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1

Early Onset Schizophrenia  

Microsoft Academic Search

\\u000a Early onset schizophrenia (EOS) describes onset of the first episode of psychosis before age 18 years. Such an earlier onset\\u000a of symptoms is often associated with a severe and chronic course of the illness, a poorer prognosis and a potentially significant\\u000a negative impact on recovery and rehabilitation. A recent emphasis on early intervention by utilizing the advances in neurobiological\\u000a and

Vishal Madaan; Yael Dvir; Durga Prasad Bestha; Daniel R. Wilson

2

Early onset idiopathic scoliosis.  

PubMed

Children with early onset scoliosis typically present before age 5 years. Radiographic criteria help to distinguish progressive cases from those that will spontaneously resolve. Severe cardiopulmonary problems may occur in untreated progressive cases. A comprehensive evaluation should be performed to identify commonly associated conditions, such as plagiocephaly, congenital heart disease, inguinal hernia, and hip dysplasia. For curves >20 degrees , magnetic resonance imaging of the neural axis is indicated to rule out occult central nervous system lesions. Surgical management should be considered when nonsurgical measures, including bracing and casting, fail to arrest progression. Surgical methods continue to evolve and are primarily directed at obtaining and maintaining curve correction while simultaneously preserving spinal and trunk growth. PMID:16467185

Gillingham, Bruce L; Fan, Ryan A; Akbarnia, Behrooz A

2006-02-01

3

Genetics Home Reference: Early-onset glaucoma  

MedlinePLUS

... studies OMIM Genetic disorder catalog Conditions > Early-onset glaucoma On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed February 2009 What is early-onset glaucoma? Glaucoma is a group of eye disorders in ...

4

Microbiology and management of periodontal infections.  

PubMed

The term periodontal disease refers to all diseases that involve the supportive structures of the periodontium. Peridontal diseases commonly begin as a gingivitis and progress to periodontitis. Necrotizing ulcerative gingivitis (NUG) is the most fulminate form of gingivitis. The two main forms of periodontitis are chronic periodontitis (also known as adult periodontitis) and aggressive periodontitis (also known as early onset periodontitis, destructive periodontitis, and juvenile periodontitis). Gingivitis treatment involves removing dental plaques and maintaining good oral hygiene. Periodontitis therapy should include root debriding, draining the infected root, and surgically resecting inflamed periodontal tissues. Systemic antimicrobials often are indicated in NUG, chronic periodontitis, and aggressive periodontitis. When possible, antimicrobial selection should be based upon culture and susceptibility testing of the subgingival flora. PMID:15055631

Brook, Itzhak

2003-01-01

5

The Influence of Tobacco Smoking on the Onset of Periodontitis in Young Persons  

PubMed Central

This paper reviews the evidence for cigarette smoking as a risk factor for the development of severe destructive periodontal disease in young adults. A high prevalence of cigarette smoking has been identified among young individuals with aggressive periodontitis and tobacco usage increases the risk of periodontal destruction most significantly in young populations. The effect appears to be dose related and is independent of levels of plaque accumulation. Young smokers have more alveolar bone loss and attachment loss than non smoking equivalents. Prolonged and heavy smoking can reduce gingival bleeding and therefore mask the clinical marker of bleeding on probing often used by dentists to monitor periodontal health. This has implications for potential misdiagnosis and failure to detect periodontitis at an early stage. Nicotine metabolites concentrate in the periodontal tissues and can have local effects as well as the potential to affect the systemic host response. Dentists are well placed to assess the smoking status of their young patients and have a role to play in the delivery of smoking cessation advice especially as it pertains to periodontal health. In this way the dental profession can also make a significant contribution to the general health and well being of our youth and future generations. PMID:19570272

Mullally, Brian H

2004-01-01

6

The Influence of Tobacco Smoking on the Onset of Periodontitis in Young Persons  

PubMed Central

This paper reviews the evidence for cigarette smoking as a risk factor for the development of severe destructive periodontal disease in young adults. A high prevalence of cigarette smoking has been identified among young individuals with aggressive periodontitis and tobacco usage increases the risk of periodontal destruction most significantly in young populations. The effect appears to be dose related and is independent of levels of plaque accumulation. Young smokers have more alveolar bone loss and attachment loss than non smoking equivalents. Prolonged and heavy smoking can reduce gingival bleeding and therefore mask the clinical marker of bleeding on probing often used by dentists to monitor periodontal health. This has implications for potential misdiagnosis and failure to detect periodontitis at an early stage. Nicotine metabolites concentrate in the periodontal tissues and can have local effects as well as the potential to affect the systemic host response. Dentists are well placed to assess the smoking status of their young patients and have a role to play in the delivery of smoking cessation advice especially as it pertains to periodontal health. In this way the dental profession can also make a significant contribution to the general health and well being of our youth and future generations.

Mullally, Brian H

2004-01-01

7

Early onset bipolar disorder Early Onset Bipolar Disorder: validation from admixture analyses and biomarkers.  

E-print Network

Early onset bipolar disorder 1 Early Onset Bipolar Disorder: validation from admixture analyses of Psychiatry / Revue Canadienene de Psychiatrie 2013;58(4):240-248" #12;Early onset bipolar disorder 2 Abstract: Objectives: Bipolar affective disorder (BD) is a multifactorial disorder with heterogeneous clinical

Paris-Sud XI, Université de

8

Early-onset Lafora body disease  

PubMed Central

The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht–Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and causes translocation of the two proteins to the nucleus. We find that Phe261Leu-PRDM8 results in excessive sequestration of laforin and malin in the nucleus and that it therefore likely represents a gain-of-function mutation that leads to an effective deficiency of cytoplasmic laforin and malin. We have identified a new progressive myoclonus epilepsy with Lafora bodies, early-onset Lafora body disease, 101 years after Lafora disease was first described. The results to date suggest that PRDM8, the early-onset Lafora body disease protein, regulates the cytoplasmic quantities of the Lafora disease enzymes. PMID:22961547

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

2012-01-01

9

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

PubMed Central

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

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

10

Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients  

Microsoft Academic Search

The aims of this cross-sectional study were (i) to compare the overall glucose metabolism between early onset and late onset Alzheimer's disease in a large sample of patients; and (ii) to investigate the pattern of glucose metabolism as a function of dementia severity in early onset versus late onset Alzheimer's disease, using a statistical parametric mapping (SPM) analysis. Subjects consisted

E. J. Kim; S. S. Cho; Y. Jeong; K. C. Park; S. J. Kang; E. Kang; S. E. Kim; K. H. Lee

2005-01-01

11

Genomic insights into early-onset obesity  

PubMed Central

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

2010-01-01

12

Childhood onset schizophrenia and early onset schizophrenia spectrum disorders.  

PubMed

The clinical severity, impact on development, and poor prognosis of childhood onset schizophrenia may represent a more homogeneous group. Positive symptoms in children are necessary for the diagnosis and hallucinations are more often multimodal. In healthy children and children with a variety of other psychiatric illnesses, hallucinations are not uncommon and diagnosis should not be based on these alone. Childhood onset schizophrenia is an extraordinarily rare illness that is poorly understood but seems continuous with the adult onset disorder. Once a diagnosis is affirmed, aggressive medication treatment combined with family education and individual counseling may defer further deterioration. PMID:24012072

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

2013-10-01

13

Growth and early onset inflammatory bowel disease.  

PubMed

In pediatrics, growth is considered one of the most important markers of overall well-being. This study looked at growth in children diagnosed with inflammatory bowel disease before they were 5 years old from a single center. The Children's Inflammatory Bowel Disease Center at Mount Sinai maintains a database of 1,150 children followed at the center. Ninety-three children were included in this study, 58% boys and 42% girls. The average age at diagnosis was 3.2 years. Sixty-two percent had ulcerative colitis and 38% had Crohn disease. Height was recorded at initial presentation and at the most recent visit to the center; from this, a height percentile and z score were calculated. A target adult height was calculated for each child on the basis of mid-parental height. This target height was compared to the actual height the children achieved or the percentile they were growing along. Ten percent of children in the study presented with growth failure. For children with early onset ulcerative colitis, 58% achieved or exceeded their projected height percentile. For children with early onset Crohn disease, 38% achieved or exceeded their projected height percentile. Fifty-nine percent of the entire group either maintained their presentation percentile or increased their height percentiles over time, with an increase in z score ranging from 0.093 to 4.137. PMID:18391796

Ceballos, Clare

2008-01-01

14

[Early-onset sarcoidosis/Blau syndrome].  

PubMed

Familial Blau syndrome and sporadic early-onset sarcoidosis (EOS) are both systemic granulomatous diseases evoked by the spontaneous activation of mutated NOD2. In Japan, the R334W amino acid substitution is more frequently identified, whereas the R334Q mutation is rare and, in contrast to western countries where disease causing mutations are typically hereditary, most Japanese cases derive from sporadic mutations. Recently, a case with a six-base deletion in the NOD2 gene was reported. This Blau syndrome/EOS patient presented with the unpainful soft swelling of the dorsal side of the wrist and ankles, as well as flexion contracture at the proximal interphalangeal joint that gradually appeared during their clinical course. These features are useful for the differential diagnosis of Blau syndrome/EOS from juvenile idiopathic arthritis. Owing to their characteristic clinical symptoms, Blau and EOS patients can be identified earlier if medical experts become more acquainted with these distinctions. Even though specific treatment based on pathophysiologic mechanism has not been explored yet, early diagnosis will prevent the progression to severe impairment, which can severely affect patients' lives. PMID:22041425

Kambe, Naotomo; Satoh, Takashi; Nakano, Michiyo; Nakamura, Yuumi; Matsue, Hiroyuki

2011-01-01

15

Early colonization of dental implants by putative periodontal pathogens in partially edentulous patients.  

PubMed

There is limited scientific information available on the early colonization of the peri-implant pockets in partially edentulous individuals. Knowledge about this process is one step in better understanding the etiology and pathogenesis of peri-implantitis. In this study, the early colonization of the peri-implant pockets by putative periodontal pathogens was studied in 20 partially edentulous individuals using anaerobic culture techniques. At baseline, the presence and levels of putative periodontal pathogens in the microflora of periodontal pockets and saliva were established. Immediately after loading of the titanium implants and after 6 and 12 months the presence and levels of selected putative periodontal pathogens were determined in periodontal and peri-implant pockets. A second aim was to detect bacterial contamination of the implant site and the inside of the implant. At baseline, the most frequently isolated species from the periodontal pockets were Fusobacterium nucleatum, Prevotella intermedia and Peptostreptococcus micros. Bacteroides forsythus, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were isolated from 9, 2 and 3 patients respectively. Six months after placing of the bridges, the majority of the implant sites had detectable levels of most periodontal bacterial species with the exception of A. actinomycetemcomitans which could not be isolated from any of the peri-implant samples during the experimental period, although 2 patients had this organism at baseline. In 2 patients with detectable subgingival P. gingivalis at baseline this species was found after 12 months in the peri-implant sites. One of these patients lost 2 implants which was associated with a high proportion of P. gingivalis in the peri-implant pockets. A second patient developed 2 fistulas around 2 implants at 8 months and this event was also associated with the presence of P. gingivalis. It is concluded that proper periodontal infection control before installment of dental implants in partially edentulous patients may prevent early bacterial complications. PMID:11168244

van Winkelhoff, A J; Goené, R J; Benschop, C; Folmer, T

2000-12-01

16

Early Onset Alzheimer's Disease and Oxidative Stress  

PubMed Central

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

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

2014-01-01

17

Evidence for a genetic etiology of early-onset delinquency  

Microsoft Academic Search

Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11 -year-old twins

Jeanette Taylor; William G. Iacono; Matt McGue

2000-01-01

18

Early onset sarcoidosis masquerading as juvenile rheumatoid arthritis.  

PubMed

Symptoms of early onset sarcoidosis characterized by skin eruptions, arthritis, and uveitis mimic those of systemic type juvenile rheumatoid arthritis (JRA). We report 2 Japanese patients with early onset sarcoidosis, both of whom were initially diagnosed and treated as having JRA. Intermittent fever and synovial swelling may mask sarcoidosis in children less than 4 years old. PMID:11044836

Yotsumoto, S; Takahashi, Y; Takei, S; Shimada, S; Miyata, K; Kanzaki, T

2000-11-01

19

Early onset sarcoidosis masquerading as juvenile rheumatoid arthritis  

Microsoft Academic Search

Symptoms of early onset sarcoidosis characterized by skin eruptions, arthritis, and uveitis mimic those of systemic type juvenile rheumatoid arthritis (JRA). We report 2 Japanese patients with early onset sarcoidosis, both of whom were initially diagnosed and treated as having JRA. Intermittent fever and synovial swelling may mask sarcoidosis in children less than 4 years old. (J Am Acad Dermatol

Shinichi Yotsumoto; Yoshihiro Takahashi; Shuji Takei; Shoko Shimada; Koichiro Miyata; Tamotsu Kanzaki

2000-01-01

20

Clinical determinants of exacerbations in severe, early-onset COPD  

Microsoft Academic Search

Chronic obstructive pulmonary disease (COPD) exacerbations impair health. The present authors analysed participants in the Boston Early-Onset COPD Study for familial aggregation and propensity for COPD exacerbations. In the present study, two exacerbation outcomes, episodes of cough and phlegm, and frequent exacerbations were analysed with multivariable modelling and generalised estimating equations. In early-onset COPD probands, passive tobacco smoke exposure within

M. G. Foreman; D. L. DeMeo; C. P. Hersh; J. J. Reilly; E. K. Silverman

2007-01-01

21

The short-term consequences of early onset cannabis use  

Microsoft Academic Search

The associations between early onset (prior to 15 years of age) cannabis use and rates of mental health or adjustment problems during the period from 15 to 16 years of age were studied in a New Zealand birth cohort. Early onset cannabis users were at increased risks of later substance use behaviors, conduct\\/oppositional disorders, juvenile offending, severe truancy, school dropout,

David M. Fergusson; Michael T. Lynskey; L. John Horwood

1996-01-01

22

How do periodontal infections affect the onset and progression of Alzheimer's disease?  

PubMed

Chronic infection can cause slow progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. Due to the fact that specific bacterial ligands can increase the expression of proinflammatory molecules that can activate innate and adaptive immune systems, inflammation may play a significant role in the pathogenesis of Alzheimer's disease (AD). Furthermore, there is a significant association between AD and various types of spirochete. Periodontitis is a prevalent and persistent peripheral infection that is associated with gram-negative anaerobic bacteria and is capable of showing localized and systemic infections in the host. Periodontal disease related pathogens and their inflammatory products contribute to systemic inflammation and the pathogenesis of AD. In this minireview, we propose a hypothetical link between periodontitis, type 2 diabetes and AD. We also present the possible mechanistic links between periodontitis-related inflammation, type 2 diabetes and AD. Since this condition is treatable, periodontitis may be a readily-modifiable risk factor for AD. PMID:24059310

Shaik, Munvar M; Ahmad, Sultan; Gan, Siew H; Abuzenadah, Adel M; Ahmad, Ejaz; Tabrez, Shams; Ahmed, Farid; Kamal, Mohammad A

2014-04-01

23

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

ERIC Educational Resources Information Center

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…

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

2010-01-01

24

Early onset myasthenia gravis with atypical features  

Microsoft Academic Search

A 14 year old boy with atypical myasthenia gravis is reported. The interesting features of the case were the onset in fi rst decade with progressive weakness of limb muscles simulating limb girdle myopathy, presence of bilateral symmetrical non fl uctuating external ophthalmoplegia with ptosis and the absence of diplopia. Differential response to choline esterase inhibitors was clinically apparent. In

Agarwal P; Chapagain U; Deewan KR; Rana PVS

2008-01-01

25

Differences Between Early and Late Onset Adult Depression  

PubMed Central

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

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

2011-01-01

26

Operational Thought in Alzheimer's Disease Early Onset and SDAT.  

ERIC Educational Resources Information Center

For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

Emery, Olga B.; Breslau, Lawrence D.

27

Early- versus late-onset bipolar II disorder.  

PubMed Central

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

Benazzi, F

2000-01-01

28

Recent advances in the management of early onset scoliosis.  

PubMed

As the undesired results of early spinal fusion have become apparent, "growth-friendly" management methods for early onset scoliosis have been increasing during recent years. Current literature supports the use of repeated corrective cast applications as the initial management for most early onset progressive spinal deformities as either definitive treatment or as a temporizing measure. If casting is not an option or the deformity cannot be controlled via casting, one of the growth-friendly instrumentation techniques is chosen. Growth-friendly surgical methods and implants have been evolving as understanding of the disease improves. PMID:25199421

Sturm, Peter F; Anadio, Jennifer M; Dede, Ozgur

2014-10-01

29

Early-onset childhood sarcoidosis with incidental multiple enchondromatosis.  

PubMed

The triad of rash, arthritis, and uveitis seems to be characteristic for early-onset childhood sarcoidosis. We describe an interesting case of early-onset childhood sarcoidosis coexisting enchondromatosis, which clinically masquerade as Langerhans cell histiocytosis. A 33 months old girl presented with skin rash, subcutaneous nodules with polyarthritis, and revealed the involvement of lymph nodes as well as spleen during work-up. She also presented with multiple osteolytic lesions which pathologically proven enchondromatosis. Oral prednisone was prescribed at 2 mg/kg/day for 2 months until when subcutaneous nodules and joint swellings almost disappeared, and then slowly tapered over a period of 5 months. We report an unusual case of early-onset childhood sarcoidosis presented with osteolytic bone lesions which were irrelevant to sarcoidosis. PMID:22219622

Lee, Jong-Hwa; Lim, Yeon-Jung; Lee, Seunghun; Joo, Kyung Bin; Choi, Yun Young; Park, Chan-Kum; Lee, Young-Ho

2012-01-01

30

[Early onset pediatric sarcoidosis, diagnostic problems].  

PubMed

Sarcoidosis, a chronic multisystem inflammatory granulomatous disorder of unknown origin, is a rare disease in children. Two distinct clinical presentations of sarcoidosis in childhood are known. Older children usually show multisystem disease, close to the adult manifestation, with lung infiltration and frequent hilar lymphadenopathy. Prior to the age of 5, sarcoidosis reveals more frequently with the classical triad of rash, arthritis, and uveitis. Due to non-specific clinical features and the lack of a specific test, recognizing sarcoidosis can be difficult in the pediatric population. Moreover, unlike in adults, lung involvement is rare in pediatric sarcoidosis. Given the lack of a definitive blood test, the World Association of Sarcoidosis and Other Granulomatous disorders (WASOG) only recommends dosing the serum angiotensin-converting enzyme (ACE). Its level is usually higher in children than in adults, but an increased ACE may help in the diagnosis. The gold standard is a biopsy specimen with typical epithelioid gigantocellular granuloma without caseating necrosis granuloma, after other disorders known to cause granulomatous disease have been reasonably excluded. We report here the case of a 4.5-year-old male with the history of polyarthritis and uveitis, considered first as juvenile rheumatoid arthritis, followed 5 years later by cutaneous involvement, which led to reconsidering the diagnosis. There were no pulmonary clinical findings. Histology provided the diagnosis of sarcoidosis. He then developed dependence on steroids. The lack of the classical triad delayed the diagnosis several years. This case shows the pediatric singularity of sarcoidosis, which needs to be known so that early and appropriate follow-up can be conducted. PMID:22652518

Deverrière, G; Flamans-Klein, A; Firmin, D; Azouzi, O; Courville, P; Le Roux, P

2012-07-01

31

Early and Late Onset Sepsis in Late Preterm Infants  

PubMed Central

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

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

2009-01-01

32

Early-onset childhood sarcoidosis: A case report  

Microsoft Academic Search

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology and it most commonly affects young adults. Childhood sarcoidosis is relatively rare; older children usually present a picture similar to that of adults, with frequent hilar lymphadenopathy and pulmonary infiltration. Early-onset (

Lai-San Wong; Ji-Chen Ho; Yu-Ta Yen

33

Early-onset neonatal sepsis due to Cellulosimicrobium cellulans.  

PubMed

Cellulosimicrobium cellulans represents a rare human pathogen. Infections have been reported in immunocompromised hosts or in patients with an underlying disease. The authors describe a rare case of early-onset neonatal sepsis due to Cellulosimicrobium cellulans in an infant without any underlying disease. The infant was successfully treated with vancomycin. PMID:20376528

Casanova-Román, M; Sanchez-Porto, A; Gomar, J L; Casanova-Bellido, M

2010-08-01

34

Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues  

ERIC Educational Resources Information Center

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…

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

35

Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders  

ERIC Educational Resources Information Center

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…

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

36

Cytomegalovirus infection in association with early onset pre-eclampsia  

Microsoft Academic Search

This case describes a woman who presented with raised ?-fetoprotein (AFP) on second trimester screening, and developed early onset fetal growth restriction (FGR) and severe pre-eclampsia (PET) before 24 weeks' gestation requiring magnesium sulphate and intravenous antihypertensives. Ultrasonography revealed a structurally normal fetus with estimated weight <3rd centile, abnormal uterine artery Dopplers and deteriorating fetal arterial Dopplers over the following

L Higgins; S Vause; C Tower

2010-01-01

37

Phenomenology of Early Childhood Onset Obsessive Compulsive Disorder  

Microsoft Academic Search

This paper describes the phenomenological features of early childhood onset obsessive compulsive disorder (OCD; defined as\\u000a children meeting DSM-IV criteria for OCD with age of onset <8 years). Fifty-eight children (ages 4–8) were included in the\\u000a sample. OCD and comorbid diagnoses were determined by structured interview, and OCD severity was measured using the Children’s\\u000a Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Mean age

Abbe M. Garcia; Jennifer B. Freeman; Michael B. Himle; Noah C. Berman; Alexandra K. Ogata; Janet Ng; Molly L. Choate-Summers; Henrietta Leonard

2009-01-01

38

Early and Phasic Cortical Metabolic Changes in Vestibular Neuritis Onset  

PubMed Central

Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF) are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN), that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [18F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients’ cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34) and Temporal (BA 38) cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34) and of the emotional response to the new pathologic condition (BA 38) respectively. These interpretations were further supported by changes in patients’ subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding knowledge about early, fast-changing, and complex cortical responses to pathological vestibular unbalanced processing. PMID:23505435

Alessandrini, Marco; Pagani, Marco; Napolitano, Bianca; Micarelli, Alessandro; Candidi, Matteo; Bruno, Ernesto; Chiaravalloti, Agostino; Di Pietro, Barbara; Schillaci, Orazio

2013-01-01

39

Early and phasic cortical metabolic changes in vestibular neuritis onset.  

PubMed

Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF) are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN), that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [(18)F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients' cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34) and Temporal (BA 38) cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34) and of the emotional response to the new pathologic condition (BA 38) respectively. These interpretations were further supported by changes in patients' subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding knowledge about early, fast-changing, and complex cortical responses to pathological vestibular unbalanced processing. PMID:23505435

Alessandrini, Marco; Pagani, Marco; Napolitano, Bianca; Micarelli, Alessandro; Candidi, Matteo; Bruno, Ernesto; Chiaravalloti, Agostino; Di Pietro, Barbara; Schillaci, Orazio

2013-01-01

40

Erythema nodosum: a presenting sign of early onset sarcoidosis.  

PubMed

"Early onset sarcoidosis" is a chronic granulomatous disease occurring in children younger than 5 years of age, and characterized by a classic symptom triad consisting of skin, eye and joint lesions, with on rare occasion pulmonary involvement. The disorder often goes unrecognized because of its rarity and, since polyarthritis and uveitis are the predominant symptoms, most of these children are misdiagnosed as having juvenile chronic arthritis (JCA). A child with erythema nodosum at 7 months of age, later diagnosed as JCA and definitively recognized as "early onset sarcoidosis" is reported. This case shows that, whenever possible, a biopsy showing the typical picture of sarcoid granulomas is crucial to distinguish these clinical conditions. PMID:9631761

Cancrini, C; Angelini, F; Colavita, M; Cortis, E; Chini, L; Mammone, F; Rossi, P; De Sanctis, R

1998-01-01

41

Different Profile of Serum Leptin between Early Onset and Late Onset Preeclampsia  

PubMed Central

Aim. This study was designed to clarify the role of leptin and adiponectin in preeclampsia (PE) pathogenesis and different subtypes of preeclampsia. Method. This case control study was performed in 45 PE patients and 45 healthy controls matched for age, BMI, and ethnicity. Serum leptin and adiponectin levels were determined by enzyme linked immunosorbent assay (ELISA). Results. Maternal serum leptin and adiponectin were significantly higher in PE women than controls. Serum leptin was elevated in early onset preeclampsia (EOPE) and late onset preeclampsia (LOPE) compared to controls. Among PE patients, serum leptin was higher in EOPE than LOPE women. However, serum adiponectin was not different between EOPE and LOPE women. The serum leptin was significantly higher in severe PE than mild PE. The serum adiponectin was significantly elevated in severe PE compared to controls. Significant positive correlation was observed between leptin and adiponectin and also between leptin and BMI in controls. Moreover significant positive correlation was observed between adiponectin and BMI in PE patients and controls. Conclusion. The present study showed that serum leptin level may play a significant role as a biomarker to differentiate early and late onset PE and also its relation to BMI and severity of disease. PMID:24591763

Salimi, Saeedeh; Farajian-Mashhadi, Farzaneh; Naghavi, Anoosh; Mokhtari, Mojgan; Shahrakipour, Mahnaz; Saravani, Mohsen; Yaghmaei, Minoo

2014-01-01

42

Early-onset bipolar disorder: a family treatment perspective.  

PubMed

Mood disorder symptoms and their associated functional impairments are hypothesized to come about as the result of the conjoint, interactive influences of genetic, biological, and psychological vulnerabilities, family distress, and life stress at different points of development. We discuss a developmental psychopathology model that delineates pathways to high family conflict and mood exacerbation among early-onset bipolar patients. New data from a treatment development study indicate that adolescent bipolar patients in high expressed emotion families have more symptomatic courses of illness over 2 years than adolescents in low expressed emotion families. Chronic and episodic stressors are also correlated with lack of mood improvement while adolescents are in treatment. Family-focused treatment (FFT) given in conjunction with pharmacotherapy appears to ameliorate the course of bipolar disorder in adults. This treatment has recently been modified to address the developmental presentation of bipolar disorder among adolescents. We present data from an open trial of FFT and pharmacotherapy (N = 20) indicating that bipolar adolescents stabilize in mania, depression, and parent-rated problem behaviors over 2 years. Future research should focus on clarifying the developmental pathways to early-onset bipolar disorder and the role of protective factors and preventative psychosocial interventions in delaying the first onset of the disorder. PMID:17064437

Miklowitz, David J; Biuckians, Adrine; Richards, Jeffrey A

2006-01-01

43

Editorial: Research Progress in Early-Onset Schizophrenia  

PubMed Central

A substantial proportion of patients with schizophrenia experience the onset of their illness by age 18. Data from phenomenological, cognitive, neuroimaging, and genetic studies suggest a similar profile of clinical and neurobiological abnormalities between early- and adult-onset patients. However, children and adolescents with schizophrenia have been found to have more severe premorbid neurodevelopmental abnormalities, worse long-term outcome, more cytogenetic anomalies, and potentially greater loading of family histories for schizophrenia and associated spectrum disorders than their adult counterparts. Together, these data support a hypothesis that early-onset schizophrenia may reflect a more severe form of the disorder associated with a greater genetic predisposition. It is anticipated that future imaging and genetic studies of this cohort will provide further insight into the neurodevelopmental origins of schizophrenia and the complexity by which genetic and environmental factors interact to modulate susceptibility and/or disease phenotype. The articles on this theme provide updated findings from brain magnetic resonance imaging, neurocognition, and clinical trials in this unique cohort. PMID:18048380

Kumra, Sanjiv; Charles Schulz, S.

2008-01-01

44

Early onset neonatal septicaemia in a level II nursery.  

PubMed

A prospective study of 486 high risk neonates admitted to a level II nursery in a relatively poor and rural area of Malaysia was carried out to determine the incidence, the spectrum of micro-organisms and predisposing factors in relation to early onset septicaemia. The incidence of proven or probable septicaemia was 57.61 per 1000 high risk newborns over 1.5 kg. The case fatality was 10.71 per cent. Coagulase negative staphylococci, Streptococcus Group B and Klebsiella species were the most commonly isolated organisms. Meconium staining of liquor was the most common risk factor for admission to the nursery, and prematurity was the most significant risk factor for early neonatal infection (P < 0.005) followed by small for gestational age (P < 0.04). Although the incidence of septicaemia was quite high in the level II nursery, the mortality rate was comparable to established figures. PMID:8057985

Malik, A S; Pennie, R A

1994-03-01

45

Evaluating the Near-Term Infant for Early Onset Sepsis  

PubMed Central

Although the rate of early onset sepsis in the near-term neonate is low (one to eight of 1000 cases), the rate of mortality and morbidity is high. As a result, infants receive multiple, broad-spectrum antibiotic therapy, many for up to 7 days despite blood cultures showing no growth. Maternal intrapartum antibiotic prophylaxis and small blood volume collections from infants are cited as reasons for the lack of confidence in negative culture results. Incorporating an additional, more rapid test could facilitate a more timely diagnosis in these infants. To this end, a 16S rDNA polymerase chain reaction (PCR) assay was compared to blood culturing for use as a tool in evaluating early onset sepsis. Of 1751 neonatal intensive care unit admissions that were screened, 1233 near-term infants met inclusion criteria. Compared to culture, PCR demonstrated excellent analytical specificity (1186 of 1216, 97.5%) and negative predictive value (1186 of 1196, 99.2%); however, PCR failed to detect a significant number of culture-proven cases. These findings underscore the cautionary stance that should be taken at this time when considering the use of a molecular amplification test for diagnosing neonatal sepsis. The experience gained from this study illustrates the need for changes in sample collection and preparation techniques so as to improve analytical sensitivity of the assay. PMID:16825509

Jordan, Jeanne A.; Durso, Mary Beth; Butchko, Allyson R.; Jones, Judith G.; Brozanski, Beverly S.

2006-01-01

46

Association of Reticular Pseudodrusen and Early Onset Drusen  

PubMed Central

Purpose. To report an association between reticular pseudodrusen, located above the retinal pigment epithelium (RPE), and Early Onset Drusen (EOD) as described using Spectral-Domain Optical Coherence Tomography (SD-OCT). Methods. Eight patients (16 eyes) with EOD were examined. EOD were classified into three entities called Large Colloid Drusen (LCD), Malattia Leventinese (ML), and Cuticular Drusen (CD). Best-corrected visual acuity, fundus examination, color fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and SD-OCT were performed in all study patients. Results. Four patients had LCD, 2 had ML, and 2 had CD. Reticular pseudodrusen were observed with SD-OCT in all study patients; all these patients had hyperreflective lesions above and below the RPE. Conclusion. Early Onset Drusen appear to be associated with reticular pseudodrusen. SD-OCT is helpful in distinguishing the location of the deposits that are above and below the RPE in EOD. Further studies are needed to understand the role of reticular pseudodrusen in the pathophysiology of EOD. PMID:24563787

De Bats, Flore; Wolff, Benjamin; Mauget-Faysse, Martine; Meunier, Isabelle; Denis, Philippe; Kodjikian, Laurent

2013-01-01

47

Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues  

PubMed Central

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

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

2013-01-01

48

Genetics of early onset bipolar affective disorder: Are we making progress?  

Microsoft Academic Search

Though considerable progress has been made in understanding the molecular genetics of bipolar affective dis order, few studies\\u000a are currently focusing on the genetics of prepubertal or early adolescent onset illness. A variety of studies of the phenomenology,\\u000a imaging and comorbidity of early onset bipolarity find significant differences from late onset illness. These studies raise\\u000a the notion that early onset

Richard D. Todd

2002-01-01

49

Early and late onset depression in old age: different aetiologies, same phenomenology  

Microsoft Academic Search

Background: Phenomenological differences between older patients with early onset (EO; onset of first major depressive episode before 60 years) and late onset (LO) depression have been inconsistent but, if real, may reflect differences in aetiology. We aimed to compare aetiological factors, phenomenology and cognitive function in older patients with depression by age of onset. Methods: Subjects were all patients ?60

Henry Brodaty; Georgina Luscombe; Gordon Parker; Kay Wilhelm; Ian Hickie; Marie-Paule Austin; Philip Mitchell

2001-01-01

50

Cognitive Function in Early Onset Schizophrenia: A Selective Review  

PubMed Central

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

Frangou, Sophia

2009-01-01

51

Living With Her Genes Early Onset Familial Alzheimer's Disease  

NSDL National Science Digital Library

When a 30-year-old genetic counselor learns that her 38-year-old sister has developed early onset familial Alzheimer’s disease (EOFAD), a dominantly inherited disorder that led to their father's death at age 42, she struggles with whether to undergo genetic testing and whether to have children. This interrupted case study examines the impact of genetic testing on people and their families when there is no treatment or cure for a disease. It covers principles of Mendelian inheritance as well as genetic and reproductive technologies ,such as gene tests, pre-implantation genetic diagnosis, and in vitro fertilization. It can be used in introductory biology courses for both majors and non-majors or adapted for more advanced courses in genetics and molecular biology.

Gildensoph, Lynne H.; Stanford, Alice M.; Wygal, Deborah D.

2008-01-01

52

C-Terminal Titin Deletions Cause a Novel Early-Onset Myopathy with Fatal  

E-print Network

C-Terminal Titin Deletions Cause a Novel Early-Onset Myopathy with Fatal Cardiomyopathy Virginie and childhood-onset fatal dilated cardiomyopathy. Skeletal muscle biopsies showed minicores, centrally located

Campbell, Kevin P.

53

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

Microsoft Academic Search

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 mech- anisms 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

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

2010-01-01

54

A Longitudinal Transactional Risk Model for Early Eating Disorder Onset  

PubMed Central

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

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

2014-01-01

55

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

ERIC Educational Resources Information Center

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…

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

56

Early onset Alzheimer's disease is associated with a distinct neuropsychological profile.  

PubMed

Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains. PMID:22366769

Smits, Lieke L; Pijnenburg, Yolande A L; Koedam, Esther L G E; van der Vlies, Annelies E; Reuling, Ilona E W; Koene, Teddy; Teunissen, Charlotte E; Scheltens, Philip; van der Flier, Wiesje M

2012-01-01

57

Early and late onset bipolar disorders: two different forms of manic-depressive illness?  

Microsoft Academic Search

Background: Conflicting results in genetic studies of bipolar disorders may be due to the clinical and genetic heterogeneity of the disease. Age at onset of bipolar disorders may be a key indicator for identifying more homogeneous clinical subtypes. We tested whether early onset and late onset bipolar illness represent two different forms of bipolar illness in terms of clinical features,

Franck Schürhoff; Frank Bellivier; Roland Jouvent; Marie-Christine Mouren-Siméoni; Manuel Bouvard; Jean-François Allilaire; Marion Leboyer

2000-01-01

58

Prediction of Early-Onset Esotropia From Components of the Infantile Squint Syndrome  

Microsoft Academic Search

Purpose. To examine the association between components of the infantile squint syndrome (ISS) and age of onset of esotropia among subjects in the Cooperative Amblyopia Classification Study (CACS). Methods. Fifty subjects were classified retrospectively as having early-onset esotropia (EOE) and 150 subjects were classified as having late-onset esotropia (LOE), depending on whether symptoms of (or treatment for) strabismus occurred before

Clifton M. Schor; Robert E. Fusaro; Nance Wilson; Suzanne P. McKee

59

Cytomegalovirus infection in association with early onset pre-eclampsia  

PubMed Central

This case describes a woman who presented with raised ?-fetoprotein (AFP) on second trimester screening, and developed early onset fetal growth restriction (FGR) and severe pre-eclampsia (PET) before 24 weeks' gestation requiring magnesium sulphate and intravenous antihypertensives. Ultrasonography revealed a structurally normal fetus with estimated weight <3rd centile, abnormal uterine artery Dopplers and deteriorating fetal arterial Dopplers over the following 2 weeks. The pregnancy ended in fetal death before a viable weight was reached. Postmortem examination revealed a growth restricted fetus (birth weight <0.4th centile) and chronic villitis secondary to placental cytomegalovirus (CMV) infection. CMV has previously been associated with PET and FGR. This case highlights its potential role in the pathogenesis of placental failure and has relevance for counselling and management for future pregnancies. Furthermore, raised AFP may represent ongoing placental damage and offers potential for future therapeutic measures—for example, antivirals or immunisations to alter the natural history and prognosis of placental infection. PMID:22789552

Higgins, L; Vause, S; Tower, C

2010-01-01

60

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

SciTech Connect

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.

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

1995-12-18

61

Family Functioning and Early Onset of Sexual Intercourse in Latino Adolescents  

ERIC Educational Resources Information Center

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,…

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

2005-01-01

62

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

ERIC Educational Resources Information Center

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…

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

2010-01-01

63

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

ERIC Educational Resources Information Center

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…

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

2009-01-01

64

Early- versus late-onset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients.  

PubMed

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

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

2014-03-01

65

Aggressive and acute periodontal diseases.  

PubMed

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

Albandar, Jasim M

2014-06-01

66

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

PubMed Central

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

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; Gu?bjartsson, Daniel; Hansel, Nadia N.; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikainen, 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.; Hallfors, Jenni; Han, Shizhong; Hartmann, Annette M.; Hayward, Caroline; Heikkila, 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; Styrkarsdottir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeboller, Heike; Boerwinkle, Eric; Boomsma, Dorret I.; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J.; Francks, Clyde; Gejman, Pablo V.; Gelernter, Joel; Grabe, Hans Jorgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kahonen, Mika; Kendler, Kenneth S.; Lehtimaki, Terho; Levinson, Douglas F.; Marazita, Mary L.; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D.; Murray, Jeffrey C.; Nothen, 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; Volzke, 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

67

Am J Med Genet B Neuropsychiatr Genet . Author manuscript European collaborative study of early-onset bipolar disorder: Evidence for  

E-print Network

of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset.mathieu@inserm.fr > # Mathieu F and Dizier MH contributed to this work equally. Abstract Bipolar disorder has a genetic between early onset bipolar type I (cut-off of 22 years) and other types of the disorder (later onset

Paris-Sud XI, Université de

68

Social Anxiety and Onset of Drinking in Early Adolescence  

ERIC Educational Resources Information Center

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…

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

2013-01-01

69

Early onset Huntington disease: a neuronal degeneration syndrome  

Microsoft Academic Search

Huntington disease (HD) is an autosomal dominant, lethal neurodegenerative disorder of the central nervous system, caused by an uncontrolled expansion of a CAG dynamic mutation in the coding region of the IT15gene. Although a majority of patients have a midlife onset of the disease, in a small number of patients the disease manifests before 20 years of age. In adults,

Sara Seneca; Dominique Fagnart; Kathelijn Keymolen; Willy Lissens; Daniele Hasaerts; Sara Debulpaep; Brigitte Desprechins; Inge Liebaers; Linda De Meirleir

2004-01-01

70

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

ERIC Educational Resources Information Center

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…

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

71

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

ERIC Educational Resources Information Center

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…

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

2008-01-01

72

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

PubMed Central

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

Vyas, Nora S.; Gogtay, Nitin

2012-01-01

73

Correlates of alcohol abuse/dependence in early-onset alcohol-using women.  

