Science.gov

Sample records for early onset periodontitis

  1. Crevicular fluid level of beta-glucuronidase in relation to clinical periodontal parameters and putative periodontal pathogens in early-onset periodontitis.

    PubMed

    Albandar, J M; Kingman, A; Lamster, I B

    1998-08-01

    Analysis of beta-glucuronidase (betaG) in the gingival crevicular fluid (GCF) provides an indication of neutrophil influx into the crevicular environment. The aim of this study was to test the hypotheses that: (1) betaG is significantly elevated in individuals with early-onset periodontitis (EOP) and that betaG activity correlates with disease severity; and (2) betaG level may reflect the local bacterial challenge in the gingival crevice. The study subjects consisted of a sub-sample of individuals examined in the National Survey of Oral Health of United States Children, which was undertaken during the 1986/87 school year. A total of 249 individuals were selected based on presence or absence of clinical attachment loss at baseline. The individuals were examined a second time 6 years later and the clinical attachment loss was assessed, and subgingival plaque and GCF were collected. The subjects were classified into 3 types of EOP and a control group. BetaG activity in the GCF and the levels of 7 putative micro-organisms in the pocket were assessed. The generalized EOP group had the highest betaG activity, followed by the localized and incidental EOP groups, and the controls, respectively. There was a significant increase in betaG activity with the increase in probing depth. Also, sites with bleeding on probing had a significantly higher betaG activity than sites without bleeding. However, the effect of gingival inflammation on betaG activity was more evident in the generalized and localized EOP groups. Sites harboring high levels of one or more of the micro-organisms tended to have high betaG activity. There were moderate differences between the organisms with respect to their effect on betaG activity, but sites with high numbers of Porphyromonas gingivalis, Prevotella intermedia, or Treponema denticola also had the highest betaG activity. The present findings suggest that betaG activity in GCF from patients with EOP can be of value in the early identification of individuals at higher risk of developing EOP The findings also suggest that host mechanisms leading to higher betaG activity in EOP represent systemic responses and are only partly related to the presence of local factors at the site-level. PMID:9722267

  2. Early Onset Sepsis.

    PubMed

    Johnson, Kyrsten; Messier, Stephen

    2016-01-01

    Early onset sepsis (EOS) is a worrisome, life-threatening condition in newborns with onset during the first week of life. Evaluation can be challenging due to the dynamic nature of the condition as the infant transitions to life ex-utero. Symptoms/signs can be nonspecific, thus, a high index of suspicion is warranted for subtle changes in condition including poor feeding, respiratory distress, or decreased activity. Common risk factors include chorioamnionitis, maternal fever, group B strep (GBS) colonization and preterm delivery. Despite universal screening and intrapartum antibiotic prophylaxis (IAP), GBS remains the most frequent cause of EOS followed by Escherichia coli (E. coli). While the gold standard for diagnosis remains a positive blood culture, lab evaluation frequently involves complete blood count (CBC) with differential, c-reactive protein (CRP), and evaluation of spinal fluid if the infant is stable. Unfortunately, there is not a lab test that is rapidly diagnostic for sepsis, so treatment should be empirically started until it is clear that the infant is not infected. Treatment often includes ampicillin and gentamicin for coverage of the most frequent pathogens. There is much debate about timing of discontinuation of antibiotics. Frequently, antibiotics can be discontinued after 48 hours in well appearing, asymptomatic infants with negative blood cultures and either normal CBC analysis or normal CRP values. PMID:26882580

  3. Early onset sebaceous carcinoma

    PubMed Central

    2011-01-01

    Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C?A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients. PMID:21892948

  4. Genetics Home Reference: early-onset glaucoma

    MedlinePlus

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

  5. Serotonin in early-onset alcoholism.

    PubMed

    Virkkunen, M; Linnoila, M

    1997-01-01

    This chapter examines current, common schemes to subgroup alcoholics to arrive at relatively homogeneous groups of patients to facilitate psychobiological and molecular genetic studies. Early-onset, male-limited alcoholism is commonly associated with antisocial personality disorder or antisocial behavioral traits. It is often preceded by early-onset aggressiveness, which is followed by conduct disorder. Early-onset alcoholism among men is associated with low central serotonin turnover rate. The data concerning platelet MAO activity and serotonin uptake to platelets among early-onset alcoholics are conflicting. Recent molecular genetic and brain imaging studies on early-onset alcoholics are preliminary but appear very promising. PMID:9122495

  6. 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

  7. Salivary Antimicrobial Peptides in Early Detection of Periodontitis

    PubMed Central

    Güncü, Güliz N.; Yilmaz, Dogukan; Könönen, Eija; Gürsoy, Ulvi K.

    2015-01-01

    In the pathogenesis of periodontitis, an infection-induced inflammatory disease of the tooth-supporting tissues, there is a complex interaction between the subgingival microbiota and host tissues. A periodontal diagnostic tool for detecting the initiation and progression of the disease, monitoring the response to therapy, or measuring the degree of susceptibility to future disease progression has been of interest for a long time. The value of various enzymes, proteins, and immunoglobulins, which are abundant constituents of saliva, as potential biomarkers has been recognized and extensively investigated for periodontal diseases. Gingival defensins and cathelicidins are small cationic antimicrobial peptides that play an important role in innate immune response. However, their applicability as salivary biomarkers is still under debate. The present review focuses on proteomic biomarkers and antimicrobial peptides, in particular, to be used at early phases of periodontitis. PMID:26734583

  8. 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…

  9. Papillon-Lefèvre syndrome with homozygous nonsense mutation of cathepsin C gene presenting with late-onset periodontitis.

    PubMed

    Ragunatha, Shivanna; Ramesh, Mudalagirigowda; Anupama, Panagar; Kapoor, Meenakshi; Bhat, Meenakshi

    2015-01-01

    Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder of keratinization caused by homozygous mutations in the gene encoding lysosomal protease cathepsin C (CTSC). It is clinically characterized by transgredient palmoplantar keratoderma (PPK) and periodontitis. A 15-year-old boy presenting with PPK from the age of 6 months and late-onset periodontitis that began at the age of 12 years is described. Mutation analysis revealed a homozygous nonsense mutation (p.Y304X) in exon 7 of the CTSC gene. Late-onset periodontitis in a patient with Papillon-Lefèvre syndrome is a rare phenotypic variation. PMID:24894642

  10. Childhood Onset Schizophrenia and Early Onset Schizophrenia spectrum disorders

    PubMed Central

    Driver, David I.; Gogtay, Nitin; Rapoport, Judith L.

    2013-01-01

    Synopsis The clinical severity, impact on development, and poor prognosis of Childhood Onset Schizophrenia (COS) may represent a more homogeneous group. Positive symptoms in children are necessary for the diagnosis and hallucinations are more often multi modal. Both in healthy children, as well as in children with a variety of other psychiatric illnesses, hallucinations are not uncommon [1] and diagnosis should not be based on these alone. COS is an extraordinarily rare illness which is poorly understood but appears continuous with the adult onset disorder. Additionally, as seen in other areas of medicine, early onset populations have more prominent progressive brain changes, and genetic risk factors [2]. Diagnosing a child with schizophrenia has profound effects on the treatment course, including the potential for neglecting another disorder, as psychosis often becomes the primary focus. Since onset is almost always insidious, the “episodes” so common in later onset disorder are rarely seen. The gold standard for diagnosis remains the use of unmodified DSM criteria, based on extensive collateral information. Once a diagnosis is affirmed, aggressive medication treatment, in majority of cases with Clozapine, combined with family education and individual counseling may defer further deterioration. PMID:24012072

  11. Genetics Home Reference: early-onset primary dystonia

    MedlinePlus

    ... Conditions early-onset primary dystonia early-onset primary dystonia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Early-onset primary dystonia is a condition characterized by progressive problems with ...

  12. 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 of social and cognitive development. Social disability in the sense of an adaptation to the expectations of the social environment, as well as symptomatology during the further course of schizophrenia, show no major differences between the genders nor between the age groups. PMID:7654792

  13. Periodontitis

    MedlinePlus

    ... Walls RM, et al, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier Mosby; 2013:chap 70. Kawar N, Gajendrareddy PK, Hart T. Periodontal disease for the primary care physician. Dis Mon . 2011; ...

  14. Periodontal Disease and the Oral Microbiota in New-Onset Rheumatoid Arthritis

    PubMed Central

    Scher, Jose U.; Ubeda, Carles; Equinda, Michele; Khanin, Raya; Buischi, Yvonne; Viale, Agnes; Lipuma, Lauren; Attur, Mukundan; Pillinger, Michael H.; Weissmann, Gerald; Littman, Dan R.; Pamer, Eric G.; Bretz, Walter A.; Abramson, Steven B.

    2012-01-01

    Objective To profile the subgingival oral microbiota abundance and diversity in never-treated, new-onset rheumatoid arthritis (NORA) patients. Methods Periodontal disease (PD) status, clinical activity and sociodemographic factors were determined in patients with NORA, chronic RA (CRA) and healthy subjects. Massively parallel pyrosequencing was used to compare the composition of subgingival microbiota and establish correlations between presence/abundance of bacteria and disease phenotypes. Anti-P. gingivalis antibodies were tested to assess prior exposure. Results The more advanced forms of periodontitis are already present at disease onset in NORA patients. The subgingival microbiota of NORA is distinct from controls. In most cases, however, these differences can be attributed to PD severity and are not inherent to RA. The presence and abundance of P. gingivalis is directly associated with PD severity as well, is not unique to RA, and does not correlate with anti-citrullinated peptide antibody (ACPA) titers. Overall exposure to P. gingivalis is similar in RA and controls, observed in 78.4% and 83.3%, respectively. Anaeroglobus geminatus correlated with ACPA/RF presence. Prevotella and Leptotrichia species are the only characteristic taxa in the NORA group irrespective of PD status. Conclusions NORA patients exhibit a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The subgingival microbiota of NORA patients is similar to CRA and healthy subjects of comparable PD severity. Although colonization with P. gingivalis correlates with PD severity, overall exposure is similar among groups. The role of A. geminatus and Prevotella/Leptotrichia species in this process merits further study. PMID:22576262

  15. [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

  16. Genomic insights into early-onset obesity.

    PubMed

    Choquet, Hlne; Meyre, David

    2010-01-01

    The biological causes of childhood obesity are complex. Environmental factors, such as massive marketing campaigns for food leading to over-nutrition and snacking and the decline in physical activity, have undoubtedly contributed to the increased prevalence of overweight and obesity in children, but these cannot be considered as the only causes. Susceptibility to obesity is also determined to a great extent by genetic factors. Furthermore, molecular mechanisms involved in the regulation of gene expression, such as epigenetic mechanisms, can increase the risk of developing early-onset obesity. There is evidence that early-onset obesity is a heritable disorder, and a range of genetic factors have recently been shown to cause monogenic, syndromic and polygenic forms of obesity, in some cases interacting with environmental exposures. Modifications of the transcriptome can lead to increased adiposity, and the gut microbiome has recently been shown to be key to the genesis of obesity. These new genomic discoveries complement previous knowledge on the development of early-onset obesity and provide new perspectives for research on the complex molecular and physiological mechanisms involved in this disease. Personalized preventive strategies and genomic medicine may become possible in the near future. PMID:20587078

  17. Early onset torsion dystonia (Oppenheim's dystonia).

    PubMed

    Kamm, Christoph

    2006-01-01

    Early onset torsion dystonia (EOTD) is a rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body. A US study estimated the prevalence at approximately 1 in 30,000. The estimated prevalence in the general population of Europe seems to be lower, ranging from 1 in 330,000 to 1 in 200,000, although precise numbers are currently not available. The estimated prevalence in the Ashkenazi Jewish population is approximately five to ten times higher, due to a founder mutation. Symptoms of EOTD typically develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. Distribution and severity of symptoms vary widely between affected individuals. The majority of cases from various ethnic groups are caused by an autosomal dominantly inherited deletion of 3 bp (GAG) in the DYT1 gene on chromosome 9q34. This gene encodes a protein named torsinA, which is presumed to act as a chaperone protein associated with the endoplasmic reticulum and the nuclear envelope. It may interact with the dopamine transporter and participate in intracellular trafficking, although its precise function within the cell remains to be determined. Molecular genetic diagnostic and genetic counseling is recommended for individuals with age of onset below 26 years, and may also be considered in those with onset after 26 years having a relative with typical early onset dystonia. Treatment options include botulinum toxin injections for focal symptoms, pharmacological therapy such as anticholinergics (most commonly trihexiphenydil) for generalized dystonia and surgical approaches such as deep brain stimulation of the internal globus pallidus or intrathecal baclofen application in severe cases. All patients have normal cognitive function, and despite a high rate of generalization of dystonia, 75% of those patients are able to maintain ambulation and independence, and therefore a comparatively good quality of life, with modern treatment modalities. PMID:17129379

  18. 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

  19. 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

  20. [Computer capillaroscopy for periodontal microcirculation assessment in patients with early atherosclerotic lesions].

    PubMed

    Grudianov, A I; Krechina, E K; Mustafina, F N; Avraamova, T V

    2014-01-01

    The study of gingival microvessels was carried out by means of computer capillaroscopy in patients with moderate periodontal disease and early symptoms of atherosclerosis of extracranial portions of cephalic arteries. The results proved the decreased density of the capillar network in the marginal gingiva, as well as of linear and volumetric blood flow velocities drop in the arterial and venular portions of capillaries in patients with periodontal diseases combined with early atherosclerosis. PMID:25377575

  1. Early Onset Alzheimer's Disease and Oxidative Stress

    PubMed Central

    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

  2. The Relationship between Early Disability Onset and Education and Employment

    ERIC Educational Resources Information Center

    Loprest, Pamela; Maag, Elaine

    2003-01-01

    The early onset of disability (at birth through young adulthood) can affect a person's employment outcomes in myriad ways. In addition to the direct effect of disability on employment, early onset of disability likely affects the acquisition of education and job skills (human capital). This reduced "investment" in human capital in turn may reduce…

  3. Could Early Rheumatoid Arthritis Resolve After Periodontitis Treatment Only?

    PubMed Central

    Salemi, Simonetta; Biondo, Michela I.; Fiorentino, Chiara; Argento, Giuseppe; Paolantonio, Michele; Di Murro, Carlo; Malagnino, Vito A.; Canzoni, Marco; Diamanti, Andrea Picchianti; D’Amelio, Raffaele

    2014-01-01

    Abstract Rheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge. A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy. It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management. PMID:25501069

  4. The association of childhood adversities and early onset mental disorders with adult onset chronic physical conditions

    PubMed Central

    Scott, Kate M.; Von Korff, Michael; Angermeyer, Matthias C.; Benjet, Corina; Bruffaerts, Ronny; de Girolamo, Giovanni; Haro, Josep Maria; Lépine, Jean-Pierre; Ormel, Johan; Posada-Villa, José; Tachimori, Hisateru; Kessler, Ronald C.

    2012-01-01

    Context The physical health consequences of childhood psychosocial adversities may be as substantial as the mental health consequences but whether this is the case remains unclear because much prior research has involved unrepresentative samples and a selective focus on particular adversities or physical outcomes. The association between early onset mental disorders and subsequent poor physical health in adulthood has not been investigated. Objective To investigate whether childhood adversities and early onset mental disorders are independently associated with increased risk of a range of adult onset chronic physical conditions in culturally diverse samples spanning the full adult age range. Design Cross-sectional community surveys of adults in ten countries. Setting General population. Participants Adults (>= 18 years; n = 18,303), with diagnostic assessment and determination of age of onset of DSM-IV mental disorders; assessment of childhood familial adversities; and age of diagnosis/onset of chronic physical conditions. Main Outcome Measures Risk (hazard ratios) of adult onset (> age 20) heart disease, asthma, diabetes, arthritis, chronic spinal pain, and chronic headache as a function of specific childhood adversities and early onset (< age 21) DSM-IV depressive and anxiety disorders, with mutual adjustment. Results A history of three or more childhood adversities was independently associated with onset of all six physical conditions (hazard ratios from 1.44–2.19). Controlling for current mental disorder made little difference to these associations. Early onset mental disorders were independently associated with onset of five physical conditions (hazard ratios from 1.43–1.66). Conclusions These results are consistent with the hypothesis that childhood adversities and early onset mental disorders have independent, broad spectrum effects that increase risks of diverse chronic physical conditions in later life. They require confirmation in a prospective design. The long time course of these associations has theoretical and research implications. PMID:21810647

  5. 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…

  6. 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

  7. Early markers of pubertal onset: height and foot size.

    PubMed

    Ford, Kanti R; Khoury, Jane C; Biro, Frank M

    2009-05-01

    This longitudinal study compared the timing of foot and height velocities with pubertal onset in girls. There was no difference between ages of increased foot and height growth velocities; both occurred before onset of secondary sexual characteristics. Change in foot size may represent an early marker for transition to puberty. PMID:19380099

  8. Early Markers of Pubertal Onset: Height and Foot Size

    PubMed Central

    Ford, Kanti R.; Khoury, Jane C.; Biro, Frank M.

    2009-01-01

    This longitudinal study compared the timing of foot and height velocities with pubertal onset in girls. There was no difference between ages of increased foot and height growth velocities; both occurred before onset of secondary sexual characteristics. Change in foot size may represent an early marker for transition to puberty. PMID:19380099

  9. Early-onset colorectal cancer: A sporadic or inherited disease?

    PubMed Central

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

    2014-01-01

    Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a “sporadic” subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the “sporadic” subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this “sporadic” early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies. PMID:25253942

  10. Longitudinal Brain Changes in Early-Onset Psychosis

    PubMed Central

    Arango, Celso; Moreno, Carmen; Martínez, Salvador; Parellada, Mara; Desco, Manuel; Moreno, Dolores; Fraguas, David; Gogtay, Nitin; James, Anthony; Rapoport, Judith

    2008-01-01

    Progressive losses of cortical gray matter volumes and increases in ventricular volumes have been reported in patients with childhood-onset schizophrenia (COS) during adolescence. Longitudinal studies suggest that the rate of cortical loss seen in COS during adolescence plateaus during early adulthood. Patients with first-episode adolescent-onset schizophrenia show less marked progressive changes, although the number of studies in this population is small. Some studies show that, although less exaggerated, progressive changes are also present in nonschizophrenia early-onset psychosis. The greater loss of brain tissue seen in COS, even some years after the first episode, as compared to adolescent- or adult-onset schizophrenia may be due to variables such as sample bias (more severe, treatment refractory sample of childhood-onset patients studied), a process uniquely related to adolescent development in COS, differential brain effects of drug treatment in this population, clinical outcome, or interactions among these variables. Findings from both cross-sectional studies of first-episode patients and longitudinal studies in COS and adolescent onset support the concept of early-onset schizophrenia as a progressive neurodevelopmental disorder with both early and late developmental abnormalities. Future studies should look for correlates at a cellular level and for pathophysiological explanations of volume changes in these populations. The association of risk genes involved in circuitries associated with schizophrenia and their relationship to developmental trajectories is another promising area of future research. PMID:18234701

  11. Early- versus late-onset bipolar II disorder.

    PubMed Central

    Benazzi, F

    2000-01-01

    OBJECTIVE: To compare the clinical features and the outcome between patients with early- and late-onset bipolar II disorder. DESIGN: Case series. SETTING: Outpatient private practice. PATIENTS: One hundred and seventy-nine consecutive outpatients with bipolar II disorder presenting for treatment of a major depressive episode. OUTCOME MEASURES: Duration of illness, severity of depression, recurrences, psychosis, chronicity, atypical features and comorbidity. RESULTS: Patients with early-onset (before 20, 25 or 30 years of age) bipolar II disorder had a significantly longer duration of illness and more recurrences compared with patients with late-onset (after 20, 25 or 30 years of age) bipolar II disorder. All other variables were not significantly different between the 2 groups. CONCLUSIONS: Indicators of worse outcome (severity of depression, psychosis, chronicity, comorbidity) were not significantly different between patients with early- and late-onset bipolar II disorder. PMID:10721685

  12. 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

  13. [Early onset Parkinson's disease. Critical review of the literature].

    PubMed

    de Andrade, L A

    1996-12-01

    Since its original description Parkinson's disease has been considered as a clinical condition which affects older people. Nonetheless, since late in the last century, cases starting in very young age have been described. A great controversy has arisen concerning the real pathology in these cases and, consequently, how should they be named. Early or young onset parkinsonism, early or young onset Parkinson's disease, juvenile parkinsonism, all these terms have been used indistinguishable. There have been few pathological descriptions in early onset parkinsonism. Some show striking differences from the cases of older patients but others are very similar to what has been considered classical Parkinson's disease. Younger starting age usually corresponds to greater possibility of other family members being affected. Dyskinesias and fluctuations due to chronic levodopa treatment are an early and almost invariable complication in the course of young patients. Comments on several aspects based on an extensive literature review are presented. PMID:9201356

  14. 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

  15. [Early onset bipolar disorder: validation from admixture analyses and biomarkers].

    TOXLINE Toxicology Bibliographic Information

    Geoffroy PA; Etain B; Jamain S; Bellivier F; Leboyer M

    2013-04-01

    OBJECTIVES: Bipolar affective disorder (BD) is a multifactorial disorder with heterogeneous clinical presentations, in particular according to age at onset (AAO). The relevance of such an indicator has been discussed as a potential specifier in future nosographical classification.METHOD: We summarize available evidence of admixture analyses and biomarkers in early onset BD.RESULTS: Numerous clinical arguments have led us to conclude that the early onset BD subgroup is clinically homogeneous, with particular, recurrent, and severe characteristics.Eight admixture studies have demonstrated the existence of 3 subgroups of patients with BD according to AAO (early, intermediate, and late AAO), with 2 cut-off points of 21 (21.33) [SD 1.41]) and 35 years (34.67 [SD 5.52]). Differential clinical features and outcome measures characterize the early onset subgroup: higher rate of suicide attempts, rapid cycling, alcohol and drugs misuse, psychotic symptoms, and comorbid anxiety disorders. This may partially explain the delayed diagnosis and late initiation of mood stabilizers. Genetic, biological, imaging, and cognitive arguments may be considered as potential markers in providing external validity of the existence of this early onset subgroup. Implementation of AAO in the algorithms of treatment may be discussed, although the level of proof for focused medication strategies remains to be consolidated.CONCLUSION: Given the high frequency (44.80%) of early onset BD, awareness of clinicians should be stimulated to provide an early and accurate detection, preventive strategies, and possibly specific treatments.The forthcoming DSM-5 should include AAO as a specifier, given its relevance for course and outcome.

  16. Markers of neurodevelopmental impairments in early-onset psychosis

    PubMed Central

    Petruzzelli, Maria Giuseppina; Margari, Lucia; Craig, Francesco; Campa, Maria Gloria; Martinelli, Domenico; Pastore, Adriana; Simone, Marta; Margari, Francesco

    2015-01-01

    Background The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001), learning difficulties (P=0.04), enuresis (P=0.0008), a lower intelligence quotient (P<0.001), and subtle motor impairments (P=0.005) than control subjects. Conclusion We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. PMID:26229474

  17. 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

  18. Periodontal therapy in young adults with severe generalized periodontitis.

    PubMed

    Gunsolley, J C; Zambon, J J; Mellott, C A; Brooks, C N; Kaugars, C C

    1994-03-01

    This study evaluated the effect of periodontal therapy on clinical and microbiological parameters in 23 subjects with severe generalized early onset periodontitis. Therapy consisted of oral hygiene instruction and root planing and scaling, followed 3 months later by open flap debridement. Subjects were monitored for both clinical measures and levels of Actinobacillus actinomycetemcomitans and Porphyromas gingivalis as identified by indirect immunofluoresence. Clinical and microbiological evaluations were done at the start of the study, 3 months after the completion of root planing and scaling and 3 months after open flap debridement. Mean probing depth was reduced by both root planing and scaling and open flap debridement and the level of reduction demonstrated by both phases of therapy was similar to reductions found in studies that utilized subjects with chronic adult periodontitis. In contrast, reductions in attachment level due to the two phases of therapy, demonstrated in previous studies of subjects with adult periodontitis were not found in the young adult subjects with severe periodontal disease utilized in this study. Levels of A. actinomycetemcomitans were not significantly affected by root planing and scaling, but were reduced by open flap debridement. P. gingivalis was virtually eliminated by root planing and scaling, demonstrating that the two bacterial types respond differently to periodontal therapy. These changes in microbiological parameters were similar to those found in studies of localized juvenile periodontitis subjects, where surgery or antibiotics have been shown to be necessary to reduce levels of A. actinomycetemcomitans. PMID:8164121

  19. Increased developmental deviance and premorbid dysfunction in early onset schizophrenia.

    PubMed

    Vourdas, Apostolos; Pipe, Roderic; Corrigall, Richard; Frangou, Sophia

    2003-07-01

    Abnormal neurodevelopment and poor premorbid function have been described in schizophrenia. It is unclear whether abnormalities in these domains are increased in patients with early onset schizophrenia (EOS; onset before the 18th birthday) and whether they act to precipitate the earlier onset of the disorder. To address these questions, we collected information based on maternal interviews about the premorbid function of 40 adolescents with recent onset schizophrenia and an equal number of healthy controls using the Developmental Scale Score, the Premorbid Schizoid and Schizotypal Trait Scale (PSST) and Premorbid Adjustment Scale (PAS). Data on the PSST and PAS were also available in 54 patients with adult onset schizophrenia (AOS; onset after the 20th birthday). Compared to healthy controls, EOS patients had (a). delayed speech milestones, difficulties in reading and spelling and greater overall developmental deviance; (b). poor premorbid adjustment in childhood, which became even more deviant in adolescence particularly in boys and (c). more schizophrenia spectrum traits. Both premorbid adjustment and personality traits were more abnormal in patients with increased developmental deviance suggesting the possibility that they represent different manifestations of ongoing abnormalities in developmental processes. EOS patients had more impaired premorbid adjustment in adolescence and schizophrenia spectrum traits compared to AOS cases. Age of onset was related to developmental deviance, premorbid schizophrenia spectrum traits and childhood adjustment in EOS patients only. PMID:12765738

  20. 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

  1. 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…

  2. 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…

  3. 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…

  4. 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

  5. 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

  6. 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…

  7. 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

  8. 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

  9. 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

  10. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    PubMed

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

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. PMID:26691295

  11. Serotonin in early onset, male alcoholics with violent behaviour.

    PubMed

    Virkkunen, M; Linnoila, M

    1990-01-01

    Several lines of evidence suggest that abnormal brain serotonin metabolism may occur in early onset, type 2 alcoholism in men. Low cerebrospinal fluid 5-hydroxy-indoleacetic acid concentration has been found to be associated with a history of paternal alcoholism, and abnormal oral glucose tolerance tests (tendency to low blood glucose nadir) in subjects who are prone to exhibit impulsive, aggressive behaviour under the influence of alcohol. Moreover, a low ratio of the concentrations of tryptophan and other large neutral amino acids in plasma seems to correlate with early onset alcohol abuse and violent tendencies. More knowledge is required about neurochemical changes in homogenous subgroups of alcoholics such as the putative type 2 so as to understand which of the relationships are causative and to provide treatment strategies for alcoholism and its complications. PMID:2291840

  12. Early microbial succession in re-developing dental biofilms in periodontal health and disease

    PubMed Central

    TELES, F.R.; TELES, R.P.; UZEL, N.G.; SONG, X.Q.; TORRESYAP, G.; SOCRANSKY, S.S.; HAFFAJEE, A.D.

    2011-01-01

    Objective To determine the order of bacterial species succession in re-developing supra and subgingival biofilms. Methods Supra and subgingival plaque samples were taken separately from 28 teeth in 38 healthy and 17 periodontitis subjects immediately after professional cleaning. Samples were taken again from 7 teeth in randomly selected quadrants after 1, 2, 4 and 7 days of no oral hygiene and analyzed using checkerboard DNA-DNA hybridization. % DNA probe counts were averaged within subjects at each time point. Ecological succession was determined using a modified moving window analysis. Results Succession in supragingival biofilms from periodontitis and health was similar. At 1 day, Streptococcus mitis and Neisseria mucosa showed increased proportions, followed by Capnocytophaga gingivalis, Eikenella corrodens, Veillonella parvula and Streptococcus oralis at 14 days. At 47 days, Campylobacter rectus, Campylobacter showae, Prevotella melaninogenica and Prevotella nigrescens became elevated. Subgingival plaque redevelopment was slower and very different from supragingival. Increased proportions were first observed for S. mitis, followed by V. parvula and C. gingivalis and, at 7 days by Capnocytophaga sputigena and P. nigrescens. No significant increase in proportions of periodontal pathogens was observed in any of the clinical groups or locations. Conclusions There is a defined order in bacterial species succession in early supra and subgingival biofilm re-development after professional cleaning. PMID:21895662

  13. 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

  14. Early diagnosis and treatment options for the periodontal problems in Papillon-Lefèvre syndrome: a literature review.

    PubMed

    Ashri, Nahed Y

    2008-07-01

    Various approaches for treating the periodontal condition associated with Papillon-Lefèvre syndrome (PLS) have been reported. These include oral hygiene instruction, use of mouth rinses, frequent debridement, multiple antibiotic regimens, periodontal surgery, extraction of hopeless teeth, and extraction of all primary teeth. The objective of this paper is to review the literature on the different treatment approaches of patients with PLS and to illustrate the importance of early diagnosis as well as treatment in long-term maintenance of oral health. Because PLS is rare, most publications are case reports, and very few document long-term successful treatment of the periodontal condition. Several treatment approaches are summarized in this paper with the long-term reports. The importance of early diagnosis is highlighted. The recommendation is that young patients with skin lesions and severe periodontal destruction together with premature loss of teeth should be referred to a periodontist as early as possible. This should prevent or delay tooth loss and enhance early replacement of missing teeth for preservation of function and esthetics. In conclusion, successful periodontal management of PLS patients remains challenging. However, as our understanding of the etiological factors increases, it is hoped that successful treatment strategies will be developed. PMID:18714933

  15. [Cerebellar ataxia of early onset: clinical symptoms and MRI findings].

    PubMed

    Yamashita, S; Miyake, S; Yamada, M; Iwamoto, H; Yamada, K

    1989-07-01

    Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmin, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjögren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. PMID:2789855

  16. Hypergonadotropic Hypogonadism, Progressive Early-Onset Spinocerebellar Ataxia, and Late-Onset Sensorineural Hearing Loss: Case Report and Literature Review

    PubMed Central

    Sarikaya, E; Ensert, CG; Gulerman, HC

    2011-01-01

    The association of ataxia, hypergonadotropic hypogonadism and hearing loss is extremely rare. Considerable heterogeneity exists in the literature of the neurological manifestations, age of onset, clinical severity and associated abnormalities. We describe a 24-year-old woman with secondary hypergonadotropic amenorrhea, early-onset progressive spinocerebellar ataxia (SCA), late-onset sensorineural hearing loss and normal intelligence and compare it with reported cases. PMID:24052715

  17. Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

    PubMed Central

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

    2013-01-01

    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 diagnostic system makes few modifications to accommodate children and adolescents. Researchers in this area have developed specific BPSD definitions that affect the generalizability of their findings to all youth with BPSD. Despite knowledge gains from the research, BPSDs are still difficult to diagnose because clinicians must: (1) consider the impact of the child’s developmental level on symptom presentation (e.g., normative behavior prevalence, environmental limitations on youth behavior, pubertal status, irritability, symptom duration); (2) weigh associated impairment and course of illness (e.g., neurocognitive functioning, failing to meet full DSM criteria, future impairment); and (3) make decisions about appropriate assessment (differentiating BPSD from medical illnesses, medications, drug use, or other psychiatric diagnoses that might better account for symptoms; comorbid disorders; informant characteristics and assessment measures to use). Research findings concerning these challenges and relevant recommendations are offered. Areas for further research to guide clinicians’ assessment of children with early-onset BPSD are highlighted. PMID:19466543

  18. Severe early-onset colitis revealing mevalonate kinase deficiency.

    PubMed

    Levy, Michael; Arion, Alina; Berrebi, Dominique; Cuisset, Laurence; Jeanne-Pasquier, Corinne; Bader-Meunier, Brigitte; Jung, Camille

    2013-09-01

    Hyperimmunoglobulinemia D is the less severe form of mevalonate kinase deficiency (MKD) caused by recessive inherited mutation in the mevalonate kinase gene. Hyperimmunoglobulinemia D is characterized by febrile attacks, often associated with transient digestive manifestations, such as abdominal pain, diarrhea, and vomiting. Here we report for the first time 2 patients with MKD revealed by severe neonatal colitis. Both patients had chronic bloody diarrhea and failure to thrive; 1 patient since the age of 1 month and the other since the age of 12 days. Total parenteral nutrition was required. A marked elevation of acute phase reactants was present, and no evidence of infection was found. In patient 1, ileocolonoscopy revealed ulcerative colitis at the age of 5 months. Patient 2 suffered from enterocolitis and shock, associated with multiple bowel adhesions at age 5 weeks; the rectosigmoidoscopy showed aphtoid lesions of the sigmoid colon. Pathologic findings of colonic biopsies revealed a dense polymorph inflammatory infiltrate associated with deep ulcerations. Febrile attacks occurred 2 months after the onset of digestive symptoms in patient 1, and at onset of disease in patient 2. Genomic sequencing of the mevalonate kinase gene revealed compound heterozygous mutations in both patients. Anti-interleukin-1 agent produced long-term remission of all digestive features and laboratory parameters. This report emphasizes that MKD may be the cause of severe early-onset inflammatory colitis, and must be considered by physicians, even in the absence of fever, after ruling out infections. Anti-interleukin-1 therapy may result in a dramatic improvement of MKD-related inflammatory bowel disease. PMID:23979089

  19. 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.…

  20. Cognitive function in early onset schizophrenia: a selective review.

    PubMed

    Frangou, Sophia

    2010-01-01

    Schizophrenia is widely regarded as the clinical outcome of aberrant neurodevelopment caused by a combination of genetic and non-genetic factors. Early Onset Schizophrenia (EOS) manifests in childhood or adolescence and represents a more severe variant of the Adult Onset form of the disorder (AOS). EOS offers a unique opportunity of exploring the impact of disease related mechanisms on the developmental trajectory of cognitive function. The present review focused on the domains of general intellectual ability (IQ), attention, executive function and memory. Significant methodological variability was noted across the different studies that examined these aspects of cognition in EOS patients. Despite this, a consistent pattern emergent from the data suggesting that (a) EOS patients compared to healthy children and adolescents show impairments of medium to large effect size in IQ, attention, memory and executive function (b) despite increased clinical severity, the cognitive profile of EOS patients is comparable to that of AOS patients (c) healthy adolescents show age-related improvement in their ability to perform tests of attention, memory and executive function; this is not present in EOS patients thus resulting in increased age-related deviance in patients' performance. This apparent decline is mostly attributable to patients' failure to acquire new information and to use more sophisticated cognitive strategies. PMID:20140271

  1. 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.

  2. Early-onset pauciarticular juvenile rheumatoid arthritis. A histopathologic study.

    PubMed

    Merriam, J C; Chylack, L T; Albert, D M

    1983-07-01

    A young girl with early-onset pauciarticular juvenile rheumatoid arthritis suffered from recurrent severe bilateral iridocyclitis. Despite intensive medical therapy, she gradually lost all useful vision and ultimately required bilateral enucleation at the age of 10 years for control of pain and photophobia. Histopathologic study of the eyes revealed in the iris and ciliary body a dense inflammatory infiltrate composed principally of plasma cells, as well as angle closure, a dense cyclitic membrane, retinal detachment, cystoid macula, and optic atrophy. Immunoperoxidase stains showed little immunoglobulin within or around the plasma cells within the ciliary body, although strong reactions for IgG and kappa- and lambda-light chains were seen in other parts of the eyes. PMID:6347150

  3. Early Identification of Autism: Early Characteristics, Onset of Symptoms, and Diagnostic Stability

    ERIC Educational Resources Information Center

    Webb, Sara Jane; Jones, Emily J. H.

    2009-01-01

    In the first year of life, infants who later go on to develop autistic spectrum disorders (ASD) may exhibit subtle disruptions in social interest and attention, communication, temperament, and head circumference growth that occur prior to the onset of clinical symptoms. These disruptions may reflect the early course of ASD development and may also…

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

    PubMed

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

    2015-12-30

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

  5. A Longitudinal Transactional Risk Model for Early Eating Disorder Onset

    PubMed Central

    Pearson, Carolyn M.; Combs, Jessica L.; Zapolski, Tamika C. B.; Smith, Gregory T.

    2014-01-01

    The presence of binge eating behavior in early middle school predicts future diagnoses and health difficulties. The authors showed that this early binge eating behavior can, itself, be predicted by risk factors assessed in elementary school. We tested the acquired preparedness model of risk, which involves transactions among personality, psychosocial learning, and binge eating. In a sample of 1,906 children assessed in the spring of fifth grade (the last year of elementary school), the fall of sixth grade, and the spring of sixth grade, we found that fifth grade negative urgency (the personality tendency to act rashly when distressed) predicted subsequent increases in the expectancy that eating helps alleviate negative affect, which in turn predicted subsequent increases in binge eating behavior. This transactional risk process appeared to continue to occur at later time points. Negative urgency in the fall of sixth grade was predicted by fifth grade pubertal onset, binge eating behavior, and expectancies. It, in turn, predicted increases in high-risk eating expectancies by the spring of sixth grade, and thus heightened risk. PMID:22428790

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

    PubMed

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

    2015-10-01

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

  7. 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

  8. 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

  9. Clinicopathological and genetic study of early-onset demyelinating neuropathy.

    PubMed

    Parman, Yesim; Battaloglu, Esra; Baris, Ibrahim; Bilir, Birdal; Poyraz, Mürüvvet; Bissar-Tadmouri, Nisrine; Williams, Anna; Ammar, Nadia; Nelis, Eva; Timmerman, Vincent; De Jonghe, Peter; Najafov, Ayaz; Necefov, Ayaz; Deymeer, Feza; Serdaroglu, Piraye; Brophy, Peter J; Said, G

    2004-11-01

    Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene. PMID:15469949

  10. Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion.

    PubMed

    Allen, Nicholas M; Conroy, Judith; Shahwan, Amre; Lynch, Bryan; Correa, Raony G; Pena, Sergio D J; McCreary, Dara; Magalhães, Tiago R; Ennis, Sean; Lynch, Sally A; King, Mary D

    2016-01-01

    Early onset epileptic encephalopathies (EOEEs) represent a significant diagnostic challenge. Newer genomic approaches have begun to elucidate an increasing number of responsible single genes as well as emerging diagnostic strategies. In this single-center study, we aimed to investigate a cohort of children with unexplained EOEE. We performed whole-exome sequencing (WES), targeting a list of 137 epilepsy-associated genes on 50 children with unexplained EOEE. We characterized all phenotypes in detail and classified children according to known electroclinical syndromes where possible. Infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We identified disease-causing variants in 11 children (22%) in the following genes: STXBP1 (n = 3), KCNB1 (n = 2), KCNT1, SCN1A, SCN2A, GRIN2A, DNM1, and KCNA2. We also identified two further variants (in GRIA3 and CPA6) in two children requiring further investigation. Eleven variants were de novo, and in one paternal testing was not possible. Phenotypes were broadened for some variants identified. This study demonstrates that WES is a clinically useful screening tool for previously investigated unexplained EOEE and allows for reanalysis of data as new genes are being discovered. Detailed phenotyping allows for expansion of specific gene disorders leading to epileptic encephalopathy and emerging sub-phenotypes. PMID:26648591

  11. Periodontal Health in Women with Early Stage Postmenopausal Breast Cancer Newly on Aromatase Inhibitors: A Pilot Study

    PubMed Central

    Taichman, LS; Inglehart, MR; Giannobile, W; Braun, T; Kolenic, G; Van Poznak, C

    2015-01-01

    Background Aromatase inhibitor (AI) use results in low estrogen levels which in turn affect bone mineral density (BMD). Periodontitis, alveolar bone loss, and tooth loss are associated with low BMD. The goal of this study was to assess the prevalence of periodontitis, perceived oral health, and evaluate salivary biomarkers in postmenopausal women who are early stage (I-IIIA) breast cancer (BCa) survivors and receive adjuvant AI therapy. Methods Participants included 58 postmenopausal women; 29 with BCa on AIs and 29 controls without BCa diagnoses. Baseline periodontal status was assessed with: (1) periodontal pocket depth (PD); (2) bleeding on probing (BOP); and (3) attachment loss (AL). Demographic and dental utilization information was gathered by questionnaire. Linear regression modeling was used to analyze the outcomes. Results No differences in mean PD or the number of teeth were found. The AI group had significantly more sites with BOP (27.8 vs. 16.7; p = 0.02), higher worst-site AL (5.2 mm vs. 4.0 mm; p < 0.01) and more sites with dental calculus than did controls (18.2 vs. 6.4; p < 0.001). Linear regression adjusted for income, tobacco use, and dental insurance, and previous radiation and chemotherapy exposure demonstrated AI use increased CAL over 2 mm (95% CI: 0.46 -3.92). Median salivary osteocalcin and Tumor Necrosis Factor levels were significantly higher in the BCa group than the control group. Conclusions This first investigation of the periodontal status of women initiating adjuvant AI therapy identifies this population as having an increased risk for periodontitis (NCT1272570). PMID:25672657

  12. Role of the NK Cell-Activating Receptor CRACC in Periodontitis

    PubMed Central

    Krämer, Benjamin; Kebschull, Moritz; Nowak, Michael; Demmer, Ryan T.; Haupt, Manuela; Körner, Christian; Perner, Sven; Jepsen, Søren

    2013-01-01

    Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cell-activating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. We delineate how Aggregatibacter actinomycetemcomitans, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis. PMID:23250953

  13. 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.

  14. 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…

  15. 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…

  16. 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

  17. 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…

  18. 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,…

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  1. 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

  2. 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…

  3. 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…

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  5. 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

  6. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

    PubMed

    von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

    2011-04-01

    Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. PMID:21392225

  7. Early results of a remotely-operated magnetic growth rod in early-onset scoliosis.

    PubMed

    Dannawi, Z; Altaf, F; Harshavardhana, N S; El Sebaie, H; Noordeen, H

    2013-01-01

    Conventional growing rods are the most commonly used distraction-based devices in the treatment of progressive early-onset scoliosis. This technique requires repeated lengthenings with the patient anaesthetised in the operating theatre. We describe the outcomes and complications of using a non-invasive magnetically controlled growing rod (MCGR) in children with early-onset scoliosis. Lengthening is performed on an outpatient basis using an external remote control with the patient awake.Between November 2009 and March 2011, 34 children with a mean age of eight years (5 to 12) underwent treatment. The mean length of follow-up was 15 months (12 to 18). In total, 22 children were treated with dual rod constructs and 12 with a single rod. The mean number of distractions per patient was 4.8 (3 to 6). The mean pre-operative Cobb angle was 69° (46° to 108°); this was corrected to a mean 47° (28° to 91°) post-operatively. The mean Cobb angle at final review was 41° (27° to 86°). The mean pre-operative distance from T1 to S1 was 304 mm (243 to 380) and increased to 335 mm (253 to 400) in the immediate post-operative period. At final review the mean distance from T1 to S1 had increased to 348 mm (260 to 420).Two patients developed a superficial wound infection and a further two patients in the single rod group developed a loss of distraction. In the dual rod group, one patient had pull-out of a hook and one developed prominent metalwork. Two patients had a rod breakage; one patient in the single rod group and one patient in the dual rod group. Our early results show that the MCGR is safe and effective in the treatment of progressive early-onset scoliosis with the avoidance of repeated surgical lengthenings. PMID:23307677

  8. Actinobacillus actinomycetemcomitans serotype e--biotypes, genetic diversity and distribution in relation to periodontal status.

