoms at initial presentation are at risk of poor outcome. They should therefore be the target of careful monitoring and more intensive interventions to address whether the disease course can be modified in this especially severely

  19. Early-onset binocularity in preterm infants reveals experience-dependent visual development in humans

    PubMed Central

    Jandó, Gábor; Mikó-Baráth, Eszter; Markó, Katalin; Hollódy, Katalin; Török, Béla; Kovacs, Ilona

    2012-01-01

    Although there is a great deal of knowledge regarding the phylo- and ontogenetic plasticity of the neocortex, the precise nature of environmental impact on the newborn human brain is still one of the most controversial issues of neuroscience. The leading model–system of experience-dependent brain development is binocular vision, also called stereopsis. Here, we show that extra postnatal visual experience in preterm human neonates leads to a change in the developmental timing of binocular vision. The onset age of binocular function, as measured by the visual evoked response to dynamic random dot correlograms (DRDC-VEP), appears to be at around the same time after birth in preterm (4.07 mo) and full-term (3.78 mo) infants. To assess the integrity of the visual pathway in the studied infants, we also measured the latency of the visual-evoked response to pattern reversal stimuli (PR-VEP). PR-VEP latency is not affected by premature birth, demonstrating that the maturation of the visual pathway follows a preprogrammed developmental course. Despite the immaturity of the visual pathway, clearly demonstrated by the PR-VEP latencies, our DRCD-VEP data show that the visual cortex is remarkably ready to accept environmental stimulation right after birth. This early plasticity makes full use of the available extra stimulation time in preterm human infants and results in an early onset of cortical binocularity. According to our data, the developmental processes preceding the onset of binocular function are not preprogrammed, and the mechanisms turning on stereopsis are extremely experience-dependent in humans. PMID:22711824

  20. The gene of an early onset progressive cataract (cerulean cataract) maps to 17q24

    SciTech Connect

    Armitage, M.M.; Ferrell, R.E.; Kivlin, J.D.

    1994-09-01

    Cerulean cataract is an autosomal dominant, fully penetrant, early onset, progressive cataract characterized by blue or white opacifications in the nucleus and cortex of the lens. A five generation family with 44 available affected members in three generations allowed exclusion of linkage of the cerulean cataract phenotype to lens structural protein genes and to all of the chromosomal regions to which autosomal dominant cataract phenotypes have previously been mapped. Exclusion of the plausible candidate instigated a genome-wide search utilizing short tandem repeat polymorphims. The genome search localized the cerulean cataract disease gene to chromosomal region 17q24. The three markers closest to the disease gene are D17S802 [Z({theta})=9.20 at ({theta})=0.086], D17S836 [Z({theta})=4.22 at ({theta})=0.061], and AFMa238yb5 [Z({theta})=7.11 at ({theta})=0.032]. Multipoint analysis yielded a maximum lod score of Z({theta})=11.4 between D17S802 and D17S836 at recombination rates of 0.048 and 0.013 respectively. Three genes that map near the 17q24 chromosomal region and are known to contain highly polymorphic microsatellites were tested for linkage. The genes, DHP-sensitive calcium channel gamma subunit (CACNLG), human somatastatin receptor (SSTR2), and the skeletal muscle sodium channel alpha subunit (SCN4A), were all excluded [Z({theta})=-{infinity} at ({theta})=0] as the gene causing cerulean cataract. The galactokinase (GK1) gene has not been cloned, but its map location is 17q23-q25. Galactokinase deficiency is characterized by a recessive, progressive, early onset cataract. Because of the map location of galactokinase, the age-at-onset, and progressive nature of cataracts associated with galactokinase deficiency, galactokinase is being investigated as a candidate gene for the cerulean cataract phenotype.

  1. Cognitive Efficacy of Quetiapine and Olanzapine in Early-Onset First-Episode Psychosis

    PubMed Central

    Zabala, Arantzazu; Bombín, Igor; Parellada, Mara; Moreno, Dolores; Ruiz-Sancho, Ana; Arango, Celso

    2011-01-01

    The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n = 26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n = 16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis. PMID:19706697

  2. Structured Regions of Alpha-synuclein Fibrils Include the Early Onset Parkinson's Disease Mutation Sites

    SciTech Connect

    Comellas Canal, Gemma; Lemkau, Luisel R.; Nieuwkoop, Andrew J.; Kloepper, Kathryn D.; Ladror, Daniel T.; Ebisu, Reika; Woods, Wendy S.; Lipton, Andrew S.; George, Julia M.; Rienstra, Chad M.

    2011-08-26

    Alpha-Synuclein (AS) fibrils constitute the major proteinaceous component of Lewy bodies (LBs), the pathological hallmark of Parkinson’s disease (PD) and other neurodegenerative diseases. Three single point mutations in the AS gene, as well as multiplication of the wild-type (WT) AS allele, have been previously identified in families with early-onset PD. Although AS fibrils have been the subject of intense study, critical details about their structure including the precise location of the B-strands and the extent of the core, the three-dimensional structure and the effects of the mutations—remain unknown. Here, we have used magic-angle spinning solid-state NMR spectroscopy to present a detailed characterization of the full-length WT AS fibrils. With improved sample preparations, isotopic labeling patterns and NMR experiments, we have confidently assigned more than 90% of the 13C and 15N backbone and sidechain chemical shifts of the detected residues from residue 39 to 97, and quantified the conformational dynamics throughout this region. Our results demonstrate that the core of AS fibrils extends with a repeated motif and that residues 30, 46 and 53-the early-onset PD mutant sites-are located in structured regions of AS fibrils.

  3. Serial elongation-derotation-flexion casting for children with early-onset scoliosis

    PubMed Central

    Canavese, Federico; Samba, Antoine; Dimeglio, Alain; Mansour, Mounira; Rousset, Marie

    2015-01-01

    Various early-onset spinal deformities, particularly infantile and juvenile scoliosis (JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion (EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and - in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois. PMID:26716089

  4. Is the NACP/Synuclein gene involved in early-onset Alheimer`s disease?

    SciTech Connect

    Champion, D.; Clerget-Darpoux, F.; Frebourg, T.

    1994-09-01

    The major component of senile plaques (SP), the most specific histologic lesion of Alzheimer`s disease (AD) is the A4 peptide, derived from a large precursor protein (APP). Recently, a second major component of SP has been isolated. This 35 AA peptide was named non-A4 component amyloid (NAC) and its precursor - a 140 AA protein - was named NACP. Computer homology search has allowed us to establish that the NACP gene is homologous to the rat synuclein gene which is expressed in neurons. Since APP mutations have been shown to cause early-onset Alzheimer`s disease (EOAD) in several families, we investigated whether the NACP/synuclein gene was also involved in familial early-onset Alzheimer`s disease (FEOAD). RT-PCR and direct sequencing of the entire NACP open reading frame did not reveal any alteration of the NACP coding sequence in lymphocytes of 26 unrelated FEOAD patients. We showed that the NACP/synuclein gene was alternatively spliced and that the different transcripts potentially encoded for distinct proteins all containing the NAC peptide. Accumulation of NAC in SP might result from a dysregulation of NACP/synuclein expression.

  5. Early-onset epileptic encephalopathies and the diagnostic approach to underlying causes

    PubMed Central

    Hwang, Su-Kyeong

    2015-01-01

    Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes. PMID:26692875

  6. Placental fractalkine is up-regulated in severe early-onset preeclampsia.

    PubMed

    Siwetz, Monika; Dieber-Rotheneder, Martina; Cervar-Zivkovic, Mila; Kummer, Daniel; Kremshofer, Julia; Weiss, Gregor; Herse, Florian; Huppertz, Berthold; Gauster, Martin

    2015-05-01

    The pathogenesis of preeclampsia (PE) includes the release of placental factors into the maternal circulation, inducing an inflammatory environment in the mother. One of the factors may be the proinflammatory chemokine fractalkine, which is expressed in the syncytiotrophoblast of human placenta, from where it is released into the maternal circulation by constitutive shedding. We examined whether placental fractalkine is up-regulated in severe early-onset PE and whether the proinflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 are able to increase the expression of fractalkine. Gene expression analysis, enzyme-linked immunosorbent assay, and immunohistochemistry consistently showed increased fractalkine expression in placentas from severe early-onset PE, compared to gestational age-matched controls. Expression of a disintegrin and metalloproteinases (ADAMs) 10 and 17, which convert transmembrane fractalkine into the soluble form, was significantly increased in these cases. Incubation of first-trimester placental explants with TNF-α provoked a significant increase in fractalkine expression and release of the soluble form, whereas IL-6 had no effect. TNF-α-mediated up-regulation of placental fractalkine was reversed in the presence of the aspirin-derivative salicylate, which impaired activation of NF-κB p65 in TNF-α-treated explants. On the basis of data from placental explants, we suggest that increased maternal TNF-α may up-regulate the expression and release of placental fractalkine, which, in turn, may contribute to an exaggerated systemic inflammatory response in PE. PMID:25769431

  7. Placental fractalkine is up-regulated in severe early onset preeclampsia

    PubMed Central

    Siwetz, Monika; Dieber-Rotheneder, Martina; Cervar-Zivkovic, Mila; Kummer, Daniel; Kremshofer, Julia; Weiss, Gregor; Herse, Florian; Huppertz, Berthold; Gauster, Martin

    2015-01-01

    The pathogenesis of preeclampsia includes the release of placental factors into the maternal circulation inducing an inflammatory environment in the mother. One of the factors may be the pro-inflammatory chemokine fractalkine, which is expressed in the syncytiotrophoblast of human placenta, from where it is released into the maternal circulation by constitutive shedding. We examined whether placental fractalkine is up-regulated in severe early onset preeclampsia and whether the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin-6 are able to increase the expression of fractalkine. Gene expression analysis, ELISA, and immunohistochemistry consistently showed increased fractalkine expression in placentas from severe early onset preeclampsia, compared to gestational age-matched controls. Expression of the metalloproteinases ADAM10 and ADAM17, which convert transmembrane fractalkine into the soluble form, was significantly increased in these cases. Incubation of first trimester placental explants with TNF-α provoked a significant increase in fractalkine expression and release of the soluble form, whereas interleukin-6 had no effect. TNF-α-mediated up-regulation of placental fractalkine was reversed in the presence of the Aspirin-derivative salicylate, which impaired activation of NF-κB p65 in TNF-α-treated explants. Based on data from placental explants we suggest that increased maternal TNF-α may up-regulate the expression and release of placental fractalkine, which in turn may contribute to an exaggerated systemic inflammatory response in preeclampsia. PMID:25769431

  8. A Survey on Current Practice of Management of Early Onset Neonatal Sepsis.

    PubMed

    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. PMID:27277355

  9. Early-onset epileptic encephalopathies and the diagnostic approach to underlying causes.

    PubMed

    Hwang, Su-Kyeong; Kwon, Soonhak

    2015-11-01

    Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes. PMID:26692875

  10. Mutations in FBXL4, Encoding a Mitochondrial Protein, Cause Early-Onset Mitochondrial Encephalomyopathy

    PubMed Central

    Gai, Xiaowu; Ghezzi, Daniele; Johnson, Mark A.; Biagosch, Caroline A.; Shamseldin, Hanan E.; Haack, Tobias B.; Reyes, Aurelio; Tsukikawa, Mai; Sheldon, Claire A.; Srinivasan, Satish; Gorza, Matteo; Kremer, Laura S.; Wieland, Thomas; Strom, Tim M.; Polyak, Erzsebet; Place, Emily; Consugar, Mark; Ostrovsky, Julian; Vidoni, Sara; Robinson, Alan J.; Wong, Lee-Jun; Sondheimer, Neal; Salih, Mustafa A.; Al-Jishi, Emtethal; Raab, Christopher P.; Bean, Charles; Furlan, Francesca; Parini, Rossella; Lamperti, Costanza; Mayr, Johannes A.; Konstantopoulou, Vassiliki; Huemer, Martina; Pierce, Eric A.; Meitinger, Thomas; Freisinger, Peter; Sperl, Wolfgang; Prokisch, Holger; Alkuraya, Fowzan S.; Falk, Marni J.; Zeviani, Massimo

    2013-01-01

    Whole-exome sequencing and autozygosity mapping studies, independently performed in subjects with defective combined mitochondrial OXPHOS-enzyme deficiencies, identified a total of nine disease-segregating FBXL4 mutations in seven unrelated mitochondrial disease families, composed of six singletons and three siblings. All subjects manifested early-onset lactic acidemia, hypotonia, and developmental delay caused by severe encephalomyopathy consistently associated with progressive cerebral atrophy and variable involvement of the white matter, deep gray nuclei, and brainstem structures. A wide range of other multisystem features were variably seen, including dysmorphism, skeletal abnormalities, poor growth, gastrointestinal dysmotility, renal tubular acidosis, seizures, and episodic metabolic failure. Mitochondrial respiratory chain deficiency was present in muscle or fibroblasts of all tested individuals, together with markedly reduced oxygen consumption rate and hyperfragmentation of the mitochondrial network in cultured cells. In muscle and fibroblasts from several subjects, substantially decreased mtDNA content was observed. FBXL4 is a member of the F-box family of proteins, some of which are involved in phosphorylation-dependent ubiquitination and/or G protein receptor coupling. We also demonstrate that FBXL4 is targeted to mitochondria and localizes in the intermembrane space, where it participates in an approximately 400 kDa protein complex. These data strongly support a role for FBXL4 in controlling bioenergetic homeostasis and mtDNA maintenance. FBXL4 mutations are a recurrent cause of mitochondrial encephalomyopathy onset in early infancy. PMID:23993194

  11. Nutrition in pregnancy and early childhood and associations with obesity in developing countries.

    PubMed

    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 (<2500 g). Low birthweight was associated with higher risk of metabolic syndrome and central 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

  12. Obesity and depression in adolescence and beyond: Reciprocal risks

    PubMed Central

    Marmorstein, Naomi R.; Iacono, William G.; Legrand, Lisa

    2014-01-01

    Objective 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. Methods 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 to 24) were assessed via structured interview (depression) and study-measured height and weight. Results 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=3.76, confidence interval= 1.33–10.59) during late adolescence among females. Obesity that developed during late adolescence predicted the onset of depression (odds ratio=5.89, confidence interval= 2.31–15.01) during early adulthood among females. Conclusions 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 females, may help in reducing risk for this form of comorbidity. PMID:24480863

  13. Plant macrofossil evidence for an early onset of the Holocene summer thermal maximum in northernmost Europe

    PubMed Central

    Väliranta, M.; Salonen, J. S.; Heikkilä, M.; Amon, L.; Helmens, K.; Klimaschewski, A.; Kuhry, P.; Kultti, S.; Poska, A.; Shala, S.; Veski, S.; Birks, H. H.

    2015-01-01

    Holocene summer temperature reconstructions from northern Europe based on sedimentary pollen records suggest an onset of peak summer warmth around 9,000 years ago. However, pollen-based temperature reconstructions are largely driven by changes in the proportions of tree taxa, and thus the early-Holocene warming signal may be delayed due to the geographical disequilibrium between climate and tree populations. Here we show that quantitative summer-temperature estimates in northern Europe based on macrofossils of aquatic plants are in many cases ca. 2 °C warmer in the early Holocene (11,700–7,500 years ago) than reconstructions based on pollen data. When the lag in potential tree establishment becomes imperceptible in the mid-Holocene (7,500 years ago), the reconstructed temperatures converge at all study sites. We demonstrate that aquatic plant macrofossil records can provide additional and informative insights into early-Holocene temperature evolution in northernmost Europe and suggest further validation of early post-glacial climate development based on multi-proxy data syntheses. PMID:25858780

  14. Early-Onset Basal Cell Carcinoma and Indoor Tanning: A Population-Based Study

    PubMed Central

    Zens, M. Scot; Li, Zhigang; Stukel, Therese A.; Perry, Ann E.; Gilbert-Diamond, Diane; Sayarath, Vicki; Stephenson, Rita S.; Barton, Dorothea; Nelson, Heather H.; Spencer, Steven K.

    2014-01-01

    OBJECTIVE: Indoor tanning with UV radiation–emitting lamps is common among adolescents and young adults. Rising incidence rates of basal cell carcinoma (BCC) have been reported for the United States and elsewhere, particularly among those diagnosed at younger ages. Recent epidemiologic studies have raised concerns that indoor tanning may be contributing to early occurrence of BCC, and younger people may be especially vulnerable to cancer risk associated with this exposure. Therefore, we sought to address these issues in a population-based case–control study from New Hampshire. METHODS: Data on indoor tanning were obtained on 657 cases of BCC and 452 controls ≤50 years of age. RESULTS: Early-onset BCC was related to indoor tanning, with an adjusted odds ratio (OR) of 1.6 (95% confidence interval, 1.3–2.1). The strongest association was observed for first exposure as an adolescent or young adult, with a 10% increase in the OR with each age younger at first exposure (OR per year of age ≤23 = 1.1; 95% confidence interval, 1.0–1.2). Associations were present for each type of device examined (ie, sunlamps, tanning beds, and tanning booths). CONCLUSIONS: Our findings suggest early exposure to indoor tanning increases the risk of early development of BCC. They also underscore the importance of counseling adolescents and young adults about the risks of indoor tanning and for discouraging parents from consenting minors to this practice. PMID:24958589

  15. Potential renoprotective effects of piceatannol in ameliorating the early-stage nephropathy associated with obesity in obese Zucker rats.

    PubMed

    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. PMID:26660756

  16. Voxel-based structural magnetic resonance imaging (MRI) study of patients with early onset schizophrenia

    PubMed Central

    Yoshihara, Yujiro; Sugihara, Genichi; Matsumoto, Hideo; Suckling, John; Nishimura, Katsuhiko; Toyoda, Takao; Isoda, Haruo; Tsuchiya, Kenji J; Takebayashi, Kiyokazu; Suzuki, Katsuaki; Sakahara, Harumi; Nakamura, Kazuhiko; Mori, Norio; Takei, Nori

    2008-01-01

    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 and the symptom

  17. Obesity Prevention: Parenting Styles Make a Difference

    ERIC Educational Resources Information Center

    Winter, Suzanne M.

    2009-01-01

    Childhood obesity is epidemic in the United States and other industrialized countries across the globe. This trend is alarming, because childhood obesity is associated with the early onset of serious health problems, including Type II diabetes, cardiovascular disease, orthopedic problems, behavioral disorders, and asthma. Mounting evidence also…

  18. Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.

    PubMed

    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.). PMID:26083206

  19. DOCK2 and a Recessive Immunodeficiency with Early-Onset Invasive Infections

    PubMed Central

    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; Ciftci, Ergin; Felgentreff, Kerstin; Ohsumi, Toshiro K.; Pedergnana, Vincent; Boisson, Bertrand; Haskoloğlu, Sule; 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; Comeau, Anne Marie; Geha, Raif S.; Abel, Laurent; Buckley, Rebecca H.; Ikincioğullari, Aydan; Al-Herz, Waleed; Helminen, Merja; Doğu, Figen; Casanova, Jean-Laurent; Boztuğ, Kaan; Notarangelo, Luigi D.

    2015-01-01

    Background Combined immunodeficiencies (CIDs) denote inborn errors of T-cell immunity with T cells present but quantitatively or functionally deficient. Impaired humoral immunity, either due to a primary B cell defect or secondary to the T-cell defect, is also frequent. Consequently, patients with CID display severe infections and/or autoimmunity. The specific molecular, cellular, and clinical features of many types of CID remain unknown. Methods We performed genetic and cellular immunological studies in five unrelated children who shared a history of early-onset invasive bacterial and viral infections, with lymphopenia and defective T-, B-, and NK-cell responses. Two patients died early in childhood, whereas the other three underwent allogeneic hematopoietic stem cell transplantation with normalization of T cell function and clinical improvement. Results We identified bi-allelic mutations in the Dedicator Of Cytokinesis 2 (DOCK2) gene in these five patients. RAC1 activation was impaired in T cells. Chemokine-induced migration and actin polymerization were defective in T, B, and NK cells. NK-cell degranulation was also affected. The production of interferon (IFN)-α and -λ by peripheral blood mononuclear cells (PBMCs) was diminished following virus infection. Moreover, in DOCK2-deficient fibroblasts, virus replication was increased and there was enhanced virus-induced cell death, which could be normalized by treatment with IFN-α2β or upon expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a Mendelian disorder with pleiotropic defects of hematopoietic and non-hematopoietic immunity. Children with clinical features of CID, especially in the presence of early-onset, invasive infections may have this condition. PMID:26083206

  20. The effect of obesity on early outcomes in adolescents undergoing reduction mammaplasty.

    PubMed

    Webb, Michelle L; Cerrato, Felecia; Rosen, Heather; DiVasta, Amy D; Greene, Arin K; Labow, Brian I

    2012-03-01

    It is not known whether obesity portends poorer outcomes following reduction mammaplasty in adolescent macromastia patients. We review symptoms in obese and nonobese adolescent macromastia patients and describe early outcomes following reduction mammaplasty. Demographics, operative details, and postoperative follow-up data were collected on 67 patients seen at our institution between 1997 and 2008. Variables were compared using 2-sample t tests or Pearson χ/Fisher exact tests. Mean age at surgery was 17.1 ± 1.6 years. Mean body mass index was 27.9 ± 4.5 kg/m, and 32.8% were obese. Thirty-four patients (50.7%) experienced minor complications; 1 patient experienced a major complication. Of patients with complications, obese patients reported a greater number than nonobese patients (P = 0.013). There were no differences in the type of complication or self-reported satisfaction between obese and nonobese patients 34.4 ± 25.7 weeks after surgery. Our findings suggest that reduction mammaplasty is well-tolerated in obese and nonobese adolescents with macromastia and that obesity is not an absolute contraindication to reduction mammaplasty in adolescents. PMID:21629095

  1. Early Adult Obesity and U.S. Women’s Lifetime Childbearing Experiences

    PubMed Central

    Frisco, Michelle L.; Weden, Margaret

    2013-01-01

    Literature from multiple disciplines suggests that women who are obese during early adulthood may accumulate social and physiological impediments to childbearing across their reproductive lives. This led the authors to investigate whether obese young women have different lifetime childbearing experiences than leaner peers by analyzing data from 1,658 female participants in the 1979 National Longitudinal Survey of Youth. Study sample members were nulliparous women ages 20 – 25 in 1982. The authors examined their childbearing experiences between 1982 and 2006 and found that young women who were obese at baseline had higher odds of remaining childless and increased odds of underachieving fertility intentions than young women who were normal weight at baseline. These results suggest that obesity has long-term ramifications for women’s childbearing experiences, with respect to whether and how many children women have in general and relative to the number of children they want. PMID:24223433

  2. Early sexual experience and later onset of illegal drug use among African American students on HBCU campuses.

    PubMed

    Wang, Yan; Storr, Carla; Browne, Dorothy C; Wagner, Fernando A

    2011-01-01

    Few studies examine whether early sexual experience is associated with subsequent illegal drug use among adolescents. A sample of 7,372 African American students who had not used illegal drugs before the age of 14 were identified in the dataset of the 2001 Historically Black Colleges and Universities (HBCU) Substance Use Survey. Using self-reported ages of onset, discrete-time survival models estimated the hazard of illegal drug use onset after age 13 subsequent to first sexual intercourse. Early sex was modestly associated with subsequent illegal drug initiation, particularly among females. Drug use prevention services should be provided to youth engaged in early sexual activity. PMID:20735190

  3. Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ondoa, Pascale; Ceulemans, Ann; Vereecken, Chris; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

    2015-01-01

    Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. PMID:26208109

  4. A Review of the Relationship Between Socioeconomic Position and the Early-Life Predictors of Obesity.

    PubMed

    Cameron, Adrian J; Spence, Alison C; Laws, Rachel; Hesketh, Kylie D; Lioret, Sandrine; Campbell, Karen J

    2015-09-01

    A range of important early-life predictors of later obesity have been identified. Children of lower socioeconomic position (SEP) have a steeper weight gain trajectory from birth with a strong socioeconomic gradient in child and adult obesity prevalence. An assessment of the association between SEP and the early-life predictors of obesity has been lacking. The review involved a two-stage process: Part 1, using previously published systematic reviews, we developed a list of the potentially modifiable determinants of obesity observable in the pre-natal, peri-natal or post-natal (pre-school) periods; and part 2, conducting a literature review of evidence for socioeconomic patterning in the determinants identified in part 1. Strong evidence was found for an inverse relationship between SEP and (1) pre-natal risk factors (pre-pregnancy maternal body mass index (BMI), diabetes and pre-pregnancy diet), (2) antenatal/peri natal risk factors (smoking during pregnancy and low birth weight) and (3) early-life nutrition (including breastfeeding initiation and duration, early introduction of solids, maternal and infant diet quality, and some aspects of the home food environment), and television viewing in young children. Less strong evidence (because of a lack of studies for some factors) was found for paternal BMI, maternal weight gain during pregnancy, child sleep duration, high birth weight and lack of physical activity in young children. A strong socioeconomic gradient exists for the majority of the early-life predictors of obesity suggesting that the die is cast very early in life (even pre-conception). Lifestyle interventions targeting disadvantaged women at or before child-bearing age may therefore be particularly important in reducing inequality. Given the likely challenges of reaching this target population, it may be that during pregnancy and their child's early years are more feasible windows for engagement. PMID:26627493

  5. Early onset degenerative dementias: demographic characteristics and etiologic classification in a tertiary referral center.

    PubMed

    Maiovis, Pantelis; Ioannidis, Panagiotis; Konstantinopoulou, Elina; Karacostas, Dimitris

    2015-03-01

    Early onset dementia (EOD) is a major diagnostic challenge as it often presents with atypical features and may be attributed to treatable diseases. Primary degenerative dementias (Alzheimer's disease-AD, frontotemporal lobar degeneration-FTLD, Lewy body dementia-LBD), although traditionally considered to affect older people, are still a main cause of EOD. 491 demented patients were assessed from January 1, 2003 to December 31, 2010 in the Neurology Department of a tertiary referral center. Patients were classified as AD, behavioral variant frontotemporal dementia (bvFTD), non-fluent agrammatic variant primary progressive aphasia (naPPA), semantic variant PPA (svPPA), corticobasal degeneration (CBD), or progressive supranuclear palsy (PSP) who also met criteria for naPPA and LBD. Finally, their demographic characteristics were analysed, according to age at onset (EOD <65 years, late onset dementia-LOD ≥65 years). From the 491 patients, 137 (27.9 %) were EOD. In the EOD group, 52 (38 %) were diagnosed with bvFTD, 34 (24.8 %) with AD, 27 (19.7 %) with naPPA, 10 (7.2 %) with svPPA, 12 (8.8 %) with CBD or PSP, and 2 (1.5 %) with LBD. Demographic characteristics did not differ significantly among diagnostic categories in the EOD group, while in the LOD group FTLD patients were younger and more frequently men compared to both AD and LBD patients. EOD patients had more years of education than LOD patients. Degenerative disorders as causes of EOD are not rare. High clinical alertness is warranted to achieve correct and timely diagnosis. PMID:24878660

  6. Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical Management

    PubMed Central

    Shuch, Brian; Vourganti, Srinivas; Ricketts, Christopher J.; Middleton, Lindsay; Peterson, James; Merino, Maria J.; Metwalli, Adam R.; Srinivasan, Ramaprasad; Linehan, W. Marston

    2014-01-01

    Purpose Approximately 5% to 8% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC germline mutation testing. We evaluate how age of onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer. Patients and Methods We analyzed the age distribution of RCC cases in the SEER-17 program and in our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary cancer syndrome. Models were established to evaluate the specific age thresholds for genetic testing. Results The median age of patients with RCC in SEER-17 was 64 years, with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (P < .05). The bottom decile cutoff was ≤ 46 years of age and slightly differed by sex, race, and histology. The mean and median ages at presentation of 608 patients with hereditary kidney cancer were 39.3 years and 37 years, respectively. Although age varied by specific syndrome, 70% of these cases were found to lie at or below the bottom age decile. Modeling age-based genetic testing thresholds demonstrated that the 10th percentile maximized sensitivity and specificity. Conclusion Early age of onset might be a sign of hereditary RCC. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines. PMID:24378414

  7. Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease

    PubMed Central

    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. Evidence for Three Loci Modifying Age-at-Onset of Alzheimer’s Disease in Early-Onset PSEN2 Families

    PubMed Central

    Marchani, Elizabeth E.; Bird, Thomas D.; Steinbart, Ellen J.; Rosenthal, Elisabeth; Yu, Chang-En; Schellenberg, Gerard D.; Wijsman, Ellen M.

