These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Subgingival microflora in smokers with early onset periodontitis.  

PubMed

Cigarette smoking is a potent risk factor which has recently been associated with periodontal disease progression. The objective of this study was to detect the microbial profile of early onset periodontitis in smokers and compare it to that of non-smokers. The study population consisted of 50 systemically healthy individuals aged 25 to 38 years, exhibiting early onset periodontitis. 25 patients were smokers (> 20 cigarettes/day) and 25 non-smokers. Two pooled bacterial samples comprised of four periodontal sites with probing depth > 5 mm each, were collected from each individual. The samples were cultured aerobically and anaerobically for bacterial isolation using selective and non-selective media. Isolates were characterized to species level by conventional biochemical tests and various identification kits. The differences in bacterial counts using the Mann Whitney U test were statistically significant for Staphylococcus aureus, Campylobacter concisus, Eikenella corrodens, Escherichia coli, Bacteroides forsythus, Bacteroides gracilis, Campylobacter rectus, Porphyromonas gingivalis, Selenomonas sputigena and Candida albicans in smokers. Statistically significant differences for Peptostreptococcus micros, Actinomyces naeslundii, Eubacterium lentum and Capnocytophaga gingivalis were detected in non-smokers. The isolation of bacteria belonging to the exogenous flora like E. coli, C. albicans and S. aureus in smokers microflora underscores the importance of the host which is adversely affected by cigarette smoking. PMID:16887581

Kamma, J J; Nakou, M

1997-01-01

2

Clinical and microbiological characteristics of smokers with early onset periodontitis.  

PubMed

Cigarette smoking is a potential risk factor which has recently been associated with periodontal disease progression. The objective of this study was to compare the microbial profile of smokers and non-smokers in a group of patients with early onset periodontitis. The study population consisted of 60 healthy individuals, 40 males and 20 females aged 22 to 35 yr, exhibiting early onset periodontitis. Thirty patients were smokers (30.9 cigarettes/d) and 30 non-smokers. Smokers had a higher proportion of deep pockets (PD >5 mm), especially in the maxilla anterior and premolar regions (p < 0.001) and presented a significantly greater mean probing depth and attachment loss (p <0.05) in diseased sites and a significantly greater alveolar bone loss (p <0.01) compared to non-smokers. Two pooled bacterial samples were obtained from each patient. Samples were collected from the deepest periodontal pockets of each quadrant. The samples were cultured anaerobically and in 10% CO2 plus air for bacterial isolation using selective and non-selective media. Isolates were characterized to species level by conventional biochemical tests and various identification kits. Smokers harboured a greater number of bacteria in total. Analysis of bacterial counts using the ANOVA (Mann-Whitney U-test) showed that Staphylococcus aureus, Peptostreptococcus micros, Campylobacter concisus, Escherichia coli, Bacteroides forsythus, C. gracilis, C. rectus, Porphyromonas gingivalis, Selenomonas sputigena, Candida albicans and Aspergillus fumigatus were found in significantly higher numbers and more frequently in smokers while Streptococcus intermedius, A. naeslundii, A. israelii and Eubacterium lentum were detected more frequently and in significantly higher proportions in non-smokers. The isolation of bacteria belonging to the exogenous flora such as E. coli, C. albicans, A. fumigatus and S. aureus in smokers' microbiota underscores the importance of the host that is adversely affected by cigarette smoking. PMID:10086883

Kamma, J J; Nakou, M; Baehni, P C

1999-01-01

3

periostin Null Mice Exhibit Dwarfism, Incisor Enamel Defects, and an Early-Onset Periodontal Disease-Like Phenotype  

PubMed Central

Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (perilacZ) embryos are grossly normal. Postnatally, however, ?14% of the nulls die before weaning and all of the remaining perilacZ nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the perilacZ nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses. PMID:16314533

Rios, Hector; Koushik, Shrinagesh V.; Wang, Haiyan; Wang, Jian; Zhou, Hong-Ming; Lindsley, Andrew; Rogers, Rhonda; Chen, Zhi; Maeda, Manabu; Kruzynska-Frejtag, Agnieszka; Feng, Jian Q.; Conway, Simon J.

2005-01-01

4

Family history and the risk of early onset persistent, early onset transient and late onset asthma  

PubMed Central

Family history of asthma and allergies strongly influences asthma risk in children but the association may differ for early onset persistent, early onset transient, and late onset asthma. We analyzed the relation between family history and these types of asthma using cross-sectional data from a school-based study of 5,046 Southern California children. Parental and/or sibling history of asthma and allergy were generally more strongly associated with early onset persistent asthma compared with early onset transient or late onset asthma. For children with two asthmatic parents relative to those with none, the prevalence ratio (PR) for early onset persistent asthma was 12.1 [95% confidence interval (CI) 7.91–18.7] compared with 7.51 (95% CI 2.62–21.5) for early onset transient asthma and 5.38 (95% CI 3.40–8.50) for late onset asthma. Maternal smoking in pregnancy was predominantly related to the risk of early onset persistent asthma in the presence of parental history of allergy and asthma and the joint effects were more than additive (interaction contrast ratio = 3.10, 95% CI 1.45–4.75). Our results confirm earlier data that parental history of asthma and allergy is most strongly associated with early onset persistent asthma and suggest that among genetically predisposed children, an early life environmental exposure, maternal smoking during pregnancy, favors the development of early onset asthma that persists into later early childhood. PMID:11505179

London, Stephanie J.; Gauderman, W. James; Avol, Edward; Rappaport, Edward B.; Peters, John M.

2006-01-01

5

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-11Apr2013 #12;Early onset bipolar disorder 3 Résumé français : Objectifs : Le Trouble Bipolaire (TB) est

Paris-Sud XI, Université de

6

Early-Onset Neonatal Sepsis  

PubMed Central

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

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

2014-01-01

7

A neuropsychological study of early onset schizophrenia  

Microsoft Academic Search

Characterizing a pattern of cognitive dysfunction in early onset schizophrenic patients may illuminate neurodevelopmental contributions to the illness. A cohort of chronically institutionalized schizophrenic patients with a variable range of age of onset (range 7–29 years) was administered a comprehensive battery of neurophsychological tests that included the Luria-Nebraska Neuropsychological Test Battery. After statistical control of age, parental socioeconomic class (SES)

Anne L. Hoff; Debra Harris; William O. Faustman; Michael Beal; Diana DeVilliers; Robert D. Mone; James A. Moses; John G. Csernansky

1996-01-01

8

Periodontal Disease and Late-Onset Aortic Prosthetic Vascular Graft Infection  

PubMed Central

Prosthetic vascular graft infection (PVGI) is a rare but significant complication of arterial reconstructive surgery. Although the relative risk is low, the clinical consequences can be catastrophic. Microbiological data on causative bacteria are limited. We present four cases of late-onset PVGI. Using a culture-independent nucleic acid amplification method for analysis of intraoperative samples, the presence of bacteria highly suggestive of an oral source was reported. Examination by an oral health specialist confirmed the presence of chronic periodontal disease. We hypothesize that chronic oral infection may be a previously unreported risk factor for the development of late-onset PVGI.

Thomas, Stephanie; Ghosh, Jonathan; Porter, Johnathan; Cockcroft, Adele; Rautemaa-Richardson, Riina

2015-01-01

9

Periodontitis  

MedlinePLUS

Pyorrhea - gum disease; Inflammation of gums - involving bone ... Periodontitis occurs when inflammation or infection of the gums ( gingivitis ) is allowed to progress without treatment. Infection ...

10

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

11

Early-onset Lafora body disease.  

PubMed

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; Minassian, Berge A

2012-09-01

12

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

13

[Brain imaging in early onset anorexia].  

PubMed

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

Bargiacchi, A

2014-05-01

14

Early onset torsion dystonia (Oppenheim's dystonia)  

PubMed Central

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

Kamm, Christoph

2006-01-01

15

Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1  

Microsoft Academic Search

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

Gabrielle Fredman; Sungwhan F. Oh; Srinivas Ayilavarapu; Hatice Hasturk; Charles N. Serhan; Thomas E. van Dyke; Dominik Hartl

2011-01-01

16

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

17

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

18

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.

19

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

PubMed Central

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

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

2014-01-01

20

Early-onset Childhood Sarcoidosis with Incidental Multiple Enchondromatosis  

PubMed Central

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

2012-01-01

21

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

PubMed

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90-100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10-20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90-100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10-20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage. PMID:24983276

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

2014-08-01

22

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

23

A New Italian Pedigree With Early-Onset Alzheimer's Disease  

Microsoft Academic Search

We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family

Innocenzo Rainero; Lodovico Bergamini; Amalia Cecilia Bruni; Luigi Ferini-Strambi; Jean-François Foncin; Giorgio Gei; Fabio Macciardi; Maria Paola Montesi; Lorenzo Pinessi; Giovanna Vaula

1994-01-01

24

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

ERIC Educational Resources Information Center

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

McIntosh, David E.; Trotter, Jeffrey S.

2006-01-01

25

Early-Onset Psychosis in Youth with Intellectual Disability  

ERIC Educational Resources Information Center

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

Friedlander, R. I.; Donnelly, T.

2004-01-01

26

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

27

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

28

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

29

Early-onset dementias: diagnostic and etiological considerations  

PubMed Central

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

2013-01-01

30

Early-onset acral basal cell carcinomas in Gorlin syndrome.  

PubMed

Two patients are reported in whom early-onset, distal papules with a histopathological diagnosis of basal cell carcinoma were the first manifestation of Gorlin syndrome (GS). These lesions showed no progression and remained stable through follow-up. Two different PTCH1 gene mutations were detected in the two patients, and thus a phenotype-genotype correlation of this manifestation of GS was not possible. PMID:24837096

Torrelo, A; Vicente, A; Navarro, L; Planaguma, M; Bueno, E; González-Sarmiento, R; Hernández-Martín, A; Noguera-Morel, L; Requena, L; Colmenero, I; Parareda, A; González-Enseñat, M A; Happle, R

2014-11-01

31

Clinicopathological and genetic study of early-onset demyelinating neuropathy  

Microsoft Academic Search

Summary Autosomal recessive demyelinating Charcot-Marie- Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a geneti- cally heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between

Yesim Parman; Ibrahim Bars; Birdal Bilir; Muruvvet Poyraz; Nisrine Bissar-Tadmouri; Anna Williams; Nadia Ammar; Eva Nelis; Vincent Timmerman; Feza Deymeer; Piraye Serdaro; Peter J. Brophy

2004-01-01

32

Patterns of axis II comorbidity in early-onset versus late-onset panic disorder in Japan  

Microsoft Academic Search

Early onset of psychiatric disorders has been reported to be associated with increased familial risk or more severe clinical symptoms. In this study, we specifically examine the association between clinical severity and early versus late onset in panic disorder. We hypothesize the existence of differences in rates of axis II disorders in these two groups that will relate to clinical

Toshiya Iketani; Nobuo Kiriike; Murray B Stein; Kouji Nagao; Naomitsu Minamikawa; Atsushi Shidao; Hidehiro Fukuhara

2004-01-01

33

Functional Connectivity of the Amygdala in Early Childhood Onset Depression  

PubMed Central

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 Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

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

2011-01-01

34

Childhood Risk Factors for Early-Onset Drinking*  

PubMed Central

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

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

2011-01-01

35

Auditory perceptual consolidation in early-onset blindness.  

PubMed

Early-onset blindness (EB) produces measurable advantages in auditory perception, attention, memory and language. Neville and Bavelier [Neville, H. J., & Bavelier, D. (2001) Variability of developmental plasticity. In J. L. McClelland, R. S. Siegler (Eds.) Mechanisms of cognitive development: Behavioral andellon symposia on cognition (pp. 271-301)] hypothesized that faster temporal processing underlies many auditory compensatory effects in the blind. We tested this hypothesis by comparing early-onset blind individuals and sighted counterparts (SC) by assessing their rates of perceptual consolidation, the accurate perceptual representation of auditory stimuli. Firstly, we first tested both groups on a temporal-order judgment task (TOJ). EB subjects had significantly lower TOJ thresholds than the SC subjects. Secondly, we assessed perceptual consolidation speed using auditory backward masking tasks, taking into account individual TOJ thresholds. Discrimination performance was unaffected at all mask delays in the EB group while the SC subjects needed a mask delay of 160 ms to perform comparably. A backward masking task using single tone stimuli found no differences between the EB and SC groups any mask delay. A simultaneous masking task demonstrated that the mask effectively impaired discrimination in EB subjects at sensory stages. These results suggest that advantages in perceptual consolidation may reflect a mechanism responsible for the short response times and better performance reported in early blind individuals across a number of complex auditory tasks. PMID:15869766

Stevens, Alexander A; Weaver, Kurt

2005-01-01

36

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

37

Menkes disease – An important cause of early onset refractory seizures  

PubMed Central

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

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

2014-01-01

38

Assessing racial/ethnic differences in the social consequences of early-onset psychiatric disorder.  

PubMed

Individuals with early onset of psychiatric disorder have worse social outcomes than individuals with adult onset. It is unknown whether this association varies by racial/ ethnic group. Identifying groups at risk for poor social outcomes is important for improving clinical and policy interventions. We compared unemployment, high school dropout, arrest, and welfare participation by race/ethnicity and time of onset using a nationally representative sample of Whites, Blacks, Asians, and Latinos with lifetime psychiatric disorder. Early onset was associated with worse social outcomes than adult onset. Significant Black-White and Latino-White differences in social outcomes were identified. The association between early onset and negative social outcomes was similar across Whites, Latinos, and Blacks. For Asians, the association between unemployment and early onset was opposite that of Whites. Increasing early detection and treatment of psychiatric illness should be prioritized. Further study will clarify the association between onset and social outcomes among sub-ethnic populations. PMID:20453376

Lê Cook, Benjamin; Carson, Nicholas; Alegria, Margarita

2010-05-01

39

Assessing Racial/Ethnic Differences in the Social Consequences of Early-Onset Psychiatric Disorder  

PubMed Central

Individuals with early onset of psychiatric disorder have worse social outcomes than individuals with adult onset. It is unknown whether this association varies by racial/ethnic group. Identifying groups at risk for poor social outcomes is important for improving clinical and policy interventions. We compared unemployment, high school dropout, arrest, and welfare participation by race/ethnicity and time of onset using a nationally representative sample of Whites, Blacks, Asians, and Latinos with lifetime psychiatric disorder. Early onset was associated with worse social outcomes than adult onset. Significant Black-White and Latino-White differences in social outcomes were identified. The association between early onset and negative social outcomes was similar across Whites, Latinos, and Blacks. For Asians, the association between unemployment and early onset was opposite that of Whites. Increasing early detection and treatment of psychiatric illness should be prioritized. Further study will clarify the association between onset and social outcomes among sub-ethnic populations. PMID:20453376

Lê Cook, Benjamin; Carson, Nicholas; Alegria, Margarita

2010-01-01

40

Epidemiology of early-onset neonatal group B streptococcal infection  

PubMed Central

OBJECTIVE To determine the difference in outcomes between universal screening and risk-based assessment for prenatal group B streptococcus (GBS) infection based on the epidemiology of early-onset GBS infection in Winnipeg, Man, and to examine its implications for prenatal GBS screening. DESIGN Retrospective random chart audit of 330 women receiving intrapartum hospital care and retrospective chart audit of all infants with early-onset neonatal GBS disease over 2 years. SETTING Each of the 3 hospitals in Winnipeg, Man, offering intrapartum services. MAIN OUTCOME MEASURES Maternal charts were audited for history of prenatal GBS screening, GBS status, clinical risk factors for neonatal GBS transmission, and use of intrapartum antibiotics to prevent neonatal GBS infection. Neonatal GBS records were audited for maternal clinical risk factors for GBS transmission, history of maternal GBS screening and GBS status, use of maternal intrapartum antibiotic prophylaxis, and neonatal outcome. RESULTS Screening revealed a 26% GBS carrier rate in our population. Among these carriers, 70% (or 18% of the population) had no other clinical risk factors for neonatal GBS transmission. The transmission rate for untreated GBS-positive women was 1.74 per 1000 women. The differences in outcomes between universal and risk-based screening were small in our population. A total of 3449 women would require universal screening to prevent a single case of early-onset neonatal GBS disease that would occur if a risk-based approach were used (3 cases per year). This number increases to 68 966 to prevent a single GBS-related death (1 case in 7 years). An additional 679 women would receive intrapartum prophylactic antibiotics per year with universal screening than would have received antibiotics with a risk-based approach. CONCLUSION The differences in neonatal GBS transmission rates resulting from universal versus risk-based screening in Winnipeg require universal screening of many women for results to become apparent. Universal screening and antibiotic prophylaxis of all GBS carriers result in increased antibiotic exposure in our population, which might carry its own risks. Therefore, patients should be involved in decisions on whether to be screened based on identification of risks and benefits. PMID:17872785

Konrad, Gerald; Katz, Alan

2007-01-01

41

Severe early-onset colitis revealing mevalonate kinase deficiency.  

PubMed

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

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

2013-09-01

42

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

ERIC Educational Resources Information Center

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

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

2009-01-01

43

The onset of galactic winds in early-type galaxies  

NASA Technical Reports Server (NTRS)

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

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

1990-01-01

44

The unique experience of spouses in early-onset dementia.  

PubMed

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

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

2013-09-01

45

Biologically inactive leptin and early-onset extreme obesity.  

PubMed

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

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

2015-01-01

46

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.

Lynne H. Gildensoph

2008-01-01

47

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

48

Cytomegalovirus infection in association with early onset pre-eclampsia.  

PubMed

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

49

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

50

Case Report: Depression vs. Early-Onset Alzheimer Disease: The Genetic Counselor's Role  

Microsoft Academic Search

Awareness of depression in the differential diagnosis of Alzheimer disease is essential for genetic counselors seeing patients at risk for early-onset familial Alzheimer disease (EOFAD). The genetic counselor is in a unique position to recognize depression as the cause of symptoms mimicking early-onset Alzheimer disease. While generating a family medical history, the counselor can evoke significant emotional history as well.

Jill S. Goldman

2001-01-01

51

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

52

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

53

Widespread Disruption of Functional Brain Organization in Early-Onset Alzheimer’s Disease  

PubMed Central

Early-onset Alzheimer’s disease (AD) patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old), 28 late-onset (?65 years old) AD patients and 15 “young” (<65 years old) and 31 “old” (?65 years old) age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls), which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive performance is needed. PMID:25080229

Adriaanse, Sofie M.; Binnewijzend, Maja A. A.; Ossenkoppele, Rik; Tijms, Betty M.; van der Flier, Wiesje M.; Koene, Teddy; Smits, Lieke L.; Wink, Alle Meije; Scheltens, Philip; van Berckel, Bart N. M.; Barkhof, Frederik

2014-01-01

54

Clonal expansions and short telomeres are associated with neoplasia in early-onset, but not late-onset, ulcerative colitis  

PubMed Central

BACKGROUND Patients with ulcerative colitis (UC) are at risk of developing colorectal cancer. We have previously reported that cancer progression is associated with the presence of clonal expansions and shorter telomeres in non-dysplastic mucosa. We sought to validate these findings in an independent case-control study. METHODS This study included 33 patients with UC: 14 Progressors (patients with high-grade dysplasia or cancer) and 19 Non-Progressors. For each patient, a mean of 5 non-dysplastic biopsies from proximal, mid, and distal colon were assessed for clonal expansions, as determined by clonal length altering mutations in polyguanine tracts, and telomere length, as measured by Quantitative-PCR. Both parameters were compared with individual clinico-pathological characteristics. RESULTS Clonal expansions and shorter telomeres were more frequent in non-dysplastic biopsies from UC Progressors than Non-Progressors, but only for patients with early-onset of UC (diagnosis at less than 50 years of age). Late-onset Progressor patients had very few or no clonal expansions and longer telomeres. A few Non-Progressors exhibited clonal expansions, which were associated with older age and shorter telomeres. In Progressors, clonal expansions were associated with proximity to dysplasia. The mean percentage of clonally expanded mutations distinguished early-onset Progressors from Non-Progressors with 100% sensitivity and 80% specificity. CONCLUSIONS Early-onset Progressors develop cancer in a field of clonally expanded epithelium with shorter telomeres. The detection of these clones in a few random non-dysplastic colon biopsies is a promising cancer biomarker in early-onset UC. Curiously, late-onset UC patients appear to develop cancer without the involvement of such fields. PMID:24097228

Salk, Jesse J.; Bansal, Aasthaa; Lai, Lisa A.; Crispin, David A.; Ussakli, Cigdem H.; Horwitz, Marshall S.; Bronner, Mary P.; Brentnall, Teresa A.; Loeb, Lawrence A.; Rabinovitch, Peter S.; Risques, Rosa Ana

2013-01-01

55

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

PubMed

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

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

2013-01-01

56

Early-onset obsessive-compulsive disorder and personality disorders in adulthood.  

PubMed

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis. PMID:18237785

Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

2008-03-15

57

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

PubMed Central

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

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

2012-01-01

58

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

2012-01-01

59

Walking strategies in subjects with congenital or early onset strabismus  

PubMed Central

Introduction: In congenital strabismus, sensory adaptations occur hampering the correct development of normal binocular vision. The aim of this study is to investigate if patients with congenital or early onset exotropic or esotropic strabismus adopt different walking strategies with respect to healthy subjects. Our hypothesis is that the abnormal binocular cooperation, occurring in patients with exotropic or esotropic strabismus, could influence neurosensorial adaptation of the gait pattern. Materials and Methods: Twenty-five patients were enrolled: 19 with esotropic (ESO) and 6 with exotropic strabismus (EXO). All patients underwent an ophthalmological and orthoptic evaluation. Biomechanical data were collected using a stereophotogrammetric system and a force platform. Twenty-seven age-matched healthy subjects (HS) were used as controls. Results: The comparison between patients with ESO and patients with EXO strabismus showed that the maximal power at the knee and at the ankle was lower in EXO group (p < 0.01 and p < 0.05, respectively). The step width was statistically different between ESO and EXO groups (p < 0.01), lower in patients with ESO and higher in patients with EXO strabismus when compared with HS (though not statistically significant). The deviation angle values showed a relationship with the step width (at the near fixation p < 0.05) and with the maximal power at the knee and at the ankle (at the far fixation for the knee p < 0.001 and for the ankle p < 0.05; at the near fixation for the knee p < 0.05): in the patients with EXO the increased angle deviation is related to larger step width and to lower power at the knee and at the ankle. In the patients with ESO strabismus this relationship is less robust. Discussion: Patients with EXO and ESO strabismus adopt different strategies to compensate their walking difficulties, and these strategies are likely due to an expanded binocular visual field in patients with EXO and to a reduced visual field in patients with ESO strabismus. PMID:25071514

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

2014-01-01

60

Early Onset Prostate Cancer Has A Significant Genetic Component  

PubMed Central

BACKGROUND Prostate cancer (PCa) affects more than 190,000 men each year with ~10% of men diagnosed at ? 55 years, i.e., early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology. METHODS We evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina’s iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS). RESULTS Significant associations existed for 13 of 14 SNPs (rs9364554 on 6q25, rs10486567 on 7p15, rs6465657 on 7q21, rs6983267 on 8q24, rs1447295 on 8q24, rs1571801 on 9q33, rs10993994 on 10q11, rs4962416 on 10q26, rs7931342 on 11q13, rs4430796 on 17q12, rs1859962 on 17q24.3, rs2735839 on 19q13, and rs5945619 on Xp11.22, but not rs2660753 on 3p12). EO PCa cases had a significantly greater cumulative number of risk alleles (mean 12.4) than iControlDB controls (mean 11.2; p=2.1×10?33) or CGEMS cases (mean 11.9; p=1.7 × 10?5). Notably, EO PCa cases had a higher frequency of the risk allele than CGEMS cases at 11 of13 associated SNPs, with significant differences for five SNPs. EO PCa cases diagnosed at <50 (mean 12.8) also had significantly more risk alleles than those diagnosed at 50–55 years (mean 12.1; p = 0.0003). CONCLUSIONS These results demonstrate the potential for identifying PCa-associated genetic variants by focusing on the subgroup of men diagnosed with EO disease. PMID:21538423

Lange, Ethan M.; Salinas, Claudia A.; Zuhlke, Kimberly A.; Ray, Anna M.; Wang, Yunfei; Lu, Yurong; Ho, Lindsey A.; Luo, Jingchun; Cooney, Kathleen A.

2011-01-01

61

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

ERIC Educational Resources Information Center

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

Schonfeld, Lawrence; And Others

62

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

ERIC Educational Resources Information Center

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

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

2005-01-01

63

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

64

Predictors of Early Adult Outcome in Pediatric-Onset Obsessive-Compulsive Disorder.  

E-print Network

??This study was conducted in order to determine childhood clinical predictors of early adult outcome in pediatric-onset obsessive-compulsive disorder (OCD). We specifically hypothesized that OCD… (more)

Craiglow, Brittany G

65

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

PubMed

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

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

2010-07-01

66

Distributional cues and the onset bias in early word segmentation.  

PubMed

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

Babineau, Mireille; Shi, Rushen

2014-12-01

67

Tyrosine hydroxylase Val-81-Met polymorphism associated with early-onset alcoholism.  

PubMed

The present study examined the association of the Tyrosine hydroxylase Val-81-Met polymorphism with alcohol dependence. One hundred and fifty-nine patients in a psychiatric unit with alcohol dependence were genotyped as well as 92 healthy volunteers. The Val allele was more frequent in patients with alcohol dependence (69.5%) than in controls (62.5%). This effect was largely due to the association with early-onset alcoholism (77.8%), whereas no difference was noted between late-onset patients and controls. Our results suggest a role for tyrosine hydroxylase in early-onset alcoholism. PMID:15722952

Dahmen, Norbert; Völp, Markus; Singer, Peter; Hiemke, Christoph; Szegedi, Armin

2005-03-01

68

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

Microsoft Academic Search

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

Deliane van Vliet; Christian Bakker; Raymond TCM Koopmans; Myrra JFJ Vernooij-Dassen; Frans RJ Verhey; Marjolein E de Vugt

2010-01-01

69

A new definition of early age at onset in alcohol dependence  

PubMed Central

Objective The accurate cut-off of an early onset of alcohol dependence is unknown. The objectives of this analysis are (1) to confirm that ages at onset variability in alcohol dependence is best described as a two sub-groups entity, (2) to define the most appropriate cut-off, and (3) to test the relevancy of such distinction. Method Data were drawn the Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This study focused on the 4,782 adults with lifetime alcohol dependence. Results The best-fit model distinguished two subgroups of age at onset of alcohol dependence, with a cut-off point at 22 years. Subjects with an earlier onset of alcohol dependence (?22 years old) reported higher lifetime rates of specific phobia, antisocial behaviors and nearly all addictive disorders. Conclusions The early onset of alcohol dependence is best defined as beginning before the age of 22 years. PMID:20018459

Le Strat, Yann; Grant, Bridget F.; Ramoz, Nicolas; Gorwood, Philip

2015-01-01

70

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

PubMed

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

Leach, Liana Sarma; Butterworth, Peter

2012-08-30

71

Family functioning and early onset of sexual intercourse in Latino adolescents.  

PubMed

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, sexual permissiveness, and such familial variables as: discipline, parental supervision, and parental support. Significant relationships were observed between early onset of sexual intercourse and parental supervision, discipline, parental support, and parents' marital status. Results suggest the key role of parents and family in prevention of HIV-risk behaviors among adolescents in terms of delaying sexual onset. Overall, the study described youths who postponed sexual activity as having greater support, supervision, and parental involvement. PMID:16468671

Vélez-Pastrana, Maria C; González-Rodríguez, Rafael A; Borges-Hernández, Adalisse

2005-01-01

72

Periodontal response to early uncovering, autonomous eruption, and orthodontic alignment of palatally impacted maxillary canines  

Microsoft Academic Search

Introduction: The purpose of this study was to evaluate differences in periodontal status, root length, and visual assessment in patients with palatally impacted maxillary canines that were surgically exposed, allowed to erupt freely into the palate, and orthodontically aligned. Methods: Clinical examinations of the maxillary lateral incisors, canines, and adjacent premolars were performed on 16 patients with unilaterally impacted canines

Andrew D. Schmidt; Vincent G. Kokich

2007-01-01

73

Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life  

E-print Network

Asthma onset prior to multiple sclerosis and the contribution of sibling exposure in early life A of higher infection load. The effect on Th1 disorders such as multiple sclerosis (MS) is less clear. Here we with a protective role for early life infections. Keywords: asthma, herpes virus, hygeine hypothesis, multiple

Cochran-Stafira, D. Liane

74

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

75

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

76

Different cellular and molecular mechanisms for early and late-onset myelin protein zero mutations.  

PubMed

Mutations in the gene MPZ, encoding myelin protein zero (MPZ), cause inherited neuropathies collectively called Charcot-Marie-Tooth type 1B (CMT1B). Based on the age of onset, clinical and pathological features, most MPZ mutations are separable into two groups: one causing a severe, early-onset, demyelinating neuropathy and a second, causing a late-onset neuropathy with prominent axonal loss. To investigate potential pathomechanisms underlying the two phenotypes, we transiently transfected HeLa cells with two late-onset (T95M, H10P) and two early-onset (H52R, S22_W28 deletion) mutations and analyzed their effects on intracellular protein trafficking, glycosylation, cell viability and intercellular adhesion. We found that the two late-onset mutations were both transported to the cell membrane and moderately reduced MPZ-mediated intercellular adhesion. The two early-onset mutations caused two distinct abnormalities. H52R was correctly glycosylated and trafficked to the plasma membrane, but strongly affected intercellular adhesion. When co-expressed with wild-type MPZ (wtMPZ), a functional dominant negative effect was observed. Alternatively, S22_W28 deletion was retained within the cytoplasm and reduced both adhesion caused by wtMPZ and cellular viability. Since the same trafficking patterns were observed in transfected murine Schwann cells, they are not an artifact of heterologous cell expression. Our results suggest that at least some late-onset mutations cause a partial loss of function in the transfected cells, whereas multiple abnormal gain of function pathways can result in early-onset neuropathy. Further characterization of these pathways will lead to a better understanding of the pathogenesis of CMT1B and a rational basis for treating these debilitating inherited neuropathies. PMID:18337304

Grandis, Marina; Vigo, Tiziana; Passalacqua, Mario; Jain, Manisha; Scazzola, Sara; La Padula, Veronica; Brucal, Michelle; Benvenuto, Federica; Nobbio, Lucilla; Cadoni, Angela; Mancardi, Gian Luigi; Kamholz, John; Shy, Michael E; Schenone, Angelo

2008-07-01

77

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

78

Early-onset colorectal cancer: a separate subset of colorectal cancer.  