    PubMed

    Doğan, B; Saarela, M H; Jousimies-Somer, H; Alaluusua, S; Asikainen, S

    1999-04-01

    Actinobacillus actinomycetemcomitans isolates from 356 individuals were screened for identification of serotype e in order to investigate its distribution in relation to periodontal status. From subjects with serotype e, 1-6 isolates per subject (n = 61) were genotyped using arbitrarily primed-polymerase chain reaction (AP-PCR) and apaH gene polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis to determine the genetic heterogeneity within the serotype. Furthermore, one serotype e strain per subject was tested for fermentation of 8 carbohydrates for biotyping. Among patients with adult periodontitis (n = 219), localized juvenile periodontitis (n = 55) and other forms of early-onset periodontitis (n = 18) serotypes b, a and c, respectively, were the most frequently detected serotypes. Non-periodontitis subjects (n = 64) were predominantly colonized with serotype c. Serotype e was found in 30 (14%) adult periodontitis patients, 2 (11%) early-onset periodontitis patients and in 5 (8%) non-periodontitis individuals, but in none of the 55 localized juvenile periodontitis patients. AP-PCR distinguished 3 and apaH gene PCR-RFLP analysis 2 genotypes among the 61 A. actinomycetemcomitans serotype e isolates, one genotype per subject. The AP-PCR genotypes 1 and 3 represented the apaH genotype 1 and the AP-PCR genotype 2 the apaH genotype 2. On the basis of variable fermentation of galactose and xylose, 3 biotypes among A. actinomycetemcomitans serotype e were established. Contrary to the absence of A. actinomycetemcomitans serotype e in localized juvenile periodontitis patients, its detection frequency was comparable among other forms of periodontitis and periodontal health. Clinical serotype e isolates form at least 2 genetic types and 3 biotypes. PMID:10219168

  9. 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 patients with ESO strabismus. PMID:25071514

  10. Benefits of Early Systemic Antibiotics in Localized Aggressive Periodontitis. A Retrospective Study

    PubMed Central

    Beliveau, Dennis; Magnusson, Ingvar; Bidwell, John A.; Zapert, Edward F.; Aukhil, Ikramuddin; Wallet, Shannon M.; Shaddox, Luciana M.

    2012-01-01

    Treatment of localized aggressive periodontitis (LAP) may include systemic antibiotics, yet it is unclear at what stage of treatment planning antibiotics are most effective. Aim This retrospective analysis compared immediate vs. delayed antibiotic therapy on clinical parameters and gingival crevicular fluid (GCF) inflammatory mediators. Material and Methods At baseline, 3 and 6 months after treatment, clinical parameters [probing depth (PD), attachment level (CAL), bleeding on probing (BoP), and plaque] and GCF were collected from LAP participants, who received a 7-day antibiotic regimen immediately (ImA) or 3 months following (DelA) mechanical therapy. Results While both groups presented significant CAL reductions at 6 months, only ImA resulted in a reduction in mean PD at both 3 and 6 months, along with reductions in CAL and BoP at 3 months following therapy. In addition, GCF mediators were higher in DelA group at 3 months post-mechanical treatment, but were significantly reduced 6 months following antibiotic therapy. Conclusions ImA and DelA regimens were both effective in improving CAL by 6 months post-therapy. However, ImA allowed for better improvement in overall clinical parameters early in the course of treatment, concomitant with lower levels of inflammatory mediators within the GCF. PMID:22931240

  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. Immediate, early, and conventional implant placement in a patient with history of periodontitis.

    PubMed

    Lanza, Alessandro; Scognamiglio, Fabio; Femiano, Felice; Lanza, Michele

    2015-01-01

    The aim of this paper is to describe a case of implant-prosthetic rehabilitation in a patient with periodontitis, focusing on the different timing of implant placement. After initial periodontal treatment, teeth with advanced mobility degree and severe bone resorption were extracted. At different healing time oral implants were placed in a prosthetic-guided position. After osseointegration period the implants were loaded and the results at one year of follow-up are presented. PMID:25949833

  13. Immediate, Early, and Conventional Implant Placement in a Patient with History of Periodontitis

    PubMed Central

    Lanza, Alessandro; Scognamiglio, Fabio; Femiano, Felice; Lanza, Michele

    2015-01-01

    The aim of this paper is to describe a case of implant-prosthetic rehabilitation in a patient with periodontitis, focusing on the different timing of implant placement. After initial periodontal treatment, teeth with advanced mobility degree and severe bone resorption were extracted. At different healing time oral implants were placed in a prosthetic-guided position. After osseointegration period the implants were loaded and the results at one year of follow-up are presented. PMID:25949833

  14. Social Anxiety and Onset of Drinking in Early Adolescence

    ERIC Educational Resources Information Center

    Tomlinson, Kristin L.; Cummins, Kevin M.; Brown, Sandra A.

    2013-01-01

    The present study examines several types of social anxiety that may be associated with the onset of alcohol use in middle school students, and whether the relationship differs by sex and grade. Students in the seventh and eighth grades (N = 2,621) completed the Social Anxiety Scale for Adolescents and a measure of lifetime drinking via schoolwide

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

    PubMed Central

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

    2011-01-01

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

  16. Smoking and Periodontal Disease

    PubMed Central

    Borojevic, Tea

    2012-01-01

    Periodontitis is a group of inflammatory diseases affecting the supporting tissues of the tooth (periodontium). The periodontium consists of four tissues : gingiva, alveolar bone and periodontal ligaments. Tobbaco use is one of the modifiable risk factors and has enormous influance on the development, progres and tretmen results of periodontal disease. The relationship between smoking and periodontal health was investigated as early as the miiddle of last century. Smoking is an independent risk factor for the initiation, extent and severity of periodontal disease. Additionally, smoking can lower the chances for successful tretment. Tretmans in patients with periodontal disease must be focused on understanding the relationship between genetic and environmental factors. Only with individual approach we can identify our pacients risks and achieve better results. PMID:23678331

  17. Smoking and periodontal disease.

    PubMed

    Borojevic, Tea

    2012-01-01

    Periodontitis is a group of inflammatory diseases affecting the supporting tissues of the tooth (periodontium). The periodontium consists of four tissues : gingiva, alveolar bone and periodontal ligaments. Tobbaco use is one of the modifiable risk factors and has enormous influance on the development, progres and tretmen results of periodontal disease. The relationship between smoking and periodontal health was investigated as early as the miiddle of last century. Smoking is an independent risk factor for the initiation, extent and severity of periodontal disease. Additionally, smoking can lower the chances for successful tretment. Tretmans in patients with periodontal disease must be focused on understanding the relationship between genetic and environmental factors. Only with individual approach we can identify our pacients risks and achieve better results. PMID:23678331

  18. 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

  19. 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…

  20. 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…

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  2. 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…

  3. 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,

  4. 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

  5. Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

    PubMed Central

    Vyas, Nora S.; Gogtay, Nitin

    2012-01-01

    Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

  6. Substance abuse treatment patients with early onset cocaine use respond as well to contingency management interventions as those with later onset cocaine use.

    PubMed

    Weiss, Lindsay M; Petry, Nancy M

    2014-08-01

    Early onset drug use is associated with increased risk of developing substance use disorders, but relatively little is known about the correlates of early drug use among adults receiving treatment. A retrospective analysis of a randomized study of contingency management treatment compared cocaine-dependent patients who reported initial cocaine use at age 14 or younger (n = 41) to those who began using after age 14 (n = 387). Patients with early onset cocaine use had more legal and psychiatric problems than those who initiated cocaine use later. Patients with early-onset cocaine use also dropped out of treatment sooner and achieved less sustained abstinence than those who began using at older ages, but the interaction between age of first use and treatment condition was not significant. Early-onset cocaine use is associated with persistent psychosocial problems and an overall poor response to treatment. However, contingency management is efficacious in improving outcomes in early onset cocaine users. PMID:24865619

  7. Aggressive and acute periodontal diseases.

    PubMed

    Albandar, Jasim M

    2014-06-01

    Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon-Lefèvre syndrome, Chediak-Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra-oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount. PMID:24738583

  8. The effect of early onset common mental disorders on educational attainment in Australia.

    PubMed

    Leach, Liana Sarma; Butterworth, Peter

    2012-08-30

    Early onset mental disorders may lead to the early termination of education and thereby have long term adverse social and economic consequences on outcomes such as employment and financial security. This issue is important to address as governments seek to develop new ways to minimise the impacts of mental health problems and maximise workforce participation. The current investigation examines the impact of early onset affective, anxiety and substance use disorders on the early termination of secondary school education in Australia. The analyses used data from those aged between 20 and 34 in the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB) (n=2055). The NSMHWB is a population based survey administered by the Australian Bureau of Statics and included a WMH-CIDI 3.0 assessment to determine whether respondents met diagnostic criteria for any lifetime affective, anxiety, and/or substance use disorder as well as age of onset information. The results show that early onset mental disorders are significantly associated with the termination of secondary education in Australia, particularly early onset substance use disorders such as alcohol, cannabis and stimulant use. These disorders were most likely to disrupt completion in the middle years of high school (year 10 completion), in comparison to the final year 12 milestone. Policies and interventions promoting prevention and early intervention and offering educational support for young people with psychiatric illness and substance use problems, should intervene prior to the middle years of high school to help prevent adverse social and economic consequences. PMID:22507527

  9. 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

  10. 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…

  11. 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…

  12. 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

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

    PubMed Central

    Silla, Irene Osorio; Rueda, Daniel; Rodrguez, Yolanda; Garca, Juan Luis; de la Cruz Vigo, Felipe; Perea, Jos

    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

  14. Early onset type 2 diabetes: risk factors, clinical impact and management

    PubMed Central

    Idris, Iskandar

    2014-01-01

    Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities’, in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic. PMID:25364491

  15. 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

  16. Early onset parkinsonism in dementia lacking distinct histopathological features.

    PubMed

    Bergareche, A; Martí-Massó, J F; Linacasoro, G; Arrinda, J M; De Arce, A

    2006-01-01

    Dementia lacking distinct histopathological features (DLDHF) belongs to the frontotemporal dementia syndromes. Behavioral, cognitive and motor symptoms are its usual clinical manifestations. However, considerable heterogeneity exists and no evident clinicopathological correlations can be performed. We report a patient who presented with a very unusual combination of behavioral abnormalities and prominent early parkinsonism progressing to a severe dementia. Pathological studies confirmed DLDHF with severe frontal and striatal neuronal loss and gliosis. PMID:16465769

  17. 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

  18. Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

    PubMed Central

    Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

  19. WT1 gene mutations in Chinese children with early onset nephrotic syndrome.

    PubMed

    Li, Jianguo; Ding, Jie; Zhao, Dan; Yu, Zihua; Fan, Qingfeng; Chen, Yan; Zhang, Hongwen; Zhong, Xuhui; Huang, Jianping; Yao, Yong; Xiao, Huijie

    2010-08-01

    In Chinese children with steroid-resistant nephrotic syndrome (SRNS), it was reported that NPHS2 mutation was detected in 4.3%, which was lower than that in Caucasians (10-30%). However, there were no data on WT1 mutation in nephrotic syndrome (NS), especially in early-onset NS of Chinese children. Thus, a study, which enrolled 36 Chinese children with early-onset (before 3 y old) NS and steroid resistance if failing steroid therapy (early-group), was conducted. As control, 35 children with SRNS and with disease onset age after 3 y old were also analyzed (control-group). WT1 gene was examined by PCR and direct sequencing. The result showed that in the early-group 6/36 (16.7%) were detected with WT1 mutations. Further analysis according to different onset age revealed that the mutation detection rates of WT1 were 26.3% (5/19), 6.3% (1/16), and 0 (0/1) in children younger than 1 y, 1-2 y, and 2-3 y, respectively. In control-group, no WT1 (0/35) mutation was detected. WT1 mutation combined with NPHS2 variant was detected in a girl. In conclusion, WT1 mutations seemed more common in Chinese children with early-onset NS. PMID:20442690

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

    PubMed

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

    2015-01-01

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

  1. 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

  2. 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

  3. The onset of galactic winds in early-type galaxies

    NASA Technical Reports Server (NTRS)

    Jones, Christine

    1992-01-01

    We completed the spectral analysis of 31 early-type galaxies to investigate whether their x-ray emission was predominantly due to thermal bremsstrahlung from a hot gaseous corona or emission from discrete, galactic sources such as x-ray binaries. If a corona dominates the x-ray emission, its spectra is expected to be relatively cool (0.5 - 1 keV) compared to the harder emission associated with x-ray binaries in our galaxy, the Magellanic Clouds and M31. While it is generally accepted that the x-ray emission in luminous E and S0 galaxies arises from hot coronae, the status of hot gas in lower luminosity (and hence lower mass) galaxies is less clear. Calculations show that, for a given supernova rate, a critical galaxy luminosity (mass) exists below which the gas cannot be gravitationally confined and a galactic wind is predicted to be effective in expelling gas from the galaxy. Since significant mass (a dark halo) is required to hold a hot, gaseous corona around a galaxy, we expect that the faintest, smallest galaxies will not have a hot corona, but their x-ray emission will be dominated by galactic sources or by an active galactic nuclei. In the sample we tested which spanned the absolute magnitude range from -21.5 to -19.5, we found that except for two galaxies whose x-ray emission was dominated by an active nucleus, that the others were consistent with emission from hot gas. We also found that there is a correlation between gas temperature and galaxy magnitude (mass), such that the brighter, more luminous galaxies have hotter gas temperatures. Thus even at relatively faint magnitudes, the dominant emission from early-type galaxies appears to be hot gas. We also carried out an investigation of the x-ray surface brightness distribution of the x-ray emission for about 100 early type galaxies to determine whether the x-ray emission from galaxies are extended. Extended x-ray emission is expected if the emission is due to a hot gaseous corona. We determined the ratio of the source counts in two annuli (0-80 arc seconds and 80-160 arc seconds) for each galaxy and analyzed these ratios using a maximum likelihood estimator to determine the errors on the ratios. Even for weak sources, this ratio provides a sensitive test for source extent. We then compared these ratios to a sample of quasars (all unresolved sources) and have determined which galaxies are extended and which are consistent with point sources. A first paper including the Einstein x-ray fluxes for 147 early-type galaxies has been published in the Astrophysical Journal Supplement Series (with Roberts, Hogg, Bregman, Forman entitled 'Interstellar Matter in Early-Type Galaxies'). A second paper will describe the spectral and extent analysis carried out for this galaxy sample. These results also have been presented at scientific conferences and in colloquia.

  4. 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

  5. Tissue engineered periodontal products.

    PubMed

    Bartold, P M; Gronthos, S; Ivanovski, S; Fisher, A; Hutmacher, D W

    2016-02-01

    Attainment of periodontal regeneration is a significant clinical goal in the management of advanced periodontal defects arising from periodontitis. Over the past 30 years numerous techniques and materials have been introduced and evaluated clinically and have included guided tissue regeneration, bone grafting materials, growth and other biological factors and gene therapy. With the exception of gene therapy, all have undergone evaluation in humans. All of the products have shown efficacy in promoting periodontal regeneration in animal models but the results in humans remain variable and equivocal concerning attaining complete biological regeneration of damaged periodontal structures. In the early 2000s, the concept of tissue engineering was proposed as a new paradigm for periodontal regeneration based on molecular and cell biology. At this time, tissue engineering was a new and emerging field. Now, 14 years later we revisit the concept of tissue engineering for the periodontium and assess how far we have come, where we are currently situated and what needs to be done in the future to make this concept a reality. In this review, we cover some of the precursor products, which led to our current position in periodontal tissue engineering. The basic concepts of tissue engineering with special emphasis on periodontal tissue engineering products is discussed including the use of mesenchymal stem cells in bioscaffolds and the emerging field of cell sheet technology. Finally, we look into the future to consider what CAD/CAM technology and nanotechnology will have to offer. PMID:25900048

  6. 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

  7. Very early-onset inflammatory bowel disease: gaining insight through focused discovery.

    PubMed

    Moran, Christopher J; Klein, Christoph; Muise, Aleixo M; Snapper, Scott B

    2015-05-01

    The pathogenesis of pediatric inflammatory bowel disease (IBD) is only partially understood. Strong evidence implicates a strong genetic component including high monozygotic twin concordance and familial disease phenotype concordance rates. Genome-wide association studies have identified associations between >160 genetic loci and the risk for developing IBD. The roles of implicated genes are largely immune-mediated, although other functions include cellular migration, oxidative stress, and carbohydrate metabolism. Additionally, growing literature describes monogenic causes of IBD that frequently present as infantile or very early-onset IBD. The interplay between IBD risk single nucleotide polymorphisms and rare genetic variants has yet to be determined. Studying patients with very early-onset IBD may elicit genetic factors that could be applied to broader populations of IBD. This review describes what is known about the genetic causes of very early-onset IBD and genetic strategies that may unravel more of the genetic causes of IBD. PMID:25895007

  8. 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.

  9. 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

  10. 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

  11. 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

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

    PubMed

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

    2008-08-01

    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. 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.

  14. 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

  15. 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

  16. Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression

    ERIC Educational Resources Information Center

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD. Method: A total of 51 children 7 through 11 years of age who had…

  17. 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

  18. 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…

  19. 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

  20. 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…

  1. 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…

  2. 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),

  3. 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

  4. 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,…

  5. 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…

  6. 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

  7. [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

  8. 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…

  9. 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),…

  10. 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…

  11. 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…

  12. 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

  13. 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.

  14. 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.…

  15. 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…

  16. 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…

  17. 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

  18. Distinct breast cancer subtypes in women with early-onset disease across races

    PubMed Central

    Singh, Mandeep; Ding, Yi; Zhang, Li-Ying; Song, Dong; Gong, Yun; Adams, Sylvia; Ross, Dara S; Wang, Jin-Hua; Grover, Shruti; Doval, Dinesh Chandra; Shao, Charles; He, Zi-Li; Chang, Victor; Chin, Warren W; Deng, Fang-Ming; Singh, Baljit; Zhang, David; Xu, Ru-Liang; Lee, Peng

    2014-01-01

    Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients. PMID:25057437

  19. 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

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

    TOXLINE Toxicology Bibliographic Information

    Thomopoulos TP; Skalkidou A; Dessypris N; Chrousos G; Karalexi MA; Karavasilis TG; Baka M; Hatzipantelis E; Kourti M; Polychronopoulou S; Sidi V; Stiakaki E; Moschovi M; Loutradis D; Petridou ET

    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.

  1. 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

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

    PubMed Central

    2012-01-01

    Background Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. Methods/Design One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. Discussion The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. Trial registration The present study is registered within The Netherlands National Trial Register (ref: NTR2124) PMID:22897903

  3. 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

  4. 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 a genuine semantic impairment may represent one of the clinical hallmarks of LOAD. PMID:26694580

  5. 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

  6. 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

  7. 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

  8. Differences between Early and Late-Onset Alzheimer’s Disease in Neuropsychological Tests

    PubMed Central

    Sá, Francisca; Pinto, Paula; Cunha, Catarina; Lemos, Raquel; Letra, Liliana; Simões, Mário; Santana, Isabel

    2012-01-01

    Although patients with Alzheimer disease (AD) share clinical and histological features regardless of age of onset, the hypothesis that early onset AD constitutes a distinct subgroup prevails. Some authors suggest that early attention or language impairment constitute patterns of differentiation in terms of neuropsychological profile, between these groups. However, investigations are not consensual in terms of cognitive domains affected in each group. Aim: To investigate whether there is early neuropsychological difference between two types of AD using the conventional dividing line of 65 years. Methods: We evaluated the results obtained in the Mini-Mental State Examination (MMSE) and in a comprehensive neuropsychological battery – Battery of Lisbon for the Assessment of Dementia (BLAD), at a Dementia clinic in the University Hospital of Coimbra and a Memory Clinic. The study was developed in consecutive patients with a clinical probable diagnosis of mild to moderate AD, using standard criteria (DSMIV and NINCDS-ADRDA). Statistical analysis was performed using Qui-square and U-Mann–Whitney, for categorical and non-categorical variables. The degree of relation between variables, was measured using the coefficient of correlation rs de Spearman. Results: The total sample included 280 patients: 109 with early onset AD and 171 with a late-onset form. Groups were comparable in terms of gender, education or severity of disease, and MMSE. In BLAD, for univariate analysis the early onset group had lower scores in Naming (p = 0.025), Right–Left Orientation (p = 0.029) and Praxis (p = 0.001), and better performances in Orientation (p = 0.001) and Visual Memory (p = 0.022). After application of Bonferroni correction for multiple comparisons only Praxis and Orientation could differentiate the two groups. No significant differences were found in other tests or functions. Discussion: The results are suggestive of dissociated profiles between early and late-onset AD. Younger patients have a major impairment in Praxis and a tendency for a great impairment in neocortical temporal functions. AD patients with late-onset forms had a tendency for worse performances in Visual Memory and Orientation, suggesting a more localized disease to the limbic structures. PMID:22593755

  9. 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.

  10. Identification of Novel Candidate Genes for Early-Onset Colorectal Cancer Susceptibility

    PubMed Central

    Weren, Robbert D. A.; Mensenkamp, Arjen R.; Gilissen, Christian; van Zelst-Stams, Wendy A.; Spruijt, Liesbeth; Kets, C. Marleen; Zhang, Junxiao; Venselaar, Hanka; Vreede, Lilian; Schubert, Nil; Tychon, Marloes; Derks, Ronny; Schackert, Hans K.; Geurts van Kessel, Ad; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.; Kuiper, Roland P.

    2016-01-01

    Approximately 25–30% of colorectal cancer (CRC) cases are expected to result from a genetic predisposition, but in only 5–10% of these cases highly penetrant germline mutations are found. The remaining CRC heritability is still unexplained, and may be caused by a hitherto-undefined set of rare variants with a moderately penetrant risk. Here we aimed to identify novel risk factors for early-onset CRC using whole-exome sequencing, which was performed on a cohort of CRC individuals (n = 55) with a disease onset before 45 years of age. We searched for genes that were recurrently affected by rare variants (minor allele frequency ≤0.001) with potentially damaging effects and, subsequently, re-sequenced the candidate genes in a replication cohort of 174 early-onset or familial CRC individuals. Two functionally relevant genes with low frequency variants with potentially damaging effects, PTPN12 and LRP6, were found in at least three individuals. The protein tyrosine phosphatase PTP-PEST, encoded by PTPN12, is a regulator of cell motility and LRP6 is a component of the WNT-FZD-LRP5-LRP6 complex that triggers WNT signaling. All variants in LRP6 were identified in individuals with an extremely early-onset of the disease (≤30 years of age), and two of the three variants showed increased WNT signaling activity in vitro. In conclusion, we present PTPN12 and LRP6 as novel candidates contributing to the heterogeneous susceptibility to CRC. PMID:26901136

  11. 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

  12. Early onset type 2 diabetes in Jamaica and in Mexico. Opportunities derived from an interethnic study.

    PubMed

    Irving, Rachael; Tusié-Luna, Ma Teresa; Mills, James; Wright-Pascoe, Rosemarie; McLaughlin, Wayne; Aguilar-Salinas, Carlos A

    2011-01-01

    Populations with Amerindian or African heritages are the one with the highest prevalence of diabetes worldwide. A large percentage of these individuals survived famine. However, the survival effect has become detrimental to their descendents living in an environment of caloric surplus. In countries, like Mexico and Jamaica, in which diabetes is highly prevalent, the onset of the disease happens at earlier ages. Our objective is to summarize diabetes data from Mexico and Jamaica and to discuss the opportunities that can result from an interethnic study. On one hand, the prevalence of diabetes in Jamaica is 17.9% in the 15+ age group. Jamaican researchers have built a cohort of families with early onset type 2 diabetes. In this population, this form of the disease is unrelated to MODY genes. On the other hand, the prevalence of diabetes in adult Mexicans is 14.4%. The group in which the greater percentual changes have occurred is the adults who are below the age of 40. More than two thirds of the early onset cases studied have a body mass index that is >25 kg/m2 and the clinical characteristics of metabolic syndrome. A minority of them has mutations in the MODY genes. The joint study of Mexican and Jamaican cohorts of early onset type 2 diabetes cases will be useful to identify new genetic and environmental players in the pathogenesis of this entity. PMID:21714438

  13. EARLY ONSET OF DELINQUENCY AND THE TRAJECTORY OF ALCOHOL-IMPAIRED DRIVING AMONG YOUNG MALES*

    PubMed Central

    Zhang, Lening; Wieczorek, William F.; Welte, John W.

    2011-01-01

    Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. PMID:21831528

  14. 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 future use as a platform to evaluate treatment effectiveness. PMID:26317230

  15. 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.

  16. Neurological and cytogenetic study in early-onset ataxia-telangiectasia patients.

    PubMed

    Leuzzi, V; Elli, R; Antonelli, A; Chessa, L; Cardona, F; Marcucci, L; Petrinelli, P

    1993-07-01

    The clinical diagnosis of ataxia-telangiectasia (AT) is difficult before the age of 4 years. We report clinical and cytogenetic data on three early-onset, early-diagnosed AT patients at the age of 12, 18 and 22 months, respectively. Postural instability of the trunk, characterized by motor impersistence, was the earliest neurological sign detected as early as 1 year of life. Dystonic movements and postures of arms and trunk and a subtle disorder of eye movement (blinking before gaze changing, increased latency and dysmetry of saccades) were observed during the 2nd year of life. All patients exhibited an unusual temper tantrum. We also observed an increased bleomycin-induced chromosomal instability in patient's cells in the early stages of the disease before all the clinical hallmarks were apparent. Our data suggest that detection of clinical indications, leading to early laboratory confirmation of AT, can reduce the age at diagnosis. PMID:7689057

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

    PubMed Central

    Weygandt, Martin; Hummel, Hannah-Maria; Schregel, Katharina; Ritter, Kerstin; Allefeld, Carsten; Dommes, Esther; Huppke, Peter; Haynes, JohnDylan; Wuerfel, Jens; Grtner, Jutta

    2014-01-01

    Currently, it is unclear whether pediatric multiple sclerosis (PMS) is a pathoetiologically homogeneous disease phenotype due to clinical and epidemiological differences between early and late onset PMS (EOPMS and LOPMS). Consequently, the question was raised whether diagnostic guidelines need to be complemented by specific EOPMS markers. To search for such markers, we analyzed cerebral MRI images acquired with standard protocols using computer-based classification techniques. Specifically, we applied classification algorithms to gray (GM) and white matter (WM) tissue probability parameters of small brain regions derived from T2-weighted MRI images of EOPMS patients (onset <12years), LOPMS patients (onset ?12years), and healthy controls (HC). This was done for PMS subgroups matched for disease duration and participant age independently. As expected, maximal diagnostic information for distinguishing PMS patients and HC was found in a periventricular WM area containing lesions (87.1% accuracy, p<2.2נ10?5). MRI-based biomarkers specific for EOPMS were identified in prefrontal cortex. Specifically, a coordinate in middle frontal gyrus contained maximal diagnostic information (77.3%, p=1.8נ10?4). Taken together, we were able to identify biomarkers reflecting pathognomonic processes specific for MS patients with very early onset. Especially GM involvement in the separation between PMS subgroups suggests that conventional MRI contains a richer set of diagnostically informative features than previously assumed. PMID:25685704

  18. Neonatal infected subgaleal hematoma: an unusual complication of early-onset E. coli sepsis.

    PubMed

    Chang, Hung-Yang; Cheng, Kun-Shan; Liu, Yu-Peng; Hung, Hsiao-Fang; Fu, Hua-Wen

    2015-04-01

    Subgaleal hematoma (SGH) is an uncommon but potentially lethal medical emergency in newborns. Delay in diagnosis may lead to mortality and morbidity. Infection of an SGH is extremely rare. We report an infected SGH with abscess formation as a complication of early-onset Escherichia coli sepsis in a term neonate. The patient was discovered to have SGH soon after birth. Early-onset E. coli sepsis developed on Day 3 of life. The SGH became infected, with abscess formation 1 week later. The infected SGH was probably due to direct hematogenous spreading of sepsis. The patient was successfully treated without complications. Clinicians should be aware that SGH is a potential site of infection and infection may be caused either by direct hematogenous extension or from traumatic scalp lesions. Appropriate antibiotic treatment and surgical debridement are necessary when an infected SGH occurs. PMID:23597516

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

    PubMed Central

    Walls, Melissa L.; Whitbeck, Les B.

    2011-01-01

    This paper 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 group residing on reservations/reserves in the upper Midwest and Canada. Results of structural equation modeling revealed that the statistically significant relationship between girls' pubertal development and early-onset substance use was mediated by both mixed-sex/romantic peer groups and favorable social definitions of substance use. Implications for substance use prevention work include addressing the multiple and overlapping effects of peer influence from culturally-relevant perspectives. PMID:22228919

  20. Psychosis in children and youth: focus on early-onset schizophrenia.

    PubMed

    Abidi, Sabina

    2013-07-01

    On the basis of strong research evidence (1)(3) very early onset (VEOS) and early onset schizophrenia (EOS) carry significant morbidity and mortality risks for children and adolescents. On the basis of strong research evidence, the pathogenesis of EOS is linked to a dysregulation of dopamine and morphologic brain changes. (6)(7) On the basis of some research evidence and consensus, development of schizophrenia is the result of the interplay between genetic and environmental risk factors. (4) On the basis of strong research evidence, antipsychotic medications are the cornerstones of treatment for EOS. (11)(12)(13) On the basis of some research evidence and consensus, (13) treatment for schizophrenia should be timely, multimodal and multidisciplinary, including both pharmacologic and nonpharmacologic modalities tooptimize recovery. PMID:23818084

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

    PubMed Central

    Caswell, Richard; Allen, Hana Lango; De Franco, Elisa; McDonald, Timothy J.; Rajala, Hanna; Ramelius, Anita; Barton, John; Heiskanen, Kaarina; Heiskanen-Kosma, Tarja; Kajosaari, Merja; Murphy, Nuala P.; Milenkovic, Tatjana; Seppnen, Mikko; Lernmark, ke; Mustjoki, Satu; Otonkoski, Timo; Kere, Juha; Morgan, Noel G.; Ellard, Sian; Hattersley, Andrew T.

    2014-01-01

    Monogenic causes of autoimmunity give key insights to the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in 5 individuals with a spectrum of early-onset autoimmune disease including type 1 diabetes. These findings emphasise the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in Hyper IgE syndrome. PMID:25038750

  2. 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…

  3. 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

  4. 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

  5. Indoor tanning and risk of early-onset basal cell carcinoma

    PubMed Central

    Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2011-01-01

    Background Despite a rise in incidence of basal cell carcinoma (BCC) among young people and the ubiquity of indoor tanning in this population, few epidemiologic studies have investigated this exposure-disease relationship. Objective Evaluate the association between indoor tanning and early-onset BCC. Methods BCC cases (n=376) and controls with minor benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on ever indoor tanning, age of initiation, frequency, duration, burns while tanning, and type of tanning device during an in-person interview. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression with never indoor tanners as the referent group. Results Ever indoor tanning was associated with a 69% increased risk of early-onset BCC (95% CI=1.15-2.48). This association was stronger among women (OR=2.14, 95% CI=1.31-3.47), for multiple BCCs (OR=2.16, 95% CI=1.26-3.70), and for BCCs on the trunk and extremities (OR=2.81, 95% CI=1.57-5.02). Risk increased dose-dependently with years used regular indoor tanning devices (p-trend=0.003), number of overall burns (p-trend=<0.001) and burns to biopsy site (p-trend=<0.001) from indoor tanning. Approximately one-quarter (27%) of early-onset BCCs (or 43% among women) could be prevented if individuals never tanned indoors. Limitations Potential recall bias of indoor tanning by cases and generalizability of the control population suggest replication in other studies is warranted. Conclusions Indoor tanning was a strong risk factor for early-onset BCC, particularly among women. Indoor tanning should continue to be targeted by both policy-based and behavioral interventions, as the impact on BCC-associated morbidity may be substantial. PMID:22153793

  6. 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

  7. Alcohol intake and early-onset basal cell carcinoma in a case-control study

    PubMed Central

    Zhang, Y; Ferrucci, L.M.; Cartmel, B.; Molinaro, A.M.; Leffell, D.J.; Bale, A.E.; Mayne, S.T.

    2014-01-01

    Background Previous epidemiologic studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) light, this has not been evaluated in existing epidemiologic studies. Objective To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Methods BCC cases (n=380) and controls with benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage during an in-person interview. Self-report data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional multivariate logistic regression in the full sample and in women only. Results There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall (above median intake vs. no regular alcohol intake OR 1.10, 95% CI 0.69-1.73) or in women only (OR 1.21, 95% CI 0.73-2.01). Similarly, intake of red wine, white wine, beer or hard liquor and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (pinteraction=0.003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping confidence intervals. Conclusions Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. PMID:25059635

  8. IL-10R Polymorphisms are Associated with Very Early-Onset Ulcerative Colitis

    PubMed Central

    Moran, Christopher J; Walters, Thomas D; Guo, Cong-Hui; Kugathasan, Subra; Klein, Christoph; Turner, Dan; Wolters, Victorien M; Bandsma, Robert H; Mouzaki, Marialena; Langer, Jacob C; Cutz, Ernest; Benseler, Susanne M; Roifman, Chaim M; Silverberg, Mark S; Griffiths, Anne M; Snapper, Scott B; Muise, Aleixo M

    2012-01-01

    Background and Aims Interleukin-10 (IL-10) signaling genes are attractive inflammatory bowel disease (IBD) candidate genes as IL-10 restricts intestinal inflammation, IL-10 polymorphisms have been associated with IBD in genome-wide association studies, and mutations in IL-10 and IL-10 receptor (IL-10R) genes have been reported in immunodeficient children with severe infantile-onset IBD. Our objective was to determine if IL-10R polymorphisms were associated with early-onset IBD (EO-IBD) and very early-onset IBD (VEO-IBD). Methods Candidate-gene analysis of IL10RA and IL10RB was performed after initial sequencing of an infantile onset-IBD patient identified a novel homozygous mutation. The discovery cohort included 188 EO-IBD subjects and 188 healthy subjects. Polymorphisms associated with IBD in the discovery cohort were genotyped in an independent validation cohort of 422 EO-IBD subjects and 480 healthy subjects. Results We identified a homozygous, splice-site point mutation in IL10RA in an infantile-onset IBD patient causing a premature stop codon (P206X) and IL-10 insensitivity. IL10RA and IL10RB sequencing in the discovery cohort identified five IL10RA polymorphisms associated with ulcerative colitis (UC) and two IL10RB polymorphisms associated with Crohn’s disease (CD). Of these polymorphisms, two IL10RA SNPs, rs2228054 and rs2228055 were associated with very early-onset UC in the discovery cohort and replicated in an independent validation cohort (OR 3.08, combined p=2×10−4; and OR 2.93, p=6×10−4, respectively). Conclusions We identified IL10RA polymorphisms that confer risk for developing VEO-UC. Additionally, we identified the first splice site mutation in IL10RA resulting in infantile-onset IBD. This study expands the phenotype of IL10RA polymorphisms to include both severe arthritis and VEO-UC. PMID:22550014

  9. 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

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

    PubMed

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

    2015-09-01

    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 months-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

  11. A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease.

    PubMed

    Esmer, Carmen; Becerra-Becerra, Rosario; Peña-Zepeda, Claudia; Bravo-Oro, Antonio

    2013-10-01

    Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect. PMID:24399866

  12. Recessive mutations in PCBD1 cause a new type of early-onset diabetes.

    PubMed

    Simaite, Deimante; Kofent, Julia; Gong, Maolian; Rüschendorf, Franz; Jia, Shiqi; Arn, Pamela; Bentler, Kristi; Ellaway, Carolyn; Kühnen, Peter; Hoffmann, Georg F; Blau, Nenad; Spagnoli, Francesca M; Hübner, Norbert; Raile, Klemens

    2014-10-01

    Mutations in several genes cause nonautoimmune diabetes, but numerous patients still have unclear genetic defects, hampering our understanding of the development of the disease and preventing pathogenesis-oriented treatment. We used whole-genome sequencing with linkage analysis to study a consanguineous family with early-onset antibody-negative diabetes and identified a novel deletion in PCBD1 (pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 α), a gene that was recently proposed as a likely cause of diabetes. A subsequent reevaluation of patients with mild neonatal hyperphenylalaninemia due to mutations in PCBD1 from the BIODEF database identified three additional patients who had developed HNF1A-like diabetes in puberty, indicating early β-cell failure. We found that Pcbd1 is expressed in the developing pancreas of both mouse and Xenopus embryos from early specification onward showing colocalization with insulin. Importantly, a morpholino-mediated knockdown in Xenopus revealed that pcbd1 activity is required for the proper establishment of early pancreatic fate within the endoderm. We provide the first genetic evidence that PCBD1 mutations can cause early-onset nonautoimmune diabetes with features similar to dominantly inherited HNF1A-diabetes. This condition responds to and can be treated with oral drugs instead of insulin, which is important clinical information for these patients. Finally, patients at risk can be detected through a newborn screening for phenylketonuria. PMID:24848070

  13. 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.

  14. Early age of onset in fatal familial insomnia. Two novel cases and review of the literature.

    PubMed

    Harder, A; Gregor, A; Wirth, T; Kreuz, F; Schulz-Schaeffer, W J; Windl, O; Plotkin, M; Amthauer, H; Neukirch, K; Kretzschmar, H A; Kuhlmann, T; Braas, R; Hahne, H H; Jendroska, K

    2004-06-01

    Fatal familial insomnia (FFI) is a prion disease exhibiting the PRNP D178N/129M genotype. Features of this autosomal dominant illness are progressive insomnia, dysautonomia, myoclonus, cognitive decline and motor signs associated with thalamic nerve cell loss and gliosis. In contrast to the new variant of Creutzfeldt-Jakob disease (vCJD) the onset of FFI is in middle to late adulthood. We report two male patients who belong to a large German FFI kindred. They were examined clinically, and postmortem neuropathological examination was carried out in collaboration with the German reference centre for prion disease. Additionally, the prion protein gene (PRNP) was analysed. To identify further patients with disease onset under 30 years of age a comprehensive literature review was carried out. Two male patients presented with typical symptoms of FFI at the age of 23 and 24 years. In their kindred, the age of onset has never before been under 44 years of age. Our literature review identified five additional early onset cases who died at age 21 to 25 years. In all 22 reviewed FFI families the median manifestation age was 49.5 years. Although phenotypic variability of FFI is common, age of onset under 30 years has been considered to be a hallmark of vCJD with a mean manifestation at 27 years of age. Our findings underline that in addition to vCJD, FFI must be considered in cases of young-onset prion disease. This has considerable impact on clinical management and genetic counselling. PMID:15311348

  15. Long-term efficacy of microbiology-driven periodontal laser-assisted therapy.

    PubMed

    Martelli, F S; Fanti, E; Rosati, C; Martelli, M; Bacci, G; Martelli, M L; Medico, E

    2016-03-01

    Periodontitis represents a highly prevalent health problem, causing severe functional impairment, reduced quality of life and increased risk of systemic disorders, including respiratory, cardiovascular and osteoarticular diseases, diabetes and fertility problems. It is a typical example of a multifactorial disease, where a polymicrobial infection inducing chronic inflammation of periodontal tissues is favoured by environmental factors, life style and genetic background. Since periodontal pathogens can colonise poorly vascularised niches, antiseptics and antibiotics are typically associated with local treatments to manage the defects, with unstable outcomes especially in early-onset cases. Here, the results of a retrospective study are reported, evaluating the efficacy of a protocol (Periodontal Biological Laser-Assisted Therapy, Perioblast™) by which microbial profiling of periodontal pockets is used to determine the extent and duration of local neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation plus conventional treatment. The protocol was applied multicentrically on 2683 patients, and found to produce a significant and enduring improvement of all clinical and bacteriological parameters, even in aggressive cases. Microbiome sequencing of selected pockets revealed major population shifts after treatment, as well as strains potentially associated with periodontitis in the absence of known pathogens. This study, conducted for the first time on such a large series, clearly demonstrates long-term efficacy of microbiology-driven non-invasive treatment of periodontal disease. PMID:26740323

  16. Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT recipients.

    PubMed

    Shingai, N; Morito, T; Najima, Y; Kobayashi, T; Doki, N; Kakihana, K; Ohashi, K; Ando, M

    2015-12-01

    Acute kidney injury (AKI) following stem-cell transplantation (SCT) contributes to a poor prognosis, yet its impact may vary depending on the timing of AKI onset. A prospective cohort study was performed to understand the significance of the onset timing in 103 allogeneic SCT (allo-SCT) recipients. AKI prior to stem-cell engraftment was defined as early AKI and subsequently occurring AKI as late AKI. Propensity score (PS) for early AKI was calculated using a logistic regression model to reduce confounding effects related to differences in clinical background between the early and late AKI groups. The cumulative incidences of early and late AKI were 22.3% and 54.9%, respectively. Non-relapse mortality (NRM) was 39.1% and 7.0%, and overall survival (OS) was 56.5% and 90.9% in early and late AKI at 100 days after AKI, respectively (P<0.001). The cumulative incidence of chronic kidney disease (CKD) over 2 years after SCT was 41.5% and 19.1% in early and late AKI, respectively (P=0.048). Logistic regression analysis adjusted for the PS showed that early AKI was significantly associated with OS (odds ratio (95% confidence interval); 4.63 (1.15-21.4), P=0.031) but with neither NRM (1.25 (0.28-5.33), P=0.766) nor CKD (1.85 (0.41-8.60), P=0.422). In conclusion, early AKI may portend a poor survival for allo-SCT recipients. PMID:26301965

  17. Association between Polymorphisms in Cancer-Related Genes and Early Onset of Esophageal Adenocarcinoma123

    PubMed Central

    Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

    2011-01-01

    There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ? 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (?55 vs >55 years, all P < .05 after adjusting for co-variates and false discovery rate). Among them, five SNPs in the NOS3, BCL2, TNFRSF10A, and CASP8 genes were known to be involved in apoptosis processes. In Kaplan-Meier analyses, rs2070744 of NOS3, rs720321 of BCL2, and rs1035142 of CASP8 were also significantly associated with early onset of EA. Moreover, there was a higher risk of developing EA at a younger age when one had more risk genotypes. In conclusion, polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner. PMID:21472143

  18. Selenoprotein N muscular dystrophy: differential diagnosis for early-onset limited mobility of the spine.

    PubMed

    Sponholz, Stefanie; von der Hagen, Maja; Hahn, Gabriele; Seifert, Jens; Richard, Pascale; Stoltenburg-Didinger, Gisela; Ferreiro, Ana; Kaindl, Angela M

    2006-04-01

    Early spinal rigidity is a nonspecific feature reported in diseases such as neuromuscular and central movement disorders. We present a male patient with rigid spine muscular dystrophy caused by newly identified compound heterozygote mutations of the selenoprotein N gene and discuss this disease as a possible differential diagnosis for early-onset reduced spine mobility. Rigid spine muscular dystrophy is a rare myopathy presenting in childhood with a typical combination of stable or slowly progressive mild to moderate muscle weakness, limitation in flexion of the spine, and progressive restrictive ventilatory disorder. The clinical features of our patient include early-onset rigidity of his spine, scoliosis, mild muscular weakness predominantly of neck and trunk flexors, and restrictive ventilatory disorder. Biopsy of the biceps muscle revealed nonspecific myopathic changes, and molecular analysis confirmed the diagnosis of rigid spine muscular dystrophy. Thus, neuromuscular diseases such as muscular dystrophy must be considered in all patients presenting with early spinal rigidity, and genetic determination is a possible way to determine the diagnosis. PMID:16900928

  19. 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

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

    PubMed Central

    2011-01-01

    Background Genetic and environmental risk factors and gene-environment interactions are linked to higher likelihood of developing schizophrenia in accordance with the neurodevelopmental model of disease; little is known about risk factors and early development in early-onset schizophrenia (EOS) and very early-onset schizophrenia (VEOS). Methods We present a case-control study of a sample of 21 patients with EOS/VEOS and a control group of 21 patients with migraine, recruited from the Child Neuropsychiatry Unit, Department of Neurologic and Psychiatric Science, University of Bari, Italy. The aim was to assess the statistical association between VEOS/EOS and family history for psychiatric disorders, obstetric complications and childhood developmental abnormalities using 2 × 2 tables and a Chi Squared or Fisher test. Results The results show a statistical association between EOS/VEOS and schizophrenia and related disorders (P = 0.02) and personality disorders (P = 0.003) in relatives, and between EOS/VEOS and developmental abnormalities of early relational skills (P = 0.008) and learning (P = 0.04); there is not a statistically relevant difference between cases and controls (P > 0.05) for any obstetric complications (pre, peri and postpartum). Conclusions This study confirms the significant role of familial liability but not of obstetric complications in the pathogenesis of VEOS/EOS; the association between childhood developmental abnormalities and EOS/VEOS supports the neurodevelopmental model of disease. PMID:21492438

  1. 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.

  2. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families.

