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Sample records for early onset periodontitis

  1. HLA region excluded by linkage analyses of early onset periodontitis

    SciTech Connect

    Sun, C.; Wang, S.; Lopez, N.

    1994-09-01

    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.

  2. Subgingival and Tongue Microbiota during Early Periodontitis

    PubMed Central

    Tanner, A.C.R.; Paster, B.J.; Lu, S.C.; Kanasi, E.; Kent, R.; Van Dyke, T.; Sonis, S.T.

    2006-01-01

    Periodontal infections have a microbial etiology. Association of species with early disease would be useful in determining which microbes initiate periodontitis. We hypothesized that the microbiota of subgingival and tongue samples would differ between early periodontitis and health. A cross-sectional evaluation of 141 healthy and early periodontitis adults was performed with the use of oligonucleotide probes and PCR. Most species differed in associations with sample sites; most subgingival species were associated with subgingival samples. Few species were detected more frequently in early periodontitis by DNA probes. Porphyromonas gingivalis and Tannerella forsythia (Tannerella forsythensis) were associated with early periodontitis by direct PCR. In conclusion, the microbiota of tongue samples was less sensitive than that of subgingival samples in detecting periodontal species, and there was overlap in species detected in health and early periodontitis. Detection of periodontal pathogens in early periodontitis suggests an etiology similar to that of more advanced disease. PMID:16567551

  3. Early-Onset Alzheimer's

    MedlinePLUS

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

  4. Salivary Antimicrobial Peptides in Early Detection of Periodontitis

    PubMed Central

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

    2015-01-01

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

  5. Early-Onset Neonatal Sepsis

    PubMed Central

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

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-?), 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

  6. Early- versus Late-Onset Systemic Sclerosis

    PubMed Central

    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

    2014-01-01

    Abstract 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

  7. Periodontal Disease and Late-Onset Aortic Prosthetic Vascular Graft Infection

    PubMed Central

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

    2015-01-01

    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. PMID:25685592

  8. Periodontitis

    MedlinePLUS

    ... brushing is always needed, even after professional tooth cleaning, to reduce your risk of gum disease. Your ... Patients with periodontitis should have a professional tooth cleaning every three months. Surgery may be necessary. Deep ...

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2015-07-01

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

  11. Periodontal management in orthognathic surgery: early screening of periodontal risk and its current management for the optimization of orthodontic and surgical treatments.

    PubMed

    Straub, B; Bouletreau, P; Breton, P

    2014-09-01

    Orthodontic preparation for orthognathic surgery requires correcting mal-occlusions and coordination of arcades. In addition to improving the aesthetics, these treatments can ensure the achievement and sustainability of prosthetics and/or implants. Nevertheless, periodontal structures are easily damaged. Orthodontic displacement can only be applied in the absence of inflammation or weakened periodontal structure. An early detection of periodontal risk should be achievable by prescribers of a surgical-orthodontic treatment. Simplified periodontal examination, with easily detectable warning signs, will help to identify the periodontal risk. Although periodontal treatment follows current "non invasive" trend, some procedures remain necessary to prevent and/or remedy periodontal defects or diseases, such as mineral periodontal reinforcement corticotomy. It is essential that the patient meets all the practitioners to plan and assess the extent of the constraints necessary to optimize results, before starting orthodontic treatment combined with orthognathic surgery. Any periodontal complication (even minor) will be considered as a failure, regardless of good aesthetic and functional results. PMID:25017293

  12. [Periodontal management in orthognathic surgery: early screening of periodontal risk and its current management for the optimization of orthodontic and surgical treatments].

    PubMed

    Straub, B; Bouletreau, P; Breton, P

    2014-09-01

    Orthodontic preparation for orthognathic surgery requires correcting malocclusions and coordination of arcades. In addition to improving the aesthetics, these treatments can ensure the achievement and sustainability of prosthetics and/or implants. Nevertheless periodontal structures are easily damaged. Orthodontic displacement can only be applied in the absence of inflammation or weakened periodontal structures. An early detection of periodontal risk should be achievable by prescribers of a surgical-orthodontic treatment. Simplified periodontal examination, with easily detectable warning signs, will help identify the periodontal risk. Although periodontal treatment follows current "non-invasive" trend, some procedures remain necessary to prevent and/or remedy periodontal defects or diseases, such as mineral periodontal reinforcement based on corticotomy principles. It is essential that the patient meet all the practitioners to plan and assess the extent of the constraints necessary to optimize results, before starting orthodontic treatment combined with orthognathic surgery. Any periodontal complication (even minor) will be considered as a failure, regardless of good aesthetic and functional results. PMID:25017292

  13. Comparison of Delayed-Onset Glaucoma and Early-Onset Glaucoma after Infantile Cataract Surgery

    PubMed Central

    Kang, Kui Dong; Biglan, Albert W

    2006-01-01

    Purpose To investigate the causes and characteristics of glaucoma in children following cataract surgery. Methods Twenty-four patients (37 eyes) with uncomplicated congenital cataracts who developed glaucoma after cataract surgery were studied retrospectively. Variables included cataract morphology, surgical techniques, post-operative complications, time to the onset of glaucoma, gonioscopic findings, presence of microcornea and the histopathologic characteristics of the filtration angle (in one case). Results There was a bimodal onset of glaucoma after cataract surgery. Early-onset glaucoma occurred at a mean age of 6 months in 15 eyes and delayed-onset glaucoma at a mean age of 12 years in 22 eyes. Early-onset glaucoma was significantly (p=0.018) more likely to be due to angle closure than delayed-onset glaucoma. With delayed-onset glaucoma, the filtration angle was open in 86% of eyes and significantly (p=0.006) more eyes in the delayed-onset group had microcornea. Medical treatment was sufficient to control intraocular pressure in the delayed-onset group while the early-onset group required surgical treatment (P<0.001). Conclusions The onset of glaucoma after cataract surgery during infancy follows a bimodal pattern that is correlated with the configuration of the filtration angle. The early-onset glaucoma group had high incidence of angle closure requiring surgical treatment, while in the delayed-onset group non-surgical treatment was sufficient to control intraocular pressure. Prophylactic iridectomy in eyes at risk for pupillary block is recommended. Eyes with delayed-onset glaucoma have open filtration angles yet also have findings of incomplete development of filtration structures. Microcornea is a risk factor for delayed-onset glaucoma. PMID:16768189

  14. [Early onset scoliosis. What are the options?].

    PubMed

    Farrington, D M; Tatay-Díaz, A

    2013-01-01

    The prognosis of children with progressive early onset scoliosis has improved considerably due to recent advances in surgical and non-surgical techniques and the understanding of the importance of preserving the thoracic space. Improvements in existing techniques and development of new methods have considerably improved the management of this condition. Derotational casting can be considered in children with documented progression of a <60° curve without previous surgical treatment. Both single and dual growing rods are effective, but the latter seem to offer better results. Hybrid constructs may be a better option in children who require a low-profile proximal anchor. The vertical expandable prosthetic titanium rib (VEPTR(®)) appears to be beneficial for patients with congenital scoliosis and fused ribs, and thoracic Insufficiency Syndrome. Children with medical comorbidities who may not tolerate repeated lengthenings should be considered for Shilla or Luque Trolley technique. Growth modulation using shape memory alloy staples or other tethers seem promising for mild curves, although more research is required to define their precise indications. PMID:24071039

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  16. Severe early onset ethylmalonic encephalopathy with West syndrome.

    PubMed

    Papetti, Laura; Garone, Giacomo; Schettini, Livia; Giordano, Carla; Nicita, Francesco; Papoff, Paola; Zeviani, Massimo; Leuzzi, Vincenzo; Spalice, Alberto

    2015-12-01

    Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome. PMID:26194623

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

    ERIC Educational Resources Information Center

    Emery, Olga B.; Breslau, Lawrence D.

    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…

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

    PubMed Central

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

    2014-01-01

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

  19. Markers of neurodevelopmental impairments in early-onset psychosis

    PubMed Central

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

    2015-01-01

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

  20. Early-onset schizophrenia: a 15-year follow-up.

    PubMed

    Röpcke, Bernd; Eggers, Christian

    2005-09-01

    The study describes the psychopathological and social outcome of patients treated for schizophrenia in adolescence (mean age at onset 16.0 years/SD 1.52) after a mean follow-up period of 15.4 years (10.2-21.2 years). Out of 55 patients consecutively admitted to hospital, 47 (85 %) could be traced and 39 (71 %) could be re-examined. At follow-up, 33/39 patients (85 %) had had at least one readmission. Full remission of global psychopathological symptoms [Clinical Global Impression (CGI) onset (CGI: Beta=0.36, GAS: Beta=-0.37). A poor outcome was seen in 22 out of 25 cases with insidious onset. All predictors together explained 58% of the variance in the Positive and Negative Syndrome (PANSS) negative symptom ratings at follow-up. Gender, duration of first inpatient treatment and duration of untreated psychosis were of no predictive value for outcome. The nature of the diagnosis in the first episode strongly predicted the diagnosis given for the whole course after 15 years. In 26/37 cases (70 %), diagnosis at onset and overall diagnoses were the same. Our finding of an incidence of 61% insidious onset is similar to that in adult onset schizophrenia (AOS), but different to very early onset schizophrenia (VEOS), which shows a higher rate of insidious onset, cognitive impairment and poor outcome. Therefore, it seems that VEOS is a special group compared with early onset schizophrenia (EOS) and AOS. PMID:16220219

  1. Early and Late Onset Sepsis in Late Preterm Infants

    PubMed Central

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

    2009-01-01

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

  2. Early-Onset Psychosis in Youth with Intellectual Disability

    ERIC Educational Resources Information Center

    Friedlander, R. I.; Donnelly, T.

    2004-01-01

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

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

    ERIC Educational Resources Information Center

    McIntosh, David E.; Trotter, Jeffrey S.

    2006-01-01

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

  4. Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

    ERIC Educational Resources Information Center

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

    2009-01-01

    Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current…

  5. Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

    Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

  8. Early-onset dementias: diagnostic and etiological considerations

    PubMed Central

    2013-01-01

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

  9. Early-onset acral basal cell carcinomas in Gorlin syndrome.

    PubMed

    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

    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

  10. Early onset Haemophilus influenzae sepsis in the newborn infant.

    PubMed

    Kinney, J S; Johnson, K; Papasian, C; Hall, R T; Kurth, C G; Jackson, M A

    1993-09-01

    Neonatal sepsis caused by Haemophilus influenzae is characterized by an early onset syndrome associated with pneumonia, shock and neutropenia. Over a 30-month period 13 infants referred to this hospital had early onset H. influenzae sepsis. Obstetric complications included preterm labor (92%), prolonged rupture of membranes > 12 hours (63%), maternal fever (64%), chorioamnionitis (43%), vaginal discharge (44%) and premature rupture of membranes (15%). All 13 infants were symptomatic at delivery and 7 required immediate intubation. Pneumonia and respiratory distress were the prominent clinical findings. H. influenzae was isolated from infant blood, maternal blood, placenta and genital tract. Isolates were predominantly non-type b, beta-lactamase-negative. A study to determine the prevalence of H. influenzae colonization of the genital tract among women attending clinic at the hospital with the most cases showed a rate of 0.3%. Perinatal risk factors and clinical findings in the infants are similar to disease caused by other organisms associated with early onset sepsis. PMID:8414801

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

    PubMed

    Giráldez, María Dolores; López-Dóriga, Adriana; Bujanda, Luis; Abulí, Anna; Bessa, Xavier; Fernández-Rozadilla, Ceres; Muñoz, Jenifer; Cuatrecasas, Miriam; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Piqué, Josep M; Carracedo, Angel; Ruiz-Ponte, Clara; Cosme, Angel; Enríquez-Navascués, José María; Moreno, Victor; Andreu, Montserrat; Castells, Antoni; Balaguer, Francesc; Castellví-Bel, Sergi

    2012-03-01

    Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies. PMID:22235025

  12. Childhood Risk Factors for Early-Onset Drinking*

    PubMed Central

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

    2011-01-01

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

  13. Early onset sepsis in very low birth weight newborn infants.

    PubMed

    Pisani, Valentina; Bizzarri, Bianca; Cardi, Veronica; Pedicino, Roberto; Natale, Fabio; Stolfi, Ilaria; Castronovo, Antonella; De Curtis, Mario

    2012-10-01

    Early onset sepsis (EOS) is a severe problem affecting very low birth weight (VLBW) infants and is associated with a threefold increased risk of mortality. Although advances in perinatal care have led to improved survival of VLBW infants over recent decades, survival without major neonatal morbidity has not increased. The authors reviewed the current literature on EOS, focusing on the peculiarities concerning risk factors, etiology, diagnosis, treatment and outcome in very low birth weight infants, and on the recent advances in the management of this condition. PMID:23016613

  14. Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

    PubMed Central

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

    2013-01-01

    Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current diagnostic system makes few modifications to accommodate children and adolescents. Researchers in this area have developed specific BPSD definitions that affect the generalizability of their findings to all youth with BPSD. Despite knowledge gains from the research, BPSDs are still difficult to diagnose because clinicians must: (1) consider the impact of the child’s developmental level on symptom presentation (e.g., normative behavior prevalence, environmental limitations on youth behavior, pubertal status, irritability, symptom duration); (2) weigh associated impairment and course of illness (e.g., neurocognitive functioning, failing to meet full DSM criteria, future impairment); and (3) make decisions about appropriate assessment (differentiating BPSD from medical illnesses, medications, drug use, or other psychiatric diagnoses that might better account for symptoms; comorbid disorders; informant characteristics and assessment measures to use). Research findings concerning these challenges and relevant recommendations are offered. Areas for further research to guide clinicians’ assessment of children with early-onset BPSD are highlighted. PMID:19466543

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

    PubMed Central

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

    2010-01-01

    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

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

    PubMed

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

    2015-12-30

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

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

    PubMed Central

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

    2015-01-01

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

  18. Deficits in facial expression recognition in male adolescents with early-onset or adolescence-onset conduct disorder

    PubMed Central

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

    2009-01-01

    Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that early-onset and adolescence-limited forms of CD are subject to different aetiological processes. Method: Male adolescents with either early-onset CD (n =42) or adolescence-onset CD (n =39), and controls with no history of serious antisocial behaviour and no current psychiatric disorder (n =40) completed tests of facial expression and facial identity recognition. Dependent measures were: (a) correct recognition of facial expressions of anger, disgust, fear, happiness, sadness, and surprise, and (b) the number of correct matches of unfamiliar faces. Results: Relative to controls, recognition of anger, disgust, and happiness in facial expressions was disproportionately impaired in participants with early-onset CD, whereas recognition of fear was impaired in participants with adolescence-onset CD. Participants with CD who were high in psychopathic traits showed impaired fear, sadness, and surprise recognition relative to those low in psychopathic traits. There were no group differences in facial identity recognition. Conclusions: Both CD subtypes were associated with impairments in facial recognition, although these were more marked in the early-onset subgroup. Variation in psychopathic traits appeared to exert an additional influence on the recognition of fear, sadness and surprise. Implications of these data for the developmental taxonomic theory of antisocial behaviour are discussed. PMID:19432683

  19. Pregnancy and early onset pauciarticular juvenile chronic arthritis

    PubMed Central

    Musiej-Nowakowska, E.; Ploski, R.