PubMed

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

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

2014-12-14

79

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

PubMed Central

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

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

2014-01-01

80

Common dysfunctional variants in ABCG2 are a major cause of early-onset gout  

PubMed Central

Gout is a common disease which mostly occurs after middle age, but more people nowadays develop it before the age of thirty. We investigated whether common dysfunction of ABCG2, a high-capacity urate transporter which regulates serum uric acid levels, causes early-onset gout. 705 Japanese male gout cases with onset age data and 1,887 male controls were genotyped, and the ABCG2 functions which are estimated by its genotype combination were determined. The onset age was 6.5?years earlier with severe ABCG2 dysfunction than with normal ABCG2 function (P = 6.14 × 10?3). Patients with mild to severe ABCG2 dysfunction accounted for 88.2% of early-onset cases (twenties or younger). Severe ABCG2 dysfunction particularly increased the risk of early-onset gout (odds ratio 22.2, P = 4.66 × 10?6). Our finding that common dysfunction of ABCG2 is a major cause of early-onset gout will serve to improve earlier prevention and therapy for high-risk individuals. PMID:23774753

Matsuo, Hirotaka; Ichida, Kimiyoshi; Takada, Tappei; Nakayama, Akiyoshi; Nakashima, Hiroshi; Nakamura, Takahiro; Kawamura, Yusuke; Takada, Yuzo; Yamamoto, Ken; Inoue, Hiroki; Oikawa, Yuji; Naito, Mariko; Hishida, Asahi; Wakai, Kenji; Okada, Chisa; Shimizu, Seiko; Sakiyama, Masayuki; Chiba, Toshinori; Ogata, Hiraku; Niwa, Kazuki; Hosoyamada, Makoto; Mori, Atsuyoshi; Hamajima, Nobuyuki; Suzuki, Hiroshi; Kanai, Yoshikatsu; Sakurai, Yutaka; Hosoya, Tatsuo; Shimizu, Toru; Shinomiya, Nariyoshi

2013-01-01

81

Blood group A: an overseen risk factor for early-onset ovarian hyperstimulation syndrome?  

PubMed

Ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication, is classified into two distinct forms, early-onset and late-onset OHSS. Few risk factors have been established, but no association with ABO blood group antigens was known. From January 2000 to October 2007, 122 patients with known blood groups and the diagnosis of OHSS were hospitalized. OHSS classification, pregnancies, age and time of in-patient treatment were collated. Two control groups were established. One group comprised 177 patients treated for infertility without developing OHSS (treatment/no OHSS) and known blood groups. A second one consisted of 2289 obstetric and gynaecological patients (O/G). OHSS grade I, II or III was found in 20, 47 and 55 patients, respectively. The pregnancy rate was 50.8% and did not differ among the different OHSS grades. Blood group A was significantly more frequent and blood group O less frequent in patients with early-onset OHSS compared with the two control cohorts (P = 0.009 versus treatment/no OHSS; P = 0.001 versus O/G). The odds ratio for patients with blood group A versus O to develop early-onset OHSS was 2.169 and 2.262, respectively. No increased risk for late-onset OHSS was found. Blood group A may be associated with early-onset OHSS in Caucasians. PMID:18681991

Binder, Helge; Flegel, Willy A; Emran, Jasmin; Müller, Andreas; Cupisti, Susanne; Beckmann, Matthias W; Eckstein, Reinhold; Dittrich, Ralf; Ringwald, Juergen

2008-08-01

82

PLACENTAL LESIONS ASSOCIATED WITH MATERNAL UNDERPERFUSION ARE MORE FREQUENT IN EARLY-ONSET THAN IN LATE-ONSET PREECLAMPSIA  

PubMed Central

Objective Preeclampsia (PE) has been classified into early- and late-onset disease. These two phenotypic variants of PE have been proposed to have a different pathophysiology. However, the gestational age cut-off to define ‘early’ versus ‘late’ PE has varied among studies. The objective of this investigation was to determine the prevalence of lesions consistent with maternal underperfusion of the placenta in patients with PE as a function of gestational age. Study design A nested case-control study of 8,307 singleton pregnant women who deliver after 20 weeks of gestation was constructed based on a cohort. Cases were defined as those with PE (n=910); controls were pregnant women who did not have a hypertensive disorder in pregnancy (n=7,397). The frequency of maternal underperfusion of the placenta (according to the criteria of the Society for Pediatric Pathology) was compared between the two groups. Logistic regression was used for analysis. Estimated relative risks were calculated from adjusted odds ratios. Results 1) The prevalence of lesions consistent with maternal underperfusion was higher in patients with PE than in the control group [43.3% vs. 15.9%; unadjusted odds ratio 4.0 (95% CI 3.5–4.7); P<0.001]; 2) the estimated relative risk of maternal underperfusion lesions in PE was higher than in the control group; 3) the lower the gestational age at delivery, the higher the relative risk for these lesions; 4) early-onset PE, regardless of the gestational age used to define it (<32, 33, 34, 35 or 37 weeks) had a significantly higher frequency of placental lesions consistent with maternal underperfusion than late-onset PE (p<0.001 for all). Conclusions 1) The earlier the gestational age of preeclampsia at delivery, the higher the frequency of placental lesions consistent with maternal underperfusion; 2) our data suggests that demonstrable placental involvement as determined by pathologic examination differs in early- and late-onset preeclampsia; and 3) this phenomenon appears to be a continuum, and we could not identify a clear and unambiguous gestational age at which lesions consistent with underperfusion would not be present. PMID:21848483

Ogge, Giovanna; Chaiworapongsa, Tinnakorn; Romero, Roberto; Hussein, Youssef; Kusanovic, Juan Pedro; Yeo, Lami; Kim, Chong Jai; Hassan, Sonia S

2011-01-01

83

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

PubMed Central

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

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

2014-01-01

84

Early Onset of Periaortic Inflammation after EVAR with Inferior Vena Cava Involvement: A Case Report.  

PubMed

Endovascular treatment of abdominal aortic aneurysm (EVAR) represents a good alternative to open surgery, also in patients who present inflammatory abdominal aortic aneurysm, resulting in reduction of the inflammatory process in many cases. Instead, the onset of periaortic inflammation after EVAR is a rare event with an unclear pathogenesis, time of onset, and clinical presentation. This is a case report of a very early onset of periaortitis after EVAR with inferior vena cava involvement and stretching, resulting in lower limb swelling and back pain, treated by corticosteroid drug with a good remission of the pathology. PMID:25304907

Mansour, Wassim; Capoccia, Laura; Garofano, Roberta; Pranteda, Chiara; Speziale, Francesco

2015-01-01

85

"Distressed aging": the differences in brain activity between early- and late-onset tinnitus.  

PubMed

Recent findings regarding different characteristics according to the age of tinnitus onset prompted us to conduct a study on the differences in tinnitus-related neural correlates between late-onset tinnitus (LOT; mean onset age, 60.4 years) and early-onset tinnitus (EOT; mean onset age, 29.7 years) groups. Hence, we collected quantitative electroencephalography findings of 29 participants with LOT and 30 with EOT, and from 59 controls. We then compared the results between the 2 groups and between the tinnitus groups and age- and sex-matched control groups using resting state electroencephalography source-localized activity and connectivity analyses. Compared with the EOT and older control groups, the LOT group demonstrated increased localized activity and functional connectivity in components of previously described tinnitus distress networks, and the default mode and intrinsic alertness networks, such as the prefrontal cortices, dorsal anterior cingulate cortex, and insula. The current findings of intrinsic differences in tinnitus-related neural activity between the LOT and EOT groups might be applicable for planning individualized treatment modalities according to age of onset. Moreover, differences with regard to the age of tinnitus onset might be a milestone for future studies on onset-related differences in other similar pathologies, such as pain or depression. PMID:23415838

Song, Jae-Jin; De Ridder, Dirk; Schlee, Winfried; Van de Heyning, Paul; Vanneste, Sven

2013-07-01

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

Approach to the Girl with Early Onset of Pubic Hair  

PubMed Central

Premature pubarche, or the development of pubic hair before the age of 8 in girls or 9 in boys, is most commonly caused by premature adrenarche. Adrenarche is the maturation of the adrenal zona reticularis in both boys and girls, resulting in the development of pubic hair, axillary hair, and adult apocrine body odor. Although originally thought to be a benign variant of normal development, premature adrenarche has been associated with insulin resistance and the later development of metabolic syndrome and polycystic ovary syndrome. Although further studies are needed to confirm these relationships, the case presented herein argues for periodic assessment of children at risk. Indeed, recognition of these associations may allow for early preventive measures. PMID:21602454

Sopher, Aviva B.; Gerken, Adrienne T.

2011-01-01

89

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 ...

90

Loss of Nfkb1 leads to early onset aging  

PubMed Central

NF-(B is a major regulator of age-dependent gene expression and the p50/NF-(B1 subunit is an integral modulator of NF-(B signaling. Here, we examined Nfkb1?/? mice to investigate the relationship between this subunit and aging. Although Nfkb1?/? mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes. In addition, aged Nfkb1?/? animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+. In vitro, serially passaged primary Nfkb1?/? MEFs have more senescent cells than comparable Nfkb1+/+ MEFs. Also, Nfkb1?/? MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1?/? animals compared to Nfkb1+/+. Finally, in wildtype animals a substantial decrease in p50 DNA binding is seen in aged tissue compared to young. Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence. Moreover, loss of p50 DNA binding is a prominent feature of aged mice relative to young. These findings support the strong link between the NF-(B pathway and mammalian aging. PMID:25553648

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

2014-01-01

91

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

PubMed Central

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

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

2013-01-01

92

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

93

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

ERIC Educational Resources Information Center

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

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

2007-01-01

94

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

ERIC Educational Resources Information Center

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

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

2012-01-01

95

Does Theory of Mind Performance Differ in Children with Early-Onset and Regressive Autism?  

ERIC Educational Resources Information Center

A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset

Matthews, Nicole L.; Goldberg, Wendy A.; Lukowski, Angela F.; Osann, Kathryn; Abdullah, Maryam M.; Ly, Agnes R.; Thorsen, Kara; Spence, M. Anne

2012-01-01

96

CDKL5 and ARX mutations in males with early-onset epilepsy  

PubMed Central

Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. While numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only ten males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. The 18 patients include eight new males with CDKL5 mutations and ten with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large data set therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy. PMID:23583054

Mirzaa, Ghayda M.; Paciorkowski, Alex R.; Marsh, Eric D.; Berry-Kravis, Elizabeth M.; Medne, Livija; Grix, Art; Wirrell, Elaine C.; Powell, Berkley R.; Nickels, Katherine C.; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B.; Das, Soma

2013-01-01

97

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

98

Does theory of mind performance differ in children with early-onset and regressive autism?  

PubMed

A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset autism and regressive autism in comparison to typically developing children. Results indicated that children in the regressive autism group performed significantly better than the early-onset autism group on the non-verbal appearance-reality task. Additionally, Fisher's exact tests indicated a pattern of lowest scores in the early-onset group and highest scores in the typically developing group, whereas the regressive autism group tended to score in between the early-onset and typically developing groups. The apparent heterogeneity in ToM performance within ASD could account for the lack of universality in ToM ability found in previous studies. PMID:22251289

Matthews, Nicole L; Goldberg, Wendy A; Lukowski, Angela F; Osann, Kathryn; Abdullah, Maryam M; Ly, Agnes R; Thorsen, Kara; Spence, M Anne

2012-01-01

99

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

100

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

101

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

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

The topography of grey matter involvement in early and late onset Alzheimer's disease  

E-print Network

The topography of grey matter involvement in early and late onset Alzheimer's disease Giovanni B, The National Centre for Research and Care of Alzheimer's and Mental Diseases, 3 Service of Neuroradiology and Telemedicine, IRCCS Centro San Giovanni di Dio FBF, The National Centre for Research and Care of Alzheimer

Thompson, Paul

104

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

ERIC Educational Resources Information Center

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

Chang, Zheng; Lichtenstein, Paul; Larsson, Henrik

2012-01-01

105

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

ERIC Educational Resources Information Center

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

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

2011-01-01

106

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

107

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

108

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

109

Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.  

PubMed

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD. PMID:15488960

Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

2004-09-30

110

DJ1 analysis in a large cohort of Italian early onset Parkinson Disease patients?  

PubMed Central

We analyzed the DJ1 gene in a large consecutive series (N = 163) of Italian unrelated Early Onset Parkinson Disease (EOPD: onset ?40 years of age) patients and 100 healthy controls (mean age 64 ± 7 years). No homozygous or compound heterozygous mutations with an obvious pathogenic effect were found. Several variants were identified, some of which were novels. All variants had similar frequency in patients and in controls. Our data suggest that DJ1 mutations are very rare in Italian EOPD. Other genes and risk factors for PD are still to be identified. PMID:24176883

Sironi, Francesca; Primignani, Paola; Ricca, Sara; Tunesi, Sara; Zini, Michela; Tesei, Silvana; Cilia, Roberto; Pezzoli, Gianni; Seia, Manuela; Goldwurm, Stefano

2013-01-01

111

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, expression study Running Title: SNAP25 Gene Variations in Early-Onset Bipolar Disorder inserm-00499665,version1-12Jul2010 #12;3 Abstract Bipolar disorder (BD) is one of the most common and persistent

Paris-Sud XI, Université de

112

Effects of Early-Onset Artificial Strabismus on Pursuit Eye Movements and on Neuronal Responses in Area MT of  

E-print Network

Effects of Early-Onset Artificial Strabismus on Pursuit Eye Movements and on Neuronal Responses to the "down- stream" areas responsible for the initiation of pursuit. Key words: artificial strabismus; visual Strabismus of early onset disrupts a number of visual functions in humans, monkeys, and cats. Improper

Movshon, Joseph Anthony

113

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

Microsoft Academic Search

BACKGROUND: The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity. METHODS: We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to

Timo D Müller; Günter Brönner; Melanie Wandolski; Jophia Carrie; Trang T Nguyen; Brandon H Greene; André Scherag; Harald Grallert; Carla IG Vogel; Susann Scherag; Winfried Rief; Hans-Erich Wichmann; Thomas Illig; Helmut Schäfer; Johannes Hebebrand; Anke Hinney

2010-01-01

114

The ionic products of bioactive glass particle dissolution enhance periodontal ligament fibroblast osteocalcin expression and enhance early mineralized tissue development.  

PubMed

This study resulted in enhanced collagen type 1 and osteocalcin expression in human periodontal ligament fibroblasts (hPDLF) when exposed to bioactive glass conditioned media that subsequently may promote early mineralized tissue development. Commercial Bioglass™ (45S5) and experimental bioactive coating glass (6P53-b), were used to make a glass conditioned media (GCM) for comparison to control medium. ICP-MS analysis showed increased concentrations of Ca(2+), PO(4) (3-), Si(4+), and Na(+), for 45S5 GCM and Mg(2+), K(+), Ca(2+), PO(4)(3-), Si(4+), and Na(+) for 6P53-b GCM (relative to control medium). Differentiating hPDLF cultures exposed to 45S5 and 6P53-b GCM showed enhanced expression of collagen type 1 (Col1?1, Col1?2), osteocalcin, and alkaline phosphatase gene expression. These GCM also enhanced osteocalcin protein expression. After 16 d of culture, 45S5 and 6P53-b GCM treated cells showed regions of deep red Alizarin staining, indicating increased Ca within their respective extracellular matrices (ECM), while control-treated cells did not exhibit these features. SEM analysis showed more developed ECM in GCM treated cultures, indicated by multiple tissue layering and abundant collagen fiber bundle formation, while control treated cells did not exhibit these features. SEM analysis showed polygonal structures suggestive of CaP in 45S5 GCM treated cultures. These results indicate the osteogenic potential of bioactive coating glass in periodontal bone defect filling applications. PMID:21548068

Varanasi, Venu G; Owyoung, Jeremy B; Saiz, Eduardo; Marshall, Sally J; Marshall, Grayson W; Loomer, Peter M

2011-08-01

115

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

SciTech Connect

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

Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F. [Univ. of South Florida, Tampa, FL (United States)] [and others

1995-02-27

116

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

117

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 on 2q14 according to age at onset. Flavie Mathieu,1,2* Marie-Hélène Dizier,3,4,5 Bruno Etain,1,2,6,13 § Mathieu F and Dizier MH contributed to this work equally. 1) INSERM, U 955, IMRB, Dept of Medical Genetics

Boyer, Edmond

118

MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis  

PubMed Central

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

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

2014-01-01

119

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

120

The TOR1A (DYT1) Gene Family and Its Role in Early Onset Torsion Dystonia  

E-print Network

The TOR1A (DYT1) Gene Family and Its Role in Early Onset Torsion Dystonia Laurie J. Ozelius,*, ,1 of the TOR1A gene (alias DYT1, DQ2), resulting in loss of a glutamic acid in the carboxy terminal of the encoded protein, torsin A. TOR1A and its homologue TOR1B (alias DQ1) are located adjacent to each other

Corey, David P.

121

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

122

Brain Expression of Presenilins in Sporadic and Early-onset, Familial Alzheimer's Disease  

Microsoft Academic Search

Background: Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD). Materials and Methods: We characterized the cel- lular localization and endoproteolysis of presenilin 2 (PS2) and presenilin 1 (PS1) in brains from 25 in- dividuals with presenilin-mutations causing FAD, as well as neurologically normal individuals and in- dividuals with sporadic Alzheimer's disease (AD). Results: Amino-terminal antibodies to both

Paul M. Mathews; Anne M. Cataldo; Benjamin H. Kao; Anna G. Rudnicki; Xi Qin; John L. Yang; Ying Jiang; Melanie Picciano; Christine Hulette; Carol F. Lippa; Thomas D. Bird; David Nochlin; Jochen Walter; Christian Haass; Lyne Lévesque; Paul E. Fraser; Athena Andreadis; Ralph A. Nixon

2000-01-01

123

Mutational Analysis in Early-Onset Familial Dementia in the Japanese Population  

Microsoft Academic Search

Background: Three major causative genes have been implicated as the cause of early-onset familial Alzheimer’s disease (AD): the amyloid precursor protein gene (APP), presenilin-1 (PSEN1) and PSEN2. Although rare, a tau-related dementia with mutations in the microtubule-associated protein tau gene (MAPT) has been identified in patients showing clinical presentations similar to those of AD. Methods: We performed mutational analysis of

Takeshi Ikeuchi; Hiroyuki Kaneko; Akinori Miyashita; Hiroaki Nozaki; Kensaku Kasuga; Tamao Tsukie; Miyuki Tsuchiya; Toru Imamura; Hideki Ishizu; Kenju Aoki; Atsushi Ishikawa; Osamu Onodera; Ryozo Kuwano; Masatoyo Nishizawa

2008-01-01

124

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

125

A Distinct Vitreo-retinal Dystrophy with Early-onset Cataract from Recessive KCNJ13 Mutations.  

PubMed

Abstract Purpose: To document a distinct vitreo-retinal dystrophy with early-onset cataract as related to recessive KCNJ13 mutations. Methods: A retrospective case series (two patients from two families) Results: A 12-year-old Saudi Arabian girl with nystagmus since birth was referred because of recent decreased vision. Parents were first cousins and a younger sister had been diagnosed with retinal dystrophy. Examination revealed total white cataract in the right eye. In the left eye, there were posterior cortical lenticular opacities and an unusual retina fundus dystrophic appearance notable for fibrosis over the optic disc and clumped pigmentation. After right eye cataract surgery, the posterior pole of the left eye was seen as similar to that of the right eye and electroretinography revealed severe cone-rod dysfunction, with only subnormal scotopic tracings recordable in both eyes. Next-generation sequencing of retinal dystrophy genes revealed homozygosity for a novel missense mutation in KCNJ13 (c.359T?>?C; p.Ile120Thr [NM_002242.4]), which co-segregated with the disease. Direct KCNJ13 sequencing for an unrelated 33-year-old Saudi Arabian male with similar clinical findings but early-adult-onset rather than juvenile cataract revealed the same homozygous mutation. Conclusions: Juvenile or early-adult-onset cataract in the setting of a congenital vitreo-retinal dystrophy notable for fibrosis over the disc and clumped pigmentation in the posterior pole is a unique phenotype that suggests recessive KCNJ13 mutations. PMID:25475713

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

2014-12-01

126

In utero arsenic exposure induces early onset of atherosclerosis in ApoE?/? mice  

PubMed Central

Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE?/?) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE?/? mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE?/? mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

2007-01-01

127

Rare autosomal copy number variations in early-onset familial Alzheimer's disease.  

PubMed

Over 200 rare and fully penetrant pathogenic mutations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of early-onset familial Alzheimer's disease (EO-FAD). Of these, 21 cases of EO-FAD families carrying unique APP locus duplications remain the only pathogenic copy number variations (CNVs) identified to date in Alzheimer's disease (AD). Using high-density DNA microarrays, we performed a comprehensive genome-wide analysis for the presence of rare CNVs in 261 EO-FAD and early/mixed-onset pedigrees. Our analysis revealed 10 novel private CNVs in 10 EO-FAD families overlapping a set of genes that includes: A2BP1, ABAT, CDH2, CRMP1, DMRT1, EPHA5, EPHA6, ERMP1, EVC, EVC2, FLJ35024 and VLDLR. In addition, CNVs encompassing two known frontotemporal dementia genes, CHMP2B and MAPT were found. To our knowledge, this is the first study reporting rare gene-rich CNVs in EO-FAD and early/mixed-onset AD that are likely to underlie pathogenicity in familial AD and perhaps related dementias. PMID:23752245

Hooli, B V; Kovacs-Vajna, Z M; Mullin, K; Blumenthal, M A; Mattheisen, M; Zhang, C; Lange, C; Mohapatra, G; Bertram, L; Tanzi, R E

2014-06-01

128

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

PubMed Central

Background There were few studies on the outcome of schizophrenia in developing countries. Whether the outcome is similar to or different from developed world is still a point for research. The main aim of the current study was to know if patients with early onset non affective psychosis can behave and function properly after few years from start of the illness or not. Other aims included investigation of possible predictors and associated factors with remission and outcome. Method The study prospectively investigated a group of 56 patients with onset of psychosis during childhood or adolescence. Diagnosis made according to DSM-IV criteria and included; schizophrenia, psychotic disorder not otherwise specified and acute psychosis. Severity of psychosis was measured by PANSS. Measures of the outcome included; remission criteria of Andreasen et al 2005, the children's global assessment scale and educational level. Results Analysis of data was done for only 37 patients. Thirty patients diagnosed as schizophrenia and 7 with Psychotic disorder not otherwise specified. Mean duration of follow up was 38.4 +/- 16.9 months. At the end of the study, 6 patients (16.2%) had one episode, 23(62.1%) had multiple episodes and 8 (21.6%) continuous course. Nineteen patients (51.4%) achieved full remission, and only 11(29.7%) achieved their average educational level for their age. Twenty seven percent of the sample had good outcome and 24.3% had poor outcome. Factors associated with non remission and poor outcome included gradual onset, low IQ, poor premorbid adjustment, negative symptoms at onset of the illness and poor adherence to drugs. Moreover, there was tendency of negative symptoms at illness start to predict poor outcome. Conclusion Some patients with early onset non affective psychosis can behave and function properly after few years from the start of the illness. Although remission is a difficult target in childhood psychosis, it is still achievable. PMID:21801438

2011-01-01

129

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

130

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

PubMed Central

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

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

2011-01-01

131

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

PubMed Central

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

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

2013-01-01

132

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

SciTech Connect

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

Baldwin, C.T.; Farrer, L.A.; Adair, R. [Boston Univ. School of Medicine, MA (United States); Dharmavaram, R.; Jimenez, S. [Thomas Jefferson Univ., Philadelphia, PA (United States); Anderson, L. [Rheumatology Associates, Portland, ME (United States)

1995-03-01

133

Attention Deficit-Hyperactivity Disorder in Adolescence Predicts Onset of Major Depressive Disorder through Early Adulthood  

PubMed Central

Background The aim of this study was to examine the prospective relationship between a history of attention deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. Method 1,507 participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Results Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance use disorder after mid-adolescence. Conclusions A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. PMID:23424020

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

2013-01-01

134

Regional Cerebral Blood Flow Abnormalities in Early-Onset Obsessive-Compulsive Disorder: An Exploratory SPECT Study  

Microsoft Academic Search

ObjectiveRecent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early-and late-onset OCD subjects.

GERALDO F. BUSATTO; CARLOS A. BUCHPIGUEL; DENIS R. ZAMIGNANI; GRISELDA E. J. GARRIDO; MICHAEL F. GLABUS; MARIA C. ROSARIO-CAMPOS; CLAUDIO C. CASTRO; ALEX MAIA; EUCLIDES T. ROCHA; PHILIP K. MCGUIRE; EURIPEDES C. MIGUEL

2001-01-01

135

A novel family with an unusual early-onset generalized dystonia.  

PubMed

We report on an Italian family in which three brothers and their maternal grandfather had a generalized early-onset dystonia with mild parkinsonian signs. Genetic testing excluded the rapid-onset dystonia-parkinsonism locus (DYT12; OMIM*128235), autosomal recessive Parkin locus (PARK2; OMIM *602544), and DYT1 dystonia. Three affected siblings were found to share an identical haplotype at the X-linked dystonia-parkinsonism locus (XDP; Lubag; OMIM*314250). This haplotype differed from the haplotype observed in Filipino patients, ruling out the hypothesis of a common underlying mutation. In addition, direct sequencing analysis of the putative disease causing changes observed in Filipino patients were not found in the Italian patients. The condition we describe could be a newly recognized dystonia syndrome with parkinsonism. PMID:15390042

Fabbrini, Giovanni; Brancati, Francesco; Vacca, Laura; Valente, Enza Maria; Nemeth, Andrea; Meesaq, Angela; Sykes, Nuala; Dallapiccola, Bruno; Berardelli, Alfredo

2005-01-01

136

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

PubMed

We describe here a rare case of early childhood-onset (5 years of age) narcolepsy. This case was interesting because of the ability to compare the patient's symptoms to the condition of her healthy monozygotic co-twin sister. The only environmental difference between the co-twins was head injury, which may be associated with the presence of narcolepsy. The co-twin was extroverted, sociable, reliable, and dexterous. In contrast, the patient could be described as introverted, gentle, honest and persevering, but was weak at conversation, assessment of a situation, memory, planning, activity (she was inactive), a sense of time, understanding of an analog clock, operating efficiency, and physical education (due to obesity). The sisters showed the same degree of appetite and dexterity with their fingers. Narcolepsy is often under-recognized or underdiagnosed, especially when the onset occurs in childhood. When we observe preschoolers with excessive daytime sleepiness, we should consider the possibility of narcolepsy with cataplexy. PMID:25336002

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

2014-10-01

137

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

PubMed

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

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

2010-12-01

138

Genetic Epidemiology of Severe, Early-onset Chronic Obstructive Pulmonary Disease Risk to Relatives for Airflow Obstruction and Chronic Bronchitis  

Microsoft Academic Search

Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pul- monary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for air- flow obstruction

EDWIN K. SILVERMAN; HAROLD A. CHAPMAN; JEFFREY M. DRAZEN; SCOTT T. WEISS; BERNARD ROSNER; EDWARD J. CAMPBELL; WALTER J. O'DONNELL; JOHN J. REILLY; LEO GINNS; STEVEN MENTZER; JOHN WAIN; FRANK E. SPEIZER

139

Immobilized chicks as a model system for early-onset developmental dysplasia of the hip.  

PubMed

We have almost no understanding of how our joints take on their range of distinctive shapes, despite the clinical relevance of joint morphogenesis to postnatal skeletal malformations such as developmental dysplasia of the hip (DDH). In this study, we investigate the role of spontaneous prenatal movements in joint morphogenesis using pharmacological immobilization of developing chicks, and assess the system as a suitable model for early-onset hip dysplasia. We show that, prior to joint cavitation, the lack of dynamic muscle contractions has little impact on the shape of the hip joint. However, after the timepoint at which cavitation occurs, a dramatic effect on hip joint morphogenesis was observed. Effects in the immobilized chicks included flattening of the proximal femur, abnormal orientation of the pelvis relative to the femur and abnormal placement and coverage of the acetabulum. Although many clinical case studies have identified reduced or restricted movement as a risk factor for DDH, this study provides the first experimental evidence of the role of prenatal movements in early hip joint development. We propose that the immobilized chick embryo serves as a suitable model system for the type of early-onset DDH which arises due to neuromuscular conditions such as spinal muscular atrophy. PMID:24590854

Nowlan, Niamh C; Chandaria, Vikesh; Sharpe, James

2014-06-01

140

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

PubMed Central

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

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

141

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

142

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

PubMed

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

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

2014-01-01

143

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

PubMed

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

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

2015-04-01

144

The natural history of early-onset dementia: the Artemis Project  

PubMed Central

Objectives The natural history of early-onset Alzheimer's disease (AD) and fronto-temporal dementia (FTD) remains to be described in detail. We seek to describe the natural history of early onset AD and FTD in terms of changes in cognitive assessment and staging, medical history and survival. Design Longitudinal prospective cohort analysis. Setting Neurodegenerative disorders research clinic. Participants In total, 155 consecutive patients with clinically confirmed sporadic early-onset AD or FTD at a neurodegenerative disorders research clinic in Subiaco, Western Australia (The Artemis Project). Methods A detailed history was recorded from the patients at baseline, including education, family history and medical history. Mini-mental state exam (MMSE), Global Deterioration Scale (GDS) and total functional capacity (TFC) were determined at each visit from 1994 until 2011. Kaplan-Meier survival analysis was performed. Results Patients with FTD were more likely to have a family history of dementia (p=0.026), to develop at least one cerebrovascular risk factor (p=0.003), manifest depression (Fisher's exact p=0.007) and to die during the follow-up period (Pearson ?2 8.97, p=0.003). Kaplan-Meier survival estimates revealed a highly significant difference in the proportion of patients surviving the follow-up period (log rank 7.25, p=0.007) with FTD patients experiencing poorer survival than those with AD. The mean MMSE and TFC were consistently lower in those with FTD compared with those with AD over a decade of follow-up; mean GDS was consistently higher in those with FTD over the follow-up period. Conclusions We believe that the difference in survival in patients with AD and FTD in our cohort might relate to the development of one or more cerebrovascular risk factors in FTD patients and the severity of the underlying pathology. PMID:23059847

Atkins, Emily R; Bulsara, Max K; Panegyres, Peter K

2012-01-01

145

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

PubMed Central

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

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

2014-01-01

146

Early Onset Salt-Sensitive Hypertension in Bradykinin B2 Receptor Null Mice  

Microsoft Academic Search

Abstract—Kinins have been implicated in the hemodynamic,adaptation to postnatal life. The present study examined,the impact of bradykinin B2 receptor (B2R) gene disruption on the postnatal changes,in blood pressure (BP) and the susceptibility to early onset salt-sensitive hypertension in mice. B 2R null (2\\/2) and wild-type (1\\/1) mice were fed normal (NS, 1% NaCl) or high (HS, 5% NaCl) salt diets

Ludek Cervenka; Lisa M. Harrison-Bernard; Susana Dipp; Ginny Primrose; John D. Imig; Samir S. El-Dahr

147

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

PubMed Central

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

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

2014-01-01

148

Reduced frontal white matter volume in children with early onset of adrenarche.  