    PubMed

    1995-10-01

    Genetic linkage studies place a gene causing early onset familial Alzheimer's disease (FAD) on chromosome 14q24.3 (refs 1-4). Five mutations within the S182 (Presenilin 1: PS-1) gene, which maps to this region, have recently been reported in several early onset FAD kindreds. We have localized the PS-1 gene to a 75 kb region and present the structure of this gene, evidence for alternative splicing and describe six novel mutations in early onset FAD pedigrees all of which alter residues conserved in the STM2 (Presenilin 2: PS-2) gene. PMID:7550356

  3. Time since onset of walking predicts tibial bone strength in early childhood.

    PubMed

    Ireland, Alex; Rittweger, Jörn; Schönau, Eckhard; Lamberg-Allardt, Christel; Viljakainen, Heli

    2014-11-01

    Bone strength in adulthood is known to be affected by health at birth and early childhood. Habitual bone loading is a primary determinant of bone strength in later childhood and adulthood. However, the effects of physical activity in early childhood (e.g. crawling, standing and walking) on bone strength are unknown. Fifty-three children (twenty-seven males) were included in a longitudinal study in their early infancy. Shortly after birth (0.3±0.3months), details of mass and height were obtained along with a pQCT scan at 20% distal-proximal tibia length. At 14.8±0.5months of age the same data were collected, along with details of age at onset of standing, crawling, supported and unsupported walking. Time since onset of walking unsupported was associated with greater bone mass, cortical bone area, pericortical circumference and polar moment of inertia of both total and cortical bone (all P<0.05). There were no significant associations between other physical activity timepoints and bone measures. Age at onset of walking was not significantly related to mass, length or bone measures at birth. The results suggest that time since attainment of independent walking - representing exposure of the tibia to the large reaction and muscular forces associated with locomotion - is a primary determinant of bone strength in early childhood. This finding raises the possible opportunity of physical activity interventions at young age in paediatric populations associated with low childhood bone strength and late walking (e.g. low birth weight, cerebral palsy and Down's Syndrome, etc.). PMID:25132490

  4. A Unified Hypothesis of Early- and Late-Onset Alzheimer's Disease Pathogenesis.

    PubMed

    Atwood, Craig S; Bowen, Richard L

    2015-01-01

    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, tau phosphorylation, formation of intracellular neurofibrillary tangles, endoreduplication and related cell cycle events in affected brain regions. Any mechanistic explanation of AD must accommodate these biochemical and neuropathological features for both forms of the disease. In this insight paper we provide a unifying hypothesis for EOFAD and LOSAD that proposes that the aberrant re-entry of terminally differentiated, post-mitotic neurons into the cell division cycle is a common pathway that explains both early and late-onset forms of AD. Cell cycle abnormalities appear very early in the disease process, prior to the appearance of plaques and tangles, and explain the biochemical (e.g. tau phosphorylation), neuropathological (e.g. neuron hypertrophy; polypoidy) and cognitive changes observed in EOFAD and LOSAD. Genetic mutations in AβPP, PSEN1, and PSEN2 that alter amyloid-β precursor protein and Notch processing drive reactivation of the cell cycle in EOFAD, while age-related reproductive endocrine dyscrasia that upregulates mitogenic TNF signaling and AβPP processing toward the amyloidogenic pathway drives reactivation of the cell cycle in LOSAD. In essence, AβPP and presenilin mutations initiate early, what endocrine dyscrasia initiates later: aberrant cell cycle re-entry of post-mitotic neurons leading to neurodegeneration and cognitive decline in AD. Inhibition of cell cycle re-entry in post-mitotic neurons may be a useful therapeutic strategy to prevent, slow or halt disease progression. PMID:26402752

  5. 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

  6. 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

  7. Early-onset pneumonia after out-of-hospital cardiac arrest.

    PubMed

    Kakavas, S; Mongardon, N; Cariou, A; Gulati, A; Xanthos, T

    2015-06-01

    Early-onset pneumonia (EOP) is a common complication after successful cardiopulmonary resuscitation. Currently, EOP diagnosis is difficult because usual diagnostic tools are blunted by the features of post-cardiac arrest syndrome and therapeutic hypothermia itself. When the diagnosis of EOP is suspected, empiric antimicrobial therapy should be considered following bronchopulmonary sampling. The onset of EOP increases the length of mechanical ventilation duration and intensive care unit stay, but its influence on survival and neurological outcome seems marginal. Therapeutic hypothermia has been recognized as an independent risk factor for this infectious complication. All together, these observations underline the need for future prospective clinical trials to better delineate pathogens and risk factors associated with EOP. In addition, there is a need for diagnostic approaches serving the accurate diagnosis of EOP. PMID:25644317

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

    PubMed

    Klein, Lisa; Saur, Ralf; Mller, 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 Tbingen 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

  9. Preventative strategies for early-onset bipolar disorder: towards a clinical staging model.

    PubMed

    McNamara, Robert K; Nandagopal, Jayasree J; Strakowski, Stephen M; DelBello, Melissa P

    2010-12-01

    Bipolar disorder is a chronic and typically recurring illness with significant psychosocial morbidity. Although the aetiological factors that contribute to the onset of mania, and by definition bipolar I disorder, are poorly understood, it most commonly occurs during the adolescent period. Putative risk factors for developing bipolar disorder include having a first-degree relative with a mood disorder, physical/sexual abuse and other psychosocial stressors, substance use disorders, psychostimulant and antidepressant medication exposure and omega-3 fatty acid deficiency. Prominent prodromal clinical features include episodic symptoms of depression, anxiety, hypomania, anger/irritability and disturbances in sleep and attention. Because prodromal mood symptoms precede the onset of mania by an average of 10 years, and there is low specificity of risk factors and prodromal features for mania, interventions initiated prior to onset of the disorder (primary prevention) or early in the course of the disorder (early or secondary prevention) must be safe and well tolerated upon long-term exposure. Indeed, antidepressant and psychostimulant medications may precipitate the onset of mania. Although mood stabilizers and atypical antipsychotic medications exhibit efficacy in youth with bipolar I disorder, their efficacy for the treatment of prodromal mood symptoms is largely unknown. Moreover, mood stabilizers and atypical antipsychotics are associated with prohibitive treatment-emergent adverse effects. In contrast, omega-3 fatty acids have neurotrophic and neuroprotective properties and have been found to be efficacious, safe and well tolerated in the treatment of manic and depressive symptoms in children and adolescents. Together, extant evidence endorses a clinical staging model in which subjects at elevated risk for developing mania are treated with safer interventions (i.e. omega-3 fatty acids, family-focused therapy) in the prodromal phase, followed by pharmacological agents with potential adverse effects for nonresponsive cases and secondary prevention. This approach warrants evaluation in prospective longitudinal trials in youth determined to be at ultra-high risk for bipolar I disorder. PMID:21090835

  10. 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…

  11. Specific antibody reactivity against a 110-kilodalton Actinobacillus actinomycetemcomitans protein in subjects with periodontitis.

    PubMed Central

    Fleming, T F; Selmair, I; Schmidt, H; Karch, H

    1996-01-01

    The purpose of the present study was to determine the serum immunoglobulin A (IgA), IgM, and IgG reactivities against proteins of Actinobacillus actinomycetemcomitans in patients with periodontitis. Serum samples from 20 patients with early-onset periodontitis, 20 patients with adult periodontitis, and 20 age- and sex-matched healthy controls were assessed by immunoblot analysis. IgG antibody reactivity against a sarcosyl-insoluble 110-kDa protein of A. actinomycetemcomitans was detected in 65 and 45% of patients with early-onset periodontitis and adult peritonitis, respectively, and IgA antibodies against this protein were found in 70 and 55% of these patients, respectively. However, control subjects showed no IgG reactivity, and IgA antibodies against the sarcosyl-insoluble 110-kDa protein were detected in only 5% of the patients (P < 0.05). There was no IgM antibody reactivity against this protein in any of the diseased or healthy subjects. The sensitivity and specificity of serum IgA antibody reactivity against the 110-kDa protein in detecting subgingival A. actinomycetemcomitans infection, as determined by PCR, were 77 and 66%, respectively. The results of the study indicated that the sarcosyl-insoluble 110-kDa protein is a potential candidate for use in the serodiagnosis of periodontal disease. PMID:8914758

  12. 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

  13. Early-onset restrictive eating disturbances in primary school boys and girls.

    PubMed

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

    2015-07-01

    This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). A total of 1,444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. 46 children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study's findings. PMID:25296563

  14. 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

  15. Early-Onset Scoliosis: A Review of History, Current Treatment, and Future Directions.

    PubMed

    Yang, Scott; Andras, Lindsay M; Redding, Gregory J; Skaggs, David L

    2016-01-01

    Early-onset scoliosis (EOS) is defined as curvature of the spine in children >10 with onset before age 10 years. Young children with EOS are at risk for impaired pulmonary function because of the high risk of progressive spinal deformity and thoracic constraints during a critical time of lung development. The treatment of EOS is very challenging because the population is inhomogeneous, often medically complex, and often needs multiple surgeries. In the past, early spinal fusion was performed in children with severe progressive EOS, which corrected scoliosis but limited spine and thoracic growth and resulted in poor pulmonary outcomes. The current goal in treatment of EOS is to maximize growth of the spine and thorax by controlling the spinal deformity, with the aim of promoting normal lung development and pulmonary function. Bracing and casting may improve on the natural history of progression of spinal deformity and are often used to delay surgical intervention or in some cases obviate surgery. Recent advances in surgical implants and techniques have led to the development of growth-friendly implants, which have replaced early spine fusion as the surgical treatment of choice. Treatment with growth-friendly implants usually requires multiple surgeries and is associated with frequent complications. However, growth-friendly spine surgery has been shown to correct spinal deformity while allowing growth of the spine and subsequently lung growth. PMID:26644484

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

    PubMed Central

    Tan, Dandan; Yang, Haipo; Yuan, Yun; Bonnemann, Carsten; Chang, Xingzhi; Wang, Shuang; Wu, Yuchen; Wu, Xiru; Xiong, Hui

    2015-01-01

    This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA)-related muscular dystrophy (MD). The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293) cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD) and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD). Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C) were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype–genotype analysis determines that some mutations are well correlated with LMNA-related MD. PMID:26098624

  17. Inactivating Mutations in GT198 in Familial and Early-Onset Breast and Ovarian Cancers

    PubMed Central

    Peng, Min; Bakker, Janine L.; DiCioccio, Richard A.; Gille, Johan J.P.; Zhao, Hua; Odunsi, Kunle; Sucheston, Lara; Jaafar, Lahcen; Mivechi, Nahid F.; Waisfisz, Quinten

    2013-01-01

    The human GT198 gene (gene symbol PSMC3IP) is located at chromosome 17q21, 470 kb proximal to BRCA1, a locus previously linked to breast and ovarian cancer predisposition. Its protein product (also known as TBPIP and Hop2) has been shown to regulate steroid hormone receptor–mediated gene activation and to stimulate homologous recombination in DNA repair. Here, we screened germline mutations in GT198 in familial and early-onset breast and ovarian cancer patients. We have identified 8 germline variants in a total of 212 index patients including reoccurring nonsense mutation c.310C>T (p.Q104X) and 5′ UTR mutation c.-37A>T, each found in 2 unrelated families. Most identified index patients from cancer families had early onsets with a median age of 35 years. c.310C>T was absent in a total of 564 control individuals analyzed. GT198 gene amplification with an imbalanced mutant copy gain was identified in the blood DNA of one of the patients carrying c.310C>T. When tested, this truncating mutation abolished DNA damage–induced Rad51 foci formation. In addition, we have identified 15 somatic mutations in 2 tumors from 1 patient carrying germline mutation c.-37A>T. The presence of a somatic mutation on the wild-type allele showed that GT198 was biallelically mutated in the tumor. The somatic mutations identified near a splicing junction site caused defective alternative splicing and truncated the open reading frame. Therefore, distinct mutations may cause a similar consequence by truncating the full-length protein and inducing a loss of the wild type. Our study provides the first evidence of the presence of inactivating mutations in GT198 in familial and early-onset breast and ovarian cancer patients. Mutations in GT198, a gene regulating DNA repair, potentially contribute to an increased risk in familial breast and ovarian cancers. PMID:23946868

  18. Inactivating Mutations in GT198 in Familial and Early-Onset Breast and Ovarian Cancers.

    PubMed

    Peng, Min; Bakker, Janine L; Dicioccio, Richard A; Gille, Johan J P; Zhao, Hua; Odunsi, Kunle; Sucheston, Lara; Jaafar, Lahcen; Mivechi, Nahid F; Waisfisz, Quinten; Ko, Lan

    2013-01-01

    The human GT198 gene (gene symbol PSMC3IP) is located at chromosome 17q21, 470 kb proximal to BRCA1, a locus previously linked to breast and ovarian cancer predisposition. Its protein product (also known as TBPIP and Hop2) has been shown to regulate steroid hormone receptor-mediated gene activation and to stimulate homologous recombination in DNA repair. Here, we screened germline mutations in GT198 in familial and early-onset breast and ovarian cancer patients. We have identified 8 germline variants in a total of 212 index patients including reoccurring nonsense mutation c.310C>T (p.Q104X) and 5' UTR mutation c.-37A>T, each found in 2 unrelated families. Most identified index patients from cancer families had early onsets with a median age of 35 years. c.310C>T was absent in a total of 564 control individuals analyzed. GT198 gene amplification with an imbalanced mutant copy gain was identified in the blood DNA of one of the patients carrying c.310C>T. When tested, this truncating mutation abolished DNA damage-induced Rad51 foci formation. In addition, we have identified 15 somatic mutations in 2 tumors from 1 patient carrying germline mutation c.-37A>T. The presence of a somatic mutation on the wild-type allele showed that GT198 was biallelically mutated in the tumor. The somatic mutations identified near a splicing junction site caused defective alternative splicing and truncated the open reading frame. Therefore, distinct mutations may cause a similar consequence by truncating the full-length protein and inducing a loss of the wild type. Our study provides the first evidence of the presence of inactivating mutations in GT198 in familial and early-onset breast and ovarian cancer patients. Mutations in GT198, a gene regulating DNA repair, potentially contribute to an increased risk in familial breast and ovarian cancers. PMID:23946868

  19. 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

  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. Late mortality among 5-year survivors of early onset cancer: a population-based register study.

    PubMed

    Kero, Andreina E; Järvelä, Liisa S; Arola, Mikko; Malila, Nea; Madanat-Harjuoja, Laura M; Matomäki, Jaakko; Lähteenmäki, Päivi M

    2015-04-01

    To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation-wide population-based registry study provides information concerning cause-specific long-term mortality among 16,769 5-year survivors of early onset cancer (aged 0-34 years at diagnosis), with follow-up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6-fold, (95% CI 4.4-4.8). Highest SMRs were found for malignancies (12.8, 95% CI 12.3-13.3), infectious (4.8, 95%CI 2.9-6.7) and cardiovascular diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non-malignancy-related mortality was due to cardiovascular disease with a steady rise throughout the follow-up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancy-related mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non-malignancy-related mortality stress the need to set up long-term individual follow-up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those. PMID:25110999

  2. 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

  3. Identification of inherited genetic variations influencing prognosis in early-onset breast cancer.

    PubMed

    Rafiq, Sajjad; Tapper, William; Collins, Andrew; Khan, Sofia; Politopoulos, Ioannis; Gerty, Sue; Blomqvist, Carl; Couch, Fergus J; Nevanlinna, Heli; Liu, Jianjun; Eccles, Diana

    2013-03-15

    Genome-Wide Association Studies (GWAS) have begun to investigate associations between inherited genetic variations and breast cancer prognosis. Here, we report our findings from a GWAS conducted in 536 patients with early-onset breast cancer aged 40 or less at diagnosis and with a mean follow-up period of 4.1 years (SD = 1.96). Patients were selected from the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer. A Bonferroni correction for multiple testing determined that a P value of 1.0 10(-7) was a statistically significant association signal. Following quality control, we identified 487,496 single nucleotide polymorphisms (SNP) for association tests in stage 1. In stage 2, 35 SNPs with the most significant associations were genotyped in 1,516 independent cases from the same early-onset cohort. In stage 2, 11 SNPs remained associated in the same direction (P ? 0.05). Fixed effects meta-analysis models identified one SNP associated at close to genome wide level of significance 556 kb upstream of the ARRDC3 locus [HR = 1.61; 95% confidence interval (CI), 1.33-1.96; P = 9.5 10(-7)]. Four further associations at or close to the PBX1, ROR?, NTN1, and SYT6 loci also came close to genome-wide significance levels (P = 10(-6)). In the first ever GWAS for the identification of SNPs associated with prognosis in patients with early-onset breast cancer, we report a SNP upstream of the ARRDC3 locus as potentially associated with prognosis (median follow-up time for genotypes: CC = 4 years, CT = 3 years, and TT = 2.7 years; Wilcoxon rank-sum test CC vs. CT, P = 4 10(-4) and CT vs. TT, P = 0.76). Four further loci may also be associated with prognosis. PMID:23319801

  4. 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

  5. A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study.

    PubMed

    Hauser, Elizabeth R; Crossman, David C; Granger, Christopher B; Haines, Jonathan L; Jones, Christopher J H; Mooser, Vincent; McAdam, Brendan; Winkelmann, Bernhard R; Wiseman, Alan H; Muhlestein, J Brent; Bartel, Alan G; Dennis, Charles A; Dowdy, Elaine; Estabrooks, Susan; Eggleston, Karen; Francis, Sheila; Roche, Kath; Clevenger, Paula W; Huang, Liling; Pedersen, Bonnie; Shah, Svati; Schmidt, Silke; Haynes, Carol; West, Sandra; Asper, Donny; Booze, Michael; Sharma, Sanjay; Sundseth, Scott; Middleton, Lefkos; Roses, Allen D; Hauser, Michael A; Vance, Jeffery M; Pericak-Vance, Margaret A; Kraus, William E

    2004-09-01

    A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide scan in 1,168 individuals from 438 families, including 493 affected sibling pairs with documented onset of CAD before 51 years of age in men and before 56 years of age in women. We prospectively defined three phenotypic subsets of families: (1) acute coronary syndrome in two or more siblings; (2) absence of type 2 diabetes in all affected siblings; and (3) atherogenic dyslipidemia in any one sibling. Genotypes were analyzed for 395 microsatellite markers. Regions were defined as providing evidence for linkage if they provided parametric two-point LOD scores >1.5, together with nonparametric multipoint LOD scores >1.0. Regions on chromosomes 3q13 (multipoint LOD = 3.3; empirical P value <.001) and 5q31 (multipoint LOD = 1.4; empirical P value <.081) met these criteria in the entire data set, and regions on chromosomes 1q25, 3q13, 7p14, and 19p13 met these criteria in one or more of the subsets. Two regions, 3q13 and 1q25, met the criteria for genomewide significance. We have identified a region on chromosome 3q13 that is linked to early-onset CAD, as well as additional regions of interest that will require further analysis. These data provide initial areas of the human genome where further investigation may reveal susceptibility genes for early-onset CAD. PMID:15272420

  6. 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

  7. 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 presentation reminiscent of LRRK2-associated PD neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS should be considered for genetic testing, and those with a known 22q11.2 deletion should be monitored for the development of parkinsonian symptoms. Molecular studies of the implicated genes, including DGCR8, may help shed light on the underlying pathophysiology of PD in 22q11.2DS and idiopathic PD. PMID:24018986

  8. 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

  9. Effects of smoking in patients with early-onset Parkinson's disease.

    PubMed

    Ishikawa, A; Miyatake, T

    1993-07-01

    Smoking a cigarette relieved symptoms in 6 patients with early-onset Parkinson's disease. In these patients smoking reduced tremor, rigidity, bradykinesia, and gait disturbance including frozen gait. These effects lasted for about 10-30 min, and relieved parkinsonian symptoms in the off-period. Nicotine chewing gum had a lesser effect. Nicotine is thought to activate the nigrostriatal dopaminergic pathway and increase the release of dopamine in the striatum, and this can explain the effects of smoking in these patients. PMID:8410063

  10. MAPPING THE PROGRESSION OF ATROPHY IN EARLY AND LATE ONSET ALZHEIMERS 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 Alzheimers 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

  11. Microbleeds in Late-Life Depression: Comparison of Early- and Late-Onset Depression

    PubMed Central

    Fang, Min; Xu, Yu; Hua, Ting; Liu, Xue-Yuan

    2014-01-01

    Late-life depression could be classified roughly as early-onset depression (EOD) and late-onset depression (LOD). LOD was proved to be associated with cerebral lesions including white matter hyperintensities (WMH) and silent brain infarctions (SBI), differently from EOD. However, it is unclear whether similar association is present between LOD and microbleeds which are also silent lesions. In this study, 195 patients of late-life depression were evaluated and divided into EOD, presenile-onset depression (POD), and LOD groups; 85 healthy elderly controls were enrolled as controls. Subjects were scanned by MRI including susceptibility weighted images to evaluate white matter hyperintensities (WMH), silent brain infarctions (SBI), and microbleeds. The severity of depression was evaluated with 15-item Geriatric Depression Scale. Psychosocial factors were investigated with Scale of Life Events and Lubben Social Network Scale. Logistic regression and linear regression were performed to identify the independent risk factors for depression. Results showed that LOD patients had higher prevalence of microbleeds than EOD, POD, and control patients. The prevalence of lobar microbleeds and microbleeds in the left hemisphere was the independent risk factor for the occurrence of LOD; a high number of microbleeds were associated with severe state of LOD, whereas life events and lack of social support were more important for EOD and POD. All these results indicated that Microbleeds especially lobar microbleeds and microbleeds in the left hemisphere were associated with LOD but not with EOD. PMID:24719883

  12. 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

  13. Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

    PubMed

    Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

    2012-12-01

    Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. PMID:22982606

  14. 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

  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. 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

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

    PubMed

    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

  19. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants

    PubMed Central

    2013-01-01

    Background Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants <29 weeks gestational age, including 11 infants who developed NEC and 21 matched controls who survived free of NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing. Urinary metabolomic profiles were assessed by NMR. Results During postnatal days 4 to 9, samples from infants who later developed NEC tended towards lower alpha diversity (Chao1 index, P = 0.086) and lacked Propionibacterium (P = 0.009) compared to controls. Furthermore, NEC was preceded by distinct forms of dysbiosis. During days 4 to 9, samples from four NEC cases were dominated by members of the Firmicutes (median relative abundance >99% versus <17% in the remaining NEC and controls, P < 0.001). During postnatal days 10 to 16, samples from the remaining NEC cases were dominated by Proteobacteria, specifically Enterobacteriaceae (median relative abundance >99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (≥98% relative abundance, days 4 to 9) or Proteobacteria (≥90% relative abundance, days 10 to 16) dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of days 4 to 9 urine samples found no metabolites associated with all NEC cases, but alanine was positively associated with NEC cases that were preceded by Firmicutes dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases preceded by Proteobacteria dysbiosis (P = 0.013). A high urinary alanine:histidine ratio was associated with microbial characteristics (P < 0.001) and provided good prediction of overall NEC (predictive value 78%, P = 0.007). Conclusions Early dysbiosis is strongly involved in the pathobiology of NEC. These striking findings require validation in larger studies but indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC. PMID:24450576

  20. IRAK-M Is Involved in the Pathogenesis of Early-Onset Persistent Asthma

    PubMed Central

    Balaci, Lenuta; Spada, MariaCristina; Olla, Nazario; Sole, Gabriella; Loddo, Laura; Anedda, Francesca; Naitza, Silvia; Zuncheddu, MariaAntonietta; Maschio, Andrea; Altea, Daniele; Uda, Manuela; Pilia, Sabrina; Sanna, Serena; Masala, Marco; Crisponi, Laura; Fattori, Matilde; Devoto, Marcella; Doratiotto, Silvia; Rassu, Stefania; Mereu, Simonetta; Giua, Enrico; Cadeddu, NatalinaGraziella; Atzeni, Roberto; Pelosi, Umberto; Corrias, Adriano; Perra, Roberto; Torrazza, PierLuigi; Pirina, Pietro; Ginesu, Francesco; Marcias, Silvano; Schintu, MariaGrazia; Giacco, GennaroSergioDel; Manconi, PaoloEmilio; Malerba, Giovanni; Bisognin, Andrea; Trabetti, Elisabetta; Boner, Attilio; Pescollderungg, Lydia; Pignatti, PierFranco; Schlessinger, David; Cao, Antonio; Pilia, Giuseppe

    2007-01-01

    Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF-?B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma. PMID:17503328

  1. Menkes disease – An important cause of early onset refractory seizures

    PubMed Central

    Jain, Puneet; Kannan, Lakshminarayanan; Chakrabarty, Biswaroop; Kumar, Atin; Gupta, Neerja; Kabra, Madhulika; Gulati, Sheffali

    2014-01-01

    Context: Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities. Aims: We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute. Setting/Design: The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported. Statistical analysis used: Descriptive statistics were used. Results: During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4), myoclonic (2) and tonic seizures (1). The electroencephalographic abnormalities included hypsarrythmia (2) and multifocal epileptiform discharges (3). The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels. Conclusions: Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis. PMID:24891895

  2. 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.

  3. 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

  4. 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.

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

    PubMed

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

    2015-12-18

    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

  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. 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

  8. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy.

    PubMed

    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

    2013-09-01

    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

  9. 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

  10. Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney Failure

    PubMed Central

    Živná, Martina; Hůlková, Helena; Matignon, Marie; Hodaňová, Kateřina; Vylet'al, Petr; Kalbáčová, Marie; Barešová, Veronika; Sikora, Jakub; Blažková, Hana; Živný, Jan; Ivánek, Robert; Stránecký, Viktor; Sovová, Jana; Claes, Kathleen; Lerut, Evelyne; Fryns, Jean-Pierre; Hart, P. Suzanne; Hart, Thomas C.; Adams, Jeremy N.; Pawtowski, Audrey; Clemessy, Maud; Gasc, Jean-Marie; Gübler, Marie-Claire; Antignac, Corinne; Elleder, Milan; Kapp, Katja; Grimbert, Philippe; Bleyer, Anthony J.; Kmoch, Stanislav

    2009-01-01

    Through linkage analysis and candidate gene sequencing, we identified three unrelated families with the autosomal-dominant inheritance of early onset anemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion (p.Leu16del) or the amino acid exchange (p.Leu16Arg) of a single leucine residue in the signal sequence of renin. Both mutations decrease signal sequence hydrophobicity and are predicted by bioinformatic analyses to damage targeting and cotranslational translocation of preprorenin into the endoplasmic reticulum (ER). Transfection and in vitro studies confirmed that both mutations affect ER translocation and processing of nascent preprorenin, resulting either in reduced (p.Leu16del) or abolished (p.Leu16Arg) prorenin and renin biosynthesis and secretion. Expression of renin and other components of the renin-angiotensin system was decreased accordingly in kidney biopsy specimens from affected individuals. Cells stably expressing the p.Leu16del protein showed activated ER stress, unfolded protein response, and reduced growth rate. It is likely that expression of the mutant proteins has a dominant toxic effect gradually reducing the viability of renin-expressing cells. This alters the intrarenal renin-angiotensin system and the juxtaglomerular apparatus functionality and leads to nephron dropout and progressive kidney failure. Our findings provide insight into the functionality of renin-angiotensin system and stress the importance of renin analysis in families and individuals with early onset hyperuricemia, anemia, and progressive kidney failure. PMID:19664745

  11. 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

  12. GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine

    PubMed Central

    Pierson, Tyler Mark; Yuan, Hongjie; Marsh, Eric D; Fuentes-Fajardo, Karin; Adams, David R; Markello, Thomas; Golas, Gretchen; Simeonov, Dimitre R; Holloman, Conisha; Tankovic, Anel; Karamchandani, Manish M; Schreiber, John M; Mullikin, James C; Tifft, Cynthia J; Toro, Camilo; Boerkoel, Cornelius F; Traynelis, Stephen F; Gahl, William A

    2014-01-01

    Objective Early-onset epileptic encephalopathies have been associated with de novo mutations of numerous ion channel genes. We employed techniques of modern translational medicine to identify a disease-causing mutation, analyze its altered behavior, and screen for therapeutic compounds to treat the proband. Methods Three modern translational medicine tools were utilized: (1) high-throughput sequencing technology to identify a novel de novo mutation; (2) in vitro expression and electrophysiology assays to confirm the variant protein's dysfunction; and (3) screening of existing drug libraries to identify potential therapeutic compounds. Results A de novo GRIN2A missense mutation (c.2434C>A; p.L812M) increased the charge transfer mediated by N-methyl-D-aspartate receptors (NMDAs) containing the mutant GluN2A-L812M subunit. In vitro analysis with NMDA receptor blockers indicated that GLuN2A-L812M-containing NMDARs retained their sensitivity to the use-dependent channel blocker memantine; while screening of a previously reported GRIN2A mutation (N615K) with these compounds produced contrasting results. Consistent with these data, adjunct memantine therapy reduced our proband's seizure burden. Interpretation This case exemplifies the potential for personalized genomics and therapeutics to be utilized for the early diagnosis and treatment of infantile-onset neurological disease. PMID:24839611

  13. 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.

  14. 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

  15. Periodontal Treatments and Procedures

    MedlinePlus

    ... Augmentation Ridge Modification Periodontal Pocket Reduction Procedures Periodontal Plastic Surgery Procedures Love the Gums You're With Member ... Augmentation Ridge Modification Periodontal Pocket Reduction Procedures Periodontal Plastic Surgery Procedures Love the Gums You're With Find ...

  16. 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

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

    PubMed

    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

  18. 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

  19. Periodontal Diseases

    MedlinePlus

    ... thought to begin when chalky white deposits called calculus accumulated near the gingiva, along the base of ... told their gingivitis would inevitably progress to periodontitis, advanced disease, and ultimately tooth loss. All people were ...

  20. 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

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

    PubMed Central

    Dobbs, Kerry; Domnguez 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; Haskolo?lu, Sule; Ensari, Arzu; Schuster, Michael; Moretta, Alessandro; Itan, Yuval; Patrizi, Ornella; Rozenberg, Flore; Lebon, Pierre; Saarela, Janna; Knip, Mikael; Petrovski, Slav; 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.; Ikincio?ullari, Aydan; Al-Herz, Waleed; Helminen, Merja; Do?u, Figen; Casanova, Jean-Laurent; Boztu?, 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)-? and -? 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-?2? 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

  2. Gray matter alterations in schizophrenia high-risk youth and early-onset schizophrenia: a review of structural MRI findings.

    PubMed

    Brent, Benjamin K; Thermenos, Heidi W; Keshavan, Matcheri S; Seidman, Larry J

    2013-10-01

    This article reviews the literature on structural magnetic resonance imaging findings in pediatric and young adult populations at clinical or genetic high-risk for schizophrenia and early-onset schizophrenia. The implications of this research are discussed for understanding the pathophysiology of schizophrenia and for early intervention strategies. The evidence linking brain structural changes in prepsychosis development and early-onset schizophrenia with disruptions of normal neurodevelopmental processes during childhood or adolescence is described. Future directions are outlined for research to address knowledge gaps regarding the neurobiological basis of brain structural abnormalities in schizophrenia and to improve the usefulness of these abnormalities for preventative interventions. PMID:24012081

  3. A longitudinal assessment of changes in bacterial community composition associated with the development of periodontal disease in dogs.

    PubMed

    Wallis, Corrin; Marshall, Mark; Colyer, Alison; O'Flynn, Ciaran; Deusch, Oliver; Harris, Stephen

    2015-12-31

    Periodontal disease is the most widespread oral disease in dogs. Whilst the involvement of bacteria in the aetiology of periodontitis is well established the role of individual species and their complex interactions with the host is not well understood. The objective of this research was therefore to perform a longitudinal study in dogs to identify the changes that occur in subgingival bacterial communities during the transition from mild gingivitis to the early stages of periodontitis (<25% attachment loss). Subgingival plaque samples were collected from individual teeth of 52 miniature schnauzer dogs every six weeks for up to 60 weeks. The microbial composition of plaque samples was determined using 454-pyrosequencing of the 16S rDNA. A group of aerobic Gram negative species, including Bergeyella zoohelcum COT-186, Moraxella sp. COT-017, Pasteurellaceae sp. COT-080, and Neisseria shayeganii COT-090 decreased in proportion as teeth progressed to mild periodontitis. In contrast, there was less evidence that increases in the proportion of individual species were associated with the onset of periodontitis, although a number of species (particularly members of the Firmicutes) became more abundant as gingivitis severity increased. There were small increases in Shannon diversity, suggesting that plaque community membership remains relatively stable but that bacterial proportions change during progression into periodontitis. This is the first study to demonstrate the temporal dynamics of the canine oral microbiota; it showed that periodontitis results from a microbial succession predominantly characterised by a reduction of previously abundant, health associated taxa. PMID:26507828

  4. 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

  5. Risk factors for periodontal disease.

    PubMed

    Genco, Robert J; Borgnakke, Wenche S

    2013-06-01

    Risk factors play an important role in an individual's response to periodontal infection. Identification of these risk factors helps to target patients for prevention and treatment, with modification of risk factors critical to the control of periodontal disease. Shifts in our understanding of periodontal disease prevalence, and advances in scientific methodology and statistical analysis in the last few decades, have allowed identification of several major systemic risk factors for periodontal disease. The first change in our thinking was the understanding that periodontal disease is not universal, but that severe forms are found only in a portion of the adult population who show abnormal susceptibility. Analysis of risk factors and the ability to statistically adjust and stratify populations to eliminate the effects of confounding factors have allowed identification of independent risk factors. These independent but modifiable, risk factors for periodontal disease include lifestyle factors, such as smoking and alcohol consumption. They also include diseases and unhealthy conditions such as diabetes mellitus, obesity, metabolic syndrome, osteoporosis, and low dietary calcium and vitamin D. These risk factors are modifiable and their management is a major component of the contemporary care of many periodontal patients. Genetic factors also play a role in periodontal disease and allow one to target individuals for prevention and early detection. The role of genetic factors in aggressive periodontitis is clear. However, although genetic factors (i.e., specific genes) are strongly suspected to have an association with chronic adult periodontitis, there is as yet no clear evidence for this in the general population. It is important to pursue efforts to identify genetic factors associated with chronic periodontitis because such factors have potential in identifying patients who have a high susceptibility for development of this disease. Many of the systemic risk factors for periodontal disease, such as smoking, diabetes and obesity, and osteoporosis in postmenopausal women, are relatively common and can be expected to affect most patients with periodontal disease seen in clinics and dental practices. Hence, risk factor identification and management has become a key component of care for periodontal patients. PMID:23574464

  6. 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

  7. Medial temporal atrophy in early and late-onset Alzheimer's disease.

    PubMed

    Cavedo, Enrica; Pievani, Michela; Boccardi, Marina; Galluzzi, Samantha; Bocchetta, Martina; Bonetti, Matteo; Thompson, Paul M; Frisoni, Giovanni B

    2014-09-01

    Late-onset and early-onset Alzheimer's disease (LOAD, EOAD) affect different neural systems and may be separate nosographic entities. The most striking differences are in the medial temporal lobe, severely affected in LOAD and relatively spared in EOAD. We assessed amygdalar morphology and volume in 18 LOAD and 18 EOAD patients and 36 aged-matched controls and explored their relationship with the hippocampal volume. Three-dimensional amygdalar shape was reconstructed with the radial atrophy mapping technique, hippocampal volume was measured using a manual method. Atrophy was greater in LOAD than EOAD: 25% versus 17% in the amygdala and 20% versus 13% in the hippocampus. In the amygdala, LOAD showed significantly greater tissue loss than EOAD in the right dorsal central, lateral, and basolateral nuclei (20%-30% loss, p < 0.03), all known to be connected to limbic regions. In LOAD but not EOAD, greater hippocampal atrophy was associated with amygdalar atrophy in the left dorsal central and medial nuclei (r = 0.6, p < 0.05) also part of the limbic system. These findings support the notion that limbic involvement is a prominent feature of LOAD but not EOAD. PMID:24721821

  8. Early onset of spring increases the phenological mismatch between plants and pollinators.

    PubMed

    Kudo, Gaku; Ida, Takashi Y

    2013-10-01

    Climate warming accelerates the timing of flowering and insect pollinator emergence, especially in spring. If these phenological shifts progress independently between species, features of plant-pollinator mutualisms may be modified. However, evidence of phenological mismatch in pollination systems is limited. We investigated the phenologies of a spring ephemeral, Corydalis ambigua, and its pollinators (bumble bees), and seed-set success over 10-14 years in three populations. Although both flowering onset and first detection of overwintered queen bees in the C. ambigua populations were closely related to snowmelt time and/or spring temperature, flowering tended to be ahead of first pollinator detection when spring came early, resulting in lower seed production owing to low pollination service. Relationships between flowering onset time, phenological mismatch, and seed-set success strongly suggest that phenological mismatch is a major limiting factor for reproduction of spring ephemerals. This report demonstrates the mechanism of phenological mismatch and its ecological impact on plant-pollinator interactions based on long-term monitoring. Frequent occurrence of mismatch can decrease seed production and may affect the population dynamics of spring ephemerals. PMID:24358716

  9. GAMMA OSCILLATION DEFICITS AND THE ONSET AND EARLY PROGRESSION OF SCHIZOPHRENIA

    PubMed Central

    Woo, Tsung-Ung W.; Spencer, Kevin; McCarley, Robert M.

    2009-01-01

    There has been a fascinating convergence of evidence in recent years implicating the disturbances of neural synchrony in the gamma frequency band (30–100 Hz) as a major pathophysiologic feature of schizophrenia. Evidence suggests that reduced glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptors that are localized to inhibitory interneurons, perhaps especially the fast-spiking cells that contain the calcium-binding protein parvalbumin (PV), may contribute to gamma band synchrony deficits, which may underlie the failure of the brain to integrate information and hence the manifestations of many symptoms and deficits of schizophrenia. Furthermore, because gamma oscillations are thought to provide the temporal structure that is necessary for synaptic plasticity, gamma deficits may disturb the developmental synaptic reorganization process that is occurring during the period of late adolescence and early adulthood, which may contribute to the onset of schizophrenia and the functional deterioration that is characteristic of the early stage of the illness. Finally, reduced NMDA neurotransmssion on inhibitory interneurons, including the PV-containing cells, may inflict excitotoxic or oxidative injury to downstream pyramidal neurons, leading to further loss of synapses and dendritic branchings. Hence, a key element in the conceptualization of rational early intervention and prevention strategies for schizophrenia may involve correcting the abnormal NMDA neurotransmission on inhibitory interneurons, possibly that on the PV-containing neurons in particular, thus normalizing gamma deficits and attenuating downstream neuronal pathology. PMID:20415633

  10. Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease.

    PubMed

    Valor, Luis M; Guiretti, Deisy; Lopez-Atalaya, Jose P; Barco, Angel

    2013-06-19

    Transcriptional dysregulation is an important early feature of polyglutamine diseases. One of its proposed causes is defective neuronal histone acetylation, but important aspects of this hypothesis, such as the precise genomic topography of acetylation deficits and the relationship between transcriptional and acetylation alterations at the whole-genome level, remain unknown. The new techniques for the mapping of histone post-translational modifications at genomic scale enable such global analyses and are challenging some assumptions about the role of specific histone modifications in gene expression. We examined here the genome-wide correlation of histone acetylation and gene expression defects in a mouse model of early onset Huntington's disease. Our analyses identified hundreds of loci that were hypoacetylated for H3K9,14 and H4K12 in the chromatin of these mice. Surprisingly, few genes with altered transcript levels in mutant mice showed significant changes in these acetylation marks and vice versa. Our screen, however, identified a subset of genes in which H3K9,14 deacetylation and transcriptional dysregulation concur. Genes in this group were consistently affected in different brain areas, mouse models, and tissue from patients, which suggests a role in the etiology of this pathology. Overall, the combination of histone acetylation and gene expression screenings demonstrates that histone deacetylation and transcriptional dysregulation are two early, largely independent, manifestations of polyglutamine disease and suggests that additional epigenetic marks or mechanisms are required for explaining the full range of transcriptional alterations associated with this disorder. PMID:23785159

  11. 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-wise and region of interest comparisons (P < 0.05). However, there were no significant differences in regional or global [11C]-labelled Pittsburgh compound-B binding between early-onset and late-onset patients. In contrast, early-onset patients showed significantly lower glucose metabolism than late-onset patients in precuneus/posterior cingulate, lateral temporo–parietal and occipital corticies (voxel-wise and region of interest comparisons, P < 0.05). Similar results were found for [11C]-labelled Pittsburgh compound-B and [18F]-labelled fluorodeoxyglucose using atrophy-corrected data. Age-at-onset correlated positively with glucose metabolism in precuneus, lateral parietal and occipital regions of interest (controlling for age, education and Mini Mental State Exam, P < 0.05), while no correlations were found between age-at-onset and [11C]-labelled Pittsburgh compound-B binding. In summary, a comparable burden of fibrillar amyloid-β was associated with greater posterior cortical hypometabolism in early-onset Alzheimer’s disease. Our data are consistent with a model in which both early amyloid-β accumulation and increased vulnerability to amyloid-β pathology play critical roles in the pathogenesis of Alzheimer’s disease in young patients. PMID:20080878

  12. 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

  13. 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

  14. Periaxin mutation causes early-onset but slow-progressive Charcot-Marie-Tooth disease.

    PubMed

    Kijima, Kazuki; Numakura, Chikahiko; Shirahata, Emi; Sawaishi, Yukio; Shimohata, Mitsuteru; Igarashi, Shuichi; Tanaka, Tomohiro; Hayasaka, Kiyoshi

    2004-01-01

    Periaxin (PRX) plays a significant role in the myelination of the peripheral nerve. To date, seven non-sense or frameshift PRX mutations have been reported in six pedigrees with Dejerine-Sottas neuropathy or severe Charcot-Marie-Tooth neuropathy (CMT). We detected a PRX mutation in three patients in the screening of 66 Japanese demyelinating CMT patients who were negative for the gene mutation causing dominant or X-linked demyelinating CMT. Three unrelated patients were homozygous for a novel R1070X mutation and presented early-onset but slowly progressive distal motor and sensory neuropathies. Mutations lacking the carboxyl-terminal acidic domain may show loss-of-function effects and cause severe demyelinating CMT. PMID:15197604

  15. 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

  16. Group B streptococcus and early-onset sepsis in the era of maternal prophylaxis.

    PubMed

    Koenig, Joyce M; Keenan, William J

    2009-06-01

    Despite an era of marked success with universal screening, Group B Streptococcus (GBS) continues to be an important cause of early-onset sepsis, and thus remains a significant public health issue. Improved eradication of GBS colonization and disease may involve universal screening in conjunction with rapid diagnostic technologies or other novel approaches. Given the complications and potential limitations associated with maternal intrapartum prophylaxis, however, vaccines may be the most effective means of preventing neonatal GBS disease. The global utility of conjugated GBS vaccines may be hampered by the variability of serotypes in diverse populations and geographic locations. Modern technologies, such as those involving proteomics and genomic sequencing, are likely to hasten the development of a universal vaccine against GBS. PMID:19501699

  17. Alternative salt bridge formation in Aβ—a hallmark of early-onset Alzheimer's disease?

    PubMed Central

    Schledorn, Maarten; Meier, Beat H.; Böckmann, Anja

    2015-01-01

    Recently the 3D structure of the Osaka mutant form (E22Δ) of Amyloid-β1-40 has been determined. We here compare the NMR chemical-shift with the published shifts of a brain-seeded form of wild-type Aβ and suggest that the determined mutant fold is accessible to the wild-type protein as well, with small conformational adaptations which accommodate the E22 residue missing in the Osaka mutant. In addition, we illustrate how other mutants could also conform to this model. The stabilization of the N-terminal part of the protein via an intermolecular salt bridge to Lys28 may represent a common structural motif for the mutants which are related to early-onset Alzheimer disease. This feature might connect to the observed increased toxicity of the mutant forms compared to wild-type Aβ1-40, where the salt bridge involving Lys28 is intramolecular. PMID:25988181

  18. Early Onset Dapsone-induced Photosensitive Dermatitis: A Rare Side Effect of a Common Drug.

    PubMed

    Karjigi, S; Murthy, S C; Kallappa, H; Kusuma, M R; Reddy, Y N K

    2015-01-01

    Dapsone, a potent anti-inflammatory compound, is mainly used in the treatment of leprosy, dermatitis herpetiformis, erythema elevatum diutinum and other dermatoses. Cutaneous adverse reactions range from acneiform eruptions to toxic epidermal necrolysis. A 30-year-old, married women who was treated with paucibacillary multi drug therapy, developed itchy skin lesions over the both forearms, 'V ' area of the neck and upper back after one week of the drug administration which worsened on exposure to sunlights. A clinical diagnosis of dapsone-induced photosensitive dermatitis was confirmed by histopathology and recurrence of symptoms and signs after re-exposure to the drug. Photosensitivity due to dapsone is rare and very few reports are available in the literature. Our patient had an unusually early onset compared to the previously reported cases. PMID:26999988

  19. Early-life vitamin D deficiency and childhood-onset coeliac disease.

    PubMed

    Tanpowpong, Pornthep; Camargo, Carlos A

    2014-04-01

    Many studies have investigated the aetiological roles of genetic and environmental factors in coeliac disease (CD) with the long-term goal of developing an effective primary prevention strategy. CD is a condition with dysregulated systemic and intestinal mucosal immune responses to dietary gluten proteins among genetically predisposed individuals. We recently described spring birth as a novel risk factor for CD in children. We believe that the association between season of birth and CD is due to seasonal differences in sunlight exposure and subsequent vitamin D status. Concomitant with global increases in CD prevalence, vitamin D deficiency also is increasingly recognized in children worldwide. Recent studies have shown that vitamin D deficiency can cause improper immune responses, abnormal intestinal mucosal integrity and impaired local defence to pathogenic microbial agents. In conjunction with other potential aetiological factors, we propose a hypothesis model of early-life vitamin D deficiency in the pathogenesis of childhood-onset CD. PMID:24581000

  20. 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

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

    PubMed

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

    2016-06-01

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

  2. 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. Severe agitation in severe early-onset Alzheimer’s disease resolves with ECT

    PubMed Central

    Aksay, Suna Su; Hausner, Lucrezia; Frölich, Lutz; Sartorius, Alexander

    2014-01-01

    Dementia-related behavioral disturbances are mostly treated with antipsychotics; however, the observed beneficial effects are modest and the risk of serious adverse effects high. We report the case of a 57-year-old woman with severe early-onset Alzheimer’s disease and severe agitation, whom we treated with electroconvulsive therapy (ECT). A significant clinical improvement was achieved over eight ECT sessions, which were tolerated well without cognitive worsening, and lasted approximately 3 months. Our case demonstrates the safe and effective use of ECT in pharmacotherapy-resistant severe agitation in Alzheimer’s disease. The risk–benefit profile of ECT for dementia-related agitation should be further investigated in clinical trials. PMID:25419138

  4. Hyperghrelinemia in Prader-Willi syndrome begins in early infancy long before the onset of hyperphagia.

    PubMed

    Kweh, Frederick A; Miller, Jennifer L; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J; Goldstone, Anthony P; Driscoll, Daniel J

    2015-01-01

    Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P < 0.001) higher in earlier nutritional phases: phase 1a (7,906  ±  5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P = 0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. PMID:25355237

  5. Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma

    PubMed Central

    Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Gordon, Patricia B.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2011-01-01

    Basal cell carcinoma (BCC) incidence is increasing, particularly among adults under age 40. Pigment-related characteristics are associated with BCC in older populations, but epidemiologic studies among younger individuals and analyses of phenotype-genotype interactions are limited. We examined self-reported phenotypes and melanocortin 1 receptor gene (MC1R) variants in relation to early-onset BCC. BCC cases (n=377) and controls with benign skin conditions (n=390) under age 40 were identified through Yale’s Dermatopathology database. Factors most strongly associated with early-onset BCC were skin reaction to first summer sun for one hour [severe sunburn vs. tan odds ratio (OR)=12.27, 95% confidence interval (CI)=4.08–36.94] and skin color (very fair vs. olive OR=11.06, 95% CI=5.90–20.74). Individuals with two or more MC1R non-synonymous variants were 3.59 times (95% CI=2.37–5.43) more likely to have BCC than those without non-synonymous variants. All host characteristics and MC1R were more strongly associated with multiple BCC cases status (37% of cases) than single BCC case status. MC1R, number of moles, skin reaction to first summer sun for one hour, and hair and skin color were independently associated with BCC. BCC risk conferred by MC1R tended to be stronger among those with darker pigment phenotypes, traditionally considered to be at low-risk of skin cancer. PMID:22158557

  6. Aberrant high-frequency desynchronization of cerebellar cortices in early-onset psychosis

    PubMed Central

    Wilson, Tony W.; Slason, Erin; Hernandez, Olivia O.; Asherin, Ryan; Reite, Martin L.; Teale, Peter D.; Rojas, Donald C.