    2011-01-01

    Families with early-onset Alzheimer’s disease (AD) sharing a single PSEN2 mutation exhibit a wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all of this variation. We performed a genome scan within nine such families for loci influencing age-at-onset, while simultaneously controlling for variation in the primary PSEN2 mutation (N141I) and APOE. We found significant evidence of linkage between age-at-onset and chromosome 1q23.3 (P < 0.001) when analysis included all families, and to chromosomes 1q23.3 (P < 0.001), 17p13.2 (P = 0.0002), 7q33 (P = 0.017), and 11p14.2 (P = 0.017) in a single large pedigree. Simultaneous analysis of these four chromosomes maintained strong evidence of linkage to chromosomes 1q23.3 and 17p13.2 when all families were analyzed, and to chromosomes 1q23.3, 7q33, and 17p13.2 within the same single pedigree. Inclusion of major gene covariates proved essential to detect these linkage signals, as all linkage signals dissipated when PSEN2 and APOE were excluded from the model. The four chromosomal regions with evidence of linkage all coincide with previous linkage signals, associated SNPs, and/or candidate genes identified in independent AD study populations. This study establishes several candidate regions for further analysis and is consistent with an oligogenic model of AD risk and age-at-onset. More generally, this study also demonstrates the value of searching for modifier loci in existing datasets previously used to identify primary causal variants for complex disease traits. PMID:20333730

  9. A randomized controlled trial to prevent childhood obesity through early childhood feeding and parenting guidance: Rationale and design of study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early and rapid growth in infants is strongly associated with early development and persistence of obesity in young children. Substantial research has linked child obesity/overweight to increased risks for serious health outcomes, which include adverse physical, psychological, behavioral, or social ...

  10. The Maudsley Early Onset Schizophrenia Study: Cognitive Function Over a 4-Year Follow-Up Period

    PubMed Central

    Frangou, Sophia; Hadjulis, Michael; Vourdas, Apostolos

    2008-01-01

    Generalized cognitive deficits have been consistently reported in adolescents with early onset schizophrenia (EOS; defined as onset before the age of 17 years). The impact on cognition of potential interactions between disease pathology and brain maturation remains unclear. We therefore compared cognitive function between 20 EOS patients and 20 healthy controls matched on age, gender, and parental socioeconomic status at 2 time points, when aged 15.58 (2.27) and after a mean interval of 4 ± 1.08 years when aged 19.46 (2.21) years. Repeated measures analyses revealed no differences between patients and controls in the degree of change over this time period in general intellectual function and planning ability as measured by the Tower of London. There was deterioration in the verbal memory and attentional control index scores from the Wechsler Memory Scale-Revised but relative improvement in Part A of the Trail Making Test. Patients’ level of symptomatology as well as the type and dose of medication were comparable at both time points. We conclude that most aspects of cognitive function remain relatively stable in EOS patients during adolescence; there is evidence for deterioration in immediate verbal memory and attention while speed of information processing may show improvement. PMID:18024468

  11. Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson's disease.

    PubMed

    Watts, Ray L; Lyons, Kelly E; Pahwa, Rajesh; Sethi, Kapil; Stern, Matthew; Hauser, Robert A; Olanow, Warren; Gray, Alex M; Adams, Bryan; Earl, Nancy L

    2010-05-15

    Levodopa-induced dyskinesia can result in significant functional disability and reduced quality of life in patients with Parkinson's disease (PD). The goal of this study was to determine if the addition of once-daily ropinirole 24-hour prolonged-release (n = 104) in PD patients not optimally controlled with levodopa after up to 3 years of therapy with less than 600 mg/d delays the onset of dyskinesia compared with increasing doses of levodopa (n = 104). During the study, 3% of the ropinirole prolonged-release group (mean dose 10 mg/d) and 17% of the levodopa group (mean additional dose 284 mg/d) developed dyskinesia (P < 0.001). There were no significant differences in change in Unified Parkinson's Disease Rating Scale activities of daily living or motor scores, suggesting comparable efficacy between the two treatments. Adverse events were comparable in the two groups with nausea, dizziness, insomnia, back pain, arthralgia, somnolence, fatigue, and pain most commonly reported. Ropinirole prolonged-release delayed the onset of dyskinesia with comparable efficacy to increased doses of levodopa in early PD patients not optimally controlled with levodopa. PMID:20461803

  12. Early- and late-onset blindness both curb audiotactile integration on the parchment-skin illusion.

    PubMed

    Champoux, François; Collignon, Olivier; Bacon, Benoit A; Lepore, Franco; Zatorre, Robert J; Théoret, Hugo

    2011-01-01

    It has been shown that congenital blindness can lead to anomalies in the integration of auditory and tactile information, at least under certain conditions. In the present study, we used the parchment-skin illusion, a robust illustration of sound-biased perception of touch based on changes in frequency, to investigate the specificities of audiotactile interactions in early- and late-onset blind individuals. Blind individuals in both groups did not experience any illusory change in tactile perception when the frequency of the auditory signal was modified, whereas sighted individuals consistently experienced the illusion. This demonstration that blind individuals had reduced susceptibility to an auditory-tactile illusion suggests either that vision is necessary for the establishment of audiotactile interactions or that auditory and tactile information can be processed more independently in blind individuals than in sighted individuals. In addition, the results obtained in late-onset blind participants suggest that visual input may play a role in the maintenance of audiotactile integration. PMID:21123856

  13. Results of late surgical intervention in children with early-onset bilateral cataracts

    PubMed Central

    Ganesh, Suma; Arora, Priyanka; Sethi, Sumita; Gandhi, Tapan K; Kalia, Amy; Chatterjee, Garga; Sinha, Pawan

    2016-01-01

    Background Cataracts are a major cause of childhood blindness globally. Although surgically treatable, it is unclear whether children would benefit from such interventions beyond the first few years of life, which are believed to constitute `critical' periods for visual development. Aims To study visual acuity outcomes after late treatment of early-onset cataracts and also to determine whether there are longitudinal changes in postoperative acuity. Methods We identified 53 children with dense cataracts with an onset within the first half-year after birth through a survey of over 20 000 rural children in India. All had accompanying nystagmus and were older than 8 years of age at the time of treatment. They underwent bilateral cataract surgery and intraocular lens implantation. We then assessed their best-corrected visual acuity 6 weeks and 6 months after surgery. Results 48 children from the pool of 53 showed improvement in their visual acuity after surgery. Our longitudinal assessments demonstrated further improvements in visual acuity for the majority of these children proceeding from the 6-week to 6-month assessment. Interestingly, older children in our subject pool did not differ significantly from the younger ones in the extent of improvement they exhibit. Conclusions and relevance Our results demonstrate that not only can significant vision be acquired until late in childhood, but that neural processes underlying even basic aspects of vision like resolution acuity remain malleable until at least adolescence. These data argue for the provision of cataract treatment to all children, irrespective of their age. PMID:24879807

  14. Polymorphisms in the PTPN22 region are associated with psoriasis of early onset

    PubMed Central

    Smith, RhLl; Warren, RB; Eyre, S; Ke, X; Young, HS; Allen, M; Strachan, D; McArdle, W; Gittins, MP; Barker, JNWN; Griffiths, CEM; Worthington, J

    2008-01-01

    Background Psoriasis, a chronic inflammatory skin disease, affects approximately 2% of the population worldwide. Although the aetiology of psoriasis is poorly understood, patients with disease of early onset (Type I, age of onset ≤ 40 years) usually have a strong genetic component to the disease. Objectives The purpose of this study was to investigate the role of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene region in susceptibility to Type I psoriasis. Patients and methods Thirteen single nucleotide polymorphisms (SNPs) mapping to the PTPN22 region were genotyped in 647 patients with Type I psoriasis and 566 normal controls. Results The rs2476601 (R620W) SNP, widely associated with other inflammatory autoimmune diseases, showed no evidence of association with susceptibility to Type I psoriasis. Two SNPs (rs1217414 and rs3789604) demonstrated significant association with Type I psoriasis and were subsequently genotyped in a further 253 unrelated patients and 2024 normal controls. rs1217414 and rs3789604 were also significantly associated with Type I psoriasis in the combined datasets (P = 0·003 and P = 0·0002, respectively); furthermore carriage of both risk alleles was also significantly associated (P = 0·002). Conclusions This study demonstrates evidence of association of two SNPs (rs1217414 and rs3789604) in the PTPN22 region with Type I psoriasis, providing evidence for a role of this gene in Type I psoriasis that is not conferred by the R620W variant previously associated with a number of inflammatory diseases. PMID:18341666

  15. Longitudinal changes of cortical thickness in early- versus late-onset Alzheimer's disease.

    PubMed

    Cho, Hanna; Jeon, Seun; Kang, Sue J; Lee, Jong-Min; Lee, Jae-Hong; Kim, Geon Ha; Shin, Ji Soo; Kim, Chi Hun; Noh, Young; Im, Kiho; Kim, Sung Tae; Chin, Juhee; Seo, Sang Won; Na, Duk L

    2013-07-01

    Early-onset Alzheimer's disease (EOAD) has been shown to progress more rapidly than late-onset Alzheimer's disease (LOAD). However, no studies have compared the topography of brain volume reduction over time. The purpose of this 3-year longitudinal study was to compare EOAD and LOAD in terms of their rates of decline in cognitive testing and topography of cortical thinning. We prospectively recruited 36 patients with AD (14 EOAD and 22 LOAD) and 14 normal controls. All subjects were assessed with neuropsychological tests and with magnetic resonance imaging at baseline, Year 1, and Year 3. The EOAD group showed more rapid decline than the LOAD group in attention, language, and frontal-executive tests. The EOAD group also showed more rapid cortical thinning in widespread association cortices. In contrast, the LOAD group presented more rapid cortical thinning than the EOAD group only in the left parahippocampal gyrus. Our study suggests that patients with EOAD show more rapid cortical atrophy than patients with LOAD, which accounts for faster cognitive decline on neuropsychological tests. PMID:23391426

  16. Early Onset of Atherosclerosis of The Carotid Bifurcation in Newborn Cadavers

    PubMed Central

    Cakmak, Yusuf Ozgur; Sehirli, Ümit; Keskinoz, Elif Nedret; Cosgun, Erdal; Arbak, Serap; Yalin, Aymelek

    2016-01-01

    Introduction The anatomy of arterial bifurcations affects blood flow and has a significant role in the development of vascular disease. Therefore, it is important to know the structural characteristics of the Common Carotid Artery (CCA) and its branches for early onset of atherosclerosis in newborns. Aim The present study was conducted to evaluate the characteristics of CCA in newborn cadavers. Materials and Methods Eight carotid arteries obtained from newborn cadavers were used. The outflow to inflow area ratios was calculated to evaluate vessel diameters. Additionally, scanning electron and light microscopic investigations were conducted with tissue samples. The brachial artery of each cadaver was used as controls. Correlation between area ratios and atherosclerotic endothelial damage was determined. Results Light microscopic investigations demonstrated that control group sections showed no positivity for Oil red O staining, while carotid bifurcation regions depicted widespread occurrence of intimal lipid accumulations. Scanning electron microscopic examination of control group sections presented regular endothelial topography, while carotid bifurcation region topography exhibited numerous blood cells and separated endothelial cells. Fibrin accumulation on endothelial surface in low area ratios was another important finding in the examination of its endothelial surface degeneration. The above-mentioned morphological findings seemed to be quite parallel to outflow to inflow area ratio data favouring low area and degeneration. Conclusion The correlation between area ratios and the histological characteristic of cerebral vessels of newborn cadavers indicate that early stages of atherosclerosis began in early embryologic life. PMID:27437199

  17. Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

    PubMed

    Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

    2016-01-01

    The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases. PMID:27187038

  18. Increased metabolic vulnerability in early-onset Alzheimer’s disease is not related to amyloid burden

    PubMed Central

    Furst, Ansgar J.; Alkalay, Adi; Racine, Caroline A.; O’Neil, James P.; Janabi, Mustafa; Baker, Suzanne L.; Agarwal, Neha; Bonasera, Stephen J.; Mormino, Elizabeth C.; Weiner, Michael W.; Gorno-Tempini, Maria L.; Rosen, Howard J.; Miller, Bruce L.; Jagust, William J.

    2010-01-01

    Patients with early age-of-onset Alzheimer’s disease show more rapid progression, more generalized cognitive deficits and greater cortical atrophy and hypometabolism compared to late-onset patients at a similar disease stage. The biological mechanisms that underlie these differences are not well understood. The purpose of this study was to examine in vivo whether metabolic differences between early-onset and late-onset Alzheimer’s disease are associated with differences in the distribution and burden of fibrillar amyloid-β. Patients meeting criteria for probable Alzheimer’s disease (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's; Disease and Related Disorders Association criteria) were divided based on estimated age at first symptom (less than or greater than 65 years) into early-onset (n = 21, mean age-at-onset 55.2 ± 5.9 years) and late-onset (n = 18, 72.0 ± 4.7 years) groups matched for disease duration and severity. Patients underwent positron emission tomography with the amyloid-β-ligand [11C]-labelled Pittsburgh compound-B and the glucose analogue [18F]-labelled fluorodeoxyglucose. A group of cognitively normal controls (n = 30, mean age 73.7 ± 6.4) was studied for comparison. [11C]-labelled Pittsburgh compound-B images were analysed using Logan graphical analysis (cerebellar reference) and [18F]-labelled fluorodeoxyglucose images were normalized to mean activity in the pons. Group differences in tracer uptake were assessed on a voxel-wise basis using statistical parametric mapping, and by comparing mean values in regions of interest. To account for brain atrophy, analyses were repeated after applying partial volume correction to positron emission tomography data. Compared to normal controls, both early-onset and late-onset Alzheimer’s disease patient groups showed increased [11C]-labelled Pittsburgh compound-B uptake throughout frontal, parietal and lateral temporal cortices and striatum on voxel

  19. Exploring the service and support needs of families with early-onset Alzheimer's disease.

    PubMed

    Gibson, Allison K; Anderson, Keith A; Acocks, Sara

    2014-11-01

    Although often cast as a disease of later life, a growing number of people are being diagnosed with Alzheimer's disease in their 50s and 60s. Early-onset Alzheimer's disease (EOAD) poses special challenges and needs for individuals and their caregivers, such as employment and access to services. In this cross-sectional study, the researchers surveyed 81 (N = 81) family caregivers to individuals with EOAD to identify service and support usage and need. Descriptive analyses revealed that families utilized a range of formal services (eg, adult day) and informal support from family and friends. In terms of challenges and needs, participants indicated that they struggled most with employment, benefits, and financial issues. Although most caregivers felt that they were coping well, they also indicated that their needs were not well understood by service providers and the public. These findings highlight the need to better understand and respond to the specific issues surrounding EOAD. PMID:25392308

  20. Effect of growing rod on sagittal and spinopelvic parameters in early-onset scoliosis patients.

    PubMed

    Sariyilmaz, Kerim; Akgul, Turgut; Ozkunt, Okan; Dikici, Fatih; Korkmaz, Murat; Sar, Cuneyt; Domanic, Unsal

    2016-05-01

    Growing rod is a commonly used surgery for early-onset scoliosis (EOS). However, the effect of growing-rod lengthening on the spinopelvic alignment is unclear. In this study, 21 EOS patients treated by growing rod were evaluated retrospectively and thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI) , sacral slope (SS), pelvic tilt (PT), and sagittal vertical axis (SVA) were measured. Preoperatively, the mean TK, LL, PI, PT, SS, and SVA were 27.4°, 35.2°, 43.8°, 7.5°, 33.8°, and 47.7 mm respectively. After the last lengthening, TK, LL, PI, PT, SS, and SVA were 28.3°, 28.06°, 41.4°, 7°, 5.2°, and 42.6 mm, respectively. The sagittal plane parameters in our EOS patients were not significantly altered during the lengthening period. PMID:27007546

  1. Early-Onset Mild Type Leukoencephalopathy Caused by a Homozygous EARS2 Mutation.

    PubMed

    Taskin, Birce Dilge; Karalok, Zeynep Selen; Gurkas, Esra; Aydin, Kursad; Aydogmus, Ummu; Ceylaner, Serdar; Karaer, Kadri; Yilmaz, Cahide; Pearl, Phillip Lawrence

    2016-06-01

    Childhood leukoencephalopathies are a broad class of diseases, which are extremely rare. The treatment and classification of these disorders are both challenging. Nearly half of children presenting with a leukoencephalopathy remain without a specific diagnosis. Leukoencephalopathy with thalamus and brain stem involvement and high lactate (LTBL) is a newly described childhood leukoencephalopathy caused by mutations in the gene encoding a mitochondrial aminoacyl-tRNA synthetase specific for glutamate, EARS2 Magnetic resonance images show a characteristic leukoencephalopathy with thalamic and brain stem involvement. Here, we report a different clinical course of LTBL supported by typical MRI features in a Turkish patient who presented with a history of failure to walk. The EARS2 gene mutation analysis identified a c.322C>T transition, predicting a p.R108W change. This is the first reported early-onset mild type LTBL caused by a homozygous EARS2 mutation case in the literature. PMID:26893310

  2. Time perspective and early-onset substance use: a model based on stress-coping theory.

    PubMed

    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. PMID:11419227

  3. Child, Parent, and Peer Predictors of Early-Onset Substance Use: A Multisite Longitudinal Study

    PubMed Central

    Kaplow, Julie B.; Curran, Patrick J.; Dodge, Kenneth A.

    2009-01-01

    The purpose of this study was to identify kindergarten-age predictors of early-onset substance use from demographic, environmental, parenting, child psychological, behavioral, and social functioning domains. Data from a longitudinal study of 295 children were gathered using multiple-assessment methods and multiple informants in kindergarten and 1st grade. Annual assessments at ages 10, 11, and 12 reflected that 21% of children reported having initiated substance use by age 12. Results from longitudinal logistic regression models indicated that risk factors at kindergarten include being male, having a parent who abused substances, lower levels of parental verbal reasoning, higher levels of overactivity, more thought problems, and more social problem solving skills deficits. Children with no risk factors had less than a 10% chance of initiating substance use by age 12, whereas children with 2 or more risk factors had greater than a 50% chance of initiating substance use. Implications for typology, etiology, and prevention are discussed. PMID:12041707

  4. Ultrasound control of magnet growing rod distraction in early onset scoliosis.

    PubMed

    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. PMID:25843064

  5. Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome.

    PubMed

    Oki, Mitsuaki; Hori, Shin-ichiro; Asayama, Shinya; Wate, Reika; Kaneko, Satoshi; Kusaka, Hirofumi

    2016-01-01

    We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of (123)I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease. PMID:26831029

  6. Early-onset hearing loss reorganizes the visual and auditory network in children without cochlear implantation.

    PubMed

    Shi, Bin; Yang, Li-Zhuang; Liu, Ying; Zhao, Shu-Li; Wang, Ying; Gu, Feng; Yang, Zhiyu; Zhou, Yifeng; Zhang, Peng; Zhang, Xiaochu

    2016-02-10

    The present study investigates the effect of early-onset hearing loss on the reorganization of visual and auditory networks in children without cochlear implants. Eleven congenitally deaf children and 12 age-matched hearing children were included in the study. Bilateral transverse temporal cortices and bilateral lateral occipital cortices were defined as auditory and visual seeds, respectively (as verified using an independent component analysis). The four seed-based connectivity maps were computed for each participant. As a result, group analysis showed that the primary auditory cortex was less connected with the motor cortex, whereas the visual cortex showed strengthened connectivity with motor and speech cortices in congenitally deaf children compared with the controls. Moreover, we found that the differences in functional connectivity between deaf and control children were not because of morphometric changes. Our results provide neural evidence for the sensorimotor coupling model of speech development. PMID:26730516

  7. Diagnosing early onset dementia and then what? A frustrating system of aftercare resources

    PubMed Central

    Chemali, Z; Schamber, S; Tarbi, EC; Acar, D; Avila-Urizar, M

    2012-01-01

    Recent studies indicate that the prevalence of early onset dementia (EOD) is more common than it was once presumed. As such, and considering the substantial challenges EOD presents to the patient, caregivers, and health care providers, this study sought to investigate the mechanism of care delivered to these patients. A medical record chart review was conducted for 85 patients attending a memory disorder unit who initially presented to rule out EOD as a working diagnosis. The results suggest that while the majority of these patients received an extensive work-up and were heavily medicated, they remained at home, where they lacked adequate age-related services and could not be placed, despite the crippling caregiver burden. This manuscript is a platform to discuss our current system limitations in the care of these patients with an eye on new opportunities for this challenging group. PMID:22287850

  8. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features.

    PubMed

    Lessel, Davor; Vaz, Bruno; Halder, Swagata; Lockhart, Paul J; Marinovic-Terzic, Ivana; Lopez-Mosqueda, Jaime; Philipp, Melanie; Sim, Joe C H; Smith, Katherine R; Oehler, Judith; Cabrera, Elisa; Freire, Raimundo; Pope, Kate; Nahid, Amsha; Norris, Fiona; Leventer, Richard J; Delatycki, Martin B; Barbi, Gotthold; von Ameln, Simon; Högel, Josef; Degoricija, Marina; Fertig, Regina; Burkhalter, Martin D; Hofmann, Kay; Thiele, Holger; Altmüller, Janine; Nürnberg, Gudrun; Nürnberg, Peter; Bahlo, Melanie; Martin, George M; Aalfs, Cora M; Oshima, Junko; Terzic, Janos; Amor, David J; Dikic, Ivan; Ramadan, Kristijan; Kubisch, Christian

    2014-11-01

    Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma. PMID:25261934

  9. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study.

    PubMed

    Fustolo-Gunnink, S F; Vlug, R D; Smits-Wintjens, V E H J; Heckman, E J; Te Pas, A B; Fijnvandraat, K; Lopriore, E

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA) neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x109/L) was found in 53% (176/329) of SGA neonates and 20% (66/330) of AGA neonates (relative risk (RR) 2.7, 95% confidence interval (CI) [2.1, 3.4]). Severe thrombocytopenia (21-50x109/L) occurred in 25 neonates (8%) in the SGA and 2 neonates (1%) in the AGA group (RR 12.5, 95% CI [3.0, 52.5]). Platelet counts <20x109/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01) and erythroblastosis (p<0.01) were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis. PMID:27177157

  10. Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer.

    PubMed

    Lin, Po-Han; Kuo, Wen-Hung; Huang, Ai-Chu; Lu, Yen-Shen; Lin, Ching-Hung; Kuo, Sung-Hsin; Wang, Ming-Yang; Liu, Chun-Yu; Cheng, Fiona Tsui-Fen; Yeh, Ming-Hsin; Li, Huei-Ying; Yang, Yu-Hsuan; Hsu, Yu-Hua; Fan, Sheng-Chih; Li, Long-Yuan; Yu, Sung-Liang; Chang, King-Jen; Chen, Pei-Lung; Ni, Yen-Hsuan; Huang, Chiun-Sheng

    2016-02-16

    Since BRCA mutations are only responsible for 10-20% of cases of breast cancer in patients with early-onset or a family history and since next-generation sequencing technology allows the simultaneous sequencing of a large number of target genes, testing for multiple cancer-predisposing genes is now being considered, but its significance in clinical practice remains unclear. We then developed a sequencing panel containing 68 genes that had cancer risk association for patients with early-onset or familial breast cancer. A total of 133 patients were enrolled and 30 (22.6%) were found to carry germline deleterious mutations, 9 in BRCA1, 11 in BRCA2, 2 in RAD50, 2 in TP53 and one each in ATM, BRIP1, FANCI, MSH2, MUTYH, and RAD51C. Triple-negative breast cancer (TNBC) was associated with the highest mutation rate (45.5%, p = 0.025). Seven of the 9 BRCA1 mutations and the single FANCI mutation were in the TNBC group; 9 of the 11 BRCA2, 1 of the 2 RAD50 as well as BRIP1, MSH2, MUTYH, and RAD51C mutations were in the hormone receptor (HR)(+)Her2(-) group, and the other RAD50, ATM, and TP53 mutations were in the HR(+)Her2(+) group. Mutation carriers were considered as high-risk to develop malignancy and advised to receive cancer screening. Screening protocols of non-BRCA genes were based on their biologic functions; for example, patients carrying RAD51C mutation received a screening protocol similar to that for BRCA, since BRCA and RAD51C are both involved in homologous recombination. In conclusion, we consider that multiple gene sequencing in cancer risk assessment is clinically valuable. PMID:26824983

  11. A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson's disease

    PubMed Central

    Kun-Rodrigues, Celia; Ganos, Christos; Guerreiro, Rita; Schneider, Susanne A.; Schulte, Claudia; Lesage, Suzanne; Darwent, Lee; Holmans, Peter; Singleton, Andrew; Bhatia, Kailash; Bras, Jose

    2015-01-01

    Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exome sequencing in full parent–child trios where the proband presents with typical PD to unequivocally identify de novo mutations. This approach allows us to test all genes in the genome in an unbiased manner. We have identified and confirmed 20 coding de novo mutations in 21 trios. We have used publicly available population genetic data to compare variant frequencies and our independent in-house dataset of exome sequencing in PD (with over 1200 cases) to identify additional variants in the same genes. Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by various sources of data to be involved in PD. We show that these genes are reported to be within a protein–protein interaction network with PD genes and that they contain additional rare, case-specific, mutations in our independent cohort of PD cases. Our results support the involvement of these three genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the identification of novel disease-causing genes. PMID:26362251

  12. Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia.