PubMed

While there is growing evidence that puberty affects brain development, very little is known about the structural brain changes associated with dehydroepiandrosterone (DHEA), an adrenal hormone that exhibits dramatic increases during adrenarche, the earliest phase of puberty. Moreover, no research has investigated whether relatively early exposure to DHEA (i.e., early adrenarche) during this period is associated with differences in brain structure. We ran a whole-brain voxel-based morphometry analysis on T1-weighted magnetic resonance imaging brain scans to compare gray (GMV) and white matter volumes (WMV) between children experiencing relatively early (n=41) vs. relatively late (n=44) adrenarche. We also investigated the correlations between GMV or WMV and DHEA levels, and finally, tested for sex differences in group and correlation analyses. We observed reduced frontal WMV in a cluster located on the left corona radiata in children experiencing earlier adrenarche. In addition, WMV in this area was negatively correlated with DHEA levels. We did not observe any effect of gender in both the group and the correlation analyses. Early onset of adrenarche (as defined by relatively early exposure to DHEA) may be associated with differences in the development of frontal white matter tracts. PMID:25459897

Klauser, Paul; Whittle, Sarah; Simmons, Julian G; Byrne, Michelle L; Mundy, Lisa K; Patton, George C; Fornito, Alex; Allen, Nicholas B

2015-02-01

149

A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain  

PubMed Central

Bipolar disorder (BD) is one of the most common and persistent psychiatric disorders. Early-onset BD has been shown to be the most severe and familial form. We recently carried out a whole-genome linkage analysis on sib-pairs affected by early-onset BD and showed that the 20p12 region was more frequently shared in our families than expected by chance. The synaptosomal associated protein SNAP25 is a presynaptic plasma membrane protein essential for the triggering of vesicular fusion and neurotransmitter release, and for which abnormal protein levels have been reported in postmortem studies of bipolar patients. We hypothesised that variations in the gene encoding SNAP25, located on chromosome 20p12, might influence the susceptibility to early-onset BD. We screened SNAP25 for mutations and performed a case-control association study in 197 patients with early-onset BD, 202 patients with late-onset BD and 136 unaffected subjects. In addition, we analysed the expression level of the two SNAP25 isoforms in 60 brains. We showed that one variant, located in the promoter region, was associated with early-onset BD but not with the late-onset subgroup. In addition, individuals homozygous for this variant showed a significant higher SNAP25b expression level in prefrontal cortex. These results show that variations in SNAP25, associated with an increased gene expression level in prefrontal cortex, might predispose to early-onset BD. Further analyses of this gene, as well as analysis of genes encoding for the SNAP25 protein partners, are required to understand the impact of such molecular mechanisms in BD. PMID:19125158

Etain, Bruno; Dumaine, Anne; Mathieu, Flavie; Chevalier, Fabien; Henry, Chantal; Kahn, Jean-Pierre; Deshommes, Jasmine; Bellivier, Frank; Leboyer, Marion; Jamain, Stéphane

2010-01-01

150

Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors  

PubMed Central

To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the ?A-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the ?-subunit, the partner of the ?A-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

2014-01-01

151

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

PubMed Central

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

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

2014-01-01

152

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

SciTech Connect

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

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

2011-08-26

153

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

154

Submersion and early-onset acute respiratory distress syndrome: a case report.  

PubMed

Drowning is a common cause of accidental death, particularly in younger people, and acute respiratory failure is common in these patients. This case report describes a healthy 18-year-old man who suffered a cardiorespiratory arrest due to submersion while swimming in a freshwater lake. First-responder cardiopulmonary resuscitation and defibrillation using an automated external defibrillator resulted in a return of spontaneous circulation. The patient was evacuated to a tertiary care center by a rotor-wing air medical crew. The crew experienced difficulties in oxygenating and ventilating the patient because of early-onset acute respiratory distress syndrome (ARDS). This case report describes the pathophysiology and prehospital management of a patient with suspected early-onset ARDS secondary to drowning. This case report is unique because it describes the oxygenation and ventilation difficulties encountered in managing this patient in the transport setting, and possible strategies to deal with these difficulties. Finally, this case report highlights the prehospital bypass decision-making process for patients requiring specialized medical care. PMID:21275574

Diamond, Wayde; MacDonald, Russell D

2011-01-01

155

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

156

Very early-onset inflammatory bowel disease (IBD) in infancy is a different disease entity from adult-onset IBD; one form of interleukin-10 receptor mutations.  

PubMed

Infantile periods may have stronger genetic influences. Recently, studies on genetic defects in the interleukin-10 (IL-10) signaling pathway have provided new insights into inflammatory bowel disease (IBD). This study is to reveal whether mutations of IL-10 signaling pathway genes contribute to the phenotypes of IBD. Forty children who were diagnosed with IBD below the age of 10 years were enrolled. We sequenced the genes interleukin-10 receptor A (IL-10RA), IL-10RB and IL-10, and analyzed the clinical characteristics of very early-onset IBD (VEO-IBD). In total, 14 out of the 40 children developed their symptoms within 1 year of age. We found mutations in IL-10RA in 7 out of the 40 children (17.5%). All seven children had developed symptoms within the first year of life. Particularly, half of the children with infantile-onset IBD had IL-10RA mutations. None of the remaining 26 children diagnosed above 1 year of age had IL-10RA mutations. No mutations were found in IL-10RB and IL-10. Identified IL-10RA mutations were p.(R101W), p.(Y91C), p.(R262C), p.(R117H) and p.(W69R). IL-10RA mutations were associated with onset of infancy (P<0.001), perianal fistulae (P<0.001), poor response to medical management (P=0.017) and early surgical interventions (P<0.001). VEO-IBD in infancy is phenotypically and genetically different disease entity from adult-onset or older child-onset IBD. It has a strong association with IL-10 receptor gene. We should consider the genotyping of genes of the IL-10 signaling pathway including IL-10RA in patients with VEO-IBD, especially in whom with onset of perianal fistulae and severe colitis. PMID:24785691

Shim, Jung Ok; Seo, Jeong Kee

2014-06-01

157

Onset-related differences in neural substrates of tinnitus-related distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early-onset tinnitus.  

PubMed

Recent findings regarding differences in tinnitus-related neural activity according to onset age have raised a question on possible onset age-related differences in neural substrates of distress. Hence we collected quantitative electroencephalography (qEEG) findings of 28 late-onset tinnitus (LOT) and 29 early-onset tinnitus (EOT) (mean onset age 52.3 and 29.0 years, respectively) participants. According to the tinnitus questionnaire (TQ) score grade, LOTs were then subdivided into 13 high distress (HD; TQ grade 3 or 4) and 15 low distress (LD; TQ grade 1 or 2), while EOTs into 14 HD and 15 LD. Compared to the EOT group, the LOT group demonstrated increased qEEG source-localized activity and functional connectivity primarily in the anterior cingulate cortex (ACC) and parahippocampus. In subgroup comparisons, the ACC was activated more in HD-LOT participants than in LD-LOT participants for the beta 1, beta 2 and gamma frequency bands, while the left orbitofrontal cortex and left dorsolateral prefrontal cortex were activated more in HD-EOT than in LD-EOT for the delta/beta and gamma frequency bands, respectively. Even with the same amount of tinnitus-related distress level, responsible neural substrates are different according to the onset age. These differences may be important for exploring different target areas of treatment according to tinnitus onset age, as well as for conducting similar studies on other pathologies, such as depression or pain. PMID:24135769

Song, Jae-Jin; Vanneste, Sven; Schlee, Winfried; Van de Heyning, Paul; De Ridder, Dirk

2015-01-01

158

Periodontal Diseases  

MedlinePLUS

... diseases. ? The primary research focus was on oral bacteria. Periodontal diseases were thought to begin when chalky ... small pocket between the tooth and gingiva, allowing bacteria to freely enter and progressively erode the bone ...

159

The association between attention-deficit/hyperactivity disorder and early-onset alcohol dependence: A retrospective study  

PubMed Central

Background: Early onset (EO) alcohol dependence (AD) has been found to represent a subtype of alcoholism with a distinct profile and prognosis compared to late onset (LO) alcohol dependence. Externalizing disorders, especially attention deficit hyperactivity disorder (ADHD) that may continue as attention deficit hyperactivity disorder, residual type (ADD, RT) in adulthood, may increase susceptibility to early-onset AD. Aims: To examine the relationship between ADHD and ADD, RT symptoms and age at onset of AD in a sample of Indian male patients. 70 male subjects with AD presenting to the De-Addiction Services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, were studied. The study had a retrospective design. Materials and Methods: Patients were examined for evidence of past ADHD in childhood and current ADD, RT using structured instruments. Chi-square tests and odds ratios were used to express the relative risk of association of ADHD with early- and late-onset AD. Results: Significantly more EO alcoholics (19/30, 63.3%) had a history of ADHD in childhood compared to LO alcoholics (7/28, 25%, P < 0.05) ADD, RT was also over-represented in EO probands. Conclusions: The results of this study are consistent with previous research that shows a high incidence of ADHD in early-onset alcoholics. This may have important management implications. PMID:19823611

Sringeri, Sujaya Kumara R.; Rajkumar, Ravi Philip; Muralidharan, Kesavan; Chandrashekar, Channapatna R.; Benegal, Vivek

2008-01-01

160

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

161

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

162

Developmental outcome after surgery in focal cortical dysplasia patients with early-onset epilepsy.  

PubMed

The purpose of this study was to investigate the developmental outcome after surgery for early-onset epilepsy in patients with focal cortical dysplasia (FCD). Among 108 patients with histopathologically confirmed FCD operated between 1985 and 2008, we selected 17 patients with epilepsy onset up to 3 years of age. Development was evaluated by the developmental quotient or intelligence quotient (DQ-IQ) and mental age was measured by the Mother-Child Counseling baby test or the Tanaka-Binet scale of intelligence. Postsurgical development outcome was evaluated by the changes in DQ-IQ and mental age as well as rate of increase in mental age (RIMA) after surgery. RIMA was calculated as the increase in mental age per chronological year (months/year; normal average rate: 12 months/year). Age at epilepsy onset of 17 patients ranged from 15 days to 36 months (mean±SD, 11.0±10.0 months). Age at surgery ranged from 18 to 145 months (75.1±32.4 months). Evaluation just before surgery showed that 13 of 17 (76.4%) patients had DQ-IQ below 70. Ten patients (58.8%) were seizure-free throughout the postsurgical follow-up period. After surgery, DQ-IQ was maintained within 10 points of the presurgical level in 13 patients (76.4%), and increased by more than 10 points in one patient (5.9%). After surgery, RIMA in patients with Engel's class I (7.5±3.8) was higher than patients with Engel's class II-IV (2.6±3.4) (unpaired t-test with Welch's correction, t=2.99, df=15, p=0.0092). RIMA was particularly low in two patients with spasm. In four patients with presurgical DQ-IQ<70, seizure-free after surgery and without spasm, DQ-IQ did not increase but RIMA improved from 3.6±2.8 before surgery to 6.9±2.5 months/year after surgery. RIMA became better from 2 years after surgery. In four patients with presurgical DQ-IQ?70 and no spasm, two showed the same or higher RIMA than normal average after surgery. In 58.8% of FCD patients with early onset epilepsy, epilepsy surgery effectively controlled seizures, and in 82.3% of patients, epilepsy surgery preserved or improved development. Residual seizures after surgery and lower DQ-IQ before surgery might be potential risk factors for poor development after surgery. In patients of Engel's class I with lower presurgical DQ-IQ, catch-up increase in mental age was observed after two years following surgery. PMID:25304919

Kimura, Nobusuke; Takahashi, Yukitoshi; Shigematsu, Hideo; Imai, Katsumi; Ikeda, Hiroko; Ootani, Hideyuki; Takayama, Rumiko; Mogami, Yukiko; Kimura, Noriko; Baba, Koichi; Matsuda, Kazumi; Tottori, Takayasu; Usui, Naotaka; Inoue, Yushi

2014-12-01

163

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

PubMed

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

Carone, Laura; Tischler, Victoria; Dening, Tom

2014-11-26

164

Comparison of clinical characteristics between familial and non-familial early onset Alzheimer’s disease  

PubMed Central

Although familial Alzheimer’s disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD. PMID:22460587

Ringman, John M.; Lee, Albert S.; Juarez, Kevin O.; Mendez, Mario F.

2012-01-01

165

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

PubMed

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

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

2014-05-31

166

Detection of the presenilin 1 gene mutation (M139T) in early-onset familial Alzheimer disease in Spain  

Microsoft Academic Search

In a family with early-onset Alzheimer disease (EOAD) from Spain we found a mutation in the presenilin 1 (PS1) gene that predicts a methionine-to-threonine change at the PS1 residue 139 (M139T). This mutation was previously reported in a independent French family. The age of onset of the disease was similar in the affected members from both families, suggesting a specific

Rosa Queralt; Mario Ezquerra; Magda Castellv??; Alberto Lleó; Rafael Blesa; Rafael Oliva

2001-01-01

167

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

PubMed Central

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

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

2011-01-01

168

Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress  

PubMed Central

Progressive cognitive deficits that emerge with aging are a result of complex interactions of genetic and environmental factors. Whereas much has been learned about the genetic underpinnings of these disorders, the nature of “acquired” contributing factors, and the mechanisms by which they promote progressive learning and memory dysfunction, remain largely unknown. Here, we demonstrate that a period of early-life “psychological” stress causes late-onset, selective deterioration of both complex behavior and synaptic plasticity: two forms of memory involving the hippocampus, were severely but selectively impaired in middle-aged, but not young adult, rats exposed to fragmented maternal care during the early postnatal period. At the cellular level, disturbances to hippocampal long-term potentiation paralleled the behavioral changes and were accompanied by dendritic atrophy and mossy fiber expansion. These findings constitute the first evidence that a short period of stress early in life can lead to delayed, progressive impairments of synaptic and behavioral measures of hippocampal function, with potential implications to the basis of age-related cognitive disorders in humans. PMID:16221841

Brunson, Kristen L.; Kramár, Enikö; Lin, Bin; Chen, Yuncai; Colgin, Laura Lee; Yanagihara, Theodore K.; Lynch, Gary; Baram, Tallie Z.

2011-01-01

169

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

PubMed Central

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

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

2008-01-01

170

Case-control study of severe pre-eclampsia of early onset.  

PubMed Central

Twenty four women with severe pre-eclampsia diagnosed before 34 weeks' gestation were compared with 48 randomly selected controls matched for age and parity. Subjects were studied in the puerperium using a questionnaire, clinical examination, and review of case records. A history of infertility, headaches (particularly migraine), pre-eclampsia in a previous pregnancy, or a raised serum alpha-fetoprotein concentration at the time of screening for neural tube defect in the index pregnancy were all identified as significant risk factors in the pre-eclamptic women. Maternal age, a history of chronic hypertension or renal disease, or excessive maternal weight were not significantly associated with pre-eclampsia. Almost all the infants of pre-eclamptic women showed retarded growth: 18 were below the 10th centile and only one weighed more than the 25th centile. Four babies died. These observations indicate that pre-eclampsia of early onset may differ from the late onset disease not only in its very high perinatal morbidity and mortality but in its distinctive maternal risk factors. PMID:6411232

Moore, M P; Redman, C W

1983-01-01

171

Prognosis after early onset of ulcerative colitis. A study from an unselected patient population.  

PubMed

All patients with onset of ulcerative colitis before the age of 20 years from a population of 65,000 inhabitants were studied. The study period was 30 years (1961 through 1990). There were 32 patients, 18 male and 14 female, giving an incidence of 0.7 patients/100,000/year. Twenty-four patients had total colitis and 8 had limited disease. The observed duration of the disease was 0-30 (mean 18, median 20) years. One patient died of fulminant disease. No colorectal carcinoma was diagnosed. In 7 patients, low-grade dysplasia was diagnosed, which did not progress during an observation period of 2-10 years. DNA aneuploidy was detected in 6 patients. Seven patients (22%) were operated on after a disease duration of 0-10 (mean 4, median 3) years on clinical grounds. No cancer-prophylactic colectomy was performed. It is concluded that, in an unselected population of patients with early onset of ulcerative colitis, mortality and cancer risk are low. The need for operative treatment during the first 15 years of the disease was around 22 per cent. Endoscopic surveillance was given preference over prophylactic colectomy in patients with low-activity or quiescent disease. PMID:8270236

Ahsgren, L; Jonsson, B; Stenling, R; Rutegård, J

1993-10-01

172

Using hip measures to avoid misdiagnosing early rapid onset osteoarthritis for osteonecrosis.  

PubMed

In the early phases, subchondral insufficiency fractures and rapidly destructive osteoarthritis of the hip are often mistaken for osteonecrosis of the hip. Three hip measures were used comparing combined subchondral insufficiency fractures and rapidly destructive 18 osteoarthritis patients to 18 osteonecrosis patients. Due to the rarity of these conditions there was no statistical power. Initial diagnoses for the osteoarthritis patients were recorded. The osteoarthritis group had significantly higher means for Tönnis angle (P < 0.001), lateral center edge angle (P = 0.006), and acetabular extrusion index (P = 0.014). Only 7 of the 18 patients were initially diagnosed without reservation as subchondral insufficiency fracture or rapidly destructive osteoarthritis. Using hip measures will reduce the misdiagnosis of rapid onset osteoarthritis of the hip for osteonecrosis. PMID:24360489

Nelson, Fred R T; Bhandarkar, Varun S; Woods, Tammy A

2014-06-01

173

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

PubMed Central

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

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

2009-01-01

174

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

175

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

176

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

PubMed Central

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

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

2013-01-01

177

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

PubMed

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

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

2012-04-01

178

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

PubMed

Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P?onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. © 2014 Wiley Periodicals, Inc. PMID:25355237

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

2015-01-01

179

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

PubMed Central

Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

2013-01-01

180

Early-Onset and Robust Amyloid Pathology in a New Homozygous Mouse Model of Alzheimer's Disease  

PubMed Central

Background Transgenic mice expressing mutated amyloid precursor protein (APP) and presenilin (PS)-1 or -2 have been successfully used to model cerebral ?-amyloidosis, one of the characteristic hallmarks of Alzheimer's disease (AD) pathology. However, the use of many transgenic lines is limited by premature death, low breeding efficiencies and late onset and high inter-animal variability of the pathology, creating a need for improved animal models. Here we describe the detailed characterization of a new homozygous double-transgenic mouse line that addresses most of these issues. Methodology/Principal Findings The transgenic mouse line (ARTE10) was generated by co-integration of two transgenes carrying the K670N/M671L mutated amyloid precursor protein (APPswe) and the M146V mutated presenilin 1 (PS1) both under control of a neuron-specific promoter. Mice, hemi- as well as homozygous for both transgenes, are viable and fertile with good breeding capabilities and a low rate of premature death. They develop robust AD-like cerebral ?-amyloid plaque pathology with glial inflammation, signs of neuritic dystrophy and cerebral amyloid angiopathy. Using our novel image analysis algorithm for semi-automatic quantification of plaque burden, we demonstrate an early onset and progressive plaque deposition starting at 3 months of age in homozygous mice with low inter-animal variability and 100%-penetrance of the phenotype. The plaques are readily detected in vivo by PiB, the standard human PET tracer for AD. In addition, ARTE10 mice display early loss of synaptic markers and age-related cognitive deficits. By applying a ?-secretase inhibitor we show a dose dependent reduction of soluble amyloid ? levels in the brain. Conclusions ARTE10 mice develop a cerebral ?-amyloidosis closely resembling the ?-amyloid-related aspects of human AD neuropathology. Unifying several advantages of previous transgenic models, this line particularly qualifies for the use in target validation and for evaluating potential diagnostic or therapeutic agents targeting the amyloid pathology of AD. PMID:19936202

Willuweit, Antje; Velden, Joachim; Godemann, Robert; Manook, Andre; Jetzek, Fritz; Tintrup, Hartmut; Kauselmann, Gunther; Zevnik, Branko; Henriksen, Gjermund; Drzezga, Alexander; Pohlner, Johannes; Schoor, Michael; Kemp, John A.; von der Kammer, Heinz

2009-01-01

181

A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.  

PubMed

Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. PMID:19161156

Sartori, Stefano; Di Rosa, Gabriella; Polli, Roberta; Bettella, Elisa; Tricomi, Giovanni; Tortorella, Gaetano; Murgia, Alessandra

2009-02-01

182

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

PubMed Central

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

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

2014-01-01

183

Plasma Proteome Analysis on Cynomolgus Monkey (Macaca Fascicularis) Pedigrees with Early Onset Drusen Formation  

PubMed Central

The central region of the primate retina is called macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create neural network adapted for high visual acuity. Damage to the fovea by macular dystrophies and age-related macular degeneration (AMD) can reduce the central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in macula differ from that in peripheral retina in expression level. Previously, we reported an early onset macular degeneration with drusen in cynomolgus monkey pedigrees. These monkeys show similar fundus findings of early stage of AMD at 2 years after birth. To elucidate mechanism of drusen formation and to find disease biomarkers for early stage of AMD, we performed plasma proteome analysis. Plasma samples were collected from four affected and control monkeys within the same pedigree. Successful fractionation of the plasma proteins by ProteoMiner and Gelfree8100 were confirmed by SDS-PAGE. Total of 245 proteins were identified from eight samples. From the results of spectral counting, we selected some proteins, Apolipoprotein E, Histidine-rich glycoprotein, and Retinol-binding protein 4 as candidate proteins that would be related with drusen formation. Candidate proteins would be potentially beneficial as biomarkers for human AMD. One of the identified proteins, Apolipoprotein E (ApoE), is structural component of drusen and also related with other neurodegenerative disease like Alzheimer disease. In this plasma proteome analysis, ApoE would be one of the possible factors of early drusen formation in these cynomolgus monkey pedigrees. PMID:25077760

Kobayashi, Hiroaki; Okamoto, Haru; Murakami, Akira; Iwata, Takeshi

2014-01-01

184

The Relationship Between Early Age of Onset of Initial Substance Use and Engaging in Multiple Health Risk Behaviors Among Young Adolescents  

Microsoft Academic Search

Background: Previous research based on problem- behavior theory has found that early age of onset of sub- stance use is associated with engaging in multiple health risk behaviors among high school students. It is unknown whether these relationships begin during early adolescence. Objective: To examine the relationships between early age of onset of cigarette, alcohol, marijuana, and co- caine use

Robert H. DuRant; Jeffrey A. Smith; Shelley R. Kreiter; Daniel P. Krowchuk

1999-01-01

185

Is the relationship between early-onset cannabis use and educational attainment causal or due to common liability?  

PubMed Central

Background Several studies have shown that early cannabis use is correlated with poor educational performance including high school drop-out. The predominant explanation for this relationship is that cannabis use causes disengagement from education. Another explanation is that the association between early cannabis use and educational attainment is not causal, but the result of overlapping risk factors that increase the likelihood of both early cannabis use and disengagement from education. These confounding factors could be of genetic and/or environmental origin. Methods Here we use data from a large community-based sample of adult twins (N=3337) who completed a comprehensive semi-structured telephone interview. We first apply the classical twin-design to determine whether genetic and/or environmental influences underlie the relationship between early-onset cannabis use (prior to age 18) and early school leaving. Next, with a co-twin control design we investigate whether the relationship between the two variables is more likely due to direct causality or overlapping risk factors. Results We find a significant phenotypic correlation between early-onset cannabis use and early school leaving (r=0.26), which could be explained by familial influences (of genetic and/or shared environmental origin). The pattern of odds ratios found in the co-twin control design is not consistent with direct causation, but rather suggests that the association is due to shared environmental factors influencing both variables. Conclusion Our findings suggest that the relationship between early-onset cannabis use and school leaving is due to shared environmental risk factors influencing both the risk of early-onset cannabis use and early school leaving. PMID:23972999

Verweij, Karin J.H.; Huizink, Anja C.; Agrawal, Arpana; Martin, Nicholas G.; Lynskey, Michael T.

2013-01-01

186

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

PubMed

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

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

2014-09-01

187

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

PubMed

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; Patel, Mulchand S

2013-10-01

188

Frequency of activating mutations in FGFR2 exon 7 in bladder tumors from patients with early-onset and regular-onset disease  

PubMed Central

The FGF/FGFR-system plays an important role in embryogenesis, tissue homeostasis and carcinogenesis. Mutational activation of FGFR2 resulting in aberrant FGFR2 signaling activation is known from both hereditary germ line alterations and somatic mutations in various malignancies (e.g. breast, gastric or ovarian cancer). FGFR2 mutations are mainly located within the hinge between Ig-like domains (exon 7), around the 3rd Ig-like domains and within the kinase domain. For bladder cancer only sparse data on FGFR2 mutations are available. Most interestingly a case of early-onset papillary carcinoma of the bladder showing a FGFR2 p.Pro253Arg mutation in exon 7 in a patient with Apert Syndrome was reported recently. To further evaluate the importance of FGFR2 exon 7 alterations in bladder cancer a cohort of 254 bladder tumors (cohort 1: unselected cases: n=139; cohort 2: early-onset bladder cancer cases (age at time of diagnosis ?45 years): n=115) was analyzed. Sections from formalin-fixed, paraffin-embedded bladder tumors were used for DNA isolation. After precise microdissection exon 7 of the FGFR2 gene was analyzed by direct Sanger sequencing. All cases could be analyzed successfully. Mutations in exon 7 of FGFR2 could not be detected in any of the cases. All tumors showed wild type sequence. Our data demonstrate that the recently reported association between early-onset papillary carcinoma of the bladder with germ line FGFR2 p.Pro253Arg mutation could not be found in our cohorts of sporadic bladder tumors. These results indicate that FGFR2 gene mutations might only play a minor role in bladder carcinogenesis. PMID:24817968

Spiegelberg, Christine; Giedl, Johannes; Gaisa, Nadine T; Rogler, Anja; Riener, Marc-Oliver; Filbeck, Thomas; Burger, Maximilian; Ruemmele, Petra; Hartmann, Arndt; Stoehr, Robert

2014-01-01

189

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

190

Higher Activity of the Inducible Nitric Oxide Synthase Contributes to Very Early Onset Inflammatory Bowel Disease  

PubMed Central

OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10?6, OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02–5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production. PMID:24430113

Dhillon, Sandeep S; Mastropaolo, Lucas A; Murchie, Ryan; Griffiths, Christopher; Thöni, Cornelia; Elkadri, Abdul; Xu, Wei; Mack, Amanda; Walters, Thomas; Guo, Conghui; Mack, David; Huynh, Hien; Baksh, Shairaz; Silverberg, Mark S; Brumell, John H; Snapper, Scott B; Muise, Aleixo M

2014-01-01

191

Two Percent of Men with Early-Onset Prostate Cancer Harbor Germline Mutations in the BRCA2 Gene  

Microsoft Academic Search

Studies of families with breast cancer have indicated that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age. To evaluate the contribution of BRCA2 mutations to early-onset prostate cancer, we screened the complete coding sequence of BRCA2 for germline mutations, in 263 men with diagnoses of prostate cancer who were 55 years

Stephen M. Edwards; Zsofia Kote-Jarai; Julia Meitz; Rifat Hamoudi; Questa Hope; Peter Osin; Rachel Jackson; Christine Southgate; Rashmi Singh; Alison Falconer; David P. Dearnaley; Audrey Ardern-Jones; Annette Murkin; Anna Dowe; Jo Kelly; Sue Williams; Richard Oram; Margaret Stevens; Dawn M. Teare; A. J. Bruce Ponder; Simon A. Gayther; Doug F. Easton; Rosalind A. Eeles

2003-01-01

192

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

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

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

195

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

196

Two Novel Mutations in the GDAP1 and PRX Genes in Early Onset Charcot-Marie-Tooth Syndrome  

PubMed Central

Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested. PMID:18504680

Auer-Grumbach, M.; Fischer, C.; Papi?, L.; John, E.; Plecko, B.; Bittner, R. E.; Bernert, G.; Pieber, T. R.; Miltenberger, G.; Schwarz, R.; Windpassinger, C.; Grill, F.; Timmerman, V.; Speicher, M. R.; Janecke, A. R.

2011-01-01

197

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

PubMed Central

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

2014-01-01

198

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

ERIC Educational Resources Information Center

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…

Nieto, Rebeca Garcia; Castellanos, F. Xavier

2011-01-01

199

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

ERIC Educational Resources Information Center

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

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

2010-01-01

200

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

PubMed Central

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

2014-01-01

201

Impact of early-onset seizures on grading and outcome in patients with subarachnoid hemorrhage.  