    2009-01-01

    Sensorimotor integration deficits are routinely observed in both schizophreniform and mood-disordered psychoses. Neurobiological theories of schizophrenia and related psychoses have proposed aberrations in large scale cortico-thalamic-cerebellar-thalamic-cortical loops may underlie integration abnormalities, and that such dysfunctional connectivity may be central to the pathophysiology. In this study, we utilized a basic mechanoreception task to probe cortical-cerebellar circuitry in early-onset psychosis. Ten adolescents with psychosis and 10 controls completed unilateral tactile stimulation of the right and left index finger, as whole-head magnetoencephalography (MEG) data were acquired. MEG data were imaged in the frequency-domain, using spatial filtering, and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise analyses of group and task effects using statistical parametric mapping. Our results indicated bilateral ERD activation of cerebellar regions and postcentral gyri in both groups during stimulation of either hand. Interestingly, during left finger stimulations, adolescents with psychosis exhibited greater alpha and gamma ERD activity in right cerebellar cortices relative to controls. Subjects with psychosis also showed greater ERD in bilateral cerebellum and the right postcentral gyrus during right finger stimulation, and these differences were statistically stronger for higher frequency bins. Lastly, controls exhibited greater alpha ERS of the right postcentral gyrus during right finger stimulation. These findings provide new data on the neurodevelopmental trajectory of basic mechanoreception in adolescents, and also indicate aberrant cerebellar functioning in early-onset psychoses, especially in the right cerebellum, which may be the crucial dysfunctional node in cortico-thalamic-cerebellar-thalamic-cortical circuits. PMID:19783411

  7. Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications.

    PubMed

    Monroy-Jaramillo, Nancy; Guerrero-Camacho, Jorge Luis; Rodrguez-Violante, Mayela; Boll-Woehrlen, Marie-Catherine; Yescas-Gmez, Petra; Alonso-Vilatela, Mara Elisa; Lpez-Lpez, Marisol

    2014-04-01

    Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed. PMID:24677602

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

    PubMed

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

    2016-02-16

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Sibonga, Jean D.

    2010-01-01

    Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition

  11. 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

  12. 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

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

    PubMed Central

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

    2016-01-01

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

  14. Hyperghrelinemia in Prader-Willi Syndrome Begins in Early Infancy Long Before the Onset of Hyperphagia

    PubMed Central

    Kweh, Frederick A.; Miller, Jennifer L.; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J.; Goldstone, Anthony P.; Driscoll, Daniel J.

    2015-01-01

    Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P<0.001) higher in earlier nutritional phases: phase 1a (7,906 ± 5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P=0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. PMID:25355237

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

    SciTech Connect

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

    1981-07-01

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

  16. Comparative Effectiveness of Second-Generation Antipsychotic Medications in Early-Onset Schizophrenia

    PubMed Central

    Olfson, Mark; Gerhard, Tobias; Huang, Cecilia; Lieberman, Jeffrey A.; Bobo, William V.; Crystal, Stephen

    2012-01-01

    Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (20012005) was analyzed focusing on outpatients, aged 617 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (?2 = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (?2 = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.571.61) for olanzapine, 1.03 (95% CI: 0.591.81) for quetiapine, 0.85 (95% CI: 0.431.70) for aripiprazole, and 1.22 (95% CI: 0.602.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications. PMID:21307041

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

    PubMed Central

    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 819 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site randomized, double-blind clinical trial comparing molindone, olanzapine or risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses. Results Seventy-seven of 116 TEOSS participants (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores. Conclusions Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. PMID:22525956

  18. Body energy reserves influence the onset of luteal activity after early weaning of beef cows.

    PubMed

    Bishop, D K; Wettemann, R P; Spicer, L J

    1994-10-01

    The influence of body energy reserves on the onset of luteal activity and concentrations of LH and IGF-I in serum was evaluated in postpartum anestrous beef cows after early weaning. Multiparous Hereford and Hereford x Angus cows (n = 24) were fed during gestation to establish body condition scores between 3 and 6 (BCS, 1 = emaciated; 9 = obese) at parturition. Concentrations of progesterone in plasma were determined weekly for 5 wk postpartum (PP). Anovulatory cows and their calves (n = 19) were confined in stalls on d 40 +/- 3 PP. Jugular cannulas were inserted on d 44 +/- 3 PP, and calves were weaned (d 0) the following day. Blood samples were collected from all cows for 4 h (every 10 min) before weaning and on d 1, 2, 4, 6, 8, and 10 after weaning and LH was quantified. Progesterone was quantified in daily blood samples until d 10, and in samples taken twice weekly until d 46. Within 25 d after weaning, 100% of the cows with BCS < or = 5 at weaning (n = 7) had initiated luteal activity, whereas only 43% (P < .01) of the cows with BCS < 5 (n = 12) had luteal activity. Mean serum IGF-I concentrations were correlated with BCS (r = .50; P < .05). Frequency of LH pulses was influenced (P < .01) by body condition at weaning but was not influenced by day after weaning. The number of LH pulses at weaning, serum IGF-I, and the interval to the onset of ovarian activity after early weaning of anestrous beef cows were influenced by BCS. PMID:7883630

  19. 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

  20. A qualitative interview study: patient accounts of medication use in early rheumatoid arthritis from symptom onset to early postdiagnosis

    PubMed Central

    Townsend, Anne; Backman, Catherine L; Adam, Paul; Li, Linda C

    2013-01-01

    Objective To examine accounts of medication use in participants with early rheumatoid arthritis (RA) from symptom onset to early postdiagnosis. Design Qualitative study with in-depth, personal interviews. Participants 37 women and one man, aged 30–70s, with a diagnosis of RA <12 months. Main outcome measure Participants’ experiences and feelings of medication use in early RA. Setting British Columbia, Canada. Results Medications were central to how people managed symptoms and disease. Two main themes were identified, showing that optimum medication use was hampered, and how this related to delayed diagnosis and effective care. The first theme, ‘paradox of prediagnosis reliance on over the counter (OTC) medications’, describes how people's self-management with OTC medications was ‘effective’. Participants relied extensively on OTC medications for pain relief and to maintain ‘normal life’. However, as this contributed to delayed medical consultation, diagnosis and effective treatment, OTC medication was also potentially detrimental to disease outcome. The second theme, ‘ambivalence around prescription medications post diagnosis’, describes how adherence was hindered by patient beliefs, priorities and ambivalence towards medications. Conclusions This study highlights how people use medications in early RA and contributes to a better understanding of medication use that may transfer to other conditions. Given the drive towards active self-management in healthcare and patients’ ambivalence about using strong medications, an in-depth understanding of how these combined factors impact patient experiences will help healthcare providers to support effective medication practices. The reported extensive reliance on OTC medications may speak to a care gap needing further investigation in the context of health behaviours and outcomes of patient self-management. PMID:23408077

  1. Early onset APOE E4-negative Alzheimer's disease patients show faster cognitive decline on non-memory domains.

    PubMed

    Smits, Lieke L; Pijnenburg, Yolande A L; van der Vlies, Annelies E; Koedam, Esther L G E; Bouwman, Femke H; Reuling, Ilona E W; Scheltens, Philip; van der Flier, Wiesje M

    2015-07-01

    Age at onset and APOE E4-genotype have been shown to influence clinical manifestation of Alzheimer's disease (AD). We investigated rate of decline in specific cognitive domains according to age at onset and APOE E4-genotype in patients with AD. 199 patients with probable AD underwent at least two annual neuropsychological assessments. Patients were classified according to age-at-onset (≤ 65 years vs >65 years) and APOE genotype (positive vs negative). The neuropsychological test battery compromised tests for memory, language, attention, executive and visuo-spatial functioning. For each domain compound z-scores were calculated, based on the baseline performance of patients. Average duration of follow-up was 1.5 ± 1 years. We used linear mixed models (LMM) to estimate effects of age, APOE and age⁎APOE on cognitive decline over time. At baseline, patients were 65 ± 8 years, 98(49%) were female and MMSE was 22 ± 4. LMM showed that early onset patients declined faster on executive functioning (β ± SE:-0.09 ± 0.06) than late onset patients, but age was not related to decline in the other cognitive domains. APOE E4 negative patients declined faster on language than APOE E4 positive patients (β ± SE:-0.1 ± 0.06). When we took age and APOE genotype into account simultaneously, we found that compared to late onset-E4 positive patients, early onset-E4 negative patients declined faster on language (β ± SE:-0.36 ± 0.1), attention (β ± SE:-0.42 ± 0.1), executive (β ± SE:-0.41 ± 0.1) and visuo-spatial functioning (β ± SE:-0.43 ± 0.1). Late onset-E4 negative and early onset-E4 positive patients showed intermediate rates of decline. We found no differences in decline on memory. We found that patients who develop AD despite absence of the two most important risk factors, show steepest cognitive decline on non-memory cognitive domains. PMID:25891378

  2. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

    PubMed

    Nagy, Eniko; Rodriguiz, Ramona M; Wetsel, William C; MacIver, Nancie J; Hale, Laura P

    2016-01-01

    Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD), a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC), using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice). Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het" dams) that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het) dams, T/I pups initially gained weight similarly to wild type (WT) pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and for development of therapies to prevent reproductive complications and/or growth failure in humans with IBD. PMID:27045690

  3. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease

    PubMed Central

    Nagy, Eniko; Rodriguiz, Ramona M.; Wetsel, William C.; MacIver, Nancie J.; Hale, Laura P.

    2016-01-01

    Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD), a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC), using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 (“T/I” mice). Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 (“T/I-het” dams) that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het) dams, T/I pups initially gained weight similarly to wild type (WT) pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and for development of therapies to prevent reproductive complications and/or growth failure in humans with IBD. PMID:27045690

  4. Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient.

    PubMed

    Abidi, Affef; Mignon-Ravix, Cécile; Cacciagli, Pierre; Girard, Nadine; Milh, Mathieu; Villard, Laurent

    2016-04-01

    Variants in the WD repeat 45 (WDR45) gene in human Xp11.23 have recently been identified in patients suffering from neurodegeneration with brain iron accumulation, a genetically and phenotypically heterogeneous condition. WDR45 variants cause a childhood-onset encephalopathy accompanied by neurodegeneration in adulthood and iron accumulation in the basal ganglia. They have been almost exclusively found in females, and male lethality was suggested. Here we describe a male patient suffering from a severe and early neurological phenotype, initially presenting early-onset epileptic spasms in clusters associated with an abnormal interictal electroencephalography showing slow background activity, large amplitude asynchronous spikes and abnormal neurological development. This patient is a carrier of a 19.9-kb microdeletion in Xp11.23 containing three genes, including WDR45. These findings reveal that males with WDR45 deletions are viable, and can present with early-onset epileptic encephalopathy without brain iron accumulation. PMID:26173968

  5. Early, But Not Late Onset Estrogen Replacement Therapy Prevents Oxidative Stress and Metabolic Alterations Caused by Ovariectomy

    PubMed Central

    López-Grueso, Raúl; Gambini, Juan; Abdelaziz, Kheira M.; Monleón, Daniel; Díaz, Ana; El Alami, Marya; Bonet-Costa, Vicent; Borrás, Consuelo

    2014-01-01

    Abstract Aims: The usefulness of estrogen replacement therapy (ERT) in preventing oxidative stress associated with menopause is controversial. We aimed to study if there is a critical time window for effective treatment of the effects of ovariectomy with estrogens at the molecular, metabolic, and cellular level. Results: Our main finding is that early, but not late onset of ERT prevents an ovariectomy-associated increase in mitochondrial hydrogen peroxide levels, oxidative damage to lipids and proteins, and a decrease in glutathione peroxidase and catalase activity in rats. This may be due to a change in the estrogen receptor (ER) expression profile: ovariectomy increases the ER α/β ratio and immediate estrogen replacement prevents it. Positron emission tomography analysis shows that ovariectomy decreases the brain glucose uptake in vivo and that estrogen administration is beneficial, but only if administered immediately after deprivation. Ovariectomy decreases GLUT-1 and 3 glucose transporters in the brain, and only early onset estrogen administration prevents it. Plasma from rats treated with estrogens immediately after ovariectomy show similar metabolomics profiles as controls. Innovation: We provide molecular basis for the recommendation of early onset ERT and explain its lack of effectiveness if a significant time period elapses after ovariectomy and probably after the onset of menopause. Conclusion: Only early, but not late onset administration of estrogens after ovariectomy has beneficial effects at molecular levels on oxidative stress, brain glucose uptake, and metabolomic profiles. Antioxid. Redox Signal. 20, 236–246. PMID:23725100

  6. Increased risk of cancer in patients with early-onset cataracts: A nationwide population-based study

    PubMed Central

    Chiang, Chun Chi; Lin, Cheng-Li; Peng, Chiao-Ling; Sung, Fung-Chang; Tsai, Yi-Yu

    2014-01-01

    Early-onset cataracts are associated with insufficient antioxidative activity, and, therefore, a potential risk of cancer. This study investigated the risk of cancer after being diagnosed with early-onset cataracts. Retrospective claims data from the Taiwan National Health Insurance Research Database were analyzed. Study subjects were comprised of patients with early-onset cataracts, aged 20–55 years (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 366.00, 366.01, 366.02, 366.03, 366.04, 366.09, 366.17 and 366.18) and newly diagnosed between 1997 and 2010 (n = 1281), and a comparison cohort without the disease (n = 5124). Both cohorts were followed up until 2010 to estimate the incidences of cancer. We used the Poisson regression model to compare incidence rate ratios and the 95% confidence interval (CI). Cox proportional hazards regression was used to assess the hazard ratio (HR) of cancer associated with early-onset cataracts. The overall incidence rate of all cancers was 2.19-fold higher in the early-onset cataract cohort than in the comparison cohort (8.06 vs 3.68 per 1000 person-years) with an adjusted HR of 2.13 (95% CI = 1.48, 3.07). The site-specific analysis also showed a strong relationship, with adjusted HR of 3.24 ((95% CI = 1.30, 8.10) for head and neck cancer, 3.29 (95% CI 1.16, 9.31) for hepatoma and 3.19 (95% CI 1.34, 7.58) for breast cancer. The present study suggests that patients with early-onset cataracts are at an increased risk of being diagnosed with cancer in subsequent years. PMID:24450445

  7. The Onset of Early Season Rainfall and its Mid-Summer Cessation in the Caribbean.

    NASA Astrophysics Data System (ADS)

    Allen, T. L.; Mapes, B. E.

    2014-12-01

    The annual rainfall cycle for the Caribbean basin reveals a distinct bimodal pattern with peaks during the late spring and late summer months. A relative minimum during the mid-summer, known as the mid-summer drought (MSD) separates the early rainfall season (ERS) from the late rainfall season. Accumulated rainfall totals during the ERS appear as a quasi-stationary rain-belt stretching across the Caribbean from the southwest to the northeast. We place late spring rains in the Caribbean in context of other subtropical convergence zones in order to address the onset and cessation of the ERS while also offering an explanation of a Caribbean rain-belt pattern. Upper tropospheric westerlies, mid-tropospheric positive temperature advection, and moist low level poleward flow are the three primary ingredients that conspire to produce the first peak of the annual bimodal rain signal and the related Caribbean early season rain-belt. The MSD ensues as the primary ingredients weaken across the Caribbean and enhanced rainfall shifts north along the North Atlantic Convergence Zone (NACZ). Seasonal rainfall totals from the ERS through the MSD periods reveal a continuous rain-belt that extends from the Caribbean to the NACZ termed the Caribbean Atlantic Rain-belt (CAR-belt). The Car-belt is present in the long term mean, but has signs of interannual variability.

  8. A study on early-onset neonatal group B streptococcal infection, Bulgaria, 2007-2011.

    PubMed

    Todorova-Christova, M; Vacheva, R; Decheva, A; Nikolov, A; Slancheva, B; Stoichkova, D; Christova, E; Shopova, E; Hitrova, S; Masseva, A; Yarakova, N; Kraleva, I; Takova, T S; Dimitrova, N; Dobreva, A

    2014-09-01

    This study examines neonatal group B streptococcal (GBS) colonization and its relation to early-onset GBS disease (EOGBSD), based upon the experience of leading obstetrics and gynecology centers in Bulgaria. The objectives of the study were to update neonatal colonization rates and to assess relationships between clinically differentiated cases (culture-proven GBS newborns) and risk factors inherent to the infant and mother, using a computerized file. The neonatal GBS colonization rate ranged from 5.48 to 12.19 per 1000 live births. Maternal-fetal infection (MFI, a provisional clinical diagnosis in culture-proven colonized infants with initial signs of infection that is usually overcome with antibiotic treatment) and/or intrapartum asphyxia (IA) have been demonstrated as the most frequent clinical manifestations, with significant correlations for the primary diagnosis, but not affirmative for the final diagnosis at discharge, resulting from adequate treatment of neonates. MFI and IA were significantly related to prematurity, and reciprocally, prematurity was associated with the risk of MFI, indirectly suggesting that preterm birth or PPROM (preterm premature rupture of membranes, an obstetric indication associated with early labor and delivery, one of the major causes of preterm birth) is a substantial risk factor for EOGBSD. The regression analysis indicated that in the case of a newborn with MFI, a birth weight 593.58 g lower than the birth weight of an infant without this diagnosis might be expected. Testing the inverse relationship, i.e., the way birth weight influences a certain diagnosis (logistic regression) established the presence of a relationship between birth weight categories (degree of prematurity) and the diagnosis of MFI. The proportions and odds ratios, converted into probabilities that a baby would develop MFI, indicate the particularly high risk for newborns with extremely low and very low birth weight: extremely low birth weight (≤1000 g), the probability of developing a MFI is 66%; very low birth weight (1001-1500 g), 81%; low birth weight (the birth weight category including premature and small for gestational age term infants: 1501-2500 g), 40%; normal birth weight (term infants) (>2500 g), 32%. In conclusion, the need to introduce separate categories for early- and late-onset GBS disease in the registration nomenclature of neonatal infectious diseases is highlighted by these results. Drawing up intrapartum antibiotic prophylaxis (IAP) guidelines is also strongly recommended. PMID:25066700

  9. Neurobiological status at initial presentation predicts neuropsychological functioning in early onset anorexia nervosa at four-year follow up.

    PubMed

    Frampton, Ian; Hutchinson, Anna; Watkins, Beth; Lask, Bryan

    2012-01-01

    This study explores whether neurobiological status (indexed by regional cerebral blood flow) at initial presentation predicts neuropsychological status at four-year follow up in a sample of children with early onset anorexia nervosa. Neuropsychological assessment was conducted on 15 females four years after their initial treatment, and matched controls. At follow up there were significant differences between subgroups (based on neurobiological status at initial presentation) and matched controls in long-term visual memory and cognitive inhibition. This study offers preliminary evidence that neurobiological abnormalities at initial presentation predict neuropsychological status at follow up, suggesting a distinct neurodevelopmental subtype of early onset anorexia nervosa. PMID:22292832

  10. Reading Aloud in Persian: ERP Evidence for an Early Locus of the Masked Onset Priming Effect

    ERIC Educational Resources Information Center

    Timmer, Kalinka; Vahid-Gharavi, Narges; Schiller, Niels O.

    2012-01-01

    The current study investigates reading aloud words in Persian, a language that does not mark all its vowels in the script. Behaviorally, a "masked onset priming effect" (MOPE) was revealed for transparent words, with faster speech onset latencies in the phoneme-matching condition (i.e. phonological prime and target onset overlap; e.g. [image…

  11. Prevalence of Traumatic Brain Injury in Early Versus Late-Onset Alzheimer’s Disease

    PubMed Central

    Mendez, Mario F.; Paholpak, Pongsatorn; Lin, Andrew; Zhang, Jeannie Y.; Teng, Edmond

    2016-01-01

    Background Traumatic brain injury (TBI) is the most established environmental risk factor for Alzheimer’s disease (AD), but it is unclear if TBI is specifically associated with early-onset AD (EOAD). Objective To evaluate the relationship between TBI and EOAD (<65 years). Methods We identified 1,449 EOAD, 4,337 late-onset AD (LOAD), and corresponding EOAD-matched and LOAD-matched normal controls (NC) in the National Alzheimer’s Coordinating Center Uniform (NACC) database and compared the prevalence of any history of TBI as well as measures of cognition, function, behavior, and neuropathology. For validation, we determined TBI prevalence among 115 well-characterized clinic patients with EOAD. Results Part A: The prevalence of any TBI in the NACC-database EOAD participants (13.3%) was comparable to that observed in the clinic EOAD patients (13.9%) but significantly higher than in the NACC-database LOAD participants (7.7%; p < 0.0001) and trended to higher compared to EOAD-matched NC (11.1%; logistic regression p = 0.053). Part B: When we compared EOAD patients with documented non-acute and non-residually impairing TBI to EOAD without a documented history of prior TBI, those with TBI had significantly more disinhibition. Part C: Autopsies did not reveal differences in AD neuropathology based on a history of TBI. Conclusions These findings suggest, but do not establish, that TBI is a specific risk factor for EOAD and may lead to disinhibition, a feature that often results from the frontal effects of head injury. This study recommends further research on the effects of TBI in EOAD in larger numbers of participants. PMID:26401777

  12. Predictors of Parkin Mutations in Early Onset Parkinson disease: the CORE-PD Study

    PubMed Central

    Marder, K; Tang, M-X; Mejia-Santana, H; Rosado, L; Louis, ED; Comella, C; Colcher, A; Siderowf, A; Jennings, D; Nance, M; Bressman, S; Scott, WK; Tanner, C; Mickel, S; Andrews, H; Waters, C; Fahn, S; Ross, B; Cote, L; Frucht, S; Ford, B; Alcalay, RN; Rezak, M; Novak, K; Friedman, JH; Pfeiffer, R; Marsh, L; Hiner, B; Greg, Neils; Verbitsky, M; Kisselev, S; Caccoppolo, E; Ottman, R; Clark, LN

    2012-01-01

    Background Mutations in the parkin gene are the most common genetic cause of early-onset Parkinson’s disease (EOPD). Results from a multi-center study of cases with PD systematically sampled by age at onset (AAO) have not been reported. Objective To determine risk factors associated with carrying mutations in the parkin gene. Design Cross-sectional observational study Setting 13 movement disorders centers Participants 956 EOPD cases defined as AAO <51. Main Outcome Measures Presence of heterozygous, homozygous or compound heterozygous parkin mutations. Results 14.7% of cases reported a family history of PD in a first-degree relative using a previously validated interview. Sixty-four cases (6.7%) had parkin mutations (3.9% heterozygous, 0.6% homozygotes, 2.2% compound heterozgyotes). Copy Number Variation (CNV) was present in 52.3% (31.6% of heterozygotes, 83.3% of homozygotes, 81.0% of compound heterozygotes). Deletions in exons 3–4 and 255delA, were common in Hispanics, and specifically, in the Puerto Rican population. Earlier AAO, Hispanic ethnicity (OR compared to White non-Hispanic 2.7 95% CI 1.3–5.7, p<0.009) and family history of PD in a first-degree relative (OR 2.8 95%CI 1.5–5.3, p<0.002) were associated with carrying any mutation in the parkin gene (heterozygous, homozygous, compound heterozygous). Hispanic ethnicity was associated with carrying a heterozygous mutation (OR compared to non-Hispanic Caucasian 2.8 95%CI 1.1–7.2, p<0.03) after adjustment for covariates. Conclusion AAO, Hispanic ethnicity and family history of PD are associated with carrying any parkin mutation (heterozygous, homozygous, compound heterozygous) and heterozygous mutations alone. The increased odds of carrying a parkin mutation in Hispanics warrants further study. PMID:20558392

  13. Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease

    PubMed Central

    Kajiya, Mikihito; Giro, Gabriela; Taubman, Martin A.; Han, Xiaozhe; Mayer, Marcia P.A.; Kawai, Toshihisa

    2010-01-01

    Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear. Therefore, this review article addresses three critical subjects. First, we discuss earlier studies of immune intervention, ultimately leading to the identification of bacteria-reactive lymphocytes as the cellular source of osteoclast-induction factor lymphokine (now called RANKL) in the context of periodontal bone resorption. Next, we consider (1) the effects of periodontal bacteria on RANKL production from a variety of adaptive immune effector cells, as well as fibroblasts, in inflamed periodontal tissue and (2) the bifunctional roles (upregulation vs. downregulation) of LPS produced from periodontal bacteria in a RANKL-induced osteoclast-signal pathway. Future studies in these two areas could lead to new therapeutic approaches for the management of PD by down-modulating RANKL production and/or RANKL-mediated osteoclastogenesis in the context of host immune responses against periodontal pathogenic bacteria. PMID:21523224

  14. Expression of Collapsin Response Mediator Protein 1 in Placenta of Normal Gestation and Link to Early-Onset Preeclampsia

    PubMed Central

    Wang, Chunhui; Jin, Feng; Zheng, Dongying; Liu, Caixia

    2014-01-01

    A human isoform of Collapsin Response Mediator Protein (CRMP) family proteins, CRMP-1, has been identified as a novel invasion suppressor. The aim of this study was to determine CRMP-1 expression pattern in placentas during normal pregnancy and elucidate the clinical significance of CRMP-1 expression in the placentas of women with early-onset preeclamptic pregnancies. We recruited 66 normal healthy pregnant Chinese women and 60 Chinese patients with preeclampsia [early-onset prereclampsia(ePE), n = 30 and late-onset preeclampsia(lPE) n = 30]. Gestational age-matched normal healthy pregnant women were used as controls of early-onset and late-onset preeclampsia, which were 23-33 + 6weeks, n = 18 and control B: 34-40 weeks, n = 20). Quantitative RT-PCR, Western blot analysis and immunohistochemistry were used to analyze the expressions of CRMP-1 in placentas. Expression of CRMP-1 was detected in syncytio- and cytotrophoblasts of all groups using immunohistochemistry. CRMP-1 was most abundantly expressed in syncytiotrophoblasts, moderately in cytotrophoblasts and the intermediate trophoblasts especially in the first trimester. The placental expression of CRMP-1 is particularly striking in the first trimester and decreases throughout pregnancy. There is a significant increase in CRMP-1 expression in the placenta of ePE but not of lPE, as compared to gestational-matched controls. The aberrant upregulation of CRMP-1 expression may link to the mechanism of developing ePE. PMID:25194153

  15. Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer.

    PubMed

    Weischenfeldt, Joachim; Simon, Ronald; Feuerbach, Lars; Schlangen, Karin; Weichenhan, Dieter; Minner, Sarah; Wuttig, Daniela; Warnatz, Hans-Jörg; Stehr, Henning; Rausch, Tobias; Jäger, Natalie; Gu, Lei; Bogatyrova, Olga; Stütz, Adrian M; Claus, Rainer; Eils, Jürgen; Eils, Roland; Gerhäuser, Clarissa; Huang, Po-Hsien; Hutter, Barbara; Kabbe, Rolf; Lawerenz, Christian; Radomski, Sylwester; Bartholomae, Cynthia C; Fälth, Maria; Gade, Stephan; Schmidt, Manfred; Amschler, Nina; Haß, Thomas; Galal, Rami; Gjoni, Jovisa; Kuner, Ruprecht; Baer, Constance; Masser, Sawinee; von Kalle, Christof; Zichner, Thomas; Benes, Vladimir; Raeder, Benjamin; Mader, Malte; Amstislavskiy, Vyacheslav; Avci, Meryem; Lehrach, Hans; Parkhomchuk, Dmitri; Sultan, Marc; Burkhardt, Lia; Graefen, Markus; Huland, Hartwig; Kluth, Martina; Krohn, Antje; Sirma, Hüseyin; Stumm, Laura; Steurer, Stefan; Grupp, Katharina; Sültmann, Holger; Sauter, Guido; Plass, Christoph; Brors, Benedikt; Yaspo, Marie-Laure; Korbel, Jan O; Schlomm, Thorsten

    2013-02-11

    Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA. PMID:23410972

  16. Do early onset and pack-years of smoking increase risk of type II diabetes?

    PubMed Central

    2014-01-01

    Background Type II diabetes is not only major public health problem but also heavy fiscal burden to each nation’s health care system around the world. This study aimed to investigate the effect of early onset and pack-years of smoking on type II diabetes risk. Methods We used the most recent cross-sectional National Health and Nutrition Examination Survey set of South Korea (2010) and the United States (2009–2010). Participants who were diagnosed with diabetes after age 20 were included (South Korea: n = 7273, 44% male; U.S.: n = 3271, 52% male). Cox proportional models, stratified by sex and country, were used to estimate hazard ratios. Results 7.1% of South Korean men, 5.5% of South Korean women, 15.5% of U.S. men, and 12.4% of U.S. women had type II diabetes; 40% of South Korean men, 34% of U.S. men, and 21% of U.S. women began smoking before age 20 (57%, 49%, 36% of those who had type II diabetes, respectively). Type II diabetic participants were older and married; have a higher BMI, low income, and less education; lack moderate physical activity, smoked more and earlier compared to those without type II diabetes. Differences in risk factors including life-style behaviors and SES were found in both diabetic and non-diabetic populations. Men who began smoking before age 16 had a higher type II diabetes risk than who never smoked (South Korea: hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.04–5.79; U.S.: HR 1.64, 95% CI 1.01–2.67), as did U.S. men who began smoking between 16 and 20 years (HR 1.58, 95% CI 1.05–2.37). Smoking pack-years were also associated with type II diabetes in U.S. men (HR 1.07, 95% CI 1.01–1.12). In women population, however, associations were not found. Conclusions Early onset of smoking increases type II diabetic risk among men in South Korea and the U.S., and type II diabetic risk increases with higher pack-years in U.S. men, however, no associations were found in women population. Underage tobacco policy and education programs are strongly needed in both countries. PMID:24548553

  17. Addressing the link between paraoxonase-1 gene variants and the incidence of early onset myocardial infarction

    PubMed Central

    Hashad, Ingy M.; Abou-Aisha, Khaled; Abdel-Maksoud, Sahar M.; Gad, Mohamed Z.

    2015-01-01

    Introduction The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was to investigate the association between PON1 Q192R polymorphism, PON1 phenotypes and the incidence of early-onset acute myocardial infarction (AMI) in Egyptians. Material and methods The study subjects consisted of 102 AMI patients and 72 age-matched healthy controls. Genotyping and enzyme activities were determined using PCR-RFLP and kinetic spectrophotometric assays, respectively. Results The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02%, RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%). Allele frequencies were also significantly different between patients (Q = 62.75%, R = 37.25%) and controls (Q = 79.17%, R = 20.83%). The genotypes QR and RR showed higher risk for AMI compared to the homozygous QQ (odds ratio (OR) = 3.231, p < 0.001). The average PON/ARE ratio in MI patients (1.187 ±0.1) did not differ significantly from controls (1.118 ±0.26). However, it showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (p = 0.0002) and controls (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (p < 0.0001). Conclusions PON1 192R allele represents an independent risk factor for early-onset AMI in Egyptians, and PON1 Q192R polymorphism modulates the paraoxonase phenotype. PMID:26170843

  18. Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation

    PubMed Central

    2010-01-01

    Background and aims There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones. Methods 3-9 years (mean 5.2 ± 1.7) after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC) and bone mineral density (BMD) as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I). Results The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m2, resumption of menses). Clinical improvement was correlated with BMC and BMD accrual (χ2 = 5.62/χ2 = 6.65, p = 0.06 / p = 0.036). The duration of amenorrhea had a negative correlation with BMD (r = -.362; p < 0.01), but not with BMC. Regular physical activity tended to show a positive effect on bone recovery, but the effect of hormone replacement therapy was not significant. Using age-related standards, the post-discharge sample for the substudy presented IGF-I levels below the 5th percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters. Conclusions Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN. PMID:20615217

  19. [Combined step-by-step rehabilitation of the patients presenting with early-onset rheumatoid arthritis].

    PubMed

    Orlova, E V; Karateev, D E; Kochetkov, A V; Denisov, L N; Surnov, A V

    2013-01-01

    The objective of the present study was to develop the program for combined step-by-step rehabilitation of the patients presenting with early-onset rheumatoid arthritis (RA); the secondary objective was to estimate the effectiveness of this program. A total of 34 patients were recruited for the participation in the study. They received medicamental therapy in combination with the rehabilitative treatment during 6 months. The hospital-based treatment included therapeutic exercises for large joints under the supervision of a specialist (45 min), occupational therapy (45 min), local aerial cryotherapy of wrist, knee, and ankle joints (10 sessions 15 min each at a temperature of -60 degrees C), ortheses, and the educational program (4 daily studies 90 min each). The outpatient and home-based treatment included therapeutic exercises for large joints (45 min), wrist exercises (45 min) three times every week, ortheses. 26 patients received only medicamental therapy (control group). The following characteristics were measured: the average power of extension of knee joints and of flexion of ankle joints (by means of En-TreeM analysis of movements), wrist grip strength, articular pain (100 mm VAS, DAS28, HAQ, RAPID3 indices). The rehabilitative program ensured excellent compliance with basal therapy, reduced requirements for symptomatic medicines, and improved adherence to the methods for the formation of the correct movement patterns, orthesis wearing, and regular therapeutic exercises. The rehabilitative treatment resulted in the relief of articular pain by 70.4% (p < 0.01), decrease of DAS28 by 31.9% (p < 0.05), HAQ by 75.8% (p < 0.01), and RAPID3 by 60.1% (p < 0.01). The grip strength of the more seriously injured wrist increased by 44.9% (p < 0.05) and that of the less damaged one by 31.3% (p < 0.05). The average extension power of the weaker knee joint increased by 88.7% (p < 0.01) and that of the stronger joint by 67.7% (p < 0.01). The average flexion power of the more seriously injured ankle joint increased by 81.6% (p < 0.01) and that of the less damaged one by 70.2% (p < 0.01). The two groups were significantly different in terms of the majority of characteristics evaluated. It is concluded that the combined rehabilitative treatment helps to control the activity of the disease, enhances the functional abilities, improves the locomotor activity and quality of life of the patients with early-onset rheumatoid arthritis. PMID:23520927

  20. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.

    PubMed

    Oláhová, Monika; Hardy, Steven A; Hall, Julie; Yarham, John W; Haack, Tobias B; Wilson, William C; Alston, Charlotte L; He, Langping; Aznauryan, Erik; Brown, Ruth M; Brown, Garry K; Morris, Andrew A M; Mundy, Helen; Broomfield, Alex; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Moeslinger, Dorothea; Koch, Johannes; Stettner, Georg M; Bonnen, Penelope E; Prokisch, Holger; Lightowlers, Robert N; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M A; Taylor, Robert W

    2015-12-01

    Mitochondrial Complex IV [cytochrome c oxidase (COX)] deficiency is one of the most common respiratory chain defects in humans. The clinical phenotypes associated with COX deficiency include liver disease, cardiomyopathy and Leigh syndrome, a neurodegenerative disorder characterized by bilateral high signal lesions in the brainstem and basal ganglia. COX deficiency can result from mutations affecting many different mitochondrial proteins. The French-Canadian variant of COX-deficient Leigh syndrome is unique to the Saguenay-Lac-Saint-Jean region of Québec and is caused by a founder mutation in the LRPPRC gene. This encodes the leucine-rich pentatricopeptide repeat domain protein (LRPPRC), which is involved in post-transcriptional regulation of mitochondrial gene expression. Here, we present the clinical and molecular characterization of novel, recessive LRPPRC gene mutations, identified using whole exome and candidate gene sequencing. The 10 patients come from seven unrelated families of UK-Caucasian, UK-Pakistani, UK-Indian, Turkish and Iraqi origin. They resemble the French-Canadian Leigh syndrome patients in having intermittent severe lactic acidosis and early-onset neurodevelopmental problems with episodes of deterioration. In addition, many of our patients have had neonatal cardiomyopathy or congenital malformations, most commonly affecting the heart and the brain. All patients who were tested had isolated COX deficiency in skeletal muscle. Functional characterization of patients' fibroblasts and skeletal muscle homogenates showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits. We also identified a Complex I assembly defect in skeletal muscle, indicating different roles for LRPPRC in post-transcriptional regulation of mitochondrial mRNAs between tissues. Patient fibroblasts showed decreased steady-state levels of mitochondrial mRNAs, although the length of poly(A) tails of mitochondrial transcripts were unaffected. Our study identifies LRPPRC as an important disease-causing gene in an early-onset, multisystem and neurological mitochondrial disease, which should be considered as a cause of COX deficiency even in patients originating outside of the French-Canadian population. PMID:26510951

  1. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population

    PubMed Central

    Oláhová, Monika; Hardy, Steven A.; Hall, Julie; Yarham, John W.; Haack, Tobias B.; Wilson, William C.; Alston, Charlotte L.; He, Langping; Aznauryan, Erik; Brown, Ruth M.; Brown, Garry K.; Morris, Andrew A. M.; Mundy, Helen; Broomfield, Alex; Barbosa, Ines A.; Simpson, Michael A.; Deshpande, Charu; Moeslinger, Dorothea; Koch, Johannes; Stettner, Georg M.; Bonnen, Penelope E.; Prokisch, Holger; Lightowlers, Robert N.; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M. A.

    2015-01-01

    Mitochondrial Complex IV [cytochrome c oxidase (COX)] deficiency is one of the most common respiratory chain defects in humans. The clinical phenotypes associated with COX deficiency include liver disease, cardiomyopathy and Leigh syndrome, a neurodegenerative disorder characterized by bilateral high signal lesions in the brainstem and basal ganglia. COX deficiency can result from mutations affecting many different mitochondrial proteins. The French-Canadian variant of COX-deficient Leigh syndrome is unique to the Saguenay-Lac-Saint-Jean region of Québec and is caused by a founder mutation in the LRPPRC gene. This encodes the leucine-rich pentatricopeptide repeat domain protein (LRPPRC), which is involved in post-transcriptional regulation of mitochondrial gene expression. Here, we present the clinical and molecular characterization of novel, recessive LRPPRC gene mutations, identified using whole exome and candidate gene sequencing. The 10 patients come from seven unrelated families of UK-Caucasian, UK-Pakistani, UK-Indian, Turkish and Iraqi origin. They resemble the French-Canadian Leigh syndrome patients in having intermittent severe lactic acidosis and early-onset neurodevelopmental problems with episodes of deterioration. In addition, many of our patients have had neonatal cardiomyopathy or congenital malformations, most commonly affecting the heart and the brain. All patients who were tested had isolated COX deficiency in skeletal muscle. Functional characterization of patients’ fibroblasts and skeletal muscle homogenates showed decreased levels of mutant LRPPRC protein and impaired Complex IV enzyme activity, associated with abnormal COX assembly and reduced steady-state levels of numerous oxidative phosphorylation subunits. We also identified a Complex I assembly defect in skeletal muscle, indicating different roles for LRPPRC in post-transcriptional regulation of mitochondrial mRNAs between tissues. Patient fibroblasts showed decreased steady-state levels of mitochondrial mRNAs, although the length of poly(A) tails of mitochondrial transcripts were unaffected. Our study identifies LRPPRC as an important disease-causing gene in an early-onset, multisystem and neurological mitochondrial disease, which should be considered as a cause of COX deficiency even in patients originating outside of the French-Canadian population. PMID:26510951

  2. Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles

    PubMed Central

    Inaba, Koji; Nakamura, Satoshi; Okamoto, Hiroyuki; Kashihara, Tairo; Kobayashi, Kazuma; Harada, Ken; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Murakami, Naoya; Ito, Yoshinori; Igaki, Hiroshi; Uno, Takashi; Itami, Jun

    2016-01-01

    Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy). PMID:26684338

  3. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

    PubMed

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

    2015-01-01

    Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts. PMID:25790282

  4. Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

    PubMed

    Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

    2016-06-01

    It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases. PMID:26979097

  5. De novo FUS mutations are the most frequent genetic cause in early-onset German ALS patients.

    PubMed

    Hübers, Annemarie; Just, Walter; Rosenbohm, Angela; Müller, Kathrin; Marroquin, Nicolai; Goebel, Ingrid; Högel, Josef; Thiele, Holger; Altmüller, Janine; Nürnberg, Peter; Weishaupt, Jochen H; Kubisch, Christian; Ludolph, Albert C; Volk, Alexander E

    2015-11-01

    In amyotrophic lateral sclerosis (ALS) patients with known genetic cause, mutations in chromosome 9 open reading frame 72 (C9orf72) and superoxide dismutase 1 (SOD1) account for most familial and late-onset sporadic cases, whereas mutations in fused in sarcoma (FUS) can be identified in just around 5% of familial and 1% of overall sporadic cases. There are only few reports on de novo FUS mutations in juvenile ALS patients. To date, no systematic evaluation on the frequency of de novo FUS mutations in early-onset ALS patients has been conducted. Here, we screened a cohort of 14 early-onset sporadic ALS patients (onset age <35 years) to determine the frequency of mutations in C9orf72, SOD1, and FUS in this defined patient cohort. All patients were recruited prospectively by a single center in a period of 38 months. No mutations were detected in SOD1 or C9orf72; however, we identified 6 individuals (43%) carrying a heterozygous FUS mutation including 1 mutation that has not been described earlier (c.1504delG [p.Asp502Thrfs*27]). Genetic testing of parents was possible in 5 families and revealed that the mutations in these patients arose de novo. Three of the 6 identified patients presented with initial bulbar symptoms. Our study identifies FUS mutations as the most frequent genetic cause in early-onset ALS. Genetic testing of FUS thus seems indicated in sporadic early-onset ALS patients especially if showing predominant bulbar symptoms and an aggressive disease course. PMID:26362943

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

    PubMed Central

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

    2015-01-01

    Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts. PMID:25790282

  7. Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

    ERIC Educational Resources Information Center

    Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

    2008-01-01

    The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

  8. Verbal Behavior in Young Children with Autism Spectrum Disorders at the Onset of an Early Behavioral Intervention Program

    ERIC Educational Resources Information Center

    Rivard, Melina; Forget, Jacques

    2012-01-01

    The scope of this study was direct observation of verbal behaviors of 14 children with autism spectrum disorders at the onset of an early behavioral intervention (EBI) program delivered in a public services agency. Objectives were to (1) describe frequencies of vocal, verbal, and listener behaviors; (2) evaluate the relationship between the…

  9. Components of Negative Affect as Moderators of the Relationship between Early Drinking Onset and Binge-Drinking Behavior

    ERIC Educational Resources Information Center

    McNamara, Robert S.; Swaim, Randall C.; Rosen, Lee A.