PubMed

Early-onset alcohol use is associated with increased vulnerability to subsequent alcohol abuse and dependence. However, not all early-onset alcohol users develop alcohol use disorders (AUDs). Using a sample of young women from the United States, we identify correlates that contribute to a greater likelihood of AUDs in early-onset alcohol users. Using interview and questionnaire data on participants of the Missouri Adolescent Female Twin Study (MOAFTS), we examine whether measures from domains including sociodemographic, pubertal development, religiosity, educational achievement, adverse life events, internalizing disorders, externalizing disorders, and family history and discipline were associated with development of AUDs in 1,158 women who had their first drink of alcohol prior to age 16. Early-onset drinkers were 3.6 times more likely to meet criteria for AUDs than later onset drinkers. While univariate analyses revealed that a host of correlates were associated with likelihood of AUDs in early-onset drinkers, multivariate analyses suggested that, even after accounting for a particularly early age of onset of drinking, those with a history of physical abuse, cotwin alcohol problems, conduct disorder, regular smoking, older peers, and peer substance use were considerably more likely to meet criteria for AUDs than early-onset drinkers without a lifetime history of these correlates. The progression from first drink to AUDs is complex, and while early age at first drink is a potent risk factor, other aspects of psychopathology, family history, conduct problems, and peer affiliations can exacerbate or alleviate the risk of AUDs in these young female drinkers. PMID:21838841

Jenkins, Mitchell B; Agrawal, Arpana; Lynskey, Michael T; Nelson, Elliot C; Madden, Pamela A F; Bucholz, Kathleen K; Heath, Andrew C

2011-01-01

74

Correlates of alcohol abuse/dependence in early-onset alcohol-using women  

PubMed Central

Background Early-onset alcohol use is associated with increased vulnerability to subsequent alcohol abuse and dependence. However, not all early-onset alcohol users develop alcohol use disorders (AUDs). Using a sample of young women from the U.S., we identify correlates that contribute to a greater likelihood of AUDs in early-onset alcohol users. Methods Using interview and questionnaire data on participants of the Missouri Adolescent Female Twin Study (MOAFTS), we examine whether measures from domains including socio-demographic, pubertal development, religiosity, educational achievement, adverse life events, internalizing disorders, externalizing disorders and family history and discipline were associated with development of AUDs in 1,158 women who had their first drink of alcohol prior to age 16. Results Early-onset drinkers were 3.6 times more likely to meet criteria for AUDs than later onset drinkers. While univariate analyses revealed that a host of correlates were associated with likelihood of AUDs in early-onset drinkers, multivariate analyses suggested that, even after accounting for a particularly early age of onset of drinking, those with a history of physical abuse, co-twin alcohol problems, conduct disorder, regular smoking, older peers and peer substance use were considerably more likely to meet criteria for AUDs than early onset drinkers without a lifetime history of these correlates. Conclusion The progression from first drink to AUDs is complex, and while early age at first drink is a potent risk factor, other aspects of psychopathology, family history, conduct problems and peer affiliations can exacerbate or alleviate the risk of AUDs in these young female drinkers. PMID:21838841

Jenkins, Mitchell B.; Agrawal, Arpana; Lynskey, Michael T.; Nelson, Elliot C.; Madden, Pamela A. F.; Bucholz, Kathleen K.; Heath, Andrew C.

2012-01-01

75

Diagnosis and course of early-onset arthritis: results of a special early arthritis clinic compared to routine patient care  

Microsoft Academic Search

SUMMARY Objective. Early arthritis patients referred to an Early Arthritis Clinic (EAC ) (n= 233) were compared to 241 patients from the routine out-patient clinic with respect to lag time between the onset of symptoms and the visit to the rheumatologist, clinical presentation and the consistency of the diagnosis after 1 yr. Results. The reduction in median lag time for

I. E. VAN DER HORST-BRUINSMA; I. SPEYER; H. VISSER; F. C. BREEDVELD; J. M. W. HAZES

1998-01-01

76

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

ERIC Educational Resources Information Center

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…

Olusanya, Bolajoko O.

2011-01-01

77

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

ERIC Educational Resources Information Center

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…

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

2009-01-01

78

Early-onset severe retinal dystrophy as the initial presentation of IFT140-related skeletal ciliopathy.  

PubMed

Early-onset severe retinal dystrophy can be isolated (Leber congenital amaurosis) or the first sign of an underlying systemic ciliopathy, such as Bardet-Biedl syndrome. Early recognition of those children with underlying systemic ciliopathy minimizes morbidity and mortality from later extraocular manifestations, the most common of which is renal disease. We report 2 unrelated children who presented with early-onset severe retinal dystrophy in the context of hypotonia, developmental delay, and a noticeably happy demeanor. Genetic analysis revealed both to harbor recessive mutations in IFT140, a cilium gene recently associated with the skeletal ciliopathy conorenal syndrome. PMID:24698627

Khan, Arif O; Bolz, Hanno J; Bergmann, Carsten

2014-04-01

79

Types of Periodontal Disease  

MedlinePLUS

Types of Periodontal Disease Gingivitis Chronic Periodontitis Aggressive Periodontitis Periodontitis Caused by Conditions of the Body Necrotizing Periodontal Diseases Periodontal disease can refer to any condition that affects the gums and ...

80

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

PubMed Central

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

Idris, Iskandar

2014-01-01

81

Early-Life Exposures and Early-Onset Uterine Leiomyomata in Black Women in the Sister Study  

PubMed Central

Background: Uterine leiomyomata (fibroids) are hormonally responsive tumors, but little is known about risk factors. Early-life exposures may influence uterine development and subsequent response to hormones in adulthood. An earlier analysis of non-Hispanic white women who participated in the Sister Study found associations between several early-life factors and early-onset fibroids. Objectives: We evaluated associations of early-life and childhood exposures with early-onset fibroids among black women and compared the results with those found among white women. Methods: We analyzed baseline data from 3,534 black women, 35–59 years of age, in the Sister Study (a nationwide cohort of women who had a sister diagnosed with breast cancer) who self-reported information on early-life and childhood exposures. Early-onset fibroids were assessed based on self-report of a physician diagnosis of fibroids by the age of 30 years (n = 561). We estimated risk ratios (RR) and 95% confidence intervals (CI) from log-binomial regression models. Results: Factors most strongly associated with early-onset fibroids were in utero diethylstilbestrol (DES; RR = 2.02; 95% CI: 1.28, 3.18), maternal prepregnancy diabetes or gestational diabetes (RR = 1.54; 95% CI: 0.95, 2.49), and monozygotic multiple birth (RR = 1.94; 95% CI: 1.26, 2.99). We also found positive associations with having been taller or thinner than peers at the age of 10 years and with early-life factors that included being the firstborn child of a teenage mother, maternal hypertensive disorder, preterm birth, and having been fed soy formula. Conclusions: With the exception of monozygotic multiple birth and maternal hypertensive disorder, early-life risk factors for early-onset fibroids for black women were similar to those found for white women. However, in contrast to whites, childhood height and weight, but not low socioeconomic status indicators, were associated with early-onset fibroids in blacks. The general consistency of early-life findings for black and white women supports a possible role of early-life factors in fibroid development. PMID:22049383

Baird, Donna D.; DeRoo, Lisa A.; Sandler, Dale P.

2011-01-01

82

Working memory and FDG–PET dissociate early and late onset Alzheimer disease patients  

Microsoft Academic Search

The aims of this study were to determine the influence of the onset of Alzheimer’s disease (AD) on 1) memory and cerebral glucose metabolism, 2) the relationships between cognitive performance and cerebral glucose metabolism. Brain metabolism was measured by 18FDG–PET in 12 early onset AD patients (age 65), with comparable mean MMSE scores. Working memory, semantic memory and episodic memory

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

2005-01-01

83

Autosomal recessive early-onset parkinsonism with diurnal fluctuation: clinicopathologic characteristics and molecular genetic identification  

Microsoft Academic Search

Autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF, syn. autosomal recessive juvenile parkinsonism, PARK2) is one of the hereditary parkinsonian syndromes. We examined subjects consisting of 43 patients from 22 families with AR-EPDF. The clinical features were relatively homogeneous, including the average age at onset of 26.1 years, beginning with dystonic gait disturbance, diurnal fluctuation of the symptoms (sleep benefit)

Yasuhiro Yamamura; Nobutaka Hattori; Hiroto Matsumine; Shigeki Kuzuhara; Yoshikuni Mizuno

2000-01-01

84

Early onset epilepsy is associated with increased mortality: a population-based study  

PubMed Central

SUMMARY We examined mortality in early onset (age <12 months) epilepsy in a population-based group of children. Children with early onset epilepsy were significantly more likely to die (case fatality, CF 8/60 versus 8/407, p<0.001; mortality rate, MR 14.5/1000 versus 2/1000 person years; standardized mortality ratio, SMR 22.25 versus 5.67). Mortality was greater in children with malignant neonatal (age <1 month) epilepsy (CF 4/12 versus 12/450, p<0.001; MR 54/1000 person years versus 2.7/1000 person year; SMR 46.55 versus 7.22). Given that only 1/8 early onset epilepsy deaths was seizure-related, mortality appears to be more affected by underlying etiology. PMID:23582606

Moseley, Brian D.; Wirrell, Elaine C.; Wong-Kisiel, Lily C.; Nickels, Katherine

2013-01-01

85

[The importance of the bitewing image in the early recognition of caries and periodontal diseases in children and adolescents].  

PubMed

In estimating of bite-wing radiographies of lateral teeth at diabetic children in different age groups and developmental dental periods carious diagnostic effect is represented in comparison with clinical observations. Calculating the caries indices for permanent teeth no statistical significant differences appear between clinical and clinical radiographical dates. A comparison of statements at the approximal surfaces shows in all age groups an equal frequency only in radiographic visible destructions of enamel. After the 14th age the number of destructions in the dentin is increasing. The essential modifications at the periodontal bone are in a direct connection with caries and restorations at the corresponding approximal surfaces. The bite-wing radiographic remains his value in recognizing the period of caries activity and should be used in diagnostic of early lesions at patients of risk. PMID:2150460

Poppe, B; Faustmann, U; Saffan, G; Dietrich, F

1990-01-01

86

Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis.  

PubMed

Dysbindin-1 is a relatively ubiquitous protein in the brain which is involved in the modulation of synaptic homeostasis. The dysbindin-1 gene (DTNBP1) has been associated with schizophrenia and bipolar disorder diagnoses. However, its contribution to the severity of the clinical and neurocognitive expression of these disorders remains controversial. We aimed to explore the association between DTNBP1 and the phenotypes which are more directly linked with the underlying biology, such as age at onset and neurocognitive impairment. The present family sample comprised 894 Caucasian individuals: 268 patients affected by functional psychosis [58% with illness onset before 18 years, mean age at onset (SD): 14.71 (2.10)], 483 parents and 143 siblings. Ten DTNBP1 single nucleotide polymorphisms were genotyped in all individuals and their transmission disequilibrium was tested in relation to: (i) the risk for psychosis; (ii) patients' age at onset; and (iii) familial neurocognitive performance (including IQ estimation and executive functioning). In early-onset families a 5-marker haplotype encompassing exons 2-4 and the surrounding introns was significantly over-transmitted to cases, while in adult-onset families two haplotypes corresponding to the region between introns 4 and 7 were over-transmitted to cases. Estimated IQ was associated with the rs760666 marker in the whole sample, whereas a significant association between executive functioning and the rs2619522 marker appeared in early-onset families. Our findings confirm the role of the dysbindin-1 gene in the risk for functional psychosis and show a differential haplotypic risk pattern in families with early as opposed to adult onset in the affected offspring. PMID:21305691

Fatjó-Vilas, Mar; Papiol, Sergi; Estrada, Gemma; Bombín, Igor; Peralta, Victor; Rosa, Araceli; Parellada, Mara; Miret, Salvador; Martín, María; Lázaro, Luisa; Campanera, Sílvia; Muñoz, Ma José; Lera-Miguel, Sara; Arias, Bárbara; Navarro, Ma Eulalia; Castro-Fornieles, Josefina; Cuesta, Manuel J; Arango, Celso; Fañanás, Lourdes

2011-04-01

87

Simultaneous Copy Number Losses within Multiple Subtelomeric Regions in Early-Onset Type2 Diabetes Mellitus  

PubMed Central

Genetic factors play very important roles in the onset and progression of type 2 diabetes mellitus (T2DM). However, the genetic factors correlating with T2DM onset have not as yet been fully clarified. We previously found that copy number losses in the subtelomeric region on chromosome 4p16.3 were detected in early-onset Japanese T2DM patients (onset age <35 years) at a high frequency. Herein, we additionally found two novel copy number losses within the subtelomeric regions on chromosomes 16q24.2-3 and 22q13.31-33, which have significant associations with early-onset Japanese T2DM. The associations were statistically significant by Fisher's exact tests with P values of 5.19×10?3 and 1.81×10?3 and odds ratios of 5.7 and 4.4 for 16q24.2-3 and 22q13.31-33, respectively. Furthermore, copy number variation (CNV) analysis of the whole genome using the CNV BeadChip system verified simultaneous copy number losses in all three subtelomeric regions in 11 of our 100 T2DM subjects, while none of 100 non-diabetic controls showed the copy number losses in all three regions. Our results suggest that the mechanism underlying induction of CNVs is involved in the pathogenesis of early-onset T2DM. Thus, copy number losses within multiple subtelomeric regions are strongly associated with early-onset T2DM and examination of simultaneous CNVs in these three regions may lead to the development of an accurate and selective procedure for detecting genetic susceptibility to T2DM. PMID:24709989

Kodama, Shinjiro; Yamada, Tetsuya; Imai, Junta; Sawada, Shojiro; Takahashi, Kei; Tsukita, Sohei; Kaneko, Keizo; Uno, Kenji; Ishigaki, Yasushi; Oka, Yoshitomo; Katagiri, Hideki

2014-01-01

88

Surgical treatment of early onset scoliosis in neurofibromatosis.  

PubMed

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

Greggi, Tiziana; Martikos, Konstantinos

2012-01-01

89

Cardiovascular and cognitive fitness at age 18 and risk of early-onset dementia.  

PubMed

Patients with early-onset dementia are a significantly under-recognized subgroup of patients with an increasing prevalence. Epidemiological studies are limited and studies of modifiable risk factors, such as physical fitness, are lacking. We aimed to investigate the associations between cardiovascular fitness individually and in combination with cognitive performance at age 18 and risk of early-onset dementia and mild cognitive impairment later in life. We performed a population-based cohort study of over 1.1 million Swedish, 18-year-old, male conscripts, who underwent conscription exams between 1968 and 2005. These males were then followed for up to 42 years. Objective data on cardiovascular fitness and cognitive performance were collected during conscription exams and were subsequently linked with hospital registries to calculate later risk of early-onset dementia and mild cognitive impairment using Cox proportional hazards models controlling for several confounders. The scores from the exams were divided into tertiles (low, medium, high) for the analyses. The mean follow-up time for the analyses was 25.7 years (standard deviation: 9.3) and the median was 27 years. In total, 30 195 315 person-years of follow-up were included in the study. In fully adjusted models, both low cardiovascular fitness and cognitive performance (compared to high) at age 18 were associated with increased risk for future early-onset dementia (cardiovascular fitness, n = 662 events: hazard ratio 2.49, 95%, confidence interval 1.87-3.32; cognitive performance, n = 657 events: hazard ratio 4.11, 95%, confidence interval 3.19-5.29) and mild cognitive impairment (cardiovascular fitness, n = 213 events: hazard ratio 3.57, 95%, confidence interval 2.23-5.74; cognitive performance, n = 212 events: hazard ratio 3.23, 95%, confidence interval 2.12-4.95). Poor performance on both cardiovascular fitness and cognitive tests was associated with a >7-fold (hazard ratio 7.34, 95%, confidence interval 5.08-10.58) and a >8-fold (hazard ratio 8.44, 95%, confidence interval 4.64-15.37) increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively. In conclusion, lower cardiovascular fitness and cognitive performance in early adulthood were associated with an increased risk of early-onset dementia and mild cognitive impairment later in life, and the greatest risks were observed for individuals with a combination of low cardiovascular fitness and low cognitive performance. PMID:24604561

Nyberg, Jenny; Åberg, Maria A I; Schiöler, Linus; Nilsson, Michael; Wallin, Anders; Torén, Kjell; Kuhn, H Georg

2014-05-01

90

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

SciTech Connect

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.

Brice, A.; Tardieu, S.; Campion, D.; Martinez, M. [and others

1995-04-24

91

A Functional Mutation in the Terminal Exon of Elastin in Severe, Early-Onset Chronic Obstructive  

E-print Network

to the pathogenesis of COPD. Keywords: chronic obstructive pulmonary disease; elastin; extracellular matrix; genetics; mutation Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary

Mecham, Robert

92

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

Microsoft Academic Search

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 29 older heroin users. Life course analysis focused on

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

2008-01-01

93

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

ERIC Educational Resources Information Center

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…

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

2013-01-01

94

Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease  

E-print Network

Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease J. Steven, and ¶Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037 Contributed by Floyd E, and behavioral levels in the Tg2576 mouse model of AD. Our data show that decreased dendritic spine density

Newman, Eric A.

95

Accelerated in vitro fibril formation by a mutant ?-synuclein linked to early-onset Parkinson disease  

Microsoft Academic Search

Two mutations in the gene encoding ?-synuclein have been linked to early-onset Parkinson's disease (PD). ?-Synuclein is a component of Lewy bodies, the fibrous cytoplasmic inclusions characteristic of nigral dopaminergic neurons in the PD brain. This connection between genetics and pathology suggests that the ?-synuclein mutations may promote PD pathogenesis by accelerating Lewy body formation. To test this, we studied

Kelly A. Conway; James D. Harper; Peter T. Lansbury

1998-01-01

96

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

ERIC Educational Resources Information Center

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…

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

2011-01-01

97

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

ERIC Educational Resources Information Center

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,…

Unsworth, Sharon

2013-01-01

98

Increased Postnatal Inflammation in Mechanically Ventilated Preterm Infants Born to Mothers with Early-Onset Preeclampsia  

Microsoft Academic Search

Background: Preeclampsia and preterm labor often underlie preterm birth, and are associated with maternal inflammation. In preterm infants, respiratory distress syndrome (RDS) and mechanical ventilation are associated with systemic inflammation. Objective: We aimed to study whether early-onset preeclampsia or preterm labor modulate the systemic inflammation affecting preterm infants with RDS. Methods: We recruited mechanically ventilated infants with gestational ages <32

Riikka Turunen; Sture Andersson; Hannele Laivuori; Eero Kajantie; Sanna Siitonen; Heikki Repo; Irmeli Nupponen

2011-01-01

99

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

ERIC Educational Resources Information Center

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.…

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

100

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

ERIC Educational Resources Information Center

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…

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

101

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

ERIC Educational Resources Information Center

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…

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

2008-01-01

102

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

ERIC Educational Resources Information Center

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…

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

2011-01-01

103

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

ERIC Educational Resources Information Center

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…

Walls, Melissa L.; Whitbeck, Les B.

2011-01-01

104

Etiology of early age onset substance use disorder: A maturational perspective  

Microsoft Academic Search

The etiology of early age onset substance use disorder (SUD), an Axis I psychiatric illness, is examined from the perspective of the multifactorial model of complex disorders. Beginning at conception, genetic and environment interactions produce a sequence of biobehavioral phenotypes during development which bias the ontogenetic pathway toward SUD. One pathway to SUD is theorized to emanate from a deviation

RALPH TARTER; MICHAEL VANYUKOV; PETER GIANCOLA; MICHAEL DAWES; TIMOTHY BLACKSON; ADA MEZZICH; DUNCAN B. CLARK

1999-01-01

105

Visual search in long-term cannabis users with early age of onset  

Microsoft Academic Search

The present research tested the hypothesis that there is a specific deficit in visual scanning in chronic users of cannabis with early onset of their drug consumption (age 14 to 16). 17 users and 20 control participants were asked to search for targets on a 5 × 5 stimulus array while their eye movements were monitored. Cannabis users showed less

Lynn Huestegge; Ralph Radach; Hans-Juergen Kunert; Dieter Heller

2002-01-01

106

Early onset ageing and service preparation in people with intellectual disabilities: Institutional managers’ perspective  

Microsoft Academic Search

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 population. We used purposive sampling to recruit 54 institutional managers who care

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

2011-01-01

107

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

SciTech Connect

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.

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

1995-06-19

108

Novel presenilin mutations within Moroccan patients with Early-Onset Alzheimer's Disease.  

PubMed

Alzheimer's disease (AD) is a progressive brain disorder that causes gradual and irreversible loss of higher brain functions and is the most common cause of dementia in the elderly, as assessed by autopsy and clinical series. Furthermore, it has an annual incidence of approximately 3% in the 65-74-year-old age group. This incidence rate doubles with every increment of 5 years above the age of 65. In Morocco, AD affects almost 30,000 individuals and this number will possibly increase to 75,000 by 2020 (projections of the World Health Organization (WHO)). Genetically, AD is caused by a mutation in one of at least 3 genes: presenilin 1 (PS1), presenilin 2 (PS2) and the amyloid precursor protein (APP). Most cases are late onset and apparently sporadic, most likely as a result of a combination of environmental and non-dominant genetic factors. In Morocco, the genes predisposing individuals to AD and predicting disease incidence remain elusive. The purpose of the present study was to evaluate the genetic contribution of mutations in PS1 and PS2 genes to familial early-onset AD cases and sporadic late-onset AD cases. Seventeen sporadic late-onset AD cases and eight familial early-onset AD cases were seen at the memory clinic of the University of Casablanca Neurology Department. These patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Direct sequencing of each exon in PS1 and PS2 genes was performed on genomic DNA of AD patients. Further, we identified 1 novel frameshift mutation in the PS1 gene and 2 novel frameshift mutations in the PS2 gene. Our mutational analysis reports a correlation between clinical symptoms and genetic factors in our cases of Early-Onset Alzheimer's Disease (EOAD). These putative mutations cosegregate with affected family members suggesting a direct mutagenic effect. PMID:24704512

El Kadmiri, N; Zaid, N; Zaid, Y; Tadevosyan, A; Hachem, A; Dubé, M-P; Hamzi, K; El Moutawakil, B; Slassi, I; Nadifi, S

2014-06-01

109

Some aspects of an early summer monsoon onset over Andaman Sea and further progress towards the Indian mainland  

NASA Astrophysics Data System (ADS)

This work addresses the mechanisms that leads to an early onset of monsoon over Andaman Sea but advances further rapidly (slowly) to the Indian mainland resulting in the early (delayed) onset over Kerala. The upper tropospheric temperature, production of kinetic energy (KE) and outgoing long wave radiation (OLR) from the month of May till onset over Kerala are analysed for two delayed onset years (1997, 1995) and two early onset years (2004, 1990). It is observed that the maximum temperature over Tibetan plateau (TP), an increase in the production of KE and strong equatorial convection in early May, is associated with early onset over Andaman Sea. However, when there is a lull in advance of monsoon after the early onset over Andaman Sea, shifting of the warm region south of TP, weak production of KE in the lower troposphere and convective region shifting to Western Pacific resulted in the delayed onset over Kerala in 1997 and 1995. During the early onset years viz. 2004 and 1990, the warm region moving westwards, high production of KE extending to mid troposphere and deep convection moving westwards in the north Indian Ocean (10-15°N) is noticed.

Nair, Sathy; Mahajan, P. N.

2010-11-01

110

Association between early-onset alcoholism and the dopamine D2 receptor gene.  

PubMed

We examined the allelic association between the dopamine D2 receptor (DRD2) gene and alcoholism in 100 biologically unrelated Japanese alcoholics and 93 unrelated controls. Genomic DNA was prepared from peripheral white blood cells using the phenol-chloroform method. A 310-bp region surrounding the TaqA site at the DRD2 locus was amplified by polymerase chain reaction (PCR), and the PCR product was incubated with TaqI. The A1 allele remained intact while the A2 allele was cut. The frequency of the A1/A1 genotype and the frequency of the A1 allele were higher in early-onset alcoholics than in controls, P < 0.05 and P < 0.01, respectively. Moreover, the frequency of the A1/A1 genotype and the frequency of the A1 allele were higher in early-onset alcoholics with family histories of alcohol dependence than in controls, P < 0.01 and P < 0.01, respectively. The results indicate that the DRD2 gene is associated with susceptibility to early-onset alcoholism, and that each additional A1 allele shifts onset of alcoholism to an earlier age. PMID:9129720

Kono, Y; Yoneda, H; Sakai, T; Nonomura, Y; Inayama, Y; Koh, J; Sakai, J; Inada, Y; Imamichi, H; Asaba, H

1997-04-18

111

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

PubMed

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

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

112

Parkin (PARK 2) Mutations Are Rare in Czech Patients with Early-Onset Parkinson's Disease  

PubMed Central

Objective The aim of the study is to determine the frequency of parkin allelic variants in Czech early-onset Parkinson's disease patients and healthy controls. Methods A total of 70 early-onset Parkinson's disease patients (age at onset ?40 years) and 75 controls were screened for the sequence variants and exon rearrangements in the parkin gene. Results Parkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous deletion of the exon 4. No mutations were obtained in control subjects. A novel sequence variant p.V380I (c.1138G>A) was identified in one control. Non-pathogenic polymorphisms p.S167N and p.D394N were seen in similar percentage in patients and controls, polymorphism p.V380L was almost twice as frequent in controls as in patients. Conclusions Our study contributes to the growing body of evidence on the low frequency of the parkin mutations in the early-onset Parkinson's disease suggesting the potential role of other genes in the pathogenesis of the disease. PMID:25238391

Fiala, Ondrej; Zahorakova, Daniela; Pospisilova, Lenka; Kucerova, Jana; Matejckova, Milada; Martasek, Pavel; Roth, Jan; Ruzicka, Evzen

2014-01-01

113

Usefulness of biomarkers in the diagnosis and prognosis of early-onset cognitive impairment.  

PubMed

Early-onset cognitive impairment diagnosis is often challenging due to the overlapping symptoms between the different degenerative and non-degenerative conditions. We aimed to evaluate the usefulness of cerebrospinal fluid (CSF) biomarkers in early-onset cognitive impairment differential diagnosis, to assess their contribution to the diagnosis of Alzheimer's disease (AD) based on the new National Institute of Aging-Alzheimer's Association (NIA-AA) workgroup's recommendations and their capacity to predict subsequent decline in early-onset mild cognitive impairment (MCI). 37 controls and 120 patients (clinical onset <65 years) with diagnosis based on criteria available in 2009 (51 MCI, 42 AD, 10 frontotemporal dementia (FTD), 3 posterior cortical atrophy, and 14 primary progressive aphasia (PPA)) were included. In addition, all subjects were also reclassified according to the revised criteria for MCI, AD, FTD, and PPA, excluding CSF data. We assessed the impact of adding the CSF data to the subject categorization according to the NIA-AA criteria. After inclusion of CSF results, 90% of amnestic and 82% of the non-amnestic AD presentation could be categorized as "high probability", while 3% of AD patients fit into the category "dementia probably not due to AD". All the 24 MCI patients who progressed to AD dementia and only 1/27 stable MCI presented pathological CSF at baseline. Only 4% of the FTD clinical diagnosis had pathological CSF levels. CSF biomarkers provide high diagnostic accuracy in a clinical context in differentiating AD, frontotemporal lobar degeneration, and controls in presenile subjects and can be used equally in amnestic and non-amnestic AD. Abnormal CSF-AD biomarker levels predict subsequent progression to AD dementia in subjects with early-onset MCI. PMID:24577466

Balasa, Mircea; Sánchez-Valle, Raquel; Antonell, Anna; Bosch, Beatriz; Olives, Jaume; Rami, Lorena; Castellví, Magda; Molinuevo, José Luis; Lladó, Albert

2014-01-01

114

A SNAP25 Promoter Variant is Associated with Early-Onset Bipolar Disorder and a High Expression Level in Brain  

E-print Network

1 A SNAP25 Promoter Variant is Associated with Early-Onset Bipolar Disorder and a High Expression;2 Keywords: SNAP-25, association study, bipolar affective disorder, attention-deficit hyperactivity disorder, expression study Running Title: SNAP25 Gene Variations in Early-Onset Bipolar Disorder inserm-00499665

Paris-Sud XI, Université de

115

Onset to First Alcohol Use in Early Adolescence: A Network Diffusion Model  

PubMed Central

A novel version of Snijders’s stochastic actor-based modeling (SABM) framework is applied to model the diffusion of first alcohol use through middle school-wide longitudinal networks of early adolescents, aged approximately 11–14 years. Models couple a standard SABM for friendship network evolution with a proportional hazard model for first alcohol use. Meta-analysis of individual models for 12 schools found significant effects for friendship selection based on the same alcohol use status, and for an increased rate of onset to first use based on exposure to already-onset peers. Onset rate was greater at higher grades and among participants who spent more unsupervised time with friends. Neither selection nor exposure effects interacted with grade, adult supervision, or gender. PMID:24039379

Light, John M.; Greenan, Charlotte C.; Rusby, Julie C.; Nies, Kimberley M.; Snijders, Tom A.B.

2013-01-01

116

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

PubMed

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

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

1993-07-01

117

Research protocol of the NeedYD-study (Needs in Young onset Dementia): a prospective cohort study on the needs and course of early onset dementia  

PubMed Central

Background Early onset dementia has serious consequences for patients and their family members. Although there has been growing attention for this patient group, health care services are still mainly targeted at the elderly. Specific knowledge of the needs of early onset dementia patients and their families is limited but necessary for the development of adequate health care services and specific guidelines. This research project is mainly targeted at delineating the course of early onset dementia, the functional characteristics and needs of early onset dementia patients and their caregivers, the risk factors for institutionalization and the interaction with the caring environment. Methods/Design The NeedYD-study (Needs in Young Onset Dementia) is a longitudinal observational study investigating early onset dementia patients and their caregivers (n = 217). Assessments are performed every six months over two years and consist of interviews and questionnaires with patients and caregivers. The main outcomes are (1) the needs of patients and caregivers, as measured by the Camberwell Assessment of Needs for the Elderly (CANE) and (2) neuropsychiatric symptoms, as measured by the NeuroPsychiatric Inventory (NPI). Qualitative analyses will be performed in order to obtain more in-depth information on the experiences of EOD patients and their family members. The results of this study will be compared with comparable data on late onset dementia from a historical cohort. Discussion The study protocol of the NeedYD-study is presented here. To our knowledge, this study is the first prospective cohort study in this research area. Although some limitations exist, these do not outweigh the strong points of this study design. PMID:20226041

2010-01-01

118

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

PubMed Central

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

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

2011-01-01

119

An Unusual Case of Early Onset Persistent Escherichia coli Septicemia Associated with Endocarditis  

PubMed Central

Escherichia coli infection is very common cause of early onset septicemia especially in very low-birth-weight newborns, but E. coli endocarditis has not been described in newborns. E. coli endocarditis, even in the adult population, is a rare and not well-characterized disease and is associated with high mortality. We report a very unusual presentation of persistent E. coli infection associated with endocarditis. PMID:24147246

Gupta, Sachin K.; Nanda, Vishakha; Malviya, Prashant; Jacobs, Norman; Naheed, Z.; Joseph, Tessy

2013-01-01

120

Homozygosity Mapping Reveals PDE6C Mutations in Patients with Early-Onset Cone Photoreceptor Disorders  

Microsoft Academic Search

Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (CD) and complete and incomplete achromatopsia (ACHM). The underlying disease mechanisms of autosomal recessive (ar)CD are largely unknown. Our aim was to identify causative genes for these disorders by genome-wide homozygosity mapping. We investigated 75 ACHM, 97 arCD, and 20 early-onset arCD probands and excluded the

Alberta A. H. J. Thiadens; Anneke I. den Hollander; Susanne Roosing; Sander B. Nabuurs; Renate C. Zekveld-Vroon; Rob W. J. Collin; Elfride De Baere; Robert K. Koenekoop; Mary J. van Schooneveld; Tim M. Strom; Janneke J. C. van Lith-Verhoeven; Andrew J. Lotery; Norka van Moll-Ramirez; Bart P. Leroy; L. Ingeborgh van den Born; Carel B. Hoyng; Frans P. M. Cremers; Caroline C. W. Klaver

2009-01-01

121

Recent advances in early-onset severe retinal degeneration: more than just basic research?  

Microsoft Academic Search

Successful treatment of early-onset severe retinal degeneration (EOSRD) in an animal model of the disease has provided the first proof-of-principle for retinal gene therapy of higher mammals. Currently, large sets of DNA samples are screened to identify patients with Leber's congenital amaurosis (LCA) carrying mutations in RPE65 as possible candidates for gene therapy trials. Research into EOSRD and LCA aims

Markus N. Preising; Steffen Heegaard

2004-01-01

122

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

Microsoft Academic Search

Early-onset bipolar disorder is an impairing condition that is strongly associated with genetic inheritance. Neurocognitive\\u000a deficits are core traits of this disorder which seem to be present in both young and adult forms. Deficits in verbal memory\\u000a and attention are persistent within euthymic phases in bipolar adults, adolescents, and children. In younger samples, including\\u000a type I or II and not

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

2011-01-01

123

Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups  

Microsoft Academic Search

The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis\\u000a (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups\\u000a of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed\\u000a on the following cognitive domains: attention,

Arantzazu Zabala; Marta Rapado; Celso Arango; Olalla Robles; Elena de la Serna; Cristina González; José Manuel Rodríguez-Sánchez; Patricia Andrés; María Mayoral; Igor Bombín

2010-01-01

124

Clinical Significance of Early-Onset Hyperuricemia in Renal Transplant Recipients  

Microsoft Academic Search

Background\\/Aims: It is undetermined whether the effect of uric acid (UA) on graft outcome is independent of graft dysfunction. This study was designed to explore whether early-onset hyperuricemia has clinical significance regardless of graft function. Methods: This study was conducted based on a retrospective chart review. We calculated time-averaged UA and estimated glomerular filtration rate from the values at 3,

Byung Ha Chung; Seok Hui Kang; Hyeon Seok Hwang; Bum Soon Choi; Cheol Whee Park; Yong-Soo Kim; Ji-Il Kim; In Sung Moon; Chul Woo Yang

2011-01-01

125

EEG and Granular Osmiophilic Elements in Early-Onset Alzheimer’s Disease  

Microsoft Academic Search

Early-onset Alzheimer’s disease (EOAD) is a rare genetic disorder mainly attributable to a mutation in the presenilin 1 (PSEN1) gene. Clinical profile and instrumental findings share common features with adult neuronal ceroid lipofuscinosis. We documented the clinical course in EOAD patients bearing mutations in PSEN1. Genetic screening for dementia, EEG acquisition and determination of granular osmiophilic elements (GRODs) from skin

Antonella Alberici; Barbara Borroni; Claudio Bonato; Chiara Agosti; Stefano Avanzi; Filippo M. Santorelli; Alessandro Simonati; Alessandro Padovani

2011-01-01

126

Demographic and Intrapartum Characteristics of Term Pregnancies with Early-Onset Neonatal Seizures  

Microsoft Academic Search

OBJECTIVE:To compare the demographic and intrapartum factors of term pregnancies in which early-onset neonatal seizures developed with the characteristics of a large, unselected control population.STUDY DESIGN:Pregnancies delivered at term (gestational age ?37 weeks) in one birthing unit between 1984 and 1995 with a discharge diagnosis of neonatal seizures were identified. Maternal and neonatal charts of these patients were reviewed to

Yoram Sorokin; Sean Blackwell; Timothy Reinke; Nadya Kazzi; Susan Berman; David Bryant

2001-01-01

127

Gender Differences in the Interpersonal Consequences of Early-Onset Depressive Symptoms  

Microsoft Academic Search

Although research has identified gender differences in the interpersonal antecedents of depressive symptoms in youth, little is known about gender differences in the interpersonal consequences of depression. The goal of the present research was to examine gender differences in the influence of early-onset depressive symptoms on adolescent friendships and self-perceived peer acceptance. Third-graders (N = 382) participated in a multiwave

Karen D. Rudolph; Gary W. Ladd; Lisa. Dinella

2007-01-01

128

Early-Onset Severe Rod-Cone Dystrophy in Young Children with RPE65 Mutations  

Microsoft Academic Search

PURPOSE. To describe the ocular phenotype of patients with RPE65 mutations in infancy and young childhood. METHODS. Four children from three families with severe early-onset visual impairment related to electrophysiologically detectable retinal dystrophy were screened for mutations in the RPE65 gene. Visual function from infancy to the age of 10 years was assessed with age-adapted methods. Clinical examinations and electroretinograms

Birgit Lorenz; Peter Gyurus; Markus Preising; Dirk Bremser; Sumin Gu; Monika Andrassi; Christina Gerth; Andreas Gal

2000-01-01

129

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

PubMed

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

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

2014-08-01

130

Indoor tanning and risk of early-onset basal cell carcinoma  

PubMed Central

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

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

2011-01-01

131

Early onset seizures and Rett-like features associated with mutations in CDKL5  

Microsoft Academic Search

Mutations in the CDKL5 gene (also known as STK9) have recently been shown to cause early onset epilepsy and severe mental retardation (ISSX or West syndrome). Patients with CDKL5 mutations sometimes also show features similar to those seen in Rett Syndrome (RTT). We have screened the CDKL5 gene in 94 patients with RTT or a RTT-like phenotype who had tested

Julie C Evans; Hayley L Archer; James P Colley; Kirstine Ravn; Jytte Bieber Nielsen; Alison Kerr; Elizabeth Williams; John Christodoulou; Jozef Gécz; Philip E Jardine; Michael J Wright; Daniela T Pilz; Lazarus Lazarou; David N Cooper; Julian R Sampson; Rachel Butler; Sharon D Whatley; Angus J Clarke

2005-01-01

132

Early onset of vegetation growth vs. rapid green-up: impacts on juvenile mountain ungulates.  

PubMed

Seasonal patterns of climate and vegetation growth are expected to be altered by global warming. In alpine environments, the reproduction of birds and mammals is tightly linked to seasonality; therefore such alterations may have strong repercussions on recruitment. We used the normalized difference vegetation index (NDVI), a satellite-based measurement that correlates strongly with aboveground net primary productivity, to explore how annual variations in the timing of vegetation onset and in the rate of change in primary production during green-up affected juvenile growth and survival of bighorn sheep (Ovis canadensis), Alpine ibex (Capra ibex), and mountain goats (Oreamnos americanus) in four different populations in two continents. We indexed timing of onset of vegetation growth by the integrated NDVI (INDVI) in May. The rate of change in primary production during green-up (early May to early July) was estimated as (1) the maximal slope between any two successive bimonthly NDVI values during this period and (2) the slope in NDVI between early May and early July. The maximal slope in NDVI was negatively correlated with lamb growth and survival in both populations of bighorn sheep, growth of mountain goat kids, and survival of Alpine ibex kids, but not with survival of mountain goat kids. There was no effect of INDVI in May and of the slope in NDVI between early May and early July on juvenile growth and survival for any species. Although rapid changes in NDVI during the green-up period could translate into higher plant productivity, they may also lead to a shorter period of availability of high-quality forage over a large spatial scale, decreasing the opportunity for mountain ungulates to exploit high-quality forage. Our results suggest that attempts to forecast how warmer winters and springs will affect animal population dynamics and life histories in alpine environments should consider factors influencing the rate of changes in primary production during green-up and the timing of vegetation onset. PMID:17479756

Pettorelli, Nathalie; Pelletier, Fanie; Von Hardenberg, Achaz; Festa-Bianchet, Marco; Côté, Steeve D

2007-02-01

133

Von Economo neuron density in the anterior cingulate cortex is reduced in early onset schizophrenia.  

PubMed

The anterior cingulate cortex (ACC) represents a phylogenetically ancient region of the mammalian brain that has undergone recent adaptive changes in humans. It contains a large spindle-shaped cell type, referred to as von Economo neuron (VEN) that has been shown to be involved in the pathophysiology of various neuropsychiatric disorders. Schizophrenia is a group of disorders that is, in part, characterised by a disruption of neuronal migration in early ontogeny and presumably secondary degeneration after the first psychotic episode in some patients. Accordingly, we tested the hypothesis that the density of VENs is reduced in a neurodevelopmental subtype of schizophrenia, which we defined by an early onset of the disorder. The density of VENs was estimated in layer Vb of Brodmann's area 24 in 20 subjects diagnosed with schizophrenia. The results were compared with 19 specimens from patients with bipolar disorder as a clinical control and 22 non-psychiatric samples. The density of VENs did not differ between the three groups. However, the VEN density in the right ACC correlated with the age at onset, and inversely with the duration of the illness in schizophrenia, but not in bipolar disorder. Thus, patients with early onset schizophrenia (and longer duration of illness) had a reduced VEN density. Age, sex, postmortem interval, brain weight, and cortical thickness had no significant impact on the results. These findings suggest that VENs in the ACC are involved in neurodevelopmental and perhaps neurodegenerative processes specific to schizophrenia. PMID:20309567

Brüne, Martin; Schöbel, Andreas; Karau, Ramona; Benali, Alia; Faustmann, Pedro M; Juckel, Georg; Petrasch-Parwez, Elisabeth

2010-06-01

134

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

PubMed

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 ?-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 ?), 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 ?-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

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

135

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

NASA Technical Reports Server (NTRS)

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.