    PubMed

    Sowmya, S; Sri Manjari, K; Ramaiah, A; Sunitha, T; Nallari, P; Jyothy, A; Venkateshwari, A

    2014-11-01

    Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (-1082 G/A; -592 A/C and -819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 -819 C allele (P = 0·003) and -592 A (P = 0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to -1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: -1082A with -819C (P = 0·0016); -1082G with -819C (P = 0·0018); -819C with -592C (P = 0·001); -1082A with -592C (P = 0·032); and -1082G with -592C (P = 0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia. PMID:24962617

  13. Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia

    PubMed Central

    Sowmya, S; Sri Manjari, K; Ramaiah, A; Sunitha, T; Nallari, P; Jyothy, A; Venkateshwari, A

    2014-01-01

    Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (−1082 G/A; −592 A/C and −819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 −819 C allele (P = 0·003) and −592 A (P = 0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to −1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: −1082A with −819C (P = 0·0016); −1082G with −819C (P = 0·0018); −819C with −592C (P = 0·001); −1082A with −592C (P = 0·032); and −1082G with −592C (P = 0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia. PMID:24962617

  14. Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer

    PubMed Central

    Lin, Po-Han; Kuo, Wen-Hung; Huang, Ai-Chu; Lu, Yen-Shen; Lin, Ching-Hung; Kuo, Sung-Hsin; Wang, Ming-Yang; Liu, Chun-Yu; Cheng, Fiona Tsui-Fen; Yeh, Ming-Hsin; Li, Huei-Ying; Yang, Yu-Hsuan; Hsu, Yu-Hua; Fan, Sheng-Chih; Li, Long-Yuan; Yu, Sung-Liang; Chang, King-Jen; Chen, Pei-Lung; Ni, Yen-Hsuan; Huang, Chiun-Sheng

    2016-01-01

    Since BRCA mutations are only responsible for 10–20% of cases of breast cancer in patients with early-onset or a family history and since next-generation sequencing technology allows the simultaneous sequencing of a large number of target genes, testing for multiple cancer-predisposing genes is now being considered, but its significance in clinical practice remains unclear. We then developed a sequencing panel containing 68 genes that had cancer risk association for patients with early-onset or familial breast cancer. A total of 133 patients were enrolled and 30 (22.6%) were found to carry germline deleterious mutations, 9 in BRCA1, 11 in BRCA2, 2 in RAD50, 2 in TP53 and one each in ATM, BRIP1, FANCI, MSH2, MUTYH, and RAD51C. Triple-negative breast cancer (TNBC) was associated with the highest mutation rate (45.5%, p = 0.025). Seven of the 9 BRCA1 mutations and the single FANCI mutation were in the TNBC group; 9 of the 11 BRCA2, 1 of the 2 RAD50 as well as BRIP1, MSH2, MUTYH, and RAD51C mutations were in the hormone receptor (HR)(+)Her2(−) group, and the other RAD50, ATM, and TP53 mutations were in the HR(+)Her2(+) group. Mutation carriers were considered as high-risk to develop malignancy and advised to receive cancer screening. Screening protocols of non-BRCA genes were based on their biologic functions; for example, patients carrying RAD51C mutation received a screening protocol similar to that for BRCA, since BRCA and RAD51C are both involved in homologous recombination. In conclusion, we consider that multiple gene sequencing in cancer risk assessment is clinically valuable. PMID:26824983

  15. Epidemiology of early-onset dementia: a review of the literature

    PubMed Central

    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. A Novel Trafficking-defective HCN4 Mutation is Associated with Early-Onset Atrial Fibrillation

    PubMed Central

    Zhang, Michael L.; Sinner, Moritz F.; Dolmatova, Elena V.; Tucker, Nathan R.; McLellan, Micheal; Shea, Marisa A.; Milan, David J.; Lunetta, Kathryn L.; Benjamin, Emelia J.; Ellinor, Patrick T.

    2014-01-01

    Background Atrial fibrillation (AF) is the most common arrhythmia, and a recent genome-wide association study identified HCN4 as a novel AF susceptibility locus. HCN4 encodes for the cardiac pacemaker channel and HCN4 mutations are associated with familial sinus bradycardia and AF. Objective To determine whether novel variants in the coding region of HCN4 contribute to the susceptibility for AF. Methods We sequenced the coding region of HCN4 for novel variants from 527 cases with early-onset AF from the Massachusetts General Hospital AF Study and 443 referents from the Framingham Heart Study. We used site-directed mutagenesis, cellular electrophysiology, immunocytochemistry and confocal microscopy to functionally characterize novel variants. Results We found the frequency of novel coding HCN4 variants was 2-fold greater for individuals with AF (seven variants) compared to the referents (three variants). We determined that one, (p.Pro257Ser, located in the amino-terminus adjacent to the first transmembrane spanning domain) of the seven novel HCN4 variants in our AF cases did not traffick to cell membrane while the remaining six were not functionally different from wild type. Also, the three novel variants in our referents did not alter function compared to wild type. Co-expression studies showed that the p.Pro257Ser mutant channel failed to co-localize with the wild type HCN4 channel on the cell membrane. Conclusion Our findings are consistent with HCN4 haploinsufficiency as the likely mechanism for early-onset AF in the p.Pro257Ser carrier. PMID:24607718

  17. MSH6 and MUTYH Deficiency Is a Frequent Event in Early-Onset Colorectal Cancer

    PubMed Central

    Giráldez, María Dolores; Balaguer, Francesc; Bujanda, Luis; Cuatrecasas, Miriam; Muñoz, Jenifer; Alonso-Espinaco, Virginia; Larzabal, Mikel; Petit, Anna; Gonzalo, Victoria; Ocaña, Teresa; Moreira, Leticia; Enríquez-Navascués, José María; Boland, C. Richard; Goel, Ajay; Castells, Antoni; Castellví-Bel, Sergi

    2011-01-01

    Purpose Early-onset colorectal cancer (CRC) is suggestive of a hereditary predisposition. Lynch syndrome is the most frequent CRC hereditary cause. The MUTYH gene has also been related to hereditary CRC. A systematic characterization of these two diseases has not been reported previously in this population. Experimental Design We studied a retrospectively collected series of 140 patients ≤50 years old diagnosed with nonpolyposis CRC. Demographic, clinical, and familial features were obtained. Mismatch repair (MMR) deficiency was determined by microsatellite instability (MSI) analysis, and immunostaining for MLH1, MSH2, MSH6, and PMS2 proteins. Germline MMR mutations were evaluated in all MMR-deficient cases. Tumor samples with loss of MLH1 or MSH2 protein expression were analyzed for somatic methylation. Germline MUTYH mutations were evaluated in all cases. BRAF V600E and KRAS somatic mutational status was also determined. Results Fifteen tumors (11.4%) were MSI, and 20 (14.3%) showed loss of protein expression (7 for MLH1/PMS2, 2 for isolated MLH1, 3 for MSH2/MSH6, 7 for isolated MSH6, and 1 for MSH6/PMS2). We identified 11 (7.8%) germline MMR mutations, 4 in MLH1, 1 in MSH2, and 6 in MSH6. Methylation analysis revealed one case with somatic MLH1 methylation. Biallelic MUTYH mutations were detected in four (2.8%) cases. KRAS and BRAF V600E mutations were present in 39 (27.9%) and 5 (3.6%) cases, respectively. Conclusions Loss of MSH6 expression is the predominant cause of MMR deficiency in early-onset CRC. Our findings prompt the inclusion of MSH6 and MUTYH screening as part of the genetic counseling of these patients and their relatives. PMID:20924129

  18. Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia

    SciTech Connect

    Taylor, G.J.; Crampton, R.S.; Gibson, R.S.; Stebbins, P.T.; Waldman, M.T.; Beller, G.A.

    1981-07-01

    The prospectively assessed time course of changes in ventricular repolarization during acute myocardial infarction (AMI) is reported in 32 patients admitted 2.0 +/- 1.8 (SD) hours after AMI onset. The initial corrected QT interval (QTc) upon hospitalization was longer in the 14 patients developing ventricular tachycardia (VT) within the first 48 hours as compared to QTc in the eight patients with frequent ventricular premature beats (VPBs) and to QTc in the 10 patients with infrequent VPBs. By the fifth day after AMI onset, the QTc shortened significantly only in the VT group, suggesting a greater initial abnormality of repolarization in these patients. All 32 patients had coronary angiography, radionuclide ventriculography, and myocardial perfusion scintigraphy before hospital discharge. Significant discriminating factors related to early phase VT in AMI included initially longer QT and QTc intervals, faster heart rate, higher peak serum levels of creatine kinase, acute anterior infarction, angiographically documented proximal stenosis of the left anterior descending coronary artery, and scintigraphic evidence of hypoperfusion of the interventricular septum. Prior infarction, angina pectoris, hypertension, multivessel coronary artery disease, and depressed left ventricular ejection fraction did not provide discrimination among the three different ventricular arrhythmia AMI groups. Researchers conclude that (1) the QT interval is frequently prolonged early in AMI, (2) the initial transiently prolonged ventricular repolarization facilitates and predicts complex ventricular tachyarrhythmias within the first 48 hours of AMI, (3) jeopardized blood supply to the interventricular septum frequently coexists, and (4) therapeutic enhancement of rapid recovery of the ventricular repolarization process merits investigation for prevention of VT in AMI.

  19. Managing the Risk for Early Onset Osteoporosis in Long-Duration Astronauts Due to Spaceflight

    NASA Technical Reports Server (NTRS)

    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

  20. A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson's disease.

    PubMed

    Kun-Rodrigues, Celia; Ganos, Christos; Guerreiro, Rita; Schneider, Susanne A; Schulte, Claudia; Lesage, Suzanne; Darwent, Lee; Holmans, Peter; Singleton, Andrew; Bhatia, Kailash; Bras, Jose

    2015-12-01

    Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exome sequencing in full parent-child trios where the proband presents with typical PD to unequivocally identify de novo mutations. This approach allows us to test all genes in the genome in an unbiased manner. We have identified and confirmed 20 coding de novo mutations in 21 trios. We have used publicly available population genetic data to compare variant frequencies and our independent in-house dataset of exome sequencing in PD (with over 1200 cases) to identify additional variants in the same genes. Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by various sources of data to be involved in PD. We show that these genes are reported to be within a protein-protein interaction network with PD genes and that they contain additional rare, case-specific, mutations in our independent cohort of PD cases. Our results support the involvement of these three genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the identification of novel disease-causing genes. PMID:26362251

  1. Relationship of Early Onset Baldness to Prostate Cancer in African-American Men

    PubMed Central

    Zeigler-Johnson, Charnita; Morales, Knashawn H.; Spangler, Elaine; Chang, Bao-Li; Rebbeck, Timothy R.

    2013-01-01

    Background Early onset baldness has been linked to prostate cancer (CaP), however, little is known about this relationship in African Americans (AA) who are at elevated CaP risk. Methods We recruited 219 AA controls and 318 AA CaP cases. We determined age-stratified associations of baldness with CaP occurrence and severity defined by high stage (T3/T4) or high grade (Gleason 7+.) Associations of androgen metabolism genotypes (CYP3A4, CYP3A5, CYP3A43, AR-CAG, SRD5A2 A49T, and SRD5A2 V89L), family history, alcohol intake, and smoking were examined by baldness status and age group by using multivariable logistic regression models. Results Baldness was associated with odds of CaP (OR=1.69, 95% CI=1.05–2.74). Frontal baldness was associated with high stage (OR=2.61, 95% CI=1.10–6.18) and high grade (OR=2.20, 95% CI=1.05–4.61) tumors. For men diagnosed less than age 60, frontal baldness was associated with high stage (OR=6.51, 95% CI=2.11–20.06) and high grade (OR=4.23, 95% CI=1.47–12.14). We also observed a suggestion of an interaction among smoking, median age and any baldness (p=0.02). Conclusions We observed significant associations between early onset baldness and CaP in AA men. Interactions with age and smoking were suggested in these associations. Studies are needed to investigate the mechanisms influencing the relationship between baldness and CaP in AA. Impact AA men present with unique risk factors including baldness patterns that may contribute to CaP disparities. PMID:23532004

  2. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study

    PubMed Central

    Vlug, R. D.; Smits-Wintjens, V. E. H. J.; Heckman, E. J.; te Pas, A. B.; Fijnvandraat, K.; Lopriore, E.

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA) neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x109/L) was found in 53% (176/329) of SGA neonates and 20% (66/330) of AGA neonates (relative risk (RR) 2.7, 95% confidence interval (CI) [2.1, 3.4]). Severe thrombocytopenia (21-50x109/L) occurred in 25 neonates (8%) in the SGA and 2 neonates (1%) in the AGA group (RR 12.5, 95% CI [3.0, 52.5]). Platelet counts <20x109/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01) and erythroblastosis (p<0.01) were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis. PMID:27177157

  3. Latent class profile analysis: an application to stage-sequential process in early-onset drinking behaviours

    PubMed Central

    Chung, Hwan; Anthony, James C.; Schafer, Joseph L.

    2016-01-01

    Summary Earlier age of drinking is a well-known predictor for a variety of adverse public health consequences in the United States and worldwide. In longitudinal research on early-onset drinkers, a great deal of attention has been paid to the identification of subgroups of individuals who follow similar sequential patterns of drinking behaviours. However, research on the sequential development of drinking behaviour can be challenging in part because it may not be possible to directly observe the particular drinking behaviour stage at a given point in time. To address this difficulty, one can use a latent class analysis (LCA) approach, which provides a set of principles for the systematic identification of homogeneous subgroups of individuals. We apply an LCA approach in an investigation of stage-sequential patterns of drinking behaviours among early-onset drinkers from early to late adolescence, using data from the ‘National Longitudinal Survey of Youth 1997.’ In this work, an identification procedure is used to sort different patterns of drinking behaviours into a small number of classes, based on responses to questions about drinking at each measurement occasion; with class assignment, next the class sequencing of early-onset drinkers over the entire set of time points is evaluated in order to identify two or more homogeneous subgroups. A condition to be satisfied is that all early-onset drinkers in a subgroup should exhibit a similar sequence of class memberships over time. This approach uncovers four common drinking behaviours in early-onset drinkers over three measurements from 1997 through 2003. The sequences of drinking behaviours can be grouped into three groups of sequential patterns representing the most probable progression of early-onset drinking behaviours. PMID:27313406

  4. Early differences in metabolic flexibility between obesity-resistant and obesity-prone mice.

    PubMed

    Bardova, Kristina; Horakova, Olga; Janovska, Petra; Hansikova, Jana; Kus, Vladimir; van Schothorst, Evert M; Hoevenaars, Femke P M; Uil, Melissa; Hensler, Michal; Keijer, Jaap; Kopecky, Jan

    2016-05-01

    Decreased metabolic flexibility, i.e. a compromised ability to adjust fuel oxidation to fuel availability supports development of adverse consequences of obesity. The aims of this study were (i) to learn whether obesity-resistant A/J and obesity-prone C57BL/6J mice differ in their metabolic flexibility right after weaning; and (ii) to characterize possible differences in control of glucose homeostasis in these animals using glucose tolerance tests (GTT). A/J and C57BL/6J mice of both genders were maintained at 20 °C and weaned to standard low-fat diet at 30 days of age. During the first day after weaning, using several separate animal cohorts, (i) GTT was performed using 1 or 3 mg glucose/g body weight (BW), while glucose was administered either orally (OGTT) or intraperitoneally (IPGTT) at 20 °C; and (ii) indirect calorimetry (INCA) was performed, either in a combination with oral gavage of 1 or 7.5 mg glucose/g BW, or during a fasting/re-feeding transition. INCA was conducted either at 20 °C or 34 °C. Results of both OGTT and IPGTT using 1 mg glucose/g BW at 20 °C, and INCA using 7.5 mg glucose/g BW at 34 °C, indicated higher glucose tolerance and higher metabolic flexibility to glucose, respectively, and lower fasting glycemia in A/J mice as compared with C57BL/6J mice. Thus, control of whole body glucose metabolism between A/J and C57BL/6J mice represents a phenotypic feature differentiating between the strains right after weaning. PMID:26607243

  5. Gut Endotoxin Leading to a Decline IN Gonadal function (GELDING) - a novel theory for the development of late onset hypogonadism in obese men.

    PubMed

    Tremellen, Kelton

    2016-01-01

    Obesity is an increasing public health problem, with two-thirds of the adult population in many Western countries now being either overweight or obese. Male obesity is associated with late onset hypogonadism, a condition characterised by decreased serum testosterone, sperm quality plus diminished fertility and quality of life. In this paper we propose a novel theory underlying the development of obesity related hypogonadism- the GELDING theory (Gut Endotoxin Leading to a Decline IN Gonadal function). Several observational studies have previously reported an association between obesity related hypogonadism (low testosterone) and systemic inflammation. However, for the first time we postulate that the trans-mucosal passage of bacterial lipopolysaccharide (LPS) from the gut lumen into the circulation is a key inflammatory trigger underlying male hypogonadism. Obesity and a high fat/high calorie diet are both reported to result in changes to gut bacteria and intestinal wall permeability, leading to the passage of bacterial endotoxin (lipopolysaccharide- LPS) from within the gut lumen into the circulation (metabolic endotoxaemia), where it initiates systemic inflammation. Endotoxin is known to reduce testosterone production by the testis, both by direct inhibition of Leydig cell steroidogenic pathways and indirectly by reducing pituitary LH drive, thereby also leading to a decline in sperm production. In this paper we also highlight the novel evolutionary benefits of the GELDING theory. Testosterone is known to be a powerful immune-suppressive, decreasing a man's ability to fight infection. Therefore we postulate that the male reproductive axis has evolved the capacity to lower testosterone production during times of infection and resulting endotoxin exposure, decreasing the immunosuppressive influence of testosterone, in turn enhancing the ability to fight infection. While this response is adaptive in times of sepsis, it becomes maladaptive in the setting of "non

  6. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

    PubMed

    Nagy, Eniko; Rodriguiz, Ramona M; Wetsel, William C; MacIver, Nancie J; Hale, Laura P

    2016-01-01

    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 for development

  7. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease

    PubMed Central

    Nagy, Eniko; Rodriguiz, Ramona M.; Wetsel, William C.; MacIver, Nancie J.; Hale, Laura P.

    2016-01-01

    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 for

  8. Obesity and Skill Attainment in Early Childhood. NBER Working Paper No. 13997

    ERIC Educational Resources Information Center

    Cawley, John; Spiess, C. Katharina

    2008-01-01

    This paper investigates the association between obesity and skill attainment in early childhood (aged 2-4 years). Data from the German Socio-Economic Panel Study are used to estimate models of developmental functioning in four critical areas (verbal skills, activities of daily living, motor skills, and social skills) as a function of various…

  9. Evaluation of Bias in Estimates of Early Childhood Obesity From Parent-Reported Heights and Weights

    PubMed Central

    Weden, Margaret M.; Lau, Christopher; Brownell, Peter; Nazarov, Zafar; Fernandes, Meenakshi

    2014-01-01

    Objectives. We evaluated bias in estimated obesity prevalence owing to error in parental reporting. We also evaluated bias mitigation through application of Centers for Disease Control and Prevention’s biologically implausible value (BIV) cutoffs. Methods. We simulated obesity prevalence of children aged 2 to 5 years in 2 panel surveys after counterfactually substituting parameters estimated from 1999–2008 National Health and Nutrition Examination Survey data for prevalence of extreme height and weight and for proportions obese in extreme height or weight categories. Results. Heights reported below the first and fifth height-for-age percentiles explained between one half and two thirds, respectively, of total bias in obesity prevalence. Bias was reduced by one tenth when excluding cases with height-for-age and weight-for-age BIVs and by one fifth when excluding cases with body mass–index-for-age BIVs. Applying BIVs, however, resulted in incorrect exclusion of nonnegligible proportions of obese children. Conclusions. Correcting the reporting of children’s heights in the first percentile alone may reduce overestimation of early childhood obesity prevalence in surveys with parental reporting by one half to two thirds. Excluding BIVs has limited effectiveness in mitigating this bias. PMID:24832432

  10. Associations of cord blood metabolites with early childhood obesity risk

    PubMed Central

    Isganaitis, Elvira; Rifas-Shiman, Sheryl L.; Oken, Emily; Dreyfuss, Jonathan; Gall, Walt; Gillman, Matthew W.; Patti, Mary-Elizabeth

    2015-01-01

    Background/Objective Rapid postnatal weight gain is a potentially modifiable risk factor for obesity and metabolic syndrome. To identify markers of rapid infancy weight gain and childhood obesity, we analyzed the metabolome in cord blood from infants differing in their postnatal weight trajectories. Methods We performed a nested case-control study within Project Viva, a longitudinal cohort of mothers and children. We selected cases (n=26) based on top quartile of change in weight-for-age 0-6 mo and BMI >85th percentile in mid-childhood (median 7.7 years). Controls (n=26) were age- and sex-matched, had normal postnatal weight gain (2nd or 3rd quartile of change in weight-for-age 0-6 mo) and normal mid-childhood weight (BMI 25th-75th percentile). Cord blood metabolites were measured using untargeted LC/MS; individual metabolites and pathways differing between cases vs. controls were compared in categorical analyses. We adjusted metabolites for maternal age, maternal BMI, and breastfeeding duration (linear regression), and assessed whether metabolites improved the ability to predict case-control status (logistic regression). Results Of 415 detected metabolites, 16 were altered in cases vs. controls (T-test, nominal P<0.05). 3 metabolites were related to tryptophan: serotonin, tryptophan betaine, and tryptophyl leucine (46%, 48% and 26% lower in cases, respectively, P<0.05). Mean levels of 2 methyl donors, dimethylglycine and N-acetylmethionine, were also lower in cases (18% and 16% respectively, P=0.01). Moreover, the glutamine:glutamate ratio was reduced by 33% (P<0.05) in cases. Levels of serotonin, tryptophyl leucine, and N-acetylmethionine remained significantly different after adjustment for maternal BMI, age, and breastfeeding. Adding metabolite levels to logistic regression models including only clinical covariates improved the ability to predict case vs. control status. Conclusions Several cord blood metabolites are associated with rapid postnatal weight gain

  11. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

    PubMed

    van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

    2015-12-01

    A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. PMID:26535877

  12. Early, But Not Late Onset Estrogen Replacement Therapy Prevents Oxidative Stress and Metabolic Alterations Caused by Ovariectomy

    PubMed Central

    López-Grueso, Raúl; Gambini, Juan; Abdelaziz, Kheira M.; Monleón, Daniel; Díaz, Ana; El Alami, Marya; Bonet-Costa, Vicent; Borrás, Consuelo

    2014-01-01

    Abstract Aims: The usefulness of estrogen replacement therapy (ERT) in preventing oxidative stress associated with menopause is controversial. We aimed to study if there is a critical time window for effective treatment of the effects of ovariectomy with estrogens at the molecular, metabolic, and cellular level. Results: Our main finding is that early, but not late onset of ERT prevents an ovariectomy-associated increase in mitochondrial hydrogen peroxide levels, oxidative damage to lipids and proteins, and a decrease in glutathione peroxidase and catalase activity in rats. This may be due to a change in the estrogen receptor (ER) expression profile: ovariectomy increases the ER α/β ratio and immediate estrogen replacement prevents it. Positron emission tomography analysis shows that ovariectomy decreases the brain glucose uptake in vivo and that estrogen administration is beneficial, but only if administered immediately after deprivation. Ovariectomy decreases GLUT-1 and 3 glucose transporters in the brain, and only early onset estrogen administration prevents it. Plasma from rats treated with estrogens immediately after ovariectomy show similar metabolomics profiles as controls. Innovation: We provide molecular basis for the recommendation of early onset ERT and explain its lack of effectiveness if a significant time period elapses after ovariectomy and probably after the onset of menopause. Conclusion: Only early, but not late onset administration of estrogens after ovariectomy has beneficial effects at molecular levels on oxidative stress, brain glucose uptake, and metabolomic profiles. Antioxid. Redox Signal. 20, 236–246. PMID:23725100

  13. Early onset of industrial-era warming across the oceans and continents.

    PubMed

    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. PMID:27558063

  14. The Onset of Early Season Rainfall and its Mid-Summer Cessation in the Caribbean.

    NASA Astrophysics Data System (ADS)

    Allen, T. L.; Mapes, B. E.

    2014-12-01

    The annual rainfall cycle for the Caribbean basin reveals a distinct bimodal pattern with peaks during the late spring and late summer months. A relative minimum during the mid-summer, known as the mid-summer drought (MSD) separates the early rainfall season (ERS) from the late rainfall season. Accumulated rainfall totals during the ERS appear as a quasi-stationary rain-belt stretching across the Caribbean from the southwest to the northeast. We place late spring rains in the Caribbean in context of other subtropical convergence zones in order to address the onset and cessation of the ERS while also offering an explanation of a Caribbean rain-belt pattern. Upper tropospheric westerlies, mid-tropospheric positive temperature advection, and moist low level poleward flow are the three primary ingredients that conspire to produce the first peak of the annual bimodal rain signal and the related Caribbean early season rain-belt. The MSD ensues as the primary ingredients weaken across the Caribbean and enhanced rainfall shifts north along the North Atlantic Convergence Zone (NACZ). Seasonal rainfall totals from the ERS through the MSD periods reveal a continuous rain-belt that extends from the Caribbean to the NACZ termed the Caribbean Atlantic Rain-belt (CAR-belt). The Car-belt is present in the long term mean, but has signs of interannual variability.

  15. A study on early-onset neonatal group B streptococcal infection, Bulgaria, 2007-2011.

    PubMed

    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

  16. Is the relationship between early-onset cannabis use and educational attainment causal or due to common liability?

    PubMed Central

    Verweij, Karin J.H.; Huizink, Anja C.; Agrawal, Arpana; Martin, Nicholas G.; Lynskey, Michael T.

    2013-01-01

    Background Several studies have shown that early cannabis use is correlated with poor educational performance including high school drop-out. The predominant explanation for this relationship is that cannabis use causes disengagement from education. Another explanation is that the association between early cannabis use and educational attainment is not causal, but the result of overlapping risk factors that increase the likelihood of both early cannabis use and disengagement from education. These confounding factors could be of genetic and/or environmental origin. Methods Here we use data from a large community-based sample of adult twins (N=3337) who completed a comprehensive semi-structured telephone interview. We first apply the classical twin-design to determine whether genetic and/or environmental influences underlie the relationship between early-onset cannabis use (prior to age 18) and early school leaving. Next, with a co-twin control design we investigate whether the relationship between the two variables is more likely due to direct causality or overlapping risk factors. Results We find a significant phenotypic correlation between early-onset cannabis use and early school leaving (r=0.26), which could be explained by familial influences (of genetic and/or shared environmental origin). The pattern of odds ratios found in the co-twin control design is not consistent with direct causation, but rather suggests that the association is due to shared environmental factors influencing both variables. Conclusion Our findings suggest that the relationship between early-onset cannabis use and school leaving is due to shared environmental risk factors influencing both the risk of early-onset cannabis use and early school leaving. PMID:23972999

  17. Parent-Child Interaction, Self-Regulation, and Obesity Prevention in Early Childhood.

    PubMed

    Anderson, Sarah E; Keim, Sarah A

    2016-06-01

    This paper describes the epidemiologic evidence linking parent-child relationships, self-regulation, and weight status with a focus on early childhood. The emotional quality of parent-child interactions may influence children's risk for obesity through multiple pathways. Prospective studies linking observer ratings of young children's self-regulation, particularly inhibitory control, to future weight status are discussed. Although findings are preliminary, promoting positive relationships between parents/caregivers and young children holds promise as a component of efforts to prevent childhood obesity. Multi-disciplinary collaborations between researchers with training in developmental science and child health should be encouraged. PMID:27037572

  18. Reading Aloud in Persian: ERP Evidence for an Early Locus of the Masked Onset Priming Effect

    ERIC Educational Resources Information Center

    Timmer, Kalinka; Vahid-Gharavi, Narges; Schiller, Niels O.