    2010-01-01

    This study examines the moderating effects of negative affect on the relationship between early drinking onset and binge-drinking behavior. Six hundred and thirty-five eleventh- and twelfth-grade students completed the American Drug and Alcohol Survey and reported on a variety of measures, including items assessing anxiety, anger, depression, age…

  10. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    ERIC Educational Resources Information Center

    Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

  11. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40

  12. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    Nieto, Rebeca Garcia; Castellanos, F. Xavier

    2011-01-01

    Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric

  13. The effect of intrapartum antibiotics on early-onset neonatal sepsis in Dhaka, Bangladesh: a propensity score matched analysis

    PubMed Central

    2014-01-01

    Background We estimate the effect of antibiotics given in the intrapartum period on early-onset neonatal sepsis in Dhaka, Bangladesh using propensity score techniques. Methods We followed 600 mother-newborn pairs as part of a cohort study at a maternity center in Dhaka. Some pregnant women received one dose of intravenous antibiotics during labor based on clinician discretion. Newborns were followed over the first seven days of life for early-onset neonatal sepsis defined by a modified version of the World Health Organization Young Infants Integrated Management of Childhood Illnesses criteria. Using propensity scores we matched women who received antibiotics with similar women who did not. A final logistic regression model predicting sepsis was run in the matched sample controlling for additional potential confounders. Results Of the 600 mother-newborn pairs, 48 mothers (8.0%) received antibiotics during the intrapartum period. Seventy-seven newborns (12.8%) were classified with early-onset neonatal sepsis. Antibiotics appeared to be protective (odds ratio 0.381, 95% confidence interval 0.115–1.258), however this was not statistically significant. The results were similar after adjusting for prematurity, wealth status, and maternal colonization status (odds ratio 0.361, 95% confidence interval 0.106–1.225). Conclusions Antibiotics administered during the intrapartum period may reduce the risk of early-onset neonatal sepsis in high neonatal mortality settings like Dhaka. PMID:24742087

  14. The Use of Voice Onset Time by Early Bilinguals to Distinguish Homorganic Stops in Canadian English and Canadian French

    ERIC Educational Resources Information Center

    Macleod, Andrea A. N.; Stoel-Gammon, Carol

    2009-01-01

    The goal of this study was to examine the extent to which bilingual speakers maintain language-specific phonological contrasts for homorganic stops when a cue is shared across both languages. To this end, voice onset time (VOT) was investigated in three groups of participants: early bilinguals speakers of Canadian French and Canadian English (n =…

  15. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    ERIC Educational Resources Information Center

    Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication

  16. A Follow-up Study of Early Onset Psychosis: Comparison between Outcome Diagnoses of Schizophrenia, Mood Disorders, and Personality Disorders.

    ERIC Educational Resources Information Center

    McClellan, Jon M.; And Others

    1993-01-01

    This study of 95 youths previously diagnosed with psychotic disorders found that at follow-up, 24 had a diagnosis of schizophrenia, 9 with psychotic mood disorders, 5 with personality disorders, and 1 with schizo-affective disorder. The study confirmed findings regarding early onset schizophrenia and psychotic mood disorders and emphasized the

  17. The Northern Ireland Early Onset Psychosis Study: Phenomenology and Co-Morbidity in the First 25 Cases

    ERIC Educational Resources Information Center

    Fulton, Karen; Short, Mary; Harvey-Smith, Diane; Rushe, Teresa M.; Mulholland, Ciaran

    2008-01-01

    Diagnosing psychotic disorders in young people is difficult. High rates of co-morbidity may be one reason for this difficulty, but it may also be the case that current diagnostic categories are not the most useful when approaching the care of young people with psychotic symptoms. The Northern Ireland Early Onset Psychosis Study is the first study

  18. The Northern Ireland Early Onset Psychosis Study: Phenomenology and Co-Morbidity in the First 25 Cases

    ERIC Educational Resources Information Center

    Fulton, Karen; Short, Mary; Harvey-Smith, Diane; Rushe, Teresa M.; Mulholland, Ciaran

    2008-01-01

    Diagnosing psychotic disorders in young people is difficult. High rates of co-morbidity may be one reason for this difficulty, but it may also be the case that current diagnostic categories are not the most useful when approaching the care of young people with psychotic symptoms. The Northern Ireland Early Onset Psychosis Study is the first study…

  19. A Meta-Analysis of Neuropsychological Functioning in Patients with Early Onset Schizophrenia and Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    Nieto, Rebeca Garcia; Castellanos, F. Xavier

    2011-01-01

    Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric…

  20. Onset of clinical and MRI efficacy occurs early after fingolimod treatment initiation in relapsing multiple sclerosis.

    PubMed

    Kappos, Ludwig; Radue, Ernst-Wilhelm; Chin, Peter; Ritter, Shannon; Tomic, Davorka; Lublin, Fred

    2016-02-01

    To minimize the clinical burden associated with multiple sclerosis (MS), early control of focal and diffuse CNS disease activity is a treatment priority. A post hoc analysis was conducted to evaluate the onset of efficacy of fingolimod treatment in patients with relapsing MS. Data from patients who received fingolimod 0.5 mg or placebo during either of two 24-month, double-blind, randomized, parallel-group clinical trials (FREEDOMS and FREEDOMS II) were pooled for analysis. Efficacy outcomes were: time to first confirmed relapse; annualized relapse rate (ARR); proportions of patients free from T1 gadolinium-enhancing lesions or new/newly enlarged T2 lesions; percentage brain volume loss (BVL); and change in Multiple Sclerosis Functional Composite (MSFC) z-score from baseline to 6 months. An early benefit was seen with fingolimod (N = 783) vs. placebo (N = 773) for ARR at both 3 and 6 months (3 months, 0.32 vs. 0.52, p = 0.0015; 6 months, 0.21 vs. 0.45, p < 0.0001). Time to first relapse was also delayed with fingolimod vs. placebo from day 48 onwards. At 6 months, more patients in the fingolimod group than in the placebo group were free from new MRI activity (65.3 vs. 40.5 %, p < 0.0001) and had less BVL (37.1 % reduction vs. placebo, p < 0.001). MSFC z-score favored fingolimod over placebo at 6 months, with improvements noted in 9-Hole Peg Test and Paced Auditory Serial Addition Test scores. Improvements in outcomes related to relapses, MRI, disability, cognition, and BVL occurred within 6 months of treatment initiation with fingolimod. PMID:26645392

  1. A Novel Recessive NEFL Mutation Causes a Severe, Early-Onset Axonal Neuropathy

    PubMed Central

    Yum, Sabrina W.; Zhang, Junxian; Mo, Katie; Li, Jian; Scherer, Steven S.

    2015-01-01

    Objective To report the first cases of homozygous recessive mutations in NEFL, the gene that encodes the light subunit of neurofilaments (NFL). Methods Clinical and electrophysiologic data of all family members were evaluated, and a sural nerve biopsy from one affected child was examined by immunohistochemistry and electron microscopy. The ability of the mutant protein to form filaments was characterized in an established cell culture system. Results Four of five siblings developed a severe, progressive neuropathy beginning in early childhood. Serial nerve conduction studies showed progressively reduced amplitudes with age, and pronounced slowing at all ages. Visual evoked responses were slowed in three children, indicating that CNS axons were subclinically involved. All four affected children were homozygous for a nonsense mutation at glutamate 210 (E210X) in the NEFL gene; both parents were heterozygous carriers. A sural nerve biopsy from an affected patient at age 16 revealed markedly reduced numbers of myelinated axons; the remaining myelinated axons were small and lacked intermediate filaments. The E210X mutant protein did not form an intermediate filament network, and did not interfere with the filament formation by wild type human NFL in SW-13 vim- cells. Interpretation This is the first demonstration of a recessive NEFL mutation, which appears to cause a simple loss-of-function, resulting in a severe, early-onset axonal neuropathy with unique features. These results confirm that neurofilaments are the main determinant of axonal caliber and conduction velocity, and demonstrate for the first time that neurofilaments are required for the maintenance of myelinated PNS axons. PMID:20039262

  2. Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis.

    PubMed

    Cizmeci, Mehmet Nevzat; Kara, Semra; Kanburoglu, Mehmet Kenan; Simavli, Serap; Duvan, Candan Iltemur; Tatli, Mustafa Mansur

    2014-03-01

    Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism's access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min-max: 118.1-8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis. PMID:24424393

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

    PubMed Central

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

    2015-01-01

    Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1)1–7 in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis1–7. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma. PMID:25261934

  4. Transcriptional Onset of Lysozyme Genes during Early Development in Olive Flounder (Paralichthys olivaceus)

    PubMed Central

    Lee, Jang-Wook; Lee, Jeong-Ho; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Kim, Kyung-Kil

    2014-01-01

    The immune system in teleost fish is not completely developed during embryonic and larval stages, therefore effective innate mechanisms is very important for survival in such an environment. However, the knowledge of the development of immune system assumed to be restricted. In many species, lysozymes have been considered as important genes of the first line immune defense. The early detection of lysozyme mRNA in previous reports, led to the investigation of its presence in oocytes. As a result, c-type lysozyme mRNA transcripts were detected in unfertilized oocytes indicating maternal transfer. Therefore, we investigated the expression patterns of lysozymes in flounder, including the matured oocyte. In our results, c-type lysozyme mRNA was first detected in unfertilized oocyte stage, observed the significantly decreased until hatching stage, and was significantly increased after hatching stage. On the other hand, g-type lysozyme mRNA transcripts were first detected at late neurula stage, and the mRNA level was significantly increased after 20 dph. It may be suggest that maternally supplied mRNAs are selectively degraded prior to the activation of embryonic transcription. This study will be help in understanding the maturation and onset of humoral immunity during development of olive flounder immune system. PMID:25949197

  5. Therapeutic implications of novel mutations of the RFX6 gene associated with early-onset diabetes.

    PubMed

    Artuso, R; Provenzano, A; Mazzinghi, B; Giunti, L; Palazzo, V; Andreucci, E; Blasetti, A; Chiuri, R M; Gianiorio, F E; Mandich, P; Monami, M; Mannucci, E; Giglio, S

    2015-02-01

    Identification of the genetic defect underlying early-onset diabetes is important for determining the specific diabetes subtype, which would then permit appropriate treatment and accurate assessment of recurrence risk in offspring. Given the extensive genetic and clinical heterogeneity of the disease, high-throughput sequencing might provide additional diagnostic potential when Sanger sequencing is ineffective. Our aim was to develop a targeted next-generation assay able to detect mutations in several genes involved in glucose metabolism. All 13 known MODY genes, genes identified from a genome-wide linkage study or genome-wide association studies as increasing the risk of type 2 diabetes and genes causing diabetes in animal models, were included in the custom panel. We selected a total of 102 genes by performing a targeting re-sequencing in 30 patients negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and IPF1 genes at the Sanger sequencing analysis. Previously unidentified variants in the RFX6 gene were found in three patients and in two of them we also detected rare variants in WFS1 and ABCC8 genes. All patients showed a good therapeutic response to dipeptidyl peptidase-4 (DPP4) inhibitors. Our study reveals that next-generation sequencing provides a highly sensitive method for identification of variants in new causative genes of diabetes. This approach may help in understanding the molecular etiology of diabetes and in providing more personalized treatment for each genetic subtype. PMID:25048417

  6. Reducing the Cost of the Diagnostic Odyssey in Early Onset Epileptic Encephalopathies

    PubMed Central

    Mansilla, M. Adela; Campbell, Colleen A.

    2016-01-01

    Whole exome sequencing (WES) has revolutionized the way we think about and diagnose epileptic encephalopathies. Multiple recent review articles discuss the benefits of WES and suggest various algorithms to follow for determining the etiology of epileptic encephalopathies. Incorporation of WES in these algorithms is leading to the discovery of new genetic diagnoses of early onset epileptic encephalopathies (EOEEs) at a rapid rate; however, WES is not yet a universally utilized diagnostic tool. Clinical WES may be underutilized due to provider discomfort in ordering the test or perceived costliness. At our hospital WES is not routinely performed for patients with EOEE due to limited insurance reimbursement. In fact for any patient with noncommercial insurance (Medicaid) the institution does not allow sending out WES as this is not “established”/“proven to be highly useful and cost effective”/“approved test” in patients with epilepsy. Recently, we performed WES on four patients from three families and identified novel mutations in known epilepsy genes in all four cases. These patients had State Medicaid as their insurance carrier and were followed up for several years for EOEE while being worked up using the traditional/approved testing methods. Following a recently proposed diagnostic pathway, we analyzed the cost savings (US dollars) that could be accrued if WES was performed earlier in the diagnostic odyssey. This is the first publication that addresses the dollar cost of traditional testing in EOEE as performed in these four cases versus WES and the potential cost savings.

  7. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    PubMed Central

    Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

  8. Assessment of the contralesional corticospinal tract in early-onset pediatric hemiplegia: Preliminary findings.

    PubMed

    Hawe, Rachel L; Dewald, Jules P A

    2014-01-01

    While pediatric hemiplegia results from a unilateral lesion, the immature state of the brain at the time of injury increases the likelihood of observing changes in the non-lesioned hemisphere as well. The purpose of this preliminary study was to use diffusion tensor imaging to evaluate the contralesional corticospinal tracts in individuals with early-onset pediatric hemiplegia. Twelve individuals with pediatric hemiplegia and ten age-matched controls underwent diffusion tensor imaging (DTI). Corticospinal projections were reconstructed using probabilistic tractography for both the lesioned and contralesional side in pediatric hemiplegia as well as the dominant and non-dominant sides in control subjects. The contralesional tract was found to have decreased white matter integrity relative to control subjects. Compared to controls, the contralesional tract also showed increased tract volume. The increase in volume suggests the presence of ipsilateral corticospinal projections from the contralesional hemisphere that are maintained during development to control the paretic extremities. Decreases in integrity may be explained by diffuse damage or incomplete maturation. The findings of this study support the notion of bilateral motor involvement in pediatric hemiplegia, and the need to address bilateral neural changes as well as motor deficits in this population. PMID:25571199

  9. Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer.

    PubMed

    Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal

    2016-01-15

    Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439

  10. Altered expression of mRNA profiles in blood of early-onset schizophrenia

    PubMed Central

    Xu, Yong; Yao Shugart, Yin; Wang, Guoqiang; Cheng, Zaohuo; Jin, Chunhui; Zhang, Kai; Wang, Jun; Yu, Hao; Yue, Weihua; Zhang, Fuquan; Zhang, Dai

    2016-01-01

    To identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes . The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD, and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ. PMID:26733343

  11. Critical slowing down as early warning for the onset of collapse in mutualistic communities.

    PubMed

    Dakos, Vasilis; Bascompte, Jordi

    2014-12-01

    Tipping points are crossed when small changes in external conditions cause abrupt unexpected responses in the current state of a system. In the case of ecological communities under stress, the risk of approaching a tipping point is unknown, but its stakes are high. Here, we test recently developed critical slowing-down indicators as early-warning signals for detecting the proximity to a potential tipping point in structurally complex ecological communities. We use the structure of 79 empirical mutualistic networks to simulate a scenario of gradual environmental change that leads to an abrupt first extinction event followed by a sequence of species losses until the point of complete community collapse. We find that critical slowing-down indicators derived from time series of biomasses measured at the species and community level signal the proximity to the onset of community collapse. In particular, we identify specialist species as likely the best-indicator species for monitoring the proximity of a community to collapse. In addition, trends in slowing-down indicators are strongly correlated to the timing of species extinctions. This correlation offers a promising way for mapping species resilience and ranking species risk to extinction in a given community. Our findings pave the road for combining theory on tipping points with patterns of network structure that might prove useful for the management of a broad class of ecological networks under global environmental change. PMID:25422412

  12. Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats

    PubMed Central

    Ofri, Ron; Reilly, Christopher M.; Maggs, David J.; Fitzgerald, Paul G.; Shilo-Benjamini, Yael; Good, Kathryn L.; Grahn, Robert A.; Splawski, Danielle D.; Lyons, Leslie A.

    2015-01-01

    Purpose A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Methods Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Results Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. Conclusions A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID:26258614

  13. Critical slowing down as early warning for the onset of collapse in mutualistic communities

    PubMed Central

    Dakos, Vasilis; Bascompte, Jordi

    2014-01-01

    Tipping points are crossed when small changes in external conditions cause abrupt unexpected responses in the current state of a system. In the case of ecological communities under stress, the risk of approaching a tipping point is unknown, but its stakes are high. Here, we test recently developed critical slowing-down indicators as early-warning signals for detecting the proximity to a potential tipping point in structurally complex ecological communities. We use the structure of 79 empirical mutualistic networks to simulate a scenario of gradual environmental change that leads to an abrupt first extinction event followed by a sequence of species losses until the point of complete community collapse. We find that critical slowing-down indicators derived from time series of biomasses measured at the species and community level signal the proximity to the onset of community collapse. In particular, we identify specialist species as likely the best-indicator species for monitoring the proximity of a community to collapse. In addition, trends in slowing-down indicators are strongly correlated to the timing of species extinctions. This correlation offers a promising way for mapping species resilience and ranking species risk to extinction in a given community. Our findings pave the road for combining theory on tipping points with patterns of network structure that might prove useful for the management of a broad class of ecological networks under global environmental change. PMID:25422412

  14. Facial, vocal and cross-modal emotion processing in early-onset schizophrenia spectrum disorders.

    PubMed

    Giannitelli, Marianna; Xavier, Jean; François, Anne; Bodeau, Nicolas; Laurent, Claudine; Cohen, David; Chaby, Laurence

    2015-10-01

    Recognition of emotional expressions plays an essential role in children's healthy development. Anomalies in these skills may result in empathy deficits, social interaction difficulties and premorbid emotional problems in children and adolescents with schizophrenia. Twenty-six subjects with early onset schizophrenia spectrum (EOSS) disorders and twenty-eight matched healthy controls (HC) were instructed to identify five basic emotions and a neutral expression. The assessment entailed presenting visual, auditory and congruent cross-modal stimuli. Using a generalized linear mixed model, we found no significant association for handedness, age or gender. However, significant associations emerged for emotion type, perception modality, and group. EOSS patients performed worse than HC in uni- and cross-modal emotional tasks with a specific negative emotion processing impairment pattern. There was no relationship between emotion identification scores and positive or negative symptoms, self-reported empathy traits or a positive history of developmental disorders. However, we found a significant association between emotional identification scores and nonverbal communication impairments. We conclude that cumulative dysfunctions in both nonverbal communication and emotion processing contribute to the social vulnerability and morbidity found in youths who display EOSS disorder. PMID:26297473

  15. Classifying early-onset colorectal cancer according to tumor location: new potential subcategories to explore

    PubMed Central

    Perea, José; Cano, Juana M; Rueda, Daniel; García, Juan L; Inglada, Lucía; Osorio, Irene; Arriba, María; Pérez, Jessica; Gaspar, Miriam; Fernández-Miguel, Tamara; Rodríguez, Yolanda; Benítez, Javier; González-Sarmiento, Rogelio; Urioste, Miguel

    2015-01-01

    Early-onset Colorectal Cancer (ECRC) represents a significant and increasing proportion of Colorectal Cancer (CRC), but it is a heterogeneous entity that probably encompasses specific subclasses. On the premise that the carcinogenetic mechanism and progression of CRC may differ with location, we analyzed molecular and clinical characteristics of ECRC according to tumor location in order to identify more homogeneous subgroups of CRC. Right-sided ECRC is a subset in which most Lynch Syndrome cases are found, with earlier stages at diagnosis and better prognosis. At this location the CpG Island Methylator Phenotype (CIMP) is predominant and Chromosomal Instability (CI) is rare. Left-sided ECRC appears as a transitional or intermediate location, except for CI tumors, that seem to predominate at this location. Finally, rectal ECRC shows Microsatellite Stability, CIMP low-0 and low CI - with recurrent altered chromosomal regions in common with left-sided ECRC-, possibly in relation with Microsatellite And Chromosomal Stable tumors, but with an unexpected familial component and worse prognosis. All this suggest that the molecular basis of ECRC varies with tumor location, which could affect the clinical management of patients. PMID:26328262

  16. NAPB - a novel SNARE-associated protein for early-onset epileptic encephalopathy.

    PubMed

    Conroy, J; Allen, N M; Gorman, K M; Shahwan, A; Ennis, S; Lynch, S A; King, M D

    2016-02-01

    Next-generation sequencing has accelerated the identification of disease genes in many rare genetic disorders including early-onset epileptic encephalopathies (EOEEs). While many of these disorders are caused by neuronal channelopathies, the role of synaptic and related neuronal proteins are increasingly being described. Here, we report a 6-year-old girl with unexplained EOEE characterized by multifocal seizures and profound global developmental delay. Recessive inheritance was considered due to parental consanguinity and Irish Traveller descent. Exome sequencing was performed. Variant prioritization identified a homozygous nonsense variant in the N-ethylmaleimide-sensitive factor attachment protein, beta (NAPB) gene resulting in a premature stop codon and 46% loss of the protein. NAPB plays a role in soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE)-complex dissociation and recycling (synaptic vesicle docking). Knockout mouse models of the murine ortholog Napb have been previously reported. These mice develop recurrent post-natal epileptic seizures in the absence of structural brain changes. The identification of a disease-causing variant in NAPB further recognizes the importance of the SNARE complex in the development of epilepsy and suggests that this gene should be considered in patients with unexplained EOEE. PMID:26235277

  17. Presence of Arp Specifically Contributes to Joint Tissue Edema Associated with Early-Onset Lyme Arthritis

    PubMed Central

    Hove, Petronella R.; Haldorson, Gary J.; Magunda, Forgivemore

    2014-01-01

    Antiserum to the Borrelia burgdorferi arthritis-related protein, Arp, has been shown to prevent or reduce arthritis in immunodeficient mice. To directly investigate the requirement for this lipoprotein in the generation of Lyme arthritis, we utilized targeted deletion to generate a B. burgdorferi clone that lacked only the arp gene locus. Infection of Lyme disease-susceptible C3H/HeN mice with the arp deletion mutant demonstrated significantly reduced tibiotarsal joint swelling during the first 6 weeks of infection compared to a wild-type control. The severity of joint swelling was restored to wild-type levels in mice infected with an arp mutant clone complemented in cis. Interestingly, the reduced swelling of joint tissues exhibited by mice infected with the arp deletion mutant did not directly correspond to reduced underlying arthritis. Histopathology data at 2 weeks postinfection showed some reduction in arthritis severity caused by the arp mutant clone; however, by 8 weeks, no significant difference was observed between joint tissues infected by the wild-type or arp mutant clones. The spirochete load in the joint tissues of mice infected with the arp mutant was found to be greater than that exhibited by the wild-type control. Our findings demonstrate that this lipoprotein contributes to the generation of early-onset joint swelling and suggests that arp expression has a negative secondary effect on total spirochete numbers in joint tissues. PMID:24101694

  18. The early Miocene onset of a ventilated circulation regime in the Arctic Ocean.

    PubMed

    Jakobsson, Martin; Backman, Jan; Rudels, Bert; Nycander, Jonas; Frank, Martin; Mayer, Larry; Jokat, Wilfried; Sangiorgi, Francesca; O'Regan, Matthew; Brinkhuis, Henk; King, John; Moran, Kathryn

    2007-06-21

    Deep-water formation in the northern North Atlantic Ocean and the Arctic Ocean is a key driver of the global thermohaline circulation and hence also of global climate. Deciphering the history of the circulation regime in the Arctic Ocean has long been prevented by the lack of data from cores of Cenozoic sediments from the Arctic's deep-sea floor. Similarly, the timing of the opening of a connection between the northern North Atlantic and the Arctic Ocean, permitting deep-water exchange, has been poorly constrained. This situation changed when the first drill cores were recovered from the central Arctic Ocean. Here we use these cores to show that the transition from poorly oxygenated to fully oxygenated ('ventilated') conditions in the Arctic Ocean occurred during the later part of early Miocene times. We attribute this pronounced change in ventilation regime to the opening of the Fram Strait. A palaeo-geographic and palaeo-bathymetric reconstruction of the Arctic Ocean, together with a physical oceanographic analysis of the evolving strait and sill conditions in the Fram Strait, suggests that the Arctic Ocean went from an oxygen-poor 'lake stage', to a transitional 'estuarine sea' phase with variable ventilation, and finally to the fully ventilated 'ocean' phase 17.5 Myr ago. The timing of this palaeo-oceanographic change coincides with the onset of the middle Miocene climatic optimum, although it remains unclear if there is a causal relationship between these two events. PMID:17581581

  19. Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism.

    PubMed

    Giusti, Betti; Saracini, Claudia; Bolli, Paola; Magi, Alberto; Martinelli, Ida; Peyvandi, Flora; Rasura, Maurizia; Volpe, Massimo; Lotta, Luca A; Rubattu, Speranza; Mannucci, Pier Mannuccio; Abbate, Rosanna

    2010-08-01

    The hypothesis underlying this study is that variations in genes involved in methionine metabolism may contribute to genetic susceptibility for early-onset ischaemic stroke. We investigated 58 polymorphisms in AHCY, BHMT, BHMT2, CBS, ENOSF1, FOLH1, MTHFD1, MTHFR, MTR, MTRR, NNMT, PON1, PON2, SLC19A1, SHMT1, TCN2, TYMS genes on genomic DNA from 501 young patients who survived ischaemic stroke and 1,211 sex and age comparable controls. Genotype distribution was significantly different between patients and controls for the following SNPs: rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, rs202680 FOLH1, rs2274976 MTHFR, rs1979277 SHMT1, rs20721958 TCN2. On multiple logistic regression analysis adjusted for traditional risk factors, rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, and rs202680 FOLH1 remained independent risk factors for stroke. After haplotype reconstruction, generalised linear model analyses adjusted for traditional risk factors and using the FDR multiple testing correction showed significant associations between ischaemic stroke and BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes. This study identifies significant genetic associations between premature ischaemic stroke and haplotypes in BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS genes involved in methionine metabolism. PMID:20458436

  20. Molecular alterations in gastric cancer with special reference to the early-onset subtype

    PubMed Central

    Skierucha, Małgorzata; Milne, Anya NA; Offerhaus, G Johan A; Polkowski, Wojciech P; Maciejewski, Ryszard; Sitarz, Robert

    2016-01-01

    Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC. PMID:26937134

  1. Molecular alterations in gastric cancer with special reference to the early-onset subtype.

    PubMed

    Skierucha, Małgorzata; Milne, Anya Na; Offerhaus, G Johan A; Polkowski, Wojciech P; Maciejewski, Ryszard; Sitarz, Robert

    2016-02-28

    Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC. PMID:26937134

  2. Early-onset bipolar disorder: how about visual-spatial skills and executive functions?

    PubMed

    Lera-Miguel, Sara; Andrés-Perpiñá, Susana; Calvo, Rosa; Fatjó-Vilas, Mar; Fañanás, Lourdes; Lourdes, Fañanás; Lázaro, Luisa

    2011-04-01

    Early-onset bipolar disorder is an impairing condition that is strongly associated with genetic inheritance. Neurocognitive deficits are core traits of this disorder which seem to be present in both young and adult forms. Deficits in verbal memory and attention are persistent within euthymic phases in bipolar adults, adolescents, and children. In younger samples, including type I or II and not otherwise specified patients, executive functions are not widely impaired and the existence of visual-spatial deficits remains unclear. The main aim of this study was to compare the neurocognitive performance in young stabilized type I or II bipolar patients and healthy controls. Fifteen medicated adolescents with bipolar disorder and 15 healthy adolescents, matched in age and gender, were compared on visual-spatial skills (reasoning, memory, visual-motor accuracy) and executive functioning (attention and working memory, set-shifting, inhibition) using t-tests and MANCOVA. Correcting for verbal competence, MANCOVA showed that patients performed significantly worse than controls in letters and numbers sequencing (P = 0.003), copy (P < 0.001) and immediate recall (P = 0.007) of the Rey Complex Figure Test, interference of the Stroop Color-Word Test (P = 0.007) and non-perseverative errors on the Wisconsin Card Sorting Test (P = 0.038). Impaired cognitive performance was found in young bipolar patients in working memory, visual-motor skills, and inhibitory control. PMID:21086134

  3. Familial early-onset dementia with complex neuropathologic phenotype and genomic background.

    PubMed

    Alexander, John; Kalev, Ognian; Mehrabian, Shima; Traykov, Latchezar; Raycheva, Margariata; Kanakis, Dimitrios; Drineas, Petros; Lutz, Mirjam I; Ströbel, Thomas; Penz, Thomas; Schuster, Michael; Bock, Christoph; Ferrer, Isidro; Paschou, Peristera; Kovacs, Gabor G

    2016-06-01

    Despite significant progress in our understanding of hereditary neurodegenerative diseases, the list of genes associated with early-onset dementia is not yet complete. In the present study, we describe a familial neurodegenerative disorder characterized clinically as the behavioral and/or dysexecutive variant of Alzheimer's disease with neuroradiologic features of Alzheimer's disease, however, lacking amyloid-β deposits in the brain. Instead, we observed a complex, 4 repeat predominant, tauopathy, together with a TAR DNA-binding protein of 43 kDa proteinopathy. Whole-exome sequencing on 2 affected siblings and 1 unaffected aunt uncovered a large number of candidate genes, including LRRK2 and SYNE2. In addition, DDI1, KRBA1, and TOR1A genes possessed novel stop-gain mutations only in the patients. Pathway, gene ontology, and network interaction analysis indicated the involvement of pathways related to neurodegeneration but revealed novel aspects also. This condition does not fit into any well-characterized category of neurodegenerative disorders. Exome sequencing did not disclose a single disease-specific gene mutation suggesting that a set of genes working together in different pathways may contribute to the etiology of the complex phenotype. PMID:27143436

  4. THE ROLE OF PROTEOMICS IN THE DIAGNOSIS OF CHORIOAMNIONITIS AND EARLY-ONSET NEONATAL SEPSIS

    PubMed Central

    Buhimschi, Catalin S.

    2010-01-01

    SYNOPSIS Intra-uterine infection is viewed as a unique pathological process which raises considerably the risk for early onset neonatal sepsis (EONS). By acting synergistically with prematurity, EONS increases the risk for adverse neonatal outcomes including intraventricular hemorrhage (IVH) and cerebral palsy which are often encountered as sequelae of sepsis. Although several distinct pathways for the pathogenesis of fetal damage have been proposed, the basic molecular mechanisms that modulate these events remain incompletely understood. Therefore, discovery of clinically and biologically relevant biomarkers able to reveal key pathogenic pathways and predict pregnancies at risk for antenatal fetal damage is a priority. Proteomics provides a unique opportunity to fill this gap. In the short run proteomic biomarkers may aid with medical decision-making including timing of delivery and steroid administration In the long run proteomic biomarkers may lead to development of targeted therapies against pathogenic variants of EONS. Herein, we aimed to illustrate the richness of the topic and set the stage for the argument that discovery of novel proteomic biomarkers is a critical step in improving outcomes and preventing long-term disability. PMID:20569812

  5. Integrating Genetic, Neuropsychological and Neuroimaging Data to Model Early-Onset Obsessive Compulsive Disorder Severity

    PubMed Central

    Mas, Sergi; Gassó, Patricia; Morer, Astrid; Calvo, Anna; Bargalló, Nuria; Lafuente, Amalia; Lázaro, Luisa

    2016-01-01

    We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the training set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our understanding of the neurobiological basis of the disorder. PMID:27093171

  6. White Matter Abnormalities and Cognitive Impairment in Early-Onset Schizophrenia-Spectrum Disorders

    PubMed Central

    Epstein, Katherine A.; Cullen, Kathryn; Mueller, Bryon; Lee, Susanne; Kumra, Sanjiv

    2014-01-01

    OBJECTIVE To characterize white matter abnormalities in adolescents with early onset schizophrenia (EOS) relative to three comparison groups (adolescents at clinical high risk for developing schizophrenia [CHR], adolescents with cannabis use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive correlates of white matter abnormalities in EOS. METHOD We used diffusion tensor imaging and tractography methods to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus in adolescents with EOS (n=55), CHR (n=21), CUD (n=31), and HC (n=55). FA in tracts that were significantly altered in EOS was correlated with neurocognitive performance. RESULTS EOS and CHR groups had significantly lower FA than HC in four tracts: bilateral CST, left ILF, and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and left ILF predicted worse neurocognitive performance in EOS. CONCLUSIONS This study identified left ILF and left IFOF as possible biomarkers of vulnerability for developing schizophrenia. Lower FA in these tracts may disrupt functioning of ventral visual and language streams, producing domain-specific neurocognitive deficits that interfere with higher order cognitive abilities. PMID:24565363

  7. Characterization of a novel genetically obese mouse model demonstrating early onset hyperphagia and hyperleptinemia.

    PubMed

    Nakahara, Keiko; Bannai, Makoto; Maruyama, Keisuke; Suzuki, Yoshihiro; Okame, Rieko; Murakami, Noboru

    2013-08-01

    Obesity is a critical risk factor for the development of metabolic syndrome, and many obese animal models are used to investigate the mechanisms responsible for the appearance of symptoms. To establish a new obese mouse model, we screened ?13,000 ICR mice and discovered a mouse demonstrating spontaneous obesity. We named this mouse "Daruma" after a traditional Japanese ornament. Following the fixation of the genotype, these animals exhibited obese phenotypes according to Mendel's law of inheritance. In the Daruma mouse, the leptin receptor gene sequence carried two base mutations that are good candidates for the variation(s) responsible for the obese phenotype. The Daruma mice developed characteristic visceral fat accumulation at 4 wk of age, and the white adipose and liver tissues exhibited increases in cell size and lipid droplets, respectively. No histological abnormalities were observed in other tissues of the Daruma mice, even after the mice reached 25 wk of age. Moreover, the onset of impaired leptin signaling was early and manifested as hyperleptinemia and hyperinsulinemia. Pair feeding completely inhibited obesity, although these mice rapidly developed hyperphagia and obesity followed by hyperleptinemia when pair feeding ceased and free-access feeding was permitted. Therefore, the Daruma mice exhibited unique characteristics and may be a good model for studying human metabolic syndrome. PMID:23736543

  8. Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

    PubMed Central

    Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439

  9. A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer

    PubMed Central

    Antelo, Marina; Balaguer, Francesc; Shia, Jinru; Shen, Yan; Hur, Keun; Moreira, Leticia; Cuatrecasas, Miriam; Bujanda, Luis; Giraldez, Maria Dolores; Takahashi, Masanobu; Cabanne, Ana; Barugel, Mario Edmundo; Arnold, Mildred; Roca, Enrique Luis; Andreu, Montserrat; Castellvi-Bel, Sergi; Llor, Xavier; Jover, Rodrigo; Castells, Antoni; Boland, C. Richard; Goel, Ajay

    2012-01-01

    Objective Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. Design We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤50 years old (n = 188), a group of sporadic CRC >50 years (MSS n = 89; MSI n = 46), and a group of Lynch syndrome CRCs (n = 20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. Results Mean LINE-1 methylation levels (±SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test). Conclusions LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC. PMID:23049789

  10. Football and dementia: A qualitative investigation of a community based sports group for men with early onset dementia.

    PubMed

    Carone, Laura; Tischler, Victoria; Dening, Tom

    2014-11-26

    This study investigates the impact of a weekly group providing sport and physical activities for men with early onset dementia established by Notts County Football in the Community (NCFC). There were three aims: to investigate the effect of early onset dementia on individuals with the condition and their carers; to examine the perceptions of current levels of service provision for people with early onset dementia; and to analyse the impact of the group. Men with dementia (n = 5) attending the sessions, their carers (n = 5), NCFC coaching staff (n = 5) and people organizing/facilitating the sessions (n = 5) were interviewed. Semi-structured interviews explored the participants' experiences of dementia, their opinions on current service provisions and on the sessions. Data were analysed using thematic analysis. Four main themes were found: loss related to the condition of dementia and its impact on relationships ('Loss'); lack of age-appropriate services for people with early onset dementia ('Lack of Resources'); enjoyment and positive anticipation related to the group for all involved ('Enjoyment and Anticipation'); and 'the Notts County Effect' which attributed the success of the sessions to the strong brand of the football club, and to personalized service in a "dementia-free" environment. The NCFC sessions provided a safe low-cost intervention with positive effects upon quality of life for both people with early onset dementia, their carers and the staff involved. This suggests that the service may be valuable to a wider range of people living in different areas. PMID:25427788

  11. Common Variants in Promoter of ADTRP Associate with Early-Onset Coronary Artery Disease in a Southern Han Chinese Population

    PubMed Central

    Huang, Lei; Wu, Qiu-Ping; Tang, Shuang-Bo; Luo, Bin; Liu, Shui-Ping; Liu, Xiao-Shan; Li, Zhao-Hui; Quan, Li; Li, Yue; Shi, He; Lv, Guo-Li; Zhao, Jian; Cheng, Jian-Ding; Liu, Chao

    2015-01-01

    The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3’UTR, rs2076189 in 5’UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105–0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD. PMID:26375920

  12. Identification of the PS1 Thr147Ile Variant in a Family with Very Early Onset Dementia and Expressive Aphasia

    PubMed Central

    Denvir, James; Neitch, Shirley; Fan, Jun; Niles, Richard M.; Boskovic, Goran; Schreurs, Bernard G.; Primerano, Donald A.; Alkon, Daniel L.

    2015-01-01

    Background Early onset dementias have variable clinical presentations and are often difficult to diagnose. We established a family pedigree that demonstrated consistent recurrence of very early onset dementia in successive generations. Objective and Method In order to refine the diagnosis in this family, we sequenced the exomes of two affected family members and relied on discrete filtering to identify disease genes and the corresponding causal variants. Results Among the 720 nonsynonymous single nucleotide polymorphisms (SNPs) shared by two affected members, we found a C to T transition that gives rise to a Thr147Ile missense substitution in the presenilin 1 (PS1) protein. The presence of this same mutation in a French early-onset Alzheimer’s disease family, other affected members of the family, and the predicted high pathogenicity of the substitution strongly suggest that it is the causal variant. In addition to exceptionally young age of onset, we also observed significant limb spasticity and early loss of speech, concurrent with progression of dementia in affected family members. These findings extend the clinical presentation associated with the Thr147Ile variant. Lastly, one member with the Thr147Ile variant was treated with the PKC epsilon activator, bryostatin, in a compassionate use trial after successful FDA review. Initial improvements with this treatment were unexpectedly clear, including return of some speech, increased attentional focus, ability to swallow, and some apparent decrease in limb spasticity. Conclusions Our findings confirm the role of the PS1 Thr147Ile substitution in Alzheimer’s disease and expand the clinical phenotype to include expressive aphasia and very early onset of dementia. PMID:25812849

  13. Nonsurgical periodontal therapy.

    PubMed

    Drisko, C H

    2001-01-01

    Regular home care by the patient in addition to professional removal of subgingival plaque is generally very effective in controlling most inflammatory periodontal diseases. When disease does recur, despite frequent recall, it can usually be attributed to lack of sufficient supragingival and subgingival plaque control or to other risk factors that influence host response, such as diabetes or smoking. Causative factors contributing to recurrent disease include deep inaccessible pockets, overhangs, poor crown margins and plaque-retentive calculus. In most cases, simply performing a thorough periodontal debridement under local anesthesia will stop disease progression and result in improvement in the clinical signs and symptoms of active disease. If however, clinical signs of disease activity persist following thorough mechanical therapy, such as increased pocket depths, loss of attachment and bleeding on probing, other pharmacotherapeutic therapies should be considered. Augmenting scaling and root planing or maintenance visits with adjunctive chemotherapeutic agents for controlling plaque and gingivitis could be as simple as placing the patient on an antimicrobial mouthrinse and/or toothpaste with agents such as fluorides, chlorhexidine or triclosan, to name a few. Since supragingival plaque reappears within hours or days after its removal, it is important that patients have access to effective alternative chemotherapeutic products that could help them achieve adequate supragingival plaque control. Recent studies, for example, have documented the positive effect of triclosan toothpaste on the long-term maintenance of both gingivitis and periodontitis patients. Daily irrigation with a powered irrigation device, with or without an antimicrobial agent, is also useful for decreasing the inflammation associated with gingivitis and periodontitis. Clinically significant changes in probing depths and attachment levels are not usually expected with irrigation alone. Recent reports, however, would indicate that, when daily irrigation with water was added to a regular oral hygiene home regimen, a significant reduction in probing depth, bleeding on probing and Gingival Index was observed. A significant reduction in cytokine levels (interleukin-1beta and prostaglandin E2, which are associated with destructive changes in inflamed tissues and bone resorption also occurs. If patient-applied antimicrobial therapy is insufficient in preventing, arresting, or reversing the disease progression, then professionally applied antimicrobial agents should be considered including sustained local drug delivery products. Other, more broadly based pharmacotherapeutic agents may be indicated for multiple failing sites. Such agents would include systemic antibiotics or host modulating drugs used in conjunction with periodontal debridement. More aggressive types of juvenile periodontitis or severe rapidly advancing adult periodontitis usually require a combination of surgical intervention in conjunction with systemic antibiotics and generally are not controlled with nonsurgical anti-infective therapy alone. It should be noted, however, that, to date, no home care products or devices currently available can completely control or eliminate the pathogenic plaques associated with periodontal diseases for extended periods of time. Daily home care and frequent recall are still paramount for long-term success. Nonsurgical therapy remains the cornerstone of periodontal treatment. Attention to detail, patient compliance and proper selection of adjunctive antimicrobial agents for sustained plaque control are important elements in achieving successful long-term results. Frequent re-evaluation and careful monitoring allows the practitioner the opportunity to intervene early in the disease state, to reverse or arrest the progression of periodontal disease with meticulous nonsurgical anti-infective therapy. PMID:11155183

  14. Early drinking onset: a study of prevalence and determinants among 13-year-old adolescents in Norway.

    PubMed

    Adolfsen, Frode; Strøm, Henriette Kyrrestad; Martinussen, Monica; Natvig, Henrik; Eisemann, Martin; Handegård, Bjørn Helge; Koposov, Roman

    2014-10-01

    Early drinking onset is associated with different psychosocial adjustment problems among adolescents. The aim of this study was to assess determinants associated with early drinking and to identify factors predicting early drinking onset among adolescents. The study included 1,550 eighth-graders with a mean age of 13.5 years from 41 schools. A total of 24% (boys 29%, girls 19%) had ever drunk alcohol, while 14% had drunk some alcohol in the last 30 days. Further, early drinking was associated with gender, religion, school performance, smoking and bullying in the bivariate tests. Predictors of early drinking onset were identified by generalized linear mixed models with two multivariable models created. The first model included social and environmental variables. Entering intentions, expectancies, attitudes and norms into the multivariable analysis resulted in a significant improvement of the model fit constituting 86% in the second model. The percentage correctly classified those (56%) who had been drinking in the second model which was two times higher compared to the first model. Gender, religion and smoking emerged as significant predictors of drinking in both models. PMID:25070139

  15. Molecular Features and Methylation Status in Early Onset (≤40 Years) Colorectal Cancer: A Population Based, Case-Control Study

    PubMed Central

    Magnani, Giulia; Furlan, Daniela; Sahnane, Nora; Reggiani Bonetti, Luca; Domati, Federica; Pedroni, Monica

    2015-01-01

    Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%). KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p = 0.02). Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis. PMID:26557847

  16. Gray Matter Alterations in Schizophrenia High-Risk Youth and Early-Onset Schizophrenia: A Review of Structural MRI Findings

    PubMed Central

    Brent, Benjamin K.; Thermenos, Heidi W.; Keshavan, Matcheri S.; Seidman, Larry J.