PubMed

OBJECT After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome. METHODS This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I-III) and poor (WFNS IV-V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0-3 was considered a good outcome and an mRS score of 4-6 was considered a poor outcome. RESULTS Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14-7.46; p = 0.03) and good outcome (OR 4.01, 97.5% CI 1.63-10.53; p = 0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p < 0.001), and poor WFNS grade (p < 0.001) were associated with poor outcome. CONCLUSIONS Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution. PMID:25479126

Fung, Christian; Balmer, Mathias; Murek, Michael; Z'Graggen, Werner J; Abu-Isa, Janine; Ozdoba, Christoph; Haenggi, Matthias; Jakob, Stephan M; Raabe, Andreas; Beck, Jürgen

2015-02-01

202

Preliminary analysis of immune activation in early onset type 2 diabetes  

PubMed Central

Introduction First Nations and other Aboriginal children are disproportionately affected by cardiometabolic diseases, including type 2 diabetes (T2D). In T2D, the disruption of insulin signalling can be driven by pro-inflammatory immunity. Pro-inflammatory responses can be fueled by toll-like receptors (TLR) on immune cells such as peripheral blood mononuclear cells (PBMC, a white blood cell population). TLR4 can bind to lipids from bacteria and food sources activating PBMC to produce cytokines tumour necrosis factor (TNF)-? and interleukin (IL)-1?. These cytokines can interfere with insulin signalling. Here, we seek to understand how TLR4 activation may be involved in early onset T2D. We hypothesized that immune cells from youth with T2D (n=8) would be more reactive upon TLR4 stimulation relative to cells from age and body mass index (BMI)-matched controls without T2D (n=8). Methods Serum samples were assayed for adipokines (adiponectin and leptin), as well as cytokines. Freshly isolated PBMC were examined for immune reactivity upon culture with TLR4 ligands bacterial lipopolysaccharide (LPS, 2 and 0.2 ng/ml) and the fatty acid palmitate (200 µM). Culture supernatants were evaluated for the amount of TNF-? and IL-1? produced by PBMC. Results Youth with T2D displayed lower median serum adiponectin levels compared to controls (395 vs. 904 ng/ml, p<0.05). PBMC isolated from youth with and without T2D produced similar levels of TNF-? and IL-1? after exposure to the higher LPS concentration. However, at the low LPS dose the T2D cohort exhibited enhanced IL-1? synthesis relative to the control cohort. Additionally, exposure to palmitate resulted in greater IL-1? synthesis in PBMCs isolated from youth with T2D versus controls (p<0.05). These differences in cytokine production corresponded to greater monocyte activation in the T2D cohort. Conclusion These preliminary results suggest that cellular immune responses are exaggerated in T2D, particularly with respect to IL-1? activity. These studies aim to improve the understanding of the biology behind early onset T2D and its vascular complications that burden First Nations people. PMID:23984304

Rempel, Julia D.; Packiasamy, Juliet; Dean, Heather J.; McGavock, Jonathon; Janke, Alyssa; Collister, Mark; Wicklow, Brandy; Sellers, Elizabeth A. C.

2013-01-01

203

A novel deleterious PTEN mutation in a patient with early-onset bilateral breast cancer  

PubMed Central

Background An early age at Breast Cancer (BC) onset may be a hallmark of inherited predisposition, but BRCA1/2 mutations are only found in a minority of younger BC patients. Among the others, a fraction may carry mutations in rarer BC genes, such as TP53, STK11, CDH1 and PTEN. As the identification of women harboring such mutations allows for targeted risk-management, the knowledge of associated manifestations and an accurate clinical and family history evaluation are warranted. Case presentation We describe the case of a woman who developed an infiltrating ductal carcinoma of the right breast at the age of 32, a contralateral BC at age 36 and another BC of the right breast at 40. When she was 39 years-old, during a dermatological examination, mucocutaneous features suggestive of Cowden Syndrome, a disorder associated to germ-line PTEN mutations, were noticed. PTEN genetic testing revealed the novel c.71A > T (p.Asp24Val) mutation, whose deleterious effect, suggested by conservation data and in silico tools, was definitely demonstrated by the incapacity of mutant PTEN to inhibit Akt phosphorylation when used to complement PTEN-null cells. In BC tissue, despite the absence of LOH or somatic mutations of PTEN, Akt phosphorylation was markedly increased in comparison to normal tissue, thus implying additional somatic events into the deregulation of the PI3K/Akt/mTOR pathway and, presumably, into carcinogenesis. Hence, known oncogenic mutations in PIK3CA (exons 10 and 21) and AKT1 (exon 2) were screened in tumor DNA with negative results, which suggests that the responsible somatic event(s) is a different, uncommon one. Conclusion This case stresses the importance of clinical/genetic assessment of early-onset BC patients in order to identify mutation carriers, who are at high risk of new events, so requiring tailored management. Moreover, it revealed a novel PTEN mutation with pathogenic effect, pointing out, however, the need for further efforts to elucidate the molecular steps of PTEN-associated carcinogenesis. PMID:24498881

2014-01-01

204

Warm temperatures lead to early onset of incubation, shorter incubation periods and greater hatching asynchrony in tree swallows Tachycineta bicolor at the extremes of their range  

Microsoft Academic Search

The onset of incubation varies in birds, with many species beginning incubation prior to clutch completion. Here we examine whether early onset is more likely to occur during high temperatures, a critical prediction of the egg-viability hypothesis, which suggest that birds begin incubation prior to clutch completion in order to maintain egg-viability. We examined onset of incubation in tree swallows

Daniel R. Ardia; Caren B. Cooper; Andre A. Dhondt

2006-01-01

205

Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases.  

PubMed

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??-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???]. 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

Li, Rui; Brockschmidt, Felix F; Kiefer, Amy K; Stefansson, Hreinn; Nyholt, Dale R; Song, Kijoung; Vermeulen, Sita H; Kanoni, Stavroula; 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; Nöthen, Markus M; Richards, J Brent

2012-05-01

206

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.; Nöthen, Markus M.; Richards, J. Brent

2012-01-01

207

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

208

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

PubMed

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

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

2010-08-01

209

Plasma 25-OH-Vitamin D Levels in Early Onset, Severe Preeclampsia  

PubMed Central

OBJECTIVE Vitamin D deficiency has been linked to adverse pregnancy outcomes. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-OH-D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). STUDY DESIGN Following IRB approval, subjects with EOSPE (< 34 weeks gestation with severe preeclampsia) were enrolled in this case-control investigation in a 1:2 ratio with gestation matched, contemporaneous controls. Demographic and outcome information was collected for each subject. Plasma total 25-OH-D levels were determined by radioimmunoassay and reported in ng/mL. Results were analyzed by Mann-Whitney U and multivariable regression. RESULTS Subjects with EOSPE (n=50) were noted to have decreased total 25-OH-D levels relative to healthy controls (n=100; p<0.001). This difference in total 25-OH-D remained significant after controlling for potential confounders. CONCLUSION Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is needed to understand the impact of vitamin D deficiency on pregnancy outcomes. PMID:20692641

ROBINSON, Christopher J.; ALANIS, Mark S.; WAGNER, Carol L.; HOLLIS, Bruce W.; JOHNSON, Donna D.

2011-01-01

210

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

PubMed

Identification of the genetic defect underlying early-onset diabetes is important for determining the specific diabetes subtype, which would then permit appropriate treatment and accurate assessment of recurrence risk in offspring. Given the extensive genetic and clinical heterogeneity of the disease, high-throughput sequencing might provide additional diagnostic potential when Sanger sequencing is ineffective. Our aim was to develop a targeted next-generation assay able to detect mutations in several genes involved in glucose metabolism. All 13 known MODY genes, genes identified from a genome-wide linkage study or genome-wide association studies as increasing the risk of type 2 diabetes and genes causing diabetes in animal models, were included in the custom panel. We selected a total of 102 genes by performing a targeting re-sequencing in 30 patients negative for mutations in the GCK, HNF1?, HNF4?, HNF1? and IPF1 genes at the Sanger sequencing analysis. Previously unidentified variants in the RFX6 gene were found in three patients and in two of them we also detected rare variants in WFS1 and ABCC8 genes. All patients showed a good therapeutic response to dipeptidyl peptidase-4 (DPP4) inhibitors. Our study reveals that next-generation sequencing provides a highly sensitive method for identification of variants in new causative genes of diabetes. This approach may help in understanding the molecular etiology of diabetes and in providing more personalized treatment for each genetic subtype. PMID:25048417

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

2015-02-01

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

Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia.  

PubMed

Previous studies indicate that founder mutations may play a noticeable role in breast cancer (BC) predisposition in Russia. Here we performed a systematic analysis of eight recurrent mutations in 302 BC cases (St.-Petersburg, Russia), which were selected due to the presence of clinical indicators of hereditary disease (bilaterality and/or early onset (< or =40 years) and/or family history). BC-associated alleles were revealed in 46 (15.2%) women. BRCA1 5382insC mutation was detected in 29 (9.6%) patients, CHEK2 1100delC in 9 (3.0%), BRCA1 4153delA in 3 (1.0%), CHEK2 IVS2+1G>A in 2 (0.7%), and BRCA1 185delAG, BRCA2 6174delT and NBS1 657del5 in 1 (0.3%) patient each. No cases with BRCA1 300T>G (C61G) mutation was identified. The obtained data suggest that a significant fraction of hereditary BC cases in Russia can be diagnosed using only a limited number of simple PCR tests. PMID:17333477

Sokolenko, Anna P; Rozanov, Maxim E; Mitiushkina, Natalia V; Sherina, Natalia Yu; Iyevleva, Aglaya G; Chekmariova, Elena V; Buslov, Konstantin G; Shilov, Evgeny S; Togo, Alexandr V; Bit-Sava, Elena M; Voskresenskiy, Dmitry A; Chagunava, Oleg L; Devilee, Peter; Cornelisse, Cees; Semiglazov, Vladimir F; Imyanitov, Evgeny N

2007-01-01

213

A method for conducting intensive psychological studies with early-onset chronically depressed patients.  

PubMed

An intensive empirical methodology is introduced to evaluate the efficacy of Cognitive Behavioral Analysis System of Psychotherapy (CBASP) treatment for outpatients with early onset chronic depression. The patient with chronic illness presents a unique measurement challenge to psychotherapists. One of the most prominent reasons is the refractory nature of the disorder. In order to measure the change process, the authors have found it helpful to use an acquisition-learning methodology to answer three questions: (1) What are we trying to teach the patient? (2) How much has the patient learned throughout the course of therapy? And, (3) how does the extent of patient learning impact the change indices at the end of treatment and during the follow-up period? Answering questions 2 and 3 allows us to superimpose the change process variables over the performance learning variables on a graph. These combined variables also allow us to test the hypothesis: By learning what psychotherapy teaches, the chronic psychological disorder may be resolved. PMID:21299171

McCullough, James P; Lord, Benjamin D; Conley, Kathryn A; Martin, Aaron M

2010-01-01

214

Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.  

PubMed

Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350. PMID:25359994

Milner, Joshua D; Vogel, Tiphanie P; Forbes, Lisa; Ma, Chi A; Stray-Pedersen, Asbjørg; Niemela, Julie E; Lyons, Jonathan J; Engelhardt, Karin R; Zhang, Yu; Topcagic, Nermina; Roberson, Elisha D O; Matthews, Helen; Verbsky, James W; Dasu, Trivikram; Vargas-Hernandez, Alexander; Varghese, Nidhy; McClain, Kenneth L; Karam, Lina B; Nahmod, Karen; Makedonas, George; Mace, Emily M; Sorte, Hanne S; Perminow, Gøri; Rao, V Koneti; O'Connell, Michael P; Price, Susan; Su, Helen C; Butrick, Morgan; McElwee, Joshua; Hughes, Jason D; Willet, Joseph; Swan, David; Xu, Yaobo; Santibanez-Koref, Mauro; Slowik, Voytek; Dinwiddie, Darrell L; Ciaccio, Christina E; Saunders, Carol J; Septer, Seth; Kingsmore, Stephen F; White, Andrew J; Cant, Andrew J; Hambleton, Sophie; Cooper, Megan A

2015-01-22

215

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

216

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

PubMed

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

Dakos, Vasilis; Bascompte, Jordi

2014-12-01

217

The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy  

PubMed Central

Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. Methods An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction. Results This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. Conclusion This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases. PMID:23356391

2013-01-01

218

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

2014-01-01

219

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

PubMed

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

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

2015-02-01

220

Laser therapy for periodontitis  

NASA Astrophysics Data System (ADS)

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

Efanov, O. I.

2001-04-01

221

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

222

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

ERIC Educational Resources Information Center

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

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

2004-01-01

223

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

224

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

PubMed

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

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

2014-08-11

225

Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer.  

PubMed

Germline variants affecting the exonuclease domains of POLE and POLD1 predispose to multiple colorectal adenomas and/or colorectal cancer (CRC). The aim of this study was to estimate the prevalence of previously described heterozygous germline variants POLE c.1270C>G, p.(Leu424Val) and POLD1 c.1433G>A, p.(Ser478Asn) in a Dutch series of unexplained familial, early onset CRC and polyposis index cases. We examined 1188 familial CRC and polyposis index patients for POLE p.(Leu424Val) and POLD1 p.(Ser478Asn) variants using competitive allele-specific PCR. In addition, protein expression of the POLE and DNA mismatch repair genes was studied by immunohistochemistry in tumours from POLE carriers. Somatic mutations were screened using semiconductor sequencing. We detected three index patients (0.25%) with a POLE p.(Leu424Val) variant. In one patient, the variant was found to be de-novo. Tumours from three patients from two families were microsatellite instable, and immunohistochemistry showed MSH6/MSH2 deficiency suggestive of Lynch syndrome. Somatic mutations but no germline MSH6 and MSH2 variants were subsequently found, and one tumour displayed a hypermutator phenotype. None of the 1188 patients carried the POLD1 p.(Ser478Asn) variant. POLE germline variant carriers are also associated with a microsatellite instable CRC. POLE DNA analysis now seems warranted in microsatellite instable CRC, especially in the absence of a causative DNA mismatch repair gene germline variant.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.242. PMID:25370038

Elsayed, Fadwa A; Kets, C Marleen; Ruano, Dina; van den Akker, Brendy; Mensenkamp, Arjen R; Schrumpf, Melanie; Nielsen, Maartje; Wijnen, Juul T; Tops, Carli M; Ligtenberg, Marjolijn J; Vasen, Hans Fa; Hes, Frederik J; Morreau, Hans; van Wezel, Tom

2014-11-01

226

A Mouse Model of Early-Onset Renal Failure Due to a Xanthine Dehydrogenase Nonsense Mutation  

PubMed Central

Chronic kidney disease (CKD) is characterized by renal fibrosis that can lead to end-stage renal failure, and studies have supported a strong genetic influence on the risk of developing CKD. However, investigations of the underlying molecular mechanisms are hampered by the lack of suitable hereditary models in animals. We therefore sought to establish hereditary mouse models for CKD and renal fibrosis by investigating mice treated with the chemical mutagen N-ethyl-N-nitrosourea, and identified a mouse with autosomal recessive renal failure, designated RENF. Three-week old RENF mice were smaller than their littermates, whereas at birth they had been of similar size. RENF mice, at 4-weeks of age, had elevated concentrations of plasma urea and creatinine, indicating renal failure, which was associated with small and irregularly shaped kidneys. Genetic studies using DNA from 10 affected mice and 91 single nucleotide polymorphisms mapped the Renf locus to a 5.8Mbp region on chromosome 17E1.3. DNA sequencing of the xanthine dehydrogenase (Xdh) gene revealed a nonsense mutation at codon 26 that co-segregated with affected RENF mice. The Xdh mutation resulted in loss of hepatic XDH and renal Cyclooxygenase-2 (COX-2) expression. XDH mutations in man cause xanthinuria with undetectable plasma uric acid levels and three RENF mice had plasma uric acid levels below the limit of detection. Histological analysis of RENF kidney sections revealed abnormal arrangement of glomeruli, intratubular casts, cellular infiltration in the interstitial space, and interstitial fibrosis. TUNEL analysis of RENF kidney sections showed extensive apoptosis predominantly affecting the tubules. Thus, we have established a mouse model for autosomal recessive early-onset renal failure due to a nonsense mutation in Xdh that is a model for xanthinuria in man. This mouse model could help to increase our understanding of the molecular mechanisms associated with renal fibrosis and the specific roles of XDH and uric acid. PMID:23024809

Gorvin, Caroline M.; Head, Rosie; Loh, Nellie Y.; Devuyst, Olivier; Thomas, Gethin; Brown, Steve D. M.; Brown, Matthew; Croucher, Peter; Cox, Roger; Thakker, Rajesh V.

2012-01-01

227

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

PubMed Central

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

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

2010-01-01

228

Case-control study of presenilin-1 intronic polymorphism in sporadic early and late onset Alzheimer's disease  

PubMed Central

OBJECTIVE—Presenilin-1 is a major causative gene for early onset familial Alzheimer's disease, and the apolipoprotein E ?4 allele is a major genetic risk factor known to influence late onset and sporadic early onset Alzheimer's disease. The presenilin-1 1/1 genotype has recently been reported to be associated with sporadic Alzheimer's disease. The purpose of this study is to determine whether Alzheimer's disease is associated with presenilin-1 gene polymorphism and the apolipoprotein E genotype in an extended case-control study.?METHODS—An examination was conducted on 217 patients with Alzheimer's disease, along with an equal number of age and sex matched controls derived from the same community in a Japanese population, by using a ?2 test for homogeneity and a logistic regression analysis. A meta-analysis of data from the literature on allele frequencies in Alzheimer's disease and control populations was used for comparison with the Japanese allele frequencies obtained in this study.?RESULTS—The presenilin-1 allele-1 frequencies were similar in patients with early onset Alzheimer's disease (0.61) and younger controls (0.61), and in those with late onset Alzheimer's disease (0.63) and elderly controls (0.63). We found no evidence for a possible association between the presenilin-1 polymorphism and the apolipoprotein E ?4 allele. However, the meta-analysis showed that the association between the presenilin-1 1/1 genotype and Alzheimer's disease was significant (Peto odds ratio=1.16, 95% confidence interval=1.04-1.31).?CONCLUSIONS—These results suggest a subtle but positive association of presenilin-1 gene polymorphism with Alzheimer's disease, although Japanese data in this study which failed to support such a relation would indicate an ethnic variation.?? PMID:10329743

Yasuda, M.; Hirono, N.; Maeda, K.; Imamura, T.; Mori, E.; Tanaka, C.

1999-01-01

229

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

230

Prevalence of BRCA1 and BRCA2 Gene Mutations in Patients With Early-Onset Breast Cancer  

Microsoft Academic Search

Background: Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast can- cer who were unselected for a family history of this disease has not been

Julian Peto; Nadine Collins; Rita Barfoot; Sheila Seal; William Warren; Nazneen Rahman; Douglas F. Easton; Christopher Evans; Judith Deacon; Michael R. Stratton

1999-01-01

231

A Novel Presenilin-1 Mutation (Leu85Pro) in Early-Onset Alzheimer Disease With Spastic Paraparesis  

Microsoft Academic Search

Patient and Methods: The patient was a 27-year-old man who developed early-onset dementia with spastic paraparesis. We examined sequences of the PSEN1, PSEN2, and APP genes from the patient and his family. To detect a possible mutation effect on the production of amyloid- peptide (A), transfected HEK293 cells were examined for A42 and A40 production. Results: We found a novel

Suzuka Ataka; Takami Tomiyama; Hiroshi Takuma; Takenari Yamashita; Hiroyuki Shimada; Tsuyoshi Tsutada; Koichi Kawabata; Hiroshi Mori; Takami Miki

2004-01-01

232

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

233

Focal 6-o'-clock Nd: YAG-capsulotomy for the treatment of early onset incomplete capsular block syndrome  

PubMed Central

We report on a patient who developed capsular block syndrome (CBS) in the early postoperative period with marked myopic shift in absence of anterior dislocation of the posterior-chamber intraocular lens (PC/IOL) and iris diaphragm. Treatment with focal 6-o'-clock Nd: YAG-capsulotomy resulted in complete visual acuity restoration. To the best of our knowledge this is the fist case of early onset CBS with significant myopic shift in absence of anterior PC/IOL dislocation, which was successfully treated with focal 6-o'-clock Nd: YAG-capsulotomy. The possible underlying pathophysiological mechanism is discussed. PMID:21311637

Kozeis, N; Gatzioufas, Z; Schirra, F; Loew, U; Seitz, B

2010-01-01

234

Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study  

PubMed Central

Objectives To examine the association between coronary heart disease and chronic Helicobacter pylori infection. Design Case-control study of myocardial infarction at young ages and study of sibling pairs with one member affected and the other not. Setting United Kingdom. Participants 1122 survivors of suspected acute myocardial infarction at ages 30-49 (mean age 44 years) and 1122 age and sex matched controls with no history of coronary heart disease; 510 age and sex matched pairs of siblings (mean age 59 years) in which one sibling had survived myocardial infarction and one had no history of coronary heart disease. Main outcome measures Serological evidence of chronic infection with H pylori. Results 472 (42%) of the 1122 cases with early onset myocardial infarction were seropositive for H pylori antibodies compared with 272 (24%) of the 1122 age and sex matched controls, giving an odds ratio of 2.28 (99% confidence interval 1.80 to 2.90). This odds ratio fell to 1.87 (1.42 to 2.47; P<0.0001) after smoking and indicators of socioeconomic status were adjusted for and to 1.75 (1.29 to 2.36) after additional adjustment for blood lipid concentrations and obesity. Only 158 of the 510 pairs of siblings were discordant for H pylori status; among these, 91 cases and 67 controls were seropositive (odds ratio 1.33 (0.86 to 2.05)). No strong correlations were observed between H pylori seropositivity and measurements of other risk factors for coronary heart disease (plasma lipids, fibrinogen, C reactive protein, albumin, etc). Conclusion In the context of results from other relevant studies, these two studies suggest a moderate association between coronary heart disease and H pylori seropositivity that cannot be fully accounted for by other risk factors. But even if this association is causal and largely reversible by eradication of chronic infection, very large randomised trials would be needed to show this. Key messagesMost previous studies of associations between chronic H pylori infection and coronary heart disease have been too small or prone to biasThis case-control study found myocardial infarction was twice as common in people infected with H pylori as in those not infectedAmong sibling pairs, myocardial infarction was about a third more common in seropositive people than those who were seronegativeThese results support a weak association between H pylori infection and coronary heart disease PMID:10541503

Danesh, John; Youngman, Linda; Clark, Sarah; Parish, Sarah; Peto, Richard; Collins, Rory

1999-01-01

235

Molecular Genetics of FAM161A in North American Patients with Early-Onset Retinitis Pigmentosa  

PubMed Central

Retinitis pigmentosa (RP) is a hereditary disease that leads to the progressive degeneration of retinal photoreceptor cells and to blindness. It is caused by mutations in several distinct genes, including the ciliary gene FAM161A, which is associated with a recessive form of this disorder. Recent investigations have revealed that defects in FAM161A represent a rather prevalent cause of hereditary blindness in Israel and the Palestinian territories, whereas they seem to be rarely present within patients from Germany. Genetic or clinical data are currently not available for other countries. In this work, we screened a cohort of patients with recessive RP from North America to determine the frequency of FAM161A mutations in this ethnically-mixed population and to assess the phenotype of positive cases. Out of 273 unrelated patients, only 3 subjects had defects in FAM161A. A fourth positive patient, the sister of one of these index cases, was also identified following pedigree analysis. They were all homozygous for the p.T452Sfx3 mutation, which was previously reported as a founder DNA variant in the Israeli and Palestinian populations. Analysis of cultured lymphoblasts from patients revealed that mutant FAM161A transcripts were actively degraded by nonsense-mediated mRNA decay. Electroretinographic testing showed 30 Hz cone flicker responses in the range of 0.10 to 0.60 microvolts in all cases at their first visit (age 12 to 23) (lower norm ?=? 50 ?V) and of 0.06 to 0.32 microvolts at their most recent examination (age 27 to 43), revealing an early-onset of this progressive disease. Our data indicate that mutations in FAM161A are responsible for 1% of recessive RP cases in North America, similar to the prevalence detected in Germany and unlike the data from Israel and the Palestinian territories. We also show that, at the molecular level, the disease is likely caused by FAM161A protein deficiency. PMID:24651477

Harper, Shyana; Weigel-DiFranco, Carol

2014-01-01

236

[Diabetes and periodontitis: A bidirectional relationship.  

PubMed

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, a defect in insulin action or a combination of both. Periodontitis is now considered a chronic localized infection of the oral cavity that can trigger inflammatory host immune responses at local and systemic levels, and can also be a source of bacteremia. It is now known that periodontitis has an influence on the pathogenesis of certain systemic diseases. The biological relationship between diabetes and periodontal disease is well documented. In the mid-90s sufficient scientific support for the association between diabetes and periodontitis was published, and periodontitis was designated as the sixth complication of diabetes. There have been studies that show an improvement in both clinical and immunological parameters of periodontitis and glycemic control in long-term diabetes after treatment of periodontal disease. In addition, scientific evidence confirms that poorer glycemic control contributes to a worse periodontal condition. The interplay between the 2 conditions highlights the importance of the need for a good communication between the internist and dentist about diabetic patients, considering always the possibility that the 2 diseases may be occurring simultaneously in order to ensure an early diagnosis of both. PMID:25192582

Bascones-Martínez, Antonio; Muñoz-Corcuera, Marta; Bascones-Ilundain, Jaime

2014-09-01

237

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

NASA Astrophysics Data System (ADS)

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

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

2009-02-01

238

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

PubMed Central

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

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

2012-01-01

239

Microbiological and host factors are involved in promoting the periodontal failure of metaloceramic crowns.  

PubMed

This study was aimed at looking into the microbiological/inflammatory parameters predicting the periodontal success/failure of fixed prostheses. Microbiological and inflammatory patterns were studied at 102 sites having metaloceramic crowns in place from 3 to 6 years and divided in healthy sites (HS), gingivitis affected (MG), and periodontitis affected (PB). Total bacterial flora and selected indicator species in subgingival plaque were quantified by quantitative real-time PCR. The concentrations of IL-1?, IL-6, and TNF-? were determined in gingival crevicular fluid (GCF) by enzyme-linked immunosorbent assays. The experimental sites showed no significant difference with respect to the age and gender of the patients and to the position of the crown margins. Poor marginal adaptation was significantly higher in MG and PB. The total amounts of bacteria per probing depth showed no significant differences among the three groups and their controls, while both MG and PB sites showed altered patterns in the distribution of specific bacteria. Both MG and PB sites showed significantly higher levels of inflammatory cytokines in GCF. The control teeth of PB subjects showed significantly higher levels of IL-1? as compared to other control sites. Data confirm that the application of metaloceramic crowns is a factor of risk for the development of gingival/periodontal inflammation. This risk is possibly associated with microbiological and host factors that predispose to the onset of periodontal alterations at sites reconstructed with metaloceramic crowns. These factors, once their role is confirmed by longitudinal studies, could be used to set up rapid tests to early predict the onset of periodontal disease at reconstructed sites. PMID:21720749

Passariello, Claudio; Puttini, Monica; Virga, Alessandra; Gigola, Pierangelo

2012-06-01

240

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

PubMed Central

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

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

2014-01-01

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

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

243

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

244

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

245

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

246

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

PubMed

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

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

2014-11-13

247

A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism  

Microsoft Academic Search

The functional loss of both alleles of the human pro-opiomelanocortin (POMC) gene leads to a very rare syndrome of hypoadrenalism, red hair and early-onset obesity. In order to examine whether more subtle genetic variants in POMC might contribute to early-onset obesity, the coding region of the gene was sequenced in 262 Caucasian subjects with a history of severe obesity from

Benjamin G. Challis; Lynn E. Pritchard; John W. M. Creemers; Jerome Delplanque; Julia M. Keogh; Nicholas J. Wareham; Giles S. H. Yeo; Sumit Bhattacharyya; Phillipe Froguel; Anne White; I. Sadaf Farooqi; Stephen O'Rahilly

2002-01-01

248

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

249

Effect of stretching stress on gene transcription related to early-phase differentiation in rat periodontal ligament cells.  

PubMed

Mechanical stress such as occlusal and orthodontic loading has been suggested to induce a homeostatic and regenerative response in periodontal ligament (PDL), but the underlying mechanism remains to be clarified. The purpose of this study was to investigate expression of mRNAs encoding proteins involved in osteogenesis and homeostasis by PDL cells following application of tensile stress and characterize the relationship between such expression and the regenerative and homeostatic functions of the PDL. PDL cells were obtained from rats and stretched by 9% or 18% at a frequency of 6 cycles/min for 12 hr to 5 days in a FX-4000T™ culture system. After stretching, expression of mRNAs encoding collagen type I (Col-I), alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-4 (BMP-4), heat shock protein 70 (HSP70) and basic fibroblast growth factor (bFGF) was investigated. The highest levels of Col-I, ALP and BMP-2 mRNA expression occurred at 12 hr, while those of BMP-4 and HSP70 occurred at 1 day and 5 days, respectively. Expression levels of Col-I, ALP, BMP-2, BMP-4 and HSP70 increased magnitude-dependently with stretching force in the stretching groups. In contrast, expression of bFGF mRNA showed statistically significant reduction in both stretching groups, with the largest reduction seen in the 9% stretching group (p<0.01). These results suggest that stretching of PDL cells provokes significant increases in expression of factors promoting osteogenic differentiation and HSP70, which protects PDL cells undergoing mechanical stress and contributes to maintenance of PDL homeostasis. However, expression of bFGF was restrained. Reduced expression of bFGF mRNA suggested that there was an optimum magnitude of stretching force for increasing expression. PMID:20877159

Enokiya, Yasunobu; Hashimoto, Sadamitsu; Muramatsu, Takashi; Jung, Han-Sung; Tazaki, Masakazu; Inoue, Takashi; Abiko, Yoshihiro; Shimono, Masaki

2010-01-01

250

Reduced sleep spindle activity in early-onset and elevated risk for depression Running head: Sleep Spindles and Adolescent MDD  

PubMed Central

Objective Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than in adulthood, and as such, may be a more sensitive measure of sleep alteration than PSG in early-onset depression. This study investigated SPA changes related to early-onset MDD, comparing those already ill and those at high-risk for MDD to healthy non-depressed controls. Method The study included 63 participants (8-15 year-olds): 21 currently depressed, 21 at high-risk for MDD based on positive family history of MDD, and 21 healthy controls with no personal or family history of psychiatric illness. All participants maintained a regular sleep/wake schedule for 5 days, followed by 2 nights in the lab. SPA was analyzed in Stage 2 of non-Rapid Eye Movement (NREM) sleep. Results SPA differed significantly between groups, particularly in the late part of the night (F2,62=7.3 p=0.001). Although, the difference was greatest between MDD and healthy controls, both the MDD (p=0.0004) and at high-risk groups (p=0.02) had significantly lower SPA compared to healthy controls. SPA deficit was more prominent in females than males (F5,62=5.19 p=0.005). Conclusions Low SPA characterizes youths with MDD and those at high-risk, particularly among girls, suggesting that early-onset depression and risk for the illness are associated with decreased neuroplasticity. PMID:20732629

Lopez, Jorge; Hoffmann, Robert; Armitage, Roseanne

2010-01-01

251

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

252

Mutation frequency of PRKAR1B and the major familial dementia genes in a Dutch early onset dementia cohort.  