    1999-01-01

    OBJECTIVES—To study interaction of early onset pauciarticular juvenile chronic arthritis (EOP-JCA) and pregnancy in the Polish population, in particular to confirm the ameliorating effect of pregnancy on disease activity reported by others and to analyse the factors that govern the occurrence of postpartum flare, with emphasis on the potential role of breast feeding.?METHODS—The reproductive outcome and disease status in 39 adult women with history of EOP- JCA was examined by means of a questionnaire and an interview. In all patients the disease onset occurred before the 6th birthday, 19 had persistent pauciarticular JCA (PeEOP-JCA) and 20 had extended pauciarticular JCA (ExEOP-JCA).?RESULTS—23 women had at least one successful pregnancy, seven had unsuccessful pregnancies but all of them had also one or more successful pregnancies. Among those who have never been pregnant (n=16) there was a higher frequency of eye disease and ExEOP-JCA compared with the rest of the group. In almost all cases pregnancy was associated with remission of disease activity, however a postpartum flare appeared after 22 pregnancies (52%). The flares were more frequent in women who had an active disease before pregnancy, had a flare after a previous pregnancy and/or were breast feeding.?CONCLUSIONS—In EOP-JCA patients pregnancy generally has a good outcome and induces amelioration of disease activity. After delivery, however, a flare of disease often appears, especially in women who were breast feeding, had a postparum flare previously or had an active disease before pregnancy. The pattern of interaction between disease and pregnancy found in EOP-JCA makes EOP-JCA similar in this respect to RA, but different from systemic lupus erythematosus and ankylosing spondylitis.?? PMID:10419865

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

    PubMed

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

    2015-10-01

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

  1. Early onset of ghrelin production in a marsupial.

    PubMed

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

    2009-02-27

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

  2. Early onset recall pneumonitis during targeted therapy with sunitinib

    PubMed Central

    2013-01-01

    Background Sunitinib interacts with radiation therapy, leading to synergism of the toxicities of these treatments. Radiation recall pneumonitis is a rare but serious complication of targeted therapy with tyrosine kinase inhibitors. Case presentation The case of a patient with metastatic renal cell cancer (RCC) who developed recall pneumonitis on the first cycle of systemic sunitinib treatment is reported here. A 65-year-old man with RCC and bone metastasis underwent radiation therapy on his thoracic vertebrae (Th5-8) with a total dose of 24 Gy. Sunitinib (37.5 mg) was started 14 days after completing the radiation therapy. On the 14th day of sunitinib treatment, the patient developed progressive fever with worsening of dyspnea and general weakness. Treatment with pulse administration of prednisolone 1,000 mg for 3 days was initiated. Thereafter, the symptoms and the radiological findings regarding the interstitial filtration gradually improved over 7 days. Conclusion To our knowledge, this is the first report of early onset recall pneumonitis during sunitinib therapy. At present, how sunitinib interacts with radiation therapy remains unclear. The possibility that tyrosine kinase inhibitor therapy, including with sunitinib, after radiation therapy may lead to adverse effects should be kept in mind. PMID:23282195

  3. Speciation of presumptive viridans streptococci from early onset neonatal sepsis.

    PubMed

    West, P W; Al-Sawan, R; Foster, H A; Electricwala, Q; Alex, A; Panigrahi, D

    1998-10-01

    Twenty isolates resembling viridans streptococci, 16 from blood and four from gastric aspirates, from 17 cases of early onset neonatal sepsis were identified by the API20 Strep, Rapid ID 32 Strep and conventional tests plus hydrolysis of methylumbelliferyl glycoside substrates. Nineteen of the isolates were identified as species of viridans streptococci and one as a Leuconostoc sp. Ten of the isolates were Streptococcus oralis, three S. mitis biotype 1, two S. mitis biotype 2 and one each of S. sanguis, S. vestibularis, S. salivarius and S. intermedius. The Rapid ID 32 Strep and conventional plus methylumbelliferyl tests gave the same species identity for 17 of the isolates. S. intermedius was identified by the Rapid ID 32 Strep as S. constellatus and S. salivarius as S. equinus, with S. salivarius at lower probability. The API20 Strep failed to identify S. vestibularis and identified S. salivarius as S. defectivus. The absence of certain critical tests, including urea hydrolysis, does not allow the API20 Strep to identify all the currently recognised species of viridans steptococci. The species distribution was unexpected and the incidence of S. oralis and other viridans streptococci in vaginal swabs from prenatal patients is being investigated further. PMID:9788817

  4. Characterization of early and late onset psoriasis in the Korean population.

    PubMed

    Youn, J I; Park, B S; Park, S B; Kim, S D; Suh, D H

    1999-10-01

    It has been proposed that two types of psoriasis can be characterized based upon age of onset. The purpose of our study was to investigate the characteristics of early and late onset psoriasis in the Korean population. A total of 986 psoriasis patients were included in this study, and the age of onset frequency proved to be bimodal. Family history in the first-degree relatives was significantly higher in the early onset group (< 40 years old) when compared with the late onset group (> or = 40 years old). A series of statistical analyses concerning the correlation between the extent of involvement and age of onset showed that earlier onset is related to more extensive involvement. A questionnaire survey concerning the influence of various external factors upon their psoriasis was given to a subgroup of 800 psoriasis patients. Multiple logistic regression analysis, controlled for confounding factors such as current age, sex and extent of involvement, revealed that early onset psoriasis patients showed significantly increased tendencies to worsen at times of psychological stress and in winter, and to improve in summer, compared with late onset psoriasis patients. In conclusion, distribution of the age of onset revealed two peaks in Korean psoriasis patients, and psoriasis with an onset prior to the age of 40 years was associated with increased inheritability, greater susceptibility to seasonal changes and more psychological stress than psoriasis with later onset. PMID:10554430

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

    SciTech Connect

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

    1995-12-18

    Recently several reports have extended the apolipoprotein E (APOE) {epsilon}4 association found in late-onset Alzheimer`s disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset {<=}60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE {epsilon}A allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that, for an individual, bearing at least one {epsilon}4 allele increases both the risk of AD before age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases. 19 refs., 3 tabs.

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

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

    ERIC Educational Resources Information Center

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

    2009-01-01

    Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

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

    ERIC Educational Resources Information Center

    Babineau, Mireille; Shi, Rushen

    2014-01-01

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

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

    PubMed

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

    2008-03-15

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Background The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent. Methods We performed a fine mapping association study of early onset IBD using high-density Immunochip genotyping on 1008 pediatric-onset IBD cases (801 Crohn’s disease; 121 ulcerative colitis and 86 IBD undetermined) and 1633 healthy controls. Of the 158 SNP genotypes obtained (out of the 163 identified in adult onset), this study replicated 4% (5 SNPs out of 136) of the SNPs identified in the Crohn’s disease (CD) cases and 0.8% (1 SNP out of 128) in the ulcerative colitis (UC) cases. Replicated SNPs implicated the well known NOD2 and IL23R. The point estimate for the odds ratio (ORs) for NOD2 was above and outside the confidence intervals reported in adult onset. A polygenic liability score weakly predicted the age of onset for a larger collection of CD cases (p< 0.03, R2= 0.007), but not for the smaller number of UC cases. Conclusions The allelic architecture of common susceptibility variants for early onset IBD is similar to that of adult onset. This immunochip genotyping study failed to identify additional common variants that may explain the distinct phenotype that characterize early onset IBD. A comprehensive dissection of genetic loci is necessary to further characterize the genetic architecture of early onset IBD. PMID:26098103

  13. Burn injury in patients with early-onset neurological impairments: 2002 ABA paper.

    PubMed

    Alden, N E; Rabbitts, A; Rolls, J A; Bessey, P Q; Yurt, R W

    2004-01-01

    Many patients suffer from sensorimotor deficits that may contribute to burn injury. This retrospective study examines burn injuries in the subgroup of patients that suffer from the early onset neurological impairments of mental retardation, cerebral palsy, spina bifida, autism, and attention deficit-hyperactivity disorder. Fifty-one patients who suffered from the above-mentioned early-onset neurological impairments were admitted to our burn center during a 4-year period. The average TBSA burned was 8.9% yet resulted in prolonged hospitalizations. This study describes our burn center's experience in treating patients admitted with early-onset neurological impairments. PMID:14726747

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

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

    ERIC Educational Resources Information Center

    Schonfeld, Lawrence; And Others

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  18. Early-Onset, Regular Cannabis Use Is Linked to IQ Decline

    MedlinePLUS

    ... Is Linked to IQ Decline Early-Onset, Regular Cannabis Use Is Linked to IQ Decline Email Facebook ... that cannabis use may harm the developing brain. Cannabis Use Correlates With Cognitive Decline The study participants ...

  19. Recurrent papilloedema and early onset optic atrophy in Behçet's syndrome.

    PubMed Central

    Teh, L S; O'Connor, G M; O'Sullivan, M M; Pandit, J C; Beck, L; Williams, B D

    1990-01-01

    Two patients with Behçet's syndrome and intracranial hypertension are reported. One developed a recurrence of papilloedema while receiving treatment but eventually made a full recovery, whereas the other developed optic atrophy within three months of onset despite treatment. Images PMID:2383068

  20. Social Anxiety and Onset of Drinking in Early Adolescence

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    PubMed

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

    2015-12-01

    Marijuana (MJ) use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n=24) and late onset (age 16 or later; n=26), and 34 healthy control participants (HCs). All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week) of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth. PMID:25936584

  2. Ipsilateral Reorganization of Language in Early-Onset Left Temporal Lobe Epilepsy.

    PubMed

    Bell, Brian; Hermann, Bruce; Seidenberg, Michael; Davies, Keith; Cariski, Denise; Rosenbek, Jay; Woodard, Austin; Rutecki, Paul; Bishop, Malachy

    2002-04-01

    Purpose. Decline in confrontation naming ability occurs in a subset of temporal lobe epilepsy (TLE) patients following left (dominant) anterior temporal lobectomy (ATL). Patients with late age of onset of seizures are most vulnerable to such decline. In addition, object names typically acquired later in language development are the words most likely to be inaccessible after ATL. Early-onset left TLE patients may be at lower risk for post-ATL dysnomia either because they have a limited preoperative lexicon that does not include most late-age-of-acquistion names or they undergo early ipsilateral language reorganization, which results in a lexicon similar to that of late-onset TLE patients but offers protection from post-ATL naming decline.Methods. Sixty-five left hemisphere speech dominant left TLE patients who had undergone ATL were assessed pre- and postoperatively on the Boston Naming Test (BNT).Results. The early- and late-onset groups performed similarly across three BNT age-of-acquisition categories at the preoperative assessment. Words acquired relatively later in life were most likely to become inaccessible postoperatively for both groups, but the early-onset patients showed significantly less overall postoperative decline in naming ability compared with the late-onset group.Conclusions. The more stable pre- to postoperative naming performance exhibited by early-onset patients cannot be attributed to lack of acquisition of the words shown to be most vulnerable to postoperative decline (i.e., late-age-of-acquisition words). Their object naming stability suggests that early-onset left TLE patients undergo intrahemispheric reorganization of language early in life that provides protective benefits. PMID:12609417

  3. Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset.

    PubMed

    Jiang, Jia-Horng; Chiu, Nan-Chang; Huang, Fu-Yang; Kao, Hsin-An; Hsu, Chyong-Hsin; Hung, Han-Yang; Chang, Jui-Hsing; Peng, Chun-Chih

    2004-10-01

    Neonatal sepsis is a major cause of death in newborns despite sophisticated neonatal intensive care. This retrospective study reviewed the clinical characteristics of cases of culture-proven sepsis in a neonatal intensive care unit from January 1992 to December 2001. Patients were divided into those with onset of sepsis in the first 7 days of life (early-onset group) and those with onset after the seventh day of life (late-onset group). A total of 270 cases with 325 episodes of sepsis and 353 isolated pathogens were identified and included in the study. The male-to-female ratio was 1.4. The majority of cases of sepsis occurred in low birth weight (75.9%) and premature babies (76.7%). Late onset occurred in 71.9% of cases. Patients with late onset had a lower mortality rate than those with early onset (11.3% vs 28.9%). Coagulase-negative staphylococci (20.1%) was the most common organism isolated, but infection with Pseudomonas aeruginosa was associated with the highest morality rate (55.0%). Late-onset sepsis was significantly more common in very low birth weight and premature infants. The most frequently encountered pathogens in the early-onset group were group B streptococci (GBS) and Escherichia coli, while in the late-onset group, the organisms were coagulase-negative staphylococci and Enterobacteriaceae, including E. coli, Klebsiella pneumoniae, and Acinetobacter baumannii. GBS infection resulted in the highest mortality when the onset of sepsis was within the first 24 hours of life. PMID:15497012

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

    ERIC Educational Resources Information Center

    Olusanya, Bolajoko O.

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed

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

    2014-12-14

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Early Onset of Adolescent Sexual Behavior and Drug Involvement.

    ERIC Educational Resources Information Center

    Rosenbaum, Emily; Kandel, Denise B.

    1990-01-01

    Investigated relationship between drug use and sexual activity prior to age 16 using data from 2 youngest birth cohorts (N=2,711) from National Longitudinal Survey of Young Adults. When other important risk factors were controlled, reported prior use of cigarettes, alcohol, marijuana, and other illicit drugs greatly increased the risk of early

  10. Assessment of Systemic Inflammatory Markers in Patients with Aggressive Periodontitis

    PubMed Central

    Iqbal, P Safar; Khan, S Nubesh; Haris, Mohamed; Narayanan, Mahesh; Laju, S; Kumar, Swaminathan Senthil

    2015-01-01

    Background: “Aggressive periodontitis (AgP) is a destructive disease characterized by the following: The involvement of multiple teeth with a distinctive pattern of periodontal tissue loss; a high rate of disease progression; an early age of onset; and the absence of systemic diseases.’’ Chronic low-level bacteremia and systemic inflammatory response have been suggested as a pathogenic link between periodontal disease and systemic disease. The present study was aimed to assess the levels of systemic inflammatory markers in patients with AgP. Methods: A sample of 50 systemically healthy patients comprised two groups, based on full mouth periodontal examination: Group I healthy individuals, includes 25 periodontally healthy subjects with fully functioning dentition. Group II includes 25 patients diagnosed clinically as AgP. Laboratory blood investigation included white blood cell (WBC) count, neutrophil count, lymphocyte count, and platelet count. Serum protein parameters included total protein (TP), albumin (ALB), and globulin (GLB). Periodontal clinical parameters including plaque index, gingival index, probing pocket depth, and clinical attachment level were recorded. Results: Data analysis shows an increase in WBC, neutrophil, lymphocyte, and platelet count and a decrease in TP, ALB, and GLB in AgP patients when compared to healthy individuals. Conclusion: Results of the present study shows an increase in blood parameters and decrease in serum protein parameters in AgP. Hence, AgP could be considered as one of the risk factors associated with the cardiovascular diseases as assessed by changes in the level of systemic inflammatory markers observed.

  11. Topical and systemic antibiotics in the management of periodontal diseases.

    PubMed

    Mombelli, Andrea; Samaranayake, Lakshman P

    2004-02-01

    Both systemic and topical antibiotics are increasingly used in the management of periodontal infections. Whilst these drugs are used mostly on an empirical basis, some contend that rational use of antibiotics should be the norm due to their wide abuse and consequential global emergence of antibiotic resistance organisms. Here we review the rationale and principles of antimicrobial therapy, treatment goals, drug delivery routes and various antibiotics that are used in the management of periodontal diseases. The pros and cons of systemic and local antibiotic therapy are described together with practical guidelines for their delivery. The available data indicate, in general, that mechanical periodontal treatment alone is adequate to ameliorate or resolve the clinical condition in most cases, but adjunctive antimicrobial agents, delivered either locally or systemically, can enhance the effect of therapy in specific situations. This is particularly true for aggressive (early onset) periodontitis, in patients with generalised systemic disease that may affect host resistance and in case of poor response to conventional mechanical therapy. Locally delivered antibiotics together with mechanical debridement are indicated for non-responding sites of focal infection or in localised recurrent disease. After resolution of the periodontal infection, the patient should be placed on an individually tailored maintenance care programme. Optimal plaque control by the patient is of paramount importance for a favourable clinical and microbiological response to any form of periodontal therapy. PMID:15005467

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

    PubMed

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

    2015-01-01

    Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely. PMID:26633520

  13. Early-onset hypoparathyroidism and chronic keratitis revealing APECED

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Simple Summary Numerous studies have documented a high prevalence of keel bone fractures in laying hens. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored. About 62% of the hens had broken keel bones at depopulation. More new fractures occurred during the time when laying rates were highest. Hens with broken keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. All birds with bumblefoot on both feet had a fracture at depopulation. Abstract Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely. PMID:26633520

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

    NASA Technical Reports Server (NTRS)

    Jones, Christine

    1992-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    SciTech Connect

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

    1995-04-24

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

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

    E-print Network

    Thompson, Paul

    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

  19. Early deglacial onset of southwestern Greenland ice-sheet retreat on the continental shelf

    E-print Network

    Carlson, Anders

    Early deglacial onset of southwestern Greenland ice-sheet retreat on the continental shelf KelseyIS) advanced onto the continental shelf during the last glacial period. While deglacial records for when the Gr of the southwestern GrIS while on the continental shelf. Sedimentation rates, and especially silt and clay fractions

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  3. Early-Onset Alcohol Use among Native American Youth: Examining Female Caretaker Influence

    ERIC Educational Resources Information Center

    Walls, Melissa L.; Whitbeck, Les B.; Hoyt, Dan R.; Johnson, Kurt D.