    2013-01-01

    Synopsis The purpose of this article is to provide a review of the literature on structural MRI findings in pediatric and young adult populations at clinical or genetic high-risk for schizophrenia, as well as in early-onset schizophrenia. The authors discuss the implications of this research for understanding the pathophysiology of schizophrenia and for early intervention strategies for prevention of the illness. The evidence linking brain structural changes in pre-psychosis development and early-onset schizophrenia with disruptions of normal neurodevelopmental processes during childhood and/or adolescence are described. In addition, the authors outline future directions for research to address current knowledge gaps regarding the neurobiological basis of brain structural abnormalities in schizophrenia and to help improve the utility of these abnormalities for preventative interventions. PMID:24012081

  17. Laser therapy for periodontitis

    NASA Astrophysics Data System (ADS)

    Efanov, O. I.

    2001-04-01

    An investigation was made of applying pulsed (lambda) equals 0.89 micrometers laser radiation in the treatment for early diagnosed periodontitis. The investigation was made on 65 patients (47 patients constituted the experimental group and 18 patients constituted a control group) affected by periodontitis. Clinical and functional tests revealed that laser therapy produced a string effect on the course of the illness. It reduced bleeding, inflammation, and pruritus. However, it did not produce an affect on electroexcitation. Biomicroscopic examinations and periodontium rheography revealed that the gingival blood flow became normal after the course of laser therapy. The capillary permeability and venous congestion decreased, which was confirmed by the increased time of vacuum tests, raised gingival temperature, reduced tissue clearance, and increased oxygen tension. Apart from that, laser therapy subsided fibrinolysis, proteolytic tissue activity, and decreased the exudative inflammation of periodontium.

  18. Excess of rare coding variants in PLD3 in late- but not early-onset Alzheimer’s disease

    PubMed Central

    Schulte, Eva C; Kurz, Alexander; Alexopoulos, Panagiotis; Hampel, Harald; Peters, Annette; Gieger, Christian; Rujescu, Dan; Diehl-Schmid, Janine; Winkelmann, Juliane

    2015-01-01

    Recently, mutations in phospholipase D3 (PLD3) were reported in late-onset Alzheimer's disease (AD). By screening the coding regions of PLD3 for variants in a European cohort of 1,089 AD cases, 182 individuals with frontotemporal lobar degeneration and 1,456 controls, we identified 32 variants with a minor allele frequency <5% and observed an excess of rare variants in individuals with late- but not early-onset AD (P=0.034, χ 2-test; odds ratio=1.46).

  19. A Bayesian three-parameter logistic model for early- and late-onset DLTs in oncology Phase I studies.

    PubMed

    Zheng, Wei; Zhao, Yang; Lu, Yuefeng; Miao, Harry; Liu, Hengchang

    2016-01-01

    We introduce a three-parameter logistic model to analyze the dose limiting toxicity (DLT) as a time-to-event endpoint in oncology Phase I trials. In the proposed model, patients are allowed to stay on trial without the constraint of a maximum follow-up time. Our model accommodates late-onset DLT as well as early-onset DLT, by both of which the dose recommendation is informed. A Bayesian approach is used to incorporate prior knowledge of the test treatment into dose recommendation. Simulation examples show that our proposed model has good operating characteristics in assessing the maximum tolerated dose (MTD). PMID:25629564

  20. Digging Deeper Using Neuroimaging Tools Reveals Important Clues to Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Kumra, Sanjiv

    2008-01-01

    The article describes the use of structural neuroimaging to understand the psychopathology of childhood-onset schizophrenia. Results showed an increase in lateral volumes, reduced total and regional volumes of gray matter in the cortex and increased basal ganglia volumes as in adult-onset schizophrenia in comparison with healthy subjects.

  1. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    ERIC Educational Resources Information Center

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and

  2. Huntington Disease: A Case Study of Early Onset Presenting as Depression

    ERIC Educational Resources Information Center

    Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

    2004-01-01

    Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

  3. Octapeptide repeat insertions in the prion protein gene and early onset dementia

    PubMed Central

    Croes, E; Theuns, J; Houwing-Duisterma..., J; Dermaut, B; Sleegers, K; Roks, G; Van den Broeck, M; van Harten, B; van Swieten, J C; Cruts, M; Van Broeckhoven, C; van Duijn, C M

    2004-01-01

    Methods: Following identification of a two-octapeptide repeat insertion in PRNP, we conducted a meta-analysis to investigate the relation of number of PRNP octapeptide repeats with age at disease onset and duration of illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used a linear mixed effects model to assess the relation of number of repeats with age at disease onset, and studied the effect of the number of inserted octapeptide repeats on disease duration with a Cox proportional hazards regression analysis. Results: We found an increasing number of repeats associated with younger age at onset (p<0.001). Duration of the disease decreased significantly with the length of the octapeptide repeat (p<0.001) when adjusting for age at onset. Conclusions: Our findings show significant inverse associations of the length of the PRNP octapeptide repeat with age at disease onset and disease duration in the spongiform encephalopathies. PMID:15258222

  4. Mode of onset of ventricular fibrillation in patients with early repolarization pattern vs. Brugada syndrome

    PubMed Central

    Nam, Gi-Byoung; Ko, Kwan-Ho; Kim, Jun; Park, Kyoung-Min; Rhee, Kyoung-Suk; Choi, Kee-Joon; Kim, You-Ho; Antzelevitch, Charles

    2010-01-01

    Aims The aim of the present study was to identify specific electrocardiogram (ECG) features that predict the development of multiple episodes of ventricular fibrillation (VF) in patients with an early repolarization (ER) pattern and to compare the mode of VF initiation with that observed in typical cases of Brugada syndrome (BrS). Methods and results The mode of the onset and the coupling intervals of the premature ventricular contractions (PVCs) initiating VF episodes were analysed in patients with BrS (n = 8) or ER who experienced sudden cardiac death/syncope or repeated appropriate implantable cardioverter defibrillator shocks. Among the 11 patients with ER, 5 presented with electrical storm (ES, four or more recurrent VF episodes/day). The five ES patients displayed a dramatic but very transient accentuation of J waves across the precordial and limb leads prior to the development of ES. Ventricular fibrillation episodes were more commonly initiated by PVCs with a short–long–short (SLS) sequence in ER (42/58, 72.4%) vs. BrS patients (13/86, 15.1%, P < 0.01). Coupling intervals were significantly shorter in the ER group compared with those with BrS [328 (320, 340) ms vs. 395 (350, 404) ms, P < 0.01]. Conclusion Our study provides additional evidence in support of the hypothesis that ER pattern in the ECG is not always benign. Transient augmentation of global J waves may be indicative of a highly arrhythmogenic substrate heralding multiple episodes of VF in patients with ER pattern. Ventricular tachycardia/VF initiation is more commonly associated with an SLS sequence, and PVCs display a shorter coupling interval in patients with ER pattern compared with those with BrS. PMID:19880418

  5. Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin Diagnostic Accuracy Studies.

    PubMed

    Chiesa, Claudio; Pacifico, Lucia; Osborn, John F; Bonci, Enea; Hofer, Nora; Resch, Bernhard

    2015-07-01

    To perform a systematic review assessing accuracy and completeness of diagnostic studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative.EONS, diagnosed during the first 3 days of life, remains a common and serious problem. Increased PCT is a potentially useful diagnostic marker of EONS, but reports in the literature are contradictory. There are several possible explanations for the divergent results including the quality of studies reporting the clinical usefulness of PCT in ruling in or ruling out EONS.We systematically reviewed PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies were eligible for inclusion in our review if they provided measures of PCT accuracy for diagnosing EONS. A data extraction form based on the STARD checklist and adapted for neonates with EONS was used to appraise the quality of the reporting of included studies.We found 18 articles (1998-2014) fulfilling our eligibility criteria which were included in the final analysis. Overall, the results of our analysis showed that the quality of studies reporting diagnostic accuracy of PCT for EONS was suboptimal leaving ample room for improvement. Information on key elements of design, analysis, and interpretation of test accuracy were frequently missing.Authors should be aware of the STARD criteria before starting a study in this field. We welcome stricter adherence to this guideline. Well-reported studies with appropriate designs will provide more reliable information to guide decisions on the use and interpretations of PCT test results in the management of neonates with EONS. PMID:26222858

  6. Higher filtration fraction in formerly early-onset preeclamptic women without comorbidity.

    PubMed

    Toering, Tsjitske J; van der Graaf, Anne Marijn; Visser, Folkert W; Groen, Henk; Faas, Marijke M; Navis, Gerjan; Lely, A Titia

    2015-04-15

    Formerly preeclamptic women have an increased risk for developing end-stage renal disease, which has been attributed to altered renal hemodynamics and abnormalities in the renin-angiotensin-aldosterone system. Whether this is due to preeclampsia itself or to comorbid conditions is unknown. Renal hemodynamics and responsiveness to ANG II during low Na(+) intake (7 days, 50 mmol Na(+)/24 h) and high Na(+) (HS) intake (7 days, 200 mmol Na(+)/24 h) were studied in 18 healthy normotensive formerly early-onset preeclamptic women (fPE women) and 18 healthy control subjects (fHP women), all selected for absence of comorbidity. At the end of each diet, renal hemodynamics and blood pressure were measured before and during graded ANG II infusion. Both HS intake and former preeclampsia increased filtration fraction (FF) without an interaction between the two. FF was highest during HS intake in fPE women [0.31 ± 0.12 vs. 0.29 ± 0.11 in fHP women, generalized estimating equation analysis (body mass index corrected), P = 0.03]. The renal response to ANG II infusion was not different between groups. In conclusion, fPE women have a higher FF compared with fHP women. As this was observed in the absence of comorbidity, preeclampsia itself might exert long-term effects on renal hemodynamics. However, we cannot exclude the presence of prepregnancy alterations in renal function, which, in itself, lead to an increased risk for preeclampsia. In experimental studies, an elevated FF has been shown to play a pathogenic role in the development of hypertension and renal damage. Future studies, however, should evaluate whether the subtle differences in renal hemodynamics after preeclampsia contribute to the increased long-term renal risk after preeclampsia. PMID:25694481

  7. Kelch-like homologue 9 mutation is associated with an early onset autosomal dominant distal myopathy

    PubMed Central

    von Deimling, Florian; Sachdev, Shrikesh; Errington, Wesley J.; Herrmann, Ralf; Bönnemann, Carsten; Brockmann, Knut; Hinderlich, Stephan; Lindner, Tom H.; Steinbrecher, Alice; Hoffmann, Katrin; Privé, Gilbert G.; Hannink, Mark; Nürnberg, Peter; Voit, Thomas

    2010-01-01

    Distal myopathies are a heterogeneous group of disorders characterized by progressive weakness and muscular atrophy, beginning in distal limb muscles and affecting proximal limb muscles at a later stage. We studied a large German kindred with 10 affected members. Weakness and atrophy of the anterior tibial muscles started between the ages of 8 and 16 years, followed by atrophy of intrinsic hand muscles. Progression was slow, and patients retained the ability to walk until the seventh decade. Serum creatinine kinase levels were increased in the range of 150–1400 U/l. Muscle biopsies showed myopathic changes, whereas immunohistochemistry showed normal expression of marker proteins for muscular dystrophies. Patients had reduced sensation with stocking-glove distribution in the distal limbs in later life. Nerve conduction studies revealed no evidence of neuropathy. Genome-wide linkage analysis in this family revealed a new locus for distal myopathy at 9p21.2-p22.3 (multipoint logarithm of the odds ratio = 4.21). By positional cloning we found a heterozygous mutation L95F in the Kelch-like homologue 9 gene, encoding a bric-a-brac Kelch protein. Molecular modelling indicated that the mutation may interfere with the interaction of the bric-a-brac domain with Cullin 3. Coimmunoprecipitation experiments confirmed that the mutation reduces association with Cullin 3 in the Kelch-like homologue 9-Cullin 3–E3 ubiquitin ligase complex, which is involved in ubiquitin-dependent protein degradation. We identified a unique form of early onset autosomal dominant distal myopathy which is associated with a Kelch-like homologue 9 mutation and interferes with normal skeletal muscle through a novel pathogenetic mechanism. PMID:20554658

  8. Disrupted rich club network in behavioral variant frontotemporal dementia and early-onset Alzheimer's disease.

    PubMed

    Daianu, Madelaine; Mezher, Adam; Mendez, Mario F; Jahanshad, Neda; Jimenez, Elvira E; Thompson, Paul M

    2016-03-01

    In network analysis, the so-called "rich club" describes the core areas of the brain that are more densely interconnected among themselves than expected by chance, and has been identified as a fundamental aspect of the human brain connectome. This is the first in-depth diffusion imaging study to investigate the rich club along with other organizational changes in the brain's anatomical network in behavioral frontotemporal dementia (bvFTD), and a matched cohort with early-onset Alzheimer's disease (EOAD). Our study sheds light on how bvFTD and EOAD affect connectivity of white matter fiber pathways in the brain, revealing differences and commonalities in the connectome among the dementias. To analyze the breakdown in connectivity, we studied three groups: 20 bvFTD, 23 EOAD, and 37 healthy elderly controls. All participants were scanned with diffusion-weighted magnetic resonance imaging (MRI), and based on whole-brain probabilistic tractography and cortical parcellations, we analyzed the rich club of the brain's connectivity network. This revealed distinct patterns of disruption in both forms of dementia. In the connectome, we detected less disruption overall in EOAD than in bvFTD [false discovery rate (FDR) critical Pperm  = 5.7 × 10(-3) , 10,000 permutations], with more involvement of richly interconnected areas of the brain (chi-squared P = 1.4 × 10(-4) )-predominantly posterior cognitive alterations. In bvFTD, we found a greater spread of disruption including the rich club (FDR critical Pperm  = 6 × 10(-4) ), but especially more peripheral alterations (chi-squared P = 6.5 × 10(-3) ), particularly in medial frontal areas of the brain, in line with the known behavioral socioemotional deficits seen in these patients. Hum Brain Mapp 37:868-883, 2016. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26678225

  9. Frequency, magnitude and character of hyperthermal events at the onset of the Early Eocene Climatic Optimum

    NASA Astrophysics Data System (ADS)

    Lauretano, V.; Littler, K.; Polling, M.; Zachos, J. C.; Lourens, L. J.

    2015-10-01

    Recent studies have shown that the Early Eocene Climatic Optimum (EECO) was preceded by a series of short-lived global warming events, known as hyperthermals. Here we present high-resolution benthic stable carbon and oxygen isotope records from ODP Sites 1262 and 1263 (Walvis Ridge, SE Atlantic) between ~ 54 and ~ 52 million years ago, tightly constraining the character, timing, and magnitude of six prominent hyperthermal events. These events, which include Eocene Thermal Maximum (ETM) 2 and 3, are studied in relation to orbital forcing and long-term trends. Our findings reveal an almost linear relationship between δ13C and δ18O for all these hyperthermals, indicating that the eccentricity-paced covariance between deep-sea temperature changes and extreme perturbations in the exogenic carbon pool persisted during these events towards the onset of the EECO, in accordance with previous observations for the Paleocene Eocene Thermal Maximum (PETM) and ETM2. The covariance of δ13C and δ18O during H2 and I2, which are the second pulses of the "paired" hyperthermal events ETM2-H2 and I1-I2, deviates with respect to the other events. We hypothesize that this could relate to a relatively higher contribution of an isotopically heavier source of carbon, such as peat or permafrost, and/or to climate feedbacks/local changes in circulation. Finally, the δ18O records of the two sites show a systematic offset with on average 0.2 ‰ heavier values for the shallower Site 1263, which we link to a slightly heavier isotopic composition of the intermediate water mass reaching the northeastern flank of the Walvis Ridge compared to that of the deeper northwestern water mass at Site 1262.

  10. ATF6 Is Mutated in Early Onset Photoreceptor Degeneration With Macular Involvement

    PubMed Central

    Xu, Mingchu; Gelowani, Violet; Eblimit, Aiden; Wang, Feng; Young, Marielle P.; Sawyer, Briana L.; Zhao, Li; Jenkins, Glen; Creel, Donnell J.; Wang, Keqing; Ge, Zhongqi; Wang, Hui; Li, Yumei; Hartnett, M. Elizabeth; Chen, Rui

    2015-01-01

    Purpose. Photoreceptor degeneration (PRD) is a genetically heterogeneous retinal disorder. Although a number of genes involved in PRD have been identified, their genetic basis remains unknown in a significant number of patients. In this study, we aimed to identify novel disease-causing genes of PRD. Methods. Comprehensive ocular examinations were performed in a 2-year-old patient diagnosed with early onset PRD. Retinal capture sequencing was performed to screen causative mutations in known retinal disease-causing loci. Whole-exome sequencing (WES) and a series of variant-filtering strategies were applied for identifying novel disease-causing genes. Retina ATF6 expression was confirmed by immunohistochemistry. RT-PCR was performed to identify ATF6 mRNA in the patient. Results. The patient showed typical PRD features, with macular involvement and ellipsoid zone irregularities. Results of retinal capture sequencing were negative. WES data led to identification of biallelic loss-of-function mutations in the ATF6 gene. The first variant generates a premature stop codon (NCBI accession no. NM_007348: c.1126C>T, p.R376*) and the second variant affects a splicing donor site (NM_007348: c.1533+1G>C). Sanger sequencing confirmed the 2 alleles are from 1 parent each. Both of the variants are extremely rare in the population. The splicing variant causes either intron inclusion or exon skipping in the patient, thus severely disrupting ATF6 functional domains. ATF6 is expressed in three neuronal cell layers of mouse retina. Conclusions. Our results support ATF6 as a novel disease-causing gene for PRD and suggest that disrupted protein quality control mechanisms may be a novel pathological mechanism underlying human retinal degeneration. PMID:26070061

  11. Stratification of Risk of Early-Onset Sepsis in Newborns ≥34 Weeks’ Gestation

    PubMed Central

    Puopolo, Karen M.; Wi, Soora; Turk, Benjamin J.; Kuzniewicz, Michael W.; Walsh, Eileen M.; Newman, Thomas B.; Zupancic, John; Lieberman, Ellice; Draper, David

    2014-01-01

    OBJECTIVE: To define a quantitative stratification algorithm for the risk of early-onset sepsis (EOS) in newborns ≥34 weeks’ gestation. METHODS: We conducted a retrospective nested case-control study that used split validation. Data collected on each infant included sepsis risk at birth based on objective maternal factors, demographics, specific clinical milestones, and vital signs during the first 24 hours after birth. Using a combination of recursive partitioning and logistic regression, we developed a risk classification scheme for EOS on the derivation dataset. This scheme was then applied to the validation dataset. RESULTS: Using a base population of 608 014 live births ≥34 weeks’ gestation at 14 hospitals between 1993 and 2007, we identified all 350 EOS cases <72 hours of age and frequency matched them by hospital and year of birth to 1063 controls. Using maternal and neonatal data, we defined a risk stratification scheme that divided the neonatal population into 3 groups: treat empirically (4.1% of all live births, 60.8% of all EOS cases, sepsis incidence of 8.4/1000 live births), observe and evaluate (11.1% of births, 23.4% of cases, 1.2/1000), and continued observation (84.8% of births, 15.7% of cases, incidence 0.11/1000). CONCLUSIONS: It is possible to combine objective maternal data with evolving objective neonatal clinical findings to define more efficient strategies for the evaluation and treatment of EOS in term and late preterm infants. Judicious application of our scheme could result in decreased antibiotic treatment in 80 000 to 240 000 US newborns each year. PMID:24366992

  12. Cognitive performance of GBA mutation carriers with early-onset PD

    PubMed Central

    Caccappolo, E.; Mejia-Santana, H.; Tang, M.-X.; Rosado, L.; Orbe Reilly, M.; Ruiz, D.; Ross, B.; Verbitsky, M.; Kisselev, S.; Louis, E.; Comella, C.; Colcher, A.; Jennings, D.; Nance, M.; Bressman, S.; Scott, W.K.; Tanner, C.; Mickel, S.; Andrews, H.; Waters, C.; Fahn, S.; Cote, L.; Frucht, S.; Ford, B.; Rezak, M.; Novak, K.; Friedman, J.H.; Pfeiffer, R.; Marsh, L.; Hiner, B.; Siderowf, A.; Payami, H.; Molho, E.; Factor, S.; Ottman, R.; Clark, L.N.; Marder, K.

    2012-01-01

    Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration–matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale–III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004). Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD. PMID:22442429

  13. Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin Diagnostic Accuracy Studies

    PubMed Central

    Chiesa, Claudio; Pacifico, Lucia; Osborn, John F.; Bonci, Enea; Hofer, Nora; Resch, Bernhard

    2015-01-01

    Abstract To perform a systematic review assessing accuracy and completeness of diagnostic studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative. EONS, diagnosed during the first 3 days of life, remains a common and serious problem. Increased PCT is a potentially useful diagnostic marker of EONS, but reports in the literature are contradictory. There are several possible explanations for the divergent results including the quality of studies reporting the clinical usefulness of PCT in ruling in or ruling out EONS. We systematically reviewed PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies were eligible for inclusion in our review if they provided measures of PCT accuracy for diagnosing EONS. A data extraction form based on the STARD checklist and adapted for neonates with EONS was used to appraise the quality of the reporting of included studies. We found 18 articles (1998–2014) fulfilling our eligibility criteria which were included in the final analysis. Overall, the results of our analysis showed that the quality of studies reporting diagnostic accuracy of PCT for EONS was suboptimal leaving ample room for improvement. Information on key elements of design, analysis, and interpretation of test accuracy were frequently missing. Authors should be aware of the STARD criteria before starting a study in this field. We welcome stricter adherence to this guideline. Well-reported studies with appropriate designs will provide more reliable information to guide decisions on the use and interpretations of PCT test results in the management of neonates with EONS. PMID:26222858

  14. Policy implications of early onset breast cancer among Mexican-origin women

    PubMed Central

    Wilkinson, Anna V.; Etzel, Carol J.; Zhou, Renke; Jones, Lovell A.; Thompson, Patricia; Bondy, Melissa L.

    2010-01-01

    Overall, Latinas are more likely to be diagnosed with a more advanced stage of breast cancer, and are 20% more likely to die of breast cancer than non-Hispanic white women. It is estimated that from 2003–2006, $82.0 billion in direct medical care expenditures, in addition to 100,000 lives annually, could be saved by eliminating health disparities experienced by Latinos and increasing the use of up to five preventive services in the U.S. An additional 3,700 lives could be saved if 90% of women ≥40 years were recently screened for breast cancer. We examined risk for breast cancer in a case-control population-based sample of Mexican-origin women in Harris County, TX (n=714), where rates of breast cancer mortality for Latina women have doubled since 1990. Half of breast cancer cases (n=119) were diagnosed before the age of 50. In a multivariable model, women with a family history of breast cancer (OR=4.3), born in Mexico and having high levels of language acculturation (OR=2.5), and without health insurance (OR=1.6) were found to have the highest risk of breast cancer. Because Mexican-origin women were found to be of high-risk for early onset pre-menopausal breast cancer, we recommend policies targeting screening, education and treatment to prevent increased disparities in mortality. The inclusion of community members and policymakers as partners in these endeavors would further safeguard against an increase in cancer health disparities, and aid in formulating a policy agenda congruent with scientifically-based, community-driven policy efforts addressing breast cancer screening, education and treatment in this vulnerable population. PMID:21319396

  15. Sibling sex ratio and birth order in early-onset gender dysphoric adolescents.

    PubMed

    Schagen, Sebastian E E; Delemarre-van de Waal, Henriette A; Blanchard, Ray; Cohen-Kettenis, Peggy T

    2012-06-01

    Several sibship-related variables have been studied extensively in sexual orientation research, especially in men. Sibling sex ratio refers to the ratio of brothers to sisters in the aggregate sibships of a group of probands. Birth order refers to the probands' position (e.g., first-born, middle-born, last-born) within their sibships. Fraternal birth order refers to their position among male siblings only. Such research was extended in this study to a large group of early-onset gender dysphoric adolescents. The probands comprised 94 male-to-female and 95 female-to-male gender dysphoric adolescents. The overwhelming majority of these were homosexual or probably prehomosexual. The control group consisted of 875 boys and 914 girls from the TRAILS study. The sibling sex ratio of the gender dysphoric boys was very high (241 brothers per 100 sisters) compared with the expected ratio (106:100). The excess of brothers was more extreme among the probands' older siblings (300:100) than among their younger siblings (195:100). Between-groups comparisons showed that the gender dysphoric boys had significantly more older brothers, and significantly fewer older sisters and younger sisters, than did the control boys. In contrast, the only notable finding for the female groups was that the gender dysphoric girls had significantly fewer total siblings than did the control girls. The results for the male probands were consistent with prior speculations that a high fraternal birth order (i.e., an excess of older brothers) is found in all homosexual male groups, but an elevated sibling sex ratio (usually caused by an additional, smaller excess of younger brothers) is characteristic of gender dysphoric homosexual males. The mechanisms underlying these phenomena remain unknown. PMID:21674256

  16. High-Resolution Taxonomic Profiling of the Subgingival Microbiome for Biomarker Discovery and Periodontitis Diagnosis

    PubMed Central

    Szafranski, Szymon P.; Wos-Oxley, Melissa L.; Vilchez-Vargas, Ramiro; Jáuregui, Ruy; Plumeier, Iris; Klawonn, Frank; Tomasch, Jürgen; Meisinger, Christa; Kühnisch, Jan; Sztajer, Helena; Pieper, Dietmar H.

    2014-01-01

    The oral microbiome plays a key role for caries, periodontitis, and systemic diseases. A method for rapid, high-resolution, robust taxonomic profiling of subgingival bacterial communities for early detection of periodontitis biomarkers would therefore be a useful tool for individualized medicine. Here, we used Illumina sequencing of the V1-V2 and V5-V6 hypervariable regions of the 16S rRNA gene. A sample stratification pipeline was developed in a pilot study of 19 individuals, 9 of whom had been diagnosed with chronic periodontitis. Five hundred twenty-three operational taxonomic units (OTUs) were obtained from the V1-V2 region and 432 from the V5-V6 region. Key periodontal pathogens like Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia could be identified at the species level with both primer sets. Principal coordinate analysis identified two outliers that were consistently independent of the hypervariable region and method of DNA extraction used. The linear discriminant analysis (LDA) effect size algorithm (LEfSe) identified 80 OTU-level biomarkers of periodontitis and 17 of health. Health- and periodontitis-related clusters of OTUs were identified using a connectivity analysis, and the results confirmed previous studies with several thousands of samples. A machine learning algorithm was developed which was trained on all but one sample and then predicted the diagnosis of the left-out sample (jackknife method). Using a combination of the 10 best biomarkers, 15 of 17 samples were correctly diagnosed. Training the algorithm on time-resolved community profiles might provide a highly sensitive tool to detect the onset of periodontitis. PMID:25452281

  17. Anti-inflammatory cytokine IL-10 and T cell cytokine profile in periodontitis granulation tissue

    PubMed Central

    Lappin, D F; Macleod, C P; Kerr, A; Mitchell, T; Kinane, D F

    2001-01-01

    Th2 cells are more abundant than Th1 cells in periodontitis lesions, but the relative importance of the Th1 and Th2 subsets in periodontal disease is not understood. In addition, the role of proinflammatory and anti-inflammatory cytokines in this disease process is unclear. Biopsies were obtained from 10 patients with early onset periodontitis (EOP) and 10 patients with adult periodontitis (AP). From all of the patients in the AP group we were able to obtain and section the gingival tissue to serve as controls. We used polyclonal monospecific antibodies to detect cells expressing IL-2, IL-4, IL-6, IL-10 and IL-15, tumour necrosis factor (TNF-α) and interferon-gamma (IFN-γ) in formalin-fixed, paraffin-embedded sections of granulation tissue from periodontitis lesions. We also employed a series of oligonucleotide probes to detect cells expressing the cytokine transcripts in the same tissue biopsies. Cells that expressed IL-4 or IL-6 were more numerous than cells expressing either IL-2 or IFN-γ. Th2 cells were more numerous in EOP and AP tissues. IL-15 substitutes for IL-2 in a number of biological activities related to the Th1 immune response, and interestingly, in periodontal lesions the IL-15-expressing cells outnumbered IL-2-expressing cells, suggesting that this is the pattern of immune regulation by T cells in the periodontium. The functional balance in the T cell subsets detected by their cytokine profiles underlies the importance of the anti-inflammatory mechanisms taking place in the diseased tissue. The numbers of inflammatory leucocytes that express the anti-inflammatory cytokine IL-10 are much more widely distributed than those that express the proinflammatory cytokines IL-6 and TNF-α. This study suggests that large numbers of infiltrating inflammatory cells as well as accessory cells are involved in the down-regulation of the inflammatory and immune response in periodontitis. PMID:11207661

  18. High-resolution taxonomic profiling of the subgingival microbiome for biomarker discovery and periodontitis diagnosis.

    PubMed

    Szafranski, Szymon P; Wos-Oxley, Melissa L; Vilchez-Vargas, Ramiro; Jáuregui, Ruy; Plumeier, Iris; Klawonn, Frank; Tomasch, Jürgen; Meisinger, Christa; Kühnisch, Jan; Sztajer, Helena; Pieper, Dietmar H; Wagner-Döbler, Irene

    2015-02-01

    The oral microbiome plays a key role for caries, periodontitis, and systemic diseases. A method for rapid, high-resolution, robust taxonomic profiling of subgingival bacterial communities for early detection of periodontitis biomarkers would therefore be a useful tool for individualized medicine. Here, we used Illumina sequencing of the V1-V2 and V5-V6 hypervariable regions of the 16S rRNA gene. A sample stratification pipeline was developed in a pilot study of 19 individuals, 9 of whom had been diagnosed with chronic periodontitis. Five hundred twenty-three operational taxonomic units (OTUs) were obtained from the V1-V2 region and 432 from the V5-V6 region. Key periodontal pathogens like Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia could be identified at the species level with both primer sets. Principal coordinate analysis identified two outliers that were consistently independent of the hypervariable region and method of DNA extraction used. The linear discriminant analysis (LDA) effect size algorithm (LEfSe) identified 80 OTU-level biomarkers of periodontitis and 17 of health. Health- and periodontitis-related clusters of OTUs were identified using a connectivity analysis, and the results confirmed previous studies with several thousands of samples. A machine learning algorithm was developed which was trained on all but one sample and then predicted the diagnosis of the left-out sample (jackknife method). Using a combination of the 10 best biomarkers, 15 of 17 samples were correctly diagnosed. Training the algorithm on time-resolved community profiles might provide a highly sensitive tool to detect the onset of periodontitis. PMID:25452281

  19. Comparison between Early-Onset and Late-Onset Alzheimer's Disease Patients with Amnestic Presentation: CSF and 18F-FDG PET Study

    PubMed Central

    Chiaravalloti, Agostino; Koch, Giacomo; Toniolo, Sofia; Belli, Lorena; Lorenzo, Francesco Di; Gaudenzi, Sara; Schillaci, Orazio; Bozzali, Marco; Sancesario, Giuseppe; Martorana, Alessandro

    2016-01-01

    Background/Aims To investigate the differences in brain glucose consumption between patients with early onset of Alzheimer's disease (EOAD, aged ≤65 years) and patients with late onset of Alzheimer's disease (LOAD, aged >65 years). Methods Differences in brain glucose consumption between the groups have been evaluated by means of Statistical Parametric Mapping version 8, with the use of age, sex, Mini-Mental State Examination and cerebrospinal fluid values of AΒ1-42, phosphorylated Tau and total Tau as covariates in the comparison between EOAD and LOAD. Results As compared to LOAD, EOAD patients showed a significant decrease in glucose consumption in a wide portion of the left parietal lobe (BA7, BA31 and BA40). No significant differences were obtained when subtracting the EOAD from the LOAD group. Conclusions The results of our study show that patients with EOAD show a different metabolic pattern as compared to those with LOAD that mainly involves the left parietal lobe. PMID:27195000

  20. Early Oligocene Onset of Deep-Water Production in the North Atlantic

    NASA Astrophysics Data System (ADS)

    Thomas, D. J.; Via, R. K.

    2005-12-01

    The present mode of meridional overturning circulation is characterized by deep-water formation in both the North Atlantic and the Southern Ocean. However, a growing body of evidence indicates that the Southern Ocean was the dominant region of deep-water formation during the extreme warmth of the early Cenozoic. Establishment of a bipolar mode of deep-water circulation occurred during the tectonic evolution of the Atlantic basins and overall cooling of the Cenozoic. However, neither the timing nor the cause of this transition is known. Formation of the Panama Isthmus is assumed to represent the final step in this transition, yet it is unclear when deep waters first began forming in the North Atlantic prior to the development of true NADW. To reconstruct the evolution of Atlantic deep-sea circulation from the early Cenozoic mode to the bipolar mode, we generated neodymium isotope records from fossil fish teeth and bones. These records come from a depth transect of three Walvis Ridge sites cored during Ocean Drilling Program Leg 208. The depth transect, spanning more than 2200m water depth, enables us to resolve the vertical water mass structure through time to reconstruct changes in the relative deep-water contributions from the Southern Ocean and North Atlantic. Nd isotope data from the three sites indicates that a single water mass encompassed the entire depth range from ~55 to at least 17 million years ago. Published data from ODP Site 689 (2080m present water depth; ~1500m paleodepth in the Paleogene) in the Weddell Sea indicate similar values and the same trend with the Walvis Ridge data from ~46 to 33 Ma, suggesting a single Southern Ocean intermediate/deep-water mass until ~33 Ma. Approximately 33 Ma, Weddell Sea ɛNd(t) values diverge from Walvis Ridge values, and remain consistently more radiogenic for the duration of the Site 689 record. Walvis Ridge ɛNd(t) values become increasingly unradiogenic to the top of the investigated section. The most plausible explanation for decrease in Walvis Ridge ɛNd(t) values as well as the divergence in Nd isotopic composition from Weddell Sea values is the onset of and gradual increase in a North Atlantic deep-water contribution to the waters in the southeastern Atlantic. Thus, we suggest that significant deep-water production began in the Atlantic 33Ma.

  1. A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS

    PubMed Central

    Vitaliti, Giovanna; Trifiletti, Rosario R.; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

    2014-01-01

    Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, “overnight” onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS. PMID:24891915

  2. A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS.

    PubMed

    Vitaliti, Giovanna; Trifiletti, Rosario R; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

    2014-01-01

    Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS. PMID:24891915

  3. Fibrinogen Degradation Products and Periodontitis: Deciphering the Connection

    PubMed Central

    2015-01-01

    Introduction Fibrinogen degradation products (e.g. D-dimer) arise from digested fibrin clots and fibrinogen. Elevated concentrations accompany activation of coagulation and fibrinolysis and indicate chronic inflammatory diseases. D-Dimer tests are a quick, noninvasive method to rule out abnormal clotting. Periodontitis strongly affects the haemostatic system and evokes a procoagulant state. Correlation of chronic periodontitis with early indicators of disease (biomarkers) might be useful. Aim The aim of the study was to examine whether the plasma D-dimer concentration reflects the progression of chronic periodontitis and the beneficial effect of periodontal therapy. Materials and Methods Forty randomly selected subjects were divided into four groups, Group I: 10 healthy subjects, Group II: 10 with mild periodontitis, Group III: 10 with moderate periodontitis, Group IV: 10 with severe periodontitis. After thorough dental and periodontal examination, 3 mL of venous blood was collected for measurement of fibrinogen degradation products. Results The patients with moderate and chronic periodontitis exhibited high concentrations of D-dimer (mean value 434.98–535.52 mcg/mL), whereas subjects with mild or no periodontitis exhibited values of 329.78–211.29 mcg/mL. Concentrations of D-dimer were significantly reduced after therapy of all classes of periodontitis. Conclusion Periodontal treatment can reduce amount of D-dimer in the plasma. A higher than normal concentration is observed in chronic periodontitis. PMID:26816985

  4. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa

    PubMed Central

    Seale, Anna C; Mwaniki, Michael; Newton, Charles R J C; Berkley, James A

    2010-01-01

    Maternal and child health are high priorities for international development. Through a Review of published work, we show substantial gaps in current knowledge on incidence (cases per live births), aetiology, and risk factors for both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa. Although existing published data suggest that sepsis causes about 10% of all maternal deaths and 26% of neonatal deaths, these are likely to be considerable underestimates because of methodological limitations. Successful intervention strategies in resource-rich settings and early studies in sub-Saharan Africa suggest that the burden of maternal and early onset neonatal bacterial sepsis could be reduced through simple interventions, including antiseptic and antibiotic treatment. An effective way to expedite evidence to guide interventions and determine the incidence, aetiology, and risk factors for sepsis in sub-Saharan Africa would be through a multiarmed factorial intervention trial aimed at reducing both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa. PMID:19555902

  5. Predictors of schizophrenia spectrum disorders in early-onset first episodes of psychosis: a support vector machine model.

    PubMed

    Pina-Camacho, Laura; Garcia-Prieto, Juan; Parellada, Mara; Castro-Fornieles, Josefina; Gonzalez-Pinto, Ana M; Bombin, Igor; Graell, Montserrat; Paya, Beatriz; Rapado-Castro, Marta; Janssen, Joost; Baeza, Inmaculada; Del Pozo, Francisco; Desco, Manuel; Arango, Celso

    2015-04-01

    Identifying early-onset schizophrenia spectrum disorders (SSD) at a very early stage remains challenging. To assess the diagnostic predictive value of multiple types of data at the emergence of early-onset first-episode psychosis (FEP), various support vector machine (SVM) classifiers were developed. The data were from a 2-year, prospective, longitudinal study of 81 patients (age 9-17 years) with early-onset FEP and a stable diagnosis during follow-up and 42 age- and sex-matched healthy controls (HC). The input was different combinations of baseline clinical, neuropsychological, magnetic resonance imaging brain volumetric and biochemical data, and the output was the diagnosis at follow-up (SSD vs. non-SSD, SSD vs. HC, and non-SSD vs. HC). Enhanced recursive feature elimination was performed for the SSD vs. non-SSD classifier to select and rank the input variables with the highest predictive value for a diagnostic outcome of SSD. After validation with a test set and considering all baseline variables together, the SSD vs. non-SSD, SSD vs. HC and non-SSD vs. HC classifiers achieved an accuracy of 0.81, 0.99 and 0.99, respectively. Regarding the SSD vs. non-SSD classifier, a combination of baseline clinical variables (severity of negative, disorganized symptoms and hallucinations or poor insight) and neuropsychological variables (impaired attention, motor coordination, and global cognition) showed the highest predictive value for a diagnostic outcome of SSD. Neuroimaging and biochemical variables at baseline did not add to the predictive value. Thus, comprehensive clinical/cognitive assessment remains the most reliable approach for differential diagnosis during early-onset FEP. SVMs may constitute promising multivariate tools in the search for predictors of diagnostic outcome in FEP. PMID:25109600

  6. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    PubMed Central

    Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

    2015-01-01

    Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

  7. Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression

    PubMed Central

    Janssen, Joost; Pol, Hilleke E Hulshoff; de Leeuw, Frank‐Erik; Schnack, Hugo G; Lampe, Indrag K; Kok, Rob M; Kahn, Rene S; Heeren, Thea J

    2007-01-01

    Background Reduced hippocampal volume and increased prevalence of subcortical white matter lesions are associated with both recurrent early onset depression (EOD) and late onset depression (LOD). It is not clear whether these two factors differentially affect the age of onset of first depression. Therefore, we wished to investigate the relationship between age of first depression onset and hippocampal volume, with adjustment for subcortical white matter lesions. Methods MRI brain scans were used to compare hippocampal volumes and white matter lesions between age matched female patients (>60 years) with recurrent EOD and LOD and healthy controls. Results When comparing the three groups and adjusting for age, the Mini‐Mental State Examination score, total brain volume and total hippocampal volume were significantly smaller in patients with EOD compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger subcortical white matter lesions was higher in patients with LOD compared with patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in hippocampal volume from patients with EOD or from controls. Conclusions In late life depression, age of first depression onset may distinguish between different independent neuropathological mechanisms. A small hippocampus volume may be a neuranatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD. PMID:17210630

  8. Predictability affects early perceptual processing of word onsets in continuous speech

    PubMed Central

    Astheimer, Lori B.; Sanders, Lisa D.

    2011-01-01

    Event-related potential (ERP) evidence indicates that listeners selectively attend to word onsets in continuous speech, but the reason for this preferential processing is unknown. The current study measured ERPs elicited by syllable onsets in an artificial language to test the hypothesis that listeners direct attention to word onsets because their identity is unpredictable. Both before and after recognition training, participants listened to a continuous stream of six nonsense words arranged in pairs, such that the second word in each pair was completely predictable. After training, first words in pairs elicited a larger negativity beginning around 100 ms after onset. This effect was not evident for the completely predictable second words in pairs. These results suggest that listeners are most likely to attend to the segments in speech that they are least able to predict. PMID:21875609

  9. Investigation of automatically detected high frequency oscillations (HFOs) as an early predictor of seizure onset zone.

    PubMed

    Su Liu; Ince, Nuri F; Abosch, Aviva; Henry, Thomas R; Zhiyi Sha

    2015-08-01

    High frequency oscillations (HFOs) during inter-ictal state have been considered as a potential biomarker of epileptogenic regions in brain. The purpose of the current study is to improve and automatize the detection of HFOs basing on HFO distinguishing features followed by unsupervised clustering method, and to predict seizure onset zone (SOZ) using the clustered HFOs. The algorithm successfully separated HFOs of different sub-categories from noise, artifacts, and inter-ictal spikes. We tested this technique on two subjects, and assessed the performance of SOZ prediction by computing the overlapping rate of HFO generative channels and seizure onset channels. In both subjects, we were able to localize the seizure onset area 3 to 4 days before the actual onset of the seizure, with high specificity over 95%. The algorithm showed significant improvement comparing to another existing technique. PMID:26737806

  10. An Inherited Small Microdeletion at 15q13.3 in a Patient with Early- Onset Obsessive-Compulsive Disorder

    PubMed Central

    Cappi, Carolina; Hounie, Ana Gabriela; Mariani, Daniel B.; Diniz, Juliana Belo; Silva, Aderbal R. T.; Reis, Viviane N. S.; Busso, Ariane F.; Silva, Amanda Gonçalves; Fidalgo, Felipe; Rogatto, Silvia Regina; Miguel, Euripedes C.; Krepischi, Ana C.; Brentani, Helena

    2014-01-01

    Copy number variations (CNVs) have been previously associated with several different neurodevelopmental psychiatric disorders, such as autism, schizophrenia, and attention deficit hyperactivity disorder (ADHD). The present study consisted of a pilot genome-wide screen for CNVs in a cohort of 16 patients with early-onset obsessive-compulsive disorder (OCD) and 12 mentally healthy individuals, using array-based comparative genomic hybridization (aCGH) on 44K arrays. A small rare paternal inherited microdeletion (∼64 kb) was identified in chromosome 15q13.3 of one male patient with very early onset OCD. The father did not have OCD. The deletion encompassed part of the FMN1 gene, which is involved with the glutamatergic system. This finding supports the hypothesis of a complex network of several genes expressed in the brain contributing for the genetic risk of OCD, and also supports the glutamatergic involvement in OCD, which has been previously reported in the literature. PMID:25303678

  11. PLA2G6 Mutations Related to Distinct Phenotypes: A New Case with Early-onset Parkinsonism

    PubMed Central

    Giri, Anamika; Guven, Gamze; Hanagasi, Hasmet; Hauser, Ann-Kathrin; Erginul-Unaltuna, Nihan; Bilgic, Basar; Gurvit, Hakan; Heutink, Peter; Gasser, Thomas; Lohmann, Ebba; Simón-Sánchez, Javier

    2016-01-01

    Background PLA2G6-associated neurodegeneration (PLAN) is a recessive neurodegenerative disorder characterized by three distinct phenotypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and PLA2G6-related dystonia–parkinsonism. Methods A consanguineous index case from Turkey was diagnosed with early-onset Parkinsonism at the Istanbul Faculty of Medicine. She and her unaffected brother were subjected to whole-genome sequencing. Results In this report, we describe a 33-year-old index case with parental consanguinity and early-onset Parkinsonism. Whole-genome sequencing of this individual revealed that a homozygous p.R747W mutation in PLA2G6 segregates with the disease in this family Discussion This result supports the importance of prioritizing this gene in mutational analysis of autosomal recessive Parkinsonism, and confirms the clinical heterogeneity of PLAN. PMID:27127721

  12. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  13. Diagnostic delays in children with early-onset epilepsy: impact, reasons, and opportunities to improve care

    PubMed Central

    Berg, Anne T.; Loddenkemper, Tobias; Baca, Christine B.