PubMed

Genetic factors are important in all forms of dementia, especially in early onset dementia. The frequency of major gene defects in dementia has not been investigated in the Netherlands. Furthermore, whether the recently in a FTD family identified PRKAR1B gene is associated with an Alzheimer's disease (AD) like phenotype, has not been studied. With this study, we aimed to investigate the mutation frequency of the major AD and FTD genes and the PRKAR1B gene in a well-defined Dutch cohort of patients with early onset dementia. Mutation analysis of the genes PSEN1, APP, MAPT, GRN, C9orf72 and PRKAR1B was performed on DNA of 229 patients with the clinical diagnosis AD and 74 patients with the clinical diagnosis FTD below the age of 70 years. PSEN1 and APP mutations were found in, respectively 3.5 and 0.4 % of AD patients, and none in FTD patients. C9orf72 repeat expansions were present in 0.4 % of AD and in 9.9 % of FTD patients, whereas MAPT and GRN mutations both were present in 0.4 % in AD patients, and in 1.4 % resp. 2.7 % in FTD patients. We did not find any pathogenic mutations in the PRKAR1B gene. PSEN1 mutations are the most common genetic cause in Dutch AD patients, whereas MAPT and GRN mutations were found in less than 5 percent. C9orf72 repeat expansions were the most common genetic defect in FTD patients. No pathogenic PRKAR1B mutations were found in the early onset AD and FTD patients of our study. PMID:25108559

Cohn-Hokke, P E; Wong, T H; Rizzu, P; Breedveld, G; van der Flier, W M; Scheltens, P; Baas, F; Heutink, P; Meijers-Heijboer, E J; van Swieten, J C; Pijnenburg, Y A L

2014-11-01

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, Sinéad; Zaiwalla, Zenobia; McShane, Tony; Mefford, Heather C.; Shears, Deborah; Stewart, Helen; Kurian, Manju A.; Scheffer, Ingrid E.; Blair, Edward; Donnelly, Peter; Kaczmarek, Leonard K.; Taylor, Jenny C.

2014-01-01

254

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

255

Basal low antioxidant capacity correlates with cognitive deficits in early onset psychosis. A 2-year follow-up study.  

PubMed

The objective of the study is to examine the association of baseline total antioxidant status (TAS) and glutathione (GSH) levels with short- and long-term cognitive functioning in patients with early onset first-episode psychosis, comparing affective and non-affective psychoses. We analysed 105 patients with an early onset-first episode psychosis (age 9-17 years) and 97 healthy controls. Blood samples were taken at admission for measurement of TAS and GSH, and cognitive performance was assessed at baseline and at 2years of follow-up. Regression analysis was used to assess the relationship between TAS/GSH levels at baseline and cognitive performance at both time points, controlling for confounders. Baseline TAS and GSH levels were significantly lower in patients than healthy controls. In patients, baseline TAS was positively associated with the global cognition score at baseline (p=0.048) and two years later (p=0.005), while TAS was not associated with cognitive functioning in healthy controls. Further, baseline TAS in patients was specifically associated with the memory domain at baseline and with the memory and attention domains two years later. Stratifying by affective and non-affective psychoses, significant associations were only found between TAS and cognition in the non-affective psychosis group. Baseline GSH levels were not associated with cognitive functioning at either time point in either group. The antioxidant defence capacity in early onset first-episode psychotic patients is directly correlated with global cognition at baseline and at 2years of follow-up, especially in non-affective psychosis. PMID:24768133

Martínez-Cengotitabengoa, Mónica; Micó, Juan Antonio; Arango, Celso; Castro-Fornieles, Josefina; Graell, Montserrat; Payá, Beatriz; Leza, Juan Carlos; Zorrilla, Iñaki; Parellada, Mara; López, M Purificación; Baeza, Inmaculada; Moreno, Carmen; Rapado-Castro, Marta; González-Pinto, Ana

2014-06-01

256

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

SciTech Connect

Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-?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 48 h 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 48 h, 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. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-? was increased, while TGF? was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGF?-pathway inhibitors had only minor effects on fibrosis markers. • Rat PCLS can be used to study the early onset of fibrosis.

Westra, Inge M. [Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen (Netherlands); Oosterhuis, Dorenda [Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen (Netherlands); Groothuis, Geny M.M. [Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen (Netherlands); Olinga, Peter, E-mail: p.olinga@rug.nl [Division of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen (Netherlands)

2014-01-15

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

A Novel Splice-Mutation in PLS3 Causes X-Linked Early-Onset Low-Turnover Osteoporosis.  

PubMed

Genetic factors play an important role in the development of osteoporosis. Several monogenic forms of osteoporosis have been recognized; most recently an X-chromosomal form resulting from mutations in the gene encoding plastin 3 (PLS3). PLS3 is a protein involved in actin bundle formation in the cytoskeleton. We present a large family with early-onset osteoporosis and X-linked inheritance. Phenotyping was performed on 19 family members and whole-exome sequencing on seven family members; five with a diagnosis of early-onset osteoporosis and two with normal bone parameters. Osteoporosis had its onset in childhood and was characterized by recurrent peripheral fractures, low BMD, vertebral compression fractures, and significant height loss in adulthood. Males were in general more severely affected than females. Bone histomorphometry findings in four males and one female showed severe trabecular osteoporosis, low amount of osteoid and decreased mineral apposition rate indicating impaired bone formation; resorption parameters were increased in some. All affected subjects shared a single base substitution (c.73-24T?>?A) in intron 2 of PLS3 on Xq23. The mutation, confirmed by Sanger sequencing, segregated according to the skeletal phenotype. The mutation introduces a new acceptor splice site with a predicted splice score of 0.99 and thereby, as confirmed by cDNA sequencing, induces the insertion of 22 bases between exons 2 and 3, causing a frameshift and premature termination of mRNA translation (p.Asp25Alafs*17). The mutation affects the first N-terminal calcium-binding EF-hand domain and abolishes all calcium- and actin-binding domains of the protein. Our results confirm the role of PLS3 mutations in early-onset osteoporosis. The mechanism whereby PLS3 affects bone health is unclear, but it may be linked to osteocyte dendrite function and skeletal mechanosensing. Future studies are needed to elucidate the role of PLS3 in osteoporosis and to define optimal treatment. © 2014 American Society for Bone and Mineral Research. PMID:25209159

Laine, Christine M; Wessman, Maija; Toiviainen-Salo, Sanna; Kaunisto, Mari A; Mäyränpää, Mervi K; Laine, Tero; Pekkinen, Minna; Kröger, Heikki; Välimäki, Ville-Valtteri; Välimäki, Matti J; Lehesjoki, Anna-Elina; Mäkitie, Outi

2014-09-10

259

Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia  

PubMed Central

Neurodevelopmental models for the pathology of schizophrenia propose both polygenetic and environmental risks, as well as early (pre/perinatal) and late (usually adolescent) developmental brain abnormalities. With the use of brain mapping algorithms, we detected striking anatomical profiles of accelerated gray matter loss in very early-onset schizophrenia; surprisingly, deficits moved in a dynamic pattern, enveloping increasing amounts of cortex throughout adolescence. Early-onset patients were rescanned prospectively with MRI, at 2-year intervals at three time points, to uncover the dynamics and timing of disease progression during adolescence. The earliest deficits were found in parietal brain regions, supporting visuospatial and associative thinking, where adult deficits are known to be mediated by environmental (nongenetic) factors. Over 5 years, these deficits progressed anteriorly into temporal lobes, engulfing sensorimotor and dorsolateral prefrontal cortices, and frontal eye fields. These emerging patterns correlated with psychotic symptom severity and mirrored the neuromotor, auditory, visual search, and frontal executive impairments in the disease. In temporal regions, gray matter loss was completely absent early in the disease but became pervasive later. Only the latest changes included dorsolateral prefrontal cortex and superior temporal gyri, deficit regions found consistently in adult studies. These emerging dynamic patterns were (i) controlled for medication and IQ effects, (ii) replicated in independent groups of males and females, and (iii) charted in individuals and groups. The resulting mapping strategy reveals a shifting pattern of tissue loss in schizophrenia. Aspects of the anatomy and dynamics of disease are uncovered, in a changing profile that implicates genetic and nongenetic patterns of deficits. PMID:11573002

Thompson, Paul M.; Vidal, Christine; Giedd, Jay N.; Gochman, Peter; Blumenthal, Jonathan; Nicolson, Robert; Toga, Arthur W.; Rapoport, Judith L.

2001-01-01

260

Diaphragm muscle weakness in mice is early-onset post-myocardial infarction and associated with elevated protein oxidation.  

PubMed

Heart failure induced by myocardial infarction (MI) causes diaphragm muscle weakness, with elevated oxidants implicated. We aimed to determine whether diaphragm muscle weakness is 1) early-onset post-MI (i.e., within the early left ventricular remodeling phase of 72 h); and 2) associated with elevated protein oxidation. Ligation of the left coronary artery to induce MI (n = 10) or sham operation (n = 10) was performed on C57BL6 mice. In vitro contractile function of diaphragm muscle fiber bundles was assessed 72 h later. Diaphragm mRNA and protein expression, enzyme activity, and individual carbonylated proteins (by two-dimensional differential in-gel electrophoresis and mass spectrometry) were subsequently assessed. Infarct size averaged 57 ± 1%. Maximal diaphragm function was reduced (P < 0.01) by 20% post-MI, with the force-frequency relationship depressed (P < 0.01) between 80 and 300 Hz. The mRNA expression of inflammation, atrophy, and regulatory Ca(2+) proteins remained unchanged post-MI, as did the protein expression of key contractile proteins. However, enzyme activity of the oxidative sources NADPH oxidase and xanthine oxidase was increased (P < 0.01) by 45 and 33%, respectively. Compared with sham, a 57 and 45% increase (P < 0.05) was observed in the carbonylation of sarcomeric actin and creatine kinase post-MI, respectively. In conclusion, diaphragm muscle weakness was rapidly induced in mice during the early left ventricular remodeling phase of 72 h post-MI, which was associated with increased oxidation of contractile and energetic proteins. Collectively, these findings suggest diaphragm muscle weakness may be early onset in heart failure, which is likely mediated in part by posttranslational oxidative modifications at the myofibrillar level. PMID:25359720

Scott Bowen, T; Mangner, Norman; Werner, Sarah; Glaser, Stefanie; Kullnick, Yvonne; Schrepper, Andrea; Doenst, Torsten; Oberbach, Andreas; Linke, Axel; Steil, Leif; Schuler, Gerhard; Adams, Volker

2015-01-01

261

Structural variations in articular cartilage matrix are associated with early-onset osteoarthritis in the spondyloepiphyseal dysplasia congenita (sedc) mouse.  

PubMed

Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+) mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA). We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc) mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA. Mutant sedc/sedc, and control (+/+) cartilages were compared at two, six and nine months of age. Tissues were fixed, decalcified, processed to paraffin sections, and stained with hematoxylin/eosin and safranin O/fast green. Samples were analyzed under the light microscope and the modified Mankin and OARSI scoring system was used to quantify the OA-like changes. Knees were stained with 1C10 antibody to detect the presence and distribution of type II collagen. Electron microscopy was used to study chondrocyte morphology and collagen fibril diameter. Compared with controls, mutant articular cartilage displayed decreased fibril diameter concomitant with increases in size of the pericellular space, Mankin and OARSI scores, cartilage thickness, chondrocyte clustering, proteoglycan staining and horizontal fissuring. In conclusion, homozygous sedc mice are subject to early-onset knee OA. We conclude that collagen in the mutant's articular cartilage (both heterozygote and homozygote) fails to provide the normal meshwork required for matrix integrity and overall cartilage stability. PMID:23939426

Macdonald, David W; Squires, Ryan S; Avery, Shaela A; Adams, Jason; Baker, Melissa; Cunningham, Christopher R; Heimann, Nicholas B; Kooyman, David L; Seegmiller, Robert E

2013-01-01

262

Structural Variations in Articular Cartilage Matrix Are Associated with Early-Onset Osteoarthritis in the Spondyloepiphyseal Dysplasia Congenita (Sedc) Mouse  

PubMed Central

Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+) mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA). We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc) mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA. Mutant sedc/sedc, and control (+/+) cartilages were compared at two, six and nine months of age. Tissues were fixed, decalcified, processed to paraffin sections, and stained with hematoxylin/eosin and safranin O/fast green. Samples were analyzed under the light microscope and the modified Mankin and OARSI scoring system was used to quantify the OA-like changes. Knees were stained with 1C10 antibody to detect the presence and distribution of type II collagen. Electron microscopy was used to study chondrocyte morphology and collagen fibril diameter. Compared with controls, mutant articular cartilage displayed decreased fibril diameter concomitant with increases in size of the pericellular space, Mankin and OARSI scores, cartilage thickness, chondrocyte clustering, proteoglycan staining and horizontal fissuring. In conclusion, homozygous sedc mice are subject to early-onset knee OA. We conclude that collagen in the mutant’s articular cartilage (both heterozygote and homozygote) fails to provide the normal meshwork required for matrix integrity and overall cartilage stability. PMID:23939426

Macdonald, David W.; Squires, Ryan S.; Avery, Shaela A.; Adams, Jason; Baker, Melissa; Cunningham, Christopher R.; Heimann, Nicholas B.; Kooyman, David L.; Seegmiller, Robert E.

2013-01-01

263

ATM germline mutations in Spanish early-onset breast cancer patients negative for BRCA1/BRCA2 mutations.  

PubMed

Heterozygous carriers of ATM (ataxia telangiectasia mutated gene) mutations have increased risk of breast cancer (BC). We have estimated the prevalence of mutations in the ATM gene among Spanish patients with early-onset BC. Forty-three patients diagnosed with BC before the age of 46 years, and negative for BRCA1 and BRCA2 mutations, were analysed for the presence of ATM mutations. A total of 34 ATM sequence variants were detected: 1 deleterious mutation, 10 unclassified variants and 23 polymorphisms. One patient (2.3%) carried the ATM deleterious mutation (3802delG that causes ataxia telangiectasia in the homozygous state) and 13 patients carried the 10 ATM unclassified variants. The truncating mutation 3802delG and eight of the rare variants were not detected in a control group of 150 individuals. Different bioinformatic sequence analysis tools were used to evaluate the effects of the unclassified ATM changes on RNA splicing and function protein. This in silico analysis predicted that the missense variants 7653 T>C and 8156 G>A could alter the splicing by disrupting an exonic splicing enhancer motif and the 3763 T>G, 6314 G>C, and 8156 G>A variants would affect the ATM protein function. These are the initial results concerning the prevalence of germline mutations in the ATM gene among BC cases in a Spanish population, and they suggest that ATM mutations can confer increased susceptibility to early-onset BC. PMID:18384426

Brunet, J; Gutiérrez-Enríquez, S; Torres, A; Bérez, V; Sanjosé, S; Galceran, J; Izquierdo, A; Menéndez, J A; Gumà, J; Borràs, J

2008-05-01

264

Periodontal Plastic Surgery  

MedlinePLUS

Periodontal plastic surgery is designed to restore form and function to the gum tissue, periodontal ligament, and the bone that supports your teeth ... tooth. The real long-term goal of any periodontal surgery is to increase the life expectancy of ...

265

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

266

IQCB1 and PDE6B Mutations Cause Similar Early Onset Retinal Degenerations in Two Closely Related Terrier Dog Breeds  

PubMed Central

Purpose. To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively. Methods. Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the “MAGIC” genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease. Results. Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs. Conclusions. Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases. PMID:24045995

Goldstein, Orly; Mezey, Jason G.; Schweitzer, Peter A.; Boyko, Adam R.; Gao, Chuan; Bustamante, Carlos D.; Jordan, Julie Ann; Aguirre, Gustavo D.; Acland, Gregory M.

2013-01-01

267

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

268

The Lambeth Early Onset (LEO) Team: randomised controlled trial of the effectiveness of specialised care for early psychosis  

Microsoft Academic Search

Objective To evaluate the effectiveness of a service for early psychosis. Design Randomised controlled clinical trial. Setting Community mental health teams in one London borough. Participants 144 people aged 16-40 years presenting to mental health services for the first or second time with non-organic, non-affective psychosis. Interventions Assertive outreach with evidence based biopsychosocial interventions (specialised care group) and standard care

Tom K J Craig; Philippa Garety; Paddy Power; Nikola Rahaman; Susannah Colbert; Miriam Fornells-Ambrojo; Graham Dunn

2004-01-01

269

Microflora and periodontal disease  

PubMed Central

Background: Periodontitis is a disease that affects and destroys the tissues that support teeth. Tissue damage results from a prolonged inflammatory response to an ecological shift in the composition of subgingival biofilms. Three bacterial species that constitute the red complex group, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, are considered the main pathogens involved in periodontitis. Materials and Methods: In the present study, a real-time polymerase chain reaction bases assay was designed to detect and quantify red complex species, then used to investigate 307 periodontal pocket samples from 127 periodontitis patients and 180 controls. Results: Significant higher prevalence of red complex species and increased amount of P. gingivalis and T. denticola were detected in periodontal pocket of periodontitis patients. Conclusions: Results demonstrated that the test is a valuable tool to improve diagnosis of periodontal disease. PMID:23814584

Scapoli, Luca; Girardi, Ambra; Palmieri, Annalisa; Testori, Tiziano; Zuffetti, Francesco; Monguzzi, Riccardo; Lauritano, Dorina; Carinci, Francesco

2012-01-01

270

Periodontal Proteomics: Wonders Never Cease!  

PubMed Central

Proteins are vital parts of living organisms, as they are integral components of the physiological metabolic pathways of cells. Periodontal tissues comprise multicompartmental groups of interacting cells and matrices that provide continuous support, attachment, proprioception, and physical protection for the teeth. The proteome map, that is, complete catalogue of the matrix and cellular proteins expressed in alveolar bone, cementum, periodontal ligament, and gingiva, is to be explored for more in-depth understanding of periodontium. The ongoing research to understand the signalling pathways that allow cells to divide, differentiate, and die in controlled manner has brought us to the era of proteomics. Proteomics is defined as the study of all proteins including their relative abundance, distribution, posttranslational modifications, functions, and interactions with other macromolecules, in a given cell or organism within a given environment and at a specific stage in the cell cycle. Its application to periodontal science can be used to monitor health status, disease onset, treatment response, and outcome. Proteomics can offer answers to critical, unresolved questions such as the biological basis for the heterogeneity in gingival, alveolar bone, and cemental cell populations. PMID:24490073

Grover, Harpreet Singh; Kapoor, Shalini; Saksena, Neha

2013-01-01

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

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

273

Sensitive pupil response of early-onset alzheimer’s patients to a dilute mixture of cholinergic antagonist and ?-Adrenergic stimulant  

Microsoft Academic Search

To investigate possible differences in pupil dilation and light reflex in Alzheimer’s disease patients that can be attributed\\u000a to the age of onset of the disease, a statistical comparison was made of pupil dilation and light reflex among early- and\\u000a late-onset Alzheimer’s disease, Down syndrome, and patients with vascular dementia, and normal controls. The subjects included\\u000a 53 probable Alzheimer’s disease

Ayumi Takagi; Masaru Miyao; Shin’ya Ishihara; Hisataka Sakakibara; Takaaki Kondo; Hideaki Toyoshima; Kazuhiko Kono; Akihisa Iguchi

1999-01-01

274

Apolipoprotein E genotype and neuropathological phenotype in two members of a German family with chromosome 14-linked early onset Alzheimer's disease  

Microsoft Academic Search

Molecular genetic analysis was performed in two autopsy-confirmed cases of early-onset Alzheimer's disease belonging to a large German pedigree [FAD2, according to the nomenclature of St. George-Hyslop, et al. (1987) Science 235:885–890]. The disease in this family has been linked to chromosome 14. As gene interactions are considered to influence the age of onset and tissue pathology in Alzheimer's disease,

R. Egensperger; S. Kösel; R. Schnabel; P. Mehraein; M. B. Graeber

1995-01-01

275

Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases  

SciTech Connect

Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ({le}age 60 years) AD (EOAD) probands has been carried out, allowing for a mixture in AD inheritance among probands. The goal was to quantify the proportion of probands that could be explained by autosomal inheritance of a rare disease allele {open_quotes}a{close_quotes} at a Mendelian dominant gene (MDG). Our data provide strong evidence for a mixture of two distributions; AD transmission is fully explained by MDG inheritance in <20% of probands. Male and female age-of-onset distributions are significantly different for {open_quotes}AA{close_quote} but not for {open_quotes}aA{close_quote} subjects. For {open_quotes}aA{close_quote} subjects the estimated penetrance value was close to 1 by age 60. For {open_quotes}AA{close_quotes} subjects, it reaches, by age 90, 10% (males) and 30% (females). We show a clear cutoff in the posterior probability of being an MDG case. 10 refs., 1 tab.

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

1996-02-16

276

Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis.  

PubMed

Blau syndrome (BS) and early onset sarcoidosis (EOS) are, respectively, the familial and sporadic forms of the pediatric granulomatous autoinflammatory disease, which belong to the group of monogenic autoinflammatory syndromes. Both of these conditions are caused by mutations in the NOD2 gene, which encodes the cytosolic NOD2 protein, one of the pivotal molecules in the regulation of innate immunity, primarily expressed in the antigen-presenting cells. Clinical onset of BS and EOS is usually in the first years of life with noncaseating epithelioid granulomas mainly affecting joints, skin, and uveal tract, variably associated with heterogeneous systemic features. The dividing line between autoinflammatory and autoimmune mechanisms is probably not so clear-cut, and the relationship existing between BS or EOS and autoimmune phenomena remains unclear. There is no established therapy for the management of BS and EOS, and the main treatment aim is to prevent ocular manifestations entailing the risk of potential blindness and to avoid joint deformities. Nonsteroidal anti-inflammatory drugs, corticosteroids and immunosuppressive drugs, such as methotrexate or azathioprine, may be helpful; when patients are unresponsive to the combination of corticosteroids and immunosuppressant agents, the tumor necrosis factor-? inhibitor infliximab should be considered. Data on anti-interleukin-1 inhibition with anakinra and canakinumab is still limited and further corroboration is required. The aim of this paper is to describe BS and EOS, focusing on their genetic, clinical, and therapeutic issues, with the ultimate goal of increasing clinicians' awareness of both of these rare but serious disorders. PMID:25182201

Caso, Francesco; Costa, Luisa; Rigante, Donato; Vitale, Antonio; Cimaz, Rolando; Lucherini, Orso Maria; Sfriso, Paolo; Verrecchia, Elena; Tognon, Sofia; Bascherini, Vittoria; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

2014-12-01

277

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

278

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

Microsoft Academic Search

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

Ripon Paul; Isaac N. Pessah; Louise Gane; Michele Ono; Paul J. Hagerman; James A. Brunberg; Flora Tassone; James A. Bourgeois; Patrick E. Adams; Danh V. Nguyen; Randi Hagerman

2010-01-01

279

A pilot genome-wide association study of early-onset breast cancer  

Microsoft Academic Search

High-density oligonucleotide microarrays containing a large number of single nucleotide polymorphisms (SNPs) have enabled\\u000a genome-wide association (GWA) analysis to become a reality. We used the early access Affymetrix Mendel Nsp 250K chips in a\\u000a GWA case–control pilot study to identify genomic regions associated with breast cancer. We included 30 randomly sampled incident\\u000a invasive breast cancer cases aged <45 years without deleterious

Muhammad G. Kibriya; Farzana Jasmine; Maria Argos; Irene L. Andrulis; Esther M. John; Jenny Chang-Claude; Habibul Ahsan

2009-01-01

280

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; Näslund, Jan; Axelman, Karin; Bird, Thomas D.; Nochlin, David; Schellenberg, Gerard D.; Wahlund, Lars-Olof; Lannfelt, Lars

2009-01-01

281

STAT3? controls inflammatory responses and early tumor onset in skin and colon experimental cancer models  

PubMed Central

Chronic inflammation is a well-recognized pathogenic factor in tumor initiation and progression. Mice lacking the pro-oncogenic transcription factor STAT3 were shown to be protected from both colitis-associated and epidermal cancers induced by the AOM/DSS and DMBA/TPA protocols, respectively. However, these murine models did not distinguish between the two STAT3 isoforms, the full-length STAT3?, believed to exert most pro-oncogenic functions attributed to STAT3, and the shorter STAT3?, often referred to as a dominant-negative, but possessing specific transcriptional activities. Here we assessed the contribution of STAT3? to inflammation-driven tumorigenesis making use of mice lacking this isoform, but still expressing STAT3? (STAT3??/??). We show that the lack of STAT3? leads to exacerbated acute responses to both TPA and DSS, thus confirming its anti-inflammatory role. Enhanced inflammation correlates with earlier tumor onset in both the epidermis and the intestine in STAT3??/?? mice. In contrast, overall tumor development and final tumor burden were unaffected. These results suggest that STAT3?, by limiting inflammation during the initial phases of tumorigenesis, contributes to tissue homeostasis and counteracts malignant transformation and initial tumor growth. Accordingly, the balance between the two STAT3 isoforms, likely determined by the complex signaling networks shaping the tumor microenvironment and driving tumor transformation and progression, is apparently crucial to determine the initial tumor transformation rates in inflammation-associated cancers. PMID:25232490

Marino, Francesca; Orecchia, Valeria; Regis, Gabriella; Musteanu, Monica; Tassone, Beatrice; Jon, Cristina; Forni, Marco; Calautti, Enzo; Chiarle, Roberto; Eferl, Robert; Poli, Valeria

2014-01-01

282

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

283

Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat.  

PubMed

Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a trinucleotide (CAG) repeat expansion in the androgen receptor gene. Patients with SBMA have weakness, atrophy, and fasciculations in the bulbar and extremity muscles. Individuals with CAG repeat lengths greater than 62 have not previously been reported. We evaluated a 29year old SBMA patient with 68 CAGs who had unusually early onset and findings not seen in others with the disease. Analysis of the androgen receptor gene confirmed the repeat length of 68 CAGs in both peripheral blood and fibroblasts. Evaluation of muscle and sensory function showed deficits typical of SBMA, and in addition the patient had manifestations of autonomic dysfunction and abnormal sexual development. These findings extend the known phenotype associated with SBMA and shed new insight into the effects of the mutated androgen receptor. PMID:25047668

Grunseich, Christopher; Kats, Ilona R; Bott, Laura C; Rinaldi, Carlo; Kokkinis, Angela; Fox, Derrick; Chen, Ke-Lian; Schindler, Alice B; Mankodi, Ami K; Shrader, Joseph A; Schwartz, Daniel P; Lehky, Tanya J; Liu, Chia-Ying; Fischbeck, Kenneth H

2014-11-01

284

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

285

High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population  

PubMed Central

Background CRB1 mutations are reported as cause of severe congenital and early-onset retinal dystrophies (EORD) with different phenotypic manifestations, including Leber congenital amaurosis (LCA), retinitis pigmentosa (RP) and cone-rod dystrophies. Comprehensive mutational scanning of the whole gene has been only performed in few cohorts, mainly in LCA patients. Here, we aimed investigating the real prevalence of CRB1 mutations in the Spanish population by extensive screening of CRB1 mutations in a large cohort of LCA and EORP cases. Methods This report integrates data from previous studies on CRB1 defects in our Spanish cohort of LCA and early-onset RP (EORP) with new findings from a comprehensive mutational screening of the whole gene. The molecular tools used include mutation genotyping arrays, whole-genome homozygosity mapping, an optimized high-resolution melting (HRM) analysis and Sanger sequencing. Results A large clinically well-characterized cohort of 404 Spanish cases was studied, 114 of which suffered from LCA and 290 from EORP. This study reveals that 11% of Spanish patients carried mutations in CRB1, ranging from 9% of EORP to 14% of LCA cases. More than three quarters of the mutations identified herein have been first described in this Spanish cohort, 13 of them are unreported new variants and 13 had been previously reported in our previous studies. Conclusions This work provides a wide spectrum of CRB1 mutations in the Spanish EORD patients and evidences the major role of CRB1 as causal gene in the Spanish EORP patients. It is noteworthy that a high rate of private mutations only described in our cohort has been found so far. To our knowledge, this study represents the most complete mutational screening of CRB1 in a Spanish LCA and EORP cohort, allowing us to establish gene-specific frequencies and to provide a wide spectrum of CRB1 mutations in the Spanish population. PMID:23379534

2013-01-01

286

The early-onset torsion dystonia-associated protein, torsinA, displays molecular chaperone activity in vitro  

PubMed Central

TorsinA is a member of the AAA+ ATPase family of proteins and, notably, is the only known ATPase localized to the ER lumen. It has been suggested to act as a molecular chaperone, while a mutant form associated with early-onset torsion dystonia, a dominantly inherited movement disorder, appears to result in a net loss of function in vivo. Thus far, no studies have examined the chaperone activity of torsinA in vitro. Here we expressed and purified both wild-type (WT) and mutant torsinA fusion proteins in bacteria and examined their ability to function as molecular chaperones by monitoring suppression of luciferase and citrate synthase (CS) aggregation. We also assessed their ability to hold proteins in an intermediate state for refolding. As measured by light scattering and SDS-PAGE, both WT and mutant torsinA effectively, and similarly, suppressed protein aggregation compared to controls. This function was not further enhanced by the presence of ATP. Further, we found that while neither form of torsinA could protect CS from heat-induced inactivation, they were both able to reactivate luciferase when ATP and rabbit reticulocyte lysate were added. This suggests that torsinA holds luciferase in an intermediate state, which can then be refolded in the presence of other chaperones. These data provide conclusive evidence that torsinA acts as a molecular chaperone in vitro and suggests that early-onset torsion dystonia is likely not a consequence of a loss in torsinA chaperone activity but might be an outcome of insufficient torsinA localization at the ER to manage protein folding or trafficking. PMID:20169475

Burdette, Alexander J.; Churchill, Perry F.; Caldwell, Guy A.

2010-01-01

287

Mutations in RAB39B Cause X-Linked Intellectual Disability and Early-Onset Parkinson Disease with ?-Synuclein Pathology.  