    2012-01-01

    The current study investigates reading aloud words in Persian, a language that does not mark all its vowels in the script. Behaviorally, a "masked onset priming effect" (MOPE) was revealed for transparent words, with faster speech onset latencies in the phoneme-matching condition (i.e. phonological prime and target onset overlap; e.g. [image…

  19. Local-to-remote cortical connectivity in early- and adulthood-onset schizophrenia.

    PubMed

    Jiang, L; Xu, Y; Zhu, X-T; Yang, Z; Li, H-J; Zuo, X-N

    2015-01-01

    Schizophrenia is increasingly thought of as a brain network or connectome disorder and is associated with neurodevelopmental processes. Previous studies have suggested the important role of anatomical distance in developing a connectome with optimized performance regarding both the cost and efficiency of information processing. Distance-related disturbances during development have not been investigated in schizophrenia. To test the distance-related miswiring profiles of connectomes in schizophrenia, we acquired resting-state images from 20 adulthood-onset (AOS) and 26 early-onset schizophrenia (EOS) patients, as well as age-matched healthy controls. All patients were drug naive and had experienced their first psychotic episode. A novel threshold-free surface-based analytic framework was developed to examine local-to-remote functional connectivity profiles in both AOS and EOS patients. We observed consistent increases of local connectivity across both EOS and AOS patients in the right superior frontal gyrus, where the connectivity strength was correlated with a positive syndrome score in AOS patients. In contrast, EOS but not AOS patients exhibited reduced local connectivity within the right postcentral gyrus and the left middle occipital cortex. These regions' remote connectivity with their interhemispheric areas and brain network hubs was altered. Diagnosis-age interactions were detectable for both local and remote connectivity profiles. The functional covariance between local and remote homotopic connectivity was present in typically developing controls, but was absent in EOS patients. These findings suggest that a distance-dependent miswiring pattern may be one of the key neurodevelopmental features of the abnormal connectome organization in schizophrenia. PMID:25966366

  20. Prevalence of Traumatic Brain Injury in Early Versus Late-Onset Alzheimer’s Disease

    PubMed Central

    Mendez, Mario F.; Paholpak, Pongsatorn; Lin, Andrew; Zhang, Jeannie Y.; Teng, Edmond

    2016-01-01

    Background Traumatic brain injury (TBI) is the most established environmental risk factor for Alzheimer’s disease (AD), but it is unclear if TBI is specifically associated with early-onset AD (EOAD). Objective To evaluate the relationship between TBI and EOAD (<65 years). Methods We identified 1,449 EOAD, 4,337 late-onset AD (LOAD), and corresponding EOAD-matched and LOAD-matched normal controls (NC) in the National Alzheimer’s Coordinating Center Uniform (NACC) database and compared the prevalence of any history of TBI as well as measures of cognition, function, behavior, and neuropathology. For validation, we determined TBI prevalence among 115 well-characterized clinic patients with EOAD. Results Part A: The prevalence of any TBI in the NACC-database EOAD participants (13.3%) was comparable to that observed in the clinic EOAD patients (13.9%) but significantly higher than in the NACC-database LOAD participants (7.7%; p < 0.0001) and trended to higher compared to EOAD-matched NC (11.1%; logistic regression p = 0.053). Part B: When we compared EOAD patients with documented non-acute and non-residually impairing TBI to EOAD without a documented history of prior TBI, those with TBI had significantly more disinhibition. Part C: Autopsies did not reveal differences in AD neuropathology based on a history of TBI. Conclusions These findings suggest, but do not establish, that TBI is a specific risk factor for EOAD and may lead to disinhibition, a feature that often results from the frontal effects of head injury. This study recommends further research on the effects of TBI in EOAD in larger numbers of participants. PMID:26401777

  1. Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy

    PubMed Central

    Lamont, P J; Udd, B; Mastaglia, F L; de Visser, M; Hedera, P; Voit, T; Bridges, L R; Fabian, V; Rozemuller, A; Laing, N G

    2006-01-01

    Background Laing early onset distal myopathy (MPD1) is an autosomal dominant myopathy caused by mutations within the slow skeletal muscle fibre myosin heavy chain gene, MYH7. It is allelic with myosin storage myopathy, with the commonest form of familial hypertrophic cardiomyopathy, and with one form of dilated cardiomyopathy. However, the clinical picture of MPD1 is distinct from these three conditions. Objective To collate and discuss the histological features reported in the muscle biopsies of MPD1 patients and to outline the clinical features. Results The phenotype of MPD1 was consistent, with initial weakness of great toe/ankle dorsiflexion, and later development of weakness of finger extension and neck flexion. Age of onset was the only variable, being from birth up to the 20s, but progression was always very slow. The pathological features were variable. In this retrospective series, there were no pathognomonic diagnostic features, although atrophic type I fibres were found in half the families. Rimmed vacuoles are consistently seen in all other distal myopathies with the exception of Myoshi distal myopathy. However, they were found in a minority of patients with MPD1, and were not prominent when present. Immunohistochemical staining for slow and fast myosin showed co‐expression of slow and fast myosin in some type I fibres, possibly indicating a switch to type II status. This may be a useful aid to diagnosis. Conclusions The pathological findings in MPD1 are variable and appear to be affected by factors such as the specific muscle biopsied, the age of the patient at biopsy, and the duration of disease manifestations. PMID:16103042

  2. Higher Activity of the Inducible Nitric Oxide Synthase Contributes to Very Early Onset Inflammatory Bowel Disease

    PubMed Central

    Dhillon, Sandeep S; Mastropaolo, Lucas A; Murchie, Ryan; Griffiths, Christopher; Thöni, Cornelia; Elkadri, Abdul; Xu, Wei; Mack, Amanda; Walters, Thomas; Guo, Conghui; Mack, David; Huynh, Hien; Baksh, Shairaz; Silverberg, Mark S; Brumell, John H; Snapper, Scott B; Muise, Aleixo M

    2014-01-01

    OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10−6, OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02–5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production. PMID:24430113

  3. Obesity

    MedlinePlus

    ... may have less time to exercise. The term eating disorder means a group of medical conditions that have ... obese, follow an unhealthy diet, and have an eating disorder all at the same time. Sometimes, medical problems ...

  4. The critical period of infant feeding for the development of early disparities in obesity.

    PubMed

    Thompson, Amanda L; Bentley, Margaret E

    2013-11-01

    Childhood obesity is an increasing public health problem, particularly among minority infants and young children. Disparities in overweight prevalence persist and widen with age, highlighting the need to identify factors contributing to early excess weight gain. We review the behavioral, social and macro-environmental factors contributing to the development of obesogenic early feeding practices among African-American infants and young children. We then examine the sociodemographic, household factors, feeding beliefs and infant characteristics associated with age-inappropriate feeding of liquids and solids (inappropriate feeding) among mothers and infants participating the U.S. Infant Care and Risk of Obesity Study, a cohort study of 217 low-income, first-time mothers and infants followed from 3 to 18 months of age. Maternal and infant anthropometry, infant diet, and maternal and household characteristics were collected at home visits at 3, 6, 9, 12 and 18 months of age. Mixed logistic regression was used to estimate the association between maternal and infant characteristics and inappropriate feeding. Rates of age-inappropriate feeding are high; over 75% of infants received solids or juice by 3 months of age. The odds of age-inappropriate feeding were higher among mothers who were single, depressed or believed that their infant is a "greedy" baby. Inappropriate feeding was associated with higher daily energy intake in infants (β = 109.28 calories, p = 0.01) and with increased odds of high infant weight-for-length (WFL; OR = 1.74, 95%CI: 1.01-3.01). Our findings suggest that age-inappropriate complementary feeding influences current energy intakes and infant WFL, factors that may increase long-term obesity risk by shaping infant appetite, food preferences, and metabolism. Given the intractability of pediatric obesity, understanding the role of early feeding in shaping long-term health disparities is critical for developing prevention strategies to stem obesity in

  5. Disease Expression and HLA Types in Early and Late Onset Disease of Malaysian Patients with Systemic Lupus Erythematosus.

    PubMed

    Radzi, A M; Huan, K S; Yahaya, N; Shahera, A; Kong, N; Mohd Noah, R

    2001-07-01

    Age has been suggested to modify systemic lupus erythematosus expression. In this study we have attempted to study 13 patients with late onset (40 years and above) and 90 with early onset disease (below 40 years) to determine whether age-related differences in disease expression exist and whether the genetic make-up influences the age of disease onset. We found that patients with late onset disease initially presented with pericarditis (31% vs 3%, P<0.005) and a lower incidence of malar rash (31% vs 57%, p<0.05). During the disease course, there was a lower incidence of mucocutaneous symptoms especially malar rash (p<0.005) and psychosis (p<0.05) in the late onset group. Serological parameters were similar in both groups. There was a prevalence of HLA-DQA1*0103 in Chinese patients with late onset disease (pcorr=0.004). These findings suggest that a subgroup of late onset patients may experience milder disease and that the risk conferred by the HLA-DQA1*0103 may be significant among these patients. PMID:22893758

  6. Disease Expression and HLA Types in Early and Late Onset Disease of Malaysian Patients with Systemic Lupus Erythematosus

    PubMed Central

    Radzi, Azizah Mohd; Huan, Kuak Soo; Yahaya, Normaznah; Shahera, Ainol; Kong, Norella; Mohd Noah, Rahim

    2001-01-01

    Age has been suggested to modify systemic lupus erythematosus expression. In this study we have attempted to study 13 patients with late onset (40 years and above) and 90 with early onset disease (below 40 years) to determine whether age-related differences in disease expression exist and whether the genetic make-up influences the age of disease onset. We found that patients with late onset disease initially presented with pericarditis (31% vs 3%, P<0.005) and a lower incidence of malar rash (31% vs 57%, p<0.05). During the disease course, there was a lower incidence of mucocutaneous symptoms especially malar rash (p<0.005) and psychosis (p<0.05) in the late onset group. Serological parameters were similar in both groups. There was a prevalence of HLA-DQA1*0103 in Chinese patients with late onset disease (pcorr=0.004). These findings suggest that a subgroup of late onset patients may experience milder disease and that the risk conferred by the HLA-DQA1*0103 may be significant among these patients. PMID:22893758

  7. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

    PubMed

    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

  8. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population

    PubMed Central

    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.

    2015-01-01

    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

  9. Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation.

    PubMed

    Bras, Jose; Djaldetti, Ruth; Alves, Ana Margarida; Mead, Simon; Darwent, Lee; Lleo, Alberto; Molinuevo, Jose Luis; Blesa, Rafael; Singleton, Andrew; Hardy, John; Clarimon, Jordi; Guerreiro, Rita

    2016-10-01

    We have previously reported the whole genome genotyping analysis of 2 consanguineous siblings clinically diagnosed with early onset Alzheimer's disease (AD). In this analysis, we identified several large regions of homozygosity shared between both affected siblings, which we suggested could be candidate loci for a recessive genetic lesion underlying the early onset AD in these cases. We have now performed exome sequencing in one of these siblings and identified the potential cause of disease: the CTSF c.1243G>A:p.Gly415Arg mutation in homozygosity. Biallelic mutations in this gene have been shown to cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis with some cases resembling the impairment seen in AD. PMID:27524508

  10. Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles

    PubMed Central

    Inaba, Koji; Nakamura, Satoshi; Okamoto, Hiroyuki; Kashihara, Tairo; Kobayashi, Kazuma; Harada, Ken; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Murakami, Naoya; Ito, Yoshinori; Igaki, Hiroshi; Uno, Takashi; Itami, Jun

    2016-01-01

    Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy). PMID:26684338

  11. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

    PubMed

    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. PMID:25790282

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

    PubMed Central

    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. PMID:25790282

  13. Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

    PubMed

    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. PMID:26979097

  14. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    ERIC Educational Resources Information Center

    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…

  15. A Follow-up Study of Early Onset Psychosis: Comparison between Outcome Diagnoses of Schizophrenia, Mood Disorders, and Personality Disorders.

    ERIC Educational Resources Information Center

    McClellan, Jon M.; And Others

    1993-01-01

    This study of 95 youths previously diagnosed with psychotic disorders found that at follow-up, 24 had a diagnosis of schizophrenia, 9 with psychotic mood disorders, 5 with personality disorders, and 1 with schizo-affective disorder. The study confirmed findings regarding early onset schizophrenia and psychotic mood disorders and emphasized the…

  16. The Northern Ireland Early Onset Psychosis Study: Phenomenology and Co-Morbidity in the First 25 Cases

    ERIC Educational Resources Information Center

    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…

  17. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    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…

  18. Prevention of neonatal early onset GBS sepsis: A clear protocol is better than none--or several.

    PubMed

    Wise, Michelle; Campbell, Norma; Darlow, Brian

    2015-11-20

    Revised New Zealand consensus guidelines on the prevention of early-onset group B streptococcus sepsis in the newborn are presented in this issue of the Journal. We provide some context for these recommendations and discuss issues considered by the multidisciplinary group in formulating the guidelines. PMID:26905981

  19. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    ERIC Educational Resources Information Center

    Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

  20. Components of Negative Affect as Moderators of the Relationship between Early Drinking Onset and Binge-Drinking Behavior

    ERIC Educational Resources Information Center

    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…

  1. Verbal Behavior in Young Children with Autism Spectrum Disorders at the Onset of an Early Behavioral Intervention Program

    ERIC Educational Resources Information Center

    Rivard, Melina; Forget, Jacques

    2012-01-01

    The scope of this study was direct observation of verbal behaviors of 14 children with autism spectrum disorders at the onset of an early behavioral intervention (EBI) program delivered in a public services agency. Objectives were to (1) describe frequencies of vocal, verbal, and listener behaviors; (2) evaluate the relationship between the…

  2. Obesity.

    PubMed

    Callaway, C W

    1987-01-01

    Obesity is not a single disease, but a variety of conditions resulting from different mechanisms and associated with various types and degrees of risks. To determine who should lose weight, how much weight should be lost, and how to undertake weight loss, the following types of information are needed: personal-demographic data, developmental patterns, family history, energy balance, body composition/fat distribution, psychological/behavioral measures, endocrine/metabolic measures, complications and associated conditions. Weight reduction should be undertaken by women with morbid obesity, with complications secondary to the obesity, with a strong family history of conditions associated with obesity, or with increased abdomen:hip ratios. In contrast, women who have excess weight localized in the hips and thighs and no personal or family history of associated conditions may not benefit from dietary restriction. Low calorie diets result in adaptive changes, "designed" to prolong survival in the face of famine. These include changes in water balance, metabolic rate, and appetite. Metabolic rate declines, allowing the individual to burn fewer and fewer calories. Each time a woman diets she tends to lose weight less rapidly than the time before. "Restrained eating" predisposes binge eating. Indeed, bulimia rarely occurs in the absence of prior caloric restrictions. Current medical definitions of obesity do not consider these nuances. Existing definitions "over-diagnose" obesity in women, in general, and in older women and nonwhite women, in particular. For example, by existing standards, more than 60 percent of black women more than 45 years of age are considered obese. In contrast, the health risks of similar degrees of obesity are substantially greater for men than for women. Part of the problems lies in the fact that many women have pear-shaped fat distribution,a pattern which is not associated with increased health risks.Current cultural definitions of obesity for

  3. Quantification of Maternal Serum Cell-Free Fetal DNA in Early-Onset Preeclampsia

    PubMed Central

    Yu, Hong; Shen, Yanting; Ge, Qinyu; He, Youji; Qiao, Dongyan; Ren, Mulan; Zhang, Jianqiong

    2013-01-01

    The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA) level of gravidas developed into early-onset preeclampsia (EOPE) subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged) cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68) was higher than controls (median, 1.79; interquartile range, 1.46–2.53). The increased level of (logged) cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG) level (r = 0.628, p < 0.001). Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = −0.516, p = 0.001; r = −0.623, p < 0.001, respectively). The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta. PMID:23567271

  4. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome and celiac disease in a 13-year-old girl: further evidence for autoimmunity?

    PubMed

    Cemeroglu, Ayse Pinar; Eng, Donna S; Most, Laura A; Stalsonburg, Carrissa M; Kleis, Lora

    2016-01-01

    Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare and potentially lethal disorder. The etiology is unclear but paraneoplastic syndrome and autoimmunity secondary to neural crest tumors have been considered, even in patients without any detectable tumor due to their tendency for spontaneous remission. We are presenting a 13-year-old girl with ROHHAD syndrome and celiac disease, which may suggest further evidence for immune-mediated etiology in the pathogenesis of ROHHAD syndrome. PMID:26352082

  5. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase

    PubMed Central

    Puppala, Anupama K.; French, Rachel L.; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS–Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*–induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  6. Regulatory T cell frequencies are increased in preterm infants with clinical early-onset sepsis.

    PubMed

    Pagel, J; Hartz, A; Figge, J; Gille, C; Eschweiler, S; Petersen, K; Schreiter, L; Hammer, J; Karsten, C M; Friedrich, D; Herting, E; Göpel, W; Rupp, J; Härtel, C

    2016-08-01

    The predisposition of preterm neonates to invasive infection is, as yet, incompletely understood. Regulatory T cells (Tregs ) are potential candidates for the ontogenetic control of immune activation and tissue damage in preterm infants. It was the aim of our study to characterize lymphocyte subsets and in particular CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) Tregs in peripheral blood of well-phenotyped preterm infants (n = 117; 23 + 0 - 36 + 6 weeks of gestational age) in the first 3 days of life in comparison to term infants and adults. We demonstrated a negative correlation of Treg frequencies and gestational age. Tregs were increased in blood samples of preterm infants compared to term infants and adults. Notably, we found an increased Treg frequency in preterm infants with clinical early-onset sepsis while cause of preterm delivery, e.g. chorioamnionitis, did not affect Treg frequencies. Our data suggest that Tregs apparently play an important role in maintaining maternal-fetal tolerance, which turns into an increased sepsis risk after preterm delivery. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics. PMID:27163159

  7. Integrating Genetic, Neuropsychological and Neuroimaging Data to Model Early-Onset Obsessive Compulsive Disorder Severity

    PubMed Central

    Mas, Sergi; Gassó, Patricia; Morer, Astrid; Calvo, Anna; Bargalló, Nuria; Lafuente, Amalia; Lázaro, Luisa

    2016-01-01

    We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the training set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our understanding of the neurobiological basis of the disorder. PMID:27093171

  8. Relationship between Maternal Serum C-Reactive Protein, Funisitis and Early-Onset Neonatal Sepsis

    PubMed Central

    Lee, Sung Youn; Jeong, Eun Ha; Oh, Kyung Joon; Ryu, Aeli; Park, Kyoung Un

    2012-01-01

    The aim of this study was to determine whether maternal serum C-reactive protein (CRP) is of value in predicting funisitis and early-onset neonatal sepsis (EONS) in women with preterm labor or preterm premature rupture of membranes (PROM). This retrospective cohort study included 306 consecutive women with preterm labor or preterm PROM who delivered preterm singleton neonates (23-35 weeks gestation) within 72 hr of CRP measurement. The CRP level was measured with a highly sensitive immunoassay. The sensitivity, specificity, positive predictive value, and negative predictive value of an elevated serum CRP level (≥ 8 mg/L) were 74.1%, 67.5%, 32.8%, and 92.4% for funisitis, and 67.7%, 63.3%, 17.2%, and 94.6% for EONS, respectively. Logistic regression analysis demonstrated that elevated levels of serum CRP were significantly associated with funisitis and EONS, even after adjusting gestational age. The maternal serum CRP level obtained up to 72 hr before delivery is an independent predictor of funisitis and EONS in women with preterm labor or preterm PROM. A low serum CRP level (< 8 mg/L) has good negative predictive value in excluding funisitis and EONS, and may therefore be used as a non-invasive adjunct to clinical judgment to identify low-risk patients. PMID:22690100

  9. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features

    PubMed Central

    Lessel, Davor; Vaz, Bruno; Halder, Swagata; Lockhart, Paul J; Marinovic-Terzic, Ivana; Lopez-Mosqueda, Jaime; Philipp, Melanie; Sim, Joe C H; Smith, Katherine R; Oehler, Judith; Cabrera, Elisa; Freire, Raimundo; Pope, Kate; Nahid, Amsha; Norris, Fiona; Leventer, Richard J; Delatycki, Martin B; Barbi, Gotthold; von Ameln, Simon; Högel, Josef; Degoricija, Marina; Fertig, Regina; Burkhalter, Martin D; Hofmann, Kay; Thiele, Holger; Altmüller, Janine; Nürnberg, Gudrun; Nürnberg, Peter; Bahlo, Melanie; Martin, George M; Aalfs, Cora M; Oshima, Junko; Terzic, Janos; Amor, David J; Dikic, Ivan; Ramadan, Kristijan; Kubisch, Christian

    2015-01-01

    Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1)1–7 in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis1–7. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma. PMID:25261934

  10. NAPB - a novel SNARE-associated protein for early-onset epileptic encephalopathy.

    PubMed

    Conroy, J; Allen, N M; Gorman, K M; Shahwan, A; Ennis, S; Lynch, S A; King, M D

    2016-02-01

    Next-generation sequencing has accelerated the identification of disease genes in many rare genetic disorders including early-onset epileptic encephalopathies (EOEEs). While many of these disorders are caused by neuronal channelopathies, the role of synaptic and related neuronal proteins are increasingly being described. Here, we report a 6-year-old girl with unexplained EOEE characterized by multifocal seizures and profound global developmental delay. Recessive inheritance was considered due to parental consanguinity and Irish Traveller descent. Exome sequencing was performed. Variant prioritization identified a homozygous nonsense variant in the N-ethylmaleimide-sensitive factor attachment protein, beta (NAPB) gene resulting in a premature stop codon and 46% loss of the protein. NAPB plays a role in soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE)-complex dissociation and recycling (synaptic vesicle docking). Knockout mouse models of the murine ortholog Napb have been previously reported. These mice develop recurrent post-natal epileptic seizures in the absence of structural brain changes. The identification of a disease-causing variant in NAPB further recognizes the importance of the SNARE complex in the development of epilepsy and suggests that this gene should be considered in patients with unexplained EOEE. PMID:26235277

  11. Brain Network Informed Subject Community Detection In Early-Onset Schizophrenia

    PubMed Central

    Yang, Zhi; Xu, Yong; Xu, Ting; Hoy, Colin W.; Handwerker, Daniel A.; Chen, Gang; Northoff, Georg; Zuo, Xi-Nian; Bandettini, Peter A.

    2014-01-01

    Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS. PMID:24989351

  12. The impact of early- and late-onset preeclampsia on umbilical cord blood cell populations.

    PubMed

    Herzog, Emilie M; Eggink, Alex J; van der Zee, Marten; Lagendijk, Jacqueline; Willemsen, Sten P; de Jonge, Robert; Steegers, Eric A P; Steegers-Theunissen, Regine P M

    2016-08-01

    Pregnancies complicated by preeclampsia (PE) are characterised by an enhanced maternal and fetal inflammatory response with increased numbers of leukocytes in maternal peripheral blood. The impact of PE on newborn umbilical cord blood cell (UCBC) populations however, has been scarcely studied. We hypothesise that PE deranges fetal haematopoiesis and subsequently UCBC populations. Therefore, the objective of this study was to investigate newborn umbilical cord blood cell populations in early- (EOPE) and late-onset PE (LOPE). A secondary cohort analysis in The Rotterdam Periconceptional Cohort was conducted comprising 23 PE cases, including 11 EOPE and 12 LOPE, and 195 controls, including 153 uncomplicated and 23 fetal growth restriction- and 19 preterm birth complicated controls. UCBC counts and differentials were quantified by flow cytometry and analysed as main outcome measures. Multivariable regression analysis revealed associations of EOPE with decreased leucocyte- (monocytes, neutrophils, eosinophils, immature granulocytes) and thrombocyte counts and increased NRBC counts (all p<0.05). EOPE remained associated with neutrophil- (β-0.92, 95%CI -1.27,-0.57, p<0.001) and NRBC counts (β1.11, 95%CI 0.27,1.95, p=0.010) after adjustment for gestational age and birth weight. LOPE did not reveal any significant association. We conclude that derangements of fetal haematopoiesis, in particular of neutrophil- and NRBC counts, are associated with EOPE only, with a potential impact for future health of the offspring. This heterogeneity in UCBC should be considered as confounder in epigenetic association studies examining EOPE. PMID:27239988

  13. Comparison Between Pathogen Associated Laboratory and Clinical Parameters in Early-Onset Sepsis of the Newborn

    PubMed Central

    Resch, Bernhard; B, Renoldner; N, Hofer

    2016-01-01

    Objectives: To identify laboratory and clinical characteristics of different pathogens associated with early-onset sepsis (EOS) of the newborn. Methods: Newborns with EOS were retrospectively analyzed regarding laboratory and clinical parameters associated with the identified pathogen. Results: We identified 125 newborns having diagnosis of culture proven EOS between 1993 and 2011. One hundred cases had diagnosis of group B streptococci (GBS) infection (80%), 11 had Escherichia coli (8.8%), eight enterococci (6.4%), and six other pathogens (4.8%). White blood cell count (WBC), immature to total neutrophil (IT) ratio, and C-reactive protein (CRP) values did not differ between groups within the first 72 hours of life. Presence of high (>30000/µL) and low (<9000/µl) WBC was significantly less found compared with IT-ratio >0.2 in GBS and E.coli EOS. High WBC were more common found than low WBC in all groups. Gram positive pathogens were more common found in late preterm and term infants (84%), and gram negative pathogens more common in very low birth weight infants (64%). E. coli was significantly associated with lower gestational age and birth weight, respectively. Conclusion: An abnormal IT-ratio was a more common finding than an abnormal WBC in GBS and E. coli EOS. E. coli was significantly associated with prematurity.

  14. SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease.

    PubMed

    Nicolas, G; Charbonnier, C; Wallon, D; Quenez, O; Bellenguez, C; Grenier-Boley, B; Rousseau, S; Richard, A-C; Rovelet-Lecrux, A; Le Guennec, K; Bacq, D; Garnier, J-G; Olaso, R; Boland, A; Meyer, V; Deleuze, J-F; Amouyel, P; Munter, H M; Bourque, G; Lathrop, M; Frebourg, T; Redon, R; Letenneur, L; Dartigues, J-F; Génin, E; Lambert, J-C; Hannequin, D; Campion, D

    2016-06-01

    The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history. PMID:26303663

  15. Reducing the Cost of the Diagnostic Odyssey in Early Onset Epileptic Encephalopathies

    PubMed Central

    Mansilla, M. Adela; Campbell, Colleen A.

    2016-01-01

    Whole exome sequencing (WES) has revolutionized the way we think about and diagnose epileptic encephalopathies. Multiple recent review articles discuss the benefits of WES and suggest various algorithms to follow for determining the etiology of epileptic encephalopathies. Incorporation of WES in these algorithms is leading to the discovery of new genetic diagnoses of early onset epileptic encephalopathies (EOEEs) at a rapid rate; however, WES is not yet a universally utilized diagnostic tool. Clinical WES may be underutilized due to provider discomfort in ordering the test or perceived costliness. At our hospital WES is not routinely performed for patients with EOEE due to limited insurance reimbursement. In fact for any patient with noncommercial insurance (Medicaid) the institution does not allow sending out WES as this is not “established”/“proven to be highly useful and cost effective”/“approved test” in patients with epilepsy. Recently, we performed WES on four patients from three families and identified novel mutations in known epilepsy genes in all four cases. These patients had State Medicaid as their insurance carrier and were followed up for several years for EOEE while being worked up using the traditional/approved testing methods. Following a recently proposed diagnostic pathway, we analyzed the cost savings (US dollars) that could be accrued if WES was performed earlier in the diagnostic odyssey. This is the first publication that addresses the dollar cost of traditional testing in EOEE as performed in these four cases versus WES and the potential cost savings. PMID:27243033

  16. Balance in subjects with congenital or early onset strabismus: Influence of age.

    PubMed

    Dickmann, Anna; Di Sipio, Enrica; Simbolotti, Chiara; Agresta, Antonio; Germanotta, Marco; Tredici, Costanza; Petroni, Sergio; Padua, Luca; Aprile, Irene

    2016-06-01

    Few studies have investigated the relationship between strabismus and balance, and those that do exist focused on patients within a limited age range, while no studies on possible age-related changes have yet been conducted. Therefore, the aim of our study was to investigate whether the balance strategies adopted by patients with congenital or early onset strabismus change with age. Forty strabismic patients and 36 healthy subjects were enrolled in the study. Both patients and healthy subjects were divided into three subgroups according to age (children, adolescents, and adults) and underwent a stabilometric evaluation. When we compared the whole group of strabismic patients with the group of healthy subjects, we found that the center of pressure area and the trunk oscillations in the former were significantly different from those in the latter; when we considered the three age groups separately, only values in children with strabismus were different from those in the age-matched control group of healthy subjects. Strabismus was found to affect balance in children by inducing a postural strategy characterized by a reduction in physiological trunk oscillations. Gaining a better insight into postural control in strabismic subjects and its evolution with age may be crucial to improving rehabilitation in such patients and planning tailored rehabilitation treatment. PMID:27109787

  17. Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders

    PubMed Central

    Juuhl-Langseth, Monica; Hartberg, Cecilie B.; Holmén, Aina; Thormodsen, Rune; Groote, Inge R.; Rimol, Lars M.; Emblem, Kyrre E.; Agartz, Ingrid; Rund, Bjørn R.