Frey, H.

1977-01-01

136

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

PubMed Central

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

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

2014-01-01

137

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

PubMed

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

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

2008-05-01

138

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

PubMed

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

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

2014-11-01

139

European Collaborative Study of Early-Onset Bipolar Disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset.  

E-print Network

- 1 - European Collaborative Study of Early-Onset Bipolar Disorder: Evidence for genetic heterogeneity of bipolar disorder Corresponding author : Flavie MATHIEU, PhD. INSERM Unité 955. EQ 15 Hôpital - ABSTRACT Bipolar disorder has a genetic component, but the mode of inheritance remains unclear. A previous

Boyer, Edmond

140

Mol Psychiatry . Author manuscript A SNAP25 promoter variant is associated with early-onset bipolar disorder  

E-print Network

influence the susceptibility to early-onset BD. We screened for mutations and performed a case1 studies have suggested that genetic factors play a major role in BD, but no causal mutation has of the disorder, a clinical approach based on candidate symptoms has been proposed. Age at onset (i.e. age

Boyer, Edmond

141

Trends in Incidence and Antimicrobial Resistance of Early-Onset Sepsis: Population-Based Surveillance in San Francisco and Atlanta  

Microsoft Academic Search

ABSTRACT. Objective. Although increased use of in- trapartum antibiotics caused significant declines in ear- ly-onset group B Streptococcus (GBS) infection, the effect on infections caused by other pathogens is not clear. The objective of this study was to determine trends in the incidence of early-onset sepsis caused by organisms other than group B streptococcus in the era of antimicro- bial

Terri B. Hyde; Tami M. Hilger; Arthur Reingold; Mph Monica M. Farley

142

The Common Single-Nucleotide Polymorphism rs2681472 Is Associated With Early-Onset Preeclampsia in Northern Han Chinese Women.  

PubMed

Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. PMID:24642721

Wan, Ji-Peng; Wang, Hong; Li, Chang-Zhong; Zhao, Han; You, Li; Shi, Dong-Hong; Sun, Xiu-Hua; Lv, Hong; Wang, Fei; Wen, Ze-Qing; Wang, Xie-Tong; Chen, Zi-Jiang

2014-11-01

143

Internet-delivered, family-based treatment for early-onset OCD: a preliminary case series.  

PubMed

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 (M Age = 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

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

144

Early-onset formation of parenchymal plaque amyloid abrogates cerebral microvascular amyloid accumulation in transgenic mice.  

PubMed

The fibrillar assembly and deposition of amyloid ? (A?) protein, a key pathology of Alzheimer disease, can occur in the form of parenchymal amyloid plaques and cerebral amyloid angiopathy (CAA). Familial forms of CAA exist in the absence of appreciable parenchymal amyloid pathology. The molecular interplay between parenchymal amyloid plaques and CAA is unclear. Here we investigated how early-onset parenchymal amyloid plaques impact the development of microvascular amyloid in transgenic mice. Tg-5xFAD mice, which produce non-mutated human A? and develop early-onset parenchymal amyloid plaques, were bred to Tg-SwDI mice, which produce familial CAA mutant human A? and develop cerebral microvascular amyloid. The bigenic mice presented with an elevated accumulation of A? and fibrillar amyloid in the brain compared with either single transgenic line. Tg-SwDI/Tg-5xFAD mice were devoid of microvascular amyloid, the prominent pathology of Tg-SwDI mice, but exhibited larger parenchymal amyloid plaques compared with Tg-5xFAD mice. The larger parenchymal amyloid deposits were associated with a higher loss of cortical neurons and elevated activated microglia in the bigenic Tg-SwDI/Tg-5xFAD mice. The periphery of parenchymal amyloid plaques was largely composed of CAA mutant A?. Non-mutated A? fibril seeds promoted CAA mutant A? fibril formation in vitro. Further, intrahippocampal administration of biotin-labeled CAA mutant A? peptide accumulated on and adjacent to pre-existing parenchymal amyloid plaques in Tg-5xFAD mice. These findings indicate that early-onset parenchymal amyloid plaques can serve as a scaffold to capture CAA mutant A? peptides and prevent their accumulation in cerebral microvessels. PMID:24828504

Xu, Feng; Kotarba, AnnMarie E; Ou-Yang, Ming-Hsuan; Fu, Ziao; Davis, Judianne; Smith, Steven O; Van Nostrand, William E

2014-06-20

145

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

PubMed Central

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

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

146

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

PubMed

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

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

147

Heterozygous ATM mutations do not contribute to early onset of breast cancer.  

PubMed

Ataxia telangiectasia (AT) is a recessive syndrome, including cerebellar degeneration, immunologic defects and cancer predisposition, attributed to mutations in the recently isolated ATM (ataxia telangiectasia, mutated) gene. AT is diagnosed in 1/40,000 to 1/100,000 live births, with carriers calculated to comprise approximately 1% of the population. Studies of AT families have suggested that female relatives presumed to be carriers have a 5 to 8-fold increased risk for developing breast cancer, raising the possibility that germline ATM mutations may account for approximately 5% of all breast cancer cases. The increased risk for breast cancer reported for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40-59 years. To test this hypothesis, we undertook a germ-line mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT. We detected a heterozygous ATM mutation in 2/202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2/401 (0.5%) women with early onset of breast cancer (P = 0.6). We conclude that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer. PMID:9054948

FitzGerald, M G; Bean, J M; Hegde, S R; Unsal, H; MacDonald, D J; Harkin, D P; Finkelstein, D M; Isselbacher, K J; Haber, D A

1997-03-01

148

PARK7, a Novel Locus for Autosomal Recessive Early-Onset Parkinsonism, on Chromosome 1p36  

Microsoft Academic Search

Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome

C. M. van Duijn; M. C. J. Dekker; V. Bonifati; R. J. Galjaard; J. J. Houwing-Duistermaat; P. J. L. M. Snijders; L. Testers; G. J. Breedveld; M. Horstink; L. A. Sandkuijl; J. C. van Swieten; B. A. Oostra; P. Heutink

2001-01-01

149

The street children of Manila are affected by early-in-life periodontal infection: description of a treatment modality: sea salt.  

PubMed

Thousands of street children of Manila are affected by early-in-life oral infection. The aim of the present investigation was to evaluate the effectiveness of a sea-salt mouthrinse solution in street children of Manila affected by mild to severe forms of periodontal disease. These children were all in need of special protection: abandoned, abused, exploited, neglected, orphaned, poor. During 3 oral-health missions in 2003, 2004 and 2005, 617 abandoned children (5 to 13 year-old), received oral examination at a non-sectarian child-caring institution in Metro Manila (Virlanie Foundation) by calibrated examiners. A treatment based on what could be done was proposed: 1. Teaching of a precise tooth brushing technique with sea-salt, controlled and reinforced every two days for one week by calibrated health educators, 2. The application of sea-salt water mouthrinse (2.5 gram in 20 ml). Periodontal measurements were repeated at the end of each mission. All children returned to child-caring institution for the followup examinations. In 2003, 10 male and 11 female (n=21) were diagnosed with aggressive periodontitis. In 2009 and 2010, none was affected by aggressive periodontitis. For all patients, the gingival index decreased from 1.08 at the first mission to 1.04 at the end of the second mission and 0.98 at the end of the third mission. The periodontal index decreased from 1.33 at the first mission to 0.98 at the second mission and 0.92 at the last mission. The present investigation confirms that prevention and early diagnosis can result in success with minimum cost. The provided oral health program empowered street children in the most desperate circumstances to be educated and become self-reliant, independent, and responsible. We propose here an antimicrobial approach which has a high degree of efficacy and tolerability, and can be implemented in virtually all parts of the world using low-cost resources. PMID:23697295

Michel, J F; Michel, M G; Nadan, J; Nowzari, H

2013-01-01

150

Mitochondrial Myopathy: A Rare Cause of Early-Onset Vocal Fold Atrophy  

PubMed Central

Objectives We present the second published case of laryngeal involvement in mitochondrial myopathy. Methods A patient with laryngeal involvement of mitochondrial myopathy is presented, together with a literature review. Results A 41-year-old man presented with progressive breathy dysphonia. His brother had mitochondrial myopathy. Biopsy of the biceps muscle demonstrated cytochrome C oxidase–negative ragged blue fibers confirming mitochondrial myopathy. Videostroboscopy showed marked vocal fold atrophy, but subsequent injection laryngoplasty did not significantly improve the patient’s voice, despite improved postoperative glottic closure. Conclusions Mitochondrial myopathy should be considered in the differential diagnosis of severe early-onset vocal fold atrophy. PMID:23577570

Kelly, Elizabeth A.; Bock, Jonathan M.; Peltier, Amanda C.; Oh, Shin J.; Garrett, C. Gaelyn

2014-01-01

151

Does Diagnostic Classification of Early-Onset Psychosis Change Over Follow-Up?  

Microsoft Academic Search

Objective  To examine the diagnostic stability and the functional outcome of patients with early-onset psychosis (EOP) over a 2-year\\u000a follow-up period.\\u000a \\u000a \\u000a \\u000a Methods  A total of 24 patients (18 males (75%) and 6 females (25%), mean age ± SD: 15.7 ± 1.6 years) with a first episode of EOP formed\\u000a the sample. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Social disability was\\u000a measured

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

2008-01-01

152

Risk factors for periodontal disease.  

PubMed

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

Genco, Robert J; Borgnakke, Wenche S

2013-06-01

153

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

PubMed Central

Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen branching enzyme (GBE). The diagnostic feature of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age of disease onset. Absence of enzyme activity is lethal in utero or in infancy affecting primarily muscle and liver. However, residual enzyme activity (5–20%) leads to juvenile or adult onset of a disorder that primarily affects muscle as well as central and peripheral nervous system. Here, we describe two mouse models of GSD IV that reflect this spectrum of disease. Homologous recombination was used to insert flippase recognition target recombination sites around exon 7 of the Gbe1 gene and a phosphoglycerate kinase-Neomycin cassette within intron 7, leading to a reduced synthesis of GBE. Mice bearing this mutation (Gbe1neo/neo) exhibit a phenotype similar to juvenile onset GSD IV, with wide spread accumulation of PG. Meanwhile, FLPe-mediated homozygous deletion of exon 7 completely eliminated GBE activity (Gbe1?/?), leading to a phenotype of lethal early onset GSD IV, with significant in utero accumulation of PG. Adult mice with residual GBE exhibit progressive neuromuscular dysfunction and die prematurely. Differently from muscle, PG in liver is a degradable source of glucose and readily depleted by fasting, emphasizing that there are structural and regulatory differences in glycogen metabolism among tissues. Both mouse models recapitulate typical histological and physiological features of two human variants of branching enzyme deficiency. PMID:21856731

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

2011-01-01

154

Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis  

PubMed Central

AIM: To investigated the molecular cause of very early-onset ulcerative colitis (UC) in an 18-mo-old affected child. METHODS: We analysed the interleukin-10 (IL10) receptor genes at the DNA and RNA level in the proband and his relatives. Beta catenin and tumor necrosis factor-? (TNF?) receptors were analysed in the proteins extracted from peripheral blood cells of the proband, his relatives and familial adenomatous polyposis (FAP) and PTEN hamartoma tumor syndrome (PHTS) patients. Samples were also collected from the proband’s inflamed colorectal mucosa and compared to healthy and tumour mucosa collected from a FAP patient and patients affected by sporadic colorectal cancer (CRC). Finally, we examined mesalazine and azathioprine effects on primary fibroblasts stabilised from UC and FAP patients. RESULTS: Our patient was a compound heterozygote for the IL10RB E47K polymorphism, inherited from his father, and for a novel point mutation within the IL10RA promoter (the -413G->T), inherited from his mother. Beta catenin and tumour necrosis factor ? receptors-I?(TNFRI) protein were both over-expressed in peripheral blood cells of the proband’s relatives more than the proband. However, TNFRII was over-expressed only in the proband. Finally, both TNF?-receptors were shown to be under-expressed in the inflamed colon mucosa and colorectal cancer tissue compared to healthy colon mucosa. Consistent with this observation, mesalazine and azathioprine induced, in primary fibroblasts, IL10RB and TNFRII over-expression and TNFRI and TNF? under-expression. We suggest that ?-catenin and TNFRI protein expression in peripheral blood cells could represent molecular markers of sub-clinical disease in apparently healthy relatives of patients with early-onset UC. CONCLUSION: A synergistic effect of several variant alleles of the IL10 receptor genes, inherited in a Mendelian manner, is involved in UC onset in this young child. PMID:24379584

Galatola, Martina; Miele, Erasmo; Strisciuglio, Caterina; Paparo, Lorella; Rega, Daniela; Delrio, Paolo; Duraturo, Francesca; Martinelli, Massimo; Rossi, Giovanni Battista; Staiano, Annamaria; Izzo, Paola; Rosa, Marina De

2013-01-01

155

Neurocognitive Outcomes in Young Adults With Early-Onset Type 1 Diabetes  

PubMed Central

OBJECTIVE The aim of this study was to reexamine the neurocognitive function of a cohort of young adults with early-onset type 1 diabetes and compare their cognitive function to a matched control group. We also examined whether cognitive function was related to prospectively obtained severe hypoglycemia history, long-term glycemic control, or severe diabetic ketoacidosis. RESEARCH DESIGN AND METHODS Testing included Wechsler Intelligence Scale for Children and Adults, Wechsler Memory Scale, Cattell Culture Fair Intelligence Test (CCFIT), Wisconsin Card Sorting Test (WCST), youth and adult self-report, and Beck Depression Inventory. We tested 34 control subjects (mean ± SE, age 19.5 ± 0.5 years) and 33 type 1 diabetic subjects (age 19.3 ± 0.5 years, age at type 1 diabetes onset 3.3 ± 0.3 years, A1C from diagnosis 8.7 ± 0.1%, and diabetes duration 16.0 ± 0.5 years). RESULTS There was no difference in full-scale IQ scores in type 1 diabetic and control subjects (100.7 ± 2.0 vs. 102.5 ± 1.4). There was no difference between groups in memory subtests or in reporting of emotional and behavioral difficulties. The type 1 diabetes group scored lower on the CCFIT for fluid intelligence compared with control subjects (P = 0.028) and also scored lower on WCST with more perseverative errors (P = 0.002) and fewer categories completed (P = 0.022). CONCLUSIONS These data suggest no difference in general intellectual ability, memory, and emotional difficulties in our cohort of young adults with early-onset type 1 diabetes compared with control subjects and no deterioration over time. There were, however, findings to suggest subtle changes leading to poorer performance on complex tasks of executive function. PMID:21844288

Ly, Trang T.; Anderson, Mike; McNamara, Kaitrin A.; Davis, Elizabeth A.; Jones, Timothy W.

2011-01-01

156

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

PubMed Central

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

Jando, Gabor; Miko-Barath, Eszter; Marko, Katalin; Hollody, Katalin; Torok, Bela; Kovacs, Ilona

2012-01-01

157

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

SciTech Connect

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.

Champion, D.; Clerget-Darpoux, F. [INSERM, Paris (France); Frebourg, T. [CHU de Rouen (France)

1994-09-01

158

HIPPOCAMPAL AND MESIAL TEMPORAL SCLEROSIS IN EARLY-ONSET FRONTOTEMPORAL LOBAR DEGENERATION vs. ALZHEIMER DISEASE  

PubMed Central

Hippocampal sclerosis (HS) and mesial temporal sclerosis (MTS) may occur with frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD), as well as with normal aging. Prior studies suggest that HS/MTS may be more closely associated with FTLD, but have not directly compared the prevalence and clinical characteristics of HS/MTS between neuropathologically confirmed early-onset (? age 65) cohorts of FTLD and AD. We identified cases of early-onset FTLD (n=136) and AD (n=267) from National Alzheimer’s Center Consortium databases and compared neuropathological and clinical data between these two groups. The FTLD group had a significantly higher prevalence of HS/MTS than the AD group. However, HS/MTS was associated with increasing age and memory impairment in the AD group, but not in the FTLD group. These findings are consistent with the hypothesis that HS/MTS in FTLD occurs as part of the primary pathological process, rather than as a secondary, nonspecific effect of aging on memory and hippocampal function. PMID:24085254

Joshi, Aditi; Teng, Edmond; Tassniyom, Kanida; Mendez, Mario F.

2014-01-01

159

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

PubMed Central

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

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

160

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

PubMed

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

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

161

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

PubMed Central

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

Živná, Martina; H?lková, Helena; Matignon, Marie; Hoda?ová, Kate?ina; Vylet'al, Petr; Kalbá?ová, 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

162

Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure.  

PubMed

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

Zivná, Martina; H?lková, Helena; Matignon, Marie; Hodanová, Katerina; Vylet'al, Petr; Kalbácová, Marie; Baresová, Veronika; Sikora, Jakub; Blazková, Hana; Zivný, 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

2009-08-01

163

New-onset Diabetes: A Clue to the Early Diagnosis of Pancreatic Cancer.  

PubMed

Pancreatic cancer is the tenth most common cancer diagnosis; however, it is the fourth most common cause of death due to cancer. Recent estimates suggest that by 2020 pancreatic cancer will become the second most common cause of cancer death in the US. The 5-year survival rate in all patients is only ~5% and has not changed significantly over the past five decades. Though the relationship between diabetes mellitus and pancreatic cancer has been known for over 125 years, it still remains to be fully understood. The complex relationship between the two diseases has been the subject of numerous clinical, epidemiological, laboratory and experimental studies. Epidemiologic studies suggest that long-standing type 2 diabetes is a modest risk factor for the development of pancreatic cancer. Meta-analysis of multiple cohort and case-control studies show that the risk of pancreatic cancer in those with diabetes for >5 years is 1.5 to 2.0 fold higher. This s not fully explained by shared risk factors between the two diseases such as obesity. There is also strong clinical, epidemiological and experimental evidence to show that pancreatic cancer causes diabetes. Hyperglycemia and diabetes mellitus occur in ~85% of pancreatic cancer subjects, with diabetes being present in 45% to 67% of pancreatic cancer patients depending on how diabetes is ascertained. Majority (~75%) of diabetes in pancreatic cancer is new-onset, i.e., less than 3 years in duration. The new-onset diabetes often resolves with resection of cancer. The notion that new-onset diabetes in pancreatic cancer is a paraneoplastic phenomenon caused by tumor secreted products was strengthened by a recent study that proposed adrenomedullin, a 52 amino-acid polypeptide, as a strong candidate for mediator of diabetes in pancreatic cancer. In previous studies adrenomedullin has been shown not only to promote pancreatic cancer aggressiveness, but also inhibits insulin exocytosis from beta cells. In the aforementioned study pancreatic cancer cell lines overexpressing adrenomedullin were shown to inhibit insulin secretion, an effect that was reversed by silencing adrenomedullin. Adrenomedullin was also shown to be overexpressed in human pancreatic cancer and plasma levels of adrenomedullin were also increased in pancreatic cancer patients, especially those with diabetes. New-onset diabetes appears to be the only clue to the presence of asymptomatic sporadic pancreatic cancer. Nearly 25% of patients with pancreatic cancer are diagnosed with diabetes 6 months to 36 months before the diagnosis of pancreatic cancer. Conversely, subjects with new-onset diabetes over age 50 years have an 8-fold higher risk for having pancreatic cancer. Thus new-onset diabetes may be a clue to the early diagnosis of the cancer. However, the success of the strategy to use new-onset diabetes as a marker of pancreatic cancer will depend on our ability to distinguish pancreatic cancer-associate diabetes from the more common type 2 diabetes. This strategy provides for diagnosis of early, asymptomatic pancreatic cancer. PMID:25262733

Chari, Suresh T

2014-01-01

164

Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis-related genes ACVRL1 and EGFL7 in early-onset disease  

PubMed Central

The underlying mechanisms behind the obstetric condition pre-eclampsia (PE) are still unclear. Manifestation of PE is heterogeneous and it has therefore been proposed to be a syndrome with different causes rather than one disease with a specific aetiology. Recently, we showed differences in circulating angiogenic factors between two subgroups—early- and late-onset PE. To further elucidate the differences between the two, we investigated placental gene expression profiles. Whole genome microarray technology and bioinformatic analysis were used to evaluate gene expression profiles in placentae from early- (24–32 gestational weeks, n = 8) and late-onset (36–41 gestational weeks, n = 7) PE. The results were verified by using quantitative real-time (qRT)–PCR. We found significant differences in the expression of 196 genes in early- compared with late-onset PE, 45 of these genes showing a fold change above 2. Bioinformatic analysis revealed alterations in angiogenesis and regulation of cell motility. Two angiogenesis-associated transcripts (Egfl7 and Acvrl1) showed lower expression in early-onset PE versus late-onset PE (P = 0.037 and P = 0.003) and versus gestational age-matched controls (P = 0.007 and P = 0.011). We conclude that angiogenesis-associated genes are regulated in a different manner in the two subgroups, and that the gene expression profiles of early- and late-onset PE diverge, supporting the hypothesis of early- and late-onset PE being at least partly two separate entities. PMID:22013081

Junus, K.; Centlow, M.; Wikstrom, A.-K.; Larsson, I.; Hansson, S.R.; Olovsson, M.

2012-01-01

165

Homozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke  

PubMed Central

We describe an autosomal recessive condition characterized with cerebral vasculopathy and early onset of stroke in 14 individuals in Old Order Amish. The phenotype of the condition was highly heterogeneous, ranging from severe developmental disability to normal schooling. Cerebral vasculopathy was a major hallmark of the condition with a common theme of multifocal stenoses and aneurysms in large arteries, accompanied by chronic ischemic changes, moyamoya morphology, and evidence of prior acute infarction and hemorrhage. Early signs of the disease included mild intrauterine growth restriction, infantile hypotonia, and irritability, followed by failure to thrive and short stature. Acrocyanosis, Raynaud’s phenomenon, chilblain lesions, low-pitch hoarse voice, glaucoma, migraine headache, and arthritis were frequently observed. The early onset or recurrence of strokes secondary to cerebral vasculopathy seems to always be associated with poor outcomes. The elevated erythrocyte sedimentation rate (ESR), IgG, neopterin, and TNF-? found in these patients suggested an immune disorder. Through genomewide homozygosity mapping, we localized the disease gene to chromosome (Chr) 20q11.22-q12. Candidate gene sequencing identified a homozygous mutation, c.1411–2A > G, in the SAMHD1 gene, being associated with this condition. The mutation appeared at the splice-acceptor site of intron 12, resulted in the skipping of exon 13, and gave rise to an aberrant protein with in-frame deletion of 31 amino acids. Immunoblotting analysis showed lack of mutant SAMHD1 protein expression in affected cell lines. The function of SAMHD1 remains unclear, but the inflammatory vasculopathies of the brain found in the patients with SAMHD1 mutation indicate its important roles in immunoregulation and cerebral vascular hemeostasis. PMID:21402907

Xin, Baozhong; Jones, Stephen; Puffenberger, Erik G.; Hinze, Claas; Bright, Alicia; Tan, Haiyan; Zhou, Aimin; Wu, Guiyun; Vargus-Adams, Jilda; Agamanolis, Dimitris; Wang, Heng

2011-01-01

166

Early Onset Mandibuloacral Dysplasia due to Compound Heterozygous Mutations in ZMPSTE24  

PubMed Central

Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by hypoplasia of the mandible and clavicles, acro-osteolysis and lipodystrophy due to mutations in LMNA or ZMPSTE24. Only six MAD patients are reported so far with ZMPSTE24 mutations and limited phenotypic data are available for them. Here, we report on two brothers (4 years and 9 months old) with early onset MAD due to ZMPSTE24 mutations in whom thin skin was noted as early as 5 months of age. Both had micrognathia, mottled hyperpigmentation, and enlarged fontanelles but little evidence of lipodystrophy. There was no delay of mental development. The older brother showed small pinched nose, short clavicles, acro-osteolysis, stunted growth, joint stiffness, and repeated fractures. There was no evidence of renal disease. Both patients were compound heterozygotes harboring a previously reported missense ZMPSTE24 mutation, p.Pro248Leu and a novel null mutation, p.Trp450stop. These patients and the review of literature reveals that compared to MAD patients with LMNA mutations, those with ZMPSTE24 mutations develop manifestations earlier in life. Other distinguishing features in MAD due to ZMPSTE24 mutations may include premature birth, renal disease, calcified skin nodules, and lack of acanthosis nigricans. We conclude that in patients with MAD due to ZMPSTE24 mutations, the onset of disease manifestations such as thin skin and micrognathia occurs as early as 5 months of age. In these patients, skeletal phenotype presents earlier whereas lipodystrophy and renal disease may occur later in life. PMID:20814950

Ahmad, Zahid; Zackai, Elaine; Medne, Livija; Garg, Abhimanyu

2010-01-01

167

Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2  

PubMed Central

BACKGROUND We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood. METHODS We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells. RESULTS All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia — phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers. CONCLUSIONS Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.) PMID:24552284

Zhou, Q.; Yang, D.; Ombrello, A.K.; Zavialov, Andrey V.; Toro, C.; Zavialov, Anton V.; Stone, D.L.; Chae, J.J.; Rosenzweig, S.D.; Bishop, K.; Barron, K.S.; Kuehn, H.S.; Hoffmann, P.; Negro, A.; Tsai, W.L.; Cowen, E.W.; Pei, W.; Milner, J.D.; Silvin, C.; Heller, T.; Chin, D.T.; Patronas, N.J.; Barber, J.S.; Lee, C.-C.R.; Wood, G.M.; Ling, A.; Kelly, S.J.; Kleiner, D.E.; Mullikin, J.C.; Ganson, N.J.; Kong, H.H.; Hambleton, S.; Candotti, F.; Quezado, M.M.; Calvo, K.R.; Alao, H.; Barham, B.K.; Jones, A.; Meschia, J.F.; Worrall, B.B.; Kasner, S.E.; Rich, S.S.; Goldbach-Mansky, R.; Abinun, M.; Chalom, E.; Gotte, A.C.; Punaro, M.; Pascual, V.; Verbsky, J.W.; Torgerson, T.R.; Singer, N.G.; Gershon, T.R.; Ozen, S.; Karadag, O.; Fleisher, T.A.; Remmers, E.F.; Burgess, S.M.; Moir, S.L.; Gadina, M.; Sood, R.; Hershfield, M.S.; Boehm, M.; Kastner, D.L.; Aksentijevich, I.

2014-01-01

168

‘Ear today gone tomorrow’: routine neonatal ear canal cultures are not useful predictors of early onset invasive bacterial sepsis  

Microsoft Academic Search

BackgroundCulture of body surfaces including the ear canal, throat and rectum are often routinely performed on new neonatal unit admissions. It has been postulated that in the early postnatal period the neonatal ear canal may still contain amniotic fluid and thus be superior to other sites for identifying maternally acquired bacteria responsible for early onset neonatal bacterial sepsis. However, the

A J Battersby; R Webster; T Neal; N Subhedar

2011-01-01

169

Periodontal breakdown in the Dmp1 null mouse model of hypophosphatemic rickets.  

PubMed

Dentin Matrix Protein 1 (DMP1) is highly expressed in alveolar bone and cementum, which are important components of the periodontium. Therefore, we hypothesized that Dmp1 is critical for the integrity of the periodontium, and that deletion may lead to increased susceptibility to disease. An early-onset periodontal defect was observed in the Dmp1 null mouse, a mouse model of hypophosphatemic rickets. The alveolar bone is porous, with increased proteoglycan expression. The cementum is also defective, as characterized by irregular, punctate fluorochrome labeling and elevated proteoglycan. The osteocyte and cementocyte lacuno-canalicular system of both alveolar bone and cementum is abnormal, with irregular lacunar walls and fewer canaliculi. As a consequence, there is significant interproximal alveolar bone loss, combined with detachment between the periodontal ligament (PDL) and cementum. We propose that defective alveolar bone and cementum may account for the periodontal breakdown and increased susceptibility to bacterial infection in Dmp1 null mice. PMID:18573980

Ye, L; Zhang, S; Ke, H; Bonewald, L F; Feng, J Q

2008-07-01

170

Juvenile periodontitis: an historical review.  

PubMed

A review of the literature on juvenile periodontitis has been undertaken. This paper traces the historical development of the appreciation of the condition. Some of the numerous early attempts to define a systemic background are noted, and the concept of 'periodontosis' and its subsequent influence, e.g. on epidemiological and clinical studies are discussed. The refining over the last 20 years of the concept of aggressive periodontal disease in the young is recorded. The patterns of bone loss in juvenile periodontitis and some forms of treatment are presented, together with evidence on its histopathology. Recent research has tended to concentrate on the microbiology and immunological background of juvenile periodontitis and a number of these studies are discussed. PMID:6752359

Saxby, M S

1982-09-01

171

Slit ventricle syndrome and early-onset secondary craniosynostosis in an infant  

PubMed Central

Patient: Female, 14 months Final Diagnosis: Slit ventricle syndrome Symptoms: Hydrocephalus • lethargy and seizure • vomiting Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Challenging differential diagnosis Background: Shunt surgery is a common solution for hydrocephalus in infancy. Slit ventricle syndrome and secondary craniosynostosis are late-onset complications after shunt placement; these 2 conditions occasionally occur together. Case Report: We report a case of early-onset secondary craniosynostosis with slit ventricle syndrome after shunt surgery in an infant, which led to a catastrophic increase in intracranial pressure (ICP). A 4-month-old girl with a Dandy-Walker malformation underwent a ventriculoperitoneal shunt procedure. Her head circumference (HC) gradually decreased to approximately the 5th percentile for her age group after shunt surgery. Seven months later, she developed increased ICP symptoms and underwent a shunt revision with a diagnosis of shunt malfunction. Her symptoms were temporarily relieved, but she repeatedly visited the emergency room (ER) for the same symptoms and finally collapsed, with an abrupt increase in ICP, 3 months later. Further evaluation revealed the emergence of sagittal synostosis at 7 months after initial shunt surgery. After reviewing all clinical data, slit ventricle syndrome combined with secondary craniosynostosis was diagnosed. Emergent cranial expansion surgery with shunt revision was performed, and the increased ICP signs subsided in the following days. Conclusions: Clinical suspicion and long-term HC monitoring are important in the diagnosis of slit ventricle syndrome and secondary craniosynostosis after shunt surgery, even in infants and young children. PMID:24944727

Ryoo, Hyun Gee; Kim, Seung-Ki; Cheon, Jung-Eun; Lee, Ji Yeoun; Wang, Kyu-Chang; Phi, Ji Hoon

2014-01-01

172

Early-onset of multiple sclerosis in a 5-year-old girl.  

PubMed

Childhood multiple sclerosis is a rare demyelinating autoimmune disease with particular features. Onset of multiple sclerosis is extremely uncommon in early childhood, particularly before 6 years of age. We report the case of a 5-year-old girl admitted to the hospital for altered consciousness and rapid onset of right hemiparaplegia. Magnetic resonance imaging (MRI) of the brain showed multifocal white matter disease with T2 hyperintense oval lesions in subcortical, periventricular, and cerebellar hemispheres. Treatment with high dose intravenous methylprednisolone (30 mg/kg/day for 3 days) improved symptoms. Intravenous corticosteroid therapy was followed by 1mg/kg/day of oral prednisone. A second MRI, 40 days later, revealed new disseminated T2 hyperintense lesions in the frontal periventricular white matter, corpus callosum, left middle cerebellar peduncle, and dorsal spinal cord, leading to the diagnosis of multiple sclerosis. Azathioprine (2.5 mg/kg/day) was started and the steroid dose was tapered before being stopped after 3 months. After 2 years of follow-up, the patient has remained asymptomatic with a normal neurological exam and with no relapse or side effects of azathioprine. This work shows the particularities in clinical and radiological features of multiple sclerosis in a child aged less than 6 years. PMID:24462295

Gargouri, L; Safi, F; Fourati, H; Kmiha, S; Turki, F; Zidi, F; Mnif, Z; Mahfoudh, A

2014-03-01

173

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

PubMed Central

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

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

2010-01-01

174

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

PubMed

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

Tanpowpong, Pornthep; Camargo, Carlos A

2014-04-01

175

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

PubMed

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

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

2014-11-01

176

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

PubMed Central

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.

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

2014-01-01

177

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

PubMed

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

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

2014-11-01

178

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

NASA Technical Reports Server (NTRS)

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

Sibonga, Jean D.

2010-01-01

179

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

PubMed Central

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 8–19 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

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

180

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

PubMed

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

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

2014-11-01

181

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

PubMed Central

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 (2001–2005) was analyzed focusing on outpatients, aged 6–17 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: 0.57–1.61) for olanzapine, 1.03 (95% CI: 0.59–1.81) for quetiapine, 0.85 (95% CI: 0.43–1.70) for aripiprazole, and 1.22 (95% CI: 0.60–2.51) 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

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

2012-01-01

182

Alu -specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder  

Microsoft Academic Search

Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene in Xp22.13 have been associated with infantile spasms, early-onset intractable epilepsy, and a Rett syndrome (RTT)-like\\u000a phenotype. Using array comparative genomic hybridization, we identified variable-sized microdeletions involving exons 1–4\\u000a of the CDKL5 gene in three females with early-onset seizures. Two of these deletions were flanked by Alu repetitive elements and may have

Ayelet Erez; Amina J. Patel; Xueqing Wang; Zhilian Xia; Samarth S. Bhatt; William Craigen; Sau Wai Cheung; Richard A. Lewis; Ping Fang; Sandra L. H. Davenport; Pawel Stankiewicz; Seema R. Lalani

2009-01-01

183

Characteristics and outcome of early-onset, severe forms of Wiskott-Aldrich syndrome.  

PubMed

On the basis of a nationwide database of 160 patients with Wiskott-Aldrich syndrome (WAS), we identified a subset of infants who were significantly more likely to be attributed with an Ochs score of 5 before the age of 2 (n = 26 of 47 [55%], P = 2.8 × 10(?7)). A retrospective analysis revealed that these patients often had severe refractory thrombocytopenia (n = 13), autoimmune hemolytic anemia (n = 15), and vasculitis (n = 6). One patient had developed 2 distinct cancers. Hemizygous mutations predictive of the absence of WAS protein were identified in 19 of the 24 tested patients, and the absence of WAS protein was confirmed in all 10 investigated cases. Allogeneic hematopoietic stem cell transplantation (HSCT) was found to be a curative treatment with a relatively good prognosis because it was successful in 17 of 22 patients. Nevertheless, 3 patients experienced significant disease sequelae and 4 patients died before HSCT. Therefore, the present study identifies a distinct subgroup of WAS patients with early-onset, life-threatening manifestations. We suggest that HSCT is a curative strategy in this subgroup of patients and should be performed as early in life as possible, even when a fully matched donor is lacking. PMID:23264593

Mahlaoui, Nizar; Pellier, Isabelle; Mignot, Cécile; Jais, Jean-Philippe; Bilhou-Nabéra, Chrystèle; Moshous, Despina; Neven, Bénédicte; Picard, Capucine; de Saint-Basile, Geneviève; Cavazzana-Calvo, Marina; Blanche, Stéphane; Fischer, Alain

2013-02-28

184

Human Papillomavirus Type 31b Infection of Human Keratinocytes and the Onset of Early Transcription  

PubMed Central

Human papillomaviruses (HPVs) cause a number of human tumors and malignancies, including cervical cancers. Epithelial differentiation is required for the complete HPV life cycle and can be achieved using the organotypic (raft) culture system. The CIN-612 9E cell line maintains episomal copies of HPV type 31b (HPV31b), an HPV type associated with cervical cancers. When grown in the raft system, CIN-612 9E cells form a differentiated epithelium such that infectious virions can be synthesized. Many aspects of the later stages of the HPV31b life cycle have been investigated in CIN-612 9E raft tissues. We used a biologically contained homogenization system for efficient virion extraction from raft epithelial tissues. Purified HPV31b virions were used to infect low-passage-number human foreskin keratinocytes and a variety of epithelial cell lines. Newly synthesized, spliced HPV31b transcripts were detected by reverse transcription and PCR (RT-PCR) following HPV31b infection. HPV31b infection was most efficient and reproducible in HaCaT cells. The onset of viral transcription following infection was also investigated using RT-PCR techniques. Spliced E1?I,E2 RNAs were present as early as 4 h postinfection (p.i.), whereas the other major viral transcripts were detected by 8 to 10 h p.i. Furthermore, we characterized the structures and temporal expression of seven novel spliced early transcripts expressed following infection. PMID:12388689

Ozbun, Michelle A.

2002-01-01

185

Quantification of Maternal Serum Cell-Free Fetal DNA in Early-Onset Preeclampsia  

PubMed Central

The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA) level of gravidas developed into early-onset preeclampsia (EOPE) subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged) cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68) was higher than controls (median, 1.79; interquartile range, 1.46–2.53). The increased level of (logged) cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG) level (r = 0.628, p < 0.001). Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = ?0.516, p = 0.001; r = ?0.623, p < 0.001, respectively). The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta. PMID:23567271

Yu, Hong; Shen, Yanting; Ge, Qinyu; He, Youji; Qiao, Dongyan; Ren, Mulan; Zhang, Jianqiong

2013-01-01

186

Neutrophil Activation in Severe, Early-Onset COPD Patients versus Healthy NonSmoker Subjects in vitro: Effects of Antioxidant Therapy  

Microsoft Academic Search

Background: Neutrophils and oxidative stress have been implicated in the pathogenesis of COPD. Severe, early-onset COPD is characterized by a rapid decline in the lung function at an early age; however, nothing is known about neutrophil activation in COPD patients. Objectives: The aim of this study was to evaluate peripheral blood neutrophil activation in severe, early-onset COPD patients versus healthy

Javier Milara; Gustavo Juan; Teresa Peiró; Adela Serrano; Julio Cortijo

2012-01-01

187

Adult-onset obesity induced by early life overnutrition could be reversed by moderate caloric restriction  

PubMed Central

Overnutrition during the suckling period (small litter, SL) results in the development of adult-onset obesity. Our aim was to investigate whether two levels of caloric restriction (CR) in the early postweaning period can reverse obese phenotype in SL rats. The normal litter (NL) had 12 pups/dam and SL had 3 male pups/dam from the postnatal day 3 until day 21. After weaning, rats consumed lab chow as indicated: 1) NL and SL groups were on ad libitum regimen up to day 140, 2) another SL group was pair-fed (SL/PF) to NL(?14% reduction), 3) SL/PF/AL group was pair-fed up to day 94 and then switched to ad libitum feeding, 4) SL/CR group received 24% reduction (moderate CR) in food intake compared with SL, and 5) SL/CR/AL group was on 24% CR up to day 94 and then switched to ad libitum feeding. Pair-feeding reduced body weight gains and serum insulin and leptin levels compared with SL rats, but these parameters were restored to SL levels in the SL/PF/AL rats after switching to ad libitum feeding. Interestingly, the moderate CR normalized these parameters in SL/CR and SL/CR/AL rats compared with NL. The expression of neuropeptide Y, proopiomelanocortin, and leptin receptor returned to control levels in hypothalami from SL/CR and SL/CR/AL rats. These results indicate that appropriate manipulation of energy intake during the early postweaning period could lead to longer-lasting effects on the regulation of body weight homeostasis via reversal of the early preweaning programming effects on the hypothalamic appetite regulation mechanism. PMID:23900419

Liu, Hung-Wen; Srinivasan, Malathi; Mahmood, Saleh; Smiraglia, Dominic J.