PubMed

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ?45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of ?-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of ?-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of ?-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders. PMID:25434005

Wilson, Gabrielle R; Sim, Joe C H; McLean, Catriona; Giannandrea, Maila; Galea, Charles A; Riseley, Jessica R; Stephenson, Sarah E M; Fitzpatrick, Elizabeth; Haas, Stefan A; Pope, Kate; Hogan, Kirk J; Gregg, Ronald G; Bromhead, Catherine J; Wargowski, David S; Lawrence, Christopher H; James, Paul A; Churchyard, Andrew; Gao, Yujing; Phelan, Dean G; Gillies, Greta; Salce, Nicholas; Stanford, Lynn; Marsh, Ashley P L; Mignogna, Maria L; Hayflick, Susan J; Leventer, Richard J; Delatycki, Martin B; Mellick, George D; Kalscheuer, Vera M; D'Adamo, Patrizia; Bahlo, Melanie; Amor, David J; Lockhart, Paul J

2014-12-01

288

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

289

Spatial learning deficits without hippocampal neuronal loss in a model of early-onset epilepsy.  

PubMed

Studies were undertaken to examine the effects recurrent early-life seizures have on the ability of rats to acquire spatial memories in adulthood. A minute quantity of tetanus toxin was injected unilaterally into the hippocampus on postnatal day 10. Within 48 h, rats developed recurrent seizures that persisted for 1 week. Between postnatal days 57 and 61, rats were trained in a Morris water maze. Toxin-injected rats were markedly deficient in learning this task. While these rats showed gradual improvement in escape latencies over 20 trials, their performance always lagged behind that of controls. Poor performance could not be explained by motor impairments or motivational difficulties since swimming speed was similar for the groups. Only eight of 16 toxin-injected animals showed focal interictal spikes in the hippocampus during electroencephalographic recordings. This suggests that learning deficiencies and chronic epilepsy may be independent products of recurrent early-life seizures. A quantitative analysis of hippocampus revealed a significant decrease in neuronal density in stratum pyramidale of experimental rats. However, the differences were largely explained by a concomitant increase in the area of stratum pyramidale. Studies of glial fibrillary acidic protein expression and spread of horseradish peroxidase-conjugated tetanus toxin in the hippocampus suggest that the dispersion of cell bodies in stratum pyramidale can neither be explained by a reactive gliosis nor the direct action of the toxin itself. Taken together, we suggest that recurrent seizures beginning in early life can lead to a significant deficiency in spatial learning without ongoing hippocampal synchronized network discharging or a substantial loss of hippocampal pyramidal cells. PMID:11744248

Lee, C L; Hannay, J; Hrachovy, R; Rashid, S; Antalffy, B; Swann, J W

2001-01-01

290

Early to mid Cretaceous vegetation of northern Gondwana - the onset of angiosperm radiation and climatic implications  

NASA Astrophysics Data System (ADS)

Early Cretaceous Northern Gondwana seems to be the cradle of many early flowering plants, especially mesangiosperms that include magnoliids and monocots and basal eudicots. So far our knowledge was based mostly on dispersed pollen and small flowering structures. New fossil finds from Brazil include more complete plants with attached roots, leaves and flowers. Taxonomic studies show that these fossils belonged to clades which are, based on macroscopic characters and molecular data, also considered to be rather basal, such as several members of Nymphaeales, Piperales, Laurales, Magnoliales, monocots (Araliaceae) and Ranunculales. Various parameters can be used in order to understand the physiology and habitat of these plants. Adaptations to climate and habitat are partly mirrored in their root anatomy (evidence of tap roots), leaf size and shape, leaf anatomy including presence of glands, and distribution of stomata. An important ecophysiolocical parameter is vein density as an indicator for the plants' cabability to pump water, and the stomatal pore index, representing the proportion of stomatal pore area on the leaf surface, which is related to the water vapor resistance of the leaf epidermis. During the mid-Cretaceous leaf vein density started to surpass that of gymnosperms, one factor that made angiosperms very successful in conquering many kinds of new environments. Using data on these parameters we deduce that during the late Early to mid Cretaceous angiosperms were already diverse, being represented as both herbs, with aquatic members, such as Nymphaeles, helophytes (e.g. some monocots) and plants that may have grown in shady locations. Other life forms included shrubs and perhaps already small trees (e.g. Magnoliales). These flowering plants occupied various habitats, ranging from xeric (e.g. some Magnoliales) to mesic and shady (e.g. Piperales) or aquatic (e.g. Araceae, Nymphaeales). Overall, it seems that several of these plants clearly exhibited some mechanisms to withstand drought, which in turn let us assume that the climate was characterized by dry and wet seasons.

Coiffard, Clément; Mohr, Barbara

2014-05-01

291

Hypoalbuminemia in early onset dentatorubral-pallidoluysian atrophy due to leakage of albumin in multiple organs.  

PubMed

We delineate a complication of hypoalbuminemia in dentatorubral-pallidoluysian atrophy (DRPLA), which we have found to be common in this disorder. In addition, we explored the pathogenesis of this phenomenon through clinical and histological examinations. Clinical course and laboratory findings of nine patients with childhood-onset DRPLA (aged 6-49 years; CAG repeat length 62-93) were retrospectively reviewed. Autopsied specimens from three patients were examined by histopathological and immunohistochemical analyses. Eight DRPLA patients showed hypoalbuminemia <3.5 g/dl in the initial stages of the disease (age, 2-32 years), which correlated with the CAG repeat length in each patient. Disease worsened in six patients, often triggered by febrile infections and accompanied by increased urinary protein excretion. One patient showed increased fecal ?1-antitripsin while another showed accumulation of radioactive albumin in the urinary and gastrointestinal tracts after intravenous infusion. Immunohistochemistry revealed albumin-containing monocytes and astrocytes in the perivascular areas of the cerebral white matter. Fluid collection in the glomerular capillaries was noted. Immunolabeling using antibodies against the expanded polyglutamine (polyQ) polypeptide was positive in cerebral cortical neurons, hepatocytes, renal collecting ducts, and glomerular podocytes, which act as filtration barrier against serum proteins. Serum albumin appears to easily leak from blood vessels in certain visceral organs in DRPLA during later stages of the illness, particularly in the kidneys of patients with largely expanded CAG repeats. We hypothesize that the accumulation of the DRPLA gene product with expanded polyQ sequences in the podocytes results in the dysfunction of the glomerular filtration barrier. PMID:23263592

Nagai, Shigehiro; Saito, Yoshiaki; Endo, Yukari; Saito, Takashi; Sugai, Kenji; Ishiyama, Akihiko; Komaki, Hirofumi; Nakagawa, Eiji; Sasaki, Masayuki; Ito, Kimiteru; Saito, Yuko; Sukigara, Sayuri; Ito, Masayuki; Goto, Yu-Ichi; Ito, Shuichi; Matsuoka, Kentaro

2013-05-01

292

The ReSTAGE Collaboration: Defining Optimal Bleeding Criteria for Onset of Early Menopausal Transition  

PubMed Central

Study objective Criteria for staging the menopausal transition are not established. This paper evaluates five bleeding criteria for defining early transition and provides empirically-based guidance regarding optimal criteria. Design/Setting Prospective menstrual calendar data from four population-based cohorts: TREMIN, Melbourne Women’s Midlife Health Project(MWMHP), Seattle Midlife Women’s Health Study(SMWHS), and Study of Women’s Health Across the Nation(SWAN) with annual serum follicle stimulating hormone (FSH) from MWMHP and SWAN. Participants 735 TREMIN, 279 SMWHS, 216 MWMHP, and 2270 SWAN women aged 35-57 at baseline who maintained menstrual calendars. Main outcome measure(s) Age at and time to menopause for: standard deviation >6 and >8 days, persistent difference in consecutive segments >6 days, irregularity, and >=45 day segment. Serum follicle stimulating hormone concentration. Results Most women experienced each of the bleeding criteria. Except for persistent >6 day difference which occurs earlier, the criteria occur at a similar age and at approximately the same age as late transition in a large proportion of women. FSH was associated with all proposed markers. Conclusions The early transition may be best described by ovarian activity consistent with the persistent >6 day difference, but further study is needed, as other proposed criterion are consistent with later menstrual changes. PMID:17681300

Harlow, Siobán D.; Mitchell, Ellen S.; Crawford, Sybil; Nan, Bin; Little, Roderick; Taffe, John

2008-01-01

293

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

294

Renal cell carcinoma in India demonstrates early age of onset & a late stage of presentation  

PubMed Central

Background & objectives: Clinical spectrum of most of the diseases in developing countries is different from the west. Similarly whether renal cell carcinomas (RCC) in a developing country like India is seen in the same spectrum in relation to the age at presentation as in the west is not described in the literature. This study was carried out to investigate the spectrum of RCC in India with regards to age of onset, stage at presentation and survival. Methods: Patients with renal tumour, treated between January 2000 to December 2012 in a tertiary care hospital in north India, were analyzed for age at presentation, clinical features and histopathological characteristics. Clinical diagnosis was made by contrast enhanced computerized tomography (CECT) scans and/or magnetic resonance imaging (MRI). Renal masses diagnosed as angiomyolipoma, infective masses and hydatid cysts were excluded from the analysis. Impact of various age groups on gender, tumour size, TNM stage, Fuhrman grade, histopathological subtypes, lymph node, inferior vena cava (IVC) involvement and survival was analyzed. Patients were grouped in five age groups i.e. ?39, 40-49, 50-59, 60-69 and more than 70 yr of age. Results: Of the total 617 patients with 617 renal tumours (2 patients had bilateral tumours but only the larger tumour was considered) clinically suspected as RCC, 586 had epithelial cell tumour and the remaining 31 had non epithelial cell tumour. The mean tumour size was 8.08±3.5 cm (median 7, range 1-25 cm). Tumour of less than 4 cm size was present in only 10.4 per cent patients. The mean age at diagnosis was 55.15±13.34 (median 56, range 14-91 yr) years. A total of 30.03 per cent of renal tumours presented in patients younger than 50 yr of age. Though there was no difference in stage, Fuhrman's grade, IVC involvement and lymph nodal spread among various age groups, younger patients had higher proportion of non clear cell RCC and only 48.59 per cent of them presented with conventional RCC. Mean survival was lower in patients younger than 39 yr with HR of 1.7 (0.8-3.2). Interpretation & conclusion: Our results showed that renal cell carcinoma was more frequent in younger people in India. One third of the patients were less than 50 yr of age and only 10.4 per cent patients had tumour of less than 4 cm (T1a). Younger patients of <39 yr of age had relatively lower survival rates. PMID:25579143

Agnihotri, Shalini; Kumar, Jatinder; Jain, Manoj; Kapoor, Rakesh; Mandhani, Anil

2014-01-01

295

Early Onset of Ground State Deformation in Neutron Deficient Polonium Isotopes  

E-print Network

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 (6)p(3)7p (5)P(2) (lambda = 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.

Cocolios, T E; Andreyev, A N; Antalic, S; Barzakh, A E; Bastin, B; Buscher, J; Darby, I G; Fedorov, D V; Fedosseyev, V N; Flanagan, K T; Franchoo, S; Fritzsche, S; Huber, G; Huyse, M; Keupers, M; Koster, U; Kudryavtsev, Yu; Mane, 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

2011-01-01

296

Early onset of ground-state deformation in the neutron-deficient polonium isotopes  

E-print Network

In-source resonant ionization laser spectroscopy of the even-$A$ polonium isotopes $^{192-210,216,218}$Po has been performed using the $6p^37s$ $^5S_2$ to $6p^37p$ $^5P_2$ ($\\lambda=843.38$ 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 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.

Cocolios, T E; Seliverstov, M D; Andreyev, A N; Antalic, S; Barzakh, A E; Bastin, B; Buscher, J; Darby, I G; Fedorov, D V; Fedosseyev, V N; Flanagan, K T; Franchoo, S; Fritzsche, S; Huber, G; Huyse, M; Keupers, M; Koster, U; Kudryavtsev, Yu; Mane, 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

2010-01-01

297

Early Onset of Ground State Deformation in Neutron Deficient Polonium Isotopes  

SciTech Connect

In-source resonant ionization laser spectroscopy of the even-A polonium isotopes {sup 192-210,216,218}Po has been performed using the 6p{sup 3}7s {sup 5}S{sub 2} to 6p{sup 3}7p {sup 5}P{sub 2} ({lambda}=843.38 nm) transition in the polonium atom (Po-I) at the CERN ISOLDE facility. The comparison of the measured isotope shifts in {sup 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.

Cocolios, T. E.; Van de Walle, J. [Instituut voor Kern- en Stralingsfysica, K.U. Leuven, B-3001 Leuven (Belgium); ISOLDE, CERN, CH-1211 Geneva 23 (Switzerland); Dexters, W.; Bastin, B.; Buescher, J.; Darby, I. G.; Huyse, M.; Keupers, M.; Kudryavtsev, Yu.; Van Duppen, P. [Instituut voor Kern- en Stralingsfysica, K.U. Leuven, B-3001 Leuven (Belgium); Seliverstov, M. D. [Instituut voor Kern- en Stralingsfysica, K.U. Leuven, B-3001 Leuven (Belgium); Petersburg Nuclear Physics Institute, 188350 Gatchina (Russian Federation); Institut fuer Physik, Johannes Gutenberg Universitaet, D-55099 Mainz (Germany); Andreyev, A. N. [Instituut voor Kern- en Stralingsfysica, K.U. Leuven, B-3001 Leuven (Belgium); School of Engineering and Science, University of West Scotland, Paisley, PA1 2BE (United Kingdom) and Scottish Universities Physics Alliance (SUPA) (United Kingdom); Antalic, S. [Department of Physics and Biophysics, Comenius University, Bratislava 842 48 (Slovakia); Barzakh, A. E.; Fedorov, D. V.; Molkanov, P. L. [Petersburg Nuclear Physics Institute, 188350 Gatchina (Russian Federation); Fedosseyev, V. N.; Marsh, B. A. [EN Department, CERN, CH-1211 Geneva 23 (Switzerland); Flanagan, K. T. [Department of Physics, University of Manchester, Manchester, M60 1AD (United Kingdom); Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse, F-91405 Orsay (France); Franchoo, S. [Institut de Physique Nucleaire d'Orsay, F-91406 Orsay (France)

2011-02-04

298

Early onset of ground-state deformation in the neutron-deficient polonium isotopes  

E-print Network

In-source resonant ionization laser spectroscopy of the even-$A$ polonium isotopes $^{192-210,216,218}$Po has been performed using the $6p^37s$ $^5S_2$ to $6p^37p$ $^5P_2$ ($\\lambda=843.38$ 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 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.

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

2010-10-11

299

Early Onset of Ground State Deformation in Neutron Deficient Polonium Isotopes  

NASA Astrophysics Data System (ADS)

In-source resonant ionization laser spectroscopy of the even-A polonium isotopes Po192-210,216,218 has been performed using the 6p37s S25 to 6p37p P25 (?=843.38nm) transition in the polonium atom (Po-I) at the CERN ISOLDE facility. The comparison of the measured isotope shifts in Po200-210 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.

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

300

The significant other history: an interpersonal-emotional history procedure used with the early-onset chronically depressed patient.  

PubMed

An interpersonal-emotional history procedure, the Significant Other History, is administered to the early-onset chronically depressed patient during the second therapy session in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP). Patients are asked to name up to six significant others and answer two questions: (1) What was it like growing up with or being around this person? (2) What is the emotional "stamp" you take from this relationship that informs who you are today? An interpersonal-emotional theme reflecting the early learning history of the patient is derived from these "stamps" or causal theory conclusions. One transference hypothesis (TH) is derived from the Significant Other History (SOH) and is formulated in one sentence, such as "If I do this, then the therapist will likely do that" (e.g., "If I make a mistake around Dr. E, then Dr. E will label me 'stupid' or 'incompetent"). The transference hypothesis highlights the interpersonal content that most likely informs the patient's expectancy of the therapist's reactions toward him or her. Throughout the therapy process, the therapist will proactively employ the transference hypothesis in a technique known as the Interpersonal Discrimination Exercise to help patients cognitively and emotionally discriminate the practitioner from hurtful significant others. The goal here is to increase the patient's felt safety within the therapeutic dyad and eventually to generalize the felt safety to the patient's other relationships. PMID:22032046

McCullough, James P; Lord, Benjamin D; Martin, Aaron M; Conley, Kathryn A; Schramm, Elisabeth; Klein, Daniel N

2011-01-01

301

Early onset of fatty liver in growth restricted rat fetuses and newborns  

PubMed Central

Intrauterine growth restricted (IUGR) newborns have increased risk of adult metabolic syndrome, including fatty liver. However, it is unclear whether the fatty liver development is “programmed” or secondary to the accompanying obesity. In this study, we examined hepatic lipid accumulation and lipid-regulatory factors (sterol regulatory element-binding protein-1c and fatty acid synthase) in IUGR and Control fetal (embryonic day 20; e20) and newborn (postnatal day 1; p1) rat pups. Notably, despite of in utero undernutrition state, IUGR fetuses demonstrated ‘fatty liver’ with upregulation of these lipogenic indices at as early as e20. Both IUGR and Control newborns exhibited the same extent of massive increase in hepatic lipid content whereas IUGR newborns continued to exhibit upregulated lipogenic indices. The persistent upregulation of the lipogenic indices in fetal and newborn IUGR suggests that fatty liver is gestationally programmed. Our study suggested that IUGR offspring were born with an altered metabolic life strategy of increased fuel/lipid storage which could be a distinct metabolic pathway of the thrifty phenotype. PMID:22103455

Yamada, Makiko; Wolfe, Diana; Han, Guang; French, Samuel W.; Ross, Michael G.; Desai, Mina

2011-01-01

302

Early-onset cortico-cortical synchronization in the hemiparkinsonian rat model.  

PubMed

Changes in synchronized neuronal oscillatory activity are reported in both cortex and basal ganglia of Parkinson's disease patients. The origin of these changes, in particular their relationship with the progressive nigrostriatal dopaminergic denervation, is unknown. Therefore, in the present study we studied interregional neuronal synchronization in motor cortex and basal ganglia during the development of dopaminergic degeneration induced by a unilateral infusion of 6-hydroxydopamine (6-OHDA) into the rat medial forebrain bundle. We performed serial local field potential recordings bilaterally in the motor cortex and the subthalamic nucleus of the lesioned hemisphere prior to, during, and after development of the nigrostriatal dopaminergic cell loss. We obtained signal from freely moving rats in both resting and walking conditions, and we computed local spectral power, interregional synchronization (using phase lag index), and directionality (using Granger causality). After neurotoxin injection the first change in phase lag index was an increment in cortico-cortical synchronization. We observed increased bidirectional Granger causality in the beta frequency band between cortex and subthalamic nucleus within the lesioned hemisphere. In the walking condition, the 6-OHDA lesion-induced changes in synchronization resembled that of the resting state, whereas the changes in Granger causality were less pronounced after the lesion. Considering the relatively preserved connectivity pattern of the cortex contralateral to the lesioned side and the early emergence of increased cortico-cortical synchronization during development of the 6-OHDA lesion, we suggest a putative compensatory role of cortico-cortical coupling. PMID:25392174

Jávor-Duray, B N; Vinck, M; van der Roest, M; Mulder, A B; Stam, C J; Berendse, H W; Voorn, P

2015-02-01

303

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

304

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

305

Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice.  

PubMed

Although the precise signaling mechanisms underlying the vulnerability of some sub-populations of motoneurons in ALS remain unclear, critical factors such as metallo-proteinase 9 expression, neuronal activity and endoplasmic reticulum stress have been shown to be involved. In the context of SOD1(G93A) ALS mouse model, we previously showed that a two-fold decrease in calreticulin (CRT) is occurring in the vulnerable fast motoneurons. Here, we asked to which extent the decrease in CRT levels was causative to muscle denervation and/or motoneuron degeneration. Toward this goal, a hemizygous deletion of the crt gene in SOD1(G93A) mice was generated since the complete ablation of crt is embryonic lethal. We observed that SOD1(G93A);crt(+/-) mice display increased and earlier muscle weakness and muscle denervation compared to SOD1(G93A) mice. While CRT reduction in motoneurons leads to a strong upregulation of two factors important in motoneuron dysfunction, ER stress and mTOR activation, it does not aggravate motoneuron death. Our results underline a prevalent role for CRT levels in the early phase of muscle denervation and support CRT regulation as a potential therapeutic approach. PMID:25277755

Bernard-Marissal, Nathalie; Sunyach, Claire; Marissal, Thomas; Raoul, Cédric; Pettmann, Brigitte

2015-01-01

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

High-functioning autism and schizophrenia: a comparison of an early and late onset neurodevelopmental disorder.  

PubMed

Autism and schizophrenia are separate neurodevelopmental disorders that share a number of interpersonal and cognitive deficits. The symptoms of autism first appear during early life while schizophrenic symptoms do not typically appear until adolescence at the earliest. Efforts have been made to characterize the pattern of cognitive function in both disorders, and certain resemblances have become apparent such as deficits in abstract reasoning and the more complex aspects of memory and language. The present study provided a comparison of cognitive function between the two disorders. The autistic sample consisted of well-diagnosed individuals with high-functioning autism (IQ> or =70). The schizophrenic sample was divided into four subgroups using Ward's method of cluster analysis. Participants received the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Halstead Category Test, the Trail Making test, and the Wisconsin Card Sorting test (WCST). The profile of the autism sample was compared with the four schizophrenia cluster profiles. The autism group resembled only one of the schizophrenia clusters, with both showing elevations on the WAIS-R Information and Block Design subtests and depressions on Comprehension and Digit Symbol. It was concluded that individuals with high-functioning autism have a cognitive profile that resembles that of an empirically derived subgroup of schizophrenia patients but that does not resemble profiles found in other schizophrenia subgroups. The pattern itself, marked by a relatively depressed score on the Comprehension subtest among the Verbal subtests and a relatively elevated score on Block Design among the Performance subtests, has been characterized in the past as a prototypic profile for high-functioning autism. PMID:14592000

Goldstein, Gerald; Minshew, Nancy J; Allen, Daniel N; Seaton, Brent E

2002-07-01

308

Rising incidence of early-onset colorectal cancer in Australia over two decades: Report and review.  

PubMed

The average age at diagnosis for colorectal cancer (CRC) in Australia is 69, and the age-specific incidence rises rapidly after age 50 years. The incidence has stabilized or is declining in older age groups in Australia during recent decades, possibly related to the increased uptake of screening and high-risk surveillance. In the same time frame, a rising incidence of CRC in younger adults has been well-documented in the United States. This rise in incidence in the young has not been reported from other countries that share long-term exposure to westernised urban lifestyles. Using data from the Australian Institute of Health and Welfare, we examined trends in national incidence rates for CRC under age 50 years and observed that rates in people under age 40 years have been rising for the last two decades. We further performed a review of the literature regarding CRC in young adults to outline the extent of current understanding, explore potential risk factors such as obesity, alcohol, and sedentary lifestyles, and to identify the questions remaining to be addressed. Although absolute numbers might not justify a population screening approach, the dispersal of young adults with CRC across the primary health-care system decreases probability of their recognition. Patient and physician awareness, aided by stool and emerging blood-screening tests and risk profiling tools, have the potential to aid in identification of those young adults who would most benefit from a colonoscopy through early detection of CRCs or by removal of advanced polyps. PMID:25251195

Young, Joanne P; Win, Aung Ko; Rosty, Christophe; Flight, Ingrid; Roder, David; Young, Graeme P; Frank, Oliver; Suthers, Graeme K; Hewett, Peter J; Ruszkiewicz, Andrew; Hauben, Ehud; Adelstein, Barbara-Ann; Parry, Susan; Townsend, Amanda; Hardingham, Jennifer E; Price, Timothy J

2015-01-01

309

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

310

Hypersexual behavior in frontotemporal dementia: a comparison with early-onset Alzheimer's disease.  

PubMed

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

2013-04-01

311

Inflammatory cues acting on the adult intestinal stem cells and the early onset of cancer (Review)  

PubMed Central

The observation that cancer often arises at sites of chronic inflammation has prompted the idea that carcinogenesis and inflammation are deeply interwoven. In fact, the current literature highlights a role for chronic inflammation in virtually all the steps of carcinogenesis, including tumor initiation, promotion and progression. The aim of the present article is to review the current literature on the involvement of chronic inflammation in the initiation step and in the very early phases of tumorigenesis, in a type of cancer where adult stem cells are assumed to be the cells of origin of neoplasia. Since the gastrointestinal tract is regarded as the best-established model system to address the liaison between chronic inflammation and neoplasia, the focus of this article will be on intestinal cancer. In fact, the anatomy of the intestinal epithelial lining is uniquely suited to study adult stem cells in their niche, and the bowel crypt is an ideal developmental biology system, as proliferation, differentiation and cell migration are all distributed linearly along the long axis of the crypt. Moreover, crypt stem cells are regarded today as the most likely targets of neoplastic transformation in bowel cancer. More specifically, the present review addresses the molecular mechanisms whereby a state of chronic inflammation could trigger the neoplastic process in the intestine, focusing on the generation of inflammatory cues evoking enhanced proliferation in cells not initiated but at risk of neoplastic transformation because of their stemness. Novel experimental approaches, based on triggering an inflammatory stimulus in the neighbourhood of adult intestinal stem cells, are warranted to address some as yet unanswered questions. A possible approach, the targeted transgenesis of Paneth cells, may be aimed at ‘hijacking’ the crypt stem cell niche from a status characterized by the maintenance of homeostasis to local chronic inflammation, with the prospect of initiating neoplastic transformation in that site. PMID:24920319

DE LERMA BARBARO, A.; PERLETTI, G.; BONAPACE, I.M.; MONTI, E.

2014-01-01

312

The diagnostic approach to monogenic very early onset inflammatory bowel disease.  

PubMed

Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel disease (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histological features of Crohn's disease, ulcerative colitis, or IBD unclassified. Defects in interleukin-10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histological and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extraintestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. In addition, we provide approaches for identifying patients likely to have these disorders. We also discuss classic approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects. PMID:25058236

Uhlig, Holm H; Schwerd, Tobias; Koletzko, Sibylle; Shah, Neil; Kammermeier, Jochen; Elkadri, Abdul; Ouahed, Jodie; Wilson, David C; Travis, Simon P; Turner, Dan; Klein, Christoph; Snapper, Scott B; Muise, Aleixo M

2014-11-01

313

Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson's Disease Patients  

PubMed Central

The impact of Parkinson's disease (PD) on psychological status and quality of life (QoL) may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3 (SD = 10.4)?yr were recruited in this study. PD patients with the onset age of ?50?yr were defined as “early-onset” (EOPD) group (n = 45), while the ones with >50?yr at the time of diagnosis were categorized as the “typical-onset” (TOPD) patients (n = 95). Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale), FSS (fatigue severity scale), MNA (mininutritional assessment), and the UPDRS. Depression score was significantly higher in EOPD group (6.3 (SD = 4.5) versus 4.5 (SD = 4.2), P = 0.02). Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 (SD = 21.6) versus 24.4 (SD = 22.7), P = 0.05). Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients.

Hadizadeh, Hasti; Farhadi, Farzaneh; Delbari, Ahmad; Lökk, Johan

2014-01-01

314

Late Rather Than Early Onset Bubbles in the Pulmonary Artery During Altitude Exposures Correlate Better with the Onset of "Pain-Only" Decompression Illness  

NASA Technical Reports Server (NTRS)

Mechanistic insight about "pain-only" decompression illness (DCI) is limited given indirect information about venous gas emboli (VGE) detected in the pulmonary artery with Doppler ultrasound. However, we show that VGE first detected late in an altitude exposure are closely associated with subsequent symptom onset. Knowing that VGE occur late is an indication that a symptom will occur soon, but this is not a sufficient condition to guarantee that a symptom will occur.

Conkin, J.; Gernhardt, M. L.; Powell, M. R.

2005-01-01

315

Periodontal treatment needs of diabetic adults  

Microsoft Academic Search

Aim: The aim of this study was to investigate diabetes-related factors in relation to periodontal treatment needs. Material and Methods: A cross-sectional study was conducted among 299 dentate diabetics attending a diabetic clinic in Tehran, Iran. A self-administered questionnaire was administered during a dental appointment in order to gather information about year of birth, year of onset of diabetes, education

S Bakhshandeh; H Murtomaa; R Mofid; MM Vehkalahti; Suomalainen K. Periodontal

2007-01-01

316

Microbiology of aggressive periodontitis.  

PubMed

For decades, Aggregatibacter actinomycetemcomitans has been considered the most likely etiologic agent in aggressive periodontitis. Implementation of DNA-based microbiologic methodologies has considerably improved our understanding of the composition of subgingival biofilms, and advanced open-ended molecular techniques even allow for genome mapping of the whole bacterial spectrum in a sample and characterization of both the cultivable and not-yet-cultivable microbiota associated with periodontal health and disease. Currently, A. actinomycetemcomitans is regarded as a minor component of the resident oral microbiota and as an opportunistic pathogen in some individuals. Its specific JP2 clone, however, shows properties of a true exogenous pathogen and has an important role in the development of aggressive periodontitis in certain populations. Still, limited data exist on the impact of other microbes specifically in aggressive periodontitis. Despite a wide heterogeneity of bacteria, especially in subgingival samples collected from patients, bacteria of the red complex in particular, and those of the orange complex, are considered as potential pathogens in generalized aggressive periodontitis. These types of bacterial findings closely resemble those found for chronic periodontitis, representing a mixed polymicrobial infection without a clear association with any specific microorganism. In aggressive periodontitis, the role of novel and not-yet-cultivable bacteria has not yet been elucidated. There are geographic and ethnic differences in the carriage of periodontitis-associated microorganisms, and they need to be taken into account when comparing study reports on periodontal microbiology in different study populations. In the present review, we provide an overview on the colonization of potential periodontal pathogens in childhood and adolescence, and on specific microorganisms that have been suspected for their role in the initiation and progression of aggressive forms of periodontal disease. PMID:24738586

Könönen, Eija; Müller, Hans-Peter

2014-06-01

317

Do Substance Use Risk Personality Dimensions Predict the Onset of Substance Use in Early Adolescence? A Variable- and Person-Centered Approach  

ERIC Educational Resources Information Center

Various studies found personality to be related to substance use, but little attention is paid to the role of personality risk dimensions with regard to an early onset of alcohol, tobacco, and marijuana use. Therefore, the current study used a variable-centered approach to examine whether anxiety sensitivity, hopelessness, sensation seeking, and…

Malmberg, Monique; Kleinjan, Marloes; Vermulst, Ad A.; Overbeek, Geertjan; Monshouwer, Karin; Lammers, Jeroen; Engels, Rutger C. M. E.