    2015-01-01

    Background Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB) in early onset schizophrenia spectrum disorders (EOS). To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS. Methods Twenty-four patients with EOS and 33 healthy controls (HC) were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables. Results The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034). There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship. Conclusion Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups. PMID:26230626

  18. Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

    PubMed Central

    Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439

  19. Assessment of the contralesional corticospinal tract in early-onset pediatric hemiplegia: Preliminary findings.

    PubMed

    Hawe, Rachel L; Dewald, Jules P A

    2014-01-01

    While pediatric hemiplegia results from a unilateral lesion, the immature state of the brain at the time of injury increases the likelihood of observing changes in the non-lesioned hemisphere as well. The purpose of this preliminary study was to use diffusion tensor imaging to evaluate the contralesional corticospinal tracts in individuals with early-onset pediatric hemiplegia. Twelve individuals with pediatric hemiplegia and ten age-matched controls underwent diffusion tensor imaging (DTI). Corticospinal projections were reconstructed using probabilistic tractography for both the lesioned and contralesional side in pediatric hemiplegia as well as the dominant and non-dominant sides in control subjects. The contralesional tract was found to have decreased white matter integrity relative to control subjects. Compared to controls, the contralesional tract also showed increased tract volume. The increase in volume suggests the presence of ipsilateral corticospinal projections from the contralesional hemisphere that are maintained during development to control the paretic extremities. Decreases in integrity may be explained by diffuse damage or incomplete maturation. The findings of this study support the notion of bilateral motor involvement in pediatric hemiplegia, and the need to address bilateral neural changes as well as motor deficits in this population. PMID:25571199

  20. Altered expression of mRNA profiles in blood of early-onset schizophrenia

    PubMed Central

    Xu, Yong; Yao Shugart, Yin; Wang, Guoqiang; Cheng, Zaohuo; Jin, Chunhui; Zhang, Kai; Wang, Jun; Yu, Hao; Yue, Weihua; Zhang, Fuquan; Zhang, Dai

    2016-01-01

    To identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes . The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD, and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ. PMID:26733343

  1. Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats

    PubMed Central

    Ofri, Ron; Reilly, Christopher M.; Maggs, David J.; Fitzgerald, Paul G.; Shilo-Benjamini, Yael; Good, Kathryn L.; Grahn, Robert A.; Splawski, Danielle D.; Lyons, Leslie A.

    2015-01-01

    Purpose A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Methods Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Results Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. Conclusions A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID:26258614

  2. Critical slowing down as early warning for the onset of collapse in mutualistic communities.

    PubMed

    Dakos, Vasilis; Bascompte, Jordi

    2014-12-01

    Tipping points are crossed when small changes in external conditions cause abrupt unexpected responses in the current state of a system. In the case of ecological communities under stress, the risk of approaching a tipping point is unknown, but its stakes are high. Here, we test recently developed critical slowing-down indicators as early-warning signals for detecting the proximity to a potential tipping point in structurally complex ecological communities. We use the structure of 79 empirical mutualistic networks to simulate a scenario of gradual environmental change that leads to an abrupt first extinction event followed by a sequence of species losses until the point of complete community collapse. We find that critical slowing-down indicators derived from time series of biomasses measured at the species and community level signal the proximity to the onset of community collapse. In particular, we identify specialist species as likely the best-indicator species for monitoring the proximity of a community to collapse. In addition, trends in slowing-down indicators are strongly correlated to the timing of species extinctions. This correlation offers a promising way for mapping species resilience and ranking species risk to extinction in a given community. Our findings pave the road for combining theory on tipping points with patterns of network structure that might prove useful for the management of a broad class of ecological networks under global environmental change. PMID:25422412

  3. The early Miocene onset of a ventilated circulation regime in the Arctic Ocean.

    PubMed

    Jakobsson, Martin; Backman, Jan; Rudels, Bert; Nycander, Jonas; Frank, Martin; Mayer, Larry; Jokat, Wilfried; Sangiorgi, Francesca; O'Regan, Matthew; Brinkhuis, Henk; King, John; Moran, Kathryn

    2007-06-21

    Deep-water formation in the northern North Atlantic Ocean and the Arctic Ocean is a key driver of the global thermohaline circulation and hence also of global climate. Deciphering the history of the circulation regime in the Arctic Ocean has long been prevented by the lack of data from cores of Cenozoic sediments from the Arctic's deep-sea floor. Similarly, the timing of the opening of a connection between the northern North Atlantic and the Arctic Ocean, permitting deep-water exchange, has been poorly constrained. This situation changed when the first drill cores were recovered from the central Arctic Ocean. Here we use these cores to show that the transition from poorly oxygenated to fully oxygenated ('ventilated') conditions in the Arctic Ocean occurred during the later part of early Miocene times. We attribute this pronounced change in ventilation regime to the opening of the Fram Strait. A palaeo-geographic and palaeo-bathymetric reconstruction of the Arctic Ocean, together with a physical oceanographic analysis of the evolving strait and sill conditions in the Fram Strait, suggests that the Arctic Ocean went from an oxygen-poor 'lake stage', to a transitional 'estuarine sea' phase with variable ventilation, and finally to the fully ventilated 'ocean' phase 17.5 Myr ago. The timing of this palaeo-oceanographic change coincides with the onset of the middle Miocene climatic optimum, although it remains unclear if there is a causal relationship between these two events. PMID:17581581

  4. Integrating Genetic, Neuropsychological and Neuroimaging Data to Model Early-Onset Obsessive Compulsive Disorder Severity.

    PubMed

    Mas, Sergi; Gassó, Patricia; Morer, Astrid; Calvo, Anna; Bargalló, Nuria; Lafuente, Amalia; Lázaro, Luisa

    2016-01-01

    We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the training set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our understanding of the neurobiological basis of the disorder. PMID:27093171

  5. Transcriptional Onset of Lysozyme Genes during Early Development in Olive Flounder (Paralichthys olivaceus)

    PubMed Central

    Lee, Jang-Wook; Lee, Jeong-Ho; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Kim, Kyung-Kil

    2014-01-01

    The immune system in teleost fish is not completely developed during embryonic and larval stages, therefore effective innate mechanisms is very important for survival in such an environment. However, the knowledge of the development of immune system assumed to be restricted. In many species, lysozymes have been considered as important genes of the first line immune defense. The early detection of lysozyme mRNA in previous reports, led to the investigation of its presence in oocytes. As a result, c-type lysozyme mRNA transcripts were detected in unfertilized oocytes indicating maternal transfer. Therefore, we investigated the expression patterns of lysozymes in flounder, including the matured oocyte. In our results, c-type lysozyme mRNA was first detected in unfertilized oocyte stage, observed the significantly decreased until hatching stage, and was significantly increased after hatching stage. On the other hand, g-type lysozyme mRNA transcripts were first detected at late neurula stage, and the mRNA level was significantly increased after 20 dph. It may be suggest that maternally supplied mRNAs are selectively degraded prior to the activation of embryonic transcription. This study will be help in understanding the maturation and onset of humoral immunity during development of olive flounder immune system. PMID:25949197

  6. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase.

    PubMed

    Puppala, Anupama K; French, Rachel L; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS-Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*-induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  7. Early-onset Purkinje cell dysfunction underlies cerebellar ataxia in peroxisomal multifunctional protein-2 deficiency.

    PubMed

    De Munter, Stephanie; Verheijden, Simon; Vanderstuyft, Esther; Malheiro, Ana Rita; Brites, Pedro; Gall, David; Schiffmann, Serge N; Baes, Myriam

    2016-10-01

    The cerebellar pathologies in peroxisomal diseases underscore that these organelles are required for the normal development and maintenance of the cerebellum, but the mechanisms have not been resolved. Here we investigated the origins of the early-onset coordination impairment in a mouse model with neural selective deficiency of multifunctional protein-2, the central enzyme of peroxisomal β-oxidation. At the age of 4weeks, Nestin-Mfp2(-/-) mice showed impaired motor learning on the accelerating rotarod and underperformed on the balance beam test. The gross morphology of the cerebellum and Purkinje cell arborization were normal. However, electrophysiology revealed a reduced Purkinje cell firing rate, a decreased excitability and an increased membrane capacitance. The distribution of climbing and parallel fiber synapses on Purkinje cells was immature and was accompanied by an increased spine length. Despite normal myelination, Purkinje cell axon degeneration was evident from the occurrence of axonal swellings containing accumulated organelles. In conclusion, the electrical activity, axonal integrity and wiring of Purkinje cells are exquisitely dependent on intact peroxisomal β-oxidation in neural cells. PMID:27353294

  8. Molecular alterations in gastric cancer with special reference to the early-onset subtype

    PubMed Central

    Skierucha, Małgorzata; Milne, Anya NA; Offerhaus, G Johan A; Polkowski, Wojciech P; Maciejewski, Ryszard; Sitarz, Robert

    2016-01-01

    Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC. PMID:26937134

  9. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.

    PubMed

    Pottier, C; Hannequin, D; Coutant, S; Rovelet-Lecrux, A; Wallon, D; Rousseau, S; Legallic, S; Paquet, C; Bombois, S; Pariente, J; Thomas-Anterion, C; Michon, A; Croisile, B; Etcharry-Bouyx, F; Berr, C; Dartigues, J-F; Amouyel, P; Dauchel, H; Boutoleau-Bretonnière, C; Thauvin, C; Frebourg, T; Lambert, J-C; Campion, D

    2012-09-01

    Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD. PMID:22472873

  10. A method for conducting intensive psychological studies with early-onset chronically depressed patients.

    PubMed

    McCullough, James P; Lord, Benjamin D; Conley, Kathryn A; Martin, Aaron M

    2010-01-01

    An intensive empirical methodology is introduced to evaluate the efficacy of Cognitive Behavioral Analysis System of Psychotherapy (CBASP) treatment for outpatients with early onset chronic depression. The patient with chronic illness presents a unique measurement challenge to psychotherapists. One of the most prominent reasons is the refractory nature of the disorder. In order to measure the change process, the authors have found it helpful to use an acquisition-learning methodology to answer three questions: (1) What are we trying to teach the patient? (2) How much has the patient learned throughout the course of therapy? And, (3) how does the extent of patient learning impact the change indices at the end of treatment and during the follow-up period? Answering questions 2 and 3 allows us to superimpose the change process variables over the performance learning variables on a graph. These combined variables also allow us to test the hypothesis: By learning what psychotherapy teaches, the chronic psychological disorder may be resolved. PMID:21299171

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

    PubMed

    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

    Previously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (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 function in patient muscle. QIL1 absence in patients' fibroblasts was associated with MICOS disassembly, abnormal cristae, mild cytochrome c oxidase defect, and sensitivity to glucose withdrawal. QIL1 expression rescued cristae defects, and promoted re-accumulation of MICOS subunits to facilitate MICOS assembly. MICOS assembly and cristae morphology were not efficiently rescued by over-expression of other MICOS subunits in patient fibroblasts. Taken together, these data provide the first evidence of altered MICOS assembly linked with a human mitochondrial disease and confirm a central role for QIL1 in stable MICOS complex formation. PMID:27623147

  12. Early-onset bipolar disorder: how about visual-spatial skills and executive functions?

    PubMed

    Lera-Miguel, Sara; Andrés-Perpiñá, Susana; Calvo, Rosa; Fatjó-Vilas, Mar; Fañanás, Lourdes; Lourdes, Fañanás; Lázaro, Luisa

    2011-04-01

    Early-onset bipolar disorder is an impairing condition that is strongly associated with genetic inheritance. Neurocognitive deficits are core traits of this disorder which seem to be present in both young and adult forms. Deficits in verbal memory and attention are persistent within euthymic phases in bipolar adults, adolescents, and children. In younger samples, including type I or II and not otherwise specified patients, executive functions are not widely impaired and the existence of visual-spatial deficits remains unclear. The main aim of this study was to compare the neurocognitive performance in young stabilized type I or II bipolar patients and healthy controls. Fifteen medicated adolescents with bipolar disorder and 15 healthy adolescents, matched in age and gender, were compared on visual-spatial skills (reasoning, memory, visual-motor accuracy) and executive functioning (attention and working memory, set-shifting, inhibition) using t-tests and MANCOVA. Correcting for verbal competence, MANCOVA showed that patients performed significantly worse than controls in letters and numbers sequencing (P = 0.003), copy (P < 0.001) and immediate recall (P = 0.007) of the Rey Complex Figure Test, interference of the Stroop Color-Word Test (P = 0.007) and non-perseverative errors on the Wisconsin Card Sorting Test (P = 0.038). Impaired cognitive performance was found in young bipolar patients in working memory, visual-motor skills, and inhibitory control. PMID:21086134

  13. THE ROLE OF PROTEOMICS IN THE DIAGNOSIS OF CHORIOAMNIONITIS AND EARLY-ONSET NEONATAL SEPSIS

    PubMed Central

    Buhimschi, Catalin S.

    2010-01-01

    SYNOPSIS Intra-uterine infection is viewed as a unique pathological process which raises considerably the risk for early onset neonatal sepsis (EONS). By acting synergistically with prematurity, EONS increases the risk for adverse neonatal outcomes including intraventricular hemorrhage (IVH) and cerebral palsy which are often encountered as sequelae of sepsis. Although several distinct pathways for the pathogenesis of fetal damage have been proposed, the basic molecular mechanisms that modulate these events remain incompletely understood. Therefore, discovery of clinically and biologically relevant biomarkers able to reveal key pathogenic pathways and predict pregnancies at risk for antenatal fetal damage is a priority. Proteomics provides a unique opportunity to fill this gap. In the short run proteomic biomarkers may aid with medical decision-making including timing of delivery and steroid administration In the long run proteomic biomarkers may lead to development of targeted therapies against pathogenic variants of EONS. Herein, we aimed to illustrate the richness of the topic and set the stage for the argument that discovery of novel proteomic biomarkers is a critical step in improving outcomes and preventing long-term disability. PMID:20569812

  14. Familial early-onset dementia with complex neuropathologic phenotype and genomic background.

    PubMed

    Alexander, John; Kalev, Ognian; Mehrabian, Shima; Traykov, Latchezar; Raycheva, Margariata; Kanakis, Dimitrios; Drineas, Petros; Lutz, Mirjam I; Ströbel, Thomas; Penz, Thomas; Schuster, Michael; Bock, Christoph; Ferrer, Isidro; Paschou, Peristera; Kovacs, Gabor G

    2016-06-01

    Despite significant progress in our understanding of hereditary neurodegenerative diseases, the list of genes associated with early-onset dementia is not yet complete. In the present study, we describe a familial neurodegenerative disorder characterized clinically as the behavioral and/or dysexecutive variant of Alzheimer's disease with neuroradiologic features of Alzheimer's disease, however, lacking amyloid-β deposits in the brain. Instead, we observed a complex, 4 repeat predominant, tauopathy, together with a TAR DNA-binding protein of 43 kDa proteinopathy. Whole-exome sequencing on 2 affected siblings and 1 unaffected aunt uncovered a large number of candidate genes, including LRRK2 and SYNE2. In addition, DDI1, KRBA1, and TOR1A genes possessed novel stop-gain mutations only in the patients. Pathway, gene ontology, and network interaction analysis indicated the involvement of pathways related to neurodegeneration but revealed novel aspects also. This condition does not fit into any well-characterized category of neurodegenerative disorders. Exome sequencing did not disclose a single disease-specific gene mutation suggesting that a set of genes working together in different pathways may contribute to the etiology of the complex phenotype. PMID:27143436

  15. Presence of Arp Specifically Contributes to Joint Tissue Edema Associated with Early-Onset Lyme Arthritis

    PubMed Central

    Hove, Petronella R.; Haldorson, Gary J.; Magunda, Forgivemore

    2014-01-01

    Antiserum to the Borrelia burgdorferi arthritis-related protein, Arp, has been shown to prevent or reduce arthritis in immunodeficient mice. To directly investigate the requirement for this lipoprotein in the generation of Lyme arthritis, we utilized targeted deletion to generate a B. burgdorferi clone that lacked only the arp gene locus. Infection of Lyme disease-susceptible C3H/HeN mice with the arp deletion mutant demonstrated significantly reduced tibiotarsal joint swelling during the first 6 weeks of infection compared to a wild-type control. The severity of joint swelling was restored to wild-type levels in mice infected with an arp mutant clone complemented in cis. Interestingly, the reduced swelling of joint tissues exhibited by mice infected with the arp deletion mutant did not directly correspond to reduced underlying arthritis. Histopathology data at 2 weeks postinfection showed some reduction in arthritis severity caused by the arp mutant clone; however, by 8 weeks, no significant difference was observed between joint tissues infected by the wild-type or arp mutant clones. The spirochete load in the joint tissues of mice infected with the arp mutant was found to be greater than that exhibited by the wild-type control. Our findings demonstrate that this lipoprotein contributes to the generation of early-onset joint swelling and suggests that arp expression has a negative secondary effect on total spirochete numbers in joint tissues. PMID:24101694

  16. Facial, vocal and cross-modal emotion processing in early-onset schizophrenia spectrum disorders.

    PubMed

    Giannitelli, Marianna; Xavier, Jean; François, Anne; Bodeau, Nicolas; Laurent, Claudine; Cohen, David; Chaby, Laurence

    2015-10-01

    Recognition of emotional expressions plays an essential role in children's healthy development. Anomalies in these skills may result in empathy deficits, social interaction difficulties and premorbid emotional problems in children and adolescents with schizophrenia. Twenty-six subjects with early onset schizophrenia spectrum (EOSS) disorders and twenty-eight matched healthy controls (HC) were instructed to identify five basic emotions and a neutral expression. The assessment entailed presenting visual, auditory and congruent cross-modal stimuli. Using a generalized linear mixed model, we found no significant association for handedness, age or gender. However, significant associations emerged for emotion type, perception modality, and group. EOSS patients performed worse than HC in uni- and cross-modal emotional tasks with a specific negative emotion processing impairment pattern. There was no relationship between emotion identification scores and positive or negative symptoms, self-reported empathy traits or a positive history of developmental disorders. However, we found a significant association between emotional identification scores and nonverbal communication impairments. We conclude that cumulative dysfunctions in both nonverbal communication and emotion processing contribute to the social vulnerability and morbidity found in youths who display EOSS disorder. PMID:26297473

  17. [Knowledge and gaps on the role of nutrition and physical activity on the onset of childhood obesity].

    PubMed

    Bautista-Castaño, Inmaculada; Sangil-Monroy, Marta; Serra-Majem, Lluís

    2004-12-01

    Childhood and adolescent obesity has increased at alarming rates over the last few years, due to the concurrence of a variety of genetic and environmental factors. The aim of this study was to conduct a review of published studies in the past ten years evaluating the development of childhood obesity in relation to energy and macronutrients intake, their distribution throughout the day and physical activity patterns. 31 articles dealing with this subject were selected. Results obtained appear to indicate that reducing dietary fat and increasing dietary carbohydrate intakes along with consuming an adequate breakfast and carrying out leisure time physical activity on a regular basis act as determining factors to prevent childhood and adolescent obesity, even though the strength of the evidence from these studies is low. It should be a priority to conduct follow-up studies with comparable methodologies in Mediterranean countries, in order to establish parameters for the prevention and control of childhood and adolescent obesity. PMID:15607072

  18. Identification of the PS1 Thr147Ile Variant in a Family with Very Early Onset Dementia and Expressive Aphasia

    PubMed Central

    Denvir, James; Neitch, Shirley; Fan, Jun; Niles, Richard M.; Boskovic, Goran; Schreurs, Bernard G.; Primerano, Donald A.; Alkon, Daniel L.

    2015-01-01

    Abstract Background: Early onset dementias have variable clinical presentations and are often difficult to diagnose. We established a family pedigree that demonstrated consistent recurrence of very early onset dementia in successive generations. Objective and Method: In order to refine the diagnosis in this family, we sequenced the exomes of two affected family members and relied on discrete filtering to identify disease genes and the corresponding causal variants. Results: Among the 720 nonsynonymous single nucleotide polymorphisms (SNPs) shared by two affected members, we found a C to T transition that gives rise to a Thr147Ile missense substitution in the presenilin 1 (PS1) protein. The presence of this same mutation in a French early-onset Alzheimer’s disease family, other affected members of the family, and the predicted high pathogenicity of the substitution strongly suggest that it is the causal variant. In addition to exceptionally young age of onset, we also observed significant limb spasticity and early loss of speech, concurrent with progression of dementia in affected family members. These findings extend the clinical presentation associated with the Thr147Ile variant. Lastly, one member with the Thr147Ile variant was treated with the PKC epsilon activator, bryostatin, in a compassionate use trial after successful FDA review. Initial improvements with this treatment were unexpectedly clear, including return of some speech, increased attentional focus, ability to swallow, and some apparent decrease in limb spasticity. Conclusions: Our findings confirm the role of the PS1 Thr147Ile substitution in Alzheimer’s disease and expand the clinical phenotype to include expressive aphasia and very early onset of dementia. PMID:25812849

  19. Common Variants in Promoter of ADTRP Associate with Early-Onset Coronary Artery Disease in a Southern Han Chinese Population

    PubMed Central

    Huang, Lei; Wu, Qiu-Ping; Tang, Shuang-Bo; Luo, Bin; Liu, Shui-Ping; Liu, Xiao-Shan; Li, Zhao-Hui; Quan, Li; Li, Yue; Shi, He; Lv, Guo-Li; Zhao, Jian; Cheng, Jian-Ding; Liu, Chao

    2015-01-01

    The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3’UTR, rs2076189 in 5’UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105–0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD. PMID:26375920

  20. Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review.

    PubMed

    Young, Joanne P; Win, Aung Ko; Rosty, Christophe; Flight, Ingrid; Roder, David; Young, Graeme P; Frank, Oliver; Suthers, Graeme K; Hewett, Peter J; Ruszkiewicz, Andrew; Hauben, Ehud; Adelstein, Barbara-Ann; Parry, Susan; Townsend, Amanda; Hardingham, Jennifer E; Price, Timothy J

    2015-01-01

    The average age at diagnosis for colorectal cancer (CRC) in Australia is 69, and the age-specific incidence rises rapidly after age 50 years. The incidence has stabilized or is declining in older age groups in Australia during recent decades, possibly related to the increased uptake of screening and high-risk surveillance. In the same time frame, a rising incidence of CRC in younger adults has been well-documented in the United States. This rise in incidence in the young has not been reported from other countries that share long-term exposure to westernised urban lifestyles. Using data from the Australian Institute of Health and Welfare, we examined trends in national incidence rates for CRC under age 50 years and observed that rates in people under age 40 years have been rising for the last two decades. We further performed a review of the literature regarding CRC in young adults to outline the extent of current understanding, explore potential risk factors such as obesity, alcohol, and sedentary lifestyles, and to identify the questions remaining to be addressed. Although absolute numbers might not justify a population screening approach, the dispersal of young adults with CRC across the primary health-care system decreases probability of their recognition. Patient and physician awareness, aided by stool and emerging blood-screening tests and risk profiling tools, have the potential to aid in identification of those young adults who would most benefit from a colonoscopy through early detection of CRCs or by removal of advanced polyps. PMID:25251195

  1. Dinitrophenol and obesity: an early twentieth-century regulatory dilemma.

    PubMed

    Colman, Eric

    2007-07-01

    In the early 1930s, the industrial chemical dinitrophenol found widespread favor as a weight-loss drug, due principally to the work of Maurice Tainter, a clinical pharmacologist from Stanford University. Unfortunately the compound's therapeutic index was razor thin and it was not until thousands of people suffered irreversible harm that mainstream physicians realized that dinitrophenol's risks outweighed its benefits and abandoned its use. Yet, it took passage of the Food, Drug, and Cosmetic Act in 1938 before federal regulators had the ability to stop patent medicine men from selling dinitrophenol to Americans lured by the promise of a drug that would safely melt one's fat away. PMID:17475379

  2. Design and methods for evaluating an early childhood obesity prevention program in the childcare center setting

    PubMed Central

    2013-01-01

    Background Many unhealthy dietary and physical activity habits that foster the development of obesity are established by the age of five. 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. We describe here the methods for conducting an obesity prevention randomized trial in the child care setting. Methods/design A randomized, controlled obesity prevention trial is currently being conducted over a three year period (2010-present). The sample consists of 28 low-income, ethnically diverse child care centers with 1105 children (sample is 60% Hispanic, 15% Haitian, 12% Black, 2% non-Hispanic White and 71% of caregivers were born outside of the US). The purpose is to test the efficacy of a parent and teacher role-modeling intervention on children’s nutrition and physical activity behaviors. . The Healthy Caregivers-Healthy Children (HC2) intervention arm schools received a combination of (1) implementing a daily curricula for teachers/parents (the nutritional gatekeepers); (2) implementing a daily curricula for children; (3) technical assistance with meal and snack menu modifications such as including more fresh and less canned produce; and (4) creation of a center policy for dietary requirements for meals and snacks, physical activity and screen time. Control arm schools received an attention control safety curriculum. Major outcome measures include pre-post changes in child body mass index percentile and z score, fruit and vegetable and other nutritious food intake, amount of physical activity, and parental nutrition and physical activity knowledge, attitudes, and beliefs, defined by intentions and behaviors. All measures were administered at the beginning and end of the school year for year one and year two of the study for a total of 4 longitudinal time points for assessment. Discussion Although few

  3. Early Onset of Drug and Polysubstance Use as Predictors of Injection Drug Use Among Adult Drug Users

    PubMed Central

    Trenz, Rebecca C.; Scherer, Michael; Harrell, Paul; Zur, Julia; Sinha, Ashish; Latimer, William

    2012-01-01

    Early onset of alcohol, marijuana, and cigarette use is an indicator of later substance use problems in adulthood such as alcohol or other drug dependence. This paper seeks to address the association between early onset alcohol, marijuana, cigarette, and polysubstance use with injection drug use among recent illicit drug users. The current study used baseline data from the Baltimore site of the NEURO-HIV Epidemiologic Study, an investigation of neuropsychological and social-behavioral risk factors of HIV, hepatitis A, hepatitis B, and Hepatitis C among both injection and non-injection drug users in Baltimore Maryland. The present study used a subset (N = 651) of the larger parent study that identified as White or Black, and reported any drug use in the past 6 months. In the full sample slightly more than half (52.5%) of study participants were IDUs. IDUs differed from non-IDUs on age of initiation for cigarettes, marijuana, and alcohol, with IDUs initiating the use of all three substances significantly earlier than non-IDUs. IDUs also had significantly greater proportions of early onset of alcohol (χ2 = 19.71, p < .01), cigarette (χ2 = 11.05, p < .01), marijuana (χ2 = 10.83, p < .01), and polysubstance use (χ2 = 23.48, p < .01) than non-IDUs. After adjusting for age, gender, and race/ethnicity, only participants identified as early onset alcohol users (AOR = 1.47, 95% CI: 1.00-2.18) and early onset polysubstance users (AOR = 1.62, 95% CI: 1.10-2.38) were more likely to have IDU status than those who reported initiating substance use later. IDU status was then stratified by race/ethnicity. After controlling for age and gender, only early polysubstance use was a significant predictor of IDU status for Whites (AOR = 2.06, 95% CI: 1.07-3.93). Consistent with literature on early substance initiation and later illicit substance use, early onset alcohol and polysubstance use is an important risk factor for IDU in adulthood. PMID:22172686

  4. Trends in Early Childhood Obesity in a Large Urban School District in the Southwestern United States, 2007–2014

    PubMed Central

    Myers, Orrin; Scharmen, Thomas; Kinyua, Peter; Jimenez, Elizabeth Yakes

    2016-01-01

    Introduction Although recent studies indicate that rates of childhood obesity and severe obesity may be declining, few studies have reported prevalence trends in early childhood or differences in trends across sociodemographic groups. The primary aim of this study was to report trends in prevalence of early childhood obesity and severe obesity 2007 through 2014 in a diverse, metropolitan school district in the southwestern United States and determine whether these trends vary by race/ethnicity, socioeconomic status, and disability status. Methods We analyzed height, weight and demographic data from 43,113 kindergarteners enrolled in a large, urban school district in the southwestern United States for 7 school years. Adjusted odds of obesity and severe obesity were calculated to assess changes in prevalence for non-Hispanic white, Hispanic, and American Indian students; free or reduced-price lunch participants and nonparticipants; and students with and without disabilities. To test for differences in obesity trends, interaction terms were added to the logistic regressions between school year and sex, race/ethnicity, free or reduced-price lunch participation, and disability status. Results The adjusted prevalence of both obesity (from 13.1% in 2007–2008 to 12.0% in 2013–20014) and severe obesity (from 2.4% in 2007–2008 to 1.2% in 2013–2014) declined overall. We found no significant interactions between the adjusted prevalence of obesity over time and any of the sociodemographic subgroups. Obesity prevalence declined more among American Indian students than among Hispanic or non-Hispanic white students. Conclusion In this district, from 2007 through 2014, severe obesity decreased and obesity did not increase, overall and across all sociodemographic subpopulations for kindergarten students. PMID:27253637

  5. Gray Matter Alterations in Schizophrenia High-Risk Youth and Early-Onset Schizophrenia: A Review of Structural MRI Findings

    PubMed Central

    Brent, Benjamin K.; Thermenos, Heidi W.; Keshavan, Matcheri S.; Seidman, Larry J.