2013-01-01

188

Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease  

PubMed Central

Background X-linked Charcot-Marie Tooth (CMT) is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions. Methods We describe two novel mutations in the connexin32 gene in two Norwegian families. Results Family 1 had a c.225delG (R75fsX83) which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y) transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands. The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25–49 m/s). Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals. Conclusion The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode. PMID:17620124

Braathen, Geir J; Sand, Jette C; Bukholm, Geir; Russell, Michael B

2007-01-01

189

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

190

A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains  

Microsoft Academic Search

We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area

Christelle Peyron; Juliette Faraco; William Rogers; Beth Ripley; Sebastiaan Overeem; Yves Charnay; Sona Nevsimalova; Michael Aldrich; David Reynolds; Roger Albin; Robin Li; Marcel Hungs; Mario Pedrazzoli; Muralidhara Padigaru; Melanie Kucherlapati; Jun Fan; Richard Maki; Gert Jan Lammers; Constantin Bouras; Raju Kucherlapati; Seiji Nishino; Emmanuel Mignot

2000-01-01

191

Early-Onset Alcoholism With Conduct Disorder: Go\\/No Go Learning Deficits, Working Memory Capacity, and Personality  

Microsoft Academic Search

Background: Two studies were conducted to investigate the disinhibitory mechanisms that (1) discrim- inate early-onset alcoholism (EOA) with conduct disorder (CD; antisocial EOA) from a nonantisocial subtype of EOA and (2) are associated with novelty-seeking and low harm avoidance. Methods: Young adults with antisocial EOA (n 96), with nonantisocial EOA (without CD; n 80), with CD alone (n 50), and

Peter R. Finn; Carlos A. Mazas; Alicia N. Justus; Joseph Steinmetz

2002-01-01

192

The early-onset torsion dystonia-associated protein, torsinA, is a homeostatic regulator of  

E-print Network

, 2010 Early-onset torsion dystonia is the most severe heritable form of dystonia, a human movement variants of human torsinA. This analysis revealed that, normally, torsinA serves a protective function of torsinA is greatly dimin- ished by the DYT1-associated deletion or mutations that prevent its

Caldwell, Guy

193

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

ERIC Educational Resources Information Center

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…

Rivard, Melina; Forget, Jacques

2012-01-01

194

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

Microsoft Academic Search

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 Bipolar Disorder (PBD). We found that individuals with PBD suffer from cognitive deficits (e.g.,

Rebeca García Nieto; F. Xavier Castellanos

2011-01-01

195

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

ERIC Educational Resources Information Center

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…

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

2008-01-01

196

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

ERIC Educational Resources Information Center

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…

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

197

Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behaviour  

Microsoft Academic Search

This study tested the hypothesis that adolescent-onset alcohol abuse (AOAA) would both mediate and moderate the effect of childhood conduct disorder on antisocial behaviour in late adolescence and early adulthood. A sample comprising 504 young men and women strategically recruited from the community were grouped using the criteria of the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association. (1994). Diagnostic

Richard Howard; Peter Finn; Paul Jose; Jennifer Gallagher

2012-01-01

198

Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behaviour  

Microsoft Academic Search

This study tested the hypothesis that adolescent-onset alcohol abuse (AOAA) would both mediate and moderate the effect of childhood conduct disorder on antisocial behaviour in late adolescence and early adulthood. A sample comprising 504 young men and women strategically recruited from the community were grouped using the criteria of the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association. (1994). Diagnostic

Richard Howard; Peter Finn; Paul Jose; Jennifer Gallagher

2011-01-01

199

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

200

Synchrotron radiation analysis of possible correlations between metal status in human cementum and periodontal disease  

Microsoft Academic Search

Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X-ray fluorescence

R. R. Martin; S. J. Naftel; A. J. Nelson; M. Edwards; H. Mithoowani; J. Stakiw

2010-01-01

201

Regional Differences in White Matter Breakdown Between Frontotemporal Dementia and Early-Onset Alzheimer's Disease1  

PubMed Central

Background White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Objective Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting. Methods We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale of Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants. Results Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group. Conclusions The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group. PMID:24150110

Lu, Po H.; Lee, Grace J.; Shapira, Jill; Jimenez, Elvira; Mather, Michelle J.; Thompson, Paul M.; Bartzokis, George; Mendez, Mario F.

2014-01-01

202

Early release of HMGB-1 from neurons after the onset of brain ischemia.  

PubMed

The nuclear protein high-mobility group box 1 (HMGB-1) promotes inflammation in sepsis, but little is known about its role in brain ischemia-induced inflammation. We report that HMGB-1 and its receptors, receptor for advanced glycation end products (RAGE), Toll-like receptor 2 (TLR2), and TLR4, were expressed in normal brain and in cultured neurons, endothelia, and glial cells. During middle cerebral artery occlusion (MCAO), in mice, HMGB-1 immunostaining rapidly disappeared from all cells within the striatal ischemic core from 1 h after onset of occlusion. High-mobility group box 1 translocation from nucleus to cytoplasm was observed within the cortical periinfarct regions 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 predominantly translocated to the cytoplasm or disappeared in cells that colabeled with the neuronal marker NeuN. Furthermore, RAGE was robustly expressed in the periinfarct region after MCAO. Cellular release of HMGB-1 was detected by immunoblotting of cerebrospinal fluid as early as 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 released from neurons, in vitro, after glutamate excitotoxicity, maintained biologic activity and induced glial expression of tumor necrosis factor alpha (TNFalpha). Anti-HMGB-1 antibody suppressed TNFalpha upregulation in astrocytes exposed to conditioned media from glutamate-treated neurons. Moreover, TNFalpha and the cytokine intercellular adhesion molecule-1 increased in cultured glia and endothelial cells, respectively, after adding recombinant HMGB-1. In conclusion, HMGB-1 is released early after ischemic injury from neurons and may contribute to the initial stages of the inflammatory response. PMID:18000511

Qiu, Jianhua; Nishimura, Masaki; Wang, Yumei; Sims, John R; Qiu, Sumei; Savitz, Sean I; Salomone, Salvatore; Moskowitz, Michael A

2008-05-01

203

Placental Nkx2.5 and Target Gene Expression in Early-Onset and Severe Preeclampsia  

PubMed Central

Objective Preeclampsia (PE) affects 2–8% of pregnancies worldwide and is a significant source of maternal and neonatal morbidity and mortality. However, the mechanisms underlying PE are poorly understood and major questions regarding etiology and risk factors remain to be addressed. Our objective was to examine whether abnormal expression of the cardiovascular developmental transcription factor, Nkx2-5, was associated with early onset and severe pre-eclampsia (EOSPE). Methods Using qPCR and immunohistochemical assay, we examined expression of Nkx2-5 and target gene expression in EOSPE and control placental tissue. We tested resulting mechanistic hypotheses in cultured cells using shRNA knockdown, qPCR and western blot. Results Nkx2-5 is highly expressed in racially disparate fashion (Caucasians > African Americans) in a subset of early EOSPE placentae. Nkx2-5 mRNA expression is highly correlated (Caucasians > African Americans) to mRNA expression of the preeclampsia marker sFlt-1, and of the Nkx2-5 target and RNA splicing factor, Sam68. Knockdown of Sam68 expression in cultured cells significantly impacts sFlt-1 mRNA isoform generation in vitro, supporting a mechanistic hypothesis that Nkx2-5 impacts EOSPE severity in a subset of patients via upregulation of Sam68 to increase sFlt-1 expression. Expression of additional Nkx2-5 targets potentially regulating metabolic stress response is also elevated in racially disparate fashion in EOSPE. Conclusions Expression of Nkx2-5 and its target genes may directly influence the genesis and racially disparate severity, and define a mechanistically distinct subclass of EOSPE. PMID:24987805

Rivers, Elena R.; Horton, Anthony J.; Hawk, Angela F.; Favre, Elizabeth G.; Senf, Katherine M.; Nietert, Paul J.; Chang, Eugene Y.; Foley, Ann C.; Robinson, Christopher J.; Lee, Kyu-Ho

2014-01-01

204

Early Pathogenesis in the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motor neurons starting in adulthood. Most of our knowledge about the pathophysiological mechanisms of ALS comes from transgenic mice models that emulate a subgroup of familial ALS cases (FALS), with mutations in the gene encoding superoxide dismutase (SOD1). In the more than 15 years since these mice were generated, a large number of abnormal cellular mechanisms underlying motor neuron degeneration have been identified, but to date this effort has led to few improvements in therapy, and no cure. Here, we consider that this surfeit of mechanisms is best interpreted by current insights that suggest a very early initiation of pathology in motor neurons, followed by a diversity of secondary cascades and compensatory mechanisms that mask symptoms for decades, until trauma and/or aging overloads their protective function. This view thus posits that adultonset ALS is the consequence of processes initiated during early development. In fact, motor neurons in neonatal mutant SOD mice display important alterations in their intrinsic electrical properties, synaptic inputs and morphology that are accompanied by subtle behavioral abnormalities. We consider evidence that human mutant SOD1 protein in neonatal hSOD1G93A mice instigates motor neuron degeneration by increasing persistent sodium currents and excitability, in turn altering synaptic circuits that control excessive motor neuron firing and leads to excitotoxicity. We also discuss how therapies that are aimed at suppressing abnormal neuronal activity might effectively mitigate or prevent the onset of irreversible neuronal damage in adulthood. PMID:22740507

van Zundert, Brigitte; Izaurieta, Pamela; Fritz, Elsa; Alvarez, Francisco J.

2013-01-01

205

Brain network informed subject community detection in early-onset schizophrenia.  

PubMed

Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS. PMID:24989351

Yang, Zhi; Xu, Yong; Xu, Ting; Hoy, Colin W; Handwerker, Daniel A; Chen, Gang; Northoff, Georg; Zuo, Xi-Nian; Bandettini, Peter A

2014-01-01

206

Measurement of forces generated during distraction of growing-rods in early onset scoliosis  

PubMed Central

AIM: To measure the forces applied during distraction of growing-rods in early onset scoliosis (EOS), aimed at developing a motorized elongation device. METHODS: A consecutive series of measurements were carried out to analyze the forces applied by the surgeon during distraction of single growing-rods in 10 patients affected by EOS (mean age 8.3 years; range 6 to 10 years) undergoing the first distraction 6 months following implantation of the rods. For each measurement, output from the transducer of a dedicated pair of distraction calipers was recorded at zero load status and at every 1 mm of distraction, up to a maximum of 12 mm for each of the two connected rods. RESULTS: Twenty measurements were obtained showing a linear increase of the load with increasing distraction, with a mean peak force of 485 N at 12 mm distraction and a single reading over 500 N. We did not observe bone fractures or ligament disruptions during or after rod elongations. There was one case of superficial wound infection in the cohort. CONCLUSION: The safe peak force carrying capacity of a motorized device for distraction of growing-rods is 500N. PMID:22470846

Teli, Marco; Grava, Giuseppe; Solomon, Victor; Andreoletti, Giuseppe; Grismondi, Emanuele; Meswania, Jay

2012-01-01

207

Cutaneous granulomas and epidermodysplasia verruciformis in early onset combined immunodeficiency syndrome.  

PubMed

Cutaneous granulomas with prominent caseating necrosis are a rare manifestation of immunodeficiency. Extensive and recalcitrant cutaneous viral infections can also be seen. We present a case of an 18-year-old white man with an early onset poorly characterized combined immunodeficiency syndrome who, over the past 5 years, developed enlarging tender red-purple plaques on his extremities and pink near-confluent macules on his chest and back. Previous biopsies of the red-purple plaques showed features of granuloma annulare. Histopathological examination of old and new biopsies revealed both sarcoidal and palisading necrobiotic granulomas with perforating features and elastophagocytosis. Stains and tissue cultures were negative for bacterial and fungal organisms. In addition, biopsy of a macule on the back demonstrated verruca plana with characteristics of epidermodysplasia verruciformis. As an infant, the patient had failure to thrive and a combined immunodeficiency, but was lost to follow-up for 15 years. He currently continues to have severe hypogammaglobinemia and cellular immunodeficiency. Intravenous immunoglobulin and prednisone were initiated and his plaques improved rapidly. Topical imiquimod was ineffective for the verruca plana. The patient and his parents are currently undergoing whole exome sequencing including evaluation for epidermodysplasia verruciformis 1 and 2 gene mutations. This case highlights the importance of including genetic immunodeficiency disorders in the clinical and histopathological differential diagnosis for cutaneous sarcoidal or palisading necrobiotic granulomas and for extensive cutaneous viral infection. PMID:24247584

Wang, Yen T; Geng, Bob; Yoo, Ki-Young; Stiehm, Ewald R; Garcia-Lloret, Maria; Wong, Derek; Smart, Chandra; Worswick, Scott; Barnhill, Raymond L

2014-02-01

208

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

PubMed

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

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

2013-08-01

209

Reduced Cortisol in Boys with Early-Onset Conduct Disorder and Callous-Unemotional Traits  

PubMed Central

Background. A growing body of evidence suggests an association between altered hypothalamic-pituitary-adrenal axis reactivity and the development of persistent antisocial behavior in children. However the effects of altered cortisol levels remain poorly understood in the complex context of conduct disorder, callous-unemotional (CU) personality traits, and frequent comorbidities, such as attention deficit hyperactivity disorder (ADHD). The aim of the current study was to investigate associations among CU traits, antisocial behavior, and comorbid ADHD symptomatology with cortisol levels in male children and adolescents. Methods. The study included 37 boys with early-onset conduct disorder (EO-CD, mean age 11.9 years) and 38 healthy boys (mean age 12.5 years). Participants were subjected to multiple daytime salivary cortisol measurements and a psychometric characterization. Results. Subjects in the EO-CD group with elevated CU traits showed a diminished cortisol awakening response compared to healthy participants. In the EO-CD group, high CU traits and impulsivity were associated with decreased diurnal cortisol levels, while associations with antisocial behavior were not detected. The cortisol awakening response was significantly inversely associated with hyperactivity (P = 0.02) and marginally significant with CU traits (P = 0.07). Conclusions. These results indicate a specific association between CU traits and a diminished stress response, which is not explained by antisocial behavior in general. PMID:23841064

von Polier, Georg G.; Herpertz-Dahlmann, Beate; Wiesler, Kristine; Rieke, Jana; Heinzel-Gutenbrunner, Monika; Bachmann, Christian J.; Vloet, Timo D.

2013-01-01

210

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

PubMed Central

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 ?-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

Busso, Dolores; Mascareno, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolas; Quiroz, Alonso; Amigo, Ludwig; Valdes, Gloria; Rigotti, Attilio

2014-01-01

211

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

PubMed

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

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

212

Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases  

PubMed Central

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p?=?2.62×10?9–1.01×10?12). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR?=?1.28, 95% confidence interval: 1.06–1.55, p?=?8.9×10?3). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR)?=?5.78, p?=?1.4×10?88]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions. PMID:22693459

Glass, Daniel; Medland, Sarah E.; Dimitriou, Maria; Waterworth, Dawn; Tung, Joyce Y.; Geller, Frank; Heilmann, Stefanie; Hillmer, Axel M.; Bataille, Veronique; Eigelshoven, Sibylle; Hanneken, Sandra; Moebus, Susanne; Herold, Christine; den Heijer, Martin; Montgomery, Grant W.; Deloukas, Panos; Eriksson, Nicholas; Heath, Andrew C.; Becker, Tim; Sulem, Patrick; Mangino, Massimo; Vollenweider, Peter; Spector, Tim D.; Dedoussis, George; Martin, Nicholas G.; Kiemeney, Lambertus A.; Mooser, Vincent; Stefansson, Kari; Hinds, David A.; Nothen, Markus M.; Richards, J. Brent

2012-01-01

213

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

PubMed

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

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

2014-10-01

214

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

PubMed Central

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

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

2013-01-01

215

High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia.  

PubMed

Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-?), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-?-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-?, IL-1?, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-?, TNFRI, IL-1?, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels. PMID:24051131

Peraçoli, Jose C; Bannwart-Castro, Camila F; Romao, Mariana; Weel, Ingrid C; Ribeiro, Vanessa R; Borges, Vera T M; Rudge, Marilza V; Witkin, Steven S; Peraçoli, Maria T

2013-12-01

216

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

ERIC Educational Resources Information Center

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.

Kumra, Sanjiv

2008-01-01

217

Opsonic antibody activity against Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.  

PubMed Central

Actinobacillus actinomycetemcomitans has been closely associated with early-onset, severe periodontitis, and such patients often have serum immunoglobulin G (IgG) antibodies reactive with antigens of this gram-negative pathogen. We examined the functionality and potential importance of these antibodies. The opsonic activity against A. actinomycetemcomitans of sera from 30 patients with rapidly progressive periodontitis (RPP) and from 28 periodontally normal subjects was tested by using polymorphonuclear leukocyte (PMN) chemiluminescence and bactericidal assays. Peak chemiluminescence values correlated strongly with killing observed in the PMN-dependent bactericidal assay (r = 0.88; P < 0.001). Neither the mean IgG titer nor the mean peak chemiluminescence differed significantly between the two groups. However, when the relationship between chemiluminescence and titer was examined, regression analysis showed that antibodies present in low-titer normal sera were significantly more effective at opsonizing A. actinomycetemcomitans than antibodies present in low-titer RPP patient sera (P = 0.04). Thus, periodontally normal individuals may be better able than RPP patients to clear A. actinomycetemcomitans in early stages of colonization, and anti-A. actinomycetemcomitans antibodies in RPP patients may be relatively ineffective in preventing infection by this organism. PMID:1398993

Sjostrom, K; Darveau, R; Page, R; Whitney, C; Engel, D

1992-01-01

218

Cognitive performance of GBA mutation carriers with early-onset PD  

PubMed Central

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

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

219

Cooperative Genome-Wide Analysis Shows Increased Homozygosity in Early Onset Parkinson's Disease  

PubMed Central

Parkinson's disease (PD) occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of homozygosity. We carried out genome wide SNP genotyping to look for extended runs of homozygosity (ROHs) in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort. There is an increased rate of genome wide homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis. PMID:22427796

Nalls, Michael A.; Martinez, Maria; Schulte, Claudia; Holmans, Peter; Gasser, Thomas; Hardy, John; Singleton, Andrew B.; Wood, Nicholas W.; Brice, Alexis; Heutink, Peter; Williams, Nigel; Morris, Huw R.

2012-01-01

220

Involvement of Galectin-9/TIM-3 Pathway in the Systemic Inflammatory Response in Early-Onset Preeclampsia  

PubMed Central

Background Preeclampsia is a common obstetrical disease affecting 3-5% of pregnancies and representing one of the leading causes of both maternal and fetal mortality. Maternal symptoms occur as an excessive systemic inflammatory reaction in response to the placental factors released by the oxidatively stressed and functional impaired placenta. The T-cell immunoglobulin domain and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction. Methods The aim of our study was to investigate the expression and function of Galectin-9 and TIM-3 molecules by peripheral blood mononuclear cells and the possible role of Galectin-9/TIM-3 pathway in the immunoregulation of healthy pregnancy and early-onset preeclampsia. We determined TIM-3 and Gal-9 expression and cytotoxicicty of peripheral lymphocytes of early-onset preeclamptic women and healthy pregnant woman using flow cytometry. Results Investigating peripheral lymphocytes of women with early-onset preeclampsia, our results showed a decreased TIM-3 expression by T cells, cytotoxic T cells, NK cells and CD56dim NK cells compared to healthy pregnant women. Interestingly, we found a notably increased frequency of Galectin-9 positive cells in each investigated lymphocyte population in the case of early-onset preeclamptic patients. We further demonstrated increased cytotoxic activity by cytotoxic T and CD56dim NK cells in women with early-onset preeclampsia. Our findings showed that the strongest cellular cytotoxic response of lymphocytes occurred in the TIM-3 positive subpopulations of different lymphocytes subsets in early-onset preeclampsia. Conclusion These data suggest that Gal-9/TIM-3 pathway could play an important role in the immune regulation during pregnancy and the altered Galectin-9 and TIM-3 expression could result an enhanced systemic inflammatory response including the activation of Th1 lymphocytes in preeclampsia. PMID:23936526

Miko, Eva; Meggyes, Matyas; Bogar, Barbara; Schmitz, Nora; Barakonyi, Aliz; Varnagy, Akos; Farkas, Balint; Tamas, Peter; Bodis, Jozsef; Szekeres-Bartho, Julia; Illes, Zsolt; Szereday, Laszlo

2013-01-01

221

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

PubMed Central

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

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

2014-01-01

222

Temporal-lobe morphology differs between healthy adolescents and those with early-onset of depression  

PubMed Central

Major depressive disorder (MDD) has previously been linked to structural changes in several brain regions, particularly in the medial temporal lobes (Bellani, Baiano, Brambilla, 2010; Bellani, Baiano, Brambilla, 2011). This has been determined using voxel-based morphometry, segmentation algorithms, and analysis of shape deformations (Bell-McGinty et al., 2002; Bergouignan et al., 2009; Posener et al., 2003; Vasic et al., 2008; Zhao et al., 2008): these are methods in which information related to the shape and the pose (the size, and anatomical position and orientation) of structures is lost. Here, we incorporate information about shape and pose to measure structural deformation in adolescents and young adults with and without depression (as measured using the Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders criteria). As a hypothesis-generating study, a significance level of p < 0.05, uncorrected for multiple comparisons, was used, so that subtle morphological differences in brain structures between adolescent depressed individuals and control participants could be identified. We focus on changes in cortical and subcortical temporal structures, and use a multi-object statistical pose and shape model to analyze imaging data from 16 females (aged 16–21) and 3 males (aged 18) with early-onset MDD, and 25 female and 1 male normal control participants, drawn from the same age range. The hippocampus, parahippocampal gyrus, putamen, and superior, inferior and middle temporal gyri in both hemispheres of the brain were automatically segmented using the LONI Probabilistic Brain Atlas (Shattuck et al., 2008) in MNI space. Points on the surface of each structure in the atlas were extracted and warped to each participant's structural MRI. These surface points were analyzed to extract the pose and shape features. Pose differences were detected between the two groups, particularly in the left and right putamina, right hippocampus, and left and right inferior temporal gyri. Shape differences were detected between the two groups, particularly in the left hippocampus and in the left and right parahippocampal gyri. Furthermore, pose measures were significantly correlated with BDI score across the whole (clinical and control) sample. Since the clinical participants were experiencing their very first episodes of MDD, morphological alteration in the medial temporal lobe appears to be an early sign of MDD, and is unlikely to result from treatment with antidepressants. Pose and shape measures of morphology, which are not usually analyzed in neuromorphometric studies, appear to be sensitive to depressive symptomatology. PMID:25379426

Ramezani, Mahdi; Johnsrude, Ingrid; Rasoulian, Abtin; Bosma, Rachael; Tong, Ryan; Hollenstein, Tom; Harkness, Kate; Abolmaesumi, Purang

2014-01-01

223

Temporal-lobe morphology differs between healthy adolescents and those with early-onset of depression.  

PubMed

Major depressive disorder (MDD) has previously been linked to structural changes in several brain regions, particularly in the medial temporal lobes (Bellani, Baiano, Brambilla, 2010; Bellani, Baiano, Brambilla, 2011). This has been determined using voxel-based morphometry, segmentation algorithms, and analysis of shape deformations (Bell-McGinty et al., 2002; Bergouignan et al., 2009; Posener et al., 2003; Vasic et al., 2008; Zhao et al., 2008): these are methods in which information related to the shape and the pose (the size, and anatomical position and orientation) of structures is lost. Here, we incorporate information about shape and pose to measure structural deformation in adolescents and young adults with and without depression (as measured using the Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders criteria). As a hypothesis-generating study, a significance level of p < 0.05, uncorrected for multiple comparisons, was used, so that subtle morphological differences in brain structures between adolescent depressed individuals and control participants could be identified. We focus on changes in cortical and subcortical temporal structures, and use a multi-object statistical pose and shape model to analyze imaging data from 16 females (aged 16-21) and 3 males (aged 18) with early-onset MDD, and 25 female and 1 male normal control participants, drawn from the same age range. The hippocampus, parahippocampal gyrus, putamen, and superior, inferior and middle temporal gyri in both hemispheres of the brain were automatically segmented using the LONI Probabilistic Brain Atlas (Shattuck et al., 2008) in MNI space. Points on the surface of each structure in the atlas were extracted and warped to each participant's structural MRI. These surface points were analyzed to extract the pose and shape features. Pose differences were detected between the two groups, particularly in the left and right putamina, right hippocampus, and left and right inferior temporal gyri. Shape differences were detected between the two groups, particularly in the left hippocampus and in the left and right parahippocampal gyri. Furthermore, pose measures were significantly correlated with BDI score across the whole (clinical and control) sample. Since the clinical participants were experiencing their very first episodes of MDD, morphological alteration in the medial temporal lobe appears to be an early sign of MDD, and is unlikely to result from treatment with antidepressants. Pose and shape measures of morphology, which are not usually analyzed in neuromorphometric studies, appear to be sensitive to depressive symptomatology. PMID:25379426

Ramezani, Mahdi; Johnsrude, Ingrid; Rasoulian, Abtin; Bosma, Rachael; Tong, Ryan; Hollenstein, Tom; Harkness, Kate; Abolmaesumi, Purang

2014-01-01

224

Differences in early onset alcohol use and heavy drinking among persons with childhood and adulthood trauma.  

PubMed

We examined predictors for age at onset of first alcohol use and onset of heaviest alcohol use among men (n = 43) and women (n = 46) with alcohol dependence and PTSD, PTSD only, alcohol dependence only, and controls, with a particular focus on individuals with child versus adult trauma. Using analysis of variance procedures, results showed differences in onset of first alcohol use and heaviest drinking between childhood and adulthood trauma victims. These preliminary results indicate that behavioral mechanisms associated with alcohol use patterns between individuals with childhood and adulthood trauma are dissimilar, suggesting greater psychopathological consequences for individuals with childhood trauma. PMID:18058407

Waldrop, Angela E; Ana, Elizabeth J Santa; Saladin, Michael E; McRae, Aimee L; Brady, Kathleen T

2007-01-01

225

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

PubMed Central

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

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

2014-01-01

226

Predictability affects early perceptual processing of word onsets in continuous speech  

PubMed Central

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

Astheimer, Lori B.; Sanders, Lisa D.

2011-01-01

227

Fathering and Early Onset Conduct Problems: Positive and Negative Parenting, Father–Son Attachment, and the Marital Context  

Microsoft Academic Search

Research literature linking negative and positive aspects of the father–child relationship with early onset conduct problems is reviewed. Evidence from the Preschool Families Project, a longitudinal study of clinic-referred preschool boys at risk for conduct disorder, is presented, including previously unpublished data on father–child attachment. Both negative (e.g., harsh, angry, and physically punitive) and positive (involvement, warmth, and secure attachment)

Michelle DeKlyen; Matthew L. Speltz; Mark T. Greenberg

1998-01-01

228

Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia  

Microsoft Academic Search

INTRODUCTION: To gain a better understanding of the clinical and economic outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with early onset ventilator-associated pneumonia (VAP), we retrospectively analyzed a multihospital US database to identify patients with VAP over a 24 month period (2002–2003). METHOD: Data recorded included physiologic, laboratory, culture, and other clinical variables from 59 institutions. VAP

Andrew F Shorr; Ying P Tabak; Vikas Gupta; RS Johannes; Larry Z Liu; Marin H Kollef

2006-01-01

229

Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2\\/PKD1 cystic tissue  

Microsoft Academic Search

Polycystin-1 expression in PKD1, early-onset PKD1, and TSC2\\/PKD1 cystic tissue.BackgroundThe mutational mechanism responsible for cyst formation in polycystic kidney disease 1 gene (PKD1) remains controversial, with data indicating a two-hit mechanism, but also evidence of polycystin-1 expression in cystic tissue.MethodsTo investigate this apparent paradox, we analyzed polycystin-1 expression in cystic renal or liver tissue from 10 patients with truncating PKD1

Albert C. M. Ong; Peter C. Harris; David R. Davies; Lynn Pritchard; Sandro Rossetti; Simon Biddolph; David J. T. Vaux; Nicola Migone; Christopher J. Ward

1999-01-01

230

Changes in erythrocyte insulin receptors in normal dogs and keeshond dogs with inheritable, early onset, insulin dependent diabetes mellitus  

Microsoft Academic Search

Validation of a procedure to evaluate insulin receptors on erythrocytes (RBC-IR) in dogs is described. The specific binding of (¹²⁵I)iodoinsulin to RBC-IR of normal dogs is significantly greater than binding in keeshonds with an inheritable form of early onset diabetes mellitus. This decreased binding was due to a significant decrease in RBC-IR affinity in the diabetic keeshonds. To determine the

Klaassen

1986-01-01

231

Fatigue-induced early onset of anticipatory postural adjustments in non-fatigued muscles: support for a centrally mediated adaptation  

Microsoft Academic Search

Muscle fatigue has been shown to result in early onset of anticipatory postural adjustments (APAs) relative to those produced\\u000a in a non-fatigued state. This adaptation is thought to reflect an attempt to preserve postural stability during a focal movement\\u000a performed in a fatigued state. It remains unclear, however, whether this adaptation is of central (e.g., central nervous system\\u000a motor command)

Adam J. Strang; William P. Berg; Mathias Hieronymus

2009-01-01

232

Is CD36 gene polymorphism in region encoding lipid-binding domain associated with early onset CAD?  

PubMed

CD36 is a fatty acid translocase in striated muscle cells and cardiomyocytes. Some study suggested that alterations in CD36 gene may be associated with coronary artery disease (CAD) risk. The aim of the current study was to compare the frequency of CD36 variants in region encoding lipid-binding domain in Caucasian patients with early-onset CAD, no-CAD adult controls and neonates. The study group comprised 100 patients with early onset CAD. The genetic control groups were 306 infants and 40 no-CAD adults aged over 70years. Exons 4, 5 and 6 including fragments of flanking introns were studied using the denaturing high-performance liquid chromatography technique and direct sequencing. Changes detected in analyzed fragment of CD36: IVS3-6 T/C (rs3173798), IVS4-10 G/A (rs3211892), C311T (Thr104Ile, not described so far) in exon 5, G550A (Asp184Asn, rs138897347), C572T (Pro191Leu, rs143150225), G573A (Pro191Pro, rs5956) and A591T (Thr197Thr, rs141680676) in exon 6. No significant differences in the CD36 genotype, allele and haplotype frequencies were found between the three groups. Only borderline differences (p=0.066) were found between early onset CAD patients and newborns in the frequencies of 591T allele (2.00% vs 0.50%) and CGCGCGT haplotype (2.00% vs 0.50%) with both IVS3-6C and 591T variant alleles. In conclusion, CD36 variants: rs3173798, rs3211892, rs138897347, rs5956, rs143150225 rs141680676 and C311T do not seem to be involved in the risk of early-onset CAD in Caucasian population. PMID:23856131

Ra?, Monika; Safranow, Krzysztof; Kurzawski, Grzegorz; Krzystolik, Andrzej; Chlubek, Dariusz

2013-11-01

233

Parental R-Rated Movie Restriction and Early-Onset Alcohol Use*  

PubMed Central

Objective: The aim of this study was to determine if parental restriction regarding Restricted-rated movies (R movies) predicts lower rates of early-onset alcohol use. Method: Students from 15 northern New England middle schools were surveyed in 1999, and never-drinkers were resurveyed 13–26 months later to determine alcohol use. Drinking was determined by the question, “Have you ever had beer, wine, or other drink with alcohol that your parents didn't know about?” R-movie restriction was assessed by the question, “How often do your parents allow you to watch movies that are rated R?” Results: The sample included 2,406 baseline never-drinkers who were surveyed at follow-up, of whom 14.8% had initiated alcohol use. At baseline, 20% reported never being allowed to watch R movies, and 21% reported being allowed all the time. Adolescents allowed to watch R-rated movies had higher rates of alcohol initiation (2.9% initiation among never allowed, 12.5% once in a while, 18.8% sometimes, and 24.4% all the time). Controlling for sociodemographics, personality characteristics, and authoritative parenting style, the adjusted odds ratios for initiating alcohol use were 3.0 (95% CI [1.7, 5.1]) for those once in a while allowed, 3.3 [1.9, 5.6] for those sometimes allowed, and 3.5 [2.0, 6.0] for those always allowed to watch R-rated movies. Alcohol initiation was more likely if R-rated movie restriction relaxed over time; tightening of restriction had a protective effect (p < .001). A structural model was developed that modeled two latent parenting constructs: (a) authoritative parenting and (b) media parenting. Both constructs had direct inverse paths to trying alcohol and indirect paths through lower exposure to R-rated movies. Conclusions: After accounting for differences in authoritative parenting style, adolescents reporting lesser restrictions for R movies have higher odds of future alcohol use. The structural model suggests that media parenting operates independently from authoritative parenting and should be incorporated explicitly into parenting prevention programs. PMID:20409440

Tanski, Susanne E.; Dal Cin, Sonya; Stoolmiller, Mike; Sargent, James D.

2010-01-01

234

TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's syndrome: association with age, hippocampal sclerosis and clinical phenotype.  

PubMed

TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the temporal cortex and hippocampus of 11 patients with autosomal dominant familial forms of Alzheimer's disease (FAD), 169 patients with sporadic AD [85 with early onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after this age (LOAD)], 50 individuals with Down's Syndrome (DS) and 5 patients with primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present, overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85 (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where 24/84 (29%) patients showed such changes. There were no demographic differences, other than onset age, between AD patients with or without TDP-43-ir pathological changes. Double immunolabelling indicated that these TDP-43-ir inclusions were frequently ubiquitinated, but were only rarely AT8 (tau) immunoreactive. Only 3 elderly DS individuals and 4/5 cases of primary HS showed similar changes. Overall, 21.7% of AD cases and 6% DS cases showed hippocampal sclerosis (HS). However, only 9% FAD cases and 16% EOAD cases showed HS, but 29% LOAD cases showed HS. The proportion of EOAD cases with both TDP-43 pathology and HS tended to be greater than those in LOAD, where nearly half of all the cases with TDP-43 pathology did not show HS. The presence of TDP-43-ir changes in AD and DS may therefore be a secondary phenomenon, relating more to ageing than to AD itself. Nevertheless, a challenge to such an interpretation comes from the finding in AD of a strong relationship between TDP-43 pathology and cognitive phenotype. Patients with TDP-43 pathology were significantly more likely to present with an amnestic syndrome than those without (p < 0.0001), in keeping with pathological changes in medial temporal lobe structures. HS was also associated more commonly with an amnestic presentation (p < 0.005), but this association disappeared when TDP-43-positive cases were excluded from the analysis. TDP-43 may, after all, be integral to the pathology of AD, and to some extent determine the clinical phenotype present. PMID:21968532

Davidson, Yvonne S; Raby, Samantha; Foulds, Penelope G; Robinson, Andrew; Thompson, Jennifer C; Sikkink, Stephen; Yusuf, Imran; Amin, Hanan; DuPlessis, Daniel; Troakes, Claire; Al-Sarraj, Safa; Sloan, Carolyn; Esiri, Margaret M; Prasher, Vee P; Allsop, David; Neary, David; Pickering-Brown, Stuart M; Snowden, Julie S; Mann, David M A

2011-12-01

235

Periodontal Plastic Surgery  

MedlinePLUS

... attachment to the teeth is abnormal and bone changes may be evident through x-rays. A dentist ... diagnosis has been made, beginning with conservative behavioral changes and extending to periodontal plastic surgery. Treating Periodontal ...

236

Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1  

PubMed Central

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression. PMID:21935407

Fredman, Gabrielle; Oh, Sungwhan F.; Ayilavarapu, Srinivas; Hasturk, Hatice; Serhan, Charles N.; Van Dyke, Thomas E.

2011-01-01

237

Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome  

PubMed Central

Introduction Several studies evaluated the prevalence of Lynch Syndrome (LS) in young onset colorectal cancer (CRC) patients and the results were extremely variable (5%-20%). Immunohistochemistry (IHC) for MMR proteins and/or MSI analysis are screening tests that are done, either by themselves or in conjunction, on colon cancer tissue to identify individuals at risk for LS. The primary aim of our study was to evaluate the prevalence of LS in a large series of early-onset CRC without family history compared with those with family history. The secondary aim was to assess the diagnostic accuracy of IHC and MSI analysis as pre-screening tools for LS. Methods Early-onset CRC patients (? 50 years) were prospectively recruited in the study. IHC and MSI analysis were performed in all the patients. Germ-line mutation analysis (GMA) was carried out in all MMR deficient tumors. A logistic regression model was performed to identify clinical features predictive of MSI-H. Results 117 early onset CRC cases were categorized in three groups (A, B, C) according with family history of CRC. IHC and MSI analysis showed MMR deficiency in 6/70 patients (8.6%) of group A, 24/40 patients (60%) of group B and none of group C. GMA showed a deleterious mutation in 19 (47.5%) patients of group B. MSI analysis had a diagnostic accuracy of 95.7% (CI 92.1-99.4) and IHC of 83.8% (CI 77.1-90.4). The logistic regression model revealed that by using a combination of the two features “No Amsterdam Criteria” and ”left sided CRC” to exclude MSI-H, accuracy was 89.7% (84.2-95.2). Conclusions Early-onset CRC patients, with left sided CRC and without family history are “at very low risk” for Lynch syndrome. The two simple criteria of family history and CRC site could be used as a pre-screening tool to evaluate whether or not patients should undergo tissue molecular screening. In the few cases of suspected LS (right sided CRC and/or Amsterdam Criteria), a reasonable approach could be to perform MSI analysis first and IHC afterwards only in MSI-H patients. PMID:24383517

2014-01-01

238

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

ERIC Educational Resources Information Center

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…

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

2009-01-01

239

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

ERIC Educational Resources Information Center

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…

Savage, Robert; Carless, Sue

2005-01-01

240

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

ERIC Educational Resources Information Center

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…

Leve, Leslie D.; Chamberlain, Patricia

2004-01-01

241

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early onset proband : supportive evidence  

E-print Network

1 Genome-wide scan for genes involved in bipolar affective disorder in 70 European families disorder, age at onset, genome wide search, linkage Running title : Genome wide scan in early onset bipolar to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might

Paris-Sud XI, Université de

242

A longitudinal study of differences in late- and early-onset geriatric depression: Depressive symptoms and psychosocial, cognitive, and neurological functioning  

Microsoft Academic Search

Objectives: Studies suggest early-onset depression (EOD) is associated with a more severe course of the depressive disorder, while late-onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume

Natalie Sachs-Ericsson; Elizabeth Corsentino; Jerad Moxley; Jennifer L. Hames; Nicole C. Rushing; Kathryn Sawyer; Thomas Joiner; Edward A. Selby; Steven Zarit; Ian H. Gotlib; David C. Steffens

2012-01-01

243

Radiographic interpretation of chronic periodontitis.  

PubMed

There has recently been a substantial change in our concept of periodontal disease and particular attention is now focused on that small proportion of the population who appear susceptible to its more aggressive forms rather than the majority in whom bone loss progresses very slowly. It is also apparent that the presently available clinical parameters are of little value in predicting future destructive activity. Under these circumstances, the aim of this paper is to review the contribution of radiography to the diagnosis of chronic periodontitis as traditionally perceived and then reassess its status in the light of these newer concepts. Panoramic radiography, followed by the appropriate periapical radiographs (taken with the paralleling technique), is proposed as an alternative to complete mouth intra-oral surveys on grounds of both diagnostic yield and radiation thrift. The five areas to which radiography, despite its limitations, can make a significant contribution are in the assessment of bone loss, mobility, occlusal trauma, calculus and marginal overhangs and crown-root ratio. The validity of the three criteria that have been proposed for the radiographic assessment of early periodontitis, loss of crestal bone height, marginal widening of the periodontal ligament and crestal irregularity, is evaluated in detail and it is concluded that only the first is of any diagnostic worth, providing at least two sequential radiographs are available. While there is an urgent need to develop techniques of greater sensitivity for the early identification of periodontal bone loss, there must be some doubt as to the value of any bone imaging technique in predicting the susceptible patient. Follow-up radiography should be limited to these sites showing clinical evidence of further disease activity. PMID:3294597

Hirschmann, P N

1987-03-01

244

Long-Term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD)  

Microsoft Academic Search

BackgroundEarly onset of mood symptoms in bipolar disorder has been associated with poor outcome in many studies; however, the factors that might contribute to poor outcome have not been adequately investigated.