    2014-01-01

    Purpose Delayed diagnosis of early-onset epilepsy is a potentially important and avoidable complication in epilepsy care. We examined the frequency of diagnostic delays in young children with newly presenting epilepsy, their developmental impact, and reasons for delays. Methods Children who developed epilepsy before their third birthday were identified in a prospective community-based cohort. An interval ≥1 month from second seizure to diagnosis was considered a delay. Testing of development at baseline and for up to three years after and of IQ 8–9 years later was performed. Detailed parental baseline interview accounts and medical records were reviewed to identify potential reasons for delays. Factors associated with delays included the parent, child, pediatrician, neurologist, and scheduling. Results Diagnostic delays occurred in 70/172 (41%) children. Delays occurred less often if children had received medical attention for the first seizure (p<0.0001), previously had neonatal or febrile seizures (p=0.02), had only convulsions before diagnosis (p=0.005) or had a college-educated parent (p=0.01). A ≥1 month diagnostic delay was associated with an average 7.4 point drop (p=0.02) in the Vineland Scales of Adaptive Behavior motor score. The effect was present at diagnosis, persisted for at least three years, and was also apparent in IQ scores 8–9 years later which were lower in association with a diagnostic delay by 8.4 points (p=0.06) for processing speed up to 14.5 points (p=0.004) for full scale IQ, after adjustment for parental education and other epilepsy-related clinical factors. Factors associated with delayed diagnosis included parents not recognizing events as seizures (N=47), pediatricians missing or deferring diagnosis (N=15), neurologists deferring diagnosis (N=7), and scheduling problems (N=11). Significance Diagnostic delays occur in many young children with epilepsy. They are associated with substantial decrements in development and IQ later in childhood. Several factors influence diagnostic delays and may represent opportunities for intervention and improved care. PMID:24313635

  14. Retinol Binding Protein 4 – A Novel Association with Early-Onset Preeclampsia

    PubMed Central

    Vaisbuch, Edi; Romero, Roberto; Mazaki-Tovi, Shali; Erez, Offer; Kim, Sun Kwon; Chaiworapongsa, Tinnakorn; Gotsch, Francesca; Than, Nandor Gabor; Dong, Zhong; Pacora, Percy; Lamont, Ronald; Yeo, Lami; Hassan, Sonia S.; Kusanovic, Juan Pedro

    2010-01-01

    Objective Dysregulation of maternal circulating adipokines has been implicated in several “great obstetrical syndromes” including preeclampsia (PE), small-for-gestational age (SGA) neonate and fetal death (FD). It has been suggested that adipokines provide a molecular link between metabolic derangements and inflammatory response in complicated pregnancies. Retinol binding protein 4 (RBP4), a novel adipokine, plays a role in obesity-related disorders, as well as in the regulation of the immune response. The aim of this study was to determine whether there are changes in maternal plasma concentrations of RBP4 in patients with PE and in those with an SGA neonate or FD. Study design This cross-sectional study included patients in the following groups: 1) normal pregnancy (n=134); 2) PE (n=104); 3) SGA neonate (n=28); and 4) FD (n=37). Maternal plasma RBP4 concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results 1) The median maternal plasma RBP4 concentration was higher among patients with PE than in those with a normal pregnancy (p=0.03); 2) The median maternal plasma RBP4 concentrations of patients with preterm PE (<37 weeks) was higher than that of those with term PE (p=0.017) and than that of those with a normal pregnancy (p=0.002); 3) The median maternal plasma RBP4 concentration did not differ significantly between patients with a normal pregnancy and those with an SGA neonate or with an FD; 4) Among normal pregnant women, the maternal plasma RBP4 concentrations did not correlate with pre-pregnancy body mass index, gestational age at blood sampling and neonatal birthweight. Conclusions 1) Preeclampsia, but not pregnancy with an SGA neonate or an FD, is associated with a higher median maternal plasma concentration of RBP4 than normal pregnancy; 2) Preterm PE, and specifically early-onset PE, is associated with higher median RBP4 concentrations in maternal plasma compared to term PE. These findings suggest a role for RBP4 in the pathogenesis of preterm PE, but not in SGA and FD. PMID:19708829

  15. Early onset psychopathology and the risk for teenage pregnancy among clinically referred girls.

    PubMed

    Kovacs, M; Krol, R S; Voti, L

    1994-01-01

    An existing longitudinal data set was used to investigate the hypothesis that a depressive disorder in childhood increases the risk of an adolescent pregnancy. Depression is characterized by low self-esteem, lowered concern about one's personal welfare, passivity, and impaired motivation--all of which may prevent teenage girls from taking steps to protect themselves from pregnancy. The 83 subjects had been referred to a child psychiatric clinic (86%) or a general medical facility (12%) in Pittsburgh, Pennsylvania, between the ages of 8-13 years (average age at intake, 11.5 years). They underwent 4 clinical assessments in the first year of study participation and 2 assessments in each subsequent year. 65 girls experienced 1 or more DSM-III-R defined depressive episodes during the study period; the rest, who served as psychopathologic controls, had conduct disorders. 25 of the 83 subjects (30%, compared to the national average of 24%) had documented pregnancies by the age of 18 years. 28% of the pregnant teens had a history of early onset depression compared with 66% of their nonpregnant counterparts. On the other hand, 76% of the pregnant teens had been diagnosed with a conduct disorder by the age of 18 compared with 24% of the nonpregnant girls. Preliminary analysis further indicated that teenage pregnancy was associated with having been born out of wedlock or to a mother aged 18 years or younger; living in an intact family at time of study enrollment and socioeconomic status were not significant correlates. In the multivariate analysis, however, only two factors retained significance: a conduct disorder diagnosis in childhood (mean time to first pregnancy was 17.3 years compared to 18.7 years among remaining subjects) and race (Blacks tended to become pregnant by 17.4 years compared to an average of 18.7 years for Whites). No significant interaction was detected between a conduct disorder and race. These findings suggest that educational interventions aimed at decreasing impulsivity and undesirable consequences should be targeted at girls with conduct disorders. PMID:8138508

  16. Genetic Analysis of PARK2 and PINK1 Genes in Brazilian Patients with Early-Onset Parkinson's Disease

    PubMed Central

    Moura, Karla Cristina Vasconcelos; Campos Junior, Mário; de Rosso, Ana Lúcia Zuma; Nicaretta, Denise Hack; Pereira, João Santos; Silva, Delson José; dos Santos, Flávia Lima; Rodrigues, Fabíola da Costa; Santos-Rebouças, Cíntia Barros; Pimentel, Márcia Mattos Gonçalves

    2013-01-01

    Parkinson's disease is the second most frequent neurodegenerative disorder in the world, affecting 1-2% of individuals over the age of 65. The etiology of Parkinson's disease is complex, with the involvement of gene-environment interactions. Although it is considered a disease of late manifestation, early-onset forms of parkinsonism contribute to 5–10% of all cases. In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic sequencing. We identified six missense variants in PARK2 gene: one known pathogenic mutation, two variants of uncertain role, and three nonpathogenic changes. No pathogenic mutation was identified in PINK1 gene, only benign polymorphisms. All putative pathogenic variants found in this study were in heterozygous state. Our data show that PARK2 point mutations are more common in Brazilian early-onset Parkinson's disease patients (2.9%) than PINK1 missense variants (0%), corroborating other studies worldwide. PMID:24167364

  17. Early-onset encephalopathy with epilepsy associated with a novel splice site mutation in SMC1A.

    PubMed

    Lebrun, Nicolas; Lebon, Sébastien; Jeannet, Pierre-Yves; Jacquemont, Sébastien; Billuart, Pierre; Bienvenu, Thierry

    2015-12-01

    We report on the clinical and molecular characterization of a female patient with early-onset epileptic encephalopathy, who was found to carry a de novo novel splice site mutation in SMC1A. This girl shared some morphologic and anthropometric traits described in patients with clinical diagnosis of Cornelia de Lange syndrome and with SMC1A mutation but also has severe encephalopathy with early-onset epilepsy. In addition, she had midline hand stereotypies and scoliosis leading to the misdiagnosis of a Rett overlap syndrome. Molecular studies found a novel de novo splice site mutation (c.1911 + 1G > T) in SMC1A. This novel splice mutation was associated with an aberrantly processed mRNA that included intron 11 of the gene. Moreover, quantitative approach by RT-PCR showed a severe reduction of the SMC1A transcript suggesting that this aberrant transcript may be unstable and degraded. Taken together, our data suggest that the phenotype may be due to a loss-of-function of SMC1A in this patient. Our findings suggest that loss-of-function mutations of SMC1A may be associated with early-onset encephalopathy with epilepsy. © 2015 Wiley Periodicals, Inc. PMID:26358754

  18. Very low birth weight neonates who survive early-onset sepsis do not have an increased risk of developing late-onset sepsis

    PubMed Central

    Lin, Cheryl B.; Hornik, Christoph P.; Clark, Reese; Cotten, C. Michael; Benjamin, Daniel K.; Cohen-Wolkoweiz, Michael; Smith, P. Brian; Wynn, James L.

    2012-01-01

    SUMMARY Background Very low birth weight neonates (≤1500 g, VLBWs) have a high rate of infection and distinct baseline immune function compared with more mature populations. In critically ill children and adults, sepsis increases subsequent infection risk. It is unknown whether sepsis modifies the risk of subsequent infection in VLBWs. Methods We conducted a retrospective cohort study of VLBWs ≤32 weeks gestation at birth cared for in 312 neonatal intensive care units in the United States from 1997–2011 (n=103,376). Early-onset sepsis (EOS, culture-positive only) and late-onset sepsis (LOS, culture-positive or clinical) cases were identified. Cox proportional hazards models were used to control for clinical variables between neonates with and without EOS to determine if EOS modified risk of LOS, necrotizing enterocolitis (NEC), or death. Results LOS occurred in 12,112/102,317 (11.8%) neonates without EOS and in 133/1059 (12.6%) of those with EOS. After adjustment for clinical variables, the risk of LOS was not different between neonates with or without a history of EOS (hazard ratio [HR]=0.92; 95% confidence interval [CI] 0.74, 1.16). EOS increased the risk of 120-day mortality (HR=1.78; 95% CI 1.49, 2.13). Conclusions In contrast to findings in children and adults, EOS was not associated with an increased risk of LOS in this cohort. Age-specific investigations are needed to determine if post-sepsis immunologic alterations are present. PMID:22840605

  19. [Periodontal disease in pediatric rheumatic diseases].

    PubMed

    Fabri, Gisele M C; Savioli, Cynthia; Siqueira, José T; Campos, Lucia M; Bonfá, Eloisa; Silva, Clovis A

    2014-01-01

    Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity. PMID:25627227

  20. Early-Onset Psychoses: Comparison of Clinical Features and Adult Outcome in 3 Diagnostic Groups

    ERIC Educational Resources Information Center

    Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

    2009-01-01

    A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a…

  1. Phonemic Segmentation, Not Onset-Rime Segmentation, Predicts Early Reading and Spelling Skills.

    ERIC Educational Resources Information Center

    Nation, Kate; Hulme, Charles

    1997-01-01

    Gives children (ages 5+ to 9+) four tests of phonological skill to investigate relationships between these measures and their predictive relationship with reading and spelling ability. Finds performance at phonemic segmentation, rhyme sound categorization, and alliteration sound categorization improved with age, but all groups performed onset-rime…

  2. Female Juvenile Offenders: Defining an Early-Onset Pathway for Delinquency

    ERIC Educational Resources Information Center

    Leve, Leslie D.; Chamberlain, Patricia

    2004-01-01

    We examined whether childhood factors predict age of first arrest in adolescent girls referred for placement and treatment for serious delinquency problems (N = 62). Measures included child characteristics (i.e., age of menstrual onset, childhood ADHD, and IQ), family environmental factors (i.e., severe punishment, parental transitions, and sexual…

  3. Phoneme Manipulation Not Onset-Rime Manipulation Ability Is a Unique Predictor of Early Reading

    ERIC Educational Resources Information Center

    Savage, Robert; Carless, Sue

    2005-01-01

    Background: Phonological awareness is known to be an excellent predictor of later reading acquisition. It remains unclear, however, whether phoneme manipulation alone best explains this association or whether an additional direct contribution of onset-rime awareness is predictive. This issue is explored here. Method: A longitudinal study is…

  4. Early-Onset Psychoses: Comparison of Clinical Features and Adult Outcome in 3 Diagnostic Groups

    ERIC Educational Resources Information Center

    Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

    2009-01-01

    A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a

  5. Loss of functional connectivity is greater outside the default mode network in nonfamilial early-onset Alzheimer's disease variants.

    PubMed

    Lehmann, Manja; Madison, Cindee; Ghosh, Pia M; Miller, Zachary A; Greicius, Michael D; Kramer, Joel H; Coppola, Giovanni; Miller, Bruce L; Jagust, William J; Gorno-Tempini, Maria L; Seeley, William W; Rabinovici, Gil D

    2015-10-01

    The common and specific involvement of brain networks in clinical variants of Alzheimer's disease (AD) is not well understood. We performed task-free ("resting-state") functional imaging in 60 nonfamilial AD patients, including 20 early-onset AD (age at onset <65 years, amnestic/dysexecutive deficits), 24 logopenic aphasia (language deficits), and 16 posterior cortical atrophy patients (visual deficits), as well as 60 healthy controls. Seed-based connectivity analyses were conducted to assess differences between groups in 3 default mode network (DMN) components (anterior, posterior, and ventral) and 4 additional non-DMN networks: left and right executive-control, language, and higher visual networks. Significant decreases in connectivity were found across AD variants compared with controls in the non-DMN networks. Within the DMN components, patients showed higher connectivity in the anterior DMN, in particular in logopenic aphasia. No significant differences were found for the posterior and ventral DMN. Our findings suggest that loss of functional connectivity is greatest in networks outside the DMN in early-onset and nonamnestic AD variants and may thus be a better biomarker in these patients. PMID:26242705

  6. High-frequency 3D echodentographic imaging modality for early assessment of periodontal diseases: in vitro study

    NASA Astrophysics Data System (ADS)

    Mahmoud, Ahmed M.; Ngan, Peter; Crout, Richard; Mukdadi, Osama M.

    2009-02-01

    The use of ultrasound in dentistry is still an open growing area of research. Currently, there is a lack of imaging modalities to accurately predict minute structures and defects in the jawbone. In particular, the inability of 2D radiographic images to detect bony periodontal defects resulted from infection of the periodontium. This study investigates the feasibility of high frequency ultrasound to reconstruct high resolution 3D surface images of human jawbone. Methods: A dentate and non-dentate mandibles were used in this study. The system employs high frequency single-element ultrasound focused transducers (15-30 MHz) for scanning. Continuous acquisition using a 1 GHz data acquisition card is synchronized with a high precision two-dimensional stage positioning system of +/-1 μm resolution for acquiring accurate and quantitative measurements of the mandible in vitro. Radio frequency (RF) signals are acquired laterally 44-45.5 μm apart for each frame. Different frames are reconstructed 500 μm apart for the 3D reconstruction. Signal processing algorithms are applied on the received ultrasound signals for filtering, focusing, and envelope detection before frame reconstruction. Furthermore, an edge detection technique is adopted to detect the bone surface in each frame. Finally, all edges are combined together in order to render a 3D surface image of the jawbone. Major anatomical landmarks on the resultant images were confirmed with the anatomical structures on the mandibles to show the efficacy of the system. Comparison were also made with conventional 2D radiographs to show the superiority of the ultrasound imaging system in diagnosing small defects in the lateral, axial and elevation planes of space. Results: The landmarks on all ultrasound images matched with those on the mandible, indicating the efficacy of the system in detecting small structures in human jaw bones. Comparison with conventional 2D radiographic images of the same mandible showed superiority of the 3D ultrasound images in detecting defects in the elevation plane of space. These results suggest that the high frequency ultrasound system shows great potential in providing a non-invasive method to characterize the jawbone and detect periodontal diseases at earlier stages.

  7. Immediate periodontal bone plate changes induced by rapid maxillary expansion in the early mixed dentition: CT findings

    PubMed Central

    Garib, Daniela Gamba; Menezes, Maria Helena Ocké; da Silva Filho, Omar Gabriel; dos Santos, Patricia Bittencourt Dutra

    2014-01-01

    Objective This study aimed at evaluating buccal and lingual bone plate changes caused by rapid maxillary expansion (RME) in the mixed dentition by means of computed tomography (CT). Methods The sample comprised spiral CT exams taken from 22 mixed dentition patients from 6 to 9 years of age (mean age of 8.1 years) presenting constricted maxillary arch treated with Haas-type expanders. Patients were submitted to spiral CT scan before expansion and after the screw activation period with a 30-day interval between T1 and T2. Multiplanar reconstruction was used to measure buccal and lingual bone plate thickness and buccal bone crest level of maxillary posterior deciduous and permanent teeth. Changes induced by expansion were evaluated using paired t test (p < 0.05). Results Thickness of buccal and lingual bone plates of posterior teeth remained unchanged during the expansion period, except for deciduous second molars which showed a slight reduction in bone thickness at the distal region of its buccal aspect. Buccal bone dehiscences were not observed in the supporting teeth after expansion. Conclusion RME performed in mixed dentition did not produce immediate undesirable effects on periodontal bone tissues. PMID:25162564

  8. Are early onset aging conditions correlated to daily activity functions in youth and adults with Down syndrome?

    PubMed

    Lin, Jin-Ding; Lin, Lan-Ping; Hsu, Shang-Wei; Chen, Wen-Xiu; Lin, Fu-Gong; Wu, Jia-Ling; Chu, Cordia

    2014-11-13

    This study aims to answer the research question of "Are early onset aging conditions correlated to daily activity functions in youth and adults with Down syndrome (DS)?" A cross-sectional survey was employed to recruit 216 individuals with DS over 15 years of age in the analyses. A structured questionnaire included demographic data, brief self-reported aging conditions, Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) and activity of daily living (ADL) scales were completed by the primary caregivers who were well-suited for providing information on the functioning conditions of the DS individuals. Results showed that the most five frequent aging conditions (sometimes, usually and always) included frailty (20.2%), vision problem (15.8%), loss of language ability (15.3%), sleep problem (14.9%) and memory impairment (14.5%). Other onset aging conditions included more chronic diseases (13.9%), hearing loss (13%), chewing ability and tooth loss (12.5%), incontinence (11.1%), depressive syndrome (7.7%), falls and gait disorder (7.2%), loss of taste and smell (7.2%). The data also showed scores of DSQIID, onset aging conditions and ADL has significant relationships each other in Pearson's correlation tests. Finally, multiple linear regression analyses indicated onset aging conditions (β=-0.735, p<0.001) can significantly predicted the variation in ADL scores after adjusting other factors (R(2)=0.381). This study suggests that the authority should initiate early intervention programs aim to improve healthy aging and ADL functions for people with DS. PMID:25462513

  9. Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior.

    PubMed

    Hallikainen, T; Saito, T; Lachman, H M; Volavka, J; Pohjalainen, T; Ryynänen, O P; Kauhanen, J; Syvälahti, E; Hietala, J; Tiihonen, J

    1999-07-01

    A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits. This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics. The 5-HTT promoter genotype was determined by a PCR-based method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls. All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics (chi2 = 4.86, P = 0.028) and healthy controls (chi2 = 8.24, P = 0.004). The odds ratio for SS genotype vs LL genotype was 3.90, 95% Cl 1.37-11.11, P = 0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior. PMID:10483057

  10. Familial periodontal disease in the cayo santiago rhesus macaques.

    PubMed

    Gonzalez, Octavio A; Orraca, Luis; Kensler, Terry B; Gonzalez-Martinez, Janis; Maldonado, Elizabeth; Ebersole, Jeffrey L

    2016-01-01

    Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5-31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all four quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease. Am. J. Primatol. 78:143-151, 2016. 2016 Wiley Periodicals, Inc. PMID:25708960

  11. IL-10 Controls Early Microglial Phenotypes and Disease Onset in ALS Caused by Misfolded Superoxide Dismutase 1.

    PubMed

    Gravel, Mathieu; Béland, Louis-Charles; Soucy, Geneviève; Abdelhamid, Essam; Rahimian, Reza; Gravel, Claude; Kriz, Jasna

    2016-01-20

    While reactive microgliosis is a hallmark of advanced stages of amyotrophic lateral sclerosis (ALS), the role of microglial cells in events initiating and/or precipitating disease onset is largely unknown. Here we provide novel in vivo evidence of a distinct adaptive shift in functional microglial phenotypes in preclinical stages of superoxide dismutase 1 (SOD1)-mutant-mediated disease. Using a mouse model for live imaging of microglial activation crossed with SOD1(G93A) and SOD1(G37R) mouse models, we discovered that the preonset phase of SOD1-mediated disease is characterized by development of distinct anti-inflammatory profile and attenuated innate immune/TLR2 responses to lipopolysaccharide (LPS) challenge. This microglial phenotype was associated with a 16-fold overexpression of anti-inflammatory cytokine IL-10 in baseline conditions followed by a 4.5-fold increase following LPS challenge. While infusion of IL-10R blocking antibody, initiated at day 60, caused a significant increase in markers of microglial activation and precipitated clinical onset of disease, a targeted overexpression of IL-10 in microglial cells, delivered via viral vectors expressed under CD11b promoter, significantly delayed disease onset and increased survival of SOD1(G93A) mice. We propose that the high IL-10 levels in resident microglia in early ALS represent a homeostatic and compensatory "adaptive immune escape" mechanism acting as a nonneuronal determinant of clinical onset of disease. Significance statement: We report here for the first time that changing the immune profile of brain microglia may significantly affect clinical onset and duration of disease in ALS models. We discovered that in presymptomatic disease microglial cells overexpress anti-inflammatory cytokine IL-10. Given that IL-10 is major homeostatic cytokine and its production becomes deregulated with aging, this may suggest that the capacity of microglia to adequately produce IL-10 may be compromised in ALS. We show that blocking IL-10 increased inflammation and precipitated clinical disease onset, whereas overexpression of IL-10 in microglia using a gene therapy approach significantly delayed disease onset and increased survival of ALS mice. Based on our results, we propose that targeted overexpression of IL-10 in microglia may have therapeutic potential in ALS. PMID:26791230

  12. Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo.

    PubMed

    Laberge, Greggory; Mailloux, Christina M; Gowan, Katherine; Holland, Paulene; Bennett, Dorothy C; Fain, Pamela R; Spritz, Richard A

    2005-08-01

    Generalized vitiligo is an autoimmune disorder in which acquired white patches of skin and overlying hair result from autoimmune loss of melanocytes from involved areas. Although usually sporadic, family clustering of vitiligo may occur, in a non-Mendelian pattern typical of multifactorial, polygenic inheritance. Sporadic vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus; these same disorders occur at increased frequency in patients' first-degree relatives. Here, we studied 133 'multiplex' generalized vitiligo families, with multiple affected family members. The age of onset of vitiligo is earlier in these 'multiplex' families than in patients with sporadic vitiligo. Affected members of the multiplex vitiligo families have elevated frequencies of autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anemia, and Addison's disease. Probands' unaffected siblings have elevated frequencies of most of these same autoimmune diseases, particularly if the proband had non-vitiligo autoimmune disease. Familial generalized vitiligo is thus characterized by earlier disease onset and a broader repertoire of associated autoimmune diseases than sporadic vitiligo. This mostly likely reflects a greater inherited genetic component of autoimmune susceptibility in these families. These findings have important implications for autoimmune disease surveillance in families in which multiple members are affected with vitiligo. PMID:16029422

  13. The Prothrombin G20210A Mutation is Associated with Young-Onset Stroke: The Genetics of Early Onset Stroke Study and Meta-Analysis

    PubMed Central

    Jiang, Baijia; Ryan, Kathleen A.; Hamedani, Ali; Cheng, Yuching; Sparks, Mary J.; Koontz, Deborah; Bean, Christopher J.; Gallagher, Margaret; Hooper, W. Craig; McArdle, Patrick F.; O'Connell, Jeffrey R.; Stine, O. Colin; Wozniak, Marcella A.; Stern, Barney J.; Mitchell, Braxton D.; Kittner, Steven J.; Cole, John W.

    2014-01-01

    Background and Purpose Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young-adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a Caucasian case-control population and additionally performed a meta-analysis Methods From the population-based Genetics of Early Onset Stroke (GEOS) study we identified 397 individuals of European ancestry aged 15-49 years with first-ever ischemic stroke and 426 matched-controls. Logistic regression was used to calculate odds ratios in the entire population and for subgroups stratified by gender, age, oral contraceptive use, migraine and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases <55 years) was also performed with and without GEOS data. Results Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5,95%CI=0.9-6.5,p=0.07). However, among adults aged 15-42 (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9,95%CI=1.2-28.1,p=0.03), whereas adults ages 42-49 were not (OR=1.4,95%CI=0.4-5.1,p=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults <=55 years (OR=1.4;95%CI=1.1-1.9;p=0.02) with significance increasing with addition of the GEOS results (OR=1.5;95%CI=1.1-2.0;p=0.005). Conclusions The prothrombin G20210A mutation is associated with ischemic stroke in young-adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger-young adult population requires replication. PMID:24619398

  14. Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature.

    PubMed

    Chen, Xuqin; Gill, Deepak; Shaw, Peter; Ouvrier, Robert; Troedson, Christopher

    2016-03-01

    The purpose of this study was to determine whether transplantation of umbilical cord blood from unrelated donors before the development of symptoms could halt the progression of early juvenile onset cases of MLD in whom the disease was diagnosed based on the family history. Three asymptomatic children (aged 2 years 4 months, 2 years 8 months and 5 years 5 months, two of whom were sisters) underwent unrelated umbilical cord blood transplantation (UCBT) and two untreated symptomatic siblings were included in the study. In 14-year and 6-year follow-ups after transplantation, clinical examination, ARSA enzyme levels, neurophysiological, neuroimaging, and psychological status were assessed. All three transplanted patients remain well, and the parameters evaluated remain stable. Of the treated patients, the two sisters had ongoing evidence of demyelinating sensorimotor neuropathy on nerve conduction tests, and with a early sensorimotor neuropathy in the older sister , and the other patient has mild intellectual impairment. One of the two un-transplanted controls, 15 years after MLD diagnosis, has relentlessly progressed to full dependency with epilepsy, severe mental retardation, dystonic movements, dysphagia and recurrent respiratory problems. Six years after diagnosis, the other control has a slowly progressive course with spastic dystonic quadriplegia, epilepsy, dysphagia, continual drooling and incontinence. Our data show that, in comparison with their untreated siblings, UCBT significantly slowed the progression of the disease in the treated patients. We conclude that UCBT benefits children with pre-symptomatic early juvenile onset MLD by favourably altering the natural history of the disease. PMID:26187619

  15. Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis

    PubMed Central

    Martin, Hilary C.; Kim, Grace E.; Pagnamenta, Alistair T.; Murakami, Yoshiko; Carvill, Gemma L.; Meyer, Esther; Copley, Richard R.; Rimmer, Andrew; Barcia, Giulia; Fleming, Matthew R.; Kronengold, Jack; Brown, Maile R.; Hudspith, Karl A.; Broxholme, John; Kanapin, Alexander; Cazier, Jean-Baptiste; Kinoshita, Taroh; Nabbout, Rima; Bentley, David; McVean, Gil; Heavin, Sinéad; Zaiwalla, Zenobia; McShane, Tony; Mefford, Heather C.; Shears, Deborah; Stewart, Helen; Kurian, Manju A.; Scheffer, Ingrid E.; Blair, Edward; Donnelly, Peter; Kaczmarek, Leonard K.; Taylor, Jenny C.

    2014-01-01

    In severe early-onset epilepsy, precise clinical and molecular genetic diagnosis is complex, as many metabolic and electro-physiological processes have been implicated in disease causation. The clinical phenotypes share many features such as complex seizure types and developmental delay. Molecular diagnosis has historically been confined to sequential testing of candidate genes known to be associated with specific sub-phenotypes, but the diagnostic yield of this approach can be low. We conducted whole-genome sequencing (WGS) on six patients with severe early-onset epilepsy who had previously been refractory to molecular diagnosis, and their parents. Four of these patients had a clinical diagnosis of Ohtahara Syndrome (OS) and two patients had severe non-syndromic early-onset epilepsy (NSEOE). In two OS cases, we found de novo non-synonymous mutations in the genes KCNQ2 and SCN2A. In a third OS case, WGS revealed paternal isodisomy for chromosome 9, leading to identification of the causal homozygous missense variant in KCNT1, which produced a substantial increase in potassium channel current. The fourth OS patient had a recessive mutation in PIGQ that led to exon skipping and defective glycophosphatidyl inositol biosynthesis. The two patients with NSEOE had likely pathogenic de novo mutations in CBL and CSNK1G1, respectively. Mutations in these genes were not found among 500 additional individuals with epilepsy. This work reveals two novel genes for OS, KCNT1 and PIGQ. It also uncovers unexpected genetic mechanisms and emphasizes the power of WGS as a clinical tool for making molecular diagnoses, particularly for highly heterogeneous disorders. PMID:24463883

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

    PubMed

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

    2016-01-01

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

  17. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments

    PubMed Central

    Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H.; McDonald, Robert; Zhang, Liang

    2015-01-01

    Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging mice following severe brain ischemia and that early anticonvulsive treatment may prevent seizure genesis and improve overall outcomes. PMID:26630670

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

    PubMed Central

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

    2016-01-01

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

  19. Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation.

    PubMed

    Hoffmann, Sandra; Clauss, Sebastian; Berger, Ina M; Weiß, Birgit; Montalbano, Antonino; Röth, Ralph; Bucher, Madeline; Klier, Ina; Wakili, Reza; Seitz, Hervé; Schulze-Bahr, Eric; Katus, Hugo A; Flachsbart, Friederike; Nebel, Almut; Guenther, Sabina Pw; Bagaev, Erik; Rottbauer, Wolfgang; Kääb, Stefan; Just, Steffen; Rappold, Gudrun A

    2016-05-01

    Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia with a strong genetic component. Molecular pathways involving the homeodomain transcription factor Shox2 control the development and function of the cardiac conduction system in mouse and zebrafish. Here we report the analysis of human SHOX2 as a potential susceptibility gene for early-onset AF. To identify causal variants and define the underlying mechanisms, results from 378 patients with early-onset AF before the age of 60 years were analyzed and compared to 1870 controls or reference datasets. We identified two missense mutations (p.G81E, p.H283Q), that were predicted as damaging. Transactivation studies using SHOX2 targets and phenotypic rescue experiments in zebrafish demonstrated that the p.H283Q mutation severely affects SHOX2 pacemaker function. We also demonstrate an association between a 3'UTR variant c.*28T>C of SHOX2 and AF (p = 0.00515). Patients carrying this variant present significantly longer PR intervals. Mechanistically, this variant creates a functional binding site for hsa-miR-92b-5p. Circulating hsa-miR-92b-5p plasma levels were significantly altered in AF patients carrying the 3'UTR variant (p = 0.0095). Finally, we demonstrate significantly reduced SHOX2 expression levels in right atrial appendages of AF patients compared to patients with sinus rhythm. Together, these results suggest a genetic contribution of SHOX2 in early-onset AF. PMID:27138930

  20. Tea, coffee, and caffeine and early-onset basal cell carcinoma in a case-control study

    PubMed Central

    Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2014-01-01

    Objectives Tea and coffee are hypothesized to play a protective role in skin carcinogenesis via bioactive components, such as caffeine, yet the epidemiologic evidence is mixed. Existing data supports an inverse association with basal cell carcinoma (BCC) more so than for melanoma or squamous cell carcinoma. To understand if tea, coffee, and caffeine are related to early-onset BCC, we evaluated data from 767 non-Hispanic Whites under age 40 in a case-control study in Connecticut. Methods BCC cases (n=377) were identified through Yale's Dermatopathology database. Controls (n=390) were randomly sampled from individuals in the same database with benign skin diagnoses and frequency matched to cases on age, gender, and biopsy site. Subjects completed an in-person interview including assessment of caffeinated coffee and hot tea. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CIs) with unconditional logistic regression for regular consumption and frequency and duration measures. Results Combined regular consumption of caffeinated coffee plus hot tea was inversely associated with early-onset BCC (OR=0.60, 95% CI=0.38–0.96). Those in the highest category of caffeine from these sources had a 43% reduced risk of BCC compared to non-consumers (OR=0.57, 95% CI=0.34–0.95, p-trend=0.037). Conclusions Our findings suggest a modest protective effect for caffeinated coffee plus tea in relation to early-onset BCC that may, in part, be due to caffeine. This study adds to the growing body of literature suggesting potential health benefits from these beverages. PMID:24841641

  1. Tea, coffee, and caffeine and early-onset basal cell carcinoma in a case-control study.

    PubMed

    Ferrucci, Leah M; Cartmel, Brenda; Molinaro, Annette M; Leffell, David J; Bale, Allen E; Mayne, Susan T

    2014-07-01

    Tea and coffee are hypothesized to play a protective role in skin carcinogenesis through bioactive components, such as caffeine, yet the epidemiologic evidence is mixed. Existing data support an inverse association with basal cell carcinoma (BCC), more so than for melanoma or squamous cell carcinoma. To understand whether tea, coffee, and caffeine are related to early-onset BCC, we evaluated data from 767 non-Hispanic Whites under age 40 in a case-control study in Connecticut. BCC cases (n=377) were identified through Yale's Dermatopathology database. Controls (n=390) were randomly sampled from individuals in the same database with benign skin diagnoses and frequency matched to cases on age, sex, and biopsy site. Participants completed an in-person interview including assessment of caffeinated coffee and hot tea. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional logistic regression for regular consumption and frequency and duration measures. Combined regular consumption of caffeinated coffee plus hot tea was inversely associated with early-onset BCC (OR=0.60, 95% CI=0.38-0.96). Those in the highest category of caffeine from these sources had a 43% reduced risk of BCC compared with nonconsumers (OR=0.57, 95% CI=0.34-0.95, P-trend=0.037). Our findings suggest a modest protective effect for caffeinated coffee plus tea in relation to early-onset BCC that may, in part, be due to caffeine. This study adds to the growing body of literature suggesting potential health benefits from these beverages. PMID:24841641

  2. Non-haemolytic and non-pigmented group b streptococcus, an infrequent cause of early onset neonatal sepsis.

    PubMed

    Rodriguez-Granger, Javier; Spellerberg, Barbara; Asam, Daniela; Rosa-Fraile, Manuel

    2015-12-01

    The haemolysin of Group B streptococci (GBS), a leading cause of neonatal infections, is a key virulence factor that has been implicated in the development of invasive infection. The frequency of non-haemolytic (NH) GBS isolates is around 5% among GBS carriers. To determine if similar rates are observed among invasive strains, we evaluated the incidence of NH strains among 199 GBS strains isolated from neonatal blood cultures (first week of life). Overall, we found two (1%) NH strains. This finding suggests that the frequency of NH GBS strains causing early onset invasive neonatal infection is lower than the reported frequency of NH GBS among colonizing strains. PMID:26449711

  3. Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

    SciTech Connect

    Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M.M.; Olinga, Peter

    2014-01-15

    Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-β1 and the fibrosis markers Hsp47, αSma and Pcol1A1 and collagen1 protein expressions were determined. The effects of the antifibrotic drugs imatinib, sorafenib and sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone, TGFβ-pathway inhibitors, were determined. After 48 h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-β1 was not changed. Hsp47, αSma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-β1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFβ-inhibitors showed marginal effects. The protein expression of collagen 1 was inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion, the increased gene expression of PDGF-B and the down-regulation of fibrosis markers by PDGF-pathway inhibitors, together with the absence of elevated TGF-β1 gene expression and the limited effect of the TGFβ-pathway inhibitors, indicated the predominance of the PDGF pathway in the early onset of fibrosis in PCLS. PCLS appear a useful model for research of the early onset of fibrosis and for testing of antifibrotic drugs acting on the PDGF pathway. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-β was increased, while TGFβ was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGFβ-pathway inhibitors had only minor effects on fibrosis markers. • Rat PCLS can be used to study the early onset of fibrosis.

  4. Childhood Ataxia with Cerebral Hypomyelination Syndrome: a Variant of Patient with Early Childhood Onset Related to EIF2B3 Mutation. A Case Report.

    PubMed

    Perfetto, F; Stoppino, L P; Calì, A; Milillo, P; Grilli, G; Vinci, R; Macarini, L

    2012-03-01

    Childhood ataxia with central nervous system hypomyelination (CACH) syndrome is an autosomal recessive transmitted leukodystrophy characterised by early childhood onset and acute deterioration following febrile illnesses or head trauma. We describe the case of a child with early onset of CACH syndrome. He presented with cerebellar ataxia beginning around two years of age with mild mental retardation. MRI showed diffuse white matter signal changes with thinning of the corpus callosum. PMID:24028880

  5. Age at the onset of senescence in birds and mammals is predicted by early-life performance

    PubMed Central

    Péron, Guillaume; Gimenez, Olivier; Charmantier, Anne; Gaillard, Jean-Michel; Crochet, Pierre-André

    2010-01-01

    Life-history theory predicts that traits involved in maturity, reproduction and survival correlate along a fast–slow continuum of life histories. Evolutionary theories and empirical results indicate that senescence-related traits vary along this continuum, with slow species senescing later and at a slower pace than fast species. Because senescence patterns are typically difficult to estimate from studies in the wild, here we propose to predict the associated trait values in the frame of life-history theory. From a comparative analysis based on 81 free-ranging populations of 72 species of birds and mammals, we find that a nonlinear combination of fecundity, age at first reproduction and survival over the immature stage can account for ca two-thirds of the variance in the age at the onset of actuarial senescence. Our life-history model performs better than a model predicting the onset based on generation time, and it only includes life-history traits during early life as explanatory variables, i.e. parameters that are both theoretically expected to shape senescence and are measurable within relatively short studies. We discuss the good-fit of our life-history model to the available data in the light of current evolutionary theories of senescence. We further use it to evaluate whether studies that provided no evidence for senescence lasted long enough to include the onset of senescence. PMID:20427343

  6. Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers.

    PubMed

    Armes, Jane E; Hammet, Fleur; de Silva, Melanie; Ciciulla, John; Ramus, Susan J; Soo, Wee-Kheng; Mahoney, Alexis; Yarovaya, Natalia; Henderson, Michael A; Gish, Kurt; Hutchins, Anne-Marie; Price, Gareth R; Venter, Deon J

    2004-07-22

    Loss of genetic material from chromosome arm 8p occurs commonly in breast carcinomas, suggesting that this region is the site of one or more tumor-suppressor genes (TSGs). Comparative genomic hybridization analysis showed that 8p loss is more common in breast cancers from pre-menopausal compared with post-menopausal patients, as well as in high-grade breast cancers, regardless of the menopausal status. Subsequent high-resolution gene expression profiling of genes mapped to chromosome arm 8p, on an extended cohort of clinical tumor samples, indicated a similar dichotomy of breast cancer clinicopathologic types. Some of these genes showed differential downregulation in early-onset and later-onset, high-grade cancers compared with lower-grade, later-onset cancers. Three such genes were analysed further by in situ technologies, performed on tissue microarrays representing breast tumor and normal tissue samples. PCM1, which encodes a centrosomal protein, and DUSP4/MKP-2, which encodes a MAP kinase phosphatase, both showed frequent gene and protein loss in carcinomas. In contrast, there was an excess of cases showing loss of expression in the absence of reduced gene copy number of SFRP1, which encodes a dominant-negative receptor for Wnt-family ligands. These candidate TSGs may constitute some of the molecular drivers of chromosome arm 8p loss in breast carcinogenesis. PMID:15184884

  7. Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort.

    PubMed

    Cacace, Rita; Van den Bossche, Tobi; Engelborghs, Sebastiaan; Geerts, Nathalie; Laureys, Annelies; Dillen, Lubina; 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; Tsolaki, Magda; Koutroumani, Maria; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Matej, Radoslav; Rohan, Zdenek; Vandenbulcke, Mathieu; Vandenberghe, Rik; De Deyn, Peter P; Cras, Patrick; van der Zee, Julie; Sleegers, Kristel; Van Broeckhoven, Christine

    2015-12-01

    Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort, as well as in European EOAD patients (N = 946) and control individuals (N = 1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P = 0.43; OR = 1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated. PMID:26411346

  8. A Young Man With Progressive Language Difficulty and Early-Onset Dementia.

    PubMed

    Botha, Hugo; Boeve, Bradley F; Jones, Lyell K; Parisi, Joseph E; Klaas, James P

    2016-05-01

    A man in his late 40s presented with cognitive decline characterized by gradually increasing difficulty expressing his thoughts and ideas. His family noted word-finding difficulty, especially with the names of people, but no problems with his memory for recent events. Initial workup findings were unremarkable, but during the course of the next decade left anterior temporal atrophy was noted on magnetic resonance imaging and the patient developed increasing reasoning difficulty, apathy, and disinhibition. Several degenerative causes were considered. The patient died 22 years after symptom onset, and the final diagnosis was confirmed at autopsy. PMID:27019131

  9. Differences and Similarities in the Transcriptional Profile of Peripheral Whole Blood in Early and Late-Onset Preeclampsia: Insights into the Molecular Basis of the Phenotype of Preeclampsia

    PubMed Central

    Chaiworapongsa, Tinnakorn; Romero, Roberto; Whitten, Amy; Tarca, Adi L; Bhatti, Gaurav; Draghici, Sorin; Chaemsaithong, Piya; Miranda, Jezid; Kim, Chong Jai; Hassan, Sonia S

    2014-01-01

    Objective Preeclampsia (PE) has been sub-divided into early- and late-onset phenotypes. The pathogenesis of these two phenotypes has not been elucidated. To gain insight into the mechanisms of disease, the transcriptional profiles of whole blood from women with early- and late-onset PE were examined. Methods A cross-sectional study was conducted to include women with: 1) early-onset PE (diagnosed prior to 34 weeks, n=25); 2) late-onset PE (after 34 weeks, n=47); and 3) uncomplicated pregnancy (n=61). Microarray analysis of mRNA expression in peripheral whole blood was undertaken using Affymetrix microarrays. Differential gene expression was evaluated using a moderated t-test (false discovery rate <0.1 and fold change >1.5), adjusting for maternal WBC count and gestational age. Validation by real-time qRT-PCR was performed in a larger sample size [early PE (n=31), late PE (n=72) and controls (n=99)] in all differentially expressed genes. Gene Ontology analysis and pathway analysis were performed. Results 1) 43 and 28 genes were differentially expressed in early- and late-onset PE compared to the control group respectively; 2) qRT-PCR confirmed the microarray results for early and late-onset PE in 77% (33/43) and 71% (20/28) of genes, respectively; 3) 20 genes that are involved in coagulation (SERPINI2), immune regulation (VSIG4, CD24), developmental process (H19) and inflammation (S100A10) were differentially expressed in early-onset PE alone. In contrast, only seven genes that encoded proteins involved in innate immunity (LTF, ELANE) and cell-to-cell recognition in the nervous system (CNTNAP3) were differentially expressed in late-onset PE alone. Thirteen genes that encode proteins involved in host defense (DEFA4, BPI, CTSG, LCN2), tight junctions in blood-brain barrier (EMP1) and liver regeneration (ECT2) were differentially expressed in both early- and late-onset PE. Conclusion Early- and late-onset PE are characterized by a common signature in the transcriptional profile of whole blood. A small set of genes were differentially regulated in early- and late-onset PE. Future studies of the biological function, expression timetable and protein expression of these genes may provide insight into the pathophysiology of PE. PMID:23793063

  10. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons.