    2013-01-01

    Synopsis The purpose of this article is to provide a review of the literature on structural MRI findings in pediatric and young adult populations at clinical or genetic high-risk for schizophrenia, as well as in early-onset schizophrenia. The authors discuss the implications of this research for understanding the pathophysiology of schizophrenia and for early intervention strategies for prevention of the illness. The evidence linking brain structural changes in pre-psychosis development and early-onset schizophrenia with disruptions of normal neurodevelopmental processes during childhood and/or adolescence are described. In addition, the authors outline future directions for research to address current knowledge gaps regarding the neurobiological basis of brain structural abnormalities in schizophrenia and to help improve the utility of these abnormalities for preventative interventions. PMID:24012081

  6. Obesity

    MedlinePlus

    ... come from muscle, bone, fat, and/or body water. Both terms mean that a person's weight is greater than what's considered healthy for his or her height. Obesity occurs over time when you eat more calories than you use. The balance between calories-in and calories-out differs for ...

  7. A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy.

    PubMed

    Audenaert, D; Claes, L; Ceulemans, B; Löfgren, A; Van Broeckhoven, C; De Jonghe, P

    2003-09-23

    Generalized epilepsy with febrile seizures plus (GEFS+) is a clinically and genetically heterogeneous syndrome with childhood onset, characterized by febrile seizures (FS) and a variety of afebrile epileptic seizure types. The authors performed a mutational analysis of SCN1B on 74 unrelated probands with GEFS+, FS, or FS plus (FS+). In a family with FS+ and early-onset absence epilepsy, a mutation was identified that predicts a deletion of five amino acids in the extracellular immunoglobulin-like domain of SCN1B and potential loss of function. SCN1B mutations are associated with GEFS+ and may have a role in the elicitation of absence seizures. PMID:14504340

  8. Obesity Correlates With Glomerulomegaly But Is Not Associated With Kidney Dysfunction Early After Donation

    PubMed Central

    Chakkera, Harini A.; Chang, Yu-Hui H.; Thomas, Leslie F.; Avula, Ramesh T.; Amer, Hatem; Lerman, Lilach O.; Denic, Aleksandar; Rule, Andrew D.

    2015-01-01

    Background Body mass index (BMI) is a convenient measure used to assess obesity and is used to select candidates for kidney donation. Glomerulomegaly is an early indicator of obesity-related kidney disease. Whether obesity assessment by BMI best reflects underlying glomerulomegaly and is predictive of adverse changes in renal function postdonation is unclear. Methods We performed a retrospective study on a cohort of 1065 living donors at the Mayo Clinic in Rochester; obesity measures by BMI and by computed tomography were compared between 20 donors with largest to 20 donors with the smallest glomerular volumes (on implantation biopsy). In addition, the change in kidney function postdonation (mean 7 months) was compared across BMI groups (<25, 25-29, 30-34, ≥35 kg/m2) in about 500 donors. Results We observed that larger glomerular volume was more strongly associated with BMI per standard deviation (SD) (odds ratio [OR] =5.0, P = 0.002) than waist circumference/height2 per SD (OR = 3.9, P = 0.02), visceral fat/height2 per SD (OR = 2.4, P = 0.02), subcutaneous fat/height2 per SD (OR = 2.0, P = 0.06), renal hilar fat/height2 per SD (OR = 1.6, P = 0.19), or peri/pararenal fat/height2 per SD (OR = 1.5, P = 0.23). Postdonation changes in glomerular filtration rate, blood pressure, and albuminuria were similar across BMI categories. Conclusions The BMI outperforms various computed tomography measures of abdominal fat in detecting obesity-related glomerulomegaly. Despite this strong association with glomerulomegaly, short-term renal function outcomes are similar across BMI categories. Long-term follow-up is required to definitively define the impact of obesity on kidney function after donation. PMID:26052546

  9. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    ERIC Educational Resources Information Center

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  10. Digging Deeper Using Neuroimaging Tools Reveals Important Clues to Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Kumra, Sanjiv

    2008-01-01

    The article describes the use of structural neuroimaging to understand the psychopathology of childhood-onset schizophrenia. Results showed an increase in lateral volumes, reduced total and regional volumes of gray matter in the cortex and increased basal ganglia volumes as in adult-onset schizophrenia in comparison with healthy subjects.

  11. High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia.

    PubMed

    Peraçoli, Jose C; Bannwart-Castro, Camila F; Romao, Mariana; Weel, Ingrid C; Ribeiro, Vanessa R; Borges, Vera T M; Rudge, Marilza V; Witkin, Steven S; Peraçoli, Maria T

    2013-12-01

    Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1β, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1β, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels. PMID:24051131

  12. Mode of onset of ventricular fibrillation in patients with early repolarization pattern vs. Brugada syndrome

    PubMed Central

    Nam, Gi-Byoung; Ko, Kwan-Ho; Kim, Jun; Park, Kyoung-Min; Rhee, Kyoung-Suk; Choi, Kee-Joon; Kim, You-Ho; Antzelevitch, Charles

    2010-01-01

    Aims The aim of the present study was to identify specific electrocardiogram (ECG) features that predict the development of multiple episodes of ventricular fibrillation (VF) in patients with an early repolarization (ER) pattern and to compare the mode of VF initiation with that observed in typical cases of Brugada syndrome (BrS). Methods and results The mode of the onset and the coupling intervals of the premature ventricular contractions (PVCs) initiating VF episodes were analysed in patients with BrS (n = 8) or ER who experienced sudden cardiac death/syncope or repeated appropriate implantable cardioverter defibrillator shocks. Among the 11 patients with ER, 5 presented with electrical storm (ES, four or more recurrent VF episodes/day). The five ES patients displayed a dramatic but very transient accentuation of J waves across the precordial and limb leads prior to the development of ES. Ventricular fibrillation episodes were more commonly initiated by PVCs with a short–long–short (SLS) sequence in ER (42/58, 72.4%) vs. BrS patients (13/86, 15.1%, P < 0.01). Coupling intervals were significantly shorter in the ER group compared with those with BrS [328 (320, 340) ms vs. 395 (350, 404) ms, P < 0.01]. Conclusion Our study provides additional evidence in support of the hypothesis that ER pattern in the ECG is not always benign. Transient augmentation of global J waves may be indicative of a highly arrhythmogenic substrate heralding multiple episodes of VF in patients with ER pattern. Ventricular tachycardia/VF initiation is more commonly associated with an SLS sequence, and PVCs display a shorter coupling interval in patients with ER pattern compared with those with BrS. PMID:19880418

  13. Identification of candidate genes for familial early-onset essential tremor.

    PubMed

    Liu, Xinmin; Hernandez, Nora; Kisselev, Sergey; Floratos, Aris; Sawle, Ashley; Ionita-Laza, Iuliana; Ottman, Ruth; Louis, Elan D; Clark, Lorraine N

    2016-07-01

    Essential tremor (ET) is one of the most common causes of tremor in humans. Despite its high heritability and prevalence, few susceptibility genes for ET have been identified. To identify ET genes, whole-exome sequencing was performed in 37 early-onset ET families with an autosomal-dominant inheritance pattern. We identified candidate genes for follow-up functional studies in five ET families. In two independent families, we identified variants predicted to affect function in the nitric oxide (NO) synthase 3 gene (NOS3) that cosegregated with disease. NOS3 is highly expressed in the central nervous system (including cerebellum), neurons and endothelial cells, and is one of three enzymes that converts l-arginine to the neurotransmitter NO. In one family, a heterozygous variant, c.46G>A (p.(Gly16Ser)), in NOS3, was identified in three affected ET cases and was absent in an unaffected family member; and in a second family, a heterozygous variant, c.164C>T (p.(Pro55Leu)), was identified in three affected ET cases (dizygotic twins and their mother). Both variants result in amino-acid substitutions of highly conserved amino-acid residues that are predicted to be deleterious and damaging by in silico analysis. In three independent families, variants predicted to affect function were also identified in other genes, including KCNS2 (KV9.2), HAPLN4 (BRAL2) and USP46. These genes are highly expressed in the cerebellum and Purkinje cells, and influence function of the gamma-amino butyric acid (GABA)-ergic system. This is in concordance with recent evidence that the pathophysiological process in ET involves cerebellar dysfunction and possibly cerebellar degeneration with a reduction in Purkinje cells, and a decrease in GABA-ergic tone. PMID:26508575

  14. No impairment of monocyte-derived Langerhans cell phenotype or function in early-onset psoriasis

    PubMed Central

    Shaw, F L; Kimber, I; Begum, R; Cumberbatch, M; Dearman, R J; Griffiths, C E M

    2012-01-01

    Background Migration of epidermal Langerhans cells (LCs) in response to the cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α is impaired in uninvolved skin of patients with early-onset psoriasis. Aim To investigate whether this impairment is a reflection of a systemic defect in dendritic cells (DCs), using an established model of monocyte-derived LC-like cells (mLCs). Methods CD14+ monocytes isolated from both patients with psoriasis and healthy control volunteers were cultured in a cytokine cocktail for 5 days to promote their differentiation into mLCs, then stimulated for 24 h with TNF-α, IL-1β (both 100 ng/mL) or medium alone. Cellular surface protein expression was quantified by flow cytometry, and the ability of cells to migrate to media supplemented with C-C motif ligand (CCL)19 was assessed using a Transwell migration assay. The cytokine and chemokine content of supernatants was analysed by cytokine array. Results CD14+ cells acquired an LC-like phenotype with high expression of CD1a and major histocompatibility complex (MHC) class II. There were no differences in the expression of activation markers or in the secretion of cytokines by mLCs isolated from patients with psoriasis and those isolated from healthy controls. Moreover, mLCs isolated from both groups displayed comparable ability to migrate in vitro. Conclusions These data suggest that the failure of LCs to migrate in response to stimulation in patients with psoriasis is not attributable to a systemic defect in DC function, but is rather a reflection of local changes in the epidermal microenvironment. PMID:21933242

  15. Kita Driven Expression of Oncogenic HRAS Leads to Early Onset and Highly Penetrant Melanoma in Zebrafish

    PubMed Central

    Santoriello, Cristina; Gennaro, Elisa; Anelli, Viviana; Distel, Martin; Kelly, Amanda; Köster, Reinhard W.; Hurlstone, Adam; Mione, Marina

    2010-01-01

    Background Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed. Methodology and Principal Findings Using the combinatorial Gal4 –UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2–4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1–3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period. Conclusions and Significance This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens. PMID:21170325

  16. Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer

    PubMed Central

    Elsayed, Fadwa A; Kets, C Marleen; Ruano, Dina; van den Akker, Brendy; Mensenkamp, Arjen R; Schrumpf, Melanie; Nielsen, Maartje; Wijnen, Juul T; Tops, Carli M; Ligtenberg, Marjolijn J; Vasen, Hans FA; Hes, Frederik J; Morreau, Hans; van Wezel, Tom

    2015-01-01

    Germline variants affecting the exonuclease domains of POLE and POLD1 predispose to multiple colorectal adenomas and/or colorectal cancer (CRC). The aim of this study was to estimate the prevalence of previously described heterozygous germline variants POLE c.1270C>G, p.(Leu424Val) and POLD1 c.1433G>A, p.(Ser478Asn) in a Dutch series of unexplained familial, early onset CRC and polyposis index cases. We examined 1188 familial CRC and polyposis index patients for POLE p.(Leu424Val) and POLD1 p.(Ser478Asn) variants using competitive allele-specific PCR. In addition, protein expression of the POLE and DNA mismatch repair genes was studied by immunohistochemistry in tumours from POLE carriers. Somatic mutations were screened using semiconductor sequencing. We detected three index patients (0.25%) with a POLE p.(Leu424Val) variant. In one patient, the variant was found to be de-novo. Tumours from three patients from two families were microsatellite instable, and immunohistochemistry showed MSH6/MSH2 deficiency suggestive of Lynch syndrome. Somatic mutations but no germline MSH6 and MSH2 variants were subsequently found, and one tumour displayed a hypermutator phenotype. None of the 1188 patients carried the POLD1 p.(Ser478Asn) variant. POLE germline variant carriers are also associated with a microsatellite instable CRC. POLE DNA analysis now seems warranted in microsatellite instable CRC, especially in the absence of a causative DNA mismatch repair gene germline variant. PMID:25370038

  17. Sibling sex ratio and birth order in early-onset gender dysphoric adolescents.

    PubMed

    Schagen, Sebastian E E; Delemarre-van de Waal, Henriette A; Blanchard, Ray; Cohen-Kettenis, Peggy T

    2012-06-01

    Several sibship-related variables have been studied extensively in sexual orientation research, especially in men. Sibling sex ratio refers to the ratio of brothers to sisters in the aggregate sibships of a group of probands. Birth order refers to the probands' position (e.g., first-born, middle-born, last-born) within their sibships. Fraternal birth order refers to their position among male siblings only. Such research was extended in this study to a large group of early-onset gender dysphoric adolescents. The probands comprised 94 male-to-female and 95 female-to-male gender dysphoric adolescents. The overwhelming majority of these were homosexual or probably prehomosexual. The control group consisted of 875 boys and 914 girls from the TRAILS study. The sibling sex ratio of the gender dysphoric boys was very high (241 brothers per 100 sisters) compared with the expected ratio (106:100). The excess of brothers was more extreme among the probands' older siblings (300:100) than among their younger siblings (195:100). Between-groups comparisons showed that the gender dysphoric boys had significantly more older brothers, and significantly fewer older sisters and younger sisters, than did the control boys. In contrast, the only notable finding for the female groups was that the gender dysphoric girls had significantly fewer total siblings than did the control girls. The results for the male probands were consistent with prior speculations that a high fraternal birth order (i.e., an excess of older brothers) is found in all homosexual male groups, but an elevated sibling sex ratio (usually caused by an additional, smaller excess of younger brothers) is characteristic of gender dysphoric homosexual males. The mechanisms underlying these phenomena remain unknown. PMID:21674256

  18. Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early-onset distal myopathy.

    PubMed

    Reis, Gerald F; de la Motte, Grant; Gooding, Rebecca; Laing, Nigel G; Margeta, Marta

    2015-12-01

    Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early-onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39-year-old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co-expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth-eaten fibers and mini-cores, lack of rimmed vacuoles and rare desmin-positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the MYH7 gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis. PMID:26094647

  19. Time perception of simultaneous and sequential events in early-onset schizophrenia.

    PubMed

    de Montalembert, M; Coulon, N; Cohen, D; Bonnot, O; Tordjman, S

    2016-08-01

    Timing disorders in schizophrenia are a well-known phenomenon. However, no studies have yet assessed the role of temporal distortions in early-onset schizophrenia (EOS), despite evidence that distorted time perception may share genetic risk factors with schizophrenia and may be a useful indicator in identifying individuals at risk for schizophrenia. In the present study, we investigated the ability of 10 patients with EOS (mean age = 21.5 years, SD = 6) matched with 20 healthy control participants (mean age = 25.3 years, SD = 4.6) in order to compare the durations of two visual events, presented either sequentially or overlapping in time, along with neuropsychological assessments of attention, working memory, and executive functions. Each participant had to judge a total of 336 stimuli. We found that temporal overlap had a greater negative effect on ability to judge the duration of a pair of stimuli in EOS patients than in healthy control participants. In addition, EOS patients showed impairments in attention and executive functions. Furthermore, in EOS patients, the scores for executive and attentional functions were significantly correlated with accuracy of temporal estimation in the overlap condition (r = 0.31, p < 0.05 and r = 0.57, p < 0.05, respectively). These preliminary results suggest that impairments in neuropsychological functions participate in the deficit in time estimation observed in patients with EOS. These conclusions highlight the importance of testing time perception in patients with EOS and could contribute to the development of cognitive remediation-based therapy for these patients. PMID:27388526

  20. Higher filtration fraction in formerly early-onset preeclamptic women without comorbidity.

    PubMed

    Toering, Tsjitske J; van der Graaf, Anne Marijn; Visser, Folkert W; Groen, Henk; Faas, Marijke M; Navis, Gerjan; Lely, A Titia

    2015-04-15

    Formerly preeclamptic women have an increased risk for developing end-stage renal disease, which has been attributed to altered renal hemodynamics and abnormalities in the renin-angiotensin-aldosterone system. Whether this is due to preeclampsia itself or to comorbid conditions is unknown. Renal hemodynamics and responsiveness to ANG II during low Na(+) intake (7 days, 50 mmol Na(+)/24 h) and high Na(+) (HS) intake (7 days, 200 mmol Na(+)/24 h) were studied in 18 healthy normotensive formerly early-onset preeclamptic women (fPE women) and 18 healthy control subjects (fHP women), all selected for absence of comorbidity. At the end of each diet, renal hemodynamics and blood pressure were measured before and during graded ANG II infusion. Both HS intake and former preeclampsia increased filtration fraction (FF) without an interaction between the two. FF was highest during HS intake in fPE women [0.31 ± 0.12 vs. 0.29 ± 0.11 in fHP women, generalized estimating equation analysis (body mass index corrected), P = 0.03]. The renal response to ANG II infusion was not different between groups. In conclusion, fPE women have a higher FF compared with fHP women. As this was observed in the absence of comorbidity, preeclampsia itself might exert long-term effects on renal hemodynamics. However, we cannot exclude the presence of prepregnancy alterations in renal function, which, in itself, lead to an increased risk for preeclampsia. In experimental studies, an elevated FF has been shown to play a pathogenic role in the development of hypertension and renal damage. Future studies, however, should evaluate whether the subtle differences in renal hemodynamics after preeclampsia contribute to the increased long-term renal risk after preeclampsia. PMID:25694481

  1. Temporal-lobe morphology differs between healthy adolescents and those with early-onset of depression

    PubMed Central

    Ramezani, Mahdi; Johnsrude, Ingrid; Rasoulian, Abtin; Bosma, Rachael; Tong, Ryan; Hollenstein, Tom; Harkness, Kate; Abolmaesumi, Purang

    2014-01-01

    Major depressive disorder (MDD) has previously been linked to structural changes in several brain regions, particularly in the medial temporal lobes (Bellani, Baiano, Brambilla, 2010; Bellani, Baiano, Brambilla, 2011). This has been determined using voxel-based morphometry, segmentation algorithms, and analysis of shape deformations (Bell-McGinty et al., 2002; Bergouignan et al., 2009; Posener et al., 2003; Vasic et al., 2008; Zhao et al., 2008): these are methods in which information related to the shape and the pose (the size, and anatomical position and orientation) of structures is lost. Here, we incorporate information about shape and pose to measure structural deformation in adolescents and young adults with and without depression (as measured using the Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders criteria). As a hypothesis-generating study, a significance level of p < 0.05, uncorrected for multiple comparisons, was used, so that subtle morphological differences in brain structures between adolescent depressed individuals and control participants could be identified. We focus on changes in cortical and subcortical temporal structures, and use a multi-object statistical pose and shape model to analyze imaging data from 16 females (aged 16–21) and 3 males (aged 18) with early-onset MDD, and 25 female and 1 male normal control participants, drawn from the same age range. The hippocampus, parahippocampal gyrus, putamen, and superior, inferior and middle temporal gyri in both hemispheres of the brain were automatically segmented using the LONI Probabilistic Brain Atlas (Shattuck et al., 2008) in MNI space. Points on the surface of each structure in the atlas were extracted and warped to each participant's structural MRI. These surface points were analyzed to extract the pose and shape features. Pose differences were detected between the two groups, particularly in the left and right putamina, right hippocampus, and left

  2. Comparison between Early-Onset and Late-Onset Alzheimer's Disease Patients with Amnestic Presentation: CSF and 18F-FDG PET Study

    PubMed Central

    Chiaravalloti, Agostino; Koch, Giacomo; Toniolo, Sofia; Belli, Lorena; Lorenzo, Francesco Di; Gaudenzi, Sara; Schillaci, Orazio; Bozzali, Marco; Sancesario, Giuseppe; Martorana, Alessandro

    2016-01-01

    Background/Aims To investigate the differences in brain glucose consumption between patients with early onset of Alzheimer's disease (EOAD, aged ≤65 years) and patients with late onset of Alzheimer's disease (LOAD, aged >65 years). Methods Differences in brain glucose consumption between the groups have been evaluated by means of Statistical Parametric Mapping version 8, with the use of age, sex, Mini-Mental State Examination and cerebrospinal fluid values of AΒ1-42, phosphorylated Tau and total Tau as covariates in the comparison between EOAD and LOAD. Results As compared to LOAD, EOAD patients showed a significant decrease in glucose consumption in a wide portion of the left parietal lobe (BA7, BA31 and BA40). No significant differences were obtained when subtracting the EOAD from the LOAD group. Conclusions The results of our study show that patients with EOAD show a different metabolic pattern as compared to those with LOAD that mainly involves the left parietal lobe. PMID:27195000

  3. A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS

    PubMed Central

    Vitaliti, Giovanna; Trifiletti, Rosario R.; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

    2014-01-01

    Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, “overnight” onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS. PMID:24891915

  4. A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS.

    PubMed

    Vitaliti, Giovanna; Trifiletti, Rosario R; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

    2014-01-01

    Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS. PMID:24891915

  5. The prodromal phase of obesity-related chronic kidney disease: early alterations in cardiovascular and renal function in obese children and adolescents.

    PubMed

    Doyon, Anke; Schaefer, Franz

    2013-11-01

    Childhood overweight and obesity is a relevant health condition with multi-organ involvement. Obesity shows significant tracking into adult life and is associated with an increased risk of serious adverse health outcomes both during childhood and later adulthood. The classical sequelae of obesity such as hypertension, metabolic syndrome and inflammation do develop at a paediatric age. Cardiovascular consequences, such as increased carotid intima-media thickness, and left ventricular hypertrophy, as well as functional alterations of the heart and arteries, are commonly traceable at an early age. Renal involvement can occur at a young age and is associated with a high probability of progressive chronic kidney disease. There is solid evidence suggesting that consequent treatment including both lifestyle changes and pharmacological therapy can reduce cardiovascular, metabolic and renal risks in obese children and adolescents. PMID:23975744

  6. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa

    PubMed Central

    Seale, Anna C; Mwaniki, Michael; Newton, Charles R J C; Berkley, James A

    2010-01-01

    Maternal and child health are high priorities for international development. Through a Review of published work, we show substantial gaps in current knowledge on incidence (cases per live births), aetiology, and risk factors for both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa. Although existing published data suggest that sepsis causes about 10% of all maternal deaths and 26% of neonatal deaths, these are likely to be considerable underestimates because of methodological limitations. Successful intervention strategies in resource-rich settings and early studies in sub-Saharan Africa suggest that the burden of maternal and early onset neonatal bacterial sepsis could be reduced through simple interventions, including antiseptic and antibiotic treatment. An effective way to expedite evidence to guide interventions and determine the incidence, aetiology, and risk factors for sepsis in sub-Saharan Africa would be through a multiarmed factorial intervention trial aimed at reducing both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa. PMID:19555902

  7. Differential Modification of Cortical and Thalamic Projections to Cat Primary Auditory Cortex Following Early- and Late-Onset Deafness.

    PubMed

    Chabot, Nicole; Butler, Blake E; Lomber, Stephen G

    2015-10-15

    Following sensory deprivation, primary somatosensory and visual cortices undergo crossmodal plasticity, which subserves the remaining modalities. However, controversy remains regarding the neuroplastic potential of primary auditory cortex (A1). To examine this, we identified cortical and thalamic projections to A1 in hearing cats and those with early- and late-onset deafness. Following early deafness, inputs from second auditory cortex (A2) are amplified, whereas the number originating in the dorsal zone (DZ) decreases. In addition, inputs from the dorsal medial geniculate nucleus (dMGN) increase, whereas those from the ventral division (vMGN) are reduced. In late-deaf cats, projections from the anterior auditory field (AAF) are amplified, whereas those from the DZ decrease. Additionally, in a subset of early- and late-deaf cats, area 17 and the lateral posterior nucleus (LP) of the visual thalamus project concurrently to A1. These results demonstrate that patterns of projections to A1 are modified following deafness, with statistically significant changes occurring within the auditory thalamus and some cortical areas. Moreover, we provide anatomical evidence for small-scale crossmodal changes in projections to A1 that differ between early- and late-onset deaf animals, suggesting that potential crossmodal activation of primary auditory cortex differs depending on the age of deafness onset. PMID:25879955

  8. Obesity and early complications following reduction mammaplasty: an analysis of 4545 patients from the 2005-2011 NSQIP datasets.