    2007-01-01

    This article investigates the influence of female caretaker substance use on early-onset youth drinking among Native American families in the Northern Midwest. Data include 603 Native American families, with reports from female caretakers and youths aged 10-13 years. Two potential caretaker influences are taken into account: adolescent modeling of…

  4. Assessing early-onset hallucinations in the touch-screen generation.

    PubMed

    Demeulemeester, Morgane; Kochman, Fréderic; Fligans, Benjamin; Tabet, Ahmed J; Thomas, Pierre; Jardri, Renaud

    2015-03-01

    The increasing development of apps for digital devices provides an opportunity for new instruments to assess hallucinations in young individuals. Here we present the Multisensory HAllucinations Scale for Children (MHASC), dedicated to assessing complex early-onset hallucinations. The MHASC will soon be translated into multilanguage versions with the support of the International Consortium of Hallucination Research. PMID:25733569

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

    ERIC Educational Resources Information Center

    Unsworth, Sharon

    2013-01-01

    This study compares the development of three different types of bilingual/second language children in their acquisition of gender-marking on adjectives in Dutch to investigate whether there is evidence for age-of-onset effects in early childhood as proposed by Meisel (2009). The three groups of children are: simultaneous bilingual children,…

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

    This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…

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

    E-print Network

    Newman, Eric A.

    Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease J. Steven. Bloom, February 7, 2006 Alzheimer's disease (AD) is a progressive neurodegenerative dis- order for which Alzheimer's disease (AD), a progressive neurodegenerative disease of the elderly, is the most common cause

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

    PubMed Central

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

    2014-01-01

    Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age-11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual SNP-based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early-onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset. PMID:25422974

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

    PubMed Central

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

    2015-01-01

    Background Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT) type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive. Methodology and Principal Findings Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability. Conclusion GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies. PMID:26244500

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

    SciTech Connect

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

    1995-06-19

    Characteristics of familial aggregation of Alzheimer`s Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer`s disease. 58 refs., 5 figs., 2 tabs.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Lee, Soon Min; Chang, Meayoung

    2015-01-01

    Neonatal sepsis remains one of the most important causes of death and co-morbidity in very-low-birth-weight (VLBW) infants. The aim of this study was to determine the current incidences of early-onset sepsis (EOS) and late-onset sepsis (LOS), the distribution of pathogens, and the impact of infection on co-morbidities in VLBW infants. We analyzed the data including sepsis episode from 2,386 VLBW infants enrolled in Korean Neonatal Network from January 2013 to June 2014. We defined EOS as a positive blood culture occurring between birth and 7 days of life and LOS after 7 days of life. Sepsis was found in 21.1% of VLBW infants. The risk of sepsis was inversely related to birth weight and gestational age. EOS was found in only 3.6% of VLBW infants, however the mortality rate was as high as 34.1%. EOS was associated with the increased odds for bronchopulmonary dysplasia and intraventricular hemorrhage. The vast majority of EOS was caused by Gram-positive organisms, particularly coagulase-negative staphylococci (30.6%). LOS developed in 19.4% of VLBW infants with a 16.1% mortality rate. Pathogens in LOS were dominated by coagulase-negative staphylococci (38.3%). Twenty-five percent and fifty percent of first LOS episode occurred after 12 days and 20 days from birth, respectively. Younger and smaller VLBW infants showed the earlier occurrence day for the 25% of first LOS episode. This study provides a recent nationwide epidemiology of sepsis in VLBW infants in Korea. Based on this study, successful strategies to reduce infections would improve survival and reduce morbidity. PMID:26566360

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

    SciTech Connect

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

    1995-02-27

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

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

    PubMed Central

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

    2015-01-01

    Early onset deformity of the spine and chest wall (initiated <8 years of age) is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old). Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old). Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8). Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55°) had decreased body weight (89%), right (59%) and left (86%) lung mass, right (74%) and left (69%) radial alveolar count, right lung volume at total lung capacity (60%), and forced vital capacity (75%). Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may also have future use as a platform to evaluate treatment effectiveness. PMID:26317230

  16. Modified areal cartography in auditory cortex following early- and late-onset deafness.

    PubMed

    Wong, Carmen; Chabot, Nicole; Kok, Melanie A; Lomber, Stephen G

    2014-07-01

    Cross-modal plasticity following peripheral sensory loss enables deprived cortex to provide enhanced abilities in remaining sensory systems. These functional adaptations have been demonstrated in cat auditory cortex following early-onset deafness in electrophysiological and psychophysical studies. However, little information is available concerning any accompanying structural compensations. To examine the influence of sound experience on areal cartography, auditory cytoarchitecture was examined in hearing cats, early-deaf cats, and cats with late-onset deafness. Cats were deafened shortly after hearing onset or in adulthood. Cerebral cytoarchitecture was revealed immunohistochemically using SMI-32, a monoclonal antibody used to distinguish auditory areas in many species. Auditory areas were delineated in coronal sections and their volumes measured. Staining profiles observed in hearing cats were conserved in early- and late-deaf cats. In all deaf cats, dorsal auditory areas were the most mutable. Early-deaf cats showed further modifications, with significant expansions in second auditory cortex and ventral auditory field. Borders between dorsal auditory areas and adjacent visual and somatosensory areas were shifted ventrally, suggesting expanded visual and somatosensory cortical representation. Overall, this study shows the influence of acoustic experience in cortical development, and suggests that the age of auditory deprivation may significantly affect auditory areal cartography. PMID:23413302

  17. ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia

    PubMed Central

    Meijer, Rowdy P. P.; Pijl, Benjamin J.; Timmermans, Janneke; Cruysberg, Johannes R. M.; Bos, Maaike M.; Schelhaas, Helenius J.; van de Warrenburg, Bart. P. C.; Knoers, Nine V. A. M.; Scheffer, Hans; Kremer, Berry

    2008-01-01

    Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS: MIM 270550) is a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. This disorder, considered to be rare, was first described in the late seventies among French Canadians in the isolated Charlevoix-Saguenay region of Quebec. Nowadays, it is known that the disorder is not only limited to this region but occurs worldwide. Our objective was to identify cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) in Dutch patients with recessive early-onset cerebellar ataxia by sequencing the complete SACS gene. In a Dutch cohort of 43 index patients with ataxia onset before age 25, we identified 16 index patients (total 23 patients) with mutations in the SACS gene. Nine of them had homozygous mutations, and seven of them had compound heterozygous mutations. Retrospectively, the phenotype of patients carrying mutations was remarkably uniform: cerebellar ataxia with onset before age 13 years, lower limb spasticity and sensorimotor axonal neuropathy, and cerebellar (vermis) atrophy on magnetic resonance imaging, consistent with the core ARSACS phenotype previously described. The high rate of mutations (37%) identified in this cohort of Dutch patients suggests that ARSACS is substantially more frequent than previously estimated. We predict that the availability of SACS mutation analysis as well as an increasing awareness of the characteristic ARSACS phenotype will lead to the diagnosis of many additional patients, possibly even at a younger age. PMID:18465152

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

    Song, Limeng; Zhong, Mei

    2015-01-01

    We conducted a case-control study to investigate the role of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) polymorphisms in the development of early-onset preeclampsia. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the polymorphisms of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872). The genotype distributions of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) confirmed with HWE in the controls, and the P value for HWE was 0.41, 0.38 and 0.26, respectively. The results of the multivariate logistic regression analysis revealed that the association of individuals expressing the CC genotype and AC+CC of IL-10 -592A/C (rs1800872) with a significantly increased risk of early-onset preeclampsia in co-dominant and dominant models, compared to the AA genotype; the OR (95% CI) for these individuals was determined to be 2.09 (1.12-3.90) and 1.66 (1.03-2.71), respectively. In the recessive model, we found that CC genotype of IL-10 -592A/C (rs1800872) was associated with the increased risk of early-onset preeclampsia when compared with AA+AC genotype (OR = 1.67; 95% CI = 1.01-2.92). In conclusion, our study has indicated that IL-10 -592A/C (rs1800872) polymorphism was associated with an increased risk of early-onset preeclampsia in a Chinese population. PMID:26617906

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

    PubMed Central

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

    2014-01-01

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

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

    E-print Network

    Corey, David P.

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  4. Executive Abilities as Reflected by Clock Hand Placement: Frontotemporal Dementia Versus Early-Onset Alzheimer Disease.

    PubMed

    Barrows, Robin J; Barsuglia, Joseph; Paholpak, Pongsatorn; Eknoyan, Donald; Sabodash, Valeriy; Lee, Grace J; Mendez, Mario F

    2015-12-01

    The clock-drawing test (CDT) is widely used in clinical practice to diagnose and distinguish patients with dementia. It remains unclear, however, whether the CDT can distinguish among the early-onset dementias. Accordingly, we examined the ability of both quantitative and qualitative CDT analyses to distinguish behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer disease (eAD), the 2 most common neurodegenerative dementias with onset <65 years of age. We hypothesized that executive aspects of the CDT would discriminate between these 2 disorders. The study compared 15 patients with bvFTD and 16 patients with eAD on the CDT using 2 different scales and correlated the findings with neuropsychological testing and magnetic resonance imaging. The total CDT scores did not discriminate bvFTD and eAD; however, specific analysis of executive hand placement items successfully distinguished the groups, with eAD exhibiting greater errors than bvFTD. The performance on those executive hand placement items correlated with measures of naming as well as visuospatial and executive function. On tensor-based morphometry of the magnetic resonance images, executive hand placement correlated with right frontal volume. These findings suggest that lower performance on executive hand placement items occurs with involvement of the right dorsolateral frontal-parietal network for executive control in eAD, a network disproportionately affected in AD of early onset. Rather than the total performance on the clock task, the analysis of specific errors, such as executive hand placement, may be useful for early differentiation of eAD, bvFTD, and other conditions. PMID:26251109

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

    Objective: To examine the diagnostic stability and the functional outcome of patients with early-onset psychosis (EOP) over a 2-year follow-up period. Methods: A total of 24 patients (18 males (75%) and 6 females (25%), mean age [plus or minus] SD: 15.7 [plus or minus] 1.6 years) with a first episode of EOP formed the sample. Psychotic symptoms…

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

    PubMed

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

    2007-02-01

    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

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

    PubMed

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

    2015-09-01

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

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

    NASA Technical Reports Server (NTRS)

    Frey, H.

    1977-01-01

    The fundamental crustal dichotomy of the Earth (high and low density crust) was established nearly 4 billion years ago. Therefore, subductable crust was concentrated at the surface of the Earth very early in its history, making possible an early onset for plate tectonics. Simple thermal history calculations spanning 1 billion years show that the basin forming impact thins the lithosphere by at least 25%, and increases the sublithosphere thermal gradients by roughly 20%. The corresponding increase in convective heat transport, combined with the highly fractured nature of the thinned basin lithosphere, suggest that lithospheric breakup or rifting occurred shortly after the formation of the basins. Conditions appropriate for early rifting persisted from some 100,000,000 years following impact. We suggest a very early stage of high temperature, fast spreading "microplate" tectonics, originating before 3.5 billion years ago, and gradually stabilizing over the Archaean into more modern large plate or Wilson Cycle tectonics.

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

    PubMed Central

    2011-01-01

    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

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

    PubMed

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

    2015-12-01

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

  12. Evidence of early onset of antidepressant effect in randomized controlled trials.

    PubMed

    Stahl, S M; Nierenberg, A A; Gorman, J M

    2001-01-01

    Although antidepressant medications are effective in approximately 70% of patients with major depressive disorder, they have a delayed onset of therapeutic effect. This latency is problematic in that it prolongs the impairments associated with depression, leaves patients vulnerable to an increased risk of suicide, increases the likelihood that a patient will prematurely discontinue therapy, and increases medical costs associated with severe depression. No adequately designed prospective trials have been conducted to evaluate comparative time to onset of antidepressant effect. However, evidence suggests that some antidepressant agents may begin to work faster than others. Citalopram, venlafaxine, and mirtazapine each have exhibited statistically significant differences in some measures of antidepressant action within the first 2 weeks of treatment, both in placebo-controlled trials and in head-to-head comparisons with other antidepressants. This article reviews the data that hint at these drug-specific differences in time to onset of action. Given the potential benefits of early-acting antidepressant treatments, the possibility of superior speed of onset of citalopram, venlafaxine, and mirtazapine presented here merits further study in adequately designed, prospective clinical trials. PMID:11229783

  13. Herlyn–Werner–Wunderlich syndrome: An “earlyonset case report and review of Literature

    PubMed Central

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

    2015-01-01

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

  14. Effectiveness and safety of antipsychotics in early onset psychoses: a long-term comparison.

    PubMed

    Cianchetti, Carlo; Ledda, Maria Giuseppina

    2011-10-30

    The effectiveness and safety of various antipsychotics was evaluated in a long-term study on 47 patients, 29 with schizophrenia and 18 with schizoaffective disorder, aged 10 to 17 years (mean 15.5) at onset. Follow-up ranged from 3 years (all 47 patients) to 11 years (19 patients). Data were collected on the following antipsychotics: haloperidol, risperidone, olanzapine, quetiapine, aripiprazole and clozapine. Cases with positive response were significantly more frequent with clozapine as compared to haloperidol, risperidone and olanzapine. Risperidone was significantly better than haloperidol at the 3-year follow-up. A comparison of the degree of clinical improvement evaluated with PANSS and CGI in patients treated with drugs in subsequent periods showed clozapine led to significantly greater improvement as compared to haloperidol, risperidone and olanzapine, and risperidone as compared to haloperidol. Data on long-term functioning significantly favored clozapine as compared to all the other drugs. Discontinuation due to side effects involved 20% patients with clozapine, lower percentage with the other drugs. The results of this study on early-onset schizophrenic and schizoaffective disorders confirm that even in the long-term, clozapine is more effective than haloperidol, risperidone and olanzapine. Despite a relevant incidence of adverse effects, clozapine seems to have unique effectiveness in treating children and adolescents with early-onset schizophrenic disorders. PMID:21570128