2012-01-01

318

Effects of Early-Onset Artificial Strabismus on Pursuit Eye Movements and on Neuronal Responses in Area MT of Macaque Monkeys  

Microsoft Academic Search

In humans, esotropia of early onset is associated with a pro- found asymmetry in smooth pursuit eye movements. When viewing is monocular, targets are tracked well only when they are moving nasally with respect to the viewing eye. To deter- mine whether this pursuit abnormality reflects an anomaly in cortical visual motion processing, we recorded eye movements and cortical neural

Lynne Kiorpes; Pamela J. Walton; Lawrence P. O'Keefe; J. Anthony Movshon; Stephen G. Lisberger

1996-01-01

319

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

320

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

321

Periodontitis associated with osteomalacia.  

PubMed

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. PMID:25425827

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

2014-09-01

322

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. PMID:25425827

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

2014-01-01

323

Complement and Periodontitis  

PubMed Central

Although the complement system is centrally involved in host defense, its overactivation or deregulation (e.g., due to inherent host genetic defects or due to pathogen subversion) may excessively amplify inflammation and contribute to immunopathology. Periodontitis is an oral infection-driven chronic inflammatory disease which exerts a systemic impact on health. This paper reviews evidence linking complement to periodontal inflammation and pathogenesis. Clinical and histological observations show a correlation between periodontal inflammatory activity and local complement activation. Certain genetic polymorphisms or deficiencies in specific complement components appear to predispose to increased susceptibility to periodontitis. Animal model studies and in vitro experiments indicate that periodontal bacteria can either inhibit or activate distinct components of the complement cascade. Porphyromonas gingivalis, a keystone species in periodontitis, subverts complement receptor 3 and C5a anaphylatoxin receptor signaling in ways that promote its adaptive fitness in the presence of non-productive inflammation. Overall, available evidence suggests that complement activation or subversion contributes to periodontal pathogenesis, although not all complement pathways or functions are necessarily destructive. Effective complement-targeted therapeutic intervention in periodontitis would require determining the precise roles of the various inductive or effector complement pathways. This information is essential as it may reveal which specific pathways need to be blocked to counteract microbial evasion and inflammatory pathology or, conversely, be enhanced to promote host immunity. PMID:20599785

Hajishengallis, George

2010-01-01

324

Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer  

PubMed Central

Changes in the methylation levels of DNA from white blood cells (WBCs) are putatively associated with an elevated risk for several cancers. The aim of this study was to investigate the association between colorectal cancer (CRC) and the methylation status of three DNA repetitive elements in DNA from peripheral blood. WBC DNA from 539 CRC cases diagnosed before 60 years of age and 242 sex and age frequency-matched healthy controls from the Australasian Colorectal Cancer Family Registry were assessed for methylation across DNA repetitive elements Alu, LINE-1 and Sat2 using MethyLight. The percentage of methylated reference (PMR) of cases and controls was calculated for each marker. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression adjusted for potential confounders. CRC cases demonstrated a significantly higher median PMR for LINE-1 (p < 0.001), Sat2 (p < 0.001) and Alu repeats (p = 0.02) when compared with controls. For each of the DNA repetitive elements, individuals with PMR values in the highest quartile were significantly more likely to have CRC compared with those in the lowest quartile (LINE-1 OR = 2.34, 95%CI = 1.48–3.70; p < 0.001, Alu OR = 1.83, 95%CI = 1.17–2.86; p = 0.01, Sat2 OR = 1.72, 95%CI = 1.10–2.71; p = 0.02). When comparing the OR for the PMR of each marker across subgroups of CRC, only the Alu marker showed a significant difference in the 5-fluoruracil treated and nodal involvement subgroups (both p = 0.002). This association between increasing methylation levels of three DNA repetitive elements in WBC DNA and early-onset CRC is novel and may represent a potential epigenetic biomarker for early CRC detection. PMID:23804018

Walters, Rhiannon J.; Williamson, Elizabeth J.; English, Dallas R.; Young, Joanne P.; Rosty, Christophe; Clendenning, Mark; Walsh, Michael D.; Parry, Susan; Ahnen, Dennis J.; Baron, John A.; Win, Aung Ko; Giles, Graham G.; Hopper, John L.; Jenkins, Mark A.; Buchanan, Daniel D.

2013-01-01

325

An Ultrasonographic Periodontal Probe  

NASA Astrophysics Data System (ADS)

Periodontal disease, commonly known as gum disease, affects millions of people. The current method of detecting periodontal pocket depth is painful, invasive, and inaccurate. As an alternative to manual probing, an ultrasonographic periodontal probe is being developed to use ultrasound echo waveforms to measure periodontal pocket depth, which is the main measure of periodontal disease. Wavelet transforms and pattern classification techniques are implemented in artificial intelligence routines that can automatically detect pocket depth. The main pattern classification technique used here, called a binary classification algorithm, compares test objects with only two possible pocket depth measurements at a time and relies on dimensionality reduction for the final determination. This method correctly identifies up to 90% of the ultrasonographic probe measurements within the manual probe's tolerance.

Bertoncini, C. A.; Hinders, M. K.

2010-02-01

326

Nicotine and periodontal tissues  

PubMed Central

Tobacco use has been recognized to be a significant risk factor for the development and progression of periodontal disease. Its use is associated with increased pocket depths, loss of periodontal attachment, alveolar bone and a higher rate of tooth loss. Nicotine, a major component and most pharmacologically active agent in tobacco is likely to be a significant contributing factor for the exacerbation of periodontal diseases. Available literature suggests that nicotine affects gingival blood flow, cytokine production, neutrophil and other immune cell function; connective tissue turnover, which can be the possible mechanisms responsible for overall effects of tobacco on periodontal tissues. Inclusion of tobacco cessation as a part of periodontal therapy encourages dental professionals to become more active in tobacco cessation counseling. This will have far reaching positive effects on our patients’ oral and general health. PMID:20922084

Malhotra, Ranjan; Kapoor, Anoop; Grover, Vishakha; Kaushal, Sumit

2010-01-01

327

A novel deletion partly removing the AVP gene causes autosomal recessive inheritance of early-onset neurohypophyseal diabetes insipidus.  

PubMed

Familial neurohypophyseal diabetes insipidus (FNDI) typically presents with age-dependent penetrance and autosomal dominant inheritance caused by missense variations in one allele of the AVP gene encoding the arginine vasopressin (AVP) prohormone. We present the molecular genetic characteristics underlying an unusual form of FNDI occurring with very early onset and seemingly autosomal recessive inheritance. By DNA amplification and sequencing, we identified a novel variant allele of the AVP gene carrying a 10,396 base pair deletion involving the majority of the AVP gene as well as its regulatory sequences in the intergenic region between the AVP and the OXT gene, encoding the oxytocin prohormone. We found two chromosomes carrying the deletion in affected family members and one in unaffected family members suspected to transmit the deleted allele. Whole-genome array analysis confirmed the results and excluded the presence of any additional major pathogenic abnormalities. The deletion is predicted to abolish the transcription of the AVP gene, thus the fact that family members heterozygous for the deletion remain healthy argues, in general, against haploinsufficiency as the pathogenic mechanism FNDI. Accordingly, our data is strong support to the prevailing idea that dominant inheritance of FNDI is due to a dominant-negative effect exerted by variant AVP prohormone. PMID:22168581

Christensen, J H; Kvistgaard, H; Knudsen, J; Shaikh, G; Tolmie, J; Cooke, S; Pedersen, S; Corydon, T J; Gregersen, N; Rittig, S

2013-01-01

328

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease  

PubMed Central

Introduction CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy. Material and methods The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique. Results IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher RV5(6) and RV5(6) + SV1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes. Conclusions Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function. PMID:24049523

Kurzawski, Grzegorz; Safranow, Krzysztof; Rac, Michal; Sagasz-Tysiewicz, Dagmara; Krzystolik, Andrzej; Poncyljusz, Wojciech; Olszewska, Maria; Dawid, Gra?yna; Chlubek, Dariusz

2012-01-01

329

Aripiprazole in the treatment of early-onset schizophrenia spectrum disorder: A case series in Korean children and adolescents  

PubMed Central

Objective: The aim of this case series was to assess the effectiveness and tol-erability of aripiprazole in Korean children and adolescents with early-onset schizophrenia spectrum (EOSS) disorder. Methods: The medical records of aripiprazole-treated patients with EOSS were retrospectively reviewed. Changes in illness severity were measured using the Clinical Global Impression-Severity of Illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales. Results: Data from 22 children and adolescents were included (12 girls, 10 boys; mean [SD] age, 14.0 [2.4] years). The mean (SD) dosage of aripiprazole was 19.8 (9.4) mg/d (median, 18.7 mg/d; mode, 15, 30 mg/d), and the range of treatment duration was 21 to 838 days. Mean (SD) CGI-S score improved significantly from baseline to end point (from 5.7 [0.7] to 4.3 [1.4]; P < 0.001). Based on changes in chart-extracted CGI-I scores, significantly greater improvement was associated with negative symptoms compared with positive symptoms (U = 25.5; P = 0.028; r = ?0.47). Aripiprazole was discontinued due to insufficient effect in 5 patients (22.7%) and treatment-emergent adverse events in 3 patients (13.6%). Conclusion: The results from this small study suggest that aripiprazole was moderately effective in reducing psychotic symptoms in these Korean children and adolescents with EOSS. PMID:24683228

Kim, Yeni; Cho, Soo-Churl; Shin, Min-Sup; Kim, Jae-Won; Choi, Sang-Chul; Kim, Boong-Nyun

2009-01-01

330

7T T2(?)-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.  

PubMed

The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(?)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ? 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. PMID:25113794

van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

2015-01-01

331

Centromere and telomere movements during early meiotic prophase of mouse and man are associated with the onset of chromosome pairing  

PubMed Central

The preconditions and early steps of meiotic chromosome pairing were studied by fluorescence in situ hybridization (FISH) with chromosome- specific DNA probes to mouse and human testis tissue sections. Premeiotic pairing of homologous chromosomes was not detected in spermatogonia of the two species. FISH with centromere- and telomere- specific DNA probes in combination with immunostaining (IS) of synaptonemal complex (SC) proteins to testis sections of prepuberal mice at days 4-12 post partum was performed to study sequentially the meiotic pairing process. Movements of centromeres and then telomeres to the nuclear envelope, and of telomeres along the nuclear envelope leading to the formation of a chromosomal bouquet were detected during mouse prophase. At the bouquet stage, pairing of a mouse chromosome-8- specific probe was observed. SC-IS and simultaneous telomere FISH revealed that axial element proteins appear as large aggregates in mouse meiocytes when telomeres are attached to the nuclear envelope. Axial element formation initiates during tight telomere clustering and transverse filament-IS indicated the initiation of synapsis during this stage. Comparison of telomere and centromere distribution patterns of mouse and human meiocytes revealed movements of centromeres and then telomeres to the nuclear envelope and subsequent bouquet formation as conserved motifs of the pairing process. Chromosome painting in human spermatogonia revealed compacted, largely mutually exclusive chromosome territories. The territories developed into long, thin threads at the onset of meiotic prophase. Based on these results a unified model of the pairing process is proposed. PMID:8794855

1996-01-01

332

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

333

Heterozygous knockout of the Bmi-1 gene causes an early onset of phenotypes associated with brain aging.  

PubMed

Previous studies reported that the polycomb group gene Bmi-1 is downregulated in the aging brain. The aim of this study was to investigate whether decreased Bmi-1 expression accelerates brain aging by analyzing the brain phenotype of adult Bmi-1 heterozygous knockout (Bmi-1(+/-)) mice. An 8-month-old Bmi-1(+/-) brains demonstrated mild oxidative stress, revealed by significant increases in hydroxy radical and nitrotyrosine, and nonsignificant increases in reactive oxygen species and malonaldehyde compared with the wild-type littermates. Bmi-1(+/-) hippocampus had high apoptotic percentage and lipofuscin deposition in pyramidal neurons associated with upregulation of cyclin-dependent kinase inhibitors p19, p27, and p53 and downregulation of anti-apoptotic protein Bcl-2. Mild activation of astrocytes was also observed in Bmi-1(+/-) hippocampus. Furthermore, Bmi-1(+/-) mice showed mild spatial memory impairment in the Morris Water Maze test. These results demonstrate that heterozygous Bmi-1 gene knockout causes an early onset of age-related brain changes, suggesting that Bmi-1 has a role in regulating brain aging. PMID:23771506

Gu, Minxia; Shen, Lihua; Bai, Lei; Gao, Junying; Marshall, Charles; Wu, Ting; Ding, Jiong; Miao, Dengshun; Xiao, Ming

2014-02-01

334

Gene Interactions and Structural Brain Change in Early-Onset Alzheimer's Disease Subjects Using the Pipeline Environment  

PubMed Central

Objective This article investigates subjects aged 55 to 65 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to broaden our understanding of early-onset (EO) cognitive impairment using neuroimaging and genetics biomarkers. Methods Nine of the subjects had EO-AD (Alzheimer's disease) and 27 had EO-MCI (mild cognitive impairment). The 15 most important neuroimaging markers were extracted with the Global Shape Analysis (GSA) Pipeline workflow. The 20 most significant single nucleotide polymorphisms (SNPs) were chosen and were associated with specific neuroimaging biomarkers. Results We identified associations between the neuroimaging phenotypes and genotypes for a total of 36 subjects. Our results for all the subjects taken together showed the most significant associations between rs7718456 and L_hippocampus (volume), and between rs7718456 and R_hippocampus (volume). For the 27 MCI subjects, we found the most significant associations between rs6446443 and R_superior_frontal_gyrus (volume), and between rs17029131 and L_Precuneus (volume). For the nine AD subjects, we found the most significant associations between rs16964473 and L_rectus gyrus (surface area), and between rs12972537 and L_rectus_gyrus (surface area). Conclusion We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 36 EO subjects in terms of neuroimaging genetics. However, larger sample sizes are needed to ensure that the effects will be detectable for a reasonable false-positive error rate using the GSA and Plink Pipeline workflows.

Dinov, Ivo D.; Zamanyan, Alen; Shi, Ran; Genco, Alex; Hobel, Sam; Thompson, Paul M.; Toga, Arthur W.

2015-01-01

335

Association of a Functional Variant in the Wnt Co-Receptor LRP6 with Early Onset Ileal Crohn's Disease  

PubMed Central

Ileal Crohn's Disease (CD), a chronic small intestinal inflammatory disorder, is characterized by reduced levels of the antimicrobial peptides DEFA5 (HD-5) and DEFA6 (HD-6). Both of these ?-defensins are exclusively produced in Paneth cells (PCs) at small intestinal crypt bases. Different ileal CD–associated genes including NOD2, ATG16L1, and recently the ?-catenin–dependant Wnt transcription factor TCF7L2 have been linked to impaired PC antimicrobial function. The Wnt pathway influences gut mucosal homeostasis and PC maturation, besides directly controlling HD-5/6 gene expression. The herein reported candidate gene study focuses on another crucial Wnt factor, the co-receptor low density lipoprotein receptor-related protein 6 (LRP6). We analysed exonic single nucleotide polymorphisms (SNPs) in a large cohort (Oxford: n?=?1,893) and prospectively tested 2 additional European sample sets (Leuven: n?=?688, Vienna: n?=?1,628). We revealed an association of a non-synonymous SNP (rs2302685; Ile1062Val) with early onset ileal CD (OR 1.8; p?=?0.00034; for homozygous carriers: OR 4.1; p?=?0.00004) and additionally with penetrating ileal CD behaviour (OR 1.3; p?=?0.00917). In contrast, it was not linked to adult onset ileal CD, colonic CD, or ulcerative colitis. Since the rare variant is known to impair LRP6 activity, we investigated its role in patient mucosa. Overall, LRP6 mRNA was diminished in patients independently from the genotype. Analysing the mRNA levels of PC product in biopsies from genotyped individuals (15 controls, 32 ileal, and 12 exclusively colonic CD), we found particularly low defensin levels in ileal CD patients who were carrying the variant. In addition, we confirmed a direct relationship between LRP6 activity and the transcriptional expression of HD-5 using transient transfection. Taken together, we identified LRP6 as a new candidate gene in ileal CD. Impairments in Wnt signalling and Paneth cell biology seem to represent pathophysiological hallmarks in small intestinal inflammation and should therefore be considered as interesting targets for new therapeutic approaches. PMID:22393312

Koslowski, Maureen J.; Teltschik, Zora; Beisner, Julia; Schaeffeler, Elke; Wang, Guoxing; Kübler, Irmgard; Gersemann, Michael; Cooney, Rachel; Jewell, Derek; Reinisch, Walter; Vermeire, Séverine; Rutgeerts, Paul; Schwab, Matthias; Stange, Eduard F.; Wehkamp, Jan

2012-01-01

336

Early-Onset Alzheimer's  

MedlinePLUS

... as possible, and ask your manager to be flexible. Possibilities include working fewer hours, reducing responsibilities, or changing positions. Work with your human resources department to make sure ...

337

Clinical evaluation of salivary periodontal pathogen levels by real-time polymerase chain reaction in patients before dental implant treatment  

PubMed Central

Objective Periodontal pathogens in dental plaque are the main causative agents of periodontitis and peri-implantitis. Detection of the presence of such periodontal pathogens early would serve as a useful tool in the diagnosis and treatment of this disease. Therefore, the purpose of this study was to investigate whether the periodontal pathogen levels in saliva were correlated with the periodontal status of patients receiving implant treatment. Materials and Methods A total of 291 patients visiting Tokyo Dental College Chiba Hospital were divided into four groups: a no-periodontitis (np) group, a mild-periodontitis (mip) group, a moderate-periodontitis (mop) group, and a severe-periodontitis (sp) group. The levels of the following five periodontal pathogens in saliva were evaluated using real-time polymerase chain reaction: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Prevotella intermedia. Results The levels of P. gingivalis and T. forsythia were significantly higher in mop group than in np group (P <  0.05). The levels of all periodontal pathogens tested except A. actinomycetemcomitans were significantly higher in sp group than in np group (P <  0.05). Conclusion The detection levels of the periodontal pathogens targeted in saliva samples were correlated with the periodontal status. This suggests that using saliva to screen for periodontopathic bacteria offers an easier-to-use clinical tool than the paper point method in the diagnosis and treatment of periodontitis and peri-implantitis. PMID:23745964

Ito, Taichi; Yasuda, Masaaki; Kaneko, Hajime; Sasaki, Hodaka; Kato, Tetsuo; Yajima, Yasutomo

2014-01-01

338

Periodontal disease in children and adolescents of Latin America.  

PubMed

Periodontal diseases are a group of infectious diseases that mainly include gingivitis and periodontitis. Gingivitis is the most prevalent form of periodontal disease in subjects of all ages, including children and adolescents. Less frequent types of periodontal disease include aggressive periodontitis, acute necrotizing ulcerative gingivitis and various diseases of herpesviral and fungal origin. This review aimed to retrieve relevant information from Latin America on the prevalence of periodontal diseases among children and adolescents of the region. Gingivitis was detected in 35% of young Latin American subjects and showed the highest frequencies in Colombia (77%) and Bolivia (73%) and the lowest frequency in Mexico (23%). The frequency of gingivitis in subjects from other Latin American countries was between 31% and 56%. Periodontitis may affect <10% of the young population in Latin America, but the data are based on only a few studies. A more precise assessment of the distribution and severity of periodontal disease in children and adolescents of Latin America may help policy makers and dentists to institute more effective public health measures to prevent and treat the disease at an early age to avoid major damage to the permanent dentition. PMID:25494597

Botero, Javier E; Rösing, Cassiano Kuchenbecker; Duque, Andres; Jaramillo, Adriana; Contreras, Adolfo

2015-02-01

339

Which Boys Will Fare Worse? Early Predictors of the Onset of Conduct Disorder in a Six-Year Longitudinal Study  

Microsoft Academic Search

ObjectiveThis article addresses the following questions: What are the best demographic and psychiatric predictors of the onset of conduct disorder (CD)? Does physical fighting play a role in the transition from oppositional defiant disorder (ODD) to CD? And what are the predictors of an earlier compared with a later onset of CD? Method: Data are presented on the follow-up of

ROLF LOEBER; STEPHANIE M. GREEN; KATE KEENAN; BENJAMIN B. LAHEY

1995-01-01

340

Localization of a Novel Locus for Autosomal Recessive Early-Onset Parkinsonism, PARK6, on Human Chromosome 1p35-p36  

PubMed Central

The cause of Parkinson disease (PD) is still unknown, but genetic factors have recently been implicated in the etiology of the disease. So far, four loci responsible for autosomal dominant PD have been identified. Autosomal recessive juvenile parkinsonism (ARJP) is a clinically and genetically distinct entity; typical PD features are associated with early onset, sustained response to levodopa, and early occurrence of levodopa-induced dyskinesias, which are often severe. To date, only one ARJP gene, Parkin, has been identified, and multiple mutations have been detected both in families with autosomal recessive parkinsonism and in sporadic cases. The Parkin-associated phenotype is broad, and some cases are indistinguishable from idiopathic PD. In ?50% of families with ARJP that have been analyzed, no mutations could be detected in the Parkin gene. We identified a large Sicilian family with four definitely affected members (the Marsala kindred). The phenotype was characterized by early-onset (range 32–48 years) parkinsonism, with slow progression and sustained response to levodopa. Linkage of the disease to the Parkin gene was excluded. A genomewide homozygosity screen was performed in the family. Linkage analysis and haplotype construction allowed identification of a single region of homozygosity shared by all the affected members, spanning 12.5 cM on the short arm of chromosome 1. This region contains a novel locus for autosomal recessive early-onset parkinsonism, PARK6. A maximum LOD score 4.01 at recombination fraction .00 was obtained for marker D1S199. PMID:11254447

Valente, Enza Maria; Bentivoglio, Anna Rita; Dixon, Peter H.; Ferraris, Alessandro; Ialongo, Tamara; Frontali, Marina; Albanese, Alberto; Wood, and Nicholas W.

2001-01-01

341

Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia  

PubMed Central

Pre-eclampsia is a serious complication of pregnancy that can affect both maternal and fetal outcomes. Early-onset pre-eclampsia (EOPET) is a severe form of pre-eclampsia that is associated with altered physiological characteristics and gene expression in the placenta. DNA methylation is a relatively stable epigenetic modification to DNA that can reflect gene expression, and can provide insight into the mechanisms underlying such expression changes. This case–control study focused on DNA methylation and gene expression of whole chorionic villi samples from 20 EOPET placentas and 20 gestational age-matched controls from pre-term births. DNA methylation was also assessed in placentas affected by late-onset pre-eclampsia (LOPET) and normotensive intrauterine growth restriction (nIUGR). The Illumina HumanMethylation450 BeadChip was used to assess DNA methylation at >480 000 cytosine-guanine dinucleotide (CpG) sites. The Illumina HT-12v4 Expression BeadChip was used to assess gene expression of >45 000 transcripts in a subset of cases and controls. DNA methylation analysis by pyrosequencing was used to follow-up the initial findings in four genes with a larger cohort of cases and controls, including nIUGR and LOPET placentas. Bioinformatic analysis was used to identify overrepresentation of gene ontology categories and transcription factor binding motifs. We identified 38 840 CpG sites with significant (false discovery rate <0.01) DNA methylation alterations in EOPET, of which 282 had >12.5% methylation difference compared with the controls. Significant sites were enriched at the enhancers and low CpG density regions of the associated genes and the majority (74.5%) of these sites were hypomethylated in EOPET. EOPET, but not associated clinical features, such as intrauterine growth restriction (IUGR), presented a distinct DNA methylation profile. CpG sites from four genes relevant to pre-eclampsia (INHBA, BHLHE40, SLC2A1 and ADAM12) showed different extent of changes in LOPET and nIUGR. Genome-wide expression in a subset of samples showed that some of the gene expression changes were negatively correlated with DNA methylation changes, particularly for genes that are responsible for angiogenesis (such as EPAS1 and FLT1). Results could be confounded by altered cell populations in abnormal placentas. Larger sample sizes are needed to fully address the possibility of sub-profiles of methylation within the EOPET cohort. Based on DNA methylation profiling, we conclude that there are widespread DNA methylation alterations in EOPET that may be associated with changes in placental function. This property may provide a useful tool for early screening of such placentas. This study identifies DNA methylation changes at many loci previously reported to have altered gene expression in EOPET placentas, as well as in novel biologically relevant genes we confirmed to be differentially expressed. These results may be useful for DNA- methylation-based non-invasive prenatal diagnosis of at-risk pregnancies. PMID:23770704

Blair, John D.; Yuen, Ryan K.C.; Lim, Brendan K.; McFadden, Deborah E.; von Dadelszen, Peter; Robinson, Wendy P.

2013-01-01

342

Nonsurgical periodontal treatment.  

PubMed

The primary goal of nonsurgical periodontal therapy is to control microbial periodontal infection by removing bacterial biofilm, calculus, and toxins from periodontally involved root surfaces. A review of the scientific literature indicates that mechanical nonsurgical periodontal treatment predictably reduces the levels of inflammation and probing pocket depths, increases the clinical attachment level and results in an apical shift of the gingival margin. Another parameter to be considered, in spite of the lack of scientific evidence, is the reduction in the degree of tooth mobility, as clinically experienced. It is important to point out that nonsurgical periodontal treatment presents limitations such as the long-term maintainability of deep periodontal pockets, the risk of disease recurrence, and the skill of the operator. A high number of posttreatment residual pockets exhibiting bleeding on probing and > 5 mm deep are related to lower clinical stability. The successful treatment of plaque-induced periodontitis will restore periodontal health, but with reduced periodontium. In such cases, anatomical damage from previous periodontal disease will persist and inverse architecture of soft tissue may impair home plaque removal. The clinician can select one of the following therapeutic options according to the individual patient's needs: - Quadrant/sextant wise instrumentation (conventional staged debridement, CSD). - Instrumentation of all pockets within a 24-hour period with (full mouth disinfection [FMD]) or without (full mouth scaling and root planing [FMSRP]) local antiseptics. Both procedures can be associated with systemic antimicrobials. -CSD or FMD in combination with laser or photodynamic therapy. Patients with aggressive periodontitis constitute a challenge to the clinician. To date there are no established protocols for controlling the disease. However, data from the literature on the application of the FMD protocol combined with amoxicillin-metronidazole systemic administration are promising. A new classification in supra- and subcrestal nonsurgical periodontal therapy will be proposed. The supracrestal therapy includes the treatment of gingivitis, nonsurgical coverage of recession-type defects, treatment of suprabony defects and papilla reconstruction techniques. Within subcrestal periodontal therapy, it is of paramount importance to preserve both marginal tissues and connective fibers inserted in the root cementum at the apical part of the bony defects. PMID:24765632

Aimetti, Mario

2014-01-01

343

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

344

Physical and Sexual Abuse and Early-Onset Bipolar Disorder in Youths Receiving Outpatient Services: Frequent, but Not Specific.  

PubMed

The objective of this study was to determine if physical and sexual abuse showed relationships to early-onset bipolar spectrum disorders (BPSD) consistent with findings from adult retrospective data. Participants (N?=?829, M?=?10.9 years old?±?3.4 SD, 60 % male, 69 % African American, and 18 % with BPSD), primarily from a low socio-economic status, presented to an urban community mental health center and a university research center. Physical abuse was reported in 21 %, sexual abuse in 20 %, and both physical and sexual abuse in 11 % of youths with BPSD. For youths without BPSD, physical abuse was reported in 16 %, sexual abuse in 15 %, and both physical and sexual abuse in 5 % of youths. Among youth with BPSD, physical abuse was significantly associated with a worse global family environment, more severe depressive and manic symptoms, a greater number of sub-threshold manic/hypomanic symptoms, a greater likelihood of suicidality, a greater likelihood of being diagnosed with PTSD, and more self-reports of alcohol or drug use. Among youth with BPSD, sexual abuse was significantly associated with a worse global family environment, more severe manic symptoms, a greater number of sub-threshold manic/hypomanic symptoms, greater mood swings, more frequent episodes, more reports of past hospitalizations, and a greater number of current and past comorbid Axis I diagnoses. These findings suggest that if physical and/or sexual abuse is reported, clinicians should note that abuse appears to be related to increased severity of symptoms, substance use, greater co-morbidity, suicidality, and a worse family environment. PMID:25118660

Du Rocher Schudlich, Tina; Youngstrom, Eric A; Martinez, Maria; KogosYoungstrom, Jennifer; Scovil, Kelly; Ross, Jody; Feeny, Norah C; Findling, Robert L

2014-08-15

345

Incidence and Risk Factors for Early-Onset Hypertension after Allogeneic Hematopoietic Stem Cell Transplantation in Children  

PubMed Central

Background and Objectives Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are at risk for developing hypertension. The objectives of this study are to evaluate the prevalence and risk factors of early onset hypertension during the engraftment period after HSCT. Subjects and Methods This is a retrospective study of 157 consecutive patients (mean age at HSCT: 9.1±5.1 years) who underwent HSCT for acute myeloid leukemia (n=47), acute lymphoblastic leukemia (n=43), severe aplastic anemia (n=41), and other reasons (n=26). Blood pressure data were collected at five time points: 0, 7, 14, 21, and 28 days after HSCT. Hypertension was defined as having systolic and/or diastolic blood pressure ?95th percentile according to age, gender, and height. To analyze the risk factors related to hypertension, data, including patients' demographic and transplant characteristics, were reviewed. Results Hypertension developed in 59 patients (38%), among whom 12 (7.6%) required long term therapy. Thirty-two (54%) patients had systolic and diastolic, 8 (14%) had only systolic, and 19 (32%) had only diastolic hypertension. Younger age, acute graft-versus-host disease, sinusoidal obstruction syndrome, treatment with antifungal agent, and greater increase in serum creatinine (Cr) levels were associated with hypertension. Multivariate analysis showed that younger age at HSCT and greater increase in serum Cr level were independent risk factors for hypertension. Conclusion Prevalence of hypertension during immediate post-HSCT period is high, especially in younger children. A greater increase in Cr after HSCT was significantly associated with hypertension. Further study is needed to elucidate long-term cardiovascular complications in pediatric HSCT survivors. PMID:24385991

Kwon, Dae Hyun; Jung, Seungwon; Lee, Jae Young; Moon, Sena; Lee, Jae Wook; Chung, Nack Gyun; Cho, Bin; Kim, Hack Ki

2013-01-01

346

Detection of periodontal markers in chronic periodontitis.  