    PubMed

    Nelson, Jonas A; Fischer, John P; Chung, Cyndi U; West, Ari; Tuggle, Charles T; Serletti, Joseph M; Kovach, Stephen J

    2014-10-01

    Reduction mammoplasty is a proven treatment for symptomatic macromastia, but the association between obesity and early postoperative complications is unclear. The purpose of this study was to perform a population level analysis in an effort to determine the impact of obesity on early complications after reduction mammaplasty. This study examined the 2005-2011 NSQIP datasets and identified all patients who underwent reduction mammoplasty. Patients were then categorised according to the World Health Organisation obesity classification. Demographics, comorbidities, and perioperative risk factors were identified among the NSQIP variables. Data was then analysed for surgical complications, wound complications, and medical complications within 30 days of surgery. In total, 4545 patients were identified; 54.4% of patients were obese (BMI > 30 kg/m(2)), of which 1308 (28.8%) were Class I (BMI = 30-34.9 kg/m(2)), 686 (15.1%) were Class II (BMI = 35-39.9 kg/m(2)), and 439 (9.7%) were Class III (BMI > 40 kg/m(2)). The presence of comorbid conditions increased across obesity classifications (p < 0.001), with significant differences noted in all cohort comparisons except when comparing class I to class II (p = 0.12). Early complications were rare (6.1%), with superficial skin and soft tissue infections accounting for 45.8% of complications. Examining any complication, a significant increase was noted with increasing obesity class (p < 0.001). This was further isolated when comparing morbidly obese patients to non-obese (p < 0.001), class I (p < 0.001), and class II (p = 0.01) patients. This population-wide analysis - the largest and most heterogeneous study to date - has demonstrated that increasing obesity class is associated with increased early postoperative complications. Morbidly obese patients are at the highest risk, with complications occurring in nearly 12% of this cohort. PMID:24506446

  9. PLA2G6 Mutations Related to Distinct Phenotypes: A New Case with Early-onset Parkinsonism

    PubMed Central

    Giri, Anamika; Guven, Gamze; Hanagasi, Hasmet; Hauser, Ann-Kathrin; Erginul-Unaltuna, Nihan; Bilgic, Basar; Gurvit, Hakan; Heutink, Peter; Gasser, Thomas; Lohmann, Ebba; Simón-Sánchez, Javier

    2016-01-01

    Background PLA2G6-associated neurodegeneration (PLAN) is a recessive neurodegenerative disorder characterized by three distinct phenotypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and PLA2G6-related dystonia–parkinsonism. Methods A consanguineous index case from Turkey was diagnosed with early-onset Parkinsonism at the Istanbul Faculty of Medicine. She and her unaffected brother were subjected to whole-genome sequencing. Results In this report, we describe a 33-year-old index case with parental consanguinity and early-onset Parkinsonism. Whole-genome sequencing of this individual revealed that a homozygous p.R747W mutation in PLA2G6 segregates with the disease in this family Discussion This result supports the importance of prioritizing this gene in mutational analysis of autosomal recessive Parkinsonism, and confirms the clinical heterogeneity of PLAN. PMID:27127721

  10. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  11. Lack of mutations in DJ-1 in a cohort of Taiwanese ethnic Chinese with early-onset parkinsonism.

    PubMed

    Lockhart, Paul J; Bounds, Rebecca; Hulihan, Mary; Kachergus, Jennifer; Lincoln, Sarah; Lin, Chin-Hsien; Wu, Ruey-Meei; Farrer, Matthew J

    2004-09-01

    Recently, mutations in DJ-1 (PARK7) were described as a novel cause of early-onset parkinsonism. We analysed the DJ-1 gene in a cohort of patients originating from Taiwan with early-onset Parkinson's disease; 41 subjects were clinically and genetically examined. These patients were evaluated previously for the presence of parkin mutations (PARK2) and were found to be negative. The entire DJ-1 open-reading frame was amplified from cDNA, analysed for size alterations indicative of mutations affecting splice motifs, and sequenced to identify coding variants. In addition, we developed quantitative polymerase chain reaction assays to examine the genomic copy number of DJ-1 exons. No potential splice site mutations, coding sequence alterations, or exon deletion/duplications were detected. Our results and previous studies suggest that alterations to DJ-1 are not a common cause of early-onset Parkinson's disease and other causes, genetic and/or environmental, remain to be identified. PMID:15372597

  12. The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women

    PubMed Central

    Al-Qasem, Abeer; Toulimat, Mohamed; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Aboussekhra, Abdelilah

    2012-01-01

    Breast cancer has a major impact on the health of women worldwide. In the Kingdom of Saudi Arabia (KSA), breast cancer incidence is on the increase and is characterized by early onset and aggressiveness. Owing to the importance of the TP53 gene in breast carcinogenesis, we analyzed the possible link between TP53 single nucleotide polymorphisms (SNPs) and the risk of breast cancer in Saudi women by direct sequencing of the TP53 gene exon 4 from 100 breast cancer tissues. The proportion of the polymorphic forms of SNP72 in the Saudi breast cancer patients were: Arg/Arg (RR), 39%; Pro/Pro (PP), 36%; and Arg/Pro (RP), 25%. The frequencies of these forms in disease-free Saudi women were 7.59, 22.22 and 60.19%, respectively. This indicates that the RR form of the codon 72 polymorphism is a potential risk factor, whereas the RP form is a protection factor against breast cancer among Saudi women (p=0.0001). Moreover, the results have shown that the p53 R72P SNP is significantly associated with the early onset of breast cancer in the Saudi population (p=0.0138). However, the codon 47 polymorphism appears to have no role in this disease among Saudi women. These results indicate that the TP53 gene could play a major role in breast carcinogenesis and the early onset of the disease among Saudi women. PMID:22741010

  13. The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women.

    PubMed

    Al-Qasem, Abeer; Toulimat, Mohamed; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Aboussekhra, Abdelilah

    2012-04-01

    Breast cancer has a major impact on the health of women worldwide. In the Kingdom of Saudi Arabia (KSA), breast cancer incidence is on the increase and is characterized by early onset and aggressiveness. Owing to the importance of the TP53 gene in breast carcinogenesis, we analyzed the possible link between TP53 single nucleotide polymorphisms (SNPs) and the risk of breast cancer in Saudi women by direct sequencing of the TP53 gene exon 4 from 100 breast cancer tissues. The proportion of the polymorphic forms of SNP72 in the Saudi breast cancer patients were: Arg/Arg (RR), 39%; Pro/Pro (PP), 36%; and Arg/Pro (RP), 25%. The frequencies of these forms in disease-free Saudi women were 7.59, 22.22 and 60.19%, respectively. This indicates that the RR form of the codon 72 polymorphism is a potential risk factor, whereas the RP form is a protection factor against breast cancer among Saudi women (p=0.0001). Moreover, the results have shown that the p53 R72P SNP is significantly associated with the early onset of breast cancer in the Saudi population (p=0.0138). However, the codon 47 polymorphism appears to have no role in this disease among Saudi women. These results indicate that the TP53 gene could play a major role in breast carcinogenesis and the early onset of the disease among Saudi women. PMID:22741010

  14. Early onset psychopathology and the risk for teenage pregnancy among clinically referred girls.

    PubMed

    Kovacs, M; Krol, R S; Voti, L

    1994-01-01

    An existing longitudinal data set was used to investigate the hypothesis that a depressive disorder in childhood increases the risk of an adolescent pregnancy. Depression is characterized by low self-esteem, lowered concern about one's personal welfare, passivity, and impaired motivation--all of which may prevent teenage girls from taking steps to protect themselves from pregnancy. The 83 subjects had been referred to a child psychiatric clinic (86%) or a general medical facility (12%) in Pittsburgh, Pennsylvania, between the ages of 8-13 years (average age at intake, 11.5 years). They underwent 4 clinical assessments in the first year of study participation and 2 assessments in each subsequent year. 65 girls experienced 1 or more DSM-III-R defined depressive episodes during the study period; the rest, who served as psychopathologic controls, had conduct disorders. 25 of the 83 subjects (30%, compared to the national average of 24%) had documented pregnancies by the age of 18 years. 28% of the pregnant teens had a history of early onset depression compared with 66% of their nonpregnant counterparts. On the other hand, 76% of the pregnant teens had been diagnosed with a conduct disorder by the age of 18 compared with 24% of the nonpregnant girls. Preliminary analysis further indicated that teenage pregnancy was associated with having been born out of wedlock or to a mother aged 18 years or younger; living in an intact family at time of study enrollment and socioeconomic status were not significant correlates. In the multivariate analysis, however, only two factors retained significance: a conduct disorder diagnosis in childhood (mean time to first pregnancy was 17.3 years compared to 18.7 years among remaining subjects) and race (Blacks tended to become pregnant by 17.4 years compared to an average of 18.7 years for Whites). No significant interaction was detected between a conduct disorder and race. These findings suggest that educational interventions aimed at

  15. Molecular Genetics of FAM161A in North American Patients with Early-Onset Retinitis Pigmentosa

    PubMed Central

    Harper, Shyana; Weigel-DiFranco, Carol

    2014-01-01

    Retinitis pigmentosa (RP) is a hereditary disease that leads to the progressive degeneration of retinal photoreceptor cells and to blindness. It is caused by mutations in several distinct genes, including the ciliary gene FAM161A, which is associated with a recessive form of this disorder. Recent investigations have revealed that defects in FAM161A represent a rather prevalent cause of hereditary blindness in Israel and the Palestinian territories, whereas they seem to be rarely present within patients from Germany. Genetic or clinical data are currently not available for other countries. In this work, we screened a cohort of patients with recessive RP from North America to determine the frequency of FAM161A mutations in this ethnically-mixed population and to assess the phenotype of positive cases. Out of 273 unrelated patients, only 3 subjects had defects in FAM161A. A fourth positive patient, the sister of one of these index cases, was also identified following pedigree analysis. They were all homozygous for the p.T452Sfx3 mutation, which was previously reported as a founder DNA variant in the Israeli and Palestinian populations. Analysis of cultured lymphoblasts from patients revealed that mutant FAM161A transcripts were actively degraded by nonsense-mediated mRNA decay. Electroretinographic testing showed 30 Hz cone flicker responses in the range of 0.10 to 0.60 microvolts in all cases at their first visit (age 12 to 23) (lower norm  =  50 μV) and of 0.06 to 0.32 microvolts at their most recent examination (age 27 to 43), revealing an early-onset of this progressive disease. Our data indicate that mutations in FAM161A are responsible for 1% of recessive RP cases in North America, similar to the prevalence detected in Germany and unlike the data from Israel and the Palestinian territories. We also show that, at the molecular level, the disease is likely caused by FAM161A protein deficiency. PMID:24651477

  16. “Greenlight Study”: A Controlled Trial of Low-Literacy, Early Childhood Obesity Prevention

    PubMed Central

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

    2014-01-01

    Children who become overweight by age 2 years have significantly greater risks of long-term health problems, and children in low-income communities, where rates of low adult literacy are highest, 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. At 4 primary-care pediatric residency training sites across the US, 865 infant-parent dyads were enrolled at the 2-month well-child checkup and are being followed through the 24-month well-child checkup. Two sites were randomly assigned to the intervention, and the other sites were assigned to an attention-control arm, implementing the American Academy of Pediatrics' The Injury Prevention Program. The intervention consists of an interactive educational toolkit, including low-literacy materials designed for use during well-child visits, and a clinician-centered curriculum for providing low-literacy guidance on obesity prevention. The study is powered to detect a 10% difference in the number of children overweight (BMI > 85%) at 24 months. Other outcome measures include observed physician–parent communication, as well as parent-reported information on child dietary intake, physical activity, and injury-prevention behaviors. The study is designed to inform evidence-based standards for early childhood obesity prevention, and more generally to inform optimal approaches for low-literacy messages and health literacy training in primary preventive care. This article describes the conceptual model, study design, intervention content, and baseline characteristics of the study population. PMID:24819570

  17. The psychopathological and psychosocial outcome of early-onset schizophrenia: Preliminary data of a 13-year follow-up

    PubMed Central

    Reichert, Andreas; Kreiker, Susanne; Mehler-Wex, Claudia; Warnke, Andreas

    2008-01-01

    Background Relatively little is known about the long-term psychopathological and psychosocial outcome of early-onset schizophrenia. The existing literature describes more severe courses of illness in these patients compared with adult-onset schizophrenia. This article reports preliminary data of a study exploring the outcome of early-onset schizophrenia 13.4 years (mean) after first admission. Predictors for interindividual outcomes were investigated. Methods We retrospectively assessed 27 former patients (mean age at first admission 15.5 years, SD = 2.0) that were consecutively admitted to the Department of Child and Adolescent Psychiatry at the University of Wuerzburg between 1990 and 2000. A multidimensional approach was chosen to assess the outcome consisting of a mail survey including different questions about psychopathological symptoms, psychosocial parameters, and standardized self-reports (ESI and ADS). Results Concerning the psychopathological outcome, 22.2% reported having acute schizophrenic symptoms. Almost one third (30.8%) described symptoms of depression and 37.0% reported having tried to commit suicide or seriously thought about it. 77.8% of the former patients were still in outpatient treatment. Compared to the general population, the number of patients without a school graduation was relatively high (18.5%). Almost half of participants still live with their parents (48.1%) or in assisted or semi-assisted living conditions (33.3%). Only 18.5% were working in the open market. Conclusion Schizophrenia with an early onset has an unfavourable prognosis. Our retrospective study of the psychopathological and psychosocial outcome concludes with a generally poor rating. PMID:18304312

  18. The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction

    PubMed Central

    Kim, Ji Min; Joung, Kyong Hye; Lee, Ju Hee; You, Bo Ram; Choi, Min Jeong; Ryu, Min Jeong; Ko, Young Bok; Lee, Min A.; Lee, Junguee; Ku, Bon Jeong; Shong, Minho; Lee, Ki Hwan; Kim, Hyun Jin

    2016-01-01

    The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance have been explored in both animal and human studies. However, our current understanding of obesity-associated insulin resistance relies on studies of artificial metabolic extremes. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in human patients with modest obesity and early metabolic dysfunction. We obtained omental adipose tissue and fasting blood samples from 51 females undergoing gynecologic surgery. We investigated serum concentrations of proinflammatory cytokines and adipokines as well as the mRNA expression of proinflammatory and macrophage phenotype markers in visceral adipose tissue using ELISA and quantitative RT-PCR. We measured adipose tissue inflammation and macrophage infiltration using immunohistochemical analysis. Serum levels of adiponectin and leptin were significantly correlated with HOMA-IR and body mass index. The levels of expression of MCP-1 and TNF-α in visceral adipose tissue were also higher in the obese group (body mass index ≥ 25). The expression of mRNA MCP-1 in visceral adipose tissue was positively correlated with body mass index (r = 0.428, p = 0.037) but not with HOMA-IR, whereas TNF-α in visceral adipose tissue was correlated with HOMA-IR (r = 0.462, p = 0.035) but not with body mass index. There was no obvious change in macrophage phenotype or macrophage infiltration in patients with modest obesity or early metabolic dysfunction. Expression of mRNA CD163/CD68 was significantly related to mitochondrial-associated genes and serum inflammatory cytokine levels of resistin and leptin. These results suggest that changes in the production of inflammatory biomolecules precede increased immune cell infiltration and induction of a macrophage phenotype switch in visceral adipose tissue. Furthermore, serum resistin and leptin have specific

  19. Early pharmacological inhibition of angiotensin-I converting enzyme activity induces obesity in adulthood

    PubMed Central

    de Picoli Souza, Kely; da Silva, Elton D.; Batista, Elice C.; Reis, Felipe C. G.; Silva, Sylvia M. A.; Castro, Charlles H. M.; Luz, Jaqueline; Pesquero, Jorge L.; dos Santos, Edson L.; Pesquero, João B.

    2015-01-01

    We have investigated early programming of body mass in order to understand the multifactorial etiology of obesity. Considering that the renin-angiotensin system (RAS) is expressed and functional in the white adipose tissue (WAT) and modulates its development, we reasoned whether early transitory inhibition of angiotensin-I converting enzyme activity after birth could modify late body mass development. Therefore, newborn Wistar rats were treated with enalapril (10 mg/kg of body mass) or saline, starting at the first day of life until the age of 16 days. Between days ninetieth and hundred and eightieth, a group of these animals received high fat diet (HFD). Molecular, biochemical, histological, and physiological data were collected. Enalapril treated animals presented hyperphagia, overweight, and increased serum level of triglycerides, total cholesterol and leptin, in adult life. Body composition analyses revealed higher fat mass with increased adipocyte size in these animals. Molecular analyses revealed that enalapril treatment increases neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) gene expression in hypothalamus, fatty acid synthase (FAS), and hormone-sensitive lipase (HSL) gene expression in retroperitoneal WAT, and decreases peroxixome proliferators-activated receptor (PPAR)γ, PPARα, uncoupling protein (UCP)2, and UCP3 gene expression in WAT. The results of the current study indicate that enalapril administration during early postnatal development increases body mass, adiposity and serum lipids in adulthood associated with enhanced food intake and decreased metabolic activity in WAT, predisposing to obesity in adulthood. PMID:25926796

  20. [Obesity and cardiovascular risk in children].

    PubMed

    Shashaj, Blegina; Graziani, Maria Pia; Tozzi, Alberto Eugenio; Manco, Melania

    2014-12-01

    Prevalence of overweight and obesity in childhood has substantially increased worldwide in recent decades with children becoming obese at progressively younger ages. Obesity in children carries a wide range of serious complications, and contributes to an increased prevalence of cardiovascular risk factors such as hypertension, hypertrygliceridema, low high-density lipoprotein cholesterol (HDL), impaired glucose metabolism and early atherosclerotic changes not only in adulthood but since in very early pediatric age. In the ORIGIN study (Outcome Reduction with an Initial Glargine Intervention), cardiometabolic risk factors including fatty liver were already detectable in preschoolers at the onset of overweight/obesity despite short-term exposure to excess weight and fairly reduced insulin sensitivity. These facts together with the evidence that early cardiometabolic impairment reverts with lifestyle intervention in pediatric age, emphasize the need to start prevention of childhood obesity and screening of cardiometabolic co-morbities at the earliest stage with multidisciplinary strategies. PMID:25533232

  1. Phoneme Manipulation Not Onset-Rime Manipulation Ability Is a Unique Predictor of Early Reading

    ERIC Educational Resources Information Center

    Savage, Robert; Carless, Sue

    2005-01-01

    Background: Phonological awareness is known to be an excellent predictor of later reading acquisition. It remains unclear, however, whether phoneme manipulation alone best explains this association or whether an additional direct contribution of onset-rime awareness is predictive. This issue is explored here. Method: A longitudinal study is…

  2. Early onset tension pneumocephalus following ventriculoperitoneal shunt insertion for normal pressure hydrocephalus: a case report.

    PubMed

    Barada, Wissam; Najjar, Marwan; Beydoun, Ahmad

    2009-04-01

    The occurrence of tension pneumocephalus following ventriculoperitoneal (v.p.) shunt insertion is extremely rare, and is usually of delayed onset. We report a patient who developed an acute subdural tension pneumocephalus within 1 day following placement of a v.p. shunt for normal pressure hydrocephalus as a complication from shunt surgery. PMID:19185417

  3. Female Juvenile Offenders: Defining an Early-Onset Pathway for Delinquency

    ERIC Educational Resources Information Center

    Leve, Leslie D.; Chamberlain, Patricia

    2004-01-01

    We examined whether childhood factors predict age of first arrest in adolescent girls referred for placement and treatment for serious delinquency problems (N = 62). Measures included child characteristics (i.e., age of menstrual onset, childhood ADHD, and IQ), family environmental factors (i.e., severe punishment, parental transitions, and sexual…

  4. Phenotypic profile of early-onset familial Alzheimer's disease caused by presenilin-1 E280A mutation.

    PubMed

    Sepulveda-Falla, Diego; Glatzel, Markus; Lopera, Francisco

    2012-01-01

    Presenilin 1 (PS1) mutations are the most common cause of early-onset familial Alzheimer's disease (EOFAD). They show a common phenotypic profile characterized by early age of onset, severe dementia and distinct neurodegeneration. The largest population of EOFAD carries the E280A mutation in PS1 and resides in Antioquia, Colombia, currently comprising around 5,000 individuals. Carriers start showing memory impairment in the third decade of life, followed by progressive impairment of language and other cognitive processes. They reach mild cognitive impairment around 45 and dementia around 50 years of age. There is some phenotypic variability among the carriers of this single PS1 mutation. Some patients present with epilepsy, verbal impairment, and cerebellar ataxia. Neuropathologically, PS1 E280A cases show pronounced brain atrophy, severe amyloid-β pathology, distinct hyperphosphorylated tau-related pathology, and cerebellar damage. The earliest event identified by functional magnetic imaging resonance is hyperactivation within the right anterior hippocampus around 33 years of age. This well-studied population with a clear pre-clinical profile and wide phenotypic variability in age of onset and clinical presentation is ideally suited for clinical trials and to study molecular mechanisms of Alzheimer's disease. PMID:22766738

  5. Loss of functional connectivity is greater outside the default mode network in nonfamilial early-onset Alzheimer's disease variants.

    PubMed

    Lehmann, Manja; Madison, Cindee; Ghosh, Pia M; Miller, Zachary A; Greicius, Michael D; Kramer, Joel H; Coppola, Giovanni; Miller, Bruce L; Jagust, William J; Gorno-Tempini, Maria L; Seeley, William W; Rabinovici, Gil D

    2015-10-01

    The common and specific involvement of brain networks in clinical variants of Alzheimer's disease (AD) is not well understood. We performed task-free ("resting-state") functional imaging in 60 nonfamilial AD patients, including 20 early-onset AD (age at onset <65 years, amnestic/dysexecutive deficits), 24 logopenic aphasia (language deficits), and 16 posterior cortical atrophy patients (visual deficits), as well as 60 healthy controls. Seed-based connectivity analyses were conducted to assess differences between groups in 3 default mode network (DMN) components (anterior, posterior, and ventral) and 4 additional non-DMN networks: left and right executive-control, language, and higher visual networks. Significant decreases in connectivity were found across AD variants compared with controls in the non-DMN networks. Within the DMN components, patients showed higher connectivity in the anterior DMN, in particular in logopenic aphasia. No significant differences were found for the posterior and ventral DMN. Our findings suggest that loss of functional connectivity is greatest in networks outside the DMN in early-onset and nonamnestic AD variants and may thus be a better biomarker in these patients. PMID:26242705

  6. Modernization and the onset of overweight and obesity in Bougainville and Solomon Islands children: cross-sectional and longitudinal comparisons between 1966 and 1986.

    PubMed

    Weitz, Charles A; Friedlaender, Françoise R; Van Horn, Andrew; Friedlaender, Jonathan S

    2012-11-01

    This set of cross-sectional and longitudinal data from children and young adults in certain Bougainville and Solomon Islands populations undergoing rapid modernization during the period 1966-1986 reveals very different responses to essentially the same stimuli-the introduction and widespread availability of western dietary items and reductions in habitual activity. Our analyses of over 2,000 children and young adults first measured in 1966-1972, with follow-up surveys in 1968-1970 and 1985-1986, show changes in overweight/obesity in these communities have their onset around puberty, and are not related to differences in childhood growth stunting. The prevalence of overweight and obesity increased substantially during the period of this study among young adults, particularly women, and in groups with more Polynesian affinities, where the frequency of overweight (BMI ≥ 25) tripled over this 20-year interval. However, the BMI of the more Papuan groups on Bougainville remained remarkably stable, even though they were close to the epicenter of modernization during this period, the Bougainville Copper Mine. PMID:23042600

  7. Early child care and obesity at 12 months of age in the Danish National Birth Cohort

    PubMed Central

    Neelon, Sara E Benjamin; Andersen, Camilla Schou; Morgen, Camilla Schmidt; Kamper-Jørgensen, Mads; Oken, Emily; Gillman, Matthew W; Sørensen, Thorkild IA

    2014-01-01

    Background/Objectives Evidence suggests that the child care environment may be more obesogenic than the family home, and previous studies have found that child care use may be associated with obesity in children. Few studies, however, have focused on child care during infancy, which may be an especially vulnerable period. This study examined child care use in infancy and weight status at 12 months of age in a country where paid maternity leave is common and early child care is not as prevalent as in other developed countries. Subjects/Methods We studied 27821 children born to mothers participating in the Danish National Birth Cohort (DNBC), a longitudinal study of pregnant women enrolled between 1997 and 2002, who were also included in the Childcare Database, a national record of child care use in Denmark. The exposure was days in child care from birth to 12 months. The outcomes were sex-specific body mass index (BMI) z-score and overweight/obesity (BMI ≥85th percentile based on the World Health Organization classification) at 12 months. We conducted multivariable linear and logistic regression analyses examining child care use and weight outcomes. Results A total of 17721 (63.7%) children attended child care during their first year of life. After adjustment for potential confounders, a 30-day increment of child care was associated with a modestly higher BMI z-score at 12 months (0.03 units; 95% CI: 0.01, 0.05; p=0.003). Similarly, child care use was associated with increased odds of being overweight/obese at 12 months of age (OR 1.05; 95% CI: 1.01, 1.10; p=0.047). Conclusions Child care in the first year of life was associated with slightly higher weight at 12 months, suggesting that child care settings may be important targets for obesity prevention in infancy. PMID:25233894

  8. Are early onset aging conditions correlated to daily activity functions in youth and adults with Down syndrome?

    PubMed

    Lin, Jin-Ding; Lin, Lan-Ping; Hsu, Shang-Wei; Chen, Wen-Xiu; Lin, Fu-Gong; Wu, Jia-Ling; Chu, Cordia

    2014-11-13

    This study aims to answer the research question of "Are early onset aging conditions correlated to daily activity functions in youth and adults with Down syndrome (DS)?" A cross-sectional survey was employed to recruit 216 individuals with DS over 15 years of age in the analyses. A structured questionnaire included demographic data, brief self-reported aging conditions, Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) and activity of daily living (ADL) scales were completed by the primary caregivers who were well-suited for providing information on the functioning conditions of the DS individuals. Results showed that the most five frequent aging conditions (sometimes, usually and always) included frailty (20.2%), vision problem (15.8%), loss of language ability (15.3%), sleep problem (14.9%) and memory impairment (14.5%). Other onset aging conditions included more chronic diseases (13.9%), hearing loss (13%), chewing ability and tooth loss (12.5%), incontinence (11.1%), depressive syndrome (7.7%), falls and gait disorder (7.2%), loss of taste and smell (7.2%). The data also showed scores of DSQIID, onset aging conditions and ADL has significant relationships each other in Pearson's correlation tests. Finally, multiple linear regression analyses indicated onset aging conditions (β=-0.735, p<0.001) can significantly predicted the variation in ADL scores after adjusting other factors (R(2)=0.381). This study suggests that the authority should initiate early intervention programs aim to improve healthy aging and ADL functions for people with DS. PMID:25462513

  9. Prediction of early-onset atrial tachyarrhythmia after successful trans-catheter device closure of atrial septal defect.