Roy H. Perlis; Sachiko Miyahara; Lauren B. Marangell; Stephen R. Wisniewski; Michael Ostacher; Melissa P. DelBello; Charles L. Bowden; Gary S. Sachs; Andrew A. Nierenberg

2004-01-01

245

Association between SLC1A1 gene and early-onset OCD in the Han Chinese population: a case-control study.  

PubMed

Obsessive-compulsive disorder (OCD) is a common and severe mental illness, and its etiology still remains unknown. The glutamate transporter gene solute carrier family 1, member 1 was previously tested as a promising candidate for OCD by several research groups. However, subsequent studies were not consistent. OCD is a heterogeneous disease. Early-onset OCD is a demographically and clinically distinct subtype of OCD and may be a more homogeneous subtype. Gender-matched 244 early-onset OCD patients, 244 late-onset OCD patients, and 244 healthy controls were genotyped with four SNPs (rs10491734, rs2228622, rs301430, and rs301443) through TaqMan SNP genotyping assays. There were statistical differences in allele and genotype frequencies of rs10491734 in early-onset OCD patients compared to late-onset OCD or control subjects. The haplotype analysis showed that the four-locus haplotype (A-A-C-C and A-G-C-C) were associated with early onset obsessive-compulsive disorder after Bonferroni correction. The present study provided suggestive evidence that the rs10491734 was significantly associated with early-onset OCD in the Han Chinese population. However, these findings need further replication. PMID:23564280

Wu, Haisu; Wang, Xuemei; Xiao, Zeping; Yu, Shunying; Zhu, Liping; Wang, Dongxiang; Jiang, Kaida; Wang, Zhen; Zhang, Tianhong; Fralick, Drew

2013-06-01

246

A model for early onset of protection against lethal challenge with highly pathogenic H5N1 influenza virus.  

PubMed

Highly pathogenic avian influenza viruses of subtype H5N1 sporadically cause severe disease in humans and involve the risk of inducing a pandemic by gaining the ability for human-to-human transmission. In naïve poultry, primarily gallinaceous birds, the virus induces fatal disease and the used inactivated vaccines occasionally are unable to provide efficient and early onset of protection. Therefore, optimized vaccines must be developed and evaluated in model systems. In our study, we tested a novel H5 neuraminidase-deleted influenza A virus variant to analyze the induction of a very early onset of immunity. Ferrets, mice and chickens were each immunized with a single vaccine dose seven, three and one day before lethal challenge infection, respectively. Sound protection was conferred in 100% of animals immunized seven days prior to challenge infection. In these animals, no clinical signs were observed, and no challenge virus RNA was detected by real-time RT-PCR analyses of swabs, nasal washings, and organ samples. Moreover, the attenuated modified-live virus variant protected all chickens, mice, and ferrets as early as three days after vaccination against severe clinical signs. Chickens and ferrets developed hemagglutinin-specific antibodies after seven days, but no neuraminidase-specific antibodies, making this kind of neuraminidase-negative strain suitable for the DIVA ("differentiating vaccinated from infected animals") strategy. PMID:24674664

Röhrs, Susanne; Kalthoff, Donata; Beer, Martin

2014-05-01

247

Early onset of reproductive function in female rats treated with a high-fat diet.  

PubMed

Puberty onset in mammals is tightly coupled to the animal's nutritional and metabolic state. In the present study, we evaluated the effects of a high-fat diet on leptin and adiponectin levels, leptin mRNA expression and puberty onset in female rats. On day 21, female rats were divided into 2 groups, normal food (NF) and high-fat food (HF). The HF group showed a significantly earlier (P<0.001) date of vaginal opening and lower body weight (P<0.001) than the NF group. The rats fed the HF food had a significantly heavier uterus (P<0.05) than those fed the NF food, whereas the serum leptin and adiponectin levels and leptin mRNA expression were not significantly different between the NF and HF groups. We speculate that the fat-induced nutritional imbalance in young females may lead to neuroendocrine dysfunction during adolescence. PMID:23154420

Fungfuang, Wirasak; Nakao, Nobuhiko; Nakada, Tomoaki; Yokosuka, Makoto; Saito, Toru R

2013-05-01

248

Early onset of reduced reproductive performance with age in the Treecreeper ( Certhia familiaris )  

Microsoft Academic Search

Reductions in reproductive performance with age have been predicted to result from a general deterioration of performance,\\u000a i.e. senescence. Variation among species in the onset and rate of this deterioration depends on the age-independent extrinsic\\u000a mortality rate. If few individuals reach a specific age, the strength of selection for mechanisms that retard senescence will\\u000a be reduced. The aim of this

Anders Enemar; Jan-Åke Nilsson

2008-01-01

249

Structural and functional abnormalities in elderly patients clinically recovered from early- and late-onset depression  

Microsoft Academic Search

Background: Structural and functional brain changes have been described in elderly patients with unipolar affective disorder. Changes appear to be more marked in patients with late-onset depression, but the reversibility of such changes after clinical recovery is not known.Methods: Magnetic resonance imaging, electroencephalography (EEG), and cognitive tests were performed in 23 elderly patients (mean age 66.5 years) clinically recovered from

Sylvia Dahabra; C. Heather Ashton; Majid Bahrainian; Peter G Britton; I. Nicol Ferrier; Victor A McAllister; V. Richard Marsh; P. Brian Moore

1998-01-01

250

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

PubMed

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

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

2014-07-01

251

Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs.  

PubMed

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 48h, viability was assessed by ATP and gene expression of PDGF-B and TGF-?1 and the fibrosis markers Hsp47, ?Sma 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, TGF?-pathway inhibitors, were determined. After 48h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-?1 was not changed. Hsp47, ?Sma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48h, which was further increased by PDGF-BB and TGF-?1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGF?-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-?1 gene expression and the limited effect of the TGF?-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. PMID:24321339

Westra, Inge M; Oosterhuis, Dorenda; Groothuis, Geny M M; Olinga, Peter

2014-01-15

252

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

PubMed

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

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

2014-06-15

253

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

PubMed Central

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

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, Sinead; 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

254

Diagnostic Utility of Neutrophil CD64 as a Marker for Early-Onset Sepsis in Preterm Neonates  

PubMed Central

Introduction Neutrophil CD64 has been proposed as an early marker of sepsis. This study aims to evaluate the diagnostic utility of neutrophil CD64 for identification of early-onset sepsis in preterm neonates. Methods The prospective study was conducted in a neonatal intensive care unit between November 2010 and June 2011. Preterm neonates in whom infection was suspected when they were <12 hours of age were enrolled. Complete blood count with differential, blood culture, neutrophil CD11b and CD64 measurement were performed. Receiver operating characteristic curve analysis was performed to evaluate the performance of neutrophil CD64 as biomarker of sepsis. Results A total of 158 preterm neonates was enrolled, 88 of whom were suspected infection. The suspected sepsis group was of lesser gestational age (P<0.001) and lower birth weight (P<0.001), compared with controls. The hematologic profiles of the suspected sepsis group were characterized by higher white blood cell count, neutrophil counts and C-reactive protein. The suspected sepsis neonates had significantly higher neutrophil CD64 expression compared with controls. Neutrophil CD64 had an area value under the curve of 0.869 with an optimal cutoff values of 1010 phycoerythrin molecules bound/cell and it had a high sensitivity (81.82%) and negative predictive value (77.4%). The level of neutrophil CD64 was independent of antibiotic therapy within 24 hours after the onset of sepsis in preterm neonates. Conclusions Neutrophil CD64 is a highly sensitive marker for suspected early-onset sepsis in preterm neonates. Our study suggests that neutrophil CD64 may be incorporated as a valuable marker to diagnose infection. PMID:25033045

Dou, Yuhong; Li, Peipei; Chen, Rui; Liu, Helu

2014-01-01

255

Racial differences in early-onset renal disease among young adults: the coronary artery risk development in young adults (CARDIA) study  

Microsoft Academic Search

Although 11 million people in the United States have chronic renal insufficiency, little is known about ethnic\\/racial disparities for early-onset renal impairment. This study sought to determine whether there is an independent association between race\\/ethnicity and early-onset renal impairment and to identify other risk factors that might account for observed disparities. All Coronary Artery Risk Development in Young Adults subjects

Catherine O. Stehman-Breen; Daniel Gillen; Michael Steffes; David R. Jacobs; Cora E. Lewis; Catarina I. Kiefe; David Siscovick

2003-01-01

256

Quality of life after multiple trauma: the effect of early onset psychotherapy on quality of life in trauma patients  

Microsoft Academic Search

Background and aims  The aim of this study was to improve health-related quality of life (HRQOL) related to depression, anxiety, pain, physical\\u000a functioning and social aspects for severely injured trauma survivors by early onset cognitive behavioural therapy applied\\u000a on the surgical ward.\\u000a \\u000a \\u000a \\u000a Materials and methods  The study was a randomised, controlled study. Of 298 primary screened patients 171 were eligible and randomised.

Nicola Pirente; Christine Blum; Silja Wortberg; Sevgi Bostanci; Eva Berger; Rolf Lefering; Bertil Bouillon; Klaus E. Rehm; Edmund A. M. Neugebauer

2007-01-01

257

Age at the onset of senescence in birds and mammals is predicted by early-life performance  

PubMed Central

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

Péron, Guillaume; Gimenez, Olivier; Charmantier, Anne; Gaillard, Jean-Michel; Crochet, Pierre-André

2010-01-01

258

Imitating actions on objects in early-onset and regressive autism: Effects and implications of task characteristics on performance  

PubMed Central

This study was designed to examine the nature of object imitation performance in early autism. We hypothesized that imitation would be relatively preserved when behaviors on objects resulted in salient instrumental effects. We designed tasks in which, in one condition, the motor action resulted in a salient, meaningful effect on an object, whereas in the other condition, the same action resulted in a less salient effect because of differing object characteristics. The motor aspects of the tasks did not vary across conditions. Four participant groups of 2- to 5-year-olds were examined: 17 children with early-onset autism, 24 children with regressive onset autism, 22 children with developmental delays, and 22 children with typical development. Groups were matched on nonverbal skills, and differences in verbal development were examined as a moderator of imitative ability. Results revealed an interaction of group by condition, with the combined autism group failing more tasks than the combined comparison groups, and failing more tasks in the less salient condition than in the more salient condition, as hypothesized. Analyses of autism subgroups revealed these effects were primarily because of the regression onset group. Accuracy of motor performance was examined by analyzing errors. Among children passing imitative acts, there were no group differences and no condition effects in the number, type, or pattern of performance errors. Among children passing the tasks, the group with autism did not demonstrate more emulation errors (imitating the goal but not the means) than other groups. There was no evidence that either motor or attentional aspects of the tasks contributed to the poorer imitative performance of the children with autism. PMID:20102648

Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

2010-01-01

259

The tumor cell-host organ interface in the early onset of metastatic organ colonisation.  

PubMed

Metastatic lesions are the leading cause of death among cancer patients. These lesions usually originate from clonal proliferation of single tumor cells dispersed from the primary tumor into the circulation which finally arrest in the capillary bed of distant organs. The microenvironment within the circulation of potential metastatic target organs provides a variety of pro- and anti- metastatic stimuli regulating the onset of organ colonisation by metastatic tumor cells. Mechanical shear stress, anoikis and cell mediated cytotoxicity within the microcirculation probably clear most circulating tumor cells. Adhesion, and eventually extravasation, are essential initial interactions of circulating tumor cells with distant organs and can provide escape from the cytotoxic environment within the circulation. Adhesion to the capillary wall is mostly controlled by the organ-specific availability of adhesion molecules on tumor cells, the endothelium, and the composition of the underlying extracellular matrix. The availability of pro-adhesive and pro-migratory paracrine signals provided by the organ specific microenvironment can further initiate the onset of metastatic organ colonisation. Tumor cell and microenvironment factors regulating survival within the microcirculation, adhesion and extravasation of tumor cells are highlighted in the review. PMID:18058027

Gassmann, Peter; Haier, Joerg

2008-01-01

260

A cotwin-control analysis of drug use and abuse/dependence risk associated with early-onset cannabis use.  

PubMed

We assessed whether, after controlling for genetic and shared environmental influences, early cannabis use remains a significant predictor of other drug use, abuse, and dependence, and whether the risk for early-users is greater than that for later cannabis users. Data from a 1992 telephone diagnostic interview of 8169 male twins (M=42.0 years at interview) who served in the U.S. military during the Vietnam-era were used to identify a subsample of 293 monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for early cannabis use (before age 18). Using cotwin-control analyses, outcomes assessed were: lifetime illegal drug use (stimulant/cocaine, sedative, opiate, and hallucinogen/PCP), lifetime DSM-III-R illegal drug abuse/dependence, and lifetime DSM-III-R alcohol dependence. After controlling for covariates, early cannabis users were at greater risk than their later/never-using cotwins for 8 of 9 substance-related comparisons, including: using other illegal drugs (ORs: 2.71-4.09), having illegal drug abuse/dependence (ORs: 2.02-2.13), and developing alcohol dependence (OR=2.36). When analyses were limited to pairs in which the cotwin used cannabis later, early and later-users only differed significantly on sedative, opiate, and hallucinogen use. After familial influences on early cannabis use were controlled for, cannabis use-regardless of the age of initiation-still conferred increased risk of other illegal drug use, drug abuse/dependence, and alcohol dependence. In contrast to previous research, there is limited evidence for increased risk associated with early-onset use in this sample of Vietnam-era veterans. PMID:19717242

Grant, Julia D; Lynskey, Michael T; Scherrer, Jeffrey F; Agrawal, Arpana; Heath, Andrew C; Bucholz, Kathleen K

2010-01-01

261

Modeling susceptibility to periodontitis.  

PubMed

Chronic inflammatory diseases like periodontitis have a complex pathogenesis and a multifactorial etiology, involving complex interactions between multiple genetic loci and infectious agents. We aimed to investigate the influence of genetic polymorphisms and bacteria on chronic periodontitis risk. We determined the prevalence of 12 single-nucleotide polymorphisms (SNPs) in immune response candidate genes and 7 bacterial species of potential relevance to periodontitis etiology, in chronic periodontitis patients and non-periodontitis control individuals (N = 385). Using decision tree analysis, we identified the presence of bacterial species Tannerella forsythia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and SNPs TNF -857 and IL-1A -889 as discriminators between periodontitis and non-periodontitis. The model reached an accuracy of 80%, sensitivity of 85%, specificity of 73%, and AUC of 73%. This pilot study shows that, on the basis of 3 periodontal pathogens and SNPs, patterns may be recognized to identify patients at risk for periodontitis. Modern bioinformatics tools are valuable in modeling the multifactorial and complex nature of periodontitis. PMID:23100272

Laine, M L; Moustakis, V; Koumakis, L; Potamias, G; Loos, B G

2013-01-01

262

The Early Onset of Asymmetric Outflow During the Planetary Nebula Formation Process  

NASA Astrophysics Data System (ADS)

We propose to study early mass loss in the planetary nebula {PN} formation process using the high resolution imaging capabilities of HST. While tremendous progress has been made in understanding the late stages of PN formation, the details of the earliest phases of this metamorphosis are still vague. A knowledge of the characteristics of the mass loss occurring as a star leaves the asymptotic giant branch {AGB} is crucial to a complete picture of the PN development, since early mass loss is thought to determine the final shape of an object by confining the faster winds that occur later in the formation process. Unfortunately, there is little observational evidence that probes the distribution of this early ejecta. Is the final morphology of a PN imprinted at early times as suggested by the formation models? Fully developed PNe display a variety of morphologies ranging from round to bipolar. Based on the formation models we might expect material ejected early in the development of a PN to also exhibit a range of morphologies. Is this what we observe? We will directly address these questions by obtaining PC2 images of a sample of AGB/post-AGB stars. We have shown, using polarimetry, that the stars in this sample possess extended scattering envelopes that are spatially unresolved from the ground, but can be resolved using HST. These observations will reveal the morphology of the ejecta in the first stages of the PN formation process, thus testing the validity of the current models of PN formation.

Trammell, Susan

1996-07-01

263

Coercive Family Process and Early-Onset Conduct Problems From Age 2 to School Entry  

PubMed Central

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

Smith, Justin D.; Dishion, Thomas J.; Shaw, Daniel S.; Wilson, Melvin N.; Winter, Charlotte C.; Patterson, Gerald R.

2013-01-01

264

Coercive family process and early-onset conduct problems from age 2 to school entry.  

PubMed

The emergence and persistence of conduct problems (CPs) during early childhood is a robust predictor of behavior problems in school and of 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 CPs (ages 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 CPs and to designing optimal strategies for reducing problem behavior in early childhood with families most in need. PMID:24690305

Smith, Justin D; Dishion, Thomas J; Shaw, Daniel S; Wilson, Melvin N; Winter, Charlotte C; Patterson, Gerald R

2014-11-01

265

Early infantile sensory-motor neuropathy with late onset respiratory distress.  

PubMed

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

Blaschek, Astrid; Gläser, Dieter; Kuhn, Marius; Schroeder, Andreas Sebastian; Wimmer, Cornelius; Heimkes, Bernd; Schön, Carola; Müller-Felber, Wolfgang

2014-03-01

266

Early onset of neurological symptoms in fragile X premutation carriers exposed to neurotoxins  

PubMed Central

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

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

267

T2 Relaxometry Using 3.0-Tesla Magnetic Resonance Imaging of the Brain in Early- and Late-Onset Restless Legs Syndrome  

PubMed Central

Background and Purpose Previous T2 relaxometry studies have provided evidence for regional brain iron deficiency in patients with restless legs syndrome (RLS). Measurement of the iron content in several brain regions, and in particular the substantia nigra (SN), in early- and late-onset RLS patients using T2 relaxometry have yielded inconsistent results. In this study the regional iron content was assessed in patients with early- and late-onset RLS using magnetic resonance imaging (MRI), and compared the results with those in controls. Methods Thirty-seven patients with idiopathic RLS (20 with early onset and 17 with late onset) and 40 control subjects were studied using a 3.0-tesla MRI with a gradient-echo sampling of free induction decay and echo pulse sequence. The regions of interest in the brain were measured independently by two trained analysts using software known as medical image processing, analysis, and visualization. The results were compared and a correlation analysis was conducted to investigate which brain areas were related to RLS clinical variables. Results The iron index in the SN was significantly lower in patients with late-onset RLS than in controls (p=0.034), while in patients with early-onset RLS there was no significant difference. There was no significant correlation between the SN iron index of the late-onset RLS group and clinical variables such as disease severity. Conclusions Late-onset RLS is associated with decreased iron content in the SN. This finding supports the hypothesis that regional brain iron deficiency plays a role in the pathophysiology of late-onset RLS. PMID:25045371

Moon, Hye-Jin; Chang, Yongmin; Lee, Yeong Seon; Song, Hee Jin; Chang, Hyuk Won; Ku, Jeonghun

2014-01-01

268

Anterior Segment Dysgenesis and Early-Onset Glaucoma in nee Mice with Mutation of Sh3pxd2b  

PubMed Central

Purpose. Mutations in SH3PXD2B cause Frank-Ter Haar syndrome, a rare condition characterized by congenital glaucoma, as well as craniofacial, skeletal, and cardiac anomalies. The nee strain of mice carries a spontaneously arising mutation in Sh3pxd2b. The purpose of this study was to test whether nee mice develop glaucoma. Methods. Eyes of nee mutants and strain-matched controls were comparatively analyzed at multiple ages by slit lamp examination, intraocular pressure recording, and histologic analysis. Cross sections of the optic nerve were analyzed to confirm glaucomatous progression. Results. Slit lamp examination showed that, from an early age, nee mice uniformly exhibited severe iridocorneal adhesions around the entire circumference of the eye. Presumably as a consequence of aqueous humor outflow blockage, they rapidly developed multiple indices of glaucoma. By 3 to 4 months of age, they exhibited high intraocular pressure (30.8 ± 12.5 mm Hg; mean ± SD), corneal opacity, and enlarged anterior chambers. Although histologic analyses at P17 did not reveal any indices of damage, similar analysis at 3 to 4 months of age revealed a course of progressive retinal ganglion cell loss, optic nerve head excavation, and axon loss. Conclusions. Eyes of nee mice exhibit anterior segment dysgenesis and early-onset glaucoma. Because SH3PXD2B is predicted to be a podosome adaptor protein, these findings implicate podosomes in normal development of the iridocorneal angle and the genes influencing podosomes as candidates in glaucoma. Because of the early-onset, high-penetrance glaucoma, nee mice offer many potential advantages as a new mouse model of the disease. PMID:21282566

Mao, Mao; Hedberg-Buenz, Adam; Koehn, Demelza; John, Simon W. M.

2011-01-01

269

Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21  

Microsoft Academic Search

Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of

Jeff M. Hall; Ming K. Lee; Beth Newman; Jan E. Morrow; Lee A. Anderson; Bing Huey; Mary-Claire King

1990-01-01

270

Early-onset dysfunction of retrosplenial cortex precedes overt amyloid plaque formation in Tg2576 mice  

PubMed Central

A mouse model of amyloid pathology was used to first examine using a cross-sectional designchanges in retrosplenial cortex activity in transgenic mice aged 5, 11, 17, and 23 months. Attention focused on: 1) overt amyloid labeled with ?-amyloid(1-42) and Congo Red staining, 2) metabolic function assessed by the enzyme, cytochrome oxidase, and 3) neuronal activity as assessed indirectly by the immediate-early gene, c-Fos. Changes in cytochrome oxidase and c-Fos activity were observed in the retrosplenial cortex in Tg2576 mice as early as 5 months of age, long before evidence of plaque formation. Subsequent analyses concentrating on this early dysfunction revealed at 5-months pervasive, amyloid precursor protein (APP)-derived peptide accumulation in the retrosplenial cortex and selective afferents (anterior thalamus, hippocampus), which was associated with the observed c-Fos hyporeactivity. These findings indicate that retrosplenial cortex dysfunction occurs during early stages of amyloid production in Tg2576 mice and may contribute to cognitive dysfunction. PMID:21093545

Poirier, Guillaume L.; Amin, Eman; Good, Mark A.; Aggleton, John P.

2014-01-01

271

Early-onset cannabis use and cognitive deficits: what is the nature of the association?  

Microsoft Academic Search

Background: Individuals who initiate cannabis use at an early age, when the brain is still developing, might be more vulnerable to lasting neuropsychological deficits than individuals who begin use later in life. Methods: We analyzed neuropsychological test results from 122 long-term heavy cannabis users and 87 comparison subjects with minimal cannabis exposure, all of whom had undergone a 28-day period

Harrison G Pope; Amanda J Gruber; James I Hudson; Geoffrey Cohane; Marilyn A Huestis; Deborah Yurgelun-Todd

2003-01-01

272

Maternal History and Uterine Artery Doppler in the Assessment of Risk for Development of Early- and Late-Onset Preeclampsia and Intrauterine Growth Restriction  

PubMed Central

Objective. To examine the value of one-step uterine artery Doppler at 20 weeks of gestation in the prediction pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). Methods. A prospective multicentre study that included all women with singleton pregnancies at 19–22 weeks of gestation (w). The mean pulsatility index (mPI) of both uterine arteries was calculated. Receiver-operating characteristics curves (ROC) were drawn to compare uterine artery Doppler and maternal risk factors for the prediction of early-onset PE and/or IUGR (before 32 w) and late-onset PE and/or IUGR. Results. 6,586 women were included in the study. Complete outcome data was recorded for 6,035 of these women (91.6%). PE developed in 75 (1.2%) and IUGR in 69 (1.1%) cases. Uterine Doppler mPI was 0.99 and the 90th centile was 1.40. For 10% false-positive rate, uterine Doppler mPI identified 70.6% of pregnancies that subsequently developed early-onset PE and 73.3% of pregnancies that developed early-onset IUGR. The test had a lower detection rate for the late-onset forms of the disease (23.5% for PE and 30% for IUGR). Maternal history has a low sensitivity in the detection of early-onset cases, although it is better at detecting late-onset PE. Conclusion. Uterine artery Doppler and maternal risk factors seem to select two different populations - early and late-onset PE which might suggest a different pathogenesis. PMID:19936122

Llurba, Elisa; Carreras, Elena; Gratacos, Eduard; Juan, Miquel; Astor, Judith; Vives, Angels; Hermosilla, Eduard; Calero, Ines; Millan, Pilar; Garcia-Valdecasas, Barbara; Cabero, Lluis

2009-01-01

273

Low levels of caries in aggressive periodontitis: A literature review  

PubMed Central

This article is a traditional literature review on caries levels in aggressive periodontitis. Aggressive periodontitis generally affects systemically healthy individuals aged <30 years (older individuals can also be affected) and is characterized by a young age of onset, rapid rate of disease progression, and familial aggregation of cases. Dental caries is caused by the dissolution of enamel by acid-producing bacteria present in the plaque biofilm, especially when the biofilm reaches critical mass due to improper oral hygiene. The association between caries level and aggressive periodontitis has long been debated. Initial research indicated that caries levels were high in patients with aggressive periodontitis, but high-quality studies have consistently shown that caries and aggressive periodontitis are inversely related. A recent in vitro study showed that Streptococcus mutans was killed more readily in the saliva of patients with aggressive periodontitis and Aggregatibacter actinomycetemcomitans positivity than in patients with A. actinomycetemcomitans negativity. Other mechanisms possibly explaining the inverse relationship between caries and aggressive periodontitis in cases of Down’s syndrome are also discussed in this literature review. The usefulness of caries level in the diagnosis of aggressive periodontitis in developing countries such as India, where the disease is diagnosed primarily on the basis of clinical and radiographic features and familial history is also discussed.

Sulugodu Ramachandra, Srinivas

2013-01-01

274

Early onset Paget's disease of bone caused by a novel mutation (78dup27) of the TNFRSF11A gene in a Chinese family  

PubMed Central

Aim: A previous study showed that individuals of Japanese descent affected by early onset familial Paget's disease of bone (PDB) carried a 27-bp duplication at position 75 (75dup27) in the TNFRSF11A gene encoding RANK. Here we report the identification of a novel mutation (78dup27) in exon 1 of TNFRSF11A in a Chinese family with early onset PDB. Methods: We conducted clinical and genetic studies in a non-consanguineous Chinese family with early onset PDB. The entire coding region of TNFRSF11A was amplified and directly sequenced directly. Results: A novel 27-bp duplication in exon 1 (78dup27) in TNFRSF11A was found in four affected individuals and one asymptomatic individual. Although this duplication was the same length as the previously identified mutation (27 bp, from bases 78 to 104), in our patients the nine duplicated amino acids in the RANK signal peptide were LLLLCALLA. The phenotypes of affected individuals in this family overlapped with both early onset PDB and classic PDB, but several distinguishing features were found in our patients. The key difference between our familial PDB and the Japanese early onset PDB was the age of onset, which in most of our patients was during their late 20s (except for the propositus' niece). Another notable difference was that the propositus' son (24 years old), who carried the 78dup27 mutation, had no clinical symptoms or bone abnormalities, except for increased serum ALP, OC and CTX. Conclusion: Our findings may provide a better understanding of the clinical features of early onset PDB and support the notion of a hot spot for mutations in exon 1 of the TNFRSF11A gene. PMID:19578385

Ke, Yao-hua; Yue, Hua; He, Jin-wei; Liu, Yu-juan; Zhang, Zhen-lin

2009-01-01

275

Risk Factors for Early-Onset Peripheral Neuropathy Caused by Vincristine in Patients With a First Administration of R-CHOP or R-CHOP-Like Chemotherapy  

PubMed Central

Background Peripheral neuropathy is a well-known side effect of vincristine (VCR), a microtubule inhibitor used for R-CHOP or R-CHOP-like (namely R-CVP and R-THP-COP) regimens. Previous studies have shown that both the total dose of VCR and the number of treatment cycles are related to the incidence of VCR-induced peripheral neuropathy (VIPN). However, VIPN will also occur during the first treatment cycle regardless of the total dose of VCR or number of treatment cycles (early-onset VIPN). There is little information about early-onset VIPN, and it is difficult to predict. The present study’s goal was to identify risk factors for early-onset VIPN. Methods We analyzed the case records of patients who had their first administration of an R-CHOP or R-CHOP-like regimen between April 2008 and August 2013 at Tokushima University Hospital in Tokushima, Japan. To identify the risk factors for early-onset VIPN, we performed univariate and multivariate logistic regression analyses. Results Forty-one patients underwent an R-CHOP or R-CHOP-like regimen for the first time at Tokushima University Hospital between April 2008 and August 2013, and 14 patients had grade 1 or higher early-onset VIPN. A univariate analysis revealed that age, the dose of VCR and the concomitant use of aprepitant appeared to be the risk factors of early-onset VIPN. In our calculation using receiver-operator characteristics curves, the cut-off value for patient age was 65 years and that of the dose of VCR was 1.9 mg. A multivariate analysis revealed that VCR dose ? 1.9 mg and the concomitant use of the antiemetic aprepitant were independent risk factors for early-onset VIPN. Conclusions Our present study showed that the patients who had VCR dose ? 1.9 mg and the concomitant use of aprepitant had the risk for early-onset VIPN. This suggests that it is important to use aprepitant in light of the risk of early-onset VIPN and the benefit of aprepitant’s antiemetic effect in R-CHOP and R-CHOP-like regimens. PMID:24883150

Okada, Naoto; Hanafusa, Takeshi; Sakurada, Takumi; Teraoka, Kazuhiko; Kujime, Toshihide; Abe, Masahiro; Shinohara, Yasuo; Kawazoe, Kazuyoshi; Minakuchi, Kazuo

2014-01-01

276

Early-Onset Conduct Problems: Intersection of Conduct Problems and Poverty  

PubMed Central

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

Shaw, Daniel S.; Shelleby, Elizabeth C.

2014-01-01

277

Early-onset drug use and risk for drug dependence problems  

Microsoft Academic Search

There is substantial evidence that alcohol, tobacco, and cannabis dependence problems surface more quickly when use of these drugs starts before adulthood, but the evidence based on other internationally regulated drugs (e.g., cocaine) is meager. With focus on an interval of up to 24 months following first drug use, we examine drug-specific and age-specific variation in profiles of early-emerging clinical features

Chuan-Yu Chen; Carla L. Storr; James C. Anthony

2009-01-01

278

Psychological disorder, conditioning experiences, and the onset of dental anxiety in early adulthood.  

PubMed

Most studies examining the origins of dental fear and anxiety have relied on cross-sectional data. These are subject to several problems, such as recall and uncertainty concerning temporal relationships. This paper uses longitudinal data from the Dunedin Multidisciplinary Health and Development Study to assess risk factors for the development of dental anxiety in persons between the ages of 18 and 26 years. It was hypothesized that psychological factors would be as important as conditioning experiences in the genesis of dental anxiety over this period. The eight-year incidence of dental anxiety was 16.5%. Five variables entered models predicting onset: multiple fears, symptoms of substance dependence, previous experience of invasive dental treatment, dental visiting pattern, and the extraction of one or more teeth. Separate analyses for those avoiding and those using dental services resulted in different explanatory models. These results indicated that both psychological and conditioning variables contributed to the development of dental anxiety in this population of young adults. PMID:11499519

Locker, D; Thomson, W M; Poulton, R

2001-06-01

279

Clinical and neuropathological features of the Arctic APP mutation causing early onset Alzheimer's disease  

PubMed Central

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

Basun, Hans; Bogdanovic, Nenad; Ingelsson, Martin; Almkvist, Ove; Naslund, Jan; Axelman, Karin; Bird, Thomas D.; Nochlin, David; Schellenberg, Gerard D.; Wahlund, Lars-Olof; Lannfelt, Lars

2009-01-01

280

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration  

PubMed Central

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1GLU7ALA), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1GLU7ALA, compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1GLU7ALA relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system. PMID:23359680

Bilguvar, Kaya; Tyagi, Navneet K.; Ozkara, Cigdem; Tuysuz, Beyhan; Bakircioglu, Mehmet; Choi, Murim; Delil, Sakir; Caglayan, Ahmet O.; Baranoski, Jacob F.; Erturk, Ozdem; Yalcinkaya, Cengiz; Karacorlu, Murat; Dincer, Alp; Johnson, Michele H.; Mane, Shrikant; Chandra, Sreeganga S.; Louvi, Angeliki; Boggon, Titus J.; Lifton, Richard P.; Horwich, Arthur L.; Gunel, Murat

2013-01-01

281

A longitudinal study of differences in late and early onset geriatric depression: Depressive symptoms and psychosocial, cognitive, and neurological functioning  

PubMed Central

Objectives Studies suggest early onset depression (EOD) is associated with a more severe course of the depressive disorder, while late onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume loss. A second goal was to determine if LOD, compared with EOD, would demonstrate more cognitive and neuroimaging changes. Method At regular intervals over a four year period non-demented, older, depressed adults were assessed on the Mini Mental Status Examination (MMSE) and the Montgomery-Asberg Depression Rating Scale (MADRS). They were also assessed on Magnetic Resonance Imaging (MRI). Results Compared with LOD, EOD had more depressive symptoms, more suicidal thoughts, and less social support. Growth curve analyses indicated that EOD demonstrated higher levels of residual depressive symptoms over time. The LOD group exhibited a greater decrement in cognitive scores. Contrary to the glucocorticoid cascade hypothesis, participants with EOD lost right hippocampal volume at a slower rate than did participants with LOD. Right cerebrum gray matter was initially smaller among participants with LOD. Conclusions EOD is associated with greater severity of depressive illness. LOD is associated with more severe cognitive and neurological changes. These differences are relevant to understanding cognitive impairment in geriatric depression. PMID:22934752

Sachs-Ericsson, Natalie; Corsentino, Elizabeth; Moxley, Jerad; Hames, Jennifer L.; Collins, Nicole; Sawyer, Kathryn; Selby, Edward A.; Joiner, Thomas; Zarit, Steven; Gotlib, Ian H.; Steffens, David C.

2012-01-01

282

A large early-onset Alzheimer`s disease pedigree linked to chromosome 14q24.3  

SciTech Connect

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.

Hannequin, D. [CHU de Rouen (France); Campion, D. [INSERM, U155 Paris (France); Brice, A. [INSERM U289, Paris (France)] [and others

1994-09-01

283

Neonatal Early-Onset Sepsis Evaluations Among Well-Appearing Infants: Projected Impact of Changes in CDC GBS Guidelines  

PubMed Central

OBJECTIVE To determine (a) the proportion of asymptomatic infants born at ? 35 weeks gestation evaluated for early-onset sepsis (EOS) and exposed to postnatal antibiotics; (b) reasons for and outcomes of the evaluations, and (c) anticipated changes when applying the CDC 2010 guidelines to this study population. DESIGN/METHODS Retrospective cohort study of infants born at ? 35 weeks gestation in 2008–2009 in a large maternity center. RESULTS 7226 infants met study criteria: 1062 (14.7%) were evaluated for EOS and half of those evaluated received empiric antibiotics. 70.4% of evaluations were performed due to maternal intrapartum fever, but 23% were prompted by inadequate GBS prophylaxis alone. Three cases of blood culture-proven infection were identified. CONCLUSION Improved approaches are needed to identify asymptomatic infants at risk for EOS to decrease unnecessary evaluations and antibiotic exposure. Transition to the 2010 CDC GBS guidelines may eliminate a quarter of EOS evaluations among these infants. PMID:22814941

Mukhopadhyay, Sagori; Eichenwald, Eric C.; Puopolo, Karen M.

2013-01-01

284

Gait Analysis in a Mecp2 Knockout Mouse Model of Rett Syndrome Reveals Early-Onset and Progressive Motor Deficits  

PubMed Central

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the Mecp2 gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male Mecp2 knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of MeCP2-dysfunction in future preclinical therapeutic studies. PMID:25392929

Riddell, John S.; Bailey, Mark E. S.; Cobb, Stuart R.

2014-01-01

285

Elevated brain aluminium and early onset Alzheimer's disease in an individual occupationally exposed to aluminium: a case report  

PubMed Central

Introduction Aluminium is a known neurotoxin and occupational exposure to aluminium has been implicated in neurological disease including Alzheimer’s disease. Here we present the first comprehensive and unequivocal data demonstrating significantly elevated brain aluminium content in an individual occupationally exposed to aluminium. Case presentation A 66-year-old Caucasian man who died with Alzheimer’s disease showed significantly elevated brain aluminium content, 2.98 (2.73) ?g/g dry weight, n?=?46, following occupational exposure to aluminium over a period of 8 years. Conclusions That the individual developed an early onset aggressive form of Alzheimer’s disease suggests a role for aluminium in disease aetiology. That the exposure to aluminium was through occupational exposure to aluminium dust suggests a prominent role for the olfactory system and lungs in the accumulation of aluminium in the brain. PMID:24513181

2014-01-01

286

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-B activation: common genetic etiology with Blau syndrome  

Microsoft Academic Search

Early-onset sarcoidosis (EOS) and inher- itable Blau syndrome (BS) share charac- teristic clinical features of juvenile-onset systemic granulomatosis syndrome that mainly affects skin, joints, and eyes. How- ever, no direct evidence has been shown for the possible common origin of these 2 diseases. Recent discovery of CARD15 mutations in BS families encouraged us to investigate similar CARD15 mutations in EOS

Nobuo Kanazawa; Ikuo Okafuji; Naotomo Kambe; Ryuta Nishikomori; Mami Nakata-Hizume; Sonoko Nagai; Akihiko Fuji; Takenosuke Yuasa; Akira Manki; Yoshihiko Sakurai; Mitsuru Nakajima; Hiroko Kobayashi; Ikuma Fujiwara; Hiroyuki Tsutsumi; Atsushi Utani; Chikako Nishigori; Toshio Heike; Tatsutoshi Nakahata; Yoshiki Miyachi

287

Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease  

Microsoft Academic Search

Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease. To determine the effect of the ACE gene insertion\\/deletion (I\\/D) polymorphism, angiotensinogen gene M235T polymorphism and the angiotensin 1 receptor gene A1166C polymorphism on the age of onset of end-stage renal failure (ESRF) in PKD1 adult autosomal-dominant polycystic kidney

Keshwar Baboolal; David Ravine; Joe Daniels; Nigel Williams; Peter Holmans; Gerald A Coles; John D Williams

1997-01-01

288

Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease  

PubMed Central

Background: Combined treatment with inhaled corticosteroids and long acting ß2 agonists is approved for the treatment of chronic obstructive pulmonary disease (COPD), but little is known about the onset of effect of the combination. Methods: Data were used from 1465 patients with COPD entered into a large 1 year double blind trial with daily measurements of peak expiratory flow (PEF) and symptom scores. Results: PEF was significantly higher after 1 day in patients treated with salmeterol 50 µg twice daily or the salmeterol/fluticasone propionate combination 50/500 µg twice daily than placebo. In patients treated with fluticasone propionate 500 µg twice daily alone, PEF differed from placebo after 2 days. The differences after 2 weeks compared with placebo were 16 l/min (95% confidence interval (CI) 11 to 21), 11 l/min (95% CI 6 to 16), and 27 l/min (95% CI 22 to 33) for salmeterol, fluticasone propionate, and the salmeterol/fluticasone propionate combination, respectively. For all treatments the effect on PEF after 2 weeks was comparable to that seen at the end of the study. The difference between the salmeterol/fluticasone propionate combination and placebo after 2 weeks as a percentage of baseline was similar for PEF and clinic forced expiratory volume in 1 second (FEV1). Differences in breathlessness scores were statistically significant after 1 day for the group treated with salmeterol alone and after 2 days for the combination group. The 2 week change in FEV1 was only partly indicative of a long term response in individual patients. Conclusions: The effects of salmeterol and fluticasone propionate, alone or in combination, on PEF and breathlessness are seen within days and most of the obtainable effect on these parameters is reached within 2 weeks. PMID:15790985

Vestbo, J; Pauwels, R; Anderson, J; Jones, P; Calverley, P; on, b

2005-01-01

289

Postweaning exposure to dietary zearalenone, a mycotoxin, promotes premature onset of puberty and disrupts early pregnancy events in female mice.  