PubMed

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 10(4) bacterial cells) and 16 (53.3%) using a higher treshold (score 3 corresponding to between >10(5) and 10(6) 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; Carlén, Anette; Bengtsson, Lisbeth; Dahlén, Gunnar

2011-01-01

347

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

PubMed Central

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. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24931423

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

2014-01-01

348

Periodontal probing: a review.  

PubMed

Periodontal probes are the main instruments that are used to assess the status of the periodontium, either for screening purposes or to evaluate periodontal changes throughout the treatment process. With increased knowledge and understanding of periodontal disease, the probes have evolved from a unidimensional manual shape into a more sophisticated computerised instrument. This is due to the need to increase the accuracy and reproducibility of readings and to improve efficiency (time, effort, money). Each probe has characteristic features that makes it unique and, in some cases, specific and limited to use. The aim of this paper is to present a brief introduction to periodontal disease and the methodology of measuring it, followed by probing limitations. The paper will also discuss the methodology of reducing probing error, examiner calibration and probing reproducibility. PMID:25198634

Al Shayeb, Kwthar Nassar A; Turner, Wendy; Gillam, David G

2014-08-01

349

Periodontitis diagnostics using resonance Raman spectroscopy on saliva  

NASA Astrophysics Data System (ADS)

In view of its wealth of molecular information, Raman spectroscopy has been the subject of active biomedical research. The aim of this work is Raman spectroscopy (RS) application for the determination of molecular biomarkers in saliva with the objective of early periodontitis detection. As was shown in our previous study, carotenoids contained in saliva can be molecular fingerprint information for the periodontitis level. It is shown here that the carotenoid RS lines at wavenumbers of 1156 and 1524 cm?1 can be easily detected and serve as reliable biomarkers of periodontitis using resonance Raman spectroscopy of dry saliva.

Gonchukov, S.; Sukhinina, A.; Bakhmutov, D.; Biryukova, T.; Tsvetkov, M.; Bagratashvily, V.

2013-07-01

350

Orthodontic elastic band-induced periodontitis - A case report.  

PubMed

Periodontal problems due to the use of elastic bands have been documented in the past. A 9-year-old girl reported to a periodontist with complaints of bleeding from gums and tooth mobility of upper right central incisor. This case, reports the early diagnosis and treatment of an acute localized periodontitis arising from the incorrect use of orthodontic elastic rubber bands to close a maxillary midline diastema. The elastic band induced periodontitis was treated with a combination of surgery, splinting, antibiotics and orthodontics. Removal of the etiologic agent improved the condition of the tooth. PMID:23960528

Al-Qutub, Montaser N

2012-01-01

351

Self-report of cognitive impairment and mini-mental state examination performance in PRKN, LRRK2, and GBA carriers with early onset Parkinson's disease  

Microsoft Academic Search

While little is known about risk factors for cognitive impairment in early onset Parkinson disease (EOPD), postmortem studies have shown an association between dementia with Lewy bodies (DLB) and glucocerebrosidase (GBA) mutation. We compared Mini-Mental State Examination (MMSE) performance and self-reported cognitive impairment in 699 EOPD participants genotyped for mutations in parkin (PRKN), leucine-rich repeat kinase-2 (LRRK2), and GBA. Logistic

Roy N. Alcalay; Helen Mejia-Santana; Ming X. Tang; Brian Rakitin; Llency Rosado; Barbara Ross; Miguel Verbitsky; Sergey Kisselev; Elan D. Louis; Cynthia L. Comella; Amy Colcher; Danna Jennings; Martha A. Nance; Susan Bressman; William K. Scott; Caroline Tanner; Susan F. Mickel; Howard F. Andrews; Cheryl H. Waters; Stanley Fahn; Lucien J. Cote; Steven J. Frucht; Blair Ford; Michael Rezak; Kevin Novak; Joseph H. Friedman; Ronald Pfeiffer; Laura Marsh; Bradley Hiner; Andrew Siderowf; Ruth Ottman; Lorraine N. Clark; Karen S. Marder; Elise Caccappolo

2010-01-01

352

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

353

Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study  

Microsoft Academic Search

The available data from preclinical and pharmacological studies on the role of the C-O-methyl transferase (COMT) support the hypothesis that abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders (MD). We examined the relationship of a common functional polymorphism (Val108\\/158Met) in the COMT gene, which accounts for four-fold variation in enzyme activity, with ‘early-onset’ (EO) forms (less

I Massat; D Souery; J Del-Favero; M Nothen; D Blackwood; W Muir; R Kaneva; A Serretti; C Lorenzi; M Rietschel; V Milanova; G N Papadimitriou; D Dikeos; C Van Broekhoven; J Mendlewicz

2005-01-01

354

Stem Cells for Periodontal Regeneration  

PubMed Central

Periodontal regeneration is considered to be biologically possible but clinically unpredictable. In periodontitis, inflammation manifests clinically as loss of supporting periodontal tissues and regeneration of damaged tissue is the main goal of treatment. For decades, periodontists have sought to repair the damage through a variety of surgical procedures, and use of grafting materials and growth factors, and of barrier membranes. Reports have emerged that demonstrate which populations of adult stem cells reside in the periodontal ligaments of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration. This review provides an overview of adult human stem cells and their potential use in periodontal regeneration. PMID:24265588

Pejcic, A; Kojovic, D; Mirkovic, D; Minic, I

355

Stem cells for periodontal regeneration.  

PubMed

Periodontal regeneration is considered to be biologically possible but clinically unpredictable. In periodontitis, inflammation manifests clinically as loss of supporting periodontal tissues and regeneration of damaged tissue is the main goal of treatment. For decades, periodontists have sought to repair the damage through a variety of surgical procedures, and use of grafting materials and growth factors, and of barrier membranes. Reports have emerged that demonstrate which populations of adult stem cells reside in the periodontal ligaments of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration. This review provides an overview of adult human stem cells and their potential use in periodontal regeneration. PMID:24265588

Pejcic, A; Kojovic, D; Mirkovic, D; Minic, I

2013-06-01

356

The Development of Early-Onset Ventilator-Associated Pneumonia after Cardiac Surgery with Cardiopulmonary Bypass is Associated with Toll-like Receptor 4 Signal Transduction Pathways.  

PubMed

We evaluated the hypothesis that early-onset ventilator-associated pneumonia (VAP) after cardiac surgery with cardiopulmonary bypass (CPB) requires Toll-like receptor 4 (TLR4)-dependent signaling pathways. We enrolled 50 patients undergoing mitral and aortic double valve replacement, collecting left atrial blood samples from all patients preoperatively (T1), when opening the atrial septum (T2), closing the atrial septum (T3), and at the end of CPB (T4). TLR4 expression on monocytes and lymphocytes was detected immediately with flow cytometry. Serum levels of tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and interleukin-10 (IL-10) were measured using enzyme-linked immunosorbent assays (ELISA). Data from flow cytometry, ELISA, and the clinical outcomes in the two groups were evaluated and compared. Seventeen patients were included for analysis, and assigned to group A (without early-onset VAP, n?=?10) and group B (with early-onset VAP, n?=?7). TLR4 expression on lymphocytes in group B at T1, T3, and T4 were significantly higher than those in group A. Serum levels of IL-10 in group A at T4 were significantly higher than for group B. We found characteristic patterns in TLR4 expression on lymphocytes in left atrial blood of patients undergoing cardiac surgery with CPB. Our findings clarify the role of TLR4 and its association with the development of postoperative pneumonia. PMID:25240766

Liu, Xiang; Wu, Yanhu; Tang, Yihu; Geng, Zhi; Han, Yaping; Zhang, Dongyue

2015-02-01

357

Obesity and periodontal disease.  

PubMed

Obesity is characterized by the abnormal or excessive deposition of fat in the adipose tissue. Its consequences go far beyond adverse metabolic effects on health, causing an increase in oxidative stress, which leads not only to endothelial dysfunction but also to negative effects in relation to periodontitis, because of the increase in proinflammatory cytokines. Thus obesity appears to participate in the multifactorial phenomenon of causality of periodontitis through the increased production of reactive oxygen species. The possible causal relationship between obesity and periodontitis and potential underlying biological mechanisms remain to be established; however, the adipose tissue actively secretes a variety of cytokines and hormones that are involved in inflammatory processes, pointing toward similar pathways involved in the pathophysiology of obesity, periodontitis and related inflammatory diseases. So the aim of this article is to get an overview of the association between obesity and periodontitis and to review adipose-tissue - derived hormones and cytokines that are involved in inflammatory processes and their relationship to periodontitis. PMID:21691545

Jagannathachary, Sunitha; Kamaraj, Dinesh

2010-04-01

358

A case-control study on risk factors for early-onset respiratory tract infection in patients admitted in ICU  

PubMed Central

Background Respiratory tract infections are common in intensive care units (ICU), with incidences reported from 10 to 65%, and case fatality rates over 20% in pneumonia. This study was designed to identify risk factors for the development of an early onset respiratory tract infection (ERI) and to review the microbiological profile and the effectiveness of first intention antibiotic therapy. Methods Case-control, retrospective clinical study of the patients admitted to the Intensive Care Unit (ICU) of our hospital, a teaching and tertiary care facility, from January to September 2000 who had a respiratory tract infection diagnosed in the first 5 days of hospital stay. Results Of the 385 patients admitted to our unit: 129 (33,5%) had a diagnosis of ERI and 86 patients were admitted to the control group. Documented aspiration (adjusted OR = 5,265; 95% CI = 1,155 – 24,007) and fractured ribs (adjusted OR = 12,150; 95% CI = 1,571 – 93,941) were found to be independent risk factors for the development of ERI (multiple logistic regression model performed with the diagnostic group as dependent variable and adjusted for age, sex, SAPS II, documented aspiration, non-elective oro-tracheal intubation (OTI), fractured ribs, pneumothorax and pleural effusion). A total of 78 organisms were isolated in 61 patients (47%). The normal flora of the upper airway (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenza and Moraxella catharralis) accounted for 72% of all isolations achieved, polimicrobian infections were responsible for 25% of all microbiological documented infections. First intention treatment was, in 62% of the patients, the association amoxacillin+clavulanate, being effective in 75% of the patients to whom it was administered. The patients with ERI needed more days of OTI (6 vs 2, p < 0,001) and mechanical ventilation (6 vs 2, p < 0,001) and had a longer ICU (7 vs 2, p < 0,001) and hospital length of stay (17 vs 11, p = 0,018), when compared with controls. Conclusion In this study documented tracheobronchial aspiration and fractured ribs were identified as independent risk factors for ERI. Microbiological profile was dominated by sensitive micro-organisms. The choice amoxacilin+clavulanate revealed to be a good option with an effectiveness rate of 77% in the patients in whom it was used. PMID:17888157

Cardoso, Teresa C; Lopes, Luís M; Carneiro, António H

2007-01-01

359

Periodontal microbiology in Latin America.  

PubMed

This review article describes the microbiota associated with periodontal disease in Latin America. This vast territory includes 22 nations, which show great ethnic diversity, with large groups of White people, Black people, Mestizo people and Native people. Widespread poverty and limited access to education and health-care services, including periodontal care, are prominent predisposing factors for destructive periodontal disease in Latin America. Black people and Mestizo people seem to have particularly severe periodontal disease and are frequently colonized by the major periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The 'red complex' bacterial pathogens and A. actinomycetemcomitans predominate in chronic and aggressive periodontitis, but gram-negative enteric rods and herpesviruses can also play important periodontopathic roles in Latin America. The key to minimizing the risk of periodontal disease is control of the pathogens, and new low-cost periodontal treatments deserve serious consideration in Latin America. PMID:25494598

Contreras, Adolfo; Moreno, Sandra M; Jaramillo, Adriana; Pelaez, Melissa; Duque, Andres; Botero, Javier E; Slots, Jørgen

2015-02-01

360

Periodontal Probe Improves Exams, Alleviates Pain  

NASA Technical Reports Server (NTRS)

Dentists, comedian Bill Cosby memorably mused, tell you not to pick your teeth with any sharp metal object. Then you sit in their chair, and the first thing they grab is an iron hook!" Conventional periodontal probing is indeed invasive, uncomfortable for the patient, and the results can vary greatly between dentists and even for repeated measurements by the same dentist. It is a necessary procedure, though, as periodontal disease is the most common dental disease, involving the loss of teeth by the gradual destruction of ligaments that hold teeth in their sockets in the jawbone. The disease usually results from an increased concentration of bacteria in the pocket, or sulcus, between the gums and teeth. These bacteria produce acids and other byproducts, which enlarge the sulcus by eroding the gums and the periodontal ligaments. The sulcus normally has a depth of 1 to 2 millimeters, but in patients with early stages of periodontal disease, it has a depth of 3 to 5 millimeters. By measuring the depth of the sulcus, periodontists can have a good assessment of the disease s progress. Presently, there are no reliable clinical indicators of periodontal disease activity, and the best available diagnostic aid, periodontal probing, can only measure what has already been lost. A method for detecting small increments of periodontal ligament breakdown would permit earlier diagnosis and intervention with less costly and time-consuming therapy, while overcoming the problems associated with conventional probing. The painful, conventional method for probing may be destined for the archives of dental history, thanks to the development of ultrasound probing technologies. The roots of ultrasound probes are in an ultrasound-based time-of-flight technique routinely used to measure material thickness and length in the Nondestructive Evaluation Sciences Laboratory at Langley Research Center. The primary applications of that technology have been for corrosion detection and bolt tension measurements (Spinoff 2005). This ultrasound measurement system was adapted to the Periodontal Structures Mapping System, invented at Langley by John A. Companion, under the supervision of Dr. Joseph S. Heyman. Support of the research and development that led to this invention was provided by NASA s Technology Applications Engineering Program and by the Naval Institute for Dental and Biomedical Research, in Great Lakes, Illinois.

2008-01-01

361

Acute periodontal lesions.  

PubMed

This review provides updates on acute conditions affecting the periodontal tissues, including abscesses in the periodontium, necrotizing periodontal diseases and other acute conditions that cause gingival lesions with acute presentation, such as infectious processes not associated with oral bacterial biofilms, mucocutaneous disorders and traumatic and allergic lesions. A periodontal abscess is clinically important because it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth and bacteria within the abscess can spread and cause infections in other body sites. Different types of abscesses have been identified, mainly classified by their etiology, and there are clear differences between those affecting a pre-existing periodontal pocket and those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, while an evaluation of the need for systemic antimicrobial therapy will be made for each case, based on local and systemic factors. The definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal diseases present three typical clinical features: papilla necrosis, gingival bleeding and pain. Although the prevalence of these diseases is not high, their importance is clear because they represent the most severe conditions associated with the dental biofilm, with very rapid tissue destruction. In addition to bacteria, the etiology of necrotizing periodontal disease includes numerous factors that alter the host response and predispose to these diseases, namely HIV infection, malnutrition, stress or tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in nonresponding conditions, being the first option metronidazole. Once the acute disease is under control, definitive treatment should be provided, including appropriate therapy for the pre-existing gingivitis or periodontitis. Among other acute conditions affecting the periodontal tissues, but not caused by the microorganisms present in oral biofilms, infectious diseases, mucocutaneous diseases and traumatic or allergic lesions can be listed. In most cases, the gingival involvement is not severe; however, these conditions are common and may prompt an emergency dental visit. These conditions may have the appearance of an erythematous lesion, which is sometimes erosive. Erosive lesions may be the direct result of trauma or a consequence of the breaking of vesicles and bullae. A proper differential diagnosis is important for adequate management of the case. PMID:24738591

Herrera, David; Alonso, Bettina; de Arriba, Lorenzo; Santa Cruz, Isabel; Serrano, Cristina; Sanz, Mariano

2014-06-01

362

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

363

Periodontal therapy for severe chronic periodontitis with periodontal regeneration and different types of prosthesis.  

PubMed

We report a patient with severe chronic periodontitis requiring regenerative periodontal surgery and different types of prosthesis in the maxillary and mandibular regions. The patient was a 57-year-old woman who presented with the chief complaint of occlusal pain. An initial clinical examination revealed that 73% of sites had a probing depth of ?4 mm, and 60% of sites exhibiting bleeding on probing. Radiographic examination revealed vertical bone defects in the molar region and widening of the periodontal ligament space around teeth #17 and 24. Initial periodontal therapy was implemented based on a clinical diagnosis of severe chronic periodontitis. Surgical periodontal therapy was subsequently performed at selected sites. Periodontal regenerative therapy using enamel matrix derivative was performed on #14, 15, and 35-37. Tunnel preparation was performed on #46 as it had a 2-wall vertical bony defect and Degree 3 furcation involvement. Other sites with residual periodontal pockets were treated by modified Widman flap surgery. After a re-evaluation, functional rehabilitation was implemented with a removable maxillary partial denture and a fixed mandibular bridge. No further deterioration was observed in the periodontal condition of most of the teeth during a 2-year period of supportive periodontal therapy (SPT). The patient is currently still undergoing SPT and some minor problems remain. However, the results suggest that treatment and subsequent maintenance for severe periodontitis with traumatic occlusion can be successful as long as the appropriate periodontal and prosthodontic treatment is planned and careful SPT carried out. PMID:25477039

Kinumatsu, Takashi; Umehara, Kazuhiro; Nagano, Kyosuke; Saito, Atsushi

2014-01-01

364

Sera from early-onset, severely preeclamptic women directly modulate HLA-E expression in the EA.hy296 endothelial cell line.  

PubMed

The expression of endothelial HLA-E in the context of the systemic inflammatory response observed in preeclampsia has not been established. An experimental study was designed to determine the effect of the sera of pregnant women on the expression of HLA-E in EA.hy296 endothelial cells. First, measurements of protein fractions were performed in sera from early-onset, severely preeclamptic women without HELLP syndrome, in which there was no significant difference in total proteins between the groups, but a reduced level of plasma albumin and an increase in ?1-globulin were observed in both groups of pregnant women compared with non-pregnant women. Measurements of colloid osmotic pressure (COP) using a recalculated albumin/globulin ratio formula determined only a significant decrease in COP in all pregnant groups compared with non-pregnant women. The expression of membrane HLA-E was increased in EA.hy296 endothelial cells stimulated with sera of early-onset, severely preeclamptic women, while recombinant interferon-? (IFN-?) significantly reduced the expression of membrane HLA-E. Pro-inflammatory cytokines were measured by Luminex in the serum samples, and increased levels of tumor necrosis factor (TNF) and decreased levels of IFN-? were observed in early-onset, severe preeclampsia compared with normal pregnancy. Moreover, soluble HLA-E was detected in these serum samples by Western blot and ELISA, but no significant difference was found. This raises the possibility that a systemic inflammatory response promotes a compensatory mechanism of COP balance in severe preeclampsia by release of inflammation-induced factors, including endothelial HLA-E. Evidence is now provided regarding HLA-E expression by EA.hy296 cells. PMID:24837231

Bueno-Sánchez, J C; Peña-Alzate, S; Peña, R B; Agudelo-Jaramillo, B; Cadavid-Jaramillo, A P; Chaouat, G; Maldonado-Estrada, J G

2014-10-01

365

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

366

[PCR "real time" to analyze the quantitative and qualitative relations microbiota of periodontal pockets].  

PubMed

The introduction of a broad medical practice PCR "real time" is just beginning and dentistry is no exception. Modern molecular genetic methods provide numerous opportunities for diagnosis, assessment and prediction in patients with inflammatory periodontal diseases. Early and accurate diagnosis can allow in the future reduce the incidence of periodontitis and the progression of its course. PMID:21716234

Zorina, O A; Kulakov, A A; Boriskina, O A; Rebrikov, D V

2011-01-01

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

Rheumatoid arthritis and periodontitis – inflammatory and infectious connections. Review of the literature  

PubMed Central

An association between oral disease/periodontitis and rheumatoid arthritis (RA) has been considered since the early 1820s. The early treatment was tooth eradication. Epidemiological studies suggest that the prevalence of RA and periodontitis may be similar and about 5% of the population are aged 50 years or older. RA is considered as an autoimmune disease whereas periodontitis has an infectious etiology with a complex inflammatory response. Both diseases are chronic and may present with bursts of disease activity. Association studies have suggested odds ratios of having RA and periodontitis varying from 1.8:1 (95% CI: 1.0–3.2, NS) to 8:1 (95% CI: 2.9–22.1, p<0.001). Genetic factors are driving the host responses in both RA and periodontitis. Tumor necrosis factor-?, a proinflammatory cytokine, regulates a cascade of inflammatory events in both RA and periodontitis. Porphyromonas gingivalis is a common pathogen in periodontal infection. P. gingivalis has also been identified in synovial fluid. The specific abilities of P. gingivalis to citrullinate host peptides by proteolytic cleavage at Arg-X peptide bonds by arginine gingipains can induce autoimmune responses in RA through development of anticyclic citrullinated peptide antibodies. In addition, P. gingivalis carries heat shock proteins (HSPs) that may also trigger autoimmune responses in subjects with RA. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Conclusions Periodontal infection (P. gingivalis) carries a unique risk for development of autoimmune antibodies associated with RA. Patients with RA have either lost many teeth or usually have severe periodontitis. Additional research, both in regards to basic mechanisms as well as clinical studies, are necessary before it can be said that there are causative links between RA and periodontitis. Cross-disciplinary research in well-defined populations should be performed to further enhance knowledge and develop clinical strategies how to coordinate therapy and risk assessments of RA and periodontitis. PMID:22347541

Rutger Persson, G.

2012-01-01

369

Lasers in periodontal therapy.  

PubMed

About 50 years ago, lasers started to be used in periodontal treatment following evidence that wounds produced in animals healed more quickly after being irradiated with low-intensity lasers. Increased production of growth factors, stimulated mainly by red and infrared lasers, may participate in this process by influencing the behavior of various types of cells. High-intensity lasers have been used as an alternative to nonsurgical periodontal therapy in root biomodification and to reduce dentin hypersensivity; low-intensity lasers are frequently employed to improve tissue repair in regenerative procedures and in antimicrobial photodynamic therapy. Despite the abundance of promising data on the advantages of their use, there is still controversy regarding the real benefits of lasers and antimicrobial photodynamic therapy in periodontal and peri-implant treatment. A huge variation in the parameters of laser application among studies makes comparisons very difficult. An overview of the current concepts and findings on lasers in periodontal therapy is presented with emphasis on data collected from Latin-American researchers. PMID:25494605

Passanezi, Euloir; Damante, Carla Andreotti; de Rezende, Maria L Rubo; Greghi, Sebastião L Aguiar

2015-02-01

370

Periodontics II: Course Proposal.  

ERIC Educational Resources Information Center

A proposal is presented for Periodontics II, a course offered at the Community College of Philadelphia to give the dental hygiene/assisting student an understanding of the disease states of the periodontium and their treatment. A standardized course proposal cover form is given, followed by a statement of purpose for the course, a list of major…

Dordick, Bruce

371

A novel mutation in the PSEN2 gene (N141Y) associated with early-onset autosomal dominant Alzheimer's disease in a Chinese Han family.  

PubMed

The mutations in the presenilin 2 (PSEN2) gene as causes of early-onset familial Alzheimer's disease (AD) have never been reported in Asia. We conducted a phenotype and pedigree study by performing neuropathological examination and target region sequencing in a family of 3 generations. Six members in this family developed dementia in their fifth decade and died in their sixth decade. The proband was diagnosed clinically with AD, which was confirmed by an autopsy. Target region sequencing showed a novel missense mutation at codon 141 (N141Y) of the PSEN2 gene that predicts an Asparagine-to-Tyrosine substitution in the affected individuals. The result was validated by Sanger sequencing in 7 family members (2 affected and 5 unaffected). The mutation was absent in the 5 clinically unaffected relatives and 188 control subjects. No influence of the APOE genotype was observed. We are the first to demonstrate a novel PSEN2 N141Y mutation in a Chinese Han family with early-onset AD. PMID:24838186

Niu, Fusheng; Yu, Shanshan; Zhang, Zhenxin; Yi, Xin; Ye, Lili; Tang, Wei; Qiu, Changchun; Wen, Hongbo; Sun, Yujing; Gao, Jing; Guo, Yupu

2014-10-01

372

Homozygous loss-of-function mutation of the LEPREL1 gene causes severe non-syndromic high myopia with early-onset cataract.  

PubMed

High myopia is a severe visual impairment which can increase the risk of retinal degeneration, subretinal hemorrhage, choroidal neovascularization, cataract and retinal detachment. We recruited an autosomal-recessive high myopia family, with affected subjects who also present early-onset cataract, retinal degeneration and other complications. Using targeted capturing and whole exome sequencing, we identified a homozygous non-sense mutation in the LEPREL1 gene which causes premature termination of the translation at the fifth amino acid (c.13C>T; p.Q5X), co-segregating with the phenotypes. LEPREL1 encodes a proline hydroxylase called prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The results show that LEPREL1 plays an important role in eye development and homozygous loss-of-function mutation of this gene can cause severely high myopia and early-onset cataract. Our study also strongly suggests that the disruption of collagen modification is one of the pathogenic mechanisms of high myopia and cataract. PMID:24172257

Guo, H; Tong, P; Peng, Y; Wang, T; Liu, Y; Chen, J; Li, Y; Tian, Q; Hu, Y; Zheng, Y; Xiao, L; Xiong, W; Pan, Q; Hu, Z; Xia, K

2014-12-01

373

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

374

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

375

The Aicardi-Goutières syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis).  

PubMed Central

Aicardi-Goutières syndrome (Mendelian inheritance in man Catalog No *225750) is an autosomal recessive encephalopathy which causes developmental arrest, intracerebral calcification, and white matter disease in the presence of chronic cerebrospinal fluid lymphocytosis, and a raised level of cerebrospinal fluid interferon-alpha (IFN-alpha). Diagnosis requires the presence of progressive encephalopathy with onset shortly after birth, and characteristic clinical neurological and neuroimaging signs together with chronic CSF lymphocytosis. The syndrome has superficial resemblance to the neurological sequelae of congenital infection, thus a rigorous search for microbiological and serological evidence of embryopathic infections should be carried out in each case. Images PMID:8592332

Tolmie, J L; Shillito, P; Hughes-Benzie, R; Stephenson, J B

1995-01-01

376

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

377

Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum.  

PubMed Central

The pathogenic potential of Fusobacterium nucleatum and its significance in the development of periodontal diseases, as well as in infections in other organs, have gained new interest for several reasons. First, this bacterium has the potential to be pathogenic because of its number and frequency in periodontal lesions, its production of tissue irritants, its synergism with other bacteria in mixed infections, and its ability to form aggregates with other suspected pathogens in periodontal disease and thus act as a bridge between early and late colonizers on the tooth surface. Second, of the microbial species that are statistically associated with periodontal disease, F. nucleatum is the most common in clinical infections of other body sites. Third, during the past few years, new techniques have made it possible to obtain more information about F. nucleatum on the genetic level, thereby also gaining better knowledge of the structure and functions of the outer membrane proteins (OMPs). OMPs are of great interest with respect to coaggregation, cell nutrition, and antibiotic susceptibility. This review covers what is known to date about F. nucleatum in general, such as taxonomy and biology, with special emphasis on its pathogenic potential. Its possible relationship to other periodontal bacteria in the development of periodontal diseases and the possible roles played by OMPs are considered. PMID:8665477

Bolstad, A I; Jensen, H B; Bakken, V

1996-01-01

378

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

379

[Metacarpal index in periodontal disease].  

PubMed

The hypothesis that there is a relationship between total bone mass reduction and alveolar bone loss in periodontal disease was studied in a group of 98 hospitalized patients free of metabolic disease. All patients had periodontitis with marked evidence of alveolar bone loss. A significant correlation of alveolar bone resorption to the total bone mass reduction in patients with periodontal disease was found. PMID:2636494

Tesseromatis, C; Myrkou, A; Dalles, C; Speggos, M

1989-07-01

380

A new mdr2(-/-) mouse model of sclerosing cholangitis with rapid fibrosis progression, early-onset portal hypertension, and liver cancer.  

PubMed

We previously characterized the Mdr2(Abcb4)(-/-) mouse as a reproducible model of chronic biliary liver disease. However, it demonstrates relatively slow fibrosis progression, possibly due to its fibrosis-resistant genetic background. We aimed to improve the model by moving it onto a fibrosis-susceptible background. We generated novel BALB/c.Mdr2(-/-) mouse via genetic backcross onto highly fibrosis-susceptible BALB/c substrain, identified in inbred mouse strain screening. Liver fibrosis, portal pressure, and hepatic tumor burden in BALB/c.Mdr2(-/-) mice were studied up to 1 year of age in direct comparison to parental strain FVB.Mdr2(-/-). BALB/c.Mdr2(-/-) mice developed periductular onion-skin type fibrotic lesions and pronounced ductular reaction starting from 4 weeks of age. Compared to parental strain, BALB/c.Mdr2(-/-) mice demonstrated dramatically accelerated liver fibrosis, with threefold increase in collagen deposition and bridging fibrosis/early signs of cirrhosis at 12 weeks. This was accompanied by early-onset severe portal hypertension and twofold to fourfold increase in profibrogenic transcripts Col1a1 [procollagen ?1(I)], Tgfb1, and Timp1. Primary liver cancers in BALB/c.Mdr2(-/-) developed earlier, with greater tumor burden compared to FVB.Mdr2(-/-). BALB/c.Mdr2(-/-) mice have unprecedented degree and rapidity of hepatic fibrosis progression and clinically relevant cirrhosis complications, such as early-onset portal hypertension and primary liver cancers. This new model will facilitate development of antifibrotic drugs and studies into mechanisms of biliary fibrosis progression. PMID:25478810

Ikenaga, Naoki; Liu, Susan B; Sverdlov, Deanna Y; Yoshida, Shuhei; Nasser, Imad; Ke, Qingen; Kang, Peter M; Popov, Yury

2015-02-01

381

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

382

Lasers in periodontics  

PubMed Central

Laser is one of the most captivating technologies in dental practice since Theodore