    PubMed

    Park, Kyoung-Min; Hwang, Jin Kyung; Chun, Kwang Jin; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Seung Woo; Kang, I-Seok; Song, Jinyoung; Huh, June

    2016-08-01

    Atrial tachyarrhythmia is a well-known long-term complication of atrial septal defect (ASD) in adults, even after successful trans-catheter closure. However, the risk factors for early-onset atrial tachyarrhythmia after trans-catheter closure remain unclear. This retrospective study enrolled adults with secundum ASD undergoing trans-catheter closure from January 2000 to March 2014. We analyzed the clinical characteristics of patients and assessed risk factors for new-onset atrial tachyarrhythmia defined as a composite of atrial fibrillation or flutter (AF/AFL) after ASD closure. We enrolled a total of 427 patients; 123 were male (28.8%) and the median age was 37.0 (interquartile range [IQR]: 18.3-49.0). Nineteen (4.4%) patients had documented atrial tachyarrhythmia during the follow-up period (median: 11.4 months [IQR: 5.4-24]). Patients with transient AF/AFL during closure showed a greater incidence of new-onset atrial tachyarrhythmia during the follow-up period than patients with consistent sinus rhythm during closure (27.3% vs 3.8%; P = 0.01). Most new-onset atrial tachyarrhythmias were documented within 6 months (median: 2.6 [IQR: 1.2-4.1] months) of closure. In the multivariate analysis, the risk for new-onset atrial tachyarrhythmia was significant in patients with AF/AFL during closure (hazard ratio [HR]: 9.90, 95% confidence interval [CI]: 2.86-34.20; P < 0.001), deficient posteroinferior rim (HR: 5.48, 95% CI: 1.15-25.72; P = 0.04), and age of closure over 48 years (HR: 3.30, 95% CI: 1.30-8.38; P = 0.01). In conclusion, transient AF/AFL during trans-catheter closure of ASD as well as deficient posteroinferior rim and age of closure over 48 years may be useful for predicting early new-onset atrial tachyarrhythmia after device closure. PMID:27583905

  10. Prediction of early-onset atrial tachyarrhythmia after successful trans-catheter device closure of atrial septal defect

    PubMed Central

    Park, Kyoung-Min; Hwang, Jin Kyung; Chun, Kwang Jin; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Seung Woo; Kang, I-Seok; Song, Jinyoung; Huh, June

    2016-01-01

    Abstract Atrial tachyarrhythmia is a well-known long-term complication of atrial septal defect (ASD) in adults, even after successful trans-catheter closure. However, the risk factors for early-onset atrial tachyarrhythmia after trans-catheter closure remain unclear. This retrospective study enrolled adults with secundum ASD undergoing trans-catheter closure from January 2000 to March 2014. We analyzed the clinical characteristics of patients and assessed risk factors for new-onset atrial tachyarrhythmia defined as a composite of atrial fibrillation or flutter (AF/AFL) after ASD closure. We enrolled a total of 427 patients; 123 were male (28.8%) and the median age was 37.0 (interquartile range [IQR]: 18.3–49.0). Nineteen (4.4%) patients had documented atrial tachyarrhythmia during the follow-up period (median: 11.4 months [IQR: 5.4–24]). Patients with transient AF/AFL during closure showed a greater incidence of new-onset atrial tachyarrhythmia during the follow-up period than patients with consistent sinus rhythm during closure (27.3% vs 3.8%; P = 0.01). Most new-onset atrial tachyarrhythmias were documented within 6 months (median: 2.6 [IQR: 1.2–4.1] months) of closure. In the multivariate analysis, the risk for new-onset atrial tachyarrhythmia was significant in patients with AF/AFL during closure (hazard ratio [HR]: 9.90, 95% confidence interval [CI]: 2.86–34.20; P < 0.001), deficient posteroinferior rim (HR: 5.48, 95% CI: 1.15–25.72; P = 0.04), and age of closure over 48 years (HR: 3.30, 95% CI: 1.30–8.38; P = 0.01). In conclusion, transient AF/AFL during trans-catheter closure of ASD as well as deficient posteroinferior rim and age of closure over 48 years may be useful for predicting early new-onset atrial tachyarrhythmia after device closure. PMID:27583905

  11. Uteroplacental Insufficiency Increases Visceral Adiposity and Visceral Adipose PPARγ2 Expression in Male Rat Offspring Prior to the Onset of Obesity

    PubMed Central

    Joss-Moore, Lisa A; Wang, Yan; Campbell, Michael S; Moore, Barry; Yu, Xing; Callaway, Christopher W; McKnight, Robert A; Desai, Mina; Moyer-Mileur, Laurie J; Lane, Robert H

    2010-01-01

    Uteroplacental insufficiency (UPI) induced intrauterine growth restriction (IUGR) predisposes individuals to adult onset metabolic morbidities, including insulin resistance and cardiovascular disease. An underlying component of the development of these morbidities is adipose dysfunction; specifically a disproportionately abundant visceral adipose tissue. We hypothesize that IUGR will increase rats visceral adiposity and visceral expression of PPARγ, a key regulator of adipogenesis. To test this hypothesis we employed a well described UPI induced IUGR rat model. Subcutaneous and visceral adipose levels were measured in adolescent control and IUGR rats using MRI. Expression of PPARγ mRNA and protein, as well as PPARγ target genes, was measured in neonatal, adolescent and adult rats. UPI induced IUGR increases the relative amount of visceral adipose tissue in male, but not female, adolescent rats in conjunction with an increase in PPARγ2mRNA and protein in male visceral adipose. Importantly, these effects are seen prior to the onset of overt obesity. We conclude that increased PPARγ2 expression in VAT of IUGR males is associated with increased visceral adiposity. We speculate that the increase in visceral adiposity may contribute to the metabolic morbidities experienced by this population. PMID:20227202

  12. The effect of an early childhood obesity intervention on father’s obesity risk behaviors: the Melbourne InFANT Program

    PubMed Central

    2014-01-01

    Background To investigate the effect of an early childhood obesity prevention intervention, incorporating a parent modelling component, on fathers’ obesity risk-related behaviours. Methods Cluster randomized-controlled trial in the setting of pre-existing first-time parents groups organised by Maternal and Child Health Nurses in Victoria, Australia. Participants were 460 first-time fathers mean age = 34.2 (s.d.4.90) years. Dietary pattern scores of fathers were derived using principal component analysis, total physical activity and total television viewing time were assessed at baseline (infant aged three to four months) and after 15 months. Results No significant beneficial intervention effect was observed on fathers’ dietary pattern scores, total physical activity or total television viewing time. Conclusion Despite a strong focus on parent modelling (targeting parents own diet, physical activity and television viewing behaviours), and beneficial impact on mothers’ obesity risk behaviours, this intervention, with mothers as the point of contact, had no effect on fathers’ obesity risk-related behaviours. Based on the established links between children’s obesity risk-related behaviors and that of their fathers, a need exists for research testing the effectiveness of interventions with a stronger engagement of fathers. PMID:24524293

  13. Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity.

    PubMed

    Peña, Lucía; Meana, Clara; Astudillo, Alma M; Lordén, Gema; Valdearcos, Martín; Sato, Hiroyasu; Murakami, Makoto; Balsinde, Jesús; Balboa, María A

    2016-09-01

    Adipogenesis is the process of differentiation of immature mesenchymal stem cells into adipocytes. Elucidation of the mechanisms that regulate adipocyte differentiation is key for the development of novel therapies for the control of obesity and related comorbidities. Cytosolic group IVA phospholipase A2 (cPLA2α) is the pivotal enzyme in receptor-mediated arachidonic acid (AA) mobilization and attendant eicosanoid production. Using primary multipotent cells and cell lines predetermined to become adipocytes, we show here that cPLA2α displays a proadipogenic function that occurs very early in the adipogenic process. Interestingly, cPLA2α levels decrease during adipogenesis, but cPLA2α-deficient preadipocytes exhibit a reduced capacity to differentiate into adipocytes, which affects early and terminal adipogenic transcription factors. Additionally, the absence of the phospholipase alters proliferation and cell-cycle progression that takes place during adipogenesis. Preconditioning of preadipocytes with AA increases the adipogenic capacity of these cells. Moreover, animals deficient in cPLA2α show resistance to obesity when fed a high fat diet that parallels changes in the expression of adipogenic transcription factors of the adipose tissue. Collectively, these results show that preadipocyte cPLA2α activation is a hitherto unrecognized factor for adipogenesis in vitro and in vivo. PMID:27317983

  14. Differences between early and late onset of substance abuse: an inpatient experience.

    PubMed

    Kashani, J H; Solomon, N A; Dugan, K; Joy, F

    1987-05-01

    Of 100 consecutive patients admitted to an inpatient alcohol and drug abuse ward, approximately four fifths reported the onset of substance use before 18 years of age. The majority used both alcohol and drugs, and had a history of problems with school authorities and suicidal ideation. We found general and sex-specific patterns of substance use among both depressed and nondepressed substance users and abusers. PMID:3576265

  15. IL-10 Controls Early Microglial Phenotypes and Disease Onset in ALS Caused by Misfolded Superoxide Dismutase 1.

    PubMed

    Gravel, Mathieu; Béland, Louis-Charles; Soucy, Geneviève; Abdelhamid, Essam; Rahimian, Reza; Gravel, Claude; Kriz, Jasna

    2016-01-20

    While reactive microgliosis is a hallmark of advanced stages of amyotrophic lateral sclerosis (ALS), the role of microglial cells in events initiating and/or precipitating disease onset is largely unknown. Here we provide novel in vivo evidence of a distinct adaptive shift in functional microglial phenotypes in preclinical stages of superoxide dismutase 1 (SOD1)-mutant-mediated disease. Using a mouse model for live imaging of microglial activation crossed with SOD1(G93A) and SOD1(G37R) mouse models, we discovered that the preonset phase of SOD1-mediated disease is characterized by development of distinct anti-inflammatory profile and attenuated innate immune/TLR2 responses to lipopolysaccharide (LPS) challenge. This microglial phenotype was associated with a 16-fold overexpression of anti-inflammatory cytokine IL-10 in baseline conditions followed by a 4.5-fold increase following LPS challenge. While infusion of IL-10R blocking antibody, initiated at day 60, caused a significant increase in markers of microglial activation and precipitated clinical onset of disease, a targeted overexpression of IL-10 in microglial cells, delivered via viral vectors expressed under CD11b promoter, significantly delayed disease onset and increased survival of SOD1(G93A) mice. We propose that the high IL-10 levels in resident microglia in early ALS represent a homeostatic and compensatory "adaptive immune escape" mechanism acting as a nonneuronal determinant of clinical onset of disease. Significance statement: We report here for the first time that changing the immune profile of brain microglia may significantly affect clinical onset and duration of disease in ALS models. We discovered that in presymptomatic disease microglial cells overexpress anti-inflammatory cytokine IL-10. Given that IL-10 is major homeostatic cytokine and its production becomes deregulated with aging, this may suggest that the capacity of microglia to adequately produce IL-10 may be compromised in ALS. We show

  16. Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature.

    PubMed

    Chen, Xuqin; Gill, Deepak; Shaw, Peter; Ouvrier, Robert; Troedson, Christopher

    2016-03-01

    The purpose of this study was to determine whether transplantation of umbilical cord blood from unrelated donors before the development of symptoms could halt the progression of early juvenile onset cases of MLD in whom the disease was diagnosed based on the family history. Three asymptomatic children (aged 2 years 4 months, 2 years 8 months and 5 years 5 months, two of whom were sisters) underwent unrelated umbilical cord blood transplantation (UCBT) and two untreated symptomatic siblings were included in the study. In 14-year and 6-year follow-ups after transplantation, clinical examination, ARSA enzyme levels, neurophysiological, neuroimaging, and psychological status were assessed. All three transplanted patients remain well, and the parameters evaluated remain stable. Of the treated patients, the two sisters had ongoing evidence of demyelinating sensorimotor neuropathy on nerve conduction tests, and with a early sensorimotor neuropathy in the older sister , and the other patient has mild intellectual impairment. One of the two un-transplanted controls, 15 years after MLD diagnosis, has relentlessly progressed to full dependency with epilepsy, severe mental retardation, dystonic movements, dysphagia and recurrent respiratory problems. Six years after diagnosis, the other control has a slowly progressive course with spastic dystonic quadriplegia, epilepsy, dysphagia, continual drooling and incontinence. Our data show that, in comparison with their untreated siblings, UCBT significantly slowed the progression of the disease in the treated patients. We conclude that UCBT benefits children with pre-symptomatic early juvenile onset MLD by favourably altering the natural history of the disease. PMID:26187619

  17. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments

    PubMed Central

    Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H.; McDonald, Robert; Zhang, Liang

    2015-01-01

    Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging

  18. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline.

    PubMed

    Hardies, Katia; Cai, Yiying; Jardel, Claude; Jansen, Anna C; Cao, Mian; May, Patrick; Djémié, Tania; Hachon Le Camus, Caroline; Keymolen, Kathelijn; Deconinck, Tine; Bhambhani, Vikas; Long, Catherine; Sajan, Samin A; Helbig, Katherine L; Suls, Arvid; Balling, Rudi; Helbig, Ingo; De Jonghe, Peter; Depienne, Christel; De Camilli, Pietro; Weckhuysen, Sarah

    2016-09-01

    SYNJ1 encodes a polyphosphoinositide phosphatase, synaptojanin 1, which contains two consecutive phosphatase domains and plays a prominent role in synaptic vesicle dynamics. Autosomal recessive inherited variants in SYNJ1 have previously been associated with two different neurological diseases: a recurrent homozygous missense variant (p.Arg258Gln) that abolishes Sac1 phosphatase activity was identified in three independent families with early onset parkinsonism, whereas a homozygous nonsense variant (p.Arg136*) causing a severe decrease of mRNA transcript was found in a single patient with intractable epilepsy and tau pathology. We performed whole exome or genome sequencing in three independent sib pairs with early onset refractory seizures and progressive neurological decline, and identified novel segregating recessive SYNJ1 defects. A homozygous missense variant resulting in an amino acid substitution (p.Tyr888Cys) was found to impair, but not abolish, the dual phosphatase activity of SYNJ1, whereas three premature stop variants (homozygote p.Trp843* and compound heterozygote p.Gln647Argfs*6/p.Ser1122Thrfs*3) almost completely abolished mRNA transcript production. A genetic follow-up screening in a large cohort of 543 patients with a wide phenotypical range of epilepsies and intellectual disability revealed no additional pathogenic variants, showing that SYNJ1 deficiency is rare and probably linked to a specific phenotype. While variants leading to early onset parkinsonism selectively abolish Sac1 function, our results provide evidence that a critical reduction of the dual phosphatase activity of SYNJ1 underlies a severe disorder with neonatal refractory epilepsy and a neurodegenerative disease course. These findings further expand the clinical spectrum of synaptic dysregulation in patients with severe epilepsy, and emphasize the importance of this biological pathway in seizure pathophysiology. PMID:27435091

  19. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis

    PubMed Central

    Martin, Hilary C.; Kim, Grace E.; Pagnamenta, Alistair T.; Murakami, Yoshiko; Carvill, Gemma L.; Meyer, Esther; Copley, Richard R.; Rimmer, Andrew; Barcia, Giulia; Fleming, Matthew R.; Kronengold, Jack; Brown, Maile R.; Hudspith, Karl A.; Broxholme, John; Kanapin, Alexander; Cazier, Jean-Baptiste; Kinoshita, Taroh; Nabbout, Rima; Bentley, David; McVean, Gil; Heavin, Sinéad; Zaiwalla, Zenobia; McShane, Tony; Mefford, Heather C.; Shears, Deborah; Stewart, Helen; Kurian, Manju A.; Scheffer, Ingrid E.; Blair, Edward; Donnelly, Peter; Kaczmarek, Leonard K.; Taylor, Jenny C.

    2014-01-01

    In severe early-onset epilepsy, precise clinical and molecular genetic diagnosis is complex, as many metabolic and electro-physiological processes have been implicated in disease causation. The clinical phenotypes share many features such as complex seizure types and developmental delay. Molecular diagnosis has historically been confined to sequential testing of candidate genes known to be associated with specific sub-phenotypes, but the diagnostic yield of this approach can be low. We conducted whole-genome sequencing (WGS) on six patients with severe early-onset epilepsy who had previously been refractory to molecular diagnosis, and their parents. Four of these patients had a clinical diagnosis of Ohtahara Syndrome (OS) and two patients had severe non-syndromic early-onset epilepsy (NSEOE). In two OS cases, we found de novo non-synonymous mutations in the genes KCNQ2 and SCN2A. In a third OS case, WGS revealed paternal isodisomy for chromosome 9, leading to identification of the causal homozygous missense variant in KCNT1, which produced a substantial increase in potassium channel current. The fourth OS patient had a recessive mutation in PIGQ that led to exon skipping and defective glycophosphatidyl inositol biosynthesis. The two patients with NSEOE had likely pathogenic de novo mutations in CBL and CSNK1G1, respectively. Mutations in these genes were not found among 500 additional individuals with epilepsy. This work reveals two novel genes for OS, KCNT1 and PIGQ. It also uncovers unexpected genetic mechanisms and emphasizes the power of WGS as a clinical tool for making molecular diagnoses, particularly for highly heterogeneous disorders. PMID:24463883

  20. Early-onset glaucoma in Axenfeld-Rieger anomaly: long-term surgical results and visual outcome.

    PubMed

    Mandal, A K; Pehere, N

    2016-07-01

    PurposeTo determine the long-term surgical and visual outcomes in Indian children with early-onset glaucoma associated with Axenfeld-Rieger anomaly (ARA).MethodsThis is a retrospective analysis of 44 eyes of 24 consecutive children with early-onset glaucoma (within 3 years of age) and ARA who underwent glaucoma surgery over a 20-year period (1991-2010) by a single surgeon. Main outcome measures were pre- and postoperative intraocular pressures (IOPs), corneal clarity, visual acuities (VAs), refractive errors, success rate, time of surgical failure, and complications.ResultsThe series consisted of 38 primary combined trabeculotomy-trabeculectomy (CTT) and 6 primary trabeculectomy procedures (Schlemm's canal could not be identified in these eyes). There was a statistically significant reduction in IOP postoperatively (27.07±4.88 vs 14.88±3.62 mm Hg; P<0.0001) with a mean reduction of 45.14%. Success probability by Kaplan-Meier survival analysis was 93% till 5 years, and then 88.1%, 82.3%, 70.5%, 56.4%, and 42.3% at year 6, 7, 8, 9, and 10, respectively. Preoperative corneal edema was present in 43/44 eyes (97.72%) and cleared in 42 eyes (97.67%). There was one case each with intraoperative hyphema and with shallow chamber postoperatively and both were successfully managed successfully. There was no incidence of endophthalmitis or any other sight-threatening complication. Data on VA were available in 34 eyes (77.3%). At final follow-up visit, 15 (44.1%) eyes had best corrected VA ⩾6/18.ConclusionsPrimary CTT is safe and effective for early-onset glaucoma associated with ARA. It leads to excellent IOP control and satisfactory visual outcome. PMID:27055677

  1. Tea, coffee, and caffeine and early-onset basal cell carcinoma in a case-control study

    PubMed Central

    Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2014-01-01

    Objectives Tea and coffee are hypothesized to play a protective role in skin carcinogenesis via bioactive components, such as caffeine, yet the epidemiologic evidence is mixed. Existing data supports an inverse association with basal cell carcinoma (BCC) more so than for melanoma or squamous cell carcinoma. To understand if tea, coffee, and caffeine are related to early-onset BCC, we evaluated data from 767 non-Hispanic Whites under age 40 in a case-control study in Connecticut. Methods BCC cases (n=377) were identified through Yale's Dermatopathology database. Controls (n=390) were randomly sampled from individuals in the same database with benign skin diagnoses and frequency matched to cases on age, gender, and biopsy site. Subjects completed an in-person interview including assessment of caffeinated coffee and hot tea. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CIs) with unconditional logistic regression for regular consumption and frequency and duration measures. Results Combined regular consumption of caffeinated coffee plus hot tea was inversely associated with early-onset BCC (OR=0.60, 95% CI=0.38–0.96). Those in the highest category of caffeine from these sources had a 43% reduced risk of BCC compared to non-consumers (OR=0.57, 95% CI=0.34–0.95, p-trend=0.037). Conclusions Our findings suggest a modest protective effect for caffeinated coffee plus tea in relation to early-onset BCC that may, in part, be due to caffeine. This study adds to the growing body of literature suggesting potential health benefits from these beverages. PMID:24841641

  2. Lactobacillus rhamnosus GG Reverses Insulin Resistance but Does Not Block Its Onset in Diet-Induced Obese Mice.

    PubMed

    Park, Kun-Young; Kim, Bobae; Hyun, Chang-Kee

    2015-05-01

    Recently, Lactobacillus rhamnosus GG (LGG) was shown to exert insulin-sensitizing and adiposity-reducing effects in high-fat (HF) diet-fed mice. In the present study, we observed that the effects were correlated with the extent of dysbiosis induced by HF diet feeding before LGG administration. LGG-treated mice were protected from HF diet-induced adiposity and/ or insulin resistance when LGG was treated after, not along with, HF diet feeding. Results indicate that, under HF dietary condition, supplemented LGG reverses insulin resistance, but does not block its onset. PMID:25433553

  3. Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis

    PubMed Central

    Pehlivan, Davut; Akdemir, Zeynep Coban; Karaca, Ender; Bayram, Yavuz; Jhangiani, Shalini; Yildiz, Edibe; Muzny, Donna; Uluc, Kayihan; Gibbs, Richard A.; Elcioglu, Nursel; Lupski, James R.; Harel, Tamar

    2015-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited distal symmetric polyneuropathies associated with mutations in genes encoding components essential for normal functioning of the Schwann cell and axon. TRIM2, encoding a ligase that ubiquitinates the neurofilament light chain, was recently associated with early onset neuropathy in a single patient. We report a TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis, allowing for further delineation of the associated phenotypic spectrum. PMID:25893792

  4. Early onset steroid induced posterior subcapsular cataract in a patient with common variable immunodeficiency: case reports and review of literature.

    PubMed

    Marefat, H; Abolhassani, H; Ghareje Daghi, M; Azizi, G; Aghamohammadi, A

    2016-09-01

    Purpose. To report early onset steroid induced posterior subcapsular cataract in a case of common variable immunodeficiency. Methods. Case report. Results. Here we report a 14-yearold male of steroid induced bilateral posterior subcapsular cataract in a common variable immunodeficiency patient with damaging mutations in Glutathione reductase gene, leading to hypersensitivity of patient to glucocorticoid (GC) products. Conclusions. In order to reduce the ocular side effects of the GCs there are some advisements, including a complete history, regular examination, GC should be prescribed in minimal dosage and minimal course, and as possible GC-sparing drugs should always be considered. PMID:27608477

  5. Early Onset Neonatal Sepsis Due to Salmonella enterica Serovar 4,5,12:i:-: A Case Report with Literature Review.

    PubMed

    Vongbhavit, Kannikar; Itdhi, Salocha; Panburana, Jantana; Prommalikit, Olarn

    2015-11-01

    The authors report a case of a 36-week male infant born via spontaneous vaginal delivery who developed Salmonella sepsis at HRH Princess Maha Chakri Sirindhorn Medical Center Srinakharinwirot University, Nakhon Nayok, Thailand. He was born to a mother without identifiable risk factors. On day 3, he developed fever tachycardia, lethargy, poor feeding and diarrhea prompting a sepsis evaluation. Blood and stool cultures were positive for S. enterica serovar 4,5,12:i:-. Therefore, Salmonella infection should be considered in the differential diagnosis of early onset neonatal sepsis (EOS) particularly in endemic areas. PMID:27276847

  6. Early-onset dementia and extrapyramidal disease: clinicopathological variant of Gerstmann-Straussler-Scheinker or Alzheimer's disease?

    PubMed Central

    Hart, J; Gordon, B

    1990-01-01

    A case of progressive dementia and extrapyramidal signs beginning at age 29, with a ten year course until death, is presented. Necropsy examination showed an assortment of plaque types (including striatal plaques), neurofibrillary tangles, granulovacuolar degeneration, and depigmentation of the substantia nigra and locus ceruleus. This case had pathological features found in both Gerstmann-Straussler-Scheinker disease and in Alzheimer's disease. While somewhat similar to several other cases with features of both diseases, it differs in the presence of dystonia and striatal plaques. Although such cases may be difficult to categorize at present, they must be considered in the differential diagnosis of early onset dementia. Images PMID:2283522

  7. Non-haemolytic and non-pigmented group b streptococcus, an infrequent cause of early onset neonatal sepsis.

    PubMed

    Rodriguez-Granger, Javier; Spellerberg, Barbara; Asam, Daniela; Rosa-Fraile, Manuel

    2015-12-01

    The haemolysin of Group B streptococci (GBS), a leading cause of neonatal infections, is a key virulence factor that has been implicated in the development of invasive infection. The frequency of non-haemolytic (NH) GBS isolates is around 5% among GBS carriers. To determine if similar rates are observed among invasive strains, we evaluated the incidence of NH strains among 199 GBS strains isolated from neonatal blood cultures (first week of life). Overall, we found two (1%) NH strains. This finding suggests that the frequency of NH GBS strains causing early onset invasive neonatal infection is lower than the reported frequency of NH GBS among colonizing strains. PMID:26449711

  8. Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

    SciTech Connect

    Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M.M.; Olinga, Peter

    2014-01-15

    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 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-β1 and the fibrosis markers Hsp47, αSma and Pcol1A1 and collagen1 protein expressions were determined. The effects of the antifibrotic drugs imatinib, sorafenib and sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone, TGFβ-pathway inhibitors, were determined. After 48 h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-β1 was not changed. Hsp47, αSma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-β1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFβ-inhibitors showed marginal effects. The protein expression of collagen 1 was inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion, the increased gene expression of PDGF-B and the down-regulation of fibrosis markers by PDGF-pathway inhibitors, together with the absence of elevated TGF-β1 gene expression and the limited effect of the TGFβ-pathway inhibitors, indicated the predominance of the PDGF pathway in the early onset of fibrosis in PCLS. PCLS appear a useful model for research of the early onset of fibrosis and for testing of antifibrotic drugs acting on the PDGF pathway. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-β was increased, while TGFβ was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGFβ-pathway inhibitors had only

  9. Early Results of Recently Introduced Laparoscopic Adjustable Gastric Banding Procedure for Morbid Obesity in Croatia

    PubMed Central

    Franjic, B. D.; Glavan, E.; Bekavac-Beslin, M.

    2006-01-01

    Introduction: Morbid obesity is a growing medical problem that has become of epidemic proportions. Various dietary and pharmaceutical approaches do not obtain acceptable long-term results. Surgery, however, especially gastric restriction, represents a viable therapeutic solution. Individuals with a body mass index (BMI) >40 kg/m2 or >35 kg/m2 with at least one severe comorbidity are considered morbidly obese and generally qualify for weight-loss surgery. Laparoscopic adjustable gastric banding (LAGB) is currently the most commonly performed procedure, because it is minimally invasive, does not cause metabolic complications, is completely reversible, and is adjustable. In Croatia, the first LAGB was performed in May 2004 at Clinical Hospital “Sestre Milosrdnice.” The aim of this report is to illustrate a newly performed surgical treatment and its results for morbid obesity in Croatia. Methods: Within a 12-month period, the adjustable gastric band was implanted in 15 morbidly obese patients (female, 8; male, 7; mean age, 46.67 years; range, 26 –59 years). The so-called “pars flaccida” technique was used. Results: One operation required conversion to laparotomy due to a gastric lesion, and 1 laparoscopy operation was terminated due to massive postoperative adhesions. The average duration of surgery was 90±30 minutes. Mean length of stay was 4.9 days (range, 3–9). An average BMI at the time of surgery was 52.21 kg/m2 (range, 45.29 to 61.59; mean body weight was 155.58 kg (range, 127 to 204). Throughout 1-, 3-, 6-, 9-, and 12-month follow-ups, an average of 18.71%, 25.06%, 34.37%, 41.23%, and 47.32% of excessive weight loss (EWL) was observed. Good tolerance and a low complication rate were noted. Conclusion: LAGB resulted in good early results and a low complication rate. LAGB appears to be a quality surgical procedure for the management of morbid obesity. PMID:17575750

  10. Onset of exercise and diet program in obese women: metabolic and anorexigenic responses related to weight loss and physical capacities.

    PubMed

    Desgorces, F D; Le Page, C; Police, C; Neveux, N; Cottart, C H; Blanc, M C; Raison, J; Toussaint, J F; Noirez, P

    2015-06-01

    Perturbations of energy balance induce compensatory processes that may alter expected weight loss. In obese patients, our aim was to investigate the relationships that occurred between fasting plasma concentrations of anorexigenic peptides and metabolic parameters, appetite, physical capacity, and weight loss in the 5 first days of a program associating exercise and caloric reduction. Thirteen obese women were monitored from day 1 to day 5 with 2 exercise sessions in day 2 and day 4. We measured, in a fasted state, changes in body weight, hunger ratings, and plasma concentrations of fatty acids, triglycerides, leptin, insulin, amylin, peptide YY, and insulin-resistance index. Physical performance was assessed by a 6-min walking test. The program resulted in significantly reduced body weight (0.75±0.4 kg; p=0.001), of plasma concentrations of triglycerides, insulin, amylin, peptide YY, and the insulin-resistance index, and also increased fatty acids (p<0.05). Hunger ratings were increased (p<0.05). Program-induced changes in fatty acids, leptin, and insulin concentrations were related to physical performance (r(2)=0.45, 0.59, and 0.52; p<0.05, respectively) and to weight loss (r(2)=0.65, 0.57, 0.55; p<0.05, respectively). Five days of diet and exercise induced weight loss, improved lipid profile, and decreased insulin resistance while hunger ratin