PubMed

Zearalenone (ZEA) is a mycotoxin commonly found in contaminated livestock feed and human food with levels in the range of ppb and low ppm. It was hypothesized that ZEA, an endocrine disruptor, could affect puberty and early pregnancy. To test this hypothesis, newly weaned (3 weeks old) C57BL/6J female mice were exposed to 0, 0.002, 4, 10, and 40 ppm ZEA and 0.05 ppm diethylstilbestrol (positive control) in phytoestrogen-free AIN-93G diet. Females exposed to 10 and 40 ppm ZEA diets showed earlier onset of vaginal opening. Those treated with 40 ppm ZEA diet also had earlier first copulation plug and irregular estrous cyclicity. At 8 weeks old, all females were mated with untreated stud males on AIN-93G diet during mating. Treatment resumed upon identification of a vaginal plug on gestation day 0.5 (D0.5). Embryo implantation was assessed on D4.5. Exposure to 40 ppm ZEA diet resulted in reduced percentage of plugged mice with implantation sites, distended uterine appearance, and retained expression of progesterone receptor in D4.5 uterine epithelium. To determine the exposure timing and mechanisms of disrupted embryo implantation, four groups of females were fed with 0 or 40 ppm ZEA diets during premating (weaning to mating) and postmating (D0.5-D4.5), respectively. Premating exposure to 40 ppm ZEA diet reduced fertilization rate, whereas postmating exposure to 40 ppm ZEA diet delayed embryo transport and preimplantation embryo development, which subsequently affected embryo implantation. These data demonstrate that postweaning exposure to dietary ZEA can promote premature onset of puberty and disrupt early pregnancy events. PMID:23291560

Zhao, Fei; Li, Rong; Xiao, Shuo; Diao, Honglu; Viveiros, Maria M; Song, Xiao; Ye, Xiaoqin

2013-04-01

290

Placental Endoplasmic Reticulum Stress and Oxidative Stress in the Pathophysiology of Unexplained Intrauterine Growth Restriction and Early Onset Preeclampsia  

PubMed Central

The pregnancy complications of unexplained intrauterine growth restriction and early onset preeclampsia are thought to share a common aetiology in placental malperfusion secondary to deficient maternal spiral artery conversion. A key question is whether the contrasting clinical manifestations reflect different placental pathologies, or whether they are due to altered maternal responses to a common factor derived from the placenta. Recently, molecular evidence of protein synthesis inhibition secondary to endoplasmic reticulum stress has provided an explanation for the small placental phenotype in both conditions. However, other pathways activated by more severe endoplasmic reticulum stress are only observed in placentas from pregnancies associated with early onset preeclampsia. Here, we review the literature and conclude that there is evidence of greater maternal vascular compromise of the placenta in these cases. We speculate that in cases of normotensive intrauterine growth restriction the placental pathology is centred predominantly around endoplasmic reticulum stress, whereas in cases complicated by preeclampsia oxidative stress is further superimposed. This causes the release of a potent mix of pro-inflammatory cytokines, anti-angiogenic factors and trophoblastic aponecrotic debris into the maternal circulation that causes the peripheral syndrome. Maternal and fetal constitutional factors may modulate how the placenta responds to the maternal vascular insult, and how the mother is affected by the placental factors released. However, the principal conclusion is that the difference between these two conditions lies in the severity of the initiating deficit in spiral arterial conversion, and the relative degrees of endoplasmic reticulum stress and oxidative stress induced in the placenta as a result. PMID:19081132

Burton, G.J.; Yung, H.-W.; Cindrova-Davies, T.; Charnock-Jones, D.S.

2009-01-01

291

A Novel Point Mutation in the KCNJ5 Gene Causing Primary Hyperaldosteronism and Early-Onset Autosomal Dominant Hypertension  

PubMed Central

Context: Aldosterone production in the adrenal zona glomerulosa is mainly regulated by angiotensin II, [K+], and ACTH. Genetic deletion of subunits of K+-selective leak (KCNK) channels TWIK-related acid sensitive K+-1 and/or TWIK-related acid sensitive K+-3 in mice results in primary hyperaldosteronism, whereas mutations in the KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) gene are implicated in primary hyperaldosteronism and, in certain cases, in autonomous glomerulosa cell proliferation in humans. Objective: The objective of the study was to investigate the role of KCNK3, KCNK5, KCNK9, and KCNJ5 genes in a family with primary hyperaldosteronism and early-onset hypertension. Patients and Methods: Two patients, a mother and a daughter, presented with severe primary hyperaldosteronism, bilateral massive adrenal hyperplasia, and early-onset hypertension refractory to medical treatment. Genomic DNA was isolated and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials. Results: Sequencing of the KCNJ5 gene revealed a single, heterozygous guanine to thymine (G ? T) substitution at nucleotide position 470 (n.G470T), resulting in isoleucine (I) to serine (S) substitution at amino acid 157 (p.I157S). This mutation results in loss of ion selectivity, cell membrane depolarization, increased Ca2+ entry in adrenal glomerulosa cells, and increased aldosterone synthesis. Sequencing of the KCNK3, KCNK5, and KCNK9 genes revealed no mutations in our patients. Conclusions: These findings explain the pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive aldosterone production. PMID:22628607

Sertedaki, Amalia; Kino, Tomoshige; Merakou, Christina; Hoffman, Dax A.; Hatch, Michael M.; Hurt, Darrell E.; Lin, Lin; Xekouki, Paraskevi; Stratakis, Constantine A.; Chrousos, George P.

2012-01-01

292

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

PubMed

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

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

2014-04-01

293

Role of Innate Host Defenses in Susceptibility to Early Onset Neonatal Sepsis  

PubMed Central

Neonatal sepsis continues to take a devastating toll globally. Although adequate to protect against invasive infection in most newborns, the distinct function of neonatal innate host defense coupled with impairments in adaptive immune responses, increases the likelihood of acquiring infection early in life with subsequent rapid dissemination and death. Unique differences exist between neonates and older populations with respect to the capacity, quantity, and quality of innate host responses to pathogens. Recent characterization of the age-dependent maturation of neonatal innate immune function has identified novel translational approaches that may lead to improved diagnostic, prophylactic and therapeutic modalities. PMID:20569810

Wynn, James L.; Levy, Ofer

2010-01-01

294

Screening models using multiple markers for early detection of late-onset preeclampsia in low-risk pregnancy  

PubMed Central

Background Our primary objective was to establish a cutoff value for the soluble fms-like tyrosine kinase 1(sFlt-1)/placental growth factor (PlGF) ratio measured using the Elecsys assay to predict late-onset preeclampsia in low-risk pregnancies. Our secondary objective was to evaluate the ability of combination models using Elecsys data, second trimester uterine artery (UtA) Doppler ultrasonography measurements, and the serum fetoplacental protein levels used for Down’s syndrome screening, to predict preeclampsia. Methods This prospective cohort study included 262 pregnant women with a low risk of preeclampsia. Plasma levels of pregnancy-associated plasma protein-A (PAPP-A) and serum levels of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A were measured, and sFlt-1/PlGF ratios were calculated. All women underwent UtA Doppler ultrasonography at 20 to 24 weeks of gestation. Results Eight of the 262 women (3.0%) developed late-onset preeclampsia. Receiver operating characteristic curve analysis showed that the third trimester sFlt-1/PlGF ratio yielded the best detection rate (DR) for preeclampsia at a fixed false-positive rate (FPR) of 10%, followed by the second trimester sFlt-1/PlGF ratio, sFlt-1 level, and PlGF level. Binary logistic regression analysis was used to determine the five best combination models for early detection of late-onset preeclampsia. The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio yielded a DR of 87.5% at a fixed FPR of 5%, the combination of second and third trimester sFlt-1/PlGF ratios yielded a DR of 87.5% at a fixed FPR of 10%, the combination of body mass index and the second trimester sFlt-1 level yielded a DR of 87.5% at a fixed FPR of 10%, the combination of the PAPP-A and inhibin-A levels yielded a DR of 50% at a fixed FPR of 10%, and the combination of the PAPP-A level and the third trimester sFlt-1/PlGF ratio yielded a DR of 62.5% at a fixed FPR of 10%. Conclusions The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio, and the combination of the second trimester sFlt-1 level with body mass index, were better predictors of late-onset preeclampsia than any individual marker. PMID:24444293

2014-01-01

295

Early smoking onset may promise initial pleasurable sensations and later addiction.  

PubMed

There is converging evidence suggesting a particular susceptibility to the addictive properties of nicotine among adolescents. The aim of the current study was to prospectively ascertain the relationship between age at first cigarette and initial smoking experiences, and to examine the combined effects of these characteristics of adolescent smoking behavior on adult smoking. It was hypothesized that the association between earlier age at first cigarette and later development of nicotine dependence may, at least in part, be attributable to differences in experiencing pleasurable early smoking sensations. Data were drawn from the participants of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study from birth to adulthood. Structured interviews at age 15, 19 and 22 years were conducted to assess the age at first cigarette, early smoking experiences and current smoking behavior in 213 young adults. In addition, the participants completed the Fagerström Test for Nicotine Dependence. Adolescents who smoked their first cigarette at an earlier age reported more pleasurable sensations from the cigarette, and they were more likely to be regular smokers at age 22. The age at first cigarette also predicted the number of cigarettes smoked and dependence at age 22. Thus, both the age of first cigarette and the pleasure experienced from the cigarette independently predicted aspects of smoking at age 22. PMID:21966958

Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Laucht, Manfred

2013-11-01

296

Onset and establishment of diazotrophs and other bacterial associates in the early life history stages of the coral Acropora millepora.  

PubMed

Early establishment of coral-microbial symbioses is fundamental to the fitness of corals, but comparatively little is known about the onset and succession of bacterial communities in their early life history stages. In this study, bacterial associates of the coral Acropora millepora were characterized throughout the first year of life, from larvae and 1-week-old juveniles reared in laboratory conditions in the absence of the dinoflagellate endosymbiont Symbiodinium to field-outplanted juveniles with established Symbiodinium symbioses, and sampled at 2 weeks and at 3, 6 and 12 months. Using an amplicon pyrosequencing approach, the diversity of both nitrogen-fixing bacteria and of bacterial communities overall was assessed through analysis of nifH and 16S rRNA genes, respectively. The consistent presence of sequences affiliated with diazotrophs of the order Rhizobiales (23-58% of retrieved nifH sequences; 2-12% of 16S rRNA sequences), across all samples from larvae to 12-month-old coral juveniles, highlights the likely functional importance of this nitrogen-fixing order to the coral holobiont. Dominance of Roseobacter-affiliated sequences (>55% of retrieved 16S rRNA sequences) in larvae and 1-week-old juveniles, and the consistent presence of sequences related to Oceanospirillales and Altermonadales throughout all early life history stages, signifies their potential importance as coral associates. Increased diversity of bacterial communities once juveniles were transferred to the field, particularly of Cyanobacteria and Deltaproteobacteria, demonstrates horizontal (environmental) uptake of coral-associated bacterial communities. Although overall bacterial communities were dynamic, bacteria with likely important functional roles remain stable throughout early life stages of Acropora millepora. PMID:25156176

Lema, Kimberley A; Bourne, David G; Willis, Bette L

2014-10-01

297

Early onset of ground state deformation in neutron deficient polonium isotopes.  

PubMed

In-source resonant ionization laser spectroscopy of the even-A polonium isotopes (192-210,216,218)Po has been performed using the 6p(3)7s (5)S(2) to 6p(3)7p (5)P(2) (?=843.38??nm) transition in the polonium atom (Po-I) at the CERN ISOLDE facility. The comparison of the measured isotope shifts in (200-210)Po with a previous data set allows us to test for the first time recent large-scale atomic calculations that are essential to extract the changes in the mean-square charge radius of the atomic nucleus. When going to lighter masses, a surprisingly large and early departure from sphericity is observed, which is only partly reproduced by beyond mean field calculations. PMID:21405388

Cocolios, T E; Dexters, W; Seliverstov, M D; Andreyev, A N; Antalic, S; Barzakh, A E; Bastin, B; Büscher, J; Darby, I G; Fedorov, D V; Fedosseyev, V N; Flanagan, K T; Franchoo, S; Fritzsche, S; Huber, G; Huyse, M; Keupers, M; Köster, U; Kudryavtsev, Yu; Mané, E; Marsh, B A; Molkanov, P L; Page, R D; Sjoedin, A M; Stefan, I; Van de Walle, J; Van Duppen, P; Venhart, M; Zemlyanoy, S G; Bender, M; Heenen, P-H

2011-02-01

298

PNPLA2 mutation: a paediatric case with early onset but indolent course.  

PubMed

Neutral lipid storage disease (NLSD) due to PNPLA2 mutation is a rare disorder with a severe muscular and cardiac outcome. All but one reported cases have been diagnosed during adulthood. It is thus ordinarily distinguished from Chanarin-Dorfman syndrome, a paediatric NLSD with a more widespread symptomatology. We report the case of a young child incidentally diagnosed with significant and persistent hyperCKemia. At 3 years, muscle biopsy showed marked lipid storage. A homozygous mutation in PNPLA2 was found. Fourteen years later, the noticeable outcome is the absence of muscle weakness at rest, a normal muscular MRI, and no cardiac involvement. Yet the patient exhibits some systemic features, notably hearing loss. This paediatric case of NLSD with myopathy indicates that important lipid accumulation may occur very early in the absence of patent clinical and imaging muscle involvement. Furthermore, PNPLA2 mutations may be associated with multisystem features more frequently encountered in Chanarin-Dorfman syndrome. PMID:24074500

Perrin, Laurine; Féasson, Léonard; Furby, Alain; Laforêt, Pascal; Petit, François M; Gautheron, Vincent; Chabrier, Stéphane

2013-12-01

299

Periodontitis associated with osteomalacia  

PubMed Central

Osteomalacia is a metabolic bone disorder characterized by an alternation of bone mineralization, bone pain, increased bone fragility and fractures. A 23-year-old female patient reported with short stature and depressed nasal bridge with oral manifestation showing partial anodontia and periodontitis. This case report attempt to highlights clinical, radiographic, biochemical features of osteomalacia and periodontitis.

Wankhede, Anand Narayanrao; Sayed, Arshad Jamal; Gattani, Deepti Rakesh; Bhutada, Girish Parashram

2014-01-01

300

Periodontal Examination and Probing  

MedlinePLUS

... and floss your teeth. The depth of the space between your tooth and gum — This space is known as the sulcus. It is the ... or periodontitis (more advanced disease). To measure these spaces, the dentist uses a periodontal probe. This is ...

301

Onset, Persistence and Structure of the Magnetic Field in the Early Earth (Invited)  

NASA Astrophysics Data System (ADS)

The Earth's magnetic field is sustained by fluid motions in the liquid iron core. A combination of thermal and compositional buoyancy drive vigorous fluid motions at the present time. However, the early Earth would have lacked compositional buoyancy from inner-core growth, requiring faster core cooling to maintain the magnetic field by thermal convection alone. The necessary heat flow at the core-mantle boundary is not prohibitive (~ 5 TW), so the dynamo does not depend on the existence of an inner core. Rapid cooling in the aftermath of a Moon-forming giant impact would almost certainly maintain a geodynamo, even if convection was mainly confined to a high temperature layer of material from the shocked core of the impactor. Lower heat flow through a mostly crystalline (but still hot) mantle is probably high enough to continue rapid cooling of the core and sustain a magnetic field for several hundred million years. A later transition to plate tectonics could plausibly extinguish the field if the efficiency of mantle convection is substantially reduced by the production of thick (and buoyant) oceanic crust. The geodynamo would restart after a sufficient decline in radiogenic heat production allowed the core to resume cooling. In order to explain the earliest paleomagnetic observations at 3.45 Ga, the surface heat flow would need to be roughly twice the present-day value. Thermal history models show that the geodynamo can switch off between 4.0 and 3.5 Ga, but the range of allowable parameters in these models is fairly narrow. It is more likely that the Earth has always possessed a magnetic field, although the structure of that field could be quite different at early times, particularly if convection is sufficiently vigorous to reduce the relative importance of rotation in the balance of forces. An unexplored question concerns the possible role of compositional buoyancy due to exsolution of dissolved components from the cooling liquid core. The initial composition of the core is complementary to the abundance of siderophile elements in the mantle. Recent experiments on the solubility of mantle minerals in liquid iron suggest that the core density deficit is compatible with chemical equilibration at mid-mantle depths and high temperature. This result appears to rule out the exsolution of O and Si, but other components have been suggested as possible candidates. The most likely choices include major elements with a large heat of solution and a small volume change. The additional source of compositional buoyancy could substantially lower the minimum heat flow needed to sustain a dynamo, but it does not alter the requirement for core cooling. Thus the existence of a magnetic field in the early Earth is a sensitive diagnostic of the internal dynamics.

Buffett, B. A.

2010-12-01

302

Chicken Embryos as a Potential New Model for Early Onset Type I Diabetes  

PubMed Central

Diabetic retinopathy (DR) is the leading cause of blindness among the American working population. The purpose of this study is to establish a new diabetic animal model using a cone-dominant avian species to address the distorted color vision and altered cone pathway responses in prediabetic and early diabetic patients. Chicken embryos were injected with either streptozotocin (STZ), high concentration of glucose (high-glucose), or vehicle at embryonic day 11. Cataracts occurred in varying degrees in both STZ- and high glucose-induced diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had decreased levels of blood insulin, glucose transporter 4 (Glut4), and phosphorylated protein kinase B (pAKT). In STZ-injected E20 embryos, the ERG amplitudes of both a- and b-waves were significantly decreased, the implicit time of the a-wave was delayed, while that of the b-wave was significantly increased. Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease in L-type voltage-gated calcium channel (L-VGCC) currents, which was reflected in the decreased level of L-VGCC?1D subunit in the STZ-diabetic retinas. Through these independent lines of evidence, STZ-injection was able to induce pathological conditions in the chicken embryonic retina, and it is promising to use chickens as a potential new animal model for type I diabetes. PMID:25133191

Shi, Liheng; Ko, Michael L.; Huang, Cathy Chia-Yu; Park, So-Young; Hong, Min-Pyo; Ko, Gladys Y.-P.

2014-01-01

303

Infrasound of lava fountains at Etna (Italy): implications for early warning eruption onset  

NASA Astrophysics Data System (ADS)

Volcano ash-eruptions produce devastating consequences for local communities and the air transport. Here we present the results of the real-time monitoring of the 2011-2012 sequences of lava fountains eruptions at Etna volcano (Italy) by means of small-aperture (250 m) infrasonic array located at 5 km of distance from the active vents. Most of the episodes generated sustained ash columns up to 10 km height with significant fallout of lapilli and ash up to 30 km of distance from summit craters causing problems at the Fontanarossa airport. The infrasonic activity before lava fountain episodes shows a clear acoustic trend and a distinctive waveform and frequency content of the recorded signals, reflecting the ongoing increasing of explosive level. Infrasound reveals that lava fountains are characterized by a sustained, low frequency, oscillations that are preceded by a violent and rhythmic strombolian activity. These characteristics allow the definition of infrasonic-based thresholds, which could be used as early warning system. The infrasonic array at Etna revealed to be a robust and efficient monitoring tool for real-time alert also in hostile weather conditions.

Ripepe, M.; Ulivieri, G.; Marchetti, E.

2012-04-01

304

Physical and sexual abuse in childhood as predictors of early onset cardiovascular events in women  

PubMed Central

Background Although child abuse is widespread and has been associated with cardiovascular disease (CVD) risk factors, its association with CVD events is not established. Methods and Results We examined associations of child abuse with CVD events among 66,798 women in the Nurses’ Health Study 2. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for myocardial infarction (n=262), stroke (n=251), and total CVD (n=513). Severe physical abuse was reported by 9% and forced sex by 11% of participants. Adjusting for age, race, childhood body type, parental education and family CVD history, the HR for CVD events was 0.91 (95% CI: 0.70–1.17) for mild physical abuse, 1.02 (0.82–1.26) for moderate physical abuse, and 1.46 (1.11–1.92) for severe physical abuse compared to none. Compared to women without childhood sexual abuse, the HR was 1.10 (0.88–1.35) for unwanted sexual touching, and 1.56 (1.23–1.99) for forced sex. After adjustment for adult lifestyle and medical risk factors, the HR for severe physical abuse was 1.13 (0.85–1.51) and that for forced sex was 1.25 (0.98–1.60); these intermediates accounted for much of the association of severe child abuse with CVD. Associations were similar for retrospectively and prospectively reported events. Women with abuse were less likely to release medical records. The associations were stronger for unconfirmed self-reported events than endpoints which were corroborated with additional information or medical record review. Conclusions Severe child abuse is a prevalent risk for early adult CVD that is partially mediated by preventable risk factors. PMID:22787111

Rich-Edwards, J.W.; Mason, S.; Rexrode, K.; Spiegelman, D.; Hibert, E.; Kawachi, I.; Jun, H.J.; Wright, R.J.

2012-01-01

305

Hypersexual Behavior in Frontotemporal Dementia: A Comparison with Early-Onset Alzheimer's Disease  

PubMed Central

The basis of hypersexual behavior among patients with dementia is not entirely clear. Hypersexual behavior may be a particular feature of behavioral variant frontotemporal dementia (bvFTD), which affects ventromedial frontal and adjacent anterior temporal regions specialized in interpersonal behavior. Recent efforts to define Hypersexual Disorder indicate an increasing awareness of heightened sexual activity as a source of personal distress and functional impairment, and clarification of hypersexuality in bvFTD could contribute to understanding the neurobiology of this behavior. This study reviewed 47 patients with bvFTD compared to 58 patients with Alzheimer’s disease (AD) for the presence of heightened sexual activity to the point of distress to caregivers and others. Hypersexual behavior occurred in 6 (13%) bvFTD patients compared to none of the AD patients. Caregivers judged all six bvFTD patients with hypersexual behavior as having a dramatic increase in sexual frequency from premorbid levels. All had general disinhibition, poor impulse control, and actively sought sexual stimulation. They had widened sexual interests and experienced sexual arousal from previously unexciting stimuli. One patient, with early and predominant right anterior temporal involvement, was easily aroused by slight stimuli, such as touching her palms. Although previously considered to be predominantly disinhibited sexual behavior as part of generalized disinhibition, these patients with dementia illustrate varying degrees of increased sexual desire. We conclude that bvFTD is uniquely associated with hypersexuality; it is more than just cognitive impairment with frontal disinhibition but also involves alterations in sexual drive, possibly from right anterior temporal-limbic involvement in this disease. PMID:23297146

Mendez, Mario F.; Shapira, Jill S.

2013-01-01

306

The Psychosis Recent Onset GRoningen Survey (PROGR-S): Defining Dimensions and Improving Outcomes in Early Psychosis  

PubMed Central

Psychotic disorders are among the most complex medical conditions. Longitudinal cohort studies may offer further insight into determinants of functional outcome after a psychotic episode. This paper describes the Psychosis Recent Onset in GRoningen Survey (PROGR-S) that currently contains data on 1076 early-episode patients with psychosis, including symptoms, personality, cognition, life events and other outcome determinants. Our goal in this report is to give an overview of PROGR-S, as a point of reference for future publications on the effect of cognition, personality and psychosocial functioning on outcomes. PROGR-S contains an extensive, diagnostic battery including anamnesis, biography, socio-demographic characteristics, clinical status, drug use, neuropsychological assessment, personality questionnaires, and physical status tests. Extensive follow-up data is available on psychopathology, physical condition, medication use, and care consumption. Sample characteristics were determined and related to existing literature. PROGR-S (period 1997–2009, n?=?718) included the majority of the expected referrals in the catchment area. The average age was 27 (SD?=?8.6) and two-thirds were male. The average IQ was lower than that in the healthy control group. The majority had been diagnosed with a psychotic spectrum disorder. A substantial number of the patients had depressive symptoms (479/718, 78%) and current cannabis or alcohol use (465/718, 75%). The level of community functioning was moderate, i.e. most patients were not in a relationship and were unemployed. The PROGR-S database contains a valuable cohort to study a range of aspects related to symptomatic and functional outcomes of recent onset psychosis, which may play a role in the treatment of this complex and disabling disorder. Results reported here show interesting starting points for future research. Thus, we aim to investigate long-term outcomes on the basis of cognition, personality, negative symptoms and physical health. Ultimately, we hope that this paper will contribute improving the health of patients with psychotic disorders. PMID:25412332

Liemburg, Edith J.; Castelein, Stynke; van Es, Frank; Scholte-Stalenhoef, Anne Neeltje; van de Willige, Gerard; Smid, Henderikus; Visser, Ellen; Knegtering, Henderikus; Bruggeman, Richard

2014-01-01

307

Elevated expression of KiSS-1 in placenta of Chinese women with early-onset preeclampsia.  

PubMed

Preeclampsia (PE) is a heterogeneous syndrome affecting 2% to 8% of all pregnancies and is the world's leading cause of fetal and maternal morbidity and mortality. In many cases of PE, shallow trophoblast invasion results in inappropriate maternal spiral artery remodeling and impaired placental function. Multiple genes have been implicated in trophoblast invasion, among which are KiSS-1 and GPR54. The gene product of KiSS-1 is metastin, which is a ligand for the receptor GPR54. Both metastin and GPR54 are expressed in the placenta of normal pregnancy and have been implicated in modulating trophoblast invasion through inhibiting migration of trophoblast cells. We have previously reported that the expression level of KiSS-1 was higher in trophoblasts from women with preeclampsia as compared to normal controls. Here, using quantitative RT-PCR, Western blot analysis and immunohistochemistry, we extend our analysis to demonstrate that elevated KiSS-1 expression occurs only in early-onset preeclampsia (ePE) and not late-onset preeclampsia (lPE). However, no difference in the expression levels of GPR54 is observed between ePE, lPE, and normal controls. Further, we show that KiSS-1 expression is also increased in placenta of intrauterine death and birth asphyxia in comparison to normal newborns of ePE and lPE. Our findings suggest that aberrant upregulation of KiSS-1 expression may contribute to the underlying mechanism of ePE as well as birth asphyxia. PMID:23145030

Qiao, Chong; Wang, Chunhui; Zhao, Jiao; Liu, Caixia; Shang, Tao

2012-01-01

308

Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia  

PubMed Central

Introduction To gain a better understanding of the clinical and economic outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with early onset ventilator-associated pneumonia (VAP), we retrospectively analyzed a multihospital US database to identify patients with VAP over a 24 month period (2002–2003). Method Data recorded included physiologic, laboratory, culture, and other clinical variables from 59 institutions. VAP was defined as new positive respiratory culture after at least 24 hours of mechanical ventilation (MV) and the presence of primary or secondary ICD-9-CM diagnosis codes of pneumonia. Outcomes measures included in-hospital morbidity and mortality for the population overall and after onset of VAP (duration of MV, intensive care unit [ICU] stay, in-hospital stay, and case mix and severity-adjusted operating cost). The overall cost was calculated at the hospital level using the Center for Medicare and Medicaid Services Cost/Charge Index for each calendar year. Results A total of 499 patients were identified as having VAP. S. aureus was the leading organism (31% of isolates). Patients with MRSA were significantly older than patients with methicillin-sensitive Staphylococcus aureus (MSSA; median age 74 versus 67 years, P < 0.05) and more likely to be medical patients. Compared with MSSA patients, MRSA patients on average consumed excess resources of 4.4 (95% confidence interval 0.6–8.2) overall MV days, 3.8 (-0.5 to +8.0) days of inpatient length of stay (LOS), 5.3 (1.0–9.7) ICU days, and US$7731 (-US$8393 to +US$23,856) total cost after controlling for case mix and other factors. Furthermore, MRSA patients needed excess resources after the onset of VAP (4.5 [95% confidence interval 1.0–8.1] MV days, 3.7 [-0.5 to +8.0] inpatient days, and 4.4 [0.4–8.4] ICU days) after controlling for the same case mix and admission severity covariates. Conclusion S. aureus remains a common cause of VAP. VAP due to MRSA was associated with increased overall LOS, ICU LOS, and attributable ICU LOS compared with MSSA-related VAP. Although not statistically significant because of small sample size and large variation, the attributable excess costs of MRSA amounted to approximately US$8000 per case after controlling for case mix and severity. PMID:16808853

Shorr, Andrew F; Tabak, Ying P; Gupta, Vikas; Johannes, RS; Liu, Larry Z; Kollef, Marin H

2006-01-01

309

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

PubMed Central

Early-onset cannabis use is widespread in many countries and might cause later onset of depression. Sound epidemiologic data across countries are missing. The authors estimated the suspected causal association that links early-onset (age <17 years) cannabis use with later-onset (age ?17 years) risk of a depression spell, using data on 85,088 subjects from 17 countries participating in the population-based World Health Organization World Mental Health Survey Initiative (2001–2005). In all surveys, multistage household probability samples were evaluated with a fully structured diagnostic interview for assessment of psychiatric conditions. The association between early-onset cannabis use and later risk of a depression spell was studied using conditional logistic regression with local area matching of cases and controls, controlling for sex, age, tobacco use, and other mental health problems. The overall association was modest (controlled for sex and age, risk ratio = 1.5, 95% confidence interval: 1.4, 1.7), was statistically robust in 5 countries, and showed no sex difference. The association did not change appreciably with statistical adjustment for mental health problems, except for childhood conduct problems, which reduced the association to nonsignificance. This study did not allow differentiation of levels of cannabis use; this issue deserves consideration in future research. PMID:20534820

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

2010-01-01

310

Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis  

PubMed Central

Background Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period. Methods and Findings We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors. Conclusions Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis. Please see later in the article for the Editors' Summary PMID:23976885

Chan, Grace J.; Lee, Anne CC; Baqui, Abdullah H.; Tan, Jingwen; Black, Robert E.

2013-01-01

311

Clinical importance of risk variants in the dihydropyrimidine dehydrogenase gene for the prediction of early-onset fluoropyrimidine toxicity.  

PubMed

We investigated the clinical relevance of dihydropyrimidine dehydrogenase gene (DPYD) variants to predict severe early-onset fluoropyrimidine (FP) toxicity, in particular of a recently discovered haplotype hapB3 and a linked deep intronic splice site mutation c.1129-5923C>G. Selected regions of DPYD were sequenced in prospectively collected germline DNA of 500 patients receiving FP-based chemotherapy. Associations of DPYD variants and haplotypes with hematologic, gastrointestinal, infectious, and dermatologic toxicity in therapy cycles 1-2 and resulting FP-dose interventions (dose reduction, therapy delay or cessation) were analyzed accounting for clinical and demographic covariates. Fifteen additional cases with toxicity-related therapy delay or cessation were retrospectively examined for risk variants. The association of c.1129-5923C>G/hapB3 (4.6% carrier frequency) with severe toxicity was replicated in an independent prospective cohort. Overall, c.1129-5923G/hapB3 carriers showed a relative risk of 3.74 (RR, 95% CI?=?2.30-6.09, p?=?2 × 10(-5) ) for severe toxicity (grades 3-5). Of 31 risk variant carriers (c.1129-5923C>G/hapB3, c.1679T>G, c.1905+1G>A or c.2846A>T), 11 (all with c.1129-5923C>G/hapB3) experienced severe toxicity (15% of 72 cases, RR?=?2.73, 95% CI?=?1.61-4.63, p?=?5 × 10(-6) ), and 16 carriers (55%) required FP-dose interventions. Seven of the 15 (47%) retrospective cases carried a risk variant. The c.1129-5923C>G/hapB3 variant is a major contributor to severe early-onset FP toxicity in Caucasian patients. This variant may substantially improve the identification of patients at risk of FP toxicity compared to established DPYD risk variants (c.1905+1G>A, c.1679T>G and c.2846A>T). Pre-therapeutic DPYD testing may prevent 20-30% of life-threatening or lethal episodes of FP toxicity in Caucasian patients. PMID:24923815

Froehlich, Tanja K; Amstutz, Ursula; Aebi, Stefan; Joerger, Markus; Largiadèr, Carlo R

2015-02-15

312

CHOP T/C and C/T haplotypes contribute to early-onset type 2 diabetes in Italians.  

PubMed

Type 2 diabetes (T2D) is characterized by impaired insulin secretion, insulin insensitivity and decreased beta-cell mass. Multiple genes contribute to T2D. The chromosome 12q13.1 region is in linkage to T2D in different populations, including our Italian dataset. CHOP is a candidate gene for the linkage, as it is located in the chromosome 12q13.1 region, and may contribute to T2D by increasing beta-cell apoptosis susceptibility and by impairing insulin sensitivity. Our goal was to identify any potential CHOP gene variants contributing to T2D in our Italian early-onset T2D families, which show linkage to the CHOP region. We directly sequenced the CHOP gene in 28 Italian probands of the linked T2D families and in 115 control subjects. We performed genotype and haplotype association tests with T2D of the identified single nucleotide polymorphisms (SNPs). We performed model-free and parametric association haplotype tests with T2D. We identified three SNPs [5'UTR-c.279T > C, 5'UTR-c.120A > G and + nt30C > T (F10F)] in CHOP. These SNPs are in complete linkage disequilibrium. The genotype association test showed an association trend with T2D of TT (F10F) and AG (-c.120A > G). The haplotype association test provided significant results for the haplotypes T/C (frequency = 0.33) and C/T (frequency = 0.01) (at 5'UTR-c.279T > C and + nt30C > T, respectively) under non-parametric analysis (P-value = 0.0000), recessive model (P-value = 0.0000) and additive model (P-value = 0.0014). Our data show that CHOP described haplotypes T/C and C/T, as an additive and as a homozygous variant, contribute significantly to T2D in our Italian early-onset group. We conclude that the CHOP T/C and C/T haplotype contributes to our T2D linkage signal on chromosome 12q13.1. PMID:18680108

Gragnoli, Claudia

2008-11-01

313

Umbilical Cord Blood IL-6 as Predictor of Early-Onset Neonatal Sepsis in Women with Preterm Prelabour Rupture of Membranes  

PubMed Central

Objective To evaluate umbilical cord interleukin (IL)-6 and funisitis as independent predictors of early-onset neonatal sepsis (EONS) in preterm prelabor rupture of membranes (PPROM). Design Prospective cohort study. Setting Evaluation of umbilical cord IL-6 and funisitis as predictors of early-onset neonatal sepsis in PPROM. Population 176 women with PPROM between 23+0?36+6 weeks of gestation. Methods Umbilical cord IL-6 was assayed by ELISA. Funisitis was defined according to the Salafia classification. Data was adjusted by gestational age at delivery and prenatal administration of corticosteroids and antibiotics. Main Outcome Measures Binary logistic regression was performed to assess the independence of umbilical cord IL-6 and funisitis to predict EONS in women complicated with PPROM. Results The rate of EONS was 7%. Funisitis was present in 18% of women. Umbilical cord IL-6 was significantly higher in women complicated with EONS than without [median (range) 389.5 pg/mL (13.9–734.8) vs 5.2 (0.1–801–4), p<0.001]. Umbilical cord IL-6 was the only independent predictor of early-onset neonatal sepsis (odds ratio 13.6, p?=?0.004). Conclusion Umbilical cord IL-6 was the only predictor of early-onset neonatal sepsis in PPROM. Contrary to what is reported, funisitis was not. PMID:23894452

Andrys, Ctirad; Drahosova, Marcela; Musilova, Ivana; Hornychova, Helena; Jacobsson, Bo

2013-01-01

314

Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer  

PubMed Central

Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP), which is characterized by colorectal multiple polyps and carcinoma(s). However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC) is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19???MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19? and p.Arg109Trp corresponded to p.Arg5? and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5? is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19? and p.Arg109Trp MUTYH variants are associated with functional impairments. PMID:24799981

Goto, Masanori; Tao, Hong; Kato, Hisami; Suzuki, Rie; Nakamura, Satoki; Matsuda, Tomonari; Yin, Guang; Morita, Makiko; Kono, Suminori

2014-01-01

315

Early onset of forced impaired forelimb use causes recovery of forelimb skilled motor function but no effect on gross sensory-motor function after capsular hemorrhage in rats  

Microsoft Academic Search

Intensive use of the impaired forelimb promotes behavioral recovery and induces plastic changes of the central nervous system after stroke. However, the optimal onset of intensive use treatment after stroke is controversial. In this study, we investigated whether early forced impaired limb use (FLU) initiated 24h after intracerebral hemorrhage (ICH) of the internal capsule affected behavioral recovery and histological damage.

Akimasa Ishida; Keigo Tamakoshi; Michiru Hamakawa; Haruka Shimada; Hiroki Nakashima; Tadashi Masuda; Hideki Hida; Kazuto Ishida

2011-01-01

316

An Assessment of the Apex Microarray Technology in Genotyping Patients with Leber Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy  

Microsoft Academic Search

PURPOSE. Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are genetically heteroge- neous, with 11 genes currently implicated. The LCA chip may be used to interrogate many variants in one hybridization reaction. The purpose of this study was to assess the utility of this technology. METHODS. One hundred fifty-three patients with LCA and EOSRD were screened using an

Robert H. Henderson; Naushin Waseem; Rowan Searle; Jacqueline van der Spuy; Isabelle Russell-Eggitt; Shomi S. Bhattacharya; Dorothy A. Thompson; Graham E. Holder; Michael E. Cheetham; Andrew R. Webster; Anthony T. Moore

317

The Marshall M. Parks memorial lecture: making sense of early-onset childhood retinal dystrophies—the clinical phenotype of Leber congenital amaurosis  

Microsoft Academic Search

A correct diagnosis of the early-onset childhood retinal dystrophies requires careful clinical evaluation, the detection of suggestive or pathognomonic ophthalmoscopic clues, the use of electrophysiology to document characteristic electroretinographic findings and, in some cases, the utilisation of newer diagnostic modalities such as optical coherence tomography. Molecular diagnosis confirms the clinical diagnosis and provides the basis for possible future gene therapy.

E. I. Traboulsi

2009-01-01

318

The School Psychologist's Primer on Early Onset Schizophrenia: A Review of Research Regarding Epidemiology, Etiology, Assessment, and Treatment  

ERIC Educational Resources Information Center

The purpose of this article is to provide school psychologists and other educational professionals with important information regarding the epidemiology, etiology, assessment, and treatment of early onset schizophrenia (EOS). The central aim herein is to bring science to practice by succinctly highlighting key considerations for school…

Hernandez, Rafael J. C.; Rime, W. Jeremy; Jimerson, Shane R.

2013-01-01

319

Detection of Periodontal Markers in Chronic Periodontitis  

PubMed Central

The aim was to compare the detection frequency of periodontopathogens by using the Pado Test 4.5 and checkerboard DNA-DNA hybridization technique in chronic periodontitis patients. Thirty patients with chronic periodontitis were tested cross-sectionally with DNA/RNA oligogenomic probe method (IAI Pado Test 4.5) and DNA/DNA whole genomic probe (checkerboard) method. Samples were taken by two paper points at the deepest site in each of the four quadrants and pooled into one sample for each of the two methods. The samples were sent to the two laboratories (IAI, Zuchwil, Switzerland, and Oral Microbiology Laboratory, University of Gothenburg, Sweden) and were analyzed in a routine setting for the presence and amount of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. While Pado Test 4.5 detected the four periodontal pathogens in 11 (36.7%) of the patients, the checkerboard method showed presence in all patients (100%) using the lower score (Score 1 corresponding to 104 bacterial cells) and 16 (53.3%) using a higher treshold (score 3 corresponding to between >105 and 106 cells). The results of the present study showed low agreement for a positive microbiological outcome using the two diagnostic methods. It was also concluded that microbiological analysis in practice should include a larger number of bacterial species to better serve as markers for a diseased associated flora in chronic periodontitis cases. PMID:21769304

Leonhardt, Asa; Carlen, Anette; Bengtsson, Lisbeth; Dahlen, Gunnar

2011-01-01

320

Are diet and feeding behaviours associated with the onset of and recovery from slow weight gain in early infancy?  