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

    PubMed

    Alsiddiky, A M

    2015-08-01

    Early-onset scoliosis is an onerous challenge to physicians. These patients are young with significant remaining growth potential. Thus, patients are likely to develop progressive deformities, cosmetic disfigurement and cardiopulmonary consequences warrant early intervention in many cases. The purpose of this review is to provide the readers with brief description of the disease, therapeutic modalities available and their indications and use. Publications and abstracts related to EOS in the last decade were carried out and synthesized into a review "an insight into early onset of scoliosis." A comprehensive understanding of the scoliosis, its impact on the thoracic development may guide in treatment, which is often required at a young age in these children to prevent irreversible pulmonary insufficiency. Current treatment techniques are based on multiple factors may include non-surgical strategies, such as Derotational body cast or brace in younger patients with curve <50 degrees. Surgical treatment of spinal deformity should be considered when nonoperative measures are failed to arrest curve progression. Growing rods have been the mainstay treatment of early-onset scoliosis which require repeated surgeries for distraction and are associated with exponential increase in complications. The vertical expandable prosthetic titanium rib may be beneficial for those patients with congenital scoliosis and fused ribs and thoracic insufficiency syndrome. Shilla technique is an alternative to growing rods that avoids the morbidity of repeated lengthening. Growth modulation using staples or tethers shows promise for milder curvatures, but further follow-up is needed to define their use. Although new technologies have improved the treatment of children with EOS but it continues to be challenging with high complication rates. PMID:26241527

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

    PubMed

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

    2014-10-01

    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

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

    PubMed

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

    2015-12-01

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

  18. A novel dystrophin deletion mutation in a becker muscular dystrophy patient with early-onset dilated cardiomyopathy.

    PubMed

    Guo, Xiaoxiao; Dai, Yi; Cui, Liying; Fang, Quan

    2014-08-01

    Becker muscular dystrophy (BMD) is a rare cause of dilated cardiomyopathy (DCM). We present a 23-year-old patient with BMD and early-onset DCM in whom cardiovascular magnetic resonance showed extensive myocardial late gadolinium enhancement and previously unreported findings of subepicardial fat infiltration in the lateral wall. In addition, this patient carried a rare mutation of dystrophin gene that might be a new genetic predisposition to early-onset DCM in BMD. PMID:24996370

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

    IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical ?-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological presentation reminiscent of LRRK2-associated PD neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS should be considered for genetic testing, and those with a known 22q11.2 deletion should be monitored for the development of parkinsonian symptoms. Molecular studies of the implicated genes, including DGCR8, may help shed light on the underlying pathophysiology of PD in 22q11.2DS and idiopathic PD. PMID:24018986

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

    PubMed

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

    2014-01-24

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

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

    PubMed Central

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

    2014-01-01

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

  10. Early onset neonatal group B streptococcus (GBS) infection: associated obstetric risk factors.

    PubMed

    Garland, S M

    1991-05-01

    An analysis of all early onset neonatal Group B streptococcal (GBS) infections at the Royal Women's Hospital, Melbourne was made for the 10-year period 1979-1988. There were 104 cases with 29 neonatal deaths (28%). One or more predisposing perinatal risk factors was evident in 82% of cases (premature labour 79%, prolonged membrane rupture (greater than 12 hours) 57%, premature rupture of the membranes 69%, maternal sepsis 29%). Overall, 88% of GBS infections were evident within 24 hours of birth, suggesting an intrapartum pathogenesis for infection. PMID:1930030

  11. Periodontal Treatments and Procedures

    MedlinePLUS

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

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

    PubMed

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

    2015-12-31

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

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

    PubMed Central

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

    2015-01-01

    The term early age-of-onset Alzheimer’s disease (EOAD) identifies patients who meet criteria for AD, but show onset of symptoms before the age of 65. We map progression of gray matter (GM) atrophy in EOAD patients compared to late onset AD (LOAD). T1-weighted MRI scans were obtained at diagnosis and one-year follow-up from 15 EOAD, 10 LOAD, and 38 age-matched controls. Voxel-based and tensor-based morphometry were used, respectively, to assess the baseline and progression of atrophy. At baseline, EOAD patients already showed a widespread atrophy in temporal, parietal, occipital and frontal cortices. After one year, EOAD had atrophy progression in medial temporal and medial parietal cortices. At baseline, LOAD patients showed atrophy in the medial temporal regions only, and, after one year, an extensive pattern of atrophy progression in the same neocortical cortices of EOAD. Although atrophy mainly involved different lateral neocortical or medial temporal hubs at baseline, it eventually progressed along the same brain default-network regions in both groups. The cortical region showing a significant progression in both groups was the medial precuneus/posterior cingulate. PMID:25737041

  14. Sulcal morphology as a new imaging marker for the diagnosis of early onset Alzheimer's disease.

    PubMed

    Hamelin, Lorraine; Bertoux, Maxime; Bottlaender, Michel; Corne, Helene; Lagarde, Julien; Hahn, Valérie; Mangin, Jean-François; Dubois, Bruno; Chupin, Marie; de Souza, Leonardo Cruz; Colliot, Olivier; Sarazin, Marie

    2015-11-01

    We investigated the utility of sulcal width measures in the diagnosis of Alzheimer's disease (AD). Sixty-six biologically confirmed AD patients (positive amyloid positron emission tomography [PET] and/or AD cerebrospinal fluid profile) were contrasted to 35 controls with negative amyloid PET. Patients were classified into prodromal or dementia stages as well as into late onset (LOAD, n = 31) or early onset (EOAD, n = 35) subgroups according to their age of onset. An automated method was used to calculate sulcal widths and hippocampal volumes (HV). In EOAD, the greatest ability to differentiate patients from age-matched controls, regardless of severity, was displayed by sulcal width of the temporoparietal cortex. In this region, diagnosis accuracy was better than the HV, especially at prodromal stage. In LOAD, HV provided the best discrimination power from age-matched controls. In conclusion, sulcal width measures are better markers than the HV for identifying prodromal AD in patients aged <65 years. In contrast, in older patients, the risk of over-diagnosis from using only sulcal enlargement is important. PMID:26256787

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. PMID:26358864

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

    PubMed

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

    2015-10-01

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

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

    SciTech Connect

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

    1994-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Diamond, Wayde; MacDonald, Russell D

    2011-01-01

    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

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

    PubMed

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

    2015-05-01

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

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

    SciTech Connect

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

    1994-09-01

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

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

    PubMed

    Zivná, Martina; H?lková, Helena; Matignon, Marie; Hodanová, Katerina; Vylet'al, Petr; Kalbácová, Marie; Baresová, Veronika; Sikora, Jakub; Blazková, Hana; Zivný, Jan; Ivánek, Robert; Stránecký, Viktor; Sovová, Jana; Claes, Kathleen; Lerut, Evelyne; Fryns, Jean-Pierre; Hart, P Suzanne; Hart, Thomas C; Adams, Jeremy N; Pawtowski, Audrey; Clemessy, Maud; Gasc, Jean-Marie; Gübler, Marie-Claire; Antignac, Corinne; Elleder, Milan; Kapp, Katja; Grimbert, Philippe; Bleyer, Anthony J; Kmoch, Stanislav

    2009-08-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2011-08-26

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

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

    PubMed Central

    Hwang, Su-Kyeong

    2015-01-01

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

  8. Germline mutations of inhibins in early-onset ovarian epithelial tumors.

    PubMed

    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

    2014-03-01

    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

  9. A volcanically induced climate warming and floral change preceded the onset of OAE1a (Early Cretaceous)

    E-print Network

    Gilli, Adrian

    A volcanically induced climate warming and floral change preceded the onset of OAE1a (Early change Climate change Early Cretaceous Negative carbon isotope excursion OAE1a Ontong Java volcanism volcanism are proposed as triggers for climate warming, altered ocean circulation patterns and elevated

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2008-07-01

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

  14. Three weeks of early-onset exercise prolongs obesity resistance in DIO rats after exercise cessation.

    PubMed

    Patterson, Christa M; Dunn-Meynell, Ambrose A; Levin, Barry E

    2008-02-01

    We assessed the effect of early-onset exercise as a means of preventing childhood obesity using juvenile male rats selectively bred to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a 31% fat high-energy diet. Voluntary wheel running begun at 36 days of age selectively reduced adiposity in DIO vs. DR rats. Other 4-wk-old DIO rats fed a high-energy diet and exercised (Ex) for 13 wk increased their core temperature, gained 22% less body weight, and had 39% lighter fat pads compared with sedentary (Sed) rats. When wheels were removed after 6 wk (6 wk Ex/7 wk Sed), rats gained less body weight over the next 7 wk than Sed rats and still had comparable adipose pad weights to 13-wk-exercised rats. In fact, only 3 wk of exercise sufficed to prevent obesity for 10 wk after wheel removal. Terminally, the 6-wk-Ex/7-wk-Sed rats had a 55% increase in arcuate nucleus proopiomelanocortin mRNA expression vs. Sed rats, suggesting that this contributed to their sustained obesity resistance. Finally, when Sed rats were calorically restricted for 6 wk to weight match them to Ex rats (6 wk Rstr/7 wk Al), they increased their intake and body weight when fed ad libitum and, after 7 wk more, had higher leptin levels and adiposity than Sed rats. Thus, early-onset exercise may favorably alter, while early caloric restriction may unfavorably influence, the development of the hypothalamic pathways controlling energy homeostasis during brain development. PMID:17989137

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

    PubMed Central

    Dobbs, Kerry; Domínguez Conde, Cecilia; Zhang, Shen-Ying; Parolini, Silvia; Audry, Magali; Chou, Janet; Haapaniemi, Emma; Keles, Sevgi; Bilic, Ivan; Okada, Satoshi; Massaad, Michel J.; Rounioja, Samuli; Alwahadneh, Adel M.; Serwas, Nina K.; Capuder, Kelly; Ciftci, Ergin; Felgentreff, Kerstin; Ohsumi, Toshiro K.; Pedergnana, Vincent; Boisson, Bertrand; Haskolo?lu, Sule; Ensari, Arzu; Schuster, Michael; Moretta, Alessandro; Itan, Yuval; Patrizi, Ornella; Rozenberg, Flore; Lebon, Pierre; Saarela, Janna; Knip, Mikael; Petrovski, Slavé; Goldstein, David B.; Parrott, Roberta E.; Savas, Berna; Schambach, Axel; Tabellini, Giovanna; Bock, Christoph; Chatila, Talal; Comeau, Anne Marie; Geha, Raif S.; Abel, Laurent; Buckley, Rebecca H.; Ikincio?ullari, Aydan; Al-Herz, Waleed; Helminen, Merja; Do?u, Figen; Casanova, Jean-Laurent; Boztu?, Kaan; Notarangelo, Luigi D.

    2015-01-01

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

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

    PubMed

    Carone, Laura; Tischler, Victoria; Dening, Tom

    2014-11-26

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

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

    PubMed Central

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

    2010-01-01

    Patients with early age-of-onset Alzheimer’s disease show more rapid progression, more generalized cognitive deficits and greater cortical atrophy and hypometabolism compared to late-onset patients at a similar disease stage. The biological mechanisms that underlie these differences are not well understood. The purpose of this study was to examine in vivo whether metabolic differences between early-onset and late-onset Alzheimer’s disease are associated with differences in the distribution and burden of fibrillar amyloid-?. Patients meeting criteria for probable Alzheimer’s disease (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's; Disease and Related Disorders Association criteria) were divided based on estimated age at first symptom (less than or greater than 65 years) into early-onset (n = 21, mean age-at-onset 55.2 ± 5.9 years) and late-onset (n = 18, 72.0 ± 4.7 years) groups matched for disease duration and severity. Patients underwent positron emission tomography with the amyloid-?-ligand [11C]-labelled Pittsburgh compound-B and the glucose analogue [18F]-labelled fluorodeoxyglucose. A group of cognitively normal controls (n = 30, mean age 73.7 ± 6.4) was studied for comparison. [11C]-labelled Pittsburgh compound-B images were analysed using Logan graphical analysis (cerebellar reference) and [18F]-labelled fluorodeoxyglucose images were normalized to mean activity in the pons. Group differences in tracer uptake were assessed on a voxel-wise basis using statistical parametric mapping, and by comparing mean values in regions of interest. To account for brain atrophy, analyses were repeated after applying partial volume correction to positron emission tomography data. Compared to normal controls, both early-onset and late-onset Alzheimer’s disease patient groups showed increased [11C]-labelled Pittsburgh compound-B uptake throughout frontal, parietal and lateral temporal cortices and striatum on voxel-wise and region of interest comparisons (P < 0.05). However, there were no significant differences in regional or global [11C]-labelled Pittsburgh compound-B binding between early-onset and late-onset patients. In contrast, early-onset patients showed significantly lower glucose metabolism than late-onset patients in precuneus/posterior cingulate, lateral temporo–parietal and occipital corticies (voxel-wise and region of interest comparisons, P < 0.05). Similar results were found for [11C]-labelled Pittsburgh compound-B and [18F]-labelled fluorodeoxyglucose using atrophy-corrected data. Age-at-onset correlated positively with glucose metabolism in precuneus, lateral parietal and occipital regions of interest (controlling for age, education and Mini Mental State Exam, P < 0.05), while no correlations were found between age-at-onset and [11C]-labelled Pittsburgh compound-B binding. In summary, a comparable burden of fibrillar amyloid-? was associated with greater posterior cortical hypometabolism in early-onset Alzheimer’s disease. Our data are consistent with a model in which both early amyloid-? accumulation and increased vulnerability to amyloid-? pathology play critical roles in the pathogenesis of Alzheimer’s disease in young patients. PMID:20080878

  18. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    PubMed Central

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury?Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett?like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto?temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome. Analysis should be considered in these patients in the clinical setting. PMID:16611748

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

    PubMed Central

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

    2011-01-01

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

  20. Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.

    PubMed

    Macedo, Maria G; Verbaan, Dagmar; Fang, Yue; van Rooden, Stephanie M; Visser, Martine; Anar, Burcu; Uras, Antonella; Groen, Justus L; Rizzu, Patrizia; van Hilten, Jacobus J; Heutink, Peter

    2009-01-30

    Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1, PINK1, LRRK2, and SNCA genes. The aim of this study is to assess the contribution of these genes in a Dutch EOPD cohort and the phenotypic characteristics of the mutation carriers. A total of 187 unrelated Dutch EOPD patients (age at onset < or = 50 years) were phenotyped and screened for mutations in all exons of Parkin, DJ-1, and PINK1 by direct sequencing and gene dosage analysis. Additionally, analysis of the A30P mutation and exon dosage of SNCA and sequencing of exons 19,31,35,38,41, and 48 of LRRK2 was performed. Pathogenic variations could explain disease in 4% (7 of 187) of the patients including five patients carrying homozygous or compound heterozygous mutations in Parkin, one with a novel homozygous deletion in DJ-1 (P158Del) and one with a heterozygous mutation in LRRK2 (T2356I). We found seven novel mutations. The phenotypic characteristics of mutation carriers varied widely, comparable to the variability seen in sporadic EOPD. Parkin is the most frequently mutated gene in this EOPD cohort, followed by DJ-1, PINK1 and LRRK2. The low overall mutation frequency indicates that the extrapolation of mutation frequencies from other populations should be applied with caution. PMID:18973254

  1. Assessment of early onset of driver fatigue using multimodal fatigue measures in a static simulator.

    PubMed

    Jagannath, M; Balasubramanian, Venkatesh

    2014-07-01

    Driver fatigue is an important contributor to road accidents. This paper reports a study that evaluated driver fatigue using multimodal fatigue measures, i.e., surface electromyography (sEMG), electroencephalography (EEG), seat interface pressure, blood pressure, heart rate and oxygen saturation level. Twenty male participants volunteered in this study by performing 60 min of driving on a static simulator. Results from sEMG showed significant physical fatigue (? < 0.05) in back and shoulder muscle groups. EEG showed significant (? < 0.05) increase of alpha and theta activities and a significant decrease of beta activity during monotonous driving. Results also showed significant change in bilateral pressure distribution on thigh and buttocks region during the study. These findings demonstrate the use of multimodal measures to assess early onset of fatigue. This will help us understand the influence of physical and mental fatigue on driver during monotonous driving. PMID:24581559

  2. Structured regions of ?-synuclein fibrils include the early-onset Parkinson’s disease mutation sites

    PubMed Central

    Comellas, 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.