    PubMed

    Nicolas, Gaël; Wallon, David; Charbonnier, Camille; Quenez, Olivier; Rousseau, Stéphane; Richard, Anne-Claire; Rovelet-Lecrux, Anne; Coutant, Sophie; Le Guennec, Kilan; Bacq, Delphine; Garnier, Jean-Guillaume; Olaso, Robert; Boland, Anne; Meyer, Vincent; Deleuze, Jean-François; Munter, Hans Markus; Bourque, Guillaume; Auld, Daniel; Montpetit, Alexandre; Lathrop, Mark; Guyant-Maréchal, Lucie; Martinaud, Olivier; Pariente, Jérémie; Rollin-Sillaire, Adeline; Pasquier, Florence; Le Ber, Isabelle; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Thomas-Antérion, Catherine; Paquet, Claire; Sauvée, Mathilde; Moreaud, Olivier; Gabelle, Audrey; Sellal, François; Ceccaldi, Mathieu; Chamard, Ludivine; Blanc, Frédéric; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

    2016-05-01

    Causative variants in APP, PSEN1 or PSEN2 account for a majority of cases of autosomal dominant early-onset Alzheimer disease (ADEOAD, onset before 65 years). Variant detection rates in other EOAD patients, that is, with family history of late-onset AD (LOAD) (and no incidence of EOAD) and sporadic cases might be much lower. We analyzed the genomes from 264 patients using whole-exome sequencing (WES) with high depth of coverage: 90 EOAD patients with family history of LOAD and no incidence of EOAD in the family and 174 patients with sporadic AD starting between 51 and 65 years. We found three PSEN1 and one PSEN2 causative, probably or possibly causative variants in four patients (1.5%). Given the absence of PSEN1, PSEN2 and APP causative variants, we investigated whether these 260 patients might be burdened with protein-modifying variants in 20 genes that were previously shown to cause other types of dementia when mutated. For this analysis, we included an additional set of 160 patients who were previously shown to be free of causative variants in PSEN1, PSEN2 and APP: 107 ADEOAD patients and 53 sporadic EOAD patients with an age of onset before 51 years. In these 420 patients, we detected no variant that might modify the function of the 20 dementia-causing genes. We conclude that EOAD patients with family history of LOAD and no incidence of EOAD in the family or patients with sporadic AD starting between 51 and 65 years have a low variant-detection rate in AD genes. PMID:26242991

  11. Alteration of Delta-like ligand 1 and Notch 1 receptor in various placental disorders with special reference to early onset preeclampsia.

    PubMed

    Shimanuki, Yota; Mitomi, Hiroyuki; Fukumura, Yuki; Makino, Shintaro; Itakura, Atsuo; Yao, Takashi; Takeda, Satoru

    2015-08-01

    Notch signaling pathway has been shown to be dysregulated in placentas with preeclampsia, but there has been a lack of studies on methylation of Notch family genes in this disorder. We therefore executed methylation-specific polymerase chain reaction and immunostaining for Notch 1 receptor and the activating ligand, Delta-like (DLL) 1, with placental tissues from cases of preeclampsia (early onset, n = 18; late-onset, n = 19) and other placental disorders, including maternal complications such as diabetes mellitus and collagen disease (n = 10), fetal growth restriction (n = 17), fetal anomaly (n = 23), preterm birth (n = 15), miscarriage (n = 25), and hydatidiform moles (n = 9) as well as term births (n = 12). The frequency of DLL1 methylation was higher in early onset preeclamptic placentas (61%) than the other subjects (0%-36%; P ≤ .016). Appreciable samples (36%) of miscarriage also represented DLL1 methylation. None of the samples studied showed Notch 1 methylation. On gestational period-matched analysis, the rate of DLL1 methylation was higher in early onset preeclampsia (83.3%) than preterm birth (13.3%; P < .001), with no significant differences in clinical backgrounds between the two. In this analysis, increase of syncytial knots and accelerated villous maturation were most prominent in DLL1-methylated placentas with early onset preeclampsia. Notch 1 and DLL1 expressions in villous trophoblasts and endothelial cells were significantly lower in early onset preeclamptic placentas as compared with preterm birth controls. In conclusion, altered Notch signaling via methylation of DLL1 is likely involved in possible disease-related mechanisms of early onset preeclampsia. Alternatively, DLL1 methylation in early onset preeclampsia could be a manifestation of a lack of placental maturation, similar to miscarriage. PMID:26014475

  12. Diaphragm muscle weakness in mice is early-onset post-myocardial infarction and associated with elevated protein oxidation

    PubMed Central

    Mangner, Norman; Werner, Sarah; Glaser, Stefanie; Kullnick, Yvonne; Schrepper, Andrea; Doenst, Torsten; Oberbach, Andreas; Linke, Axel; Steil, Leif; Schuler, Gerhard; Adams, Volker

    2014-01-01

    Heart failure induced by myocardial infarction (MI) causes diaphragm muscle weakness, with elevated oxidants implicated. We aimed to determine whether diaphragm muscle weakness is 1) early-onset post-MI (i.e., within the early left ventricular remodeling phase of 72 h); and 2) associated with elevated protein oxidation. Ligation of the left coronary artery to induce MI (n = 10) or sham operation (n = 10) was performed on C57BL6 mice. In vitro contractile function of diaphragm muscle fiber bundles was assessed 72 h later. Diaphragm mRNA and protein expression, enzyme activity, and individual carbonylated proteins (by two-dimensional differential in-gel electrophoresis and mass spectrometry) were subsequently assessed. Infarct size averaged 57 ± 1%. Maximal diaphragm function was reduced (P < 0.01) by 20% post-MI, with the force-frequency relationship depressed (P < 0.01) between 80 and 300 Hz. The mRNA expression of inflammation, atrophy, and regulatory Ca2+ proteins remained unchanged post-MI, as did the protein expression of key contractile proteins. However, enzyme activity of the oxidative sources NADPH oxidase and xanthine oxidase was increased (P < 0.01) by 45 and 33%, respectively. Compared with sham, a 57 and 45% increase (P < 0.05) was observed in the carbonylation of sarcomeric actin and creatine kinase post-MI, respectively. In conclusion, diaphragm muscle weakness was rapidly induced in mice during the early left ventricular remodeling phase of 72 h post-MI, which was associated with increased oxidation of contractile and energetic proteins. Collectively, these findings suggest diaphragm muscle weakness may be early onset in heart failure, which is likely mediated in part by posttranslational oxidative modifications at the myofibrillar level. PMID:25359720

  13. Increased oxidized low-density lipoprotein causes blood-brain barrier disruption in early-onset preeclampsia through LOX-1

    PubMed Central

    Schreurs, Malou P. H.; Hubel, Carl A.; Bernstein, Ira M.; Jeyabalan, Arun; Cipolla, Marilyn J.

    2013-01-01

    Early-onset preeclampsia (EPE) is a severe form of preeclampsia that involves life-threatening neurological complications. However, the underlying mechanism by which EPE affects the maternal brain is not known. We hypothesized that plasma from women with EPE increases blood-brain barrier (BBB) permeability vs. plasma from women with late-onset preeclampsia (LPE) or normal pregnancy (NP) and investigated its underlying mechanism by perfusing cerebral veins from nonpregnant rats (n=6–7/group) with human plasma from women with EPE, LPE, or NP and measuring permeability. We show that plasma from women with EPE significantly increased BBB permeability vs. plasma from women with LPE or NP (P<0.001). BBB disruption in response to EPE plasma was due to a 260% increase of circulating oxidized LDL (oxLDL) binding to its receptor, LOX-1, and subsequent generation of peroxynitrite (P<0.001). A rat model with pathologically high lipid levels in pregnancy showed symptoms of preeclampsia, including elevated blood pressure, growth-restricted fetuses, and LOX-1-dependent BBB disruption, similar to EPE (P<0.05). Thus, we have identified LOX-1 activation by oxLDL and subsequent peroxynitrite generation as a novel mechanism by which disruption of the BBB occurs in EPE. As increased BBB permeability is a primary means by which seizure and other neurological symptoms ensue, our findings highlight oxLDL, LOX-1, and peroxynitrite as important therapeutic targets in EPE.—Schreurs, M. P. H., Hubel, C. A., Bernstein, I. M., Jeyabalan, A., and Cipolla, M. J. Increased oxidized low-density lipoprotein causes blood-brain barrier disruption in early-onset preeclampsia through LOX-1. PMID:23230281

  14. Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis

    PubMed Central

    Trump, Natalie; McTague, Amy; Brittain, Helen; Papandreou, Apostolos; Meyer, Esther; Ngoh, Adeline; Palmer, Rodger; Morrogh, Deborah; Boustred, Christopher; Hurst, Jane A; Jenkins, Lucy; Kurian, Manju A; Scott, Richard H

    2016-01-01

    Background We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. Methods In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis. Results We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing. Conclusions Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype–phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis. PMID:26993267

  15. ATM germline mutations in Spanish early-onset breast cancer patients negative for BRCA1/BRCA2 mutations.

    PubMed

    Brunet, J; Gutirrez-Enrquez, S; Torres, A; Brez, V; Sanjos, S; Galceran, J; Izquierdo, A; Menndez, J A; Gum, J; Borrs, J

    2008-05-01

    Heterozygous carriers of ATM (ataxia telangiectasia mutated gene) mutations have increased risk of breast cancer (BC). We have estimated the prevalence of mutations in the ATM gene among Spanish patients with early-onset BC. Forty-three patients diagnosed with BC before the age of 46 years, and negative for BRCA1 and BRCA2 mutations, were analysed for the presence of ATM mutations. A total of 34 ATM sequence variants were detected: 1 deleterious mutation, 10 unclassified variants and 23 polymorphisms. One patient (2.3%) carried the ATM deleterious mutation (3802delG that causes ataxia telangiectasia in the homozygous state) and 13 patients carried the 10 ATM unclassified variants. The truncating mutation 3802delG and eight of the rare variants were not detected in a control group of 150 individuals. Different bioinformatic sequence analysis tools were used to evaluate the effects of the unclassified ATM changes on RNA splicing and function protein. This in silico analysis predicted that the missense variants 7653 T>C and 8156 G>A could alter the splicing by disrupting an exonic splicing enhancer motif and the 3763 T>G, 6314 G>C, and 8156 G>A variants would affect the ATM protein function. These are the initial results concerning the prevalence of germline mutations in the ATM gene among BC cases in a Spanish population, and they suggest that ATM mutations can confer increased susceptibility to early-onset BC. PMID:18384426

  16. Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood Leukemia

    PubMed Central

    Healy, Jasmine; Bourgey, Mathieu; Richer, Chantal; Sinnett, Daniel; Roy-Gagnon, Marie-Helene

    2010-01-01

    Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry (MS) required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry (MA) when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad/case-control hybrid design provides valid tests for maternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia (ALL). We identified putative fetomaternal effects at loci CDKN2A rs36228834 (P = .017) and CDKN2B rs36229158 (P = .022) that modulate the risk of childhood ALL. These data further corroborate the importance of the mother's genotype on the susceptibility to early-onset diseases. PMID:20617153

  17. Early representation of shape by onset synchronization of border-ownership-selective cells in the V1-V2 network.

    PubMed

    Hatori, Yasuhiro; Sakai, Ko

    2014-04-01

    Construction of surface is a crucial step toward the representation of shape through the integration of local information. Physiological studies have reported that the primary visual cortex (V1) codes the medial axis (MA) that is a skeletal structure equidistant from nearby contours, suggesting the early representation of surface in V1. Although the neural basis of surface construction has not been clarified, the onset synchronization of border ownership (BO)-selective cells is a plausible candidate for the generation of surface. We investigated computationally the representation of surface in a biophysically detailed model of primate V1-V2 networks. The simulation results showed that the simultaneous arrival of signals from BO-selective cells evoked strong responses of V1 cells located around the MA. The simulation results lead to a prediction that the perception of the direction of figure (DOF) depends on the degree of synchronous presentation of contour. We conducted a psychophysical experiment and showed that the perception of the DOF is biased toward a highly synchronized contour. These results suggest a crucial role of the onset synchronization of BO-selective cells for the construction of early representation of shape. PMID:24695133

  18. Effects of early-onset voluntary exercise on adult physical activity and associated phenotypes in mice.

    PubMed

    Acosta, Wendy; Meek, Thomas H; Schutz, Heidi; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

    2015-10-01

    The purpose of this study was to evaluate the effects of early-life exercise on adult physical activity (wheel running, home-cage activity), body mass, food consumption, and circulating leptin levels in males from four replicate lines of mice selectively bred for high voluntary wheel running (High Runner or HR) and their four non-selected control (C) lines. Half of the mice were given wheel access shortly after weaning for three consecutive weeks. Wheel access was then removed for 52 days, followed by two weeks of adult wheel access for all mice. A blood sample taken prior to adult wheel testing was analyzed for circulating leptin concentration. Early-life wheel access significantly increased adult voluntary exercise on wheels during the first week of the second period of wheel access, for both HR and C mice, and HR ran more than C mice. During this same time period, activity in the home cages was not affected by early-age wheel access, and did not differ statistically between HR and C mice. Throughout the study, all mice with early wheel access had lower body masses than their sedentary counterparts, and HR mice had lower body masses than C mice. With wheel access, HR mice also ate significantly more than C mice. Early-life wheel access increased plasma leptin levels (adjusted statistically for fat-pad mass as a covariate) in C mice, but decreased them in HR mice. At sacrifice, early-life exercise had no statistically significant effects on visceral fat pad, heart (ventricle), liver or spleen masses (all adjusted statistically for variation in body mass). Results support the hypothesis that early-age exercise in mice can have at least transitory positive effects on adult levels of voluntary exercise, in addition to reducing body mass, and may be relevant for the public policy debates concerning the importance of physical education for children. PMID:26079567

  19. Carbonate platform evidence of ocean acidification at the onset of the early Toarcian oceanic anoxic event

    NASA Astrophysics Data System (ADS)

    Trecalli, Alberto; Spangenberg, Jorge; Adatte, Thierry; Föllmi, Karl B.; Parente, Mariano

    2012-12-01

    The early Toarcian oceanic anoxic event (Early Jurassic;˜183 Myr ago) is associated with one of the largest negative carbon isotope excursion (CIE) in the whole Phanerozoic (3-7‰). Estimates of the magnitude and rate of CO2 injection in the ocean-atmosphere system are compatible with a scenario of ocean acidification. Many carbonate platforms drowned in the Pliensbachian, well before the early Toarcian event. In this paper we test the hypothesis of surface water ocean acidification by presenting data from a resilient carbonate platform: the Apennine Carbonate Platform of southern Italy. The studied sections document a dramatic shift of the carbonate factory from massive biocalcification to chemical precipitation. Lithiotis bivalves and calcareous algae (Palaeodasycladus mediterraneus), which were the most prolific carbonate producers of Pliensbachian carbonate platforms, disappear during the first phase of the early Toarcian CIE, before the most depleted values are reached. We discuss the local versus supraregional significance of this shift and propose a scenario involving abrupt decline of carbonate saturation, forced by CO2 release at the beginning of the early Toarcian CIE, followed by a calcification overshoot, driven by the recovery of ocean alkalinity. Attribution of the demise of carbonate platform hypercalcifiers to ocean acidification is supported by palaeophysiology and reinforced by experimental data on the detrimental effects of ocean acidification on recent shellfishes and calcareous algae.

  20. Coercive Family Process and Early-Onset Conduct Problems From Age 2 to School Entry

    PubMed Central

    Smith, Justin D.; Dishion, Thomas J.; Shaw, Daniel S.; Wilson, Melvin N.; Winter, Charlotte C.; Patterson, Gerald R.

    2013-01-01

    The emergence and persistence of conduct problems during early childhood is a robust predictor of behavior problems in school and future maladaptation. In this study we examined the reciprocal influences between observed coercive interactions between children and caregivers, oppositional and aggressive behavior, and growth in parent report of early childhood (ages 2–5) and school-age conduct problems (age 7.5 and 8.5). Participants were drawn from the Early Steps multisite randomized prevention trial that includes an ethnically diverse sample of male and female children and their families (N = 731). A parallel process growth model combining latent trajectory and cross-lagged approaches revealed the amplifying effect of observed coercive caregiver–child interactions on children's noncompliance, whereas child oppositional and aggressive behaviors did not consistently predict increased coercion. The slope and initial levels of child oppositional and aggressive behaviors and the stability of caregiver–child coercion were predictive of teacher-reported oppositional behavior at school age. Families assigned to the Family Check-Up condition had significantly steeper declines in child oppositional and aggressive behavior and moderate reductions in oppositional behavior in school and in coercion at age 3. Results were not moderated by child gender, race/ethnicity, or assignment to the intervention condition. The implications of these findings are discussed with respect to understanding the early development of conduct problems and to designing optimal strategies for reducing problem behavior in early childhood with families most in need. PMID:24690305

  1. Deletion of Ku86 causes early onset of senescence in mice

    PubMed Central

    Vogel, Hannes; Lim, Dae-Sik; Karsenty, Gerard; Finegold, Milton; Hasty, Paul

    1999-01-01

    DNA double-strand breaks formed during the assembly of antigen receptors or after exposure to ionizing radiation are repaired by proteins important for nonhomologous end joining that include Ku86, Ku70, DNA-PKCS, Xrcc4, and DNA ligase IV. Here we show that ku86-mutant mice, compared with control littermates, prematurely exhibited age-specific changes characteristic of senescence that include osteopenia, atrophic skin, hepatocellular degeneration, hepatocellular inclusions, hepatic hyperplastic foci, and age-specific mortality. Cancer and likely sepsis (indicated by reactive immune responses) partly contributed to age-specific mortality for both cohorts, and both conditions occurred earlier in ku86−/− mice. These data indicate that Ku86-dependent chromosomal metabolism is important for determining the onset of age-specific changes characteristic of senescence in mice. PMID:10485901

  2. Early infantile sensory-motor neuropathy with late onset respiratory distress.

    PubMed

    Blaschek, Astrid; Gläser, Dieter; Kuhn, Marius; Schroeder, Andreas Sebastian; Wimmer, Cornelius; Heimkes, Bernd; Schön, Carola; Müller-Felber, Wolfgang

    2014-03-01

    Children with spinal muscular atrophy with respiratory distress (SMARD1) usually present within their first year of life, with respiratory failure due to diaphragmatic paralysis and progressive distal limb weakness. We present a child with a confirmed compound heterozygous IGHMBP2 mutation c.[676G>T];[2083A>T] in whom severe sensory-motor neuropathy preceded diaphragmatic paralysis by almost 3years. Autonomic system involvement with neurogenic bladder and urine retention were found at 3years. In summary, our patient highlights the broad spectrum of phenotypes observed in SMARD1. Currently, no prediction of phenotype according to genotype is possible, suggesting that yet unknown factors cause the observed phenotypic variation. Even in the absence of obvious diaphragmatic weakness, SMARD1 should be considered in severe infantile onset neuropathies. High throughput techniques, such as next generation sequencing, will possibly offer a useful approach in the heterogeneous group of inherited neuropathies. PMID:24342282

  3. Medical decision support using machine learning for early detection of late-onset neonatal sepsis

    PubMed Central

    Mani, Subramani; Ozdas, Asli; Aliferis, Constantin; Varol, Huseyin Atakan; Chen, Qingxia; Carnevale, Randy; Chen, Yukun; Romano-Keeler, Joann; Nian, Hui; Weitkamp, Jörn-Hendrik

    2014-01-01

    Objective The objective was to develop non-invasive predictive models for late-onset neonatal sepsis from off-the-shelf medical data and electronic medical records (EMR). Design The data used in this study are from 299 infants admitted to the neonatal intensive care unit in the Monroe Carell Jr. Children’s Hospital at Vanderbilt and evaluated for late-onset sepsis. Gold standard diagnostic labels (sepsis negative, culture positive sepsis, culture negative/clinical sepsis) were assigned based on all the laboratory, clinical and microbiology data available in EMR. Only data that were available up to 12 h after phlebotomy for blood culture testing were used to build predictive models using machine learning (ML) algorithms. Measurement We compared sensitivity, specificity, positive predictive value and negative predictive value of sepsis treatment of physicians with the predictions of models generated by ML algorithms. Results The treatment sensitivity of all the nine ML algorithms and specificity of eight out of the nine ML algorithms tested exceeded that of the physician when culture-negative sepsis was included. When culture-negative sepsis was excluded both sensitivity and specificity exceeded that of the physician for all the ML algorithms. The top three predictive variables were the hematocrit or packed cell volume, chorioamnionitis and respiratory rate. Conclusions Predictive models developed from off-the-shelf and EMR data using ML algorithms exceeded the treatment sensitivity and treatment specificity of clinicians. A prospective study is warranted to assess the clinical utility of the ML algorithms in improving the accuracy of antibiotic use in the management of neonatal sepsis. PMID:24043317

  4. Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).

    PubMed

    Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J

    2015-09-01

    Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. PMID:26033473

  5. Early pubertal onset and its relationship with sexual risk taking, substance use and anti-social behaviour: a preliminary cross-sectional study

    PubMed Central

    2009-01-01

    Background In many countries age at pubertal onset has declined substantially. Relatively little attention has been paid to how this decline may affect adolescent behaviours such as substance use, violence and unprotected sex and consequently impact on public health. Methods In the UK, two opportunistic samples (aged 16-45 years), paper-based (n = 976) and online (n = 1117), examined factors associated with earlier pubertal onset and whether earlier age of onset predicted sexual risk-taking, substance use and anti-social behaviours during early adolescence. Results Overall, 45.6% of females reported menarche ? 12 years and 53.3% of males were categorised as having pubertal onset ? 11 years. For both sexes earlier pubertal onset was associated with poorer parental socio-economic status. Other pre-pubertal predictors of early onset were being overweight, more childhood illnesses (females) and younger age at time of survey (males). For both sexes earlier puberty predicted having drunk alcohol, been drunk, smoked and used drugs <14 years as well as having a sexual debut and unprotected sex <16 years. Males with earlier pubertal onset were more likely to report fighting and aggressive responses to emotional upset during early adolescence while females were more likely to report being bullied and having taken more time off school. Conclusion Results provide sufficient evidence for changes in age of pubertal onset to be further explored as a potential influence on trends in adolescent risk behaviours. Further insight into the relationship between early puberty and both obesity and socio-economic status may help inform early interventions to tackle the development of risk behaviours and health inequalities during early adolescence. PMID:19958543

  6. Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins

    PubMed Central

    Paul, Ripon; Pessah, Isaac N.; Gane, Louise; Ono, Michele; Hagerman, Paul J.; Brunberg, James A.; Tassone, Flora; Bourgeois, James A.; Adams, Patrick E.; Nguyen, Danh V.; Hagerman, Randi

    2014-01-01

    We present four cases of fragile X premutation carriers with early neurological symptoms, including symptoms consistent with multiple sclerosis (MS) and fragile X-associated tremor/ataxia syndrome (FXTAS). Each patient had significant exposure to one or more environmental neurotoxicants that have documented neurotoxicity (i.e. hexachlorocyclopentadiene or C56, Agent Orange, and 2,4- or 2,6-toluene diisocyanate and dichlormate). We hypothesize that premutation carriers are a vulnerable group to neurotoxins because elevated mRNA in the premutation can lead to early cell death and brain disease, leading to neuropsychiatric and neurological symptoms consistent with FXTAS. PMID:20466021

  7. Does Theory of Mind Performance Differ in Children with Early-Onset and Regressive Autism?

    ERIC Educational Resources Information Center

    Matthews, Nicole L.; Goldberg, Wendy A.; Lukowski, Angela F.; Osann, Kathryn; Abdullah, Maryam M.; Ly, Agnes R.; Thorsen, Kara; Spence, M. Anne

    2012-01-01

    A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset…

  8. IQCB1 and PDE6B Mutations Cause Similar Early Onset Retinal Degenerations in Two Closely Related Terrier Dog Breeds

    PubMed Central

    Goldstein, Orly; Mezey, Jason G.; Schweitzer, Peter A.; Boyko, Adam R.; Gao, Chuan; Bustamante, Carlos D.; Jordan, Julie Ann; Aguirre, Gustavo D.; Acland, Gregory M.

    2013-01-01

    Purpose. To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively. Methods. Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the “MAGIC” genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease. Results. Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs. Conclusions. Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases. PMID:24045995

  9. Onset of the DNA Replication Checkpoint in the Early Drosophila Embryo

    PubMed Central

    Crest, Justin; Oxnard, Nathan; Ji, Jun-Yuan; Schubiger, Gerold

    2007-01-01

    The Drosophila embryo is a promising model for isolating gene products that coordinate S phase and mitosis. We have reported before that increasing maternal Cyclin B dosage to up to six copies (six cycB) increases Cdk1–Cyclin B (CycB) levels and activity in the embryo, delays nuclear migration at cycle 10, and produces abnormal nuclei at cycle 14. Here we show that the level of CycB in the embryo inversely correlates with the ability to lengthen interphase as the embryo transits from preblastoderm to blastoderm stages and defines the onset of a checkpoint that regulates mitosis when DNA replication is blocked with aphidicolin. A screen for modifiers of the six cycB phenotypes identified 10 new suppressor deficiencies. In addition, heterozygote dRPA2 (a DNA replication gene) mutants suppressed only the abnormal nuclear phenotype at cycle 14. Reduction of dRPA2 also restored interphase duration and checkpoint efficacy to control levels. We propose that lowered dRPA2 levels activate Grp/Chk1 to counteract excess Cdk1–CycB activity and restore interphase duration and the ability to block mitosis in response to aphidicolin. Our results suggest an antagonistic interaction between DNA replication checkpoint activation and Cdk1–CycB activity during the transition from preblastoderm to blastoderm cycles. PMID:17151243

  10. Clinical and neuropathological features of the Arctic APP mutation causing early onset Alzheimer's disease

    PubMed Central

    Basun, Hans; Bogdanovic, Nenad; Ingelsson, Martin; Almkvist, Ove; Nslund, Jan; Axelman, Karin; Bird, Thomas D.; Nochlin, David; Schellenberg, Gerard D.; Wahlund, Lars-Olof; Lannfelt, Lars

    2009-01-01

    Background A majority of mutations within the amyloid ? (A?) region of the amyloid precursor protein (APP) gene cause inherited forms of intracerebral haemorrhage. Most of these mutations may also cause cognitive impairment, but the Arctic APP mutation is the only known intra-A? mutation to date causing the more typical clinical picture of Alzheimer's disease (AD). Objective To describe features of one Swedish and one American family with the previously reported Arctic APP mutation. Subjects Affected and non-affected carriers of the Arctic APP mutation from the Swedish and American families were investigated clinically. In addition, one brain from each family was investigated neuropathologically. Results The clinical picture, with age at disease onset in the sixth to seventh decade of life and dysfunction in multiple cognitive areas, is indicative of AD and similar to the phenotype for other AD APP mutations. Several affected mutation carriers displayed general brain atrophy and reduced blood flow of the parietal lobe, as demonstrated by magnetic resonance imaging and single photon emission computed tomography. One Swedish and one American case with the Arctic APP mutation have come to autopsy, neither of which showed any signs of haemorrhage but revealed severe congophilic angiopathy, region-specific neurofibrillary tangle pathology as well as abundant amyloid plaques. Intriguingly, a majority of plaques from both of these cases had a characteristic ring-like character. Conclusions Overall, our findings corroborate that the Arctic APP mutation causes a clinical and neuropathological picture compatible with AD. PMID:18413473

  11. Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration.

    PubMed

    Holzerova, Eliska; Danhauser, Katharina; Haack, Tobias B; Kremer, Laura S; Melcher, Marlen; Ingold, Irina; Kobayashi, Sho; Terrile, Caterina; Wolf, Petra; Schaper, Jörg; Mayatepek, Ertan; Baertling, Fabian; Friedmann Angeli, José Pedro; Conrad, Marcus; Strom, Tim M; Meitinger, Thomas; Prokisch, Holger; Distelmaier, Felix

    2016-02-01

    Thioredoxin 2 (TXN2; also known as Trx2) is a small mitochondrial redox protein essential for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Exome sequencing in a 16-year-old adolescent suffering from an infantile-onset neurodegenerative disorder with severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy, uncovered a homozygous stop mutation in TXN2. Analysis of patient-derived fibroblasts demonstrated absence of TXN2 protein, increased reactive oxygen species levels, impaired oxidative stress defence and oxidative phosphorylation dysfunction. Reconstitution of TXN2 expression restored all these parameters, indicating the causal role of TXN2 mutation in disease development. Supplementation with antioxidants effectively suppressed cellular reactive oxygen species production, improved cell viability and mitigated clinical symptoms during short-term follow-up. In conclusion, our report on a patient with TXN2 deficiency suggests an important role of reactive oxygen species homeostasis for human neuronal maintenance and energy metabolism. PMID:26626369

  12. Early onset of pulmonary gas exchange disturbance during progressive exercise in healthy active men.

    PubMed

    Aguilaniu, B; Flore, P; Maitre, J; Ochier, J; Lacour, J R; Perrault, H

    2002-05-01

    Some recent studies of competitive athletes have shown exercise-induced hypoxemia to begin in submaximal exercise. We examined the role of ventilatory factors in the submaximal exercise gas exchange disturbance (GED) of healthy men involved in regular work-related exercise but not in competitive activities. From the 38 national mountain rescue workers evaluated (36 +/- 1 yr), 14 were classified as GED and were compared with 14 subjects matched for age, height, weight, and maximal oxygen uptake (VO2 max; 3.61 +/- 0.12 l/min) and showing a normal response (N). Mean arterial PO2 was already lower than N (P = 0.05) at 40% VO2 max and continued to fall until VO2 max (GED: 80.2 +/- 1.6 vs. N: 91.7 +/- 1.3 Torr). A parallel upward shift in the alveolar-arterial oxygen difference vs. %VO2 max relationship was observed in GED compared with N from the onset throughout the incremental protocol. At submaximal intensities, ideal alveolar PO2, tidal volume, respiratory frequency, and dead space-to-tidal volume ratio were identical between groups. As per the higher arterial PCO2 of GED at VO2 max, subjects with an exaggerated submaximal alveolar-arterial oxygen difference also showed a relative maximal hypoventilation. Results thus suggest the existence of a common denominator that contributes to the GED of submaximal exercise and affects the maximal ventilatory response. PMID:11960937

  13. Early-Onset Conduct Problems: Intersection of Conduct Problems and Poverty

    PubMed Central

    Shaw, Daniel S.; Shelleby, Elizabeth C.

    2014-01-01

    The current paper reviewed extant literature on the intersection between poverty and the development of conduct problems (CP) in early childhood. Associations between exposure to poverty and disruptive behavior were reviewed through the framework of models emphasizing how the stressors associated with poverty indirectly influence child CP by compromising parent psychological resources, investments in children’s welfare, and/or caregiving quality. We expanded upon the most well studied of these models, the family stress model, by emphasizing the mediating contribution of parent psychological resources on children’s risk for early CP, in addition to the mediating effects of parenting. Specifically, in we focused on the contribution of maternal depression, both in terms of compromising parenting quality and exposing children to even higher levels of stressful events and contexts. Implications of the adapted family stress model were then discussed in terms of its implications for the prevention and treatment of young children’s emerging CP. PMID:24471370

  14. Optimizing Treatment of Intra-amniotic Infection and Early-Onset Postpartum Endometritis: Advantages of Single-Agent Therapy

    PubMed Central

    Stiglich, Norma; Alston, Meredith; vanSwam, Simone

    2011-01-01

    Introduction: Intra-amniotic infection (IAI) and early-onset postpartum endometritis (PPE) require prompt antibiotic treatment and are generally treated by either of two regimens. A complicated multi-agent regimen is most commonly used, despite a lack of clear evidence that it produces better outcomes than a simpler single-agent regimen. Objective: We compared treatment outcomes between a multi-agent regimen of ampicillin, gentamicin, and clindamycin versus a single-agent regimen of ampicillin/sulbactam for IAI and early-onset PPE. Methods: We conducted an observational retrospective cohort study by collecting data from the records of all patients at Denver Health Medical Center treated for IAI or PPE during two 6-month periods: a baseline period during which a regimen of ampicillin, gentamicin, and clindamycin was used and a subsequent period when ampicillin/sulbactam was used. Primary outcomes were prolonged antibiotic treatment and readmission for endometritis or wound cellulitis. Results: Of potential study participants, 323 women met inclusion criteria; 179 were treated with the multi-agent regimen and 144 were treated with the single-agent regimen. The groups were statistically similar for demographic and intrapartum characteristics, except for a lower rate of premature rupture of membranes in the single-agent treatment group. Twelve patients required prolonged treatment, and 2 were readmitted; these subgroups were combined for statistical analyses. The primary outcomes were significantly associated with cesarean delivery and blood loss >500 mL for vaginal deliveries and >1000 mL for cesarean deliveries; however, there was no significant difference in the incidence of the primary outcomes between the 2 treatment groups when adjusted for these variables. Treatment with ampicillin/sulbactam resulted in fewer antibiotic doses administered to patients with an uncomplicated treatment course. Conclusion: Ampicillin/sulbactam treatment of IAI and early-onset PPE reduces the number of antibiotic doses administered and results in patient outcomes similar to those for the standard multi-agent therapy of ampicillin, gentamicin, and clindamycin. PMID:22058666

  15. A large early-onset Alzheimer`s disease pedigree linked to chromosome 14q24.3

    SciTech Connect

    Hannequin, D.; Campion, D.; Brice, A.

    1994-09-01

    A large French pedigree including 34 subjects with early-onset progressive dementia was identified. In patients, the mean age-at-onset was 46 {plus_minus} 3.5 (SD) years and the mean age at death 52.6 {plus_minus} 5.7 (SD) years. No evidence for anticipation or genetic imprinting was found. Twelve patients were clinically diagnosed as probable Alzheimer`s disease (AD) according to the NINCDS-ADRDA criteria. Myoclonus and extrapyramidal signs were common and seizures were found in all affected subjects. At autopsy, neuropathological changes typical of AD were present in two brains. A significant lod score of 5.38 was observed at a recombination fraction of {theta} = 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. Furthermore, no obligate recombinant was observed with markers D14S77 and D14S71. Typing other genetic markers in this region will allow us to localize more precisely the pathological gene.

  16. Urinary (1)H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis.

    PubMed

    Fanos, Vassilios; Caboni, Pierluigi; Corsello, Giovanni; Stronati, Mauro; Gazzolo, Diego; Noto, Antonio; Lussu, Milena; Dessì, Angelica; Giuffrè, Mario; Lacerenza, Serafina; Serraino, Francesca; Garofoli, Francesca; Serpero, Laura Domenica; Liori, Barbara; Carboni, Roberta; Atzori, Luigi

    2014-03-01

    The purpose of this article is to study one of the most significant causes of neonatal morbidity and mortality: neonatal sepsis. This pathology is due to a bacterial or fungal infection acquired during the perinatal period. Neonatal sepsis has been categorized into two groups: early onset if it occurs within 3-6 days and late onset after 4-7 days. Due to the not-specific clinical signs, along with the inaccuracy of available biomarkers, the diagnosis is still a major challenge. In this regard, the use of a combined approach based on both nuclear magnetic resonance ((1)H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques, coupled with a multivariate statistical analysis, may help to uncover features of the disease that are still hidden. The objective of our study was to evaluate the capability of the metabolomics approach to identify a potential metabolic profile related to the neonatal septic condition. The study population included 25 neonates (15 males and 10 females): 9 (6 males and 3 females) patients had a diagnosis of sepsis and 16 were healthy controls (9 males and 7 females). This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05). PMID:24709468

  17. Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases

    SciTech Connect

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

    1996-02-16

    Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ({le}age 60 years) AD (EOAD) probands has been carried out, allowing for a mixture in AD inheritance among probands. The goal was to quantify the proportion of probands that could be explained by autosomal inheritance of a rare disease allele {open_quotes}a{close_quotes} at a Mendelian dominant gene (MDG). Our data provide strong evidence for a mixture of two distributions; AD transmission is fully explained by MDG inheritance in <20% of probands. Male and female age-of-onset distributions are significantly different for {open_quotes}AA{close_quote} but not for {open_quotes}aA{close_quote} subjects. For {open_quotes}aA{close_quote} subjects the estimated penetrance value was close to 1 by age 60. For {open_quotes}AA{close_quotes} subjects, it reaches, by age 90, 10% (males) and 30% (females). We show a clear cutoff in the posterior probability of being an MDG case. 10 refs., 1 tab.

  18. Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease.

    PubMed

    Barber, Imelda S; García-Cárdenas, Jennyfer M; Sakdapanichkul, Chidchanok; Deacon, Christopher; Zapata Erazo, Gabriela; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Guetta-Baranes, Tamar; Braae, Anne; Clement, Naomi; Patel, Tulsi; Brookes, Keeley; Medway, Christopher; Chappell, Sally; Mann, David M; Morgan, Kevin

    2016-03-01

    Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ≤65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 known causative mutations: p.A713T, p.V717I, and p.V717G; this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a nonsignificantly increased minor allele frequency in our sEOAD cohort (0.006) compared to LOAD (0.002) and controls (0.002). To assess the effect of the 6-bp deletion on splicing, COS-7 and BE(2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harboring the deletion found no evidence of transcripts with exon 17 removed. PMID:26803359

  19. Hypoalbuminemia in early onset dentatorubral-pallidoluysian atrophy due to leakage of albumin in multiple organs.

    PubMed

    Nagai, Shigehiro; Saito, Yoshiaki; Endo, Yukari; Saito, Takashi; Sugai, Kenji; Ishiyama, Akihiko; Komaki, Hirofumi; Nakagawa, Eiji; Sasaki, Masayuki; Ito, Kimiteru; Saito, Yuko; Sukigara, Sayuri; Ito, Masayuki; Goto, Yu-Ichi; Ito, Shuichi; Matsuoka, Kentaro

    2013-05-01

    We delineate a complication of hypoalbuminemia in dentatorubral-pallidoluysian atrophy (DRPLA), which we have found to be common in this disorder. In addition, we explored the pathogenesis of this phenomenon through clinical and histological examinations. Clinical course and laboratory findings of nine patients with childhood-onset DRPLA (aged 6-49 years; CAG repeat length 62-93) were retrospectively reviewed. Autopsied specimens from three patients were examined by histopathological and immunohistochemical analyses. Eight DRPLA patients showed hypoalbuminemia <3.5 g/dl in the initial stages of the disease (age, 2-32 years), which correlated with the CAG repeat length in each patient. Disease worsened in six patients, often triggered by febrile infections and accompanied by increased urinary protein excretion. One patient showed increased fecal α1-antitripsin while another showed accumulation of radioactive albumin in the urinary and gastrointestinal tracts after intravenous infusion. Immunohistochemistry revealed albumin-containing monocytes and astrocytes in the perivascular areas of the cerebral white matter. Fluid collection in the glomerular capillaries was noted. Immunolabeling using antibodies against the expanded polyglutamine (polyQ) polypeptide was positive in cerebral cortical neurons, hepatocytes, renal collecting ducts, and glomerular podocytes, which act as filtration barrier against serum proteins. Serum albumin appears to easily leak from blood vessels in certain visceral organs in DRPLA during later stages of the illness, particularly in the kidneys of patients with largely expanded CAG repeats. We hypothesize that the accumulation of the DRPLA gene product with expanded polyQ sequences in the podocytes results in the dysfunction of the glomerular filtration barrier. PMID:23263592

  20. Early T2 Changes predict Onset of Radiographic Knee Osteoarthritis – Data from the Osteoarthritis Initiative

    PubMed Central

    Liebl, Hans; Joseph, Gabby; Nevitt, Michael C.; Singh, Nathan; Heilmeier, Ursula; Subburaj, Karupppasamy; Jungmann, Pia M.; McCulloch, Chuck E.; Lynch, John A.; Lane, Nancy E.; Link, Thomas M.

    2014-01-01

    Objective To evaluate whether T2 relaxation time measurements obtained at 3 Tesla Magnetic Resonance Imaging (MRI) predict the onset of radiographic knee osteoarthritis (OA). Methods and Materials We performed a nested case-control study of incident radiographic knee OA in the Osteoarthritis Initiative (OAI) cohort. Cases were 50 knees with baseline KL grade of 0 that developed KL grade of 2 or more over a 4-year period. Controls were 80 knees with KL grade of 0 after four years of follow-up. Baseline T2 relaxation time measurements and laminar analysis of T2 in deep and superficial layers were performed in all knee compartments. The association of T2 values with incident OA was assessed with logistic regression and differences in T2 values by case-control status with linear regression, adjusting for age, sex, body mass index (BMI) and other covariates. Results Baseline T2 values in all compartments except the medial tibia were significantly higher in knees that developed OA compared to controls, and were particularly elevated in the superficial cartilage layers in all compartments. There was an increased likelihood of incident knee OA associated with higher baseline T2 values particularly in the patella, adjusted odds ratio (OR) per 1 SD increase in T2: 3.37 (95% CI: 1.72; 6.62), but also in the medial femur: 1.90 (1.07; 3.39), lateral femur: 2.17 (1.11; 4.25) and lateral tibia: 2.23 (1.16; 4.31). Conclusions These findings suggest that T2 values assessed when radiographic changes are not yet apparent may be useful in predicting the development of radiological tibiofemoral OA. PMID:24615539

  1. Genetic Identification Is Critical for the Diagnosis of Parkinsonism: A Chinese Pedigree with Early Onset of Parkinsonism

    PubMed Central

    Yang, Yang; Tang, Bei-sha; Weng, Ling; Li, Nan; Shen, Lu; Wang, Jian; Zuo, Chuan-tao; Yan, Xin-xiang; Xia, Kun; Guo, Ji-feng

    2015-01-01

    Background A number of hereditary neurological diseases display indistinguishable features at the early disease stage. Parkinsonian symptoms can be found in numerous diseases, making it difficult to get a definitive early diagnosis of primary causes for patients with onset of parkinsonism. The accurate and early diagnosis of the causes of parkinsonian patients is important for effective treatments of these patients. Methods We have identified a Chinese family (82 family members over four generations with 21 affected individuals) that manifested the characterized symptoms of parkinsonism and was initially diagnosed as Parkinson’s disease. We followed up with the family for two years, during which we carried out clinical observations, Positron Emission Tomography-Computed Tomography neuroimaging analysis, and exome sequencing to correctly diagnose the case. Results During the two-year follow-up period, we performed comprehensive medical history collection, physical examination, and structural and functional neuroimaging studies of this Chinese family. We found that the patient exhibited progressive deteriorated parkinsonism with Parkinson disease-like neuropathology and also had a good response to the initial levodopa treatment. However, exome sequencing identified a missense mutation, N279K, in exon 10 of MAPT gene, verifying that the early parkinsonian symptoms in this family are caused by the genetic mutation for hereditary frontotemporal lobar dementia. Conclusions For the inherited parkinsonian patients who even show the neuropathology similar to that in Parkinson’s disease and have initial response to levodopa treatment, genetic identification of the molecular basis for the disease is still required for defining the early diagnosis and correct treatment. PMID:26295349

  2. Early to mid Cretaceous vegetation of northern Gondwana - the onset of angiosperm radiation and climatic implications

    NASA Astrophysics Data System (ADS)

    Coiffard, Clément; Mohr, Barbara

    2014-05-01

    Early Cretaceous Northern Gondwana seems to be the cradle of many early flowering plants, especially mesangiosperms that include magnoliids and monocots and basal eudicots. So far our knowledge was based mostly on dispersed pollen and small flowering structures. New fossil finds from Brazil include more complete plants with attached roots, leaves and flowers. Taxonomic studies show that these fossils belonged to clades which are, based on macroscopic characters and molecular data, also considered to be rather basal, such as several members of Nymphaeales, Piperales, Laurales, Magnoliales, monocots (Araliaceae) and Ranunculales. Various parameters can be used in order to understand the physiology and habitat of these plants. Adaptations to climate and habitat are partly mirrored in their root anatomy (evidence of tap roots), leaf size and shape, leaf anatomy including presence of glands, and distribution of stomata. An important ecophysiolocical parameter is vein density as an indicator for the plants' cabability to pump water, and the stomatal pore index, representing the proportion of stomatal pore area on the leaf surface, which is related to the water vapor resistance of the leaf epidermis. During the mid-Cretaceous leaf vein density started to surpass that of gymnosperms, one factor that made angiosperms very successful in conquering many kinds of new environments. Using data on these parameters we deduce that during the late Early to mid Cretaceous angiosperms were already diverse, being represented as both herbs, with aquatic members, such as Nymphaeles, helophytes (e.g. some monocots) and plants that may have grown in shady locations. Other life forms included shrubs and perhaps already small trees (e.g. Magnoliales). These flowering plants occupied various habitats, ranging from xeric (e.g. some Magnoliales) to mesic and shady (e.g. Piperales) or aquatic (e.g. Araceae, Nymphaeales). Overall, it seems that several of these plants clearly exhibited some mechanisms to withstand drought, which in turn let us assume that the climate was characterized by dry and wet seasons.

  3. What is the Contribution of Genetics to Periodontal Risk?