PubMed

Infants with slow weight gain cause concern in parents and professionals, but it is difficult to be certain whether such infants are genetically small or whether their energy intake is insufficient. The aim of the present study was to assess the impact of diet and feeding behaviours on slow weight gain early in infancy. The sample was 11 499 term infants from the Avon Longitudinal Study of Parents and Children (ALSPAC). A total of 507 cases of slow weight gain from birth to 8 weeks were identified and the remaining 10 992 infants were used as controls. It was found that infants who gained weight slowly between birth and 8 weeks were more likely to exhibit feeding problems such as weak sucking and slow feeding during this period. Feeding problems were substantially reduced during the recovery phase (8 weeks to 2 years) when these infants exhibited enhanced catch-up in weight. The proportion of mothers breast-feeding in the 4th week after birth was higher for slow weight gainers, but they were more likely to switch to formula at the start of recovery. During recovery, slow-weight gain infants had a slightly higher energy intake from formula and solids than controls. In conclusion, feeding problems seem to be the most important factors associated with the onset of early slow weight gain. Subsequently, a reduction of feeding problems and an increase in overall energy intake may contribute to their weight recovery. Health professionals should look for feeding problems in the first few weeks after birth and help mothers establish adequate feeding practices. PMID:24502920

Hollén, Linda I; Din, Zia ud; Jones, Louise R; Emond, Alan M; Emmett, Pauline

2014-05-01

321

Mutations in RD3 Are Associated with an Extremely Rare and Severe Form of Early Onset Retinal Dystrophy  

PubMed Central

Purpose. To identify the underlying mutation and describe the phenotype in a consanguineous Kurdish family with Leber's congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD). Methods. Members of the index family were followed up to 22 years by ophthalmological examinations, including best corrected visual acuity (BCVA), Goldmann visual field (GVF), two-color-threshold perimetry (2CTP) and Ganzfeld electroretinogram (ERG), fundus photographs, fundus autofluorescence (FAF), and optical coherence tomography (OCT). After excluding seven of nine known LCA/EOSRD genes in the index patient, linkage analysis was performed in the family using a microarray followed by microsatellite fine mapping and direct sequencing of candidate genes. RD3 was screened by direct sequencing of 85 independent patients with LCA/EOSRD presenting with a BCVA ? 1.0 LogMAR before the age of 2 years to assess the prevalence of RD3 mutations in LCA/EOSRD. Since RD3 and RetGC1 have a functional relation, study authors screened for a modifying effect of RD3 mutations in 17 independent patients with mutations in GUCY2D. Results. BCVA was severely reduced from the earliest examinations (as early as 3 months), never exceeding 1.3 LogMAR. The disease presented as cone-rod dystrophy with dystrophic changes in the macula and bone spicules in the periphery on progression. Linkage analysis narrowed the region of interest towards the LCA12 locus. Direct sequencing of RD3 revealed a homozygous nonsense mutation (c.180C > A) in all affected members tested. Screening of additional unrelated LCA/EOSRD patients revealed only polymorphisms in RD3. Conclusions. This is the second family reported so far with mutations in RD3. Mutations in RD3 are a very rare cause of LCA associated with an extremely severe form of retinal dystrophy. PMID:22531706

Preising, Markus N.; Hausotter-Will, Nora; Solbach, Manuel C.; Friedburg, Christoph; Ruschendorf, Franz; Lorenz, Birgit

2012-01-01

322

Functional and structural changes throughout the auditory system following congenital and early-onset deafness: implications for hearing restoration  

PubMed Central

The absence of auditory input, particularly during development, causes widespread changes in the structure and function of the auditory system, extending from peripheral structures into auditory cortex. In humans, the consequences of these changes are far-reaching and often include detriments to language acquisition, and associated psychosocial issues. Much of what is currently known about the nature of deafness-related changes to auditory structures comes from studies of congenitally deaf or early-deafened animal models. Fortunately, the mammalian auditory system shows a high degree of preservation among species, allowing for generalization from these models to the human auditory system. This review begins with a comparison of common methods used to obtain deaf animal models, highlighting the specific advantages and anatomical consequences of each. Some consideration is also given to the effectiveness of methods used to measure hearing loss during and following deafening procedures. The structural and functional consequences of congenital and early-onset deafness have been examined across a variety of mammals. This review attempts to summarize these changes, which often involve alteration of hair cells and supporting cells in the cochleae, and anatomical and physiological changes that extend through subcortical structures and into cortex. The nature of these changes is discussed, and the impacts to neural processing are addressed. Finally, long-term changes in cortical structures are discussed, with a focus on the presence or absence of cross-modal plasticity. In addition to being of interest to our understanding of multisensory processing, these changes also have important implications for the use of assistive devices such as cochlear implants. PMID:24324409

Butler, Blake E.; Lomber, Stephen G.

2013-01-01

323

Functional Analysis of a De Novo GRIN2A Missense Mutation Associated with Early-onset Epileptic Encephalopathy  

PubMed Central

NMDA receptors (NMDAR), ligand-gated ion channels, play important roles in various neurological disorders, including epilepsy. Here we show the functional analysis of a de novo missense mutation (L812M) in a gene encoding NMDAR subunit GluN2A (GRIN2A). The mutation, identified in a patient with early-onset epileptic encephalopathy and profound developmental delay, is located in the linker region between the ligand-binding and transmembrane domains. Electrophysiological recordings revealed that the mutation enhances agonist potency, decreases sensitivity to negative modulators including magnesium, protons and zinc, prolongs the synaptic response time course, and increases single channel open probability. The functional changes of this amino acid apply to all other NMDAR subunits, suggesting an important role of this residue on the function of NMDARs. Taken together, these data suggest that the L812M mutation causes over-activation of NMDARs and drives neuronal hyperexcitability. We hypothesize that this mechanism underlies the patient’s epileptic phenotype as well as cerebral atrophy. PMID:24504326

Yuan, Hongjie; Hansen, Kasper B.; Zhang, Jing; Pierson, Tyler Mark; Markello, Thomas C.; Fuentes Fajardo, Karin V.; Holloman, Conisha M.; Golas, Gretchen; Adams, David R.; Boerkoel, Cornelius F.; Gahl, William A.; Traynelis, Stephen F.

2014-01-01

324

Adolescent-onset alcohol abuse exacerbates the influence of childhood conduct disorder on late adolescent and early adult antisocial behaviour  

PubMed Central

This study tested the hypothesis that adolescent-onset alcohol abuse (AOAA) would both mediate and moderate the effect of childhood conduct disorder on antisocial behaviour in late adolescence and early adulthood. A sample comprising 504 young men and women strategically recruited from the community were grouped using the criteria of the Diagnostic and Statistical Manual (DSM-IV, American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: APA), as follows: neither childhood conduct disorder (CCD) nor alcohol abuse/dependence; CCD but no alcohol abuse or dependence; alcohol abuse/dependence but no CCD; both CCD and alcohol abuse/dependence. The outcome measure was the sum of positive responses to 55 interview items capturing a variety of antisocial behaviours engaged in since age 15. Severity of lifetime alcohol-related and CCD problems served as predictor variables in regression analysis. Antisocial behaviour problems were greatest in individuals with a history of co-occurring conduct disorder (CD) and alcohol abuse/dependence. While CCD was strongly predictive of adult antisocial behaviour, this effect was both mediated and moderated (exacerbated) by AOAA. PMID:23459369

Howard, Richard; Finn, Peter; Jose, Paul; Gallagher, Jennifer

2012-01-01

325

Patterns and correlates of expressed emotion, perceived criticism, and rearing style in first admitted early-onset schizophrenia spectrum disorders.  

PubMed

The aim of this study was to assess patterns and correlates of family variables in 31 adolescents treated for their first episode of a schizophrenia spectrum disorder (early-onset schizophrenia [EOS]). Expressed emotion, perceived criticism, and rearing style were assessed. Potential correlates were patient psychopathology, premorbid adjustment, illness duration, quality of life (QoL), sociodemographic variables, patient and caregiver "illness concept," and caregiver personality traits and support. Families were rated as critical more frequently by patients than raters (55% vs. 13%). Perceived criticism was associated with worse QoL in relationship with parents and peers. An adverse rearing style was associated with a negative illness concept in patients, particularly with less trust in their physician. Future research should examine perceived criticism as a predictor of relapse and indicator of adolescents with EOS who need extended support and treatment. Rearing style should be carefully observed because of its link with patients' illness concept and, potentially, to service engagement and medication adherence. PMID:25259947

von Polier, Georg G; Meng, Heiner; Lambert, Martin; Strauss, Monika; Zarotti, Gianni; Karle, Michael; Dubois, Reinmar; Stark, Fritz-Michael; Neidhart, Sibylle; Zollinger, Ruedi; Bürgin, Dieter; Felder, Wilhelm; Resch, Franz; Koch, Eginhard; Schulte-Markwort, Michael; Schimmelmann, Benno G

2014-11-01

326

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

PubMed

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

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

2014-10-01

327

Changes in erythrocyte insulin receptors in normal dogs and keeshond dogs with inheritable, early onset, insulin dependent diabetes mellitus  

SciTech Connect

Validation of a procedure to evaluate insulin receptors on erythrocytes (RBC-IR) in dogs is described. The specific binding of (/sup 125/I)iodoinsulin to RBC-IR of normal dogs is significantly greater than binding in keeshonds with an inheritable form of early onset diabetes mellitus. This decreased binding was due to a significant decrease in RBC-IR affinity in the diabetic keeshonds. To determine the effect on RBC-IR, normal dogs were treated with either dexamethasone (0.1 mg/kg) or prednisone (0.3 mg/kg) for 10 days: concentrations of plasma cortisol, glucose, and insulin, plus binding characteristics of RBC-IR were determined. In the dexamethasone treated group, plasma glucose concentrations were elevated significantly by day 6 and continued through day 10. Insulin concentrations were elevated significantly by day 3 and remained elevated through day 10. In the prednisone treated group, glucose concentrations were elevated significantly by day 3, while insulin concentrations were elevated significantly by day 8. Maximum binding of RBC-IR was unaffected by prednisone and neither affinities nor receptor numbers were significantly different from day 1. No changes in plasma cortisol concentration were seen. Diabetic keeshonds on daily insulin treatment were removed from exogenous insulin therapy for 48 hours. Significant increases in glucose concentrations were observed, but no significant changes in cortisol, insulin, average receptor binding affinity, or RBC-IR number per cell occurred.

Klaassen, J.K.

1986-01-01

328

Sequence of Alcohol Involvement from Early Onset to Young Adult Alcohol Abuse: Differential Predictors and Moderation by Family-Focused Preventive Intervention  

PubMed Central

Aims This study tests risk factors for four dimensions of alcohol use in the sequence from (a) early onset prior to age 13 to (b) adolescent alcohol use and (c) alcohol problems to (d) young adult alcohol abuse. It also examines whether family-focused preventive interventions buffer predictive relationships. Design Data were from a randomized prevention trial extending from ages 11 to 21. Setting Families of sixth graders enrolled in 33 rural schools in the Midwestern United States were invited to participate. Participants Families (N = 667) were pretested and randomly assigned to a control group (n = 208) or to family interventions (n = 459). The average age of participating youth was 11.3 years when the study began (52% female). Measurements: Questionnaire data were collected on alcohol dimensions during adolescence (early onset, alcohol use, alcohol problems) and young adulthood (alcohol abuse), and on risk factors in early adolescence (male gender, impulsive behaviors, aggression-hostility, peer deviance, and parent problem drinking). Findings Impulsive behaviors predicted early onset, peer deviance predicted alcohol use, and parent problem drinking predicted alcohol problems (p < .05). Aggression-hostility and alcohol problems predicted alcohol abuse in the control group (p < .05), but not in the family interventions group (p > .05). Conclusions Different dimensions of alcohol use and problems from before age 13 to young adulthood are predicted by different risk factors. Family-focused preventive interventions can reduce the influence of some of these risk factors, including early adolescent aggression-hostility and late adolescent alcohol problems. PMID:22724619

Spoth, Richard L.

2012-01-01

329

Papillon-Lefevre syndrome (PLS) without cathepsin C mutation: A rare early onset partially penetrant variant of PLS  

PubMed Central

Papillon–Lefevre syndrome (PLS) is a very rare, autosomal recessive syndrome characterized by palmar–plantar hyperkeratosis and severe destructive periodontitis. Most patients present with PLS harbor mutations in the cathepsin C gene, but recent studies have identified individuals with classic PLS symptoms without such mutations. This suggests more genetic heterogeneity for PLS than previously thought. Here we present an individual’s manifesting characteristic clinical features of PLS with no mutations in the coding sequence of cathepsin C. We suggest there must be alternative genetic causes for such forms of PLS. PMID:24526825

Khan, Fayiza Yaqoob; Jan, Suhail Majid; Mushtaq, Mubashir

2013-01-01

330

Papillon-Lefevre syndrome (PLS) without cathepsin C mutation: A rare early onset partially penetrant variant of PLS.  

PubMed

Papillon-Lefevre syndrome (PLS) is a very rare, autosomal recessive syndrome characterized by palmar-plantar hyperkeratosis and severe destructive periodontitis. Most patients present with PLS harbor mutations in the cathepsin C gene, but recent studies have identified individuals with classic PLS symptoms without such mutations. This suggests more genetic heterogeneity for PLS than previously thought. Here we present an individual's manifesting characteristic clinical features of PLS with no mutations in the coding sequence of cathepsin C. We suggest there must be alternative genetic causes for such forms of PLS. PMID:24526825

Khan, Fayiza Yaqoob; Jan, Suhail Majid; Mushtaq, Mubashir

2014-01-01

331

Novel APP K724M mutation causes Chinese early-onset familial Alzheimer's disease and increases amyloid-?42 to amyloid-?40 ratio.  

PubMed

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly individuals. Although there are several million cases of AD estimated in China with the most population in the world, no Chinese early-onset familial AD caused by new APP gene mutation has ever been reported. Here, we first described a Chinese family with early-onset AD that was inherited in autosomal dominant manner, and the age of onset was 46.6 ± 7.7 years (n = 5; range, 40-58 years). By using genetic analysis of 3 collected patients' DNA samples, we identified a heterozygous APP gene mutation (g.275363A>T, K724M according to APP770). Finally, when APP695 with K724M mutation was ectopically expressed in HEK293 cell, the ratio of amyloid-?42 to amyloid-?40 was 2.23-fold higher than that of wild-type control. Together, our data suggest that APP K724M gene mutation may contribute to the cause of this Chinese early-onset familial AD. PMID:25018108

Peng, Xiang-Lei; Hou, Lei; Xu, Shao-Hua; Hua, Ying; Zhou, Shu-Jie; Zhang, Ying; Zheng, Yan-Peng; Fu, Yuan-Hui; Xu, Qing; Zhang, Li-Shu; Wang, Jun; Guan, Xiao-Ting; He, Jin-Sheng

2014-11-01

332

Biomaterials for periodontal regeneration  

PubMed Central

Periodontal disease is characterized by the destruction of periodontal tissues. Various methods of regenerative periodontal therapy, including the use of barrier membranes, bone replacement grafts, growth factors and the combination of these procedures have been investigated. The development of biomaterials for tissue engineering has considerably improved the available treatment options above. They fall into two broad classes: ceramics and polymers. The available ceramic-based materials include calcium phosphate (eg, tricalcium phosphate and hydroxyapatite), calcium sulfate and bioactive glass. The bioactive glass bonds to the bone with the formation of a layer of carbonated hydroxyapatite in situ. The natural polymers include modified polysaccharides (eg, chitosan,) and polypeptides (collagen and gelatin). Synthetic polymers [eg, poly(glycolic acid), poly(L-lactic acid)] provide a platform for exhibiting the biomechanical properties of scaffolds in tissue engineering. The materials usually work as osteogenic, osteoconductive and osteoinductive scaffolds. Polymers are more widely used as a barrier material in guided tissue regeneration (GTR). They are shown to exclude epithelial downgrowth and allow periodontal ligament and alveolar bone cells to repopulate the defect. An attempt to overcome the problems related to a collapse of the barrier membrane in GTR or epithelial downgrowth is the use of a combination of barrier membranes and grafting materials. This article reviews various biomaterials including scaffolds and membranes used for periodontal treatment and their impacts on the experimental or clinical management of periodontal defect. PMID:23507891

Shue, Li; Yufeng, Zhang; Mony, Ullas

2012-01-01

333

A case of early-onset benign occipital seizure susceptibility syndrome: decreased cerebral blood flow in the occipital region detected by interictal single photon emission computed tomography, corresponding to the epileptogenic focus  

Microsoft Academic Search

Early-onset benign childhood occipital seizure susceptibility syndrome (EBOSS) recently described by Panayiotopoulos, is an early-onset variant of benign childhood epilepsy with occipital paroxysms. EBOSS is characterized by partial seizures that are predominantly manifested at night and associated with deviation of the eyes, vomiting and impairment of consciousness, but without ictal visual symptoms or postictal headache. The clinical features of our

Masanori Sakagami; Yukihiro Takahashi; Hiroaki Matsuoka; Tohru Hoshida; Kazushi Izaki; Sadao Nouka; Akira Yoshioka

2001-01-01

334

The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome  

PubMed Central

The gene encoding the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A (DYRK1A) is located in the Down syndrome (DS) critical region of chromosome 21. The third copy of DYRK1A is believed to contribute to abnormal brain development in patients with DS. In vitro studies showing that DYRK1A phosphorylates tau protein suggest that this kinase is also involved in tau protein phosphorylation in the human brain and contributes to neurofibrillary degeneration, and that this contribution might be enhanced in patients with DS. To explore this hypothesis, the brain tissue from 57 subjects including 16 control subjects, 21 patients with DS, and 20 patients with sporadic Alzheimer's disease (AD) was examined with two antibodies to the amino-terminus of DYRK1A (7F3 and G-19), as well as two polyclonal antibodies to its carboxy-terminus (X1079 and 324446). Western blots demonstrated higher levels of full-length DYRK1A in the brains of patients with DS when compared to control brains. Immunocytochemistry revealed that DYRK1A accumulates in neurofibrillary tangles (NFTs) in subjects with sporadic AD and in subjects with DS/AD. Overexpression of DYRK1A in patients with DS was associated with an increase in DYRK1A-positive NFTs in a gene dosage-dependent manner. Results support the hypothesis that overexpressed DYRK1A contributes to neurofibrillary degeneration in DS more significantly than in subjects with two copies of the DYRK1A gene and sporadic AD. Immunoreactivity with antibodies against DYRK1A not only in NFTs but also in granules in granulovacuolar degeneration and in corpora amylacea suggests that DYRK1A is involved in all three forms of degeneration and that overexpression of this kinase may contribute to the early onset of these pathologies in DS. PMID:18696092

Wegiel, Jerzy; Dowjat, Karol; Kaczmarski, Wojciech; Kuchna, Izabela; Nowicki, Krzysztof; Frackowiak, Janusz; Kolecka, Bozena Mazur; Wegiel, Jarek; Silverman, Wayne P.; Reisberg, Barry; deLeon, Mony; Wisniewski, Thomas; Gong, Cheng-Xin; Liu, Fei; Adayev, Tatyana; Chen-Hwang, Mo-Chou; Hwang, Yu-Wen

2009-01-01

335

A three year descriptive study of early onset neonatal sepsis in a refugee population on the Thailand Myanmar border  

PubMed Central

Background Each year an estimated four million neonates die, the majority in the first week of life. One of the major causes of death is sepsis. Proving the incidence and aetiology of neonatal sepsis is difficult, particularly in resource poor settings where the majority of the deaths occur. Methods We conducted a three year observational study of clinically diagnosed early onset (<7 days of age) neonatal sepsis (EONS) in infants born to mothers following antenatal care at the Shoklo Malaria Research Unit clinic in Maela camp for displaced persons on the Thailand-Myanmar border. Episodes of EONS were identified using a clinical case definition. Conventional and molecular microbiological techniques were employed in order to determine underlying aetiology. Results From April 2009 until April 2012, 187 infants had clinical signs of EONS, giving an incidence rate of 44.8 per 1000 live births (95% CI 38.7-51.5). One blood culture was positive for Escherichia coli, E. coli was detected in the cerebrospinal fluid specimen in this infant, and in an additional two infants, by PCR. Therefore, the incidence of bacteriologically proven EONS was 0.7 per 1000 live births (95% CI 0.1 – 2.1). No infants enrolled in study died as a direct result of EONS. Conclusion A low incidence of bacteriologically proven EONS was seen in this study, despite a high incidence of clinically diagnosed EONS. The use of molecular diagnostics and nonspecific markers of infection need to be studied in resource poor settings to improve the diagnosis of EONS and rationalise antibiotic use. PMID:24359288

2013-01-01

336

Identification of a Novel De Novo Mutation Associated with PRKAG2 Cardiac Syndrome and Early Onset of Heart Failure  

PubMed Central

Introduction The major structure elements of the AMP-activated protein kinase (AMPK) are ?, ?, and ? sunbunits. Mutations in ?2 subunit (PRKAG2) have been associated with a cardiac syndrome including inherited ventricular preexcitation, conduction disorder and hypertrophy mimicking hypertrophic cardiomyopathy. The aim of the present study was to identify PRKAG2 syndrome among patients presenting with left ventricular hypertrophy (LVH). Methods and Results Nineteen unrelated subjects with unexplained LVH were clinically and genetically evaluated. Among 4 patients with bradycardia, manifestations of preexcitation were only found in a 19 year old male who also developed congestive heart failure 3 years later. Electrophysiological study of this case identified the coexistence of an AV accessory pathway and AV conduction defect. Histological analysis of his ventricular tissue isolated by biopsy confirmed excessive glycogen accumulation, prominent myofibrillar disarray and interstitial fibrosis. Direct sequencing of his DNA revealed a heterozygous mutation in PRKAG2 consisting of an A-to-G transition at nucleotide 1453 (c.1453A>G), predicting a substitution of a glutamic acid for lysine at highly-conserved residue 485 (p.Lys485Glu, K485E), which was absent in his unaffected family members and in 215 healthy controls. To assess the role of K485 in the structure and function of the protein, computational modeling calculations and conservation analyses were performed. Electrostatic calculations indicate that K485 forms a salt bridge with the conserved D248 residue in the AMPK ? subunit, which is critical for proper regulation of the enzyme, and the K485E mutant disrupts the connection. Conclusions Our study identifies a novel de novo PRKAG2 mutation in a young, in which progression of the disease warrants close medical attention. It also underlines the importance of molecular screening of PRKAG2 gene in patients with unexplained LVH, ventricular preexcitation, conduction defect, and/or early onset of heart failure. PMID:23741347

Liu, Yang; Bai, Rong; Wang, Lin; Zhang, Cuntai; Zhao, Ruifu; Wan, Deli; Chen, Xinshan; Caceres, Gabriel; Barr, Daniel; Barajas-Martinez, Hector; Antzelevitch, Charles; Hu, Dan

2013-01-01

337

Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene.  

PubMed

Fanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and a missense mutation (c.7802A>G, p.Tyr2601Cys). The diagnosis of FA was confirmed by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR analysis revealed that the c.7802A>G BRCA2 variation was in fact a splicing mutation that creates an aberrant splicing donor site and results partly into an aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The atypical FA phenotype observed within this family was probably explained by the residual amount of BRCA2 with the point mutation c.7802A>G in the patients harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in a single family, it suggests that CRCs may be part of the tumour spectrum associated with FANCD1/BRCA2 biallelic mutations and that the presence of such mutations should be considered in families with CRCs, even in the absence of cardinal features of FA. PMID:24301060

Degrolard-Courcet, Emilie; Sokolowska, Joanna; Padeano, Marie-Martine; Guiu, Séverine; Bronner, Myriam; Chery, Carole; Coron, Fanny; Lepage, Côme; Chapusot, Caroline; Loustalot, Catherine; Jouve, Jean-Louis; Hatem, Cyril; Ferrant, Emmanuelle; Martin, Laurent; Coutant, Charles; Baurand, Amandine; Couillault, Gérard; Delignette, Alexandra; El Chehadeh, Salima; Lizard, Sarab; Arnould, Laurent; Fumoleau, Pierre; Callier, Patrick; Mugneret, Francine; Philippe, Christophe; Frebourg, Thierry; Jonveaux, Philippe; Faivre, Laurence

2014-08-01

338

Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population  

PubMed Central

Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years) were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T), and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study. PMID:23289006

Laraqui, Abdelilah; Uhrhammer, Nancy; Lahlou-Amine, Idriss; EL Rhaffouli, Hicham; El Baghdadi, Jamila; Dehayni, Mohamed; Moussaoui, Rahali Driss; Ichou, Mohamed; Sbitti, Yassir; Al Bouzidi, Abderrahman; Amzazi, Said; Bignon, Yves-Jean

2013-01-01

339

Periodontal Microflora of HIV Infected Patients with Periodontitis  

Microsoft Academic Search

The aim of this study was to determine the microbial profile of periodontal lesions in HIV seropositive patients and to compare it with rapidly progressing periodontal lesions in systemically healthy patients. The subgingival microflora of 20 CDC II, 20 CDC III, 20 CDC IV\\/V and 20 systemically healthy patients with rapidly progressing periodontitis was examined. Four sites with greatest probing

M Nakou; J Kamma; P Gargalianos; G Laskaris; F Mitsis

1997-01-01

340

Reassessment of motor-behavioural test analyses enables the detection of early disease-onset in a transgenic mouse model of amyotrophic lateral sclerosis.  

PubMed

As a model for amyotrophic lateral sclerosis (ALS), transgenic hSOD1(G93A) mice constitute the standard tool for evaluating future therapeutic strategies. Due to axonal retraction from neuromuscular junctions, the animals suffer from muscle wasting leading to weakness and paralysis of the extremities, which in early stages can be detected by measuring weight loss. Suspecting that underlying mechanisms might yield subtle neuromuscular abnormalities ahead of weight loss onset, we wanted to determine a behavioural test to detect disease onset time earlier. We compared the monitoring of weight with the "forced" examination of grip strength and the investigation of freely behaving animals within an open field. Additionally, we compared two different data analysis methods: (1) two-way ANOVA with Bonferroni correction (2) break point analysis calculating symptom onset time points for each animal. Break point analysis revealed onset times that significantly preceded those obtained by standard two-way ANOVA. Open field analysis of freely moving animals could not give an advantage over weight loss measurements. Grip strength assessment of hindlimbs detected disease onset 36 days before the first evidence of weight loss, providing a maximal treatment window of 84 days on average before the death of male animals. We conclude that grip strength analysis of hindlimbs is a very sensitive and reproducible motor behavioural test, which can even be applied to small cohorts of animals. Combined with break point analysis, it represents the method of choice to detect early disease onset in hSOD1(G93A) mice. PMID:21723884

Schäfer, Sabrina; Hermans, Emmanuel

2011-11-20

341

Differential activation of placental unfolded protein response pathways implies heterogeneity in causation of early- and late-onset pre-eclampsia.  

PubMed

Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (?34 weeks) forms. Recently, the distinction between 'placental' and 'maternal' causation has been proposed, with 'placental' cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPK? in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia-reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1?, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from ? 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term 'controls' delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O2 ) induced equivalent activation of UPR pathways, including P-eIF2?, ATF6, P-IRE1?, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNF? and IL-1? induced only mild activation of P-eIF2? and GRP78. AKT, a central regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. PMID:24931423

Yung, Hong Wa; Atkinson, Daniel; Campion-Smith, Tim; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J

2014-10-01

342

Next-generation sequencing (NGS) as a diagnostic tool for retinal degeneration reveals a much higher detection rate in early-onset disease  

PubMed Central

Inherited retinal degeneration (IRD) is a common cause of visual impairment (prevalence ?1/3500). There is considerable phenotype and genotype heterogeneity, making a specific diagnosis very difficult without molecular testing. We investigated targeted capture combined with next-generation sequencing using Nimblegen 12plex arrays and the Roche 454 sequencing platform to explore its potential for clinical diagnostics in two common types of IRD, retinitis pigmentosa and cone-rod dystrophy. 50 patients (36 unknowns and 14 positive controls) were screened, and pathogenic mutations were identified in 25% of patients in the unknown, with 53% in the early-onset cases. All patients with new mutations detected had an age of onset <21 years and 44% had a family history. Thirty-one percent of mutations detected were novel. A de novo mutation in rhodopsin was identified in one early-onset case without a family history. Bioinformatic pipelines were developed to identify likely pathogenic mutations and stringent criteria were used for assignment of pathogenicity. Analysis of sequencing metrics revealed significant variability in capture efficiency and depth of coverage. We conclude that targeted capture and next-generation sequencing are likely to be very useful in a diagnostic setting, but patients with earlier onset of disease are more likely to benefit from using this strategy. The mutation-detection rate suggests that many patients are likely to have mutations in novel genes. PMID:22968130

Shanks, Morag E; Downes, Susan M; Copley, Richard R; Lise, Stefano; Broxholme, John; Hudspith, Karl AZ; Kwasniewska, Alexandra; Davies, Wayne IL; Hankins, Mark W; Packham, Emily R; Clouston, Penny; Seller, Anneke; Wilkie, Andrew OM; Taylor, Jenny C; Ragoussis, Jiannis; Nemeth, Andrea H

2013-01-01

343

Novel mutations in the GDAP1 gene in patients affected with early-onset axonal Charcot-Marie-Tooth type 4A.  

PubMed

We report a detailed study of eight patients from four Italian families presenting with autosomal recessive axonal Charcot-Marie-Tooth disease (AR-CMT2), characterized by early-onset and progressive severe weakness of all limbs. Vocal cord paresis was present in two cases. Sural nerve biopsy performed in three patients showed a severe neuropathy characterized by a predominant axonal involvement. Five novel mutations (p.Gln99stop, p.Gln122Lys, p.Arg125stop, p.Val219Asp, p.Asn297Lys) and one previously reported mutation (p.Leu239Phe) were identified in GDAP1 gene. GDAP1 mutations should be considered both in recessive and sporadic cases of early-onset axonal CMT. PMID:19500985

Moroni, Isabella; Morbin, Michela; Milani, Micaela; Ciano, Claudia; Bugiani, Marianna; Pagliano, Emanuela; Cavallaro, Tiziana; Pareyson, Davide; Taroni, Franco

2009-07-01

344

A Novel Mutation in the Aprataxin (APTX) Gene in an Iranian Individual Suffering Early-Onset Ataxia with Oculomotor Apraxia Type 1(AOA1) Disease  

PubMed Central

Background Ataxia with oculomotor apraxia type 1 (AOA1) shows early onset with autosomal recessive inheritance and is caused by a mutation in the aprataxin (APTX) gene encoding for the APTX protein. Methods In this study, a 7-year-old girl born of a first-cousin consanguineous marriage was described with early-onset progressive ataxia and AOA, with increased cholesterol concentration and decreased albumin concentration in serum. PCR and direct DNA sequencing was performed after DNA extraction. Results Sequencing analysis revealed a novel homozygous deletion in c.643 and A>T single nucleotide polymorphism in c.641 in exon 6 of the APTX gene [ENST00000379825]. Conclusion It seems that this region of exon 6 is probably a hot spot; however, no deletions have been reported in exon 6 yet. PMID:23183622

Nouri, Nayereh; Nouri, Narges; Aryani, Omid; Kamalidehghan, Behnam; Sedghi, Maryam; Houshmand, Massoud

2012-01-01

345

Causative novel PNKP mutations and concomitant PCDH15 mutations in a patient with microcephaly with early-onset seizures and developmental delay syndrome and hearing loss.  

PubMed

We report on a 1-year-old boy with microcephaly with a simplified gyral pattern, early-onset seizures, congenital hearing loss and a severe developmental delay. Trio-based whole-exome sequencing identified candidate compound heterozygous mutations in two genes: c.163G>T (p.Ala55Ser) and c.874G>A (p.Gly292Arg) in polynucleotide kinase 3'-phosphatase gene (PNKP), and c.195G>A (p.Met65Ile) and c.1210A>C (p.Ser404Arg) in PCDH15. PNKP and PCDH15 mutations have been reported in autosomal recessive microcephaly with early-onset seizures and developmental delay syndrome, and Usher syndrome type 1F, respectively. Our patient showed neurological features similar to reported cases of both syndromes that could be explained by the observed mutations in both PNKP and PCDH15, which therefore appear to be pathogenic in this case. PMID:24965255

Nakashima, Mitsuko; Takano, Kyoko; Osaka, Hitoshi; Aida, Noriko; Tsurusaki, Yoshinori; Miyake, Noriko; Saitsu, Hirotomo; Matsumoto, Naomichi

2014-08-01

346

A Role for Nrf2 in Redox Signalling of the Invasive Extravillous Trophoblast in Severe Early Onset IUGR Associated with Preeclampsia  

PubMed Central

Background Preeclampsia (PE) is characterized by increased lipid oxidation and diminished antioxidant capacity, while intrauterine growth restriction (IUGR) is characterized by impaired invasion of the extravillous trophoblast. Vascular endothelial growth factor (VEGF) has been reported to be altered in preeclampsia. A relationship between VEGF and nuclear factor erythroid 2-related factor-2 (Nrf2) has been shown in vitro, where VEGF prevents oxidative damage via activation of the Nrf2 pathway. In this study the expression of Nrf2, VEGF and 4-hydroxynonenal (4-HNE), was determined in interstitial and endovascular/intramural extravillous trophoblast (EVT) in normal pregnancies and those complicated by severe early onset IUGR associated with preeclampsia IUGR/PE. Materials and Methods Full-thickness uterine tissues derived from caesarean hysterectomies performed in 5 healthy normotensive women delivering term infants and 6 women with severe early onset IUGR with preeclampsia (29–34 weeks gestation) were analyzed. Interstitial and endovascular extravillous trophoblast were quantified after immunohistochemical staining of paraffin sections using antibodies against Nrf2, 4-HNE, VEGF, and cytokeratin 7. Results Uterine tissues from women suffering from severe early onset IUGR/PE were characterized by reduced invasion of extravillous trophoblast into the endometrial and myometrial segments of spiral arteries in the placental bed. Extravillous trophoblast showed an increased cytoplasmic expression of Nrf2 and 4-HNE in IUGR/PE cases. The increased expression of Nrf2 in cases of IUGR/PE was associated with decreased expression of VEGF in these cells compared to controls. Conclusion Our data suggests that besides villous cytotrophoblast, also the extravillous trophoblast is a source of Nrf2-dependent genes. VEGF deficiency may cause higher oxidative stress in extravillous trophoblast in cases with IUGR/PE. The resulting reduced basal defence against oxidative stress and the higher vulnerability to oxidative damage may play a role in the limited trophoblast invasion into spiral arteries in cases suffering from severe early onset IUGR/PE. PMID:23056578

Kweider, Nisreen; Huppertz, Berthold; Wruck, Christoph Jan; Beckmann, Rainer; Rath, Werner; Pufe, Thomas; Kadyrov, Mamed

2012-01-01

347

Tumor Necrosis Factor Induces Early-Onset Endothelial Adhesivity by Protein Kinase C-Dependent Activation of Intercellular Adhesion Molecule1  

Microsoft Academic Search

We tested the hypothesis that TNF- induces early-onset endothelial adhesivity toward PMN by activating the constitutive endothelial cell surface ICAM-1, the 2-integrin (CD11\\/CD18) counter-receptor. Stimulation of human pulmonary artery endothelial cells with TNF- resulted in phosphorylation of ICAM-1 within 1 minute, a response that was sustained up to 15 minutes after TNF- challenge. We observed that TNF- induced 10-fold increase

Kamran Javaid; Arshad Rahman; Khandaker N. Anwar; Randall S. Frey; Richard D. Minshall; Asrar B. Malik

348

Commentary on 'Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years'.  

PubMed

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Furlong M, McGilloway S, Bywater T, Hutchings J, Smith SM, Donnelly M. Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD008225. DoI: 10.1002/14651858.CD008225.pub2. PMID:23877887

Haroon, Munib

2013-03-01

349

12\\/15Lipoxygenase Is Required for the Early Onset of High Fat Diet-Induced Adipose Tissue Inflammation and Insulin Resistance in Mice  

Microsoft Academic Search

BackgroundRecent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12\\/15-lipoxygenase (12\\/15LO) regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12\\/15LO is involved in the onset of high fat diet (HFD)-induced insulin resistance.Methodology\\/Principal FindingsCells

Dorothy D. Sears; Philip D. Miles; Justin Chapman; Jachelle M. Ofrecio; Felicidad Almazan; Divya Thapar; Yury I. Miller

2009-01-01

350

Mutation analysis of candidate genes within the 2q33.3 linkage area for familial early-onset generalised osteoarthritis  

Microsoft Academic Search

In a genome-wide linkage scan of seven families with familial early-onset osteoarthritis (FOA), we mapped a FOA locus to a 5 cM region on chromosome 2q33.3–2q34 with a maximum LOD score of 6.05. To identify causal variants, 17 positional candidate genes and FRZB were sequenced for coding, splice sites, and 5? and 3? untranslated regions. The pathogenicity of possible disease-causing

Josine L Min; Ingrid Meulenbelt; Margreet Kloppenburg; Cornelia M van Duijn; P Eline Slagboom

2007-01-01

351

C-Reactive Protein, Detected with a Highly Sensitive Assay, in Non-Infected Newborns and Those with Early Onset Infection  

Microsoft Academic Search

Backgound: The aim of this study was to investigate C-reactive protein (CRP), measured by a highly sensitive method (hsCRP) in non-infected newborns and in those with suspected early onset bacterial infection (EOBI) as well as to test whether EOBI would be detectable earlier by hsCRP than by a nephelometric CRP (nsCRP) assay (thresholds > 10 mg\\/l) or IL-8. Patients and

Melanie Muenzenmaier; Marita Depperschmid; Christian Gille; Christian F. Poets; Thorsten W. Orlikowsky

2008-01-01

352

Linkage analysis in German breast cancer families with early onset of the disease, using highly polymorphic markers from the chromosome 17q11-q24 region  

Microsoft Academic Search

Linkage analysis in German breast cancer families with early onset of the disease by using six markers on chromosome 17q11-q24 has been carried out. In the region between markers D17S250 and GH, three markers showed positive LOD scores at an estimated distance of zero. Evidence for linkage is greatest for D17S250, with a LOD score of 2.42. 14 refs., 1

W. Zimmermann; E. Bender; K. Rohde; A. Reis; H. Krause; H. Prokoph; S. Werner; S. Scherneck; R. Wiseman; A. Futreal

1993-01-01

353

A two-year follow-up investigation of parenting and peer influences on tobacco use onset among Italian early adolescents  

Microsoft Academic Search

The aim of this study was to investigate the influence of peer and family influences on tobacco use onset among Italian early adolescents at two-year follow-up. Participants were 161 adolescents aged 11 to 12 (M = 11.14, SD = 0.39; 49% female) living in the northwest of Italy. Multiple logistic regressions were used. Results indicated that increases in positive family climate were negatively associated

Fabrizia Giannotta; Enrique Ortega; Silvia Ciairano

2011-01-01

354

Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene  

Microsoft Academic Search

Purpose  To identify the genetic defect, and to phenotype, three consanguineous Tunisian families presenting with early-onset retinal degeneration (EORD).Methods  All accessible family members were included. They underwent blood sampling and ophthalmological examination including, when possible, full-field ERG and pupillometry. A genome-wide linkage analysis was initiated. Mutation analysis of the RPE65 gene within the linked interval was performed by bi-directional sequencing.Results  Eleven out of

Leila El Matri; Aude Ambresin; Daniel F. Schorderet; Aki Kawasaki; Mathias W. Seeliger; Andreas Wenzel; Yvan Arsenijevic; Francis L. Munier

2006-01-01

355

Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty  

PubMed Central

Purpose Long-acting gonadotropin-releasing hormone agonists (GnRHa) are commonly used to treat central precocious puberty (CPP) in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects. Methods This retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate) at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate. Results Six serious side effects (0.9%) were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621). Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE) in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy. Conclusion Sterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

Lee, Ji Woo; Kim, Hyung Jin; Choe, Yun Mee; Kang, Hee Suk; Kim, Soon Ki; Jun, Yong Hoon

2014-01-01

356

A new paradigm in the periodontal disease progression: Gingival connective tissue remodeling with simultaneous collagen degradation and fibers thickening  

Microsoft Academic Search

Bacterial dental plaque is considered to be the main cause of periodontal diseases, but progression of the disease is also related to the host inflammatory response. The earliest affected tissue is the gingiva, but the specific mechanisms involved in the onset of this condition remain unclear. Frequently, collagen degradation is pointed as the main marker of periodontal disease progression, but

M. Lorencini; J. A. F. Silva; C. A. Almeida; A. Bruni-Cardoso; H. F. Carvalho; D. R. Stach-Machado

2009-01-01

357

Minor role of BRCA2 mutation (Exon2 and Exon11) in patients with early-onset breast cancer amongst Iranian Azeri-Turkish women  

PubMed Central

Objective(s): Breast cancer is the most common cancer in women. Every year, one million new cases are reported worldwide, representing 18% of the total number of cancer in women. Hereditary BRCA1 and BRCA2 mutations account for about 60% of inherited breast cancer and are the only known causes of hereditary breast cancer syndrome. The aim of this study was to determine the frequency of BRCA2 (exon2 and exon11) gene mutation in patients with early-onset breast cancer among Iranian Azeri-Turkish women. Materials and Methods: We obtained clinical information, family history and peripheral blood from 110 women under the age of 45 with early-onset breast cancer for scanning germline mutations in the exon2 and 11 of BRCA2 genes which comprises over 50% of the gene. Single-strand conformation polymorphism assay was used in order for screening potential mutations on amplified regions followed by direct sequencing analysis to determine the genotypes. Results: Overall, 11 sequence variants were identified in this study group, including four homozygotes and seven heterozygotes silent substitution of c.3807T to C, p.Val1269Val (rs543304). Conclusion: Mutations in BRCA2 were surprisingly infrequent in the early onset breast cancer patients among Iranian Azeri-Turkish women. PMID:24711893

Karimian Fathi, Nahid; Shekari Khaniani, Mahmood; Montazeri, Vahid; Mansoori Derakhshan, Sima

2014-01-01

358

Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease.  

