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Sample records for early onset muscarinic

  1. 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 ...

  2. 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

  3. 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…

  4. 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

  5. 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

  6. [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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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)

  13. 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) ...

  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. 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…

  16. Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice

    PubMed Central

    Pancani, Tristano; Foster, Daniel J.; Moehle, Mark S.; Bichell, Terry Jo; Bradley, Emma; Bridges, Thomas M.; Klar, Rebecca; Poslusney, Mike; Rook, Jerri M.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Wood, Michael R.; Bowman, Aaron B.; Lindsley, Craig W.; Xiang, Zixiu; Conn, P. Jeffrey

    2015-01-01

    Mutations that lead to Huntington’s disease (HD) result in increased transmission at glutamatergic corticostriatal synapses at early presymptomatic stages that have been postulated to set the stage for pathological changes and symptoms that are observed at later ages. Based on this, pharmacological interventions that reverse excessive corticostriatal transmission may provide a novel approach for reducing early physiological changes and motor symptoms observed in HD. We report that activation of the M4 subtype of muscarinic acetylcholine receptor reduces transmission at corticostriatal synapses and that this effect is dramatically enhanced in presymptomatic YAC128 HD and BACHD relative to wild-type mice. Furthermore, chronic administration of a novel highly selective M4 positive allosteric modulator (PAM) beginning at presymptomatic ages improves motor and synaptic deficits in 5-mo-old YAC128 mice. These data raise the exciting possibility that selective M4 PAMs could provide a therapeutic strategy for the treatment of HD. PMID:26508634

  17. Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice.

    PubMed

    Pancani, Tristano; Foster, Daniel J; Moehle, Mark S; Bichell, Terry Jo; Bradley, Emma; Bridges, Thomas M; Klar, Rebecca; Poslusney, Mike; Rook, Jerri M; Daniels, J Scott; Niswender, Colleen M; Jones, Carrie K; Wood, Michael R; Bowman, Aaron B; Lindsley, Craig W; Xiang, Zixiu; Conn, P Jeffrey

    2015-11-10

    Mutations that lead to Huntington's disease (HD) result in increased transmission at glutamatergic corticostriatal synapses at early presymptomatic stages that have been postulated to set the stage for pathological changes and symptoms that are observed at later ages. Based on this, pharmacological interventions that reverse excessive corticostriatal transmission may provide a novel approach for reducing early physiological changes and motor symptoms observed in HD. We report that activation of the M4 subtype of muscarinic acetylcholine receptor reduces transmission at corticostriatal synapses and that this effect is dramatically enhanced in presymptomatic YAC128 HD and BACHD relative to wild-type mice. Furthermore, chronic administration of a novel highly selective M4 positive allosteric modulator (PAM) beginning at presymptomatic ages improves motor and synaptic deficits in 5-mo-old YAC128 mice. These data raise the exciting possibility that selective M4 PAMs could provide a therapeutic strategy for the treatment of HD. PMID:26508634

  18. 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

  19. 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

  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. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. [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

  10. 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

  11. 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

  12. 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…

  13. 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…

  14. 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…

  15. [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

  16. 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…

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.…

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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,…

  8. 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…

  9. 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

  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. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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…

  17. 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…

  18. 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…

  19. 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,…

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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…

  7. 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…

  8. 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…

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  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. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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…

  18. 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…

  19. 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

  20. 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,…

  1. [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

  2. 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…

  3. 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…

  4. 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.

  5. 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…

  6. 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.…

  7. 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

  8. 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…

  9. 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…

  10. 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),…

  11. 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…

  12. 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…

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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…

  12. 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

  13. 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

  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. 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

  17. 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

  18. 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.

  19. 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

  20. Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography.

    PubMed

    Claus, J J; Dubois, E A; Booij, J; Habraken, J; de Munck, J C; van Herk, M; Verbeeten, B; van Royen, E A

    1997-06-01

    Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer's disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [123I]4-iododexetimide in five mildly affected patients with probable Alzheimer's disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [123I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intra-observer variability was 3.6% and inter-observer results showed consistent differences in [123I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [123I]4-iododexetimide binding is reduced in patients with mild probable Alzheimer's disease in areas of temporal and temporo-parietal cortex. PMID:9169565

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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…

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  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. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  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. 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

  1. 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

  2. Muscarinic receptors in perirhinal cortex control trace conditioning.

    PubMed

    Bang, Sun Jung; Brown, Thomas H

    2009-04-01

    Trace conditioning requires that a transient representation of the conditional stimulus (CS) persists during the time interval between the CS offset and the onset of the unconditional stimulus. According to one hypothesis, this transient CS representation is supported by endogenous activity in "persistent-firing" neurons of perirhinal cortex (PR). By definition, persistent-firing neurons discharge for tens of seconds or minutes after the termination of the original spike-initiating stimulus. This continued spiking does not depend on recurrent circuit activity and can be reliably and completely blocked by muscarinic receptor antagonists. The present study evaluated the role of PR muscarinic receptors in trace fear conditioning. Before conditioning, rats received bilateral intra-PR infusions with either saline or scopolamine, a nonselective muscarinic receptor antagonist. Scopolamine infusions profoundly impaired trace conditioning but had no effect on delay conditioning or context conditioning. The results encourage a more general understanding of muscarinic receptors in PR and they motivate additional tests of the emerging theory that persistent-firing neurons support aspects of transient memory. PMID:19357262

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  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. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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