    2011-01-01

    ?-Synuclein (AS) fibrils are the major component of Lewy bodies, the pathological hallmark of Parkinson’s disease (PD). Here, we use results from an extensive investigation employing solid-state NMR to present a detailed structural characterization and conformational dynamics quantification of full-length AS fibrils. Our results show that the core extends with a repeated structural motif. This result disagrees with the previously proposed fold of AS fibrils obtained with limited solid-state NMR data. Additionally, our results demonstrate that the three single point mutations associated with early-onset PD—A30P, E46K and A53T—are located in structured regions. We find that E46K and A53T mutations, located in rigid ?-strands of the wild-type fibrils, are associated with major and minor structural perturbations, respectively. PMID:21718702

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

    PubMed Central

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

    2015-01-01

    Recently the 3D structure of the Osaka mutant form (E22?) of Amyloid-?1-40 has been determined. We here compare the NMR chemical-shift with the published shifts of a brain-seeded form of wild-type A? and suggest that the determined mutant fold is accessible to the wild-type protein as well, with small conformational adaptations which accommodate the E22 residue missing in the Osaka mutant. In addition, we illustrate how other mutants could also conform to this model. The stabilization of the N-terminal part of the protein via an intermolecular salt bridge to Lys28 may represent a common structural motif for the mutants which are related to early-onset Alzheimer disease. This feature might connect to the observed increased toxicity of the mutant forms compared to wild-type A?1-40, where the salt bridge involving Lys28 is intramolecular. PMID:25988181

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Sibonga, Jean D.

    2010-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    SciTech Connect

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

    1981-07-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

    PubMed

    van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

    2015-12-01

    A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. PMID:26535877

  13. Maternal antibiotic exposure and risk of antibiotic resistance in neonatal early-onset sepsis: a case-cohort study.

    PubMed

    Wright, Alissa Jade; Unger, Sharon; Coleman, Brenda L; Lam, Po-Po; McGeer, Allison J

    2012-11-01

    In a case-cohort study of early-onset sepsis, antibiotic resistance was more likely for infections in neonates born to mothers who were given antibiotics during pregnancy (odds ratio 4.6; 95% confidence interval: 1.1-19;P = 0.05). Risk of resistance increased with duration of antibiotics and number of antibiotic courses during pregnancy. Preterm birth and hospitalization during pregnancy were also associated with resistance. These risk factors should be considered when selecting empiric antibiotics for therapy of early-onset sepsis in infants. PMID:22926208

  14. BRCA mutations, molecular markers, and clinical variables in early-onset breast cancer: a population-based study.

    PubMed

    Musolino, Antonino; Bella, Maria A; Bortesi, Beatrice; Michiara, Maria; Naldi, Nadia; Zanelli, Paola; Capelletti, Marzia; Pezzuolo, Debora; Camisa, Roberta; Savi, Mario; Neri, Tauro M; Ardizzoni, Andrea

    2007-06-01

    Early age at onset is generally considered an indicator of genetic susceptibility to breast cancer. To address both the proportion of early-onset breast cancer associated with BRCA-1 or BRCA-2 germline mutation and the contribution of germline mutations to the clinical features and outcome of these tumors, we analyzed molecular status and clinical variables of a population-based sample of 66 Italian women diagnosed with breast cancer before the age of 40 who were unselected for family history. BRCA mutations were screened by automated sequencing of the entire BRCA-1 and BRCA-2 coding regions and splice junctions. Twenty-eight late-onset (over 45 years), sporadic, breast cancers were designated as "control group" for comparisons with early-onset cases. BRCA mutations (10 BRCA-1 and 6 BRCA-2) were detected in 15 (22.7%) out of 66 tested patients. The combination of ER, PR, HER-2/neu negativity and p53 positivity was significantly more frequent in BRCA-1 positive tumors than in BRCA-2 positive and non-BRCA tumors (P=0.03). Taken collectively, BRCA-positive tumors correlated with high histologic grade and ER negativity compared with non-BRCA and sporadic tumors (P=0.05 and 0.003, respectively). There were no significant differences between BRCA-associated breast cancers (BABC) and non-BABC in relapse-free, event-free, and overall survival. Our data confirm that the combination of age at onset and tumor phenotype can provide an efficient model for identifying individuals with a high probability of carrying BRCA mutations and support the hypothesis that breast cancer in BRCA carriers is qualitatively distinct from other early-onset breast cancers and from late-onset, sporadic, breast carcinomas. Further studies on incident cases are necessary to define the independent prognostic significance of germline BRCA mutations. PMID:17257844

  15. A Long-Term Longitudinal Examination of the Effect of Early Onset of Alcohol and Drug Use on Later Alcohol Abuse

    PubMed Central

    Ohannessian, Christine McCauley; Finan, Laura J.; Schulz, Jessica; Hesselbrock, Victor

    2015-01-01

    Background Early onset of alcohol use has been linked to later alcohol problems in adulthood. Currently, it is not clear whether early onset of marijuana and tobacco use similarly predicts alcohol problems. Moreover, most studies examining the effect of early substance use onset on later problems only have followed youth into their early 20s. Therefore, the primary goal of this study was to examine whether early onset of alcohol, marijuana, and tobacco use predicts alcohol problems beyond the transition to adulthood. Methods The sample included 225 15-19 year old youth (60% girls; 62% Caucasian) who were surveyed in 1993-1998 (Time 1), 1998–2003 (Time 2), and 2003-2007 (Time 3). Participants reported their age of onset for regular drinking, tobacco use, and marijuana use. At each time of measurement, they also completed surveys relating to their alcohol use and abuse. Results Participants with an earlier age of onset of drinking regularly scored higher on the Michigan Alcoholism Screening Test (MAST) and drank more frequently to get high and drunk throughout their twenties. Tobacco use onset and marijuana use onset were not associated with later alcohol use or abuse. Conclusions Results from this study suggest that the relationship between the onset of substance use and later substance abuse may be substance specific. Of note, early onset of regular drinking was associated with alcohol problems during adulthood, underscoring the importance of delaying the onset of regular alcohol use among youth. PMID:25671782

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

    PubMed

    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

    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

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

    PubMed Central

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

    2007-01-01

    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

  18. Motor phenotype of LRRK2 G2019S carriers in Early Onset Parkinson Disease

    PubMed Central

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

    2010-01-01

    Objective To determine the motor phenotype of LRRK2 G2019S mutation carriers Background LRRK2 mutation carriers were previously reported to manifest the tremor-dominant (TD) motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared to the postural instability gait difficulty (PIGD) phenotype. Design Cross sectional observational study Setting 13 movement disorders centers Participants 925 Early Onset Parkinson Disease (EOPD) cases defined as age at onset (AAO) ?50. Main Outcome Measures LRRK2 mutation status and PD motor phenotype: TD or PIGD Methods Demographic information, family history of PD (FHPD), and the Unified Parkinson Disease Rating Scale (UPDRS) were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish (AJ) ancestry, levodopa dose, and FHPD. Results 34 cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be AJ (55.9% vs. 11.9% p<0.001), but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (p=0.026) and were more likely to have a PIGD phenotype (92.3% vs. 58.9% p=0.003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and AJ (OR= 17.7, p< 0.001). Conclusion EOPD G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course. PMID:20008657

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  20. Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant.

    PubMed

    Potic, Ana; Pavlovic, Aleksandra M; Uziel, Graziella; Kozic, Dusko; Ostojic, Jelena; Rovelli, Attilio; Sternic, Nadezda; Bjelan, Mladen; Sarto, Elisa; Di Bella, Daniela; Taroni, Franco

    2013-08-01

    The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe. PMID:23681646

  1. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    PubMed Central

    Mirrakhimov, Aibek E.; Khan, Farah N.

    2012-01-01

    We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient's headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer. PMID:23119207

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

    PubMed Central

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    McClellan, Jon M.; And Others

    1993-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  6. Mapping Callosal Morphology in Early-and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical

    E-print Network

    Thompson, Paul

    depression, with potentially important implications for research and therapy. Neuropsychopharmacology advanceMapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, USA

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

    ERIC Educational Resources Information Center

    Nieto, Rebeca Garcia; Castellanos, F. Xavier

    2011-01-01

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

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

    E-print Network

    Movshon, Joseph Anthony

    Effects of Early-Onset Artificial Strabismus on Pursuit Eye Movements and on Neuronal Responses pursuit eye movements. When viewing is monocular, targets are tracked well only when they are moving an anomaly in cortical visual motion processing, we recorded eye movements and cortical neural responses

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Serum immunoglobulin G subclass concentrations in periodontally healthy and diseased individuals.

    PubMed Central

    Lu, H; Wang, M; Gunsolley, J C; Schenkein, H A; Tew, J G

    1994-01-01

    Patients with localized juvenile periodontitis (LJP) often have high titers of antibody reactive with the serotype-specific immunodominant carbohydrate antigen of Actinobacillus actinomycetemcomitans serotype b. The vast majority of this A. actinomycetemcomitans serotype b-specific antibody is immunoglobulin G2 (IgG2). The present study was undertaken to determine whether the overall total levels of IgG2 in the sera of LJP patients are elevated. LJP patients and nonperiodontitis (NP) controls matched for age, race (black and white), and gender were studied. Additional controls included patients with adult periodontitis (AP) and patients similar in age to LJP patients but with the more-severe, generalized form of early-onset periodontitis (SP). Sera from over 700 periodontally characterized subjects were examined by using radial immunodiffusion to quantitate IgG2 as well as IgG1, -3, and -4, which were included for comparison. Serum IgG2 levels increased with age, and this was most dramatic around puberty. Black subjects in all periodontal groups had nearly 1 mg more IgG2 per ml than their white counterparts. Serum IgG2 levels were elevated (about 30 to 40%) in LJP patients of both races compared with their age- and race-matched NP controls (P < 0.01). In contrast, SP patients and AP patients had IgG2 levels comparable to their age- and race-matched NP controls. No other IgG subclass concentration correlated with periodontal diagnosis except for IgG3, which was elevated in white LJP patients. We reason that the high levels of serum IgG2 in LJP may be helpful in localizing periodontal destruction. PMID:8168929

  15. Laser therapy for periodontitis

    NASA Astrophysics Data System (ADS)

    Efanov, O. I.

    2001-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2016-01-01

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

  1. Children's parasympathetic reactivity to specific emotions moderates response to intervention for early-onset aggression.

    PubMed

    Gatzke-Kopp, Lisa M; Greenberg, Mark; Bierman, Karen

    2015-01-01

    Following theories that individual differences in respiratory sinus arrhythmia (RSA) denote differential sensitivity to environmental influences, this study examines whether differences in RSA reactivity to specific emotional challenges predict differential response to intervention. We present data from a randomized clinical trial of a targeted intervention for early onset aggression. In collaboration with a high-risk urban school district, 207 kindergarten children (73% African American, 66% male), identified by their teachers as having high levels of aggressive and disruptive behavior, were recruited. All children received a universal social-emotional curriculum. One hundred children were randomly assigned to an additional intervention consisting of weekly peer-based social skills training. Complete RSA data were available for 139 of the children. Teacher-reported externalizing symptoms and emotion regulation in 1st grade (post intervention) were examined controlling for baseline levels. First-grade peer nominations of aggressive behavior, controlling for baseline nominations, were also examined as outcomes. No effect of resting RSA was found. However, greater reactivity to anger was associated with higher externalizing symptoms and lower emotion regulation skills in 1st grade relative to low reactive children. Lower reactivity to fear was associated with greater improvement over time, an effect that was enhanced in the targeted intervention condition. Results suggest that measures of affective reactivity may provide insight into children's capacity to benefit from different types of interventions. PMID:24308798

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders

    PubMed Central

    Juuhl-Langseth, Monica; Hartberg, Cecilie B.; Holmén, Aina; Thormodsen, Rune; Groote, Inge R.; Rimol, Lars M.; Emblem, Kyrre E.; Agartz, Ingrid; Rund, Bjørn R.

    2015-01-01

    Background Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB) in early onset schizophrenia spectrum disorders (EOS). To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS. Methods Twenty-four patients with EOS and 33 healthy controls (HC) were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables. Results The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034). There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship. Conclusion Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups. PMID:26230626

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

    PubMed Central

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

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000?UI of ?-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

  6. Contemporary context for early-onset group B streptococcal sepsis of the newborn.

    PubMed

    Cimolai, N; Roscoe, D L

    1995-01-01

    We examined early-onset newborn group B streptococcal (GBS) infection among the population of a large obstetric center in western Canada for the contemporary period 1987 to 1992. Attack rates for "definite" (bacteremic) and "presumptive" (urine group B antigen positive with clinical evidence) GBS infections were 0.85 and 0.90 per 1000. Ten GBS-associated stillbirths were recorded. Seven deaths occurred among bacteremic newborns (18.4%). Using definitions of Boyer and Gotoff, 87.2% of all mothers with infected newborns manifested at least one risk factor, and 69.8% of all febrile pregnancies with either definition of infected newborn and 61.9% of a subset of the same with bacteremic offspring had maternal temperature 38 degrees C or higher prior to delivery. For our population, recommendations for universal antepartum GBS screening and intrapartum prophylaxis must be discussed in the context of an existing low frequency of bacteremic disease and with the understanding that fever in pregnancy may be enough to warrant greater intervention that might further reduce the rate of infection. PMID:7710577

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

    PubMed Central

    Dakos, Vasilis; Bascompte, Jordi

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2007-06-21

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

  10. On the early onset of the NLC season 2013 as observed at ALOMAR

    NASA Astrophysics Data System (ADS)

    Fiedler, Jens; Baumgarten, Gerd; Berger, Uwe; Gabriel, Axel; Latteck, Ralph; Lübken, Franz-Josef

    2015-05-01

    On 21 May the ALOMAR RMR-lidar in Northern Norway detected the first noctilucent clouds (NLC) in 2013. This unusual early NLC onset was accompanied by ?6 K lower temperatures and higher water vapor mixing ratios at NLC altitudes from the end of April until the beginning of June. The zonal mean temperature and dynamic conditions in the Arctic middle atmosphere deviated in spring 2013 significantly from the mean conditions of the last 20 years. Furthermore the planetary wave activity in the high latitude stratosphere was enhanced from 20 April to beginning of May. The colder and wetter upper mesosphere in May 2013 is attributed to this unusual late planetary wave activity in the stratosphere, introducing a strong upwelling in the mesosphere, lower temperatures and an upward transport of water vapor, which finally resulted in earlier existence conditions for mesospheric ice particles. We regard this as a first evidence for intra-hemispheric coupling in the northern hemisphere extending from the stratosphere into the mesopause region. Yet it is unclear whether this is an unusual extreme event or an indicator for a change in the circulation due to the observed long-term cooling of the middle atmosphere.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

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

    2013-01-01

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

  14. From apneic spells to the development of hypertensive hydrocephalus: a case report of homocystinuria with early onset.

    PubMed

    Cerbo, Rosa Maria; Cabano, Rita; Lombardi, Giuseppina; Bollani, Lina; Colombo, Roberto; Stronati, Mauro

    2010-03-01

    Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of homocysteine in the serum and an increased excretion of homocysteine in the urine. The infantile form is severe: the main clinical findings are neurologic signs, associated with hematological signs and bone alterations. Immediate restoration of plasma amino acids is the primary goal and early diagnosis is crucial not to delay the onset of possible treatment. We report a case of homocystinuria with early onset: an initial symptomatology was undervalued by the pediatrician with a delay in diagnosis. Despite the therapy, the patient developed tetraventricular hydrocephalus requiring ventricular drainage. In conclusion, we want to remember the necessity to perform a complete metabolic workup in a patient with clinical manifestations suggestive for homocystinuria, and the importance of early recognition of the signs and symptoms of hypertensive hydrocephalus, a possible complication of this condition. PMID:19509410

  15. Characterization of a Novel Periodontal Ligament-specific Periostin Isoform

    PubMed Central

    Yamada, S.; Tauchi, T.; Awata, T.; Maeda, K.; Kajikawa, T.; Yanagita, M.; Murakami, S.

    2014-01-01

    Periostin is a mesenchymal cell marker predominantly expressed in collagen-rich fibrous connective tissues, including heart valves, tendons, perichondrium, periosteum, and periodontal ligament (PDL). Knockdown of periostin expression in mice results in early-onset periodontitis and failure of cardiac healing after acute myocardial infarction, suggesting that periostin is essential for connective tissue homeostasis and regeneration. However, its role(s) in periodontal tissues has not yet been fully defined. In this study, we describe a novel human isoform of periostin (PDL-POSTN). Isoform-specific analysis by reverse-transcription polymerase chain-reaction (RT-PCR) revealed that PDL-POSTN was predominantly expressed in the PDL, with much lower expression in other tissues and organs. A PDL cell line transfected with PDL-POSTN showed enhanced alkaline phosphatase (ALPase) activity and calcified nodule formation, compared with cells transfected with the full-length periostin isoform. A neutralizing antibody against integrin-?v inhibited both ALPase activity and calcified nodule formation in cells transfected with PDL-POSTN. Furthermore, co-immunoprecipitation assays revealed that PDL-POSTN bound to integrin ?v?3 more strongly than the common isoform of periostin, resulting in strong activation of the integrin ?v?3-focal adhesion kinase (FAK) signaling pathway. These results suggest that PDL-POSTN positively regulates cytodifferentiation and mineralization in PDL cells through integrin ?v?3. PMID:25012810

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

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

    ERIC Educational Resources Information Center

    Kumra, Sanjiv

    2008-01-01

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

  18. Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early-onset distal myopathy.

    PubMed

    Reis, Gerald F; de la Motte, Grant; Gooding, Rebecca; Laing, Nigel G; Margeta, Marta

    2015-12-01

    Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early-onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39-year-old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co-expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth-eaten fibers and mini-cores, lack of rimmed vacuoles and rare desmin-positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the MYH7 gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis. PMID:26094647

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    Recent studies have shown that the Early Eocene Climatic Optimum (EECO) was preceded by a series of short-lived global warming events, known as hyperthermals. Here we present high-resolution benthic stable carbon and oxygen isotope records from ODP Sites 1262 and 1263 (Walvis Ridge, SE Atlantic) between ~ 54 and ~ 52 million years ago, tightly constraining the character, timing, and magnitude of six prominent hyperthermal events. These events, which include Eocene Thermal Maximum (ETM) 2 and 3, are studied in relation to orbital forcing and long-term trends. Our findings reveal an almost linear relationship between ?13C and ?18O for all these hyperthermals, indicating that the eccentricity-paced covariance between deep-sea temperature changes and extreme perturbations in the exogenic carbon pool persisted during these events towards the onset of the EECO, in accordance with previous observations for the Paleocene Eocene Thermal Maximum (PETM) and ETM2. The covariance of ?13C and ?18O during H2 and I2, which are the second pulses of the "paired" hyperthermal events ETM2-H2 and I1-I2, deviates with respect to the other events. We hypothesize that this could relate to a relatively higher contribution of an isotopically heavier source of carbon, such as peat or permafrost, and/or to climate feedbacks/local changes in circulation. Finally, the ?18O records of the two sites show a systematic offset with on average 0.2 ‰ heavier values for the shallower Site 1263, which we link to a slightly heavier isotopic composition of the intermediate water mass reaching the northeastern flank of the Walvis Ridge compared to that of the deeper northwestern water mass at Site 1262.

  2. Stratification of Risk of Early-Onset Sepsis in Newborns ?34 Weeks’ Gestation

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-12-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. Newly Identified Pathogens Associated with Periodontitis

    PubMed Central

    Pérez-Chaparro, P.J.; Gonçalves, C.; Figueiredo, L.C.; Faveri, M.; Lobão, E.; Tamashiro, N.; Duarte, P.; Feres, M.

    2014-01-01

    There is substantial evidence supporting the role of certain oral bacteria species in the onset and progression of periodontitis. Nevertheless, results of independent-culture diagnostic methods introduced about a decade ago have pointed to the existence of new periodontal pathogens. However, the data of these studies have not been evaluated together, which may generate some misunderstanding on the actual role of these microorganisms in the etiology of periodontitis. The aim of this systematic review was to determine the current weight of evidence for newly identified periodontal pathogens based on the results of “association” studies. This review was conducted and reported in accordance with the PRISMA statement. The MEDLINE, EMBASE, and Cochrane databases were searched up to September 2013 for studies (1) comparing microbial data of subgingival plaque samples collected from subjects with periodontitis and periodontal health and (2) evaluating at least 1 microorganism other than the already-known periodontal pathogens. From 1,450 papers identified, 41 studies were eligible. The data were extracted and registered in predefined piloted forms. The results suggested that there is moderate evidence in the literature to support the association of 17 species or phylotypes from the phyla Bacteroidetes, Candidatus Saccharibacteria, Firmicutes, Proteobacteria, Spirochaetes, and Synergistetes. The phylum Candidatus Saccharibacteria and the Archaea domain also seem to have an association with disease. These data point out the importance of previously unidentified species in the etiology of periodontitis and might guide future investigations on the actual role of these suspected new pathogens in the onset and progression of this infection. PMID:25074492

  6. Phenotypic profile of early-onset familial Alzheimer's disease caused by presenilin-1 E280A mutation.

    PubMed

    Sepulveda-Falla, Diego; Glatzel, Markus; Lopera, Francisco

    2012-01-01

    Presenilin 1 (PS1) mutations are the most common cause of early-onset familial Alzheimer's disease (EOFAD). They show a common phenotypic profile characterized by early age of onset, severe dementia and distinct neurodegeneration. The largest population of EOFAD carries the E280A mutation in PS1 and resides in Antioquia, Colombia, currently comprising around 5,000 individuals. Carriers start showing memory impairment in the third decade of life, followed by progressive impairment of language and other cognitive processes. They reach mild cognitive impairment around 45 and dementia around 50 years of age. There is some phenotypic variability among the carriers of this single PS1 mutation. Some patients present with epilepsy, verbal impairment, and cerebellar ataxia. Neuropathologically, PS1 E280A cases show pronounced brain atrophy, severe amyloid-? pathology, distinct hyperphosphorylated tau-related pathology, and cerebellar damage. The earliest event identified by functional magnetic imaging resonance is hyperactivation within the right anterior hippocampus around 33 years of age. This well-studied population with a clear pre-clinical profile and wide phenotypic variability in age of onset and clinical presentation is ideally suited for clinical trials and to study molecular mechanisms of Alzheimer's disease. PMID:22766738

  7. [Case of DYT1 dystonia (early-onset torsion dystonia) showing long-term focal dystonia in the arm].

    PubMed

    Hayashi, Masaharu; Nagao, Yuri; Kimura, Kazue; Hachimori, Kei; Nomura, Yoshiko; Segawa, Masaya

    2008-11-01

    DYTI dystonia (DYT1-D, early-onset torsion dystonia) is caused by a GAG deletion in the DYTI gene. Here we report a girl with child-onset familial DYT1-D showing localized arm involvement. The patient developed postural and action dystonia in the right and left arms at 7 and 9 years, respectively. She was misdiagnosed as hysteria due to lack of abnormalities on laboratory tests. At 11 years of age she was introduced to our clinic. Increased muscle tonus and dystonic discharges seen on surface electromyogram in the right arm and the sternocleidomastoid muscle led to the diagnosis of dystonia. A GAG deletion in the DYTI gene was confirmed in the patient, her healthy father and paternal grandfather with torsion dystonia. Titration of levodopa resulted in the fluctuation of her arm dystonia. Combined therapy by levodopa and trihexyphenidyl relieved postural dystonia in the right arm but not action dystonia in the left. Both types of dystonia in the right and left arms were well ameliorated by the additional increase of levodopa. Somatosensory evoked potentials demonstrated abnormal premovement gating. The latency and accuracy of the amplitude were disturbed in visually guided saccadic eye movement. Now at more than 11 years after onset, the patient has not shown torsion or involvement of the lower extremities. Most DYT1-D patients are refractory to medication and early surgical intervention is recommended. However, the presence of DYT1-D patients showing a milder disease course should also be considered. PMID:19039992

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  9. Gum (Periodontal) Disease

    MedlinePLUS

    ... forms of gum disease are gingivitis and periodontitis. Gingivitis and Periodontitis In gingivitis, the gums become red, swollen and can bleed easily. Gingivitis can usually be reversed with daily brushing and ...

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

    PubMed Central

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

    2015-01-01

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

  11. Early-Onset Atopic Dermatitis in Children: Which Are the Phenotypes at Risk of Asthma? Results from the ORCA Cohort

    PubMed Central

    Amat, Flore; Saint-Pierre, Philippe; Bourrat, Emmanuelle; Nemni, Ariane; Couderc, Rémy; Boutmy-Deslandes, Emmanuelle; Sahraoui, Fatiha; Pansé, Isabelle; Bagot, Martine; Foueré, Sébastien; Just, Jocelyne

    2015-01-01

    Background Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term “atopic march”. However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma. Methods We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6. Results We identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called “AD with low sensitization”; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called “AD with multiple sensitizations” - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called “AD with familial history of asthma”. Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01). Conclusion Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma. PMID:26107938

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

    PubMed Central

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

    2014-01-01

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

  13. Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis

    PubMed Central

    Pham, Bao Tung; van Haaften, Wouter Tobias; Oosterhuis, Dorenda; Nieken, Judith; de Graaf, Inge Anne Maria; Olinga, Peter

    2015-01-01

    Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72 h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24 h of incubation, whereas mPCIS and hPCIS were viable up to 72 h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-?1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-?1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-?1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF. PMID:25907784

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

    PubMed

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

    2014-01-15

    Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 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

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

    SciTech Connect

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

    2014-01-15

    Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-?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.

  16. Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis.

    PubMed

    Pehlivan, Davut; Coban Akdemir, Zeynep; Karaca, Ender; Bayram, Yavuz; Jhangiani, Shalini; Yildiz, Edibe Pembegul; Muzny, Donna; Uluc, Kayihan; Gibbs, Richard A; Elcioglu, Nursel; Lupski, James R; Harel, Tamar

    2015-06-01

    Charcot-Marie-Tooth disease is a heterogeneous group of inherited distal symmetric polyneuropathies associated with mutations in genes encoding components essential for normal functioning of the Schwann cell and axon. TRIM2, encoding a ligase that ubiquitinates the neurofilament light chain, was recently associated with early-onset neuropathy in a single patient. We report a TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis, allowing for further delineation of the associated phenotypic spectrum. PMID:25893792

  17. Alteration of Delta-like ligand 1 and Notch 1 receptor in various placental disorders with special reference to early onset preeclampsia.

    PubMed

    Shimanuki, Yota; Mitomi, Hiroyuki; Fukumura, Yuki; Makino, Shintaro; Itakura, Atsuo; Yao, Takashi; Takeda, Satoru

    2015-08-01

    Notch signaling pathway has been shown to be dysregulated in placentas with preeclampsia, but there has been a lack of studies on methylation of Notch family genes in this disorder. We therefore executed methylation-specific polymerase chain reaction and immunostaining for Notch 1 receptor and the activating ligand, Delta-like (DLL) 1, with placental tissues from cases of preeclampsia (early onset, n = 18; late-onset, n = 19) and other placental disorders, including maternal complications such as diabetes mellitus and collagen disease (n = 10), fetal growth restriction (n = 17), fetal anomaly (n = 23), preterm birth (n = 15), miscarriage (n = 25), and hydatidiform moles (n = 9) as well as term births (n = 12). The frequency of DLL1 methylation was higher in early onset preeclamptic placentas (61%) than the other subjects (0%-36%; P ? .016). Appreciable samples (36%) of miscarriage also represented DLL1 methylation. None of the samples studied showed Notch 1 methylation. On gestational period-matched analysis, the rate of DLL1 methylation was higher in early onset preeclampsia (83.3%) than preterm birth (13.3%; P < .001), with no significant differences in clinical backgrounds between the two. In this analysis, increase of syncytial knots and accelerated villous maturation were most prominent in DLL1-methylated placentas with early onset preeclampsia. Notch 1 and DLL1 expressions in villous trophoblasts and endothelial cells were significantly lower in early onset preeclamptic placentas as compared with preterm birth controls. In conclusion, altered Notch signaling via methylation of DLL1 is likely involved in possible disease-related mechanisms of early onset preeclampsia. Alternatively, DLL1 methylation in early onset preeclampsia could be a manifestation of a lack of placental maturation, similar to miscarriage. PMID:26014475

  18. Early life loss and trauma: eating disorder onset in a middle-aged male--a case study.

    PubMed

    McCormack, Lynne; Lewis, Vivienne; Wells, Jonathan R

    2014-03-01

    The onset of an eating disorder in middle-age men is poorly researched as are eating disorders in men generally. Therefore, life events that influence eating disorders in men, including delayed onset of an eating disorder remains unknown. Given the limited understanding of males with eating disorders and limited access to large samples of men with eating disorders, an in-depth analysis of a single case of a male in middle age with an eating disorder was chosen to gain insight and understanding into this phenomenon. A Life History approach explored the case of Joseph (pseudonym), who was diagnosed at age 44 years with an Eating Disorder Not Otherwise Specified. Data were collected through (a) life course open-ended questioning through interviews, (b) written statements, and (c) comments on transcripts. Three themes emerged, loss and unworthiness, becoming bigger, and wanting to change reflecting eating behaviors associated with attachment disruption, loss and trauma, body dissatisfaction, and negative affect. Later in life, an emotional "tipping point" precipitated an eating disorder. Results indicate traumatic loss leading to early attachment disruption as influential in Joseph's delayed onset of an eating disorder. The value of thorough narrative life histories during therapy when eating disorders occur late in life is discussed as well as the significance for men. PMID:23884788

  19. Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort.

    PubMed

    Cacace, Rita; Van den Bossche, Tobi; Engelborghs, Sebastiaan; Geerts, Nathalie; Laureys, Annelies; Dillen, Lubina; Graff, Caroline; Thonberg, Håkan; Chiang, Huei-Hsin; Pastor, Pau; Ortega-Cubero, Sara; Pastor, Maria A; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Benussi, Luisa; Ghidoni, Roberta; Binetti, Giuliano; Nacmias, Benedetta; Sorbi, Sandro; Sanchez-Valle, Raquel; Lladó, Albert; Gelpi, Ellen; Almeida, Maria Rosário; Santana, Isabel; Tsolaki, Magda; Koutroumani, Maria; Clarimon, Jordi; Lleó, Alberto; Fortea, Juan; de Mendonça, Alexandre; Martins, Madalena; Borroni, Barbara; Padovani, Alessandro; Matej, Radoslav; Rohan, Zdenek; Vandenbulcke, Mathieu; Vandenberghe, Rik; De Deyn, Peter P; Cras, Patrick; van der Zee, Julie; Sleegers, Kristel; Van Broeckhoven, Christine

    2015-12-01

    Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort, as well as in European EOAD patients (N = 946) and control individuals (N = 1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P = 0.43; OR = 1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated. PMID:26411346

  20. Autofluorescence Imaging and Phenotypic variance in a Sibling pair with Early Onset Retinal Dystrophy due to defective CRB1 function

    PubMed Central

    Tosi, Joaquin; Tsui, Ilene; Lima, Luiz; Wang, Nan Kai; Tsang, Stephen H.

    2009-01-01

    Purpose To phenotype two siblings with autosomal recessive early onset retinal dystrophy due to CRB1 mutations. Methods Autofluorescence (AF) imaging, high resolution optical coherence tomography (OCT), and full-field electroretinography (ERG) were performed. The results of DNA sequencing from polymerase chain reaction (PCR) products of the CRB1 gene were obtained from hospital records. Results Two siblings, 14-years-old and 17-years-old, were compound heterozygote for 749 del Ser and C948Y mutations in the gene encoding CRB1. AF imaging documented the preservation of retinal pigment epithelium (RPE) along the arterioles. High resolution OCT showed abnormally thick retinae with increased lamination. Conclusion Leber congenital amaurosis caused by CRB1 is a unique form of early onset retinal dystrophy because it spares the para-arteriolar RPE and causes abnormal retinal lamination with thickening. These findings, detectable with AF imaging and high resolution OCT, can be combined with electrophysiology and genetic testing to molecularly classify retinal degenerations efficiently. PMID:19401883

  1. Early representation of shape by onset synchronization of border-ownership-selective cells in the V1-V2 network.

    PubMed

    Hatori, Yasuhiro; Sakai, Ko

    2014-04-01

    Construction of surface is a crucial step toward the representation of shape through the integration of local information. Physiological studies have reported that the primary visual cortex (V1) codes the medial axis (MA) that is a skeletal structure equidistant from nearby contours, suggesting the early representation of surface in V1. Although the neural basis of surface construction has not been clarified, the onset synchronization of border ownership (BO)-selective cells is a plausible candidate for the generation of surface. We investigated computationally the representation of surface in a biophysically detailed model of primate V1-V2 networks. The simulation results showed that the simultaneous arrival of signals from BO-selective cells evoked strong responses of V1 cells located around the MA. The simulation results lead to a prediction that the perception of the direction of figure (DOF) depends on the degree of synchronous presentation of contour. We conducted a psychophysical experiment and showed that the perception of the DOF is biased toward a highly synchronized contour. These results suggest a crucial role of the onset synchronization of BO-selective cells for the construction of early representation of shape. PMID:24695133

  2. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives

    PubMed Central

    Sng, J-H; Chang, J; Feroze, F; Rahman, N; Tan, W; Lim, S; Lehnert, M; Pool, S van der; Wong, J

    2000-01-01

    The purpose of this study was to determine the prevalence of BRCA1 mutations in Chinese breast cancer patients in Singapore. BRCA1 analysis was conducted in consecutive patients with breast cancer before the age of 40 years (76 women), or whose relatives had breast or ovarian cancer (16 women). Ten patients had both early onset breast cancer and affected relatives. Genomic DNA from peripheral mononuclear blood cells was studied by using the protein transcription–translation assay (exon 11) and single-strand conformational polymorphism, with subsequent DNA sequencing. All six disease-causing mutations occurred in women under 40 years (8.6%) with three occurring in patients under 35 years (three out of 22 patients, 13.6%). Mis-sense mutations of unknown significance were found in three patients. Two of the ten women with affected relatives under 40 years had BRCA1 mutations. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that observed in Caucasian women. Most Chinese patients with affected relatives were not carriers of BRCA1 mutations. © 2000 Cancer Research Campaign PMID:10682662

  3. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease.

    PubMed

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T; Zaal, Kristien; Chandrasekharappa, Settara C; P Hanson, Eric; Yu, Zhen; Mullikin, James C; Hasni, Sarfaraz A; Wertz, Ingrid E; Ombrello, Amanda K; Stone, Deborah L; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K; Leavis, Helen L; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D; Gül, Ahmet; Siegel, Richard M; Boehm, Manfred; Milner, Joshua D; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M; Kastner, Daniel L; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-?B regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-?B signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of I?B? and nuclear translocation of the NF-?B p65 subunit together with increased expression of NF-?B-mediated proinflammatory cytokines. A20 restricts NF-?B signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-?B-dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease. PMID:26642243

  4. 3-Day versus 5-Day Course of Intravenous Antibiotics for Suspected Early Onset Neonatal Sepsis: A Randomized Controlled Trial

    PubMed Central

    Pasha, Yadollah Zahed; Ahmadpour-Kacho, Mussa; Behmadi, Reza; Jahangir, Tahereh

    2014-01-01

    Objective: The objective of this randomized controlled trial was to compare the treatment failure of suspected early onset neonatal sepsis with either 3-day or 5-day course of empirical antibiotic therapy. Methods: Infants with birth weight over 1500 g and/or gestational age over 34 weeks within 7 days postnatal age with clinical symptoms of neonatal sepsis received empirical antibiotics (Ampicillin + Amikacin) in two neonatal intensive care units. After 72 hours if the result of blood culture was negative and symptoms resolved they were randomly allocated to 3-day or 5-day groups. The main outcome was treatment failure which was defined as reappearance of symptoms of sepsis within two weeks after discontinuation of antibiotics. Infants with congenital anomalies, localized infections, asphyxia, those undergoing surgery or when serum C-reactive protein levels remained abnormal despite treatment, were not included. Randomization was accomplished with simple randomization procedure. Findings: Sixty patients were randomized in a 1:1 ratio to either group. Baseline characteristics were similar between two groups. The follow-up period was 2 weeks with no lost to follow-up. One infant in 3-day group had treatment failure compared with no treatment failure in 5-day group (P=0.5). No serious harm was observed due to our empirical antibiotic regimen. Conclusion: The results of this study indicated no evidence that treatment failure differs between 3-day and 5-day course antibiotic therapy for suspected early onset uncomplicated neonatal sepsis in late preterm and term newborns. PMID:26019770

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

    PubMed Central

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

    2014-01-01

    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

  6. Long-term outcomes of early-onset wheeze and asthma

    PubMed Central

    Grad, Roni; Morgan, Wayne J

    2012-01-01

    Evidence from longitudinal cohort studies demonstrates that wheezing which begins in early life and continues into the school age years generally persists into adulthood. This persistent wheezing is associated with lung function deficits and airways hyperresponsiveness that appear to be established in the first few years of life. Allergic sensitization early in life, early life infection with rhinovirus, or colonization with any of a number of bacteria have been associated with increased risk of persistent wheeze. Early life, whether in utero or in the first few years of life, presents a window of vulnerability during which airway injury results in persistent airways dysfunction. Available data futher suggest that a second such window of vulnerability may be present in the preadolescent and adolescent years. Lung function growth patterns established by age 6 generally continue into early to mid-adulthood, typically leaving groups of individuals with wheezing that persists into or relapses in adulthood with mean FEV1 about 10% predicted lower than their peers who do not wheeze. Subgroups of patients with persistent asthma, however, may have progressive declines in lung function, and enter adulthood with even lower lung function. The concern exists that these deficits in lung function apparent in early adulthood may put individuals at risk for the later development of chronic obstructive pulmonary disease. PMID:22738675

  7. CTLA4+49G allele associates with early onset of type 1 diabetes in North Indians.

    PubMed

    Kumar, N; Kaur, G; Kanga, U; Mehra, N K; Neolia, S C; Tandon, N; Zucman, S C

    2015-12-01

    Type 1 diabetes (T1D) is a complex autoimmune disease with strong genetic influence. In this study, we investigated +49A/G SNP (rs 231775) in exon 1 of cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) by PCR-RFLP and its influence as a risk factor for the disease in the North Indian population. This polymorphism at codon 17 results in an amino acid substitution (Thr/Ala) in the leader peptide of the molecule. The study included 232 patients with T1D (age at onset of disease (AOD): 0.5-37 years) and 305 ethnically matched healthy controls. The DNA obtained from these 537 individuals was amplified using a set of specific primers followed by restriction enzyme digestion with Fnu4HI. The +49G allele as well as its homozygous genotype G/G was observed to be significantly higher in patients as compared to the healthy controls {(37.3% vs. 25.6%, P = 4.96E(-05) , OR = 1.73; 95%CI = 1.33-2.25) (15.52% vs. 6.6%, P = 0.001, OR = 2.62; 95% CI = 1.48-4.63) respectively}. The frequency of G/G genotype was significantly higher in patients with early age at onset of disease (AOD:<12 years) as compared to that in the late-onset patients with AOD: ?12 years (21.1% vs. 10.6%, P = 0.042, OR = 2.26; 95% CI = 1.09-4.67) as well as to that in the healthy controls (21.1% vs. 6.6%, P = 0.00004, OR = 3.8; 95% CI = 2.01-7.2). Further analysis revealed that the median AOD significantly reduced (P = 0.049) from 14 years in patients with A/A genotype to 11 and 10 years in those with A/G and G/G genotypes, respectively. These results suggest that CTLA4+49G allele, particularly in homozygous G/G condition, associates with early onset of T1D. PMID:26385826

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-11-01

    The emergence and persistence of conduct problems (CPs) during early childhood is a robust predictor of behavior problems in school and of future maladaptation. In this study we examined the reciprocal influences between observed coercive interactions between children and caregivers, oppositional and aggressive behavior, and growth in parent report of early childhood (ages 2-5) and school-age CPs (ages 7.5 and 8.5). Participants were drawn from the Early Steps multisite randomized prevention trial that includes an ethnically diverse sample of male and female children and their families (N = 731). A parallel-process growth model combining latent trajectory and cross-lagged approaches revealed the amplifying effect of observed coercive caregiver-child interactions on children's noncompliance, whereas child oppositional and aggressive behaviors did not consistently predict increased coercion. The slope and initial levels of child oppositional and aggressive behaviors and the stability of caregiver-child coercion were predictive of teacher-reported oppositional behavior at school age. Families assigned to the Family Check-Up condition had significantly steeper declines in child oppositional and aggressive behavior and moderate reductions in oppositional behavior in school and in coercion at age 3. Results were not moderated by child gender, race/ethnicity, or assignment to the intervention condition. The implications of these findings are discussed with respect to understanding the early development of CPs and to designing optimal strategies for reducing problem behavior in early childhood with families most in need. PMID:24690305

  10. Prevalence of periodontal disease in an active duty military population as indicated by an experimental periodontal index.

    PubMed

    Querna, J C; Rossmann, J A; Kerns, D G

    1994-03-01

    An experimental periodontal screening examination and index was used to measure the prevalence of gingivitis and periodontitis among 1,334 soldiers at Fort Knox, Kentucky. Although 12.1% of the subjects demonstrated no disease, 40.3% were found to have gingivitis. In this sample group, the occurrence of gingivitis decreased with increasing age. Early periodontitis (probing depths of 3-5 mm) was detected in 35.7% of the subjects, and subjects with moderate to advanced periodontitis (probing depths greater than 5 mm) comprised 11.9% of the sample. The screening exam used is suggested for use as part of each soldier's annual dental examination. PMID:8041472

  11. Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation in CDKN1B.

    PubMed

    Elston, Marianne S; Meyer-Rochow, Goswin Y; Dray, Michael; Swarbrick, Michael; Conaglen, John V

    2015-01-01

    Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes: MEN1, CASR, or CDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations in CDKN1B and those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novel CDKN1B germline mutation (heterozygote for a missense mutation in exon 1 of the CDKN1B gene (c.378G>C) (p.E126D)). The implication from this case is that CDKN1B germline mutations may be associated with PHPT at an earlier age than previously thought. PMID:26257968

  12. Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation in CDKN1B

    PubMed Central

    Elston, Marianne S.; Meyer-Rochow, Goswin Y.; Dray, Michael; Swarbrick, Michael; Conaglen, John V.

    2015-01-01

    Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes: MEN1, CASR, or CDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations in CDKN1B and those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novel CDKN1B germline mutation (heterozygote for a missense mutation in exon 1 of the CDKN1B gene (c.378G>C) (p.E126D)). The implication from this case is that CDKN1B germline mutations may be associated with PHPT at an earlier age than previously thought. PMID:26257968

  13. Early detection of familial Creutzfeldt-Jakob disease on diffusion-weighted imaging before symptom onset.

    PubMed

    Terasawa, Yuka; Fujita, Koji; Izumi, Yuishin; Kaji, Ryuji

    2012-08-15

    Familial Creutzfeldt-Jakob disease (CJD) with V180I shows different clinical characteristics from classical CJD and is difficult to diagnose in the early stage. We report a CJD180 patient in whom results of diffusion-weighted imaging (DWI) led us to suspect CJD before symptoms started. A 68-year-old woman presented to our hospital with headache and nausea and underwent magnetic resonance imaging. DWI showed cortical hyperintensity. Three months later, cognitive function started to decline and CJD180 was diagnosed following genetic examination. In the early stage, ADC values were not decreased and single positron emission computed tomography demonstrated a decreased pattern like Alzheimer disease. PMID:22640903

  14. Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression.

    PubMed

    Pajer, K; Andrus, B M; Gardner, W; Lourie, A; Strange, B; Campo, J; Bridge, J; Blizinsky, K; Dennis, K; Vedell, P; Churchill, G A; Redei, E E

    2012-01-01

    Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective. Biological markers of early-onset MDD could increase diagnostic specificity, but no such biomarker exists. Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD. We carried out unbiased analyses of this combined set of 26 candidate blood transcriptomic markers in a sample of 15-19-year-old subjects with MDD (N=14) and subjects with no disorder (ND, N=14). A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths. These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies. PMID:22832901

  15. Early-onset Parkinson's disease due to PINK1 p.Q456X mutation - clinical and functional study

    PubMed Central

    Siuda, Joanna; Jasinska-Myga, Barbara; Boczarska-Jedynak, Magdalena; Opala, Grzegorz; Fiesel, Fabienne C.; Moussaud-Lamodière, Elisabeth L.; Scarffe, Leslie A.; Dawson, Valina L.; Ross, Owen A.; Springer, Wolfdieter; Dawson, Ted M.; Wszolek, Zbigniew K.

    2014-01-01

    Background Recessive mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause early-onset Parkinson's disease (EOPD). The clinical phenotype of families that have this PINK1-associated disease may present with different symptoms, including typical PD. The loss of the PINK1 protein may lead to mitochondrial dysfunction, which causes dopaminergic neuron death. Methods The clinical phenotypes of a large Polish family with EOPD and an identified PINK1 homozygous nonsense mutation were assessed. Ubiquitination and degradation of mitochondrial parkin substrates as well as mitochondrial bioenergetics were investigated as direct functional readouts for PINK1's kinase activity in biopsied dermal fibroblasts. Results A four-generation family was genealogically evaluated. Genetic screening identified two affected subjects who were both homozygous carriers of the pathogenic PINK1 p.Q456X substitution. Both patients presented with dystonia and gait disorders at symptom onset. Seven heterozygous mutation carriers remained unaffected. Functional studies revealed that the PINK1 p.Q456X protein is non-functional in activating the downstream ubiquitin ligase parkin and priming the ubiquitination of its substrates, and that the RNA levels of PINK1 were significantly reduced. Conclusions The PINK1 p.Q456X mutation leads to a decrease in mRNA and a loss of protein function. The foot dystonia and gait disorders seen at disease onset in affected members of our family, which were accompanied by parkinsonism had a similar clinical presentation to what has been described in previous reports of PINK1 mutation carriers. PMID:25226871

  16. Genetic Identification Is Critical for the Diagnosis of Parkinsonism: A Chinese Pedigree with Early Onset of Parkinsonism

    PubMed Central

    Yang, Yang; Tang, Bei-sha; Weng, Ling; Li, Nan; Shen, Lu; Wang, Jian; Zuo, Chuan-tao; Yan, Xin-xiang; Xia, Kun; Guo, Ji-feng

    2015-01-01

    Background A number of hereditary neurological diseases display indistinguishable features at the early disease stage. Parkinsonian symptoms can be found in numerous diseases, making it difficult to get a definitive early diagnosis of primary causes for patients with onset of parkinsonism. The accurate and early diagnosis of the causes of parkinsonian patients is important for effective treatments of these patients. Methods We have identified a Chinese family (82 family members over four generations with 21 affected individuals) that manifested the characterized symptoms of parkinsonism and was initially diagnosed as Parkinson’s disease. We followed up with the family for two years, during which we carried out clinical observations, Positron Emission Tomography-Computed Tomography neuroimaging analysis, and exome sequencing to correctly diagnose the case. Results During the two-year follow-up period, we performed comprehensive medical history collection, physical examination, and structural and functional neuroimaging studies of this Chinese family. We found that the patient exhibited progressive deteriorated parkinsonism with Parkinson disease-like neuropathology and also had a good response to the initial levodopa treatment. However, exome sequencing identified a missense mutation, N279K, in exon 10 of MAPT gene, verifying that the early parkinsonian symptoms in this family are caused by the genetic mutation for hereditary frontotemporal lobar dementia. Conclusions For the inherited parkinsonian patients who even show the neuropathology similar to that in Parkinson’s disease and have initial response to levodopa treatment, genetic identification of the molecular basis for the disease is still required for defining the early diagnosis and correct treatment. PMID:26295349

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

    SciTech Connect

    Hannequin, D.; Campion, D.; Brice, A.

    1994-09-01

    A large French pedigree including 34 subjects with early-onset progressive dementia was identified. In patients, the mean age-at-onset was 46 {plus_minus} 3.5 (SD) years and the mean age at death 52.6 {plus_minus} 5.7 (SD) years. No evidence for anticipation or genetic imprinting was found. Twelve patients were clinically diagnosed as probable Alzheimer`s disease (AD) according to the NINCDS-ADRDA criteria. Myoclonus and extrapyramidal signs were common and seizures were found in all affected subjects. At autopsy, neuropathological changes typical of AD were present in two brains. A significant lod score of 5.38 was observed at a recombination fraction of {theta} = 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. Furthermore, no obligate recombinant was observed with markers D14S77 and D14S71. Typing other genetic markers in this region will allow us to localize more precisely the pathological gene.

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

    SciTech Connect

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

    1996-02-16

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

  19. Multiphasic Scaffolds for Periodontal Tissue Engineering

    PubMed Central

    Ivanovski, S.; Vaquette, C.; Gronthos, S.; Hutmacher, D.W.; Bartold, P.M.

    2014-01-01

    For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3-dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor–based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials. PMID:25139362

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    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

    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

  2. Postweaning Exposure to Dietary Zearalenone, a Mycotoxin, Promotes Premature Onset of Puberty and Disrupts Early Pregnancy Events in Female Mice

    PubMed Central

    Ye, Xiaoqin

    2013-01-01

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

  3. Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with ?-synuclein pathology.

    PubMed

    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

    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

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

    PubMed Central

    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.

    2014-01-01

    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

  5. Ozone therapy in periodontics

    PubMed Central

    Gupta, G; Mansi, B

    2012-01-01

    Gingival and Periodontal diseases represent a major concern both in dentistry and medicine. The majority of the contributing factors and causes in the etiology of these diseases are reduced or treated with ozone in all its application forms (gas, water, oil). The beneficial biological effects of ozone, its anti-microbial activity, oxidation of bio-molecules precursors and microbial toxins implicated in periodontal diseases and its healing and tissue regeneration properties, make the use of ozone well indicated in all stages of gingival and periodontal diseases. The primary objective of this article is to provide a general review about the clinical applications of ozone in periodontics. The secondary objective is to summarize the available in vitro and in vivo studies in Periodontics in which ozone has been used. This objective would be of importance to future researchers in terms of what has been tried and what the potentials are for the clinical application of ozone in Periodontics. PMID:22574088

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

    PubMed

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

    2013-05-01

    We delineate a complication of hypoalbuminemia in dentatorubral-pallidoluysian atrophy (DRPLA), which we have found to be common in this disorder. In addition, we explored the pathogenesis of this phenomenon through clinical and histological examinations. Clinical course and laboratory findings of nine patients with childhood-onset DRPLA (aged 6-49 years; CAG repeat length 62-93) were retrospectively reviewed. Autopsied specimens from three patients were examined by histopathological and immunohistochemical analyses. Eight DRPLA patients showed hypoalbuminemia <3.5 g/dl in the initial stages of the disease (age, 2-32 years), which correlated with the CAG repeat length in each patient. Disease worsened in six patients, often triggered by febrile infections and accompanied by increased urinary protein excretion. One patient showed increased fecal ?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

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

    NASA Astrophysics Data System (ADS)

    Coiffard, Clément; Mohr, Barbara

    2014-05-01

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

  8. Concurrent early-onset peripartum cardiomyopathy in a preeclampsia patient with acute pulmonary edema.

    PubMed

    Belen, Erdal; Tipi, Fahri Fatih; Helvaci, Aysen; Bayyigit, Akif

    2015-01-01

    We herein report the case of a preeclampsia patient with comorbid peripartum cardiomyopathy (PPCMP). A 22-year-old woman in the 26th week of gestation was admitted with acute pulmonary edema. Hypertension and proteinuria were detected, and echocardiography showed an ejection fraction of 33%. It is remarkable that PPCMP particularly that associated with preeclampsia was observed in the early gestational period. In conclusion, while dyspnea and pretibial edema are often noted during normal pregnancies, the potential for PPCMP should be considered if these symptoms are excessive and/or comorbid paroxysmal nocturnal dyspnea and orthopnea are present, even in patients with preeclampsia. PMID:25876574

  9. Point-of-care diagnosis of periodontitis using saliva: technically feasible but still a challenge

    PubMed Central

    Ji, Suk; Choi, Youngnim

    2015-01-01

    Periodontitis is a chronic inflammation of the periodontium caused by persistent bacterial infection that leads to the breakdown of connective tissue and bone. Because the ability to reconstruct the periodontium is limited after alveolar bone loss, early diagnosis and intervention should be the primary goals of periodontal treatment. However, periodontitis often progresses without noticeable symptoms, and many patients do not seek professional dental care until the periodontal destruction progresses to the point of no return. Furthermore, the current diagnosis of periodontitis depends on time-consuming clinical measurements. Therefore, there is an unmet need for near-patient testing to diagnose periodontitis. Saliva is an optimal biological fluid to serve as a near-patient diagnostic tool for periodontitis. Recent developments in point-of-care (POC) testing indicate that a diagnostic test for periodontitis using saliva is now technically feasible. A number of promising salivary biomarkers associated with periodontitis have been reported. A panel of optimal biomarkers must be carefully selected based on the pathogenesis of periodontitis. The biggest hurdle for the POC diagnosis of periodontitis using saliva may be the process of validation in a large, diverse patient population. Therefore, we propose the organization of an International Consortium for Biomarkers of Periodontitis, which will gather efforts to identify, select, and validate salivary biomarkers for the diagnosis of periodontitis. PMID:26389079

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

    PubMed

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

    2014-10-01

    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

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

    PubMed

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

    2013-11-01

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

  12. Multiple rare alleles at LDLR and APOA5 confer risk for early-onset myocardial infarction

    PubMed Central

    Do, Ron; Stitziel, Nathan O.; Won, Hong-Hee; Jørgensen, Anders Berg; Duga, Stefano; Merlini, Pier Angelica; Kiezun, Adam; Farrall, Martin; Goel, Anuj; Zuk, Or; Guella, Illaria; Asselta, Rosanna; Lange, Leslie A.; Peloso, Gina M.; Auer, Paul L.; Girelli, Domenico; Martinelli, Nicola; Farlow, Deborah N.; DePristo, Mark A.; Roberts, Robert; Stewart, Alexander F.R.; Saleheen, Danish; Danesh, John; Epstein, Stephen E.; Sivapalaratnam, Suthesh; Hovingh, G. Kees; Kastelein, John J.; Samani, Nilesh J.; Schunkert, Heribert; Erdmann, Jeanette; Shah, Svati H.; Kraus, William E.; Davies, Robert; Nikpay, Majid; Johansen, Christopher T.; Wang, Jian; Hegele, Robert A.; Hechter, Eliana; Marz, Winfried; Kleber, Marcus E.; Huang, Jie; Johnson, Andrew D.; Li, Mingyao; Burke, Greg L.; Gross, Myron; Liu, Yongmei; Assimes, Themistocles L.; Heiss, Gerardo; Lange, Ethan M.; Folsom, Aaron R.; Taylor, Herman A.; Olivieri, Oliviero; Hamsten, Anders; Clarke, Robert; Reilly, Dermot F.; Yin, Wu; Rivas, Manuel A.; Donnelly, Peter; Rossouw, Jacques E.; Psaty, Bruce M.; Herrington, David M.; Wilson, James G.; Rich, Stephen S.; Bamshad, Michael J.; Tracy, Russell P.; Cupples, L. Adrienne; Rader, Daniel J.; Reilly, Muredach P.; Spertus, John A.; Cresci, Sharon; Hartiala, Jaana; Tang, W.H. Wilson; Hazen, Stanley L.; Allayee, Hooman; Reiner, Alex P.; Carlson, Christopher S.; Kooperberg, Charles; Jackson, Rebecca D.; Boerwinkle, Eric; Lander, Eric S.; Schwartz, Stephen M.; Siscovick, David S.; McPherson, Ruth; Tybjaerg-Hansen, Anne; Abecasis, Goncalo R.; Watkins, Hugh; Nickerson, Deborah A.; Ardissino, Diego; Sunyaev, Shamil R.; O’Donnell, Christopher J.; Altshuler, David; Gabriel, Stacey; Kathiresan, Sekar

    2014-01-01

    Summary Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance1,2. When MI occurs early in life, the role of inheritance is substantially greater1. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families3–8 whereas common variants at more than 45 loci have been associated with MI risk in the population9–15. Here, we evaluate the contribution of rare mutations to MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (?50 years in males and ?60 years in females) along with MI-free controls. We identified two genes where rare coding-sequence mutations were more frequent in cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare, damaging mutations (3.1% of cases versus 1.3% of controls) were at 2.4-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). This sequence-based estimate of the proportion of early MI cases due to LDLR mutations is remarkably similar to an estimate made more than 40 years ago using total cholesterol16. At apolipoprotein A-V (APOA5), carriers of rare nonsynonymous mutations (1.4% of cases versus 0.6% of controls) were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase15,17 and apolipoprotein C318,19. When combined, these observations suggest that, beyond LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk. PMID:25487149

  13. Early deglacial onset of southwestern Greenland ice-sheet retreat on the continental shelf

    NASA Astrophysics Data System (ADS)

    Winsor, Kelsey; Carlson, Anders E.; Welke, Bethany M.; Reilly, Brendan

    2015-11-01

    The Greenland ice sheet (GrIS) advanced onto the continental shelf during the last glacial period. While deglacial records for when the GrIS withdrew onto the modern coastline are relatively abundant, the timing of early GrIS retreat on the shelf is poorly constrained. Here we use planktic foraminiferal ?18O, sediment grain size, sedimentation rates, and 14C ages in southeastern Davis Strait core HU87033-008 to develop an early deglaciation chronology of the southwestern GrIS while on the continental shelf. Sedimentation rates, and especially silt and clay fractions, are high between ?20.5 and ?17.1 ka, suggesting that the southwestern GrIS margin was near or at the shelf break, where it released subglacially derived sediment-laden meltwater. A peak in sedimentation rates of ?110 cm ka-1 between ?19.3 ka and ?18.6 ka, combined with an initial decrease in planktic ?18O of ?0.5 per mil, suggests an early deglacial pull back of the GrIS margin from the shelf break with a concurrent increase in surface ocean meltwater discharge. A subsequent planktic ?18O decrease of ?1.0 per mil combined with a drop in silt and clay sedimentation rates at 18-17 ka likely record further GrIS retreat inland from the shelf break. Terrestrial 10Be surface exposure ages indicate that the GrIS margin remained on the continental shelf until ?11 ka, yet the cause of this subsequent ice-margin stability on the inner shelf is not known. Our new records provide the first evidence that the southwestern GrIS margin may have begun to deglaciate at the same time as other Northern Hemisphere ice sheets. As Labrador Sea water temperatures likely remained near glacial values until ?15 ka, we suggest that initial southwestern GrIS retreat was in response to rising global sea level from retreat of other ice sheets and/or the initial deglacial rise in boreal summer insolation.

  14. Early Pleistocene British-Irish ice rafting: Was the onset of Northern Hemisphere glaciation more widespread than previously assumed?

    NASA Astrophysics Data System (ADS)

    Thierens, M. M.; Tyrrell, S.; Wheeler, A. J.

    2011-12-01

    The late Pliocene - early Pleistocene onset and intensification of Northern Hemisphere glaciation marks an important threshold in Earth's climate system. Unravelling the extent and dynamics of early ice-sheet development is crucial to our understanding of the processes driving Quaternary glaciations and hence, affecting global climate and its variability[1]. In the North Atlantic Ocean, ice-rafted detritus (IRD) layers attest to the development of marine-terminating ice sheets, discharging sediment-loaded icebergs into the ocean. So far, Early-Pleistocene IRD deposition has been predominantly linked to the intensified glaciation of high-latitudinal regions surrounding the North Atlantic (Canada, Greenland, Iceland and Scandinavia), while the extent and role of early ice build-up in more temperate mid-latitudinal regions is still poorly understood. Here we present results from a multiproxy provenance analysis of the unique, Pleistocene IRD record that has been preserved in the Challenger Mound sequence (IODP Expedition 307; Irish NE Atlantic continental margin). This archive has, recently, revealed the first evidence supporting substantial and repeated ice build-up on the British-Irish Isles (57° - 52°N) since the earliest Pleistocene (ca 2.6 Ma) [2]. Nd-Sr isotopic analysis of multiple IRD intervals throughout the sequence show a dominant sediment input from the adjacent British-Irish Isles, even for the early Pleistocene IRD deposits. Furthermore, the Pb isotopic composition of detrital, and apparently ice-rafted, K-feldspar grains shows excellent correspondence to a NW Irish Mainland source, definitively ruling out more far-travelled, northern sources for these grains. The long-term development of an ice sheet on NW Ireland, even in the early stages of Northern Hemisphere glacial expansion, is evidenced and discussed in this study. Overall, widespread circum-Atlantic ice-sheet development at more temperate, mid-latitudes appears to be a persistent feature of the Pleistocene climate system and, hence, should be accounted for. References [1] e.g. Raymo, M.E., Huybers, P., 2008. Unlocking the mysteries of the ice ages. Nature 451, 284-285. [2] Thierens, M., Pirlet, H., Colin, C., et al. 2011. Ice-rafting from the British-Irish ice sheet since the earliest Pleistocene (2.6 million years ago): implications for long-term mid-latitudinal ice-sheet growth in the North Atlantic region. Quaternary Science Reviews, 10.1016/j.quascirev.2010.12.020.

  15. Microbiology of aggressive periodontitis.

    PubMed

    Könönen, Eija; Müller, Hans-Peter

    2014-06-01

    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

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

    PubMed Central

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

    2010-01-01

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

  17. Early Pliocene onset of modern Nordic Seas circulation related to ocean gateway changes

    PubMed Central

    De Schepper, Stijn; Schreck, Michael; Beck, Kristina Marie; Matthiessen, Jens; Fahl, Kirsten; Mangerud, Gunn

    2015-01-01

    The globally warm climate of the early Pliocene gradually cooled from 4 million years ago, synchronous with decreasing atmospheric CO2 concentrations. In contrast, palaeoceanographic records indicate that the Nordic Seas cooled during the earliest Pliocene, before global cooling. However, a lack of knowledge regarding the precise timing of Nordic Seas cooling has limited our understanding of the governing mechanisms. Here, using marine palynology, we show that cooling in the Nordic Seas was coincident with the first trans-Arctic migration of cool-water Pacific mollusks around 4.5 million years ago, and followed by the development of a modern-like Nordic Seas surface circulation. Nordic Seas cooling precedes global cooling by 500,000 years; as such, we propose that reconfiguration of the Bering Strait and Central American Seaway triggered the development of a modern circulation in the Nordic Seas, which is essential for North Atlantic Deep Water formation and a precursor for more widespread Greenland glaciation in the late Pliocene. PMID:26