PubMed

Presenilin 1 (PSEN1) gene mutations are found in 30-70% of familial early-onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment were completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family. PMID:24495933

Cornejo-Olivas, Mario R; Yu, Chang-En; Mazzetti, Pilar; Mata, Ignacio F; Meza, Maria; Lindo-Samanamud, Saul; Leverenz, James B; Bird, Thomas D

2014-03-20

359

The onset of childhood amnesia in childhood: A prospective investigation of the course and determinants of forgetting of early-life events.  

PubMed

The present research was an examination of the onset of childhood amnesia and how it relates to maternal narrative style, an important determinant of autobiographical memory development. Children and their mothers discussed unique events when the children were 3 years of age. Different subgroups of children were tested for recall of the events at ages 5, 6, 7, 8, and 9 years. At the later session they were interviewed by an experimenter about the events discussed 2 to 6 years previously with their mothers (early-life events). Children aged 5, 6, and 7 remembered 60% or more of the early-life events. In contrast, children aged 8 and 9 years remembered fewer than 40% of the early-life events. Overall maternal narrative style predicted children's contributions to mother-child conversations at age 3 years; it did not have cross-lagged relations to memory for early-life events at ages 5 to 9 years. Maternal deflections of the conversational turn to the child predicted the amount of information children later reported about the early-life events. The findings have implications for our understanding of the onset of childhood amnesia and the achievement of an adult-like distribution of memories in the school years. They highlight the importance of forgetting processes in explanations of the amnesia. PMID:24236647

Bauer, Patricia J; Larkina, Marina

2014-11-01

360

Manganese exposure among smelting workers: Relationship between blood manganese-iron ratio and early onset neurobehavioral alterations  

PubMed Central

A biomarker for detection of early onset neurobehavioral alterations in manganism remains unknown. The purpose of this study was to use a neurobehavioral test battery to identify subtle changes in Mn-induced motor and memory dysfunction and to relate the quantifiable neurological dysfunction to an established Mn-exposure index such as blood manganese–iron ratio (MIR). A total of 323 subjects were recruited to control (n = 106), low-exposure (122), and high-exposure (95) groups. The test battery consisted of standard testing procedures including the nine-hole and groove-type steadiness tester, Benton visual retention test, and Purdue pegboard coordination test. No significant health problems or clinically diagnosed neurological dysfunctions were observed. Benton test did not reveal any abnormal memory deficits among Mn-exposed smelters, nor did the groove and nine-hole tests detect any abnormality in dynamic and static steadiness in tested subjects. Purdue pegboard test showed a remarkable age-related decline in fine movement coordination among all study participants regardless of the Mn-exposure condition. Mn exposure significantly exacerbated this age-related deterioration. Statistical modeling revealed that the plasma and erythrocyte MIR (i.e., pMIR and eMIR, respectively) were associated with Purdue pegboard scores. Among all subjects whose MIR were above the cut-off value (COV), pMIR was significantly correlated with pegboard scores (r = ?0.261, p = 0.002), whereas for those subjects over the age of 40, the eMIR, but not pMIR, was associated with declined pegboard performance (r = ?0.219, p = 0.069). When both factors were taken into account (i.e., age > 40 and MIR > the COV), only pMIR was inversely associated with pegboard scores. Combining their usefulness in Mn-exposure assessment, we recommend that the blood Mn–Fe ratio may serve as a reasonable biomarker not only for assessment of Mn exposure but also for health risk assessment. PMID:19963104

Cowan, Dallas M.; Zheng, Wei; Zou, Yan; Shi, Xiujuan; Chen, Jian; Rosenthal, Frank S.; Fan, Qiyuan

2014-01-01

361

Lack of mutations in spinocerebellar ataxia type 2 and 3 genes in a Taiwanese (ethnic Chinese) cohort of familial and early-onset parkinsonism.  

PubMed

Recent reports suggest that CAG triplet expansions of spinocerebellar ataxia type 2 and 3 (SCA2 and SCA3) genes are the cause of typical levodopa-responsive Parkinson's disease (PD) in familial cases, several of which were ethnic Chinese. To investigate the role of SCA2 and SCA3 mutations in Chinese familial and early-onset PD patients, we analyzed CAG triplet repeat expansions of SCA2 and SCA3 genes in a cohort of 73 Taiwanese/Ethnic Chinese familial and early-onset PD patients [mean age at onset 42.70 +/- 7.17 years (mean +/- SD)]. Thirteen of them (17.8%) had positive family history. All patients received comprehensive clinical evaluation including a thorough neurological examination, laboratory tests, and neuroimaging studies to exclude secondary causes and atypical parkinsonism. The CAG repeat length in these genes was determined using polymerase chain reaction polyacrylamide gel electrophoresis. SCA2 gene CAG repeats ranged from 15 to 26 repeats with a median of 20, and SCA3 gene CAG repeats ranged from 15 to 40 with a median of 15. No long pathogenic repeats were found in either SCA2 or SCA3, although borderline CAG repeat number was detected in the SCA3 gene of four patients. Thus, mutations of SCA2 or SCA3 did not play a major role in familial or early-onset PD in our study cohort. PD patients without autosomal dominant family history or obvious cerebellar ataxia should not be candidates for routine screening of SCA2 or SCA3 mutations for cost-effectiveness. PMID:17440947

Lin, Chin-Hsien; Hwu, Wuh-Liang; Chiang, Shu-Chuan; Tai, Chun-Hwei; Wu, Ruey-Meei

2007-06-01

362

Management of the neonate at risk for early-onset Group B streptococcal disease (GBS EOD): new paediatric guidelines in Belgium.  

PubMed

Despite group B streptococcal (GBS) screening in late pregnancy and intrapartum antimicrobial prophylaxis, early-onset sepsis in neonates remains a common source of neonatal morbidity and mortality especially in preterm neonates. The identification of neonates with early-onset sepsis is usually based on perinatal risk factors. Clinical signs are aspecific and laboratory tests are not sensitive. Therefore, many clinicians will overtreat at-risk infants. Inappropriate treatment with antibiotics increases the risk for late-onset sepsis, necrotizing enterocolitis, mortality, and prolongs hospitalisation and costs. In 2003, the Belgian Health Council published guidelines for the prevention of perinatal GBS infections. This report presents the Belgian paediatric management guidelines, which have been endorsed by the Belgian and Flemish societies of neonatology and paediatrics. The most imported changes in the 2014 guidelines are the following: recommendations for a lumbar puncture; clarification of normal spinal fluid parameters and blood neutrophil indices corrected for gestation age; specific timing for diagnostic testing after birth; no indication for diagnostic testing in asymptomatic newborns unless additional risk factors; a revised algorithm for management of neonates according to maternal and neonatal risk factors; and premature infants described as those below 35 weeks instead of 37 weeks. The guidelines were made on the basis of the best evidence and on expert opinion when inadequate evidence exists. PMID:25056493

Mahieu, L; Langhendries, J-P; Cossey, V; De Praeter, C; Lepage, P; Melin, P

2014-10-01

363

Diagnostic Value of Simultaneous Measurement of Procalcitonin, Interleukin-6 and hs-CRP in Prediction of Early-Onset Neonatal Sepsis  

PubMed Central

Neonatal sepsis is a major cause of morbidities and mortalities mostly remarkable in the third world nations.We aimed to assess the value of simultaneous measurement of procalcitonin (PCT) and interleukin-6 (IL-6) in association with high sensitive- C reactive protein(hs-CRP) in prediction of early neonatal sepsis. A follow-up study was performed on 95 neonates who were below 12 hours (h) of age and had clinical signs of sepsis or maternal risk factors for sepsis. Neonates were assigned to 4 groups including “proven early-onset sepsis”, “clinical early-onset sepsis”, “negative infectious status”, and “uncertain infectious status”. Blood samples were obtained within the first 12 h of birth repeated between 24 hours and 36 hours of age for determination of serum levels of PCT, IL-6, hs-CRP, and white blood cell (WBC) count. On admission, neonates with sepsis had a higher WBC count, IL-6, PCT, and hs-CRP levels compared with those neonates without sepsis. This remained significant even after 12–24 hours of admission. Also, patients with clinical evidences of sepsis had a higher serum level of PCT and IL-6 within 12–24 hours after admission compared to the patients with uncertain sepsis. The combination of PCT and IL-6 yielded had a sensitivity of 88% and PCT and CRP (using the cutoff value of 8 mg/L) a sensitivity of 82%.The areas under the ROC curve for the two periods were 0.801, and 0.819 respectively. In final The combination of IL-6, hs-CRP, and PCT seems to be predictive in diagnosis of early onset neonatal sepsis. PMID:22708043

Abdollahi, Alireza; Shoar, Saeed; Nayyeri, Fatemeh; Shariat, Mamak

2012-01-01

364

Warm temperatures lead to early onset of incubation, shorter incubation periods and greater hatching asynchrony in tree swallows  

E-print Network

hatching asynchrony in tree swallows Tachycineta bicolor at the extremes of their range Daniel R. Ardia in tree swallows Tachycineta bicolor at the extremes of their range. Á/ J. Avian Biol. 37: 137Á/ 142 completion in order to maintain egg-viability. We examined onset of incubation in tree swallows Tachycineta

Ardia, Dan

365

The hydrologic response of Mars to the onset of a colder climate and to the thermal evolution of its early crust  

NASA Technical Reports Server (NTRS)

Morphologic similarities between the Martian valley networks and terrestrial runoff channel have been cited as evidence that the early Martian climate was originally more Earth-like, with temperatures and pressures high enough to permit the precipitation of H2O as snow or rain. Although unambiguous evidence that Mars once possessed a warmer, wetter climate is lacking, a study of the transition from such conditions to the present climate can benefit our understanding of both the early development of the cryosphere and the various ways in which the current subsurface hydrology of Mars is likely to differ from that of the Earth. Viewed from this perspective, the early hydrologic evolution of Mars is essentially identical to considering the hydrologic response of the Earth to the onset of a global subfreezing climate.

Clifford, S. M.

1993-01-01

366

Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse  

SciTech Connect

An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA-1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA-1 repeat was found in males, but not females, with {open_quotes}long{close_quotes} alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. 22 refs., 1 fig., 3 tabs.

Vanyukov, M.M.; Moss, H.B.; Tarter, R.E. [Univ. of Pittsburg, PA (United States)] [and others

1995-04-24

367

A longitudinal assessment of periodontal disease in 52 miniature schnauzers  

PubMed Central

Background Periodontal disease (PD) is the most widespread oral disease in dogs and has been associated with serious systemic diseases. The disease is more prevalent in small breeds compared to large breeds and incidence increases with advancing age. In prevalence studies 84% of beagles over the age of 3 and 100% of poodles over the age of 4 were diagnosed with PD. Current knowledge of the rate of progression of PD is limited. The objective of this study was to determine the rate of PD progression in miniature schnauzers, an at risk small breed of dog. Dogs (n?=?52, age 1.3-6.9 years) who had received a regular oral care regime prior to this study were assessed for levels of gingivitis and periodontitis around the whole gingival margin in every tooth under general anaesthetic. Assessments were conducted approximately every six weeks for up to 60 weeks following the cessation of the oral care regime. Results All of the 2155 teeth assessed entered the study with some level of gingivitis. 23 teeth entered the study with periodontitis, observed across 12 dogs aged between 1.3 and 6.9 years. 35 dogs had at least 12 teeth progress to periodontitis within 60 weeks. Of the teeth that progressed to periodontitis, 54% were incisors. The lingual aspect of the incisors was significantly more likely to be affected (p?periodontitis-affected teeth was variable with 24% of the aspects affected having very mild gingivitis, 36% mild gingivitis and 40% moderate gingivitis. Periodontitis progression rate was significantly faster in older dogs. Only one dog (age 3.5) did not have any teeth progress to periodontitis after 60 weeks. Conclusions This is the first study to have assessed the progression rate of periodontitis in miniature schnauzers and highlights that with no oral care regime, the early stages of periodontitis develop rapidly in this breed. An oral care regime and twice yearly veterinary dental health checks should be provided from an early age for this breed and other breeds with similar periodontitis incidence rates. PMID:25179569

2014-01-01

368

Periodontal regeneration using periodontal ligament stem cell-transferred amnion.  

PubMed

Periodontal disease is characterized by the destruction of tooth supporting tissues. Regeneration of periodontal tissues using ex vivo expanded cells has been introduced and studied, although appropriate methodology has not yet been established. We developed a novel cell transplant method for periodontal regeneration using periodontal ligament stem cell (PDLSC)-transferred amniotic membrane (PDLSC-amnion). The aim of this study was to investigate the regenerative potential of PDLSC-amnion in a rat periodontal defect model. Cultured PDLSCs were transferred onto amniotic membranes using a glass substrate treated with polyethylene glycol and photolithography. The properties of PDLSCs were investigated by flow cytometry and in vitro differentiation. PDLSC-amnion was transplanted into surgically created periodontal defects in rat maxillary molars. Periodontal regeneration was evaluated by microcomputed tomography (micro-CT) and histological analysis. PDLSCs showed mesenchymal stem cell-like characteristics such as cell surface marker expression (CD90, CD44, CD73, CD105, CD146, and STRO-1) and trilineage differentiation ability (i.e., into osteoblasts, adipocytes, and chondrocytes). PDLSC-amnion exhibited a single layer of PDLSCs on the amniotic membrane and stability of the sheet even with movement and deformation caused by surgical instruments. We observed that the PDLSC-amnion enhanced periodontal tissue regeneration as determined by micro-CT and histology by 4 weeks after transplantation. These data suggest that PDLSC-amnion has therapeutic potential as a novel cell-based regenerative periodontal therapy. PMID:24032400

Iwasaki, Kengo; Komaki, Motohiro; Yokoyama, Naoki; Tanaka, Yuichi; Taki, Atsuko; Honda, Izumi; Kimura, Yasuyuki; Takeda, Masaki; Akazawa, Keiko; Oda, Shigeru; Izumi, Yuichi; Morita, Ikuo

2014-02-01

369

Neuroaxonal dystrophy presenting with neonatal dysmorphic features, early onset of peripheral gangrene, and a rapidly lethal course.  

PubMed

Infantile neuroaxonal dystrophy (IND) is a well-established autosomal recessive neurodegenerative disease. Clinical signs generally begin toward the end of the first or during the second year of life. We are aware of at least 4 cases of pre- or perinatal onset of this condition, and report here on 2 brothers who were affected at birth and had an unusual clinical course with onset of peripheral gangrene that progressed to autoamputation of digits. Both boys died in infancy with pathological changes compatible with IND. The somewhat different clinical course in these brothers leaves open the possibility that this is a variant of neuroaxonal dystrophy due to an X-linked recessive mutation. PMID:3314508

Hunter, A G; Jimenez, C L; Carpenter, B F; MacDonald, I

1987-09-01

370

An increased level of antibodies to ?-ltoglobulin is a risk determinant for early-onset Type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow's milk  

Microsoft Academic Search

Summary  Using a case-control design we have studied whether antibodies to cow's milk proteins are risk determinants for childhood-onset Type 1 (insulin-dependent) diabetes mellitus independent of early exposure to cow's milk formula and islet cell antibodies. Sera from 116 recentonset diabetic children and 112 age- and sex- matched control children were analysed for cow's milk protein IgA, IgG and IgM antibodies,

G. Dahlquist; E. Savilahti; M. Landin-Olsson

1992-01-01

371

Composition of Human Peri-implantitis and Periodontitis Lesions.  

PubMed

The aim of the present study was to examine differences in cellular characteristics of human peri-implantitis and periodontitis lesions. Two groups of patients were included: 40 patients with generalized severe chronic periodontitis and 40 patients presenting with severe peri-implantitis. Soft tissue biopsies were obtained from diseased sites (probing pocket depth ? 7 mm with bleeding on probing) and prepared for histologic and immunohistochemical analysis. In contrast to periodontitis samples, peri-implantitis lesions were more than twice as large and contained significantly larger area proportions, numbers, and densities of CD138-, CD68-, and MPO-positive cells than periodontitis lesions. Peri-implantitis lesions also extended to a position that was apical of the pocket epithelium and not surrounded by noninfiltrated connective tissue. They further presented with significantly larger densities of vascular structures in the connective tissue area lateral to the infiltrated connective tissue than within the infiltrate. This study suggests that peri-implantitis and periodontitis lesions exhibit critical histopathologic differences, which contribute to the understanding of dissimilarities in onset and progression between the 2 diseases. PMID:25261052

Carcuac, O; Berglundh, T

2014-11-01

372

The prevalence of PALB2 germline mutations in BRCA1\\/BRCA2 negative Chinese women with early onset breast cancer or affected relatives  

Microsoft Academic Search

PALB2 has been recently identified as breast cancer susceptibility gene in western populations. To investigate the contribution\\u000a of PALB2 mutations to Chinese non-BRCA1\\/BRCA2 hereditary breast cancer, we screened all coding exons and intron-exon boundaries\\u000a of PALB2 in 360 Chinese women with early-onset breast cancer or affected relatives from five breast disease clinical centers\\u000a in China by utilizing PCR-DHPLC and DNA

A-Yong Cao; Juan Huang; Zhen Hu; Wen-Feng Li; Zhong-Liang Ma; Li-Li Tang; Bin Zhang; Feng-Xi Su; Jie Zhou; Gen-Hong Di; Kun-Wei Shen; Jiong Wu; Jin-Song Lu; Jian-Min Luo; Wen-Tao Yuan; Zhen-Zhou Shen; Wei Huang; Zhi-Ming Shao

2009-01-01

373

Genome Wide Association (GWA) Study for Early Onset Extreme Obesity Supports the Role of Fat Mass and Obesity Associated Gene (FTO) Variants  

PubMed Central

Background Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA) for early onset (extreme) obesity. Methodology/Principal Findings a) GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 single nucleotide polymorphisms) for early onset extreme obesity based on 487 extremely obese young German individuals and 442 healthy lean German controls; b) confirmatory analyses on 644 independent families with at least one obese offspring and both parents. We aimed to identify and subsequently confirm the 15 SNPs (minor allele frequency ?10%) with the lowest p-values of the GWA by four genetic models: additive, recessive, dominant and allelic. Six single nucleotide polymorphisms (SNPs) in FTO (fat mass and obesity associated gene) within one linkage disequilibrium (LD) block including the GWA SNP rendering the lowest p-value (rs1121980; log-additive model: nominal p?=?1.13×10?7, corrected p?=?0.0494; odds ratio (OR)CT 1.67, 95% confidence interval (CI) 1.22–2.27; ORTT 2.76, 95% CI 1.88–4.03) belonged to the 15 SNPs showing the strongest evidence for association with obesity. For confirmation we genotyped 11 of these in the 644 independent families (of the six FTO SNPs we chose only two representing the LD bock). For both FTO SNPs the initial association was confirmed (both Bonferroni corrected p<0.01). However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium. Conclusions/Significance Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only the FTO SNPs represent true positive findings. PMID:18159244

Hinney, Anke; Nguyen, Thuy Trang; Scherag, Andre; Friedel, Susann; Bronner, Gunter; Muller, Timo Dirk; Grallert, Harald; Illig, Thomas; Wichmann, H.-Erich; Rief, Winfried; Schafer, Helmut; Hebebrand, Johannes

2007-01-01

374

Alcohol Consumption Increases Periodontitis Risk  

Microsoft Academic Search

Alcohol consumption impairs neutrophil, macrophage, and T-cell functions, increasing the likelihood of infections. We examined the association between alcohol consumption and periodontitis, prospectively, among 39,461 male health professionals aged 40 to 75 years and free of periodontitis at the start of follow-up. Alcohol intake was assessed at baseline and updated every 4 years by a food-frequency questionnaire. Periodontal disease status

W. Pitiphat; A. T. Merchant; E. B. Rimm; K. J. Joshipura

2003-01-01

375

Aggressive Periodontitis with  

E-print Network

Acute streptococcal gingivitis is an acute inflammation of the oral mucosa and also may be seen with the other oral diseases as aggressive periodontitis that is characterized by a considerable attachment loss over a relatively short period of time. Streptococcal infections of gingiva are seen rarely; also the origin of this gingival inflammation is occasionally different from that of routine plaque-associated gingivitis. The clinical features and treatment methods of these diseases are already reported in previous literatures. This case report describes a patient who presented with severe gingival inflammation and attachment loss that was diagnosed as an acute streptococcal infection associated with aggressive periodontitis. In this study a supportive treatment option was demonstrated based on these data and antacid treatment as adjunctive to the recommended treatment modalities was used for streptococcal gingivitis. (Eur J Dent 2007;1:251-255)

Cankat Kara A; Turgut Demir A

376

Cytological analysis of the periodontal pocket in patients with aggressive periodontitis and chronic periodontitis  

PubMed Central

Background: Oral exfoliative cytology includes the study and interpretation of the features cells exfoliated from the oral mucosa. The aim of this study was to analyze cytological changes in the periodontal pocket of patients with different clinical stages of aggressive periodontitis (AP) and chronic periodontitis (CP). Materials and Methods: Patients aged 24–54 years, of whom 41 were diagnosed with AP, 40 with CP, sub-classified as mild, moderate and severe periodontitis, and 40 healthy individuals who were the control group. Samples of the epithelium of the periodontal pocket were taken for the cytological study. Results: Superficial and intermediate cell values were significantly greater in patients with AP than in patients with CP or the control group. Histiocyte number was higher in patients with CP than in those with AP, and differed significantly in both types of periodontitis compared to the control group. There were significant differences in polymorphonuclear neutrophil leukocytes when both types of periodontitis were compared to the control group. Microbial flora was statistically higher in patients with CP, and there were differences between patients with periodontitis and the control group. Conclusions: The cytological study demonstrated that patients with AP had greater tissue damage, shown by the increase in intermediate and superficial cells of the epithelium of the periodontal pocket compared to the group of healthy subjects and to a lesser extent, to patients with CP. Only superficial cells made it possible to differentiate the sub-stages of the disease.

Cecilia, E. Castro; Myriam, A. Koss; Maria, E. Lopez

2014-01-01

377

Physical mapping of the major early-onset familial Alzheimer`s disease locus on chromosome 14 and analysis of candidate gene sequences  

SciTech Connect

Genetic studies of kindreds displaying evidence for familial AD (FAD) have led to the localization of gene defects responsible for this disorder on chromosomes 14, 19, and 21. A minor early-onset FAD gene on chromosome 21 has been identified to enode the amyloid precursor protein (APP), and the late-onset FAD susceptibility locus on chromosome 19 has been shown to be in linkage disequilibrium with the E4 allele of the APOE gene. Meanwhile, the locus responsible for the major form of early-onset FAD on chromosome 14q24 has not yet been identified. By recombinational analysis, we have refined the minimal candidate region containing the gene defect to approximately 3 megabases in 14q24. We will describe our laboratory`s progress on attempts to finely localize this locus, as well as test known candidate genes from this region for either inclusion in the minimal candidate region or the presence of pathogenic mutations. Candidate genes that have been tested so far include cFOS, heat shock protein 70 member (HSF2A), transforming growth factor beta (TGFB3), the trifunctional protein C1-THF synthase (MTHFD), bradykinin receptor (BR), and the E2k component of a-ketoglutarate dehydrogenase. HSP2A, E2k, MTHFD, and BR do not map to the current defined minimal candidate region; however, sequence analysis must be performed to confirm exclusion of these genes as true candidates. Meanwhile, no pathogenic mutations have yet been found in cFOS or TGFB3. We have also isolated a large number of novel transcribed sequences from the minimal candidate region in the form of {open_quotes}trapped exons{close_quotes} from cosmids identified by hybridization to select YAC clones; we are currently in the process of searching for pathogenic mutations in these exons in affected individuals from FAD families.

Tanzi, R.E.; Romano, D.M.; Crowley, A.C. [Harvard Medical School, Charlestown, MA (United States)] [and others

1994-09-01

378

Establishment of an Improved Mouse Model for Infantile Neuroaxonal Dystrophy That Shows Early Disease Onset and Bears a Point Mutation in Pla2g6  

PubMed Central

Calcium-independent group VIA phospholipase A2 (iPLA2?), encoded by PLA2G6, has been shown to be involved in various physiological and pathological processes, including immunity, cell death, and cell membrane homeostasis. Mutations in the PLA2G6 gene have been recently identified in patients with infantile neuroaxonal dystrophy (INAD). Subsequently, it was reported that similar neurological impairment occurs in gene-targeted mice with a null mutation of iPLA2?, whose disease onset became apparent approximately 1 to 2 years after birth. Here, we report the establishment of an improved mouse model for INAD that bears a point mutation in the ankyrin repeat domain of Pla2g6 generated by N-ethyl-N-nitrosourea mutagenesis. These mutant mice developed severe motor dysfunction, including abnormal gait and poor performance in the hanging grip test, as early as 7 to 8 weeks of age, in a manner following Mendelian law. Neuropathological examination revealed widespread formation of spheroids containing tubulovesicular membranes similar to human INAD. Molecular and biochemical analysis revealed that the mutant mice expressed Pla2g6 mRNA and protein, but the mutated Pla2g6 protein had no glycerophospholipid-catalyzing enzyme activity. Because of the significantly early onset of the disease, this mouse mutant (Pla2g6-inad) could be highly useful for further studies of pathogenesis and experimental interventions in INAD and neurodegeneration. PMID:19893029

Wada, Haruka; Yasuda, Takuwa; Miura, Ikuo; Watabe, Kazuhiko; Sawa, Chika; Kamijuku, Hajime; Kojo, Satoshi; Taniguchi, Masaru; Nishino, Ichizo; Wakana, Shigeharu; Yoshida, Hisahiro; Seino, Ken-ichiro

2009-01-01

379

Establishment of an improved mouse model for infantile neuroaxonal dystrophy that shows early disease onset and bears a point mutation in Pla2g6.  

PubMed

Calcium-independent group VIA phospholipase A(2) (iPLA(2)beta), encoded by PLA2G6, has been shown to be involved in various physiological and pathological processes, including immunity, cell death, and cell membrane homeostasis. Mutations in the PLA2G6 gene have been recently identified in patients with infantile neuroaxonal dystrophy (INAD). Subsequently, it was reported that similar neurological impairment occurs in gene-targeted mice with a null mutation of iPLA(2)beta, whose disease onset became apparent approximately 1 to 2 years after birth. Here, we report the establishment of an improved mouse model for INAD that bears a point mutation in the ankyrin repeat domain of Pla2g6 generated by N-ethyl-N-nitrosourea mutagenesis. These mutant mice developed severe motor dysfunction, including abnormal gait and poor performance in the hanging grip test, as early as 7 to 8 weeks of age, in a manner following Mendelian law. Neuropathological examination revealed widespread formation of spheroids containing tubulovesicular membranes similar to human INAD. Molecular and biochemical analysis revealed that the mutant mice expressed Pla2g6 mRNA and protein, but the mutated Pla2g6 protein had no glycerophospholipid-catalyzing enzyme activity. Because of the significantly early onset of the disease, this mouse mutant (Pla2g6-inad) could be highly useful for further studies of pathogenesis and experimental interventions in INAD and neurodegeneration. PMID:19893029

Wada, Haruka; Yasuda, Takuwa; Miura, Ikuo; Watabe, Kazuhiko; Sawa, Chika; Kamijuku, Hajime; Kojo, Satoshi; Taniguchi, Masaru; Nishino, Ichizo; Wakana, Shigeharu; Yoshida, Hisahiro; Seino, Ken-ichiro

2009-12-01

380

Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease?  

PubMed Central

Early-onset Alzheimer's disease (EOAD) represents 1%–2% of the Alzheimer's disease (AD) cases, and it is generally characterized by a positive family history and a rapidly progressive symptomatology. Rare coding and fully penetrant variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the only causative mutations reported for autosomal dominant AD. Thus, in this study we used exome sequencing data to rapidly screen rare coding variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47 unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is pivotal for a premortem diagnosis of autosomal dominant EOAD and for the differential diagnosis with other early onset dementias such as frontotemporal dementia (FTD) and Creutzfeldt-Jakob disease (CJD). PMID:24880964

Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael; Ding, Jinhui; Lupton, Michelle K.; Troakes, Claire; Lunnon, Katie; Al-Sarraj, Safa; Brown, Kristelle S.; Medway, Chirstopher; Lord, Jenny; Turton, James; Mann, David; Snowden, Julie; Neary, David; Harris, Jeniffer; Bras, Jose; Morgan, Kevin; Powell, John F.; Singleton, Andrew; Hardy, John

2014-01-01

381

Early Onset of Overweight and Obesity among Low-Income 1- to 5Year Olds in New York City  

Microsoft Academic Search

Early-childhood obesity has reached epidemic proportions, particularly among low-income, minority, urban children. Understanding\\u000a the progression of obesity prevalence rates from infancy through early childhood can inform public health efforts to combat\\u000a this epidemic and create developmentally appropriate strategies. In this study, we assessed the prevalence of overweight and\\u000a obesity among urban 1- to 5-year olds and estimated risk by age

Matilde Irigoyen; Melissa E. Glassman; Shaofu Chen; Sally E. Findley

2008-01-01

382

A cotwin-control analysis of drug use and abuse\\/dependence risk associated with early-onset cannabis use  

Microsoft Academic Search

We assessed whether, after controlling for genetic and shared environmental influences, early cannabis use remains a significant predictor of other drug use, abuse, and dependence, and whether the risk for early-users is greater than that for later cannabis users. Data from a 1992 telephone diagnostic interview of 8169 male twins (M=42.0 years at interview) who served in the U.S. military during

Julia D. Grant; Michael T. Lynskey; Jeffrey F. Scherrer; Arpana Agrawal; Andrew C. Heath; Kathleen K. Bucholz

2010-01-01

383

Outcomes of nonsurgical periodontal therapy in severe generalized aggressive periodontitis  

PubMed Central

Purpose Aggressive periodontitis, especially in its severe form, was traditionally considered to have an unfavourable prognosis. It required a complex treatment and its stabilization was often achieved by surgical therapy. The aim of this study was to investigate the results of nonsurgical periodontal treatment in severe generalized forms of aggressive periodontitis. Methods Patients with advanced generalized aggressive periodontitis were included in the study. Probing depth (PD) of pockets ?7 mm and clinical attachment level (CAL) of sites with attachment loss ?5 mm were measured at baseline before nonsurgical periodontal treatment, at re-evaluation, and after treatment. The following other parameters were recorded: resolution of inflammation and bone fill. We compared the baseline values with re-evaluation and posttreatment values using the Friedman test. The Wilcoxon test with the Bonferroni correction was used for both re-evaluation and posttreatment values. Results Seven patients with 266 periodontal sites were examined. A significant difference was found between values, reported as medians with interquartile ranges, for PD at baseline (7.94 [7.33-8.19] mm) and both re-evaluation (4.33 [3.63-5.08] mm) and posttreatment (3.54 [3.33-4.11] mm) values (P=0.002). A significant difference was also found between values for CAL at baseline (9.02 [7.5-9.2] mm) and both re-evaluation (6.55 [6.30-6.87] mm) and posttreatment (6.45 [5.70-6.61] mm) (P=0.002). Inflammation was resolved and angular bone defects were repaired in all cases. Conclusions These therapeutic results suggest that this form of periodontitis could have positive outcomes after nonsurgical periodontal treatment. The reparative potential of tissue affected by severe aggressive periodontitis should encourage clinicians to save apparently hopeless teeth in cases of this form of periodontitis. Graphical Abstract PMID:25177522

2014-01-01

384

College of Dentistry PER Periodontics  

E-print Network

College of Dentistry PER Periodontics KEY: # = new course * = course changed = course dropped University of Kentucky 2013-2014 Undergraduate Bulletin 1 PER 626 ADVANCED CONCEPTS IN GENERAL DENTISTRY. (1 dentistry that are essential to the clinical practice of periodontics. It includes advanced instruction

MacAdam, Keith

385

Bilingual language processing after a lesion in the left thalamic and temporal regions. A case report with early childhood onset  

SciTech Connect

This case study concerns an 18-year-old bilingual girl who suffered a radiation lesion in the left (dominant) thalamic and temporal region when she was 4 years old. Language and memory assessment revealed deficits in auditory short-term memory, auditory word comprehension, nonword repetition, syntactic processing, word fluency, and confrontation naming tasks. Both languages (English and Dutch) were found to be affected in a similar manner, despite the fact that one language (English) was acquired before and the other (Dutch) after the period of lesion onset. Most of the deficits appear to be related to verbal (short-term) memory dysfunction. Several hypotheses of subcortical involvement in memory processes are discussed with reference to existing theories in this area.

van Lieshout, P.; Renier, W.; Eling, P.; de Bot, K.; Slis, I. (Univ. of Nijmegen (Netherland))

1990-02-01

386

Onset of Disordered Eating Attitudes and Behaviors in Early Adolescence: Interplay of Pubertal Status, Gender, Weight, and Age.  

ERIC Educational Resources Information Center

Investigates the interplay of puberty, gender, weight, and age in regard to body image and disordered eating behaviors and attitudes in a sample of early adolescents. Results reveal that after menarche, females had increased personal expectations and were dissatisfied with weight/shape changes. Young males at puberty desired to build up their…

O'Dea, Jennifer A.; Abraham, Suzanne

1999-01-01

387

Inheritance of a Novel COL8A2 Mutation Defines a Distinct Early-Onset Subtype of Fuchs  

E-print Network

thickening of Descem- et's membrane and the development of nodular excrescences called guttae. This early for a point mutation altering the collagen helix domain of the 2 chain of type VIII collagen (COL8A2), substi- tuting a lysine for a glutamine (Q455K). Because collagen VIII is a major component of Descemet

Broman, Karl W.

388

Periodontal Disease Status in Gullah African Americans with Type 2 Diabetes living in South Carolina  

PubMed Central

Background African Americans have a disproportionate burden of diabetes. Gullah African Americans are the most genetically homogeneous population of African descent in the US, with an estimated European Caucasian admixture of only 3.5%. This study assessed the previously unknown prevalence of periodontal disease among a sample of Gullah African Americans with diabetes and investigated the association between diabetes control and presence of periodontal disease. Methods Gullah African Americans with Type 2 diabetes (n=235) were included. Diabetes control was assessed by HbA1C, and divided into three categories: well controlled, <7%; moderately controlled, 7–8.5%; and poorly controlled, >8.5%. Participants were categorized as healthy, having no clinical attachment loss (CAL) or bleeding on probing (BOP); early periodontitis, having CAL ?1 mm in ?2 teeth; moderate periodontitis, having 3 sites with CAL ?4 mm and at least 2 sites with probing depth (PD) ?3 mm; and severe periodontitis, having CAL ?6 mm in ?2 teeth and PD ?5 mm in ?1 site. Observed prevalences of periodontitis were compared to rates reported for the NHANES studies. Results All subjects had evidence of periodontal disease: 70.6% had moderate periodontitis and 28.5% had severe disease. Diabetes control was not associated with periodontal disease. The periodontal disease proportions were significantly higher than the reported national prevalence of 10.6% among African Americans without diabetes. Conclusions Our sample of Gullah African Americans with type 2 diabetes exhibits higher prevalence of periodontal disease than African Americans, both with and without diabetes, described in NHANES III and NHANES 1999–2000. PMID:19563285

Fernandes, Jyotika K; Wiegand, Ryan E; Salinas, Carlos F.; Grossi, Sarah G; Sanders, John J; Lopes-Virella, Maria F.; Slate, Elizabeth H.

2010-01-01

389

Magnetostratigraphic evidence of a mid-Pliocene onset of the Nihewan Formation - implications for early fauna and hominid occupation in the Nihewan Basin, North China  

NASA Astrophysics Data System (ADS)

The fluvio-lacustrine sediments in the Nihewan Basin of North China, known as the Nihewan Formation, are well-known for an abundance of Early Pleistocene mammalian fossils (known as the Nihewan Fauna sensu lato) and Paleolithic sites. The age at which the sedimentation started is thus crucial for our understanding of early fauna and hominid occupation and infilling history of the basin, but it is poorly constrained to date. Here we report on a detailed paleomagnetic investigation of the Yangshuizhan section that crops out in the northeastern Nihewan Basin, supplemented by rock magnetic analyses into the carriers of the natural remanent magnetization. Magnetite and hematite are shown to be the main carriers of the characteristic remanent magnetization. Magnetostratigraphic correlation to the geomagnetic polarity timescale indicates that the onset of the Nihewan Formation in this section occurs at ˜3.7 Ma, just below the Gilbert-Gauss boundary and ca 1-Myr earlier than previously established evidence. This pushes the lower limit of the Nihewan Formation back in time from very late Pliocene (<2.8 Ma) to (at least) the mid-Pliocene. Combining the previously established magnetostratigraphic data with the present study, we arrive at a better understanding of the chronological framework and spatio-temporal history of the deposition of the terrestrial Nihewan Formation. Furthermore, it provides new perspectives of early fauna and hominid occupation in the Nihewan Basin.

Ao, Hong; Dekkers, Mark J.; An, Zhisheng; Xiao, Guoqiao; Li, Yongxiang; Zhao, Hui; Qiang, Xiaoke; Chang, Hong; Chang, Qiufang; Wu, Dacheng

2013-01-01

390

Early nutritional stress impairs development of a song-control brain region in both male and female juvenile song sparrows (Melospiza melodia) at the onset of song learning.  

PubMed

Birdsong is a sexually selected trait and is often viewed as an indicator of male quality. The developmental stress hypothesis proposes a model by which song could be an indicator; the time during early development, when birds learn complex songs and/or local variants of song, is of rapid development and nutritional stress. Birds that cope best with this stress may better learn to produce the most effective songs. The developmental stress hypothesis predicts that early food restriction should impair development of song-control brain regions at the onset of song learning. We examined the effect of food restriction on song-control brain regions in fledgling (both sexes, 23-26 days old) song sparrows (Melospiza melodia). Food restriction selectively reduced HVC volume in both sexes. In addition, sex differences were evident in all three song-control regions. This study lends further support to a growing body of literature documenting a variety of behavioural, physiological and neural detriments in several songbird species resulting from early developmental stress. PMID:16959649

MacDonald, Ian F; Kempster, Bethany; Zanette, Liana; MacDougall-Shackleton, Scott A

2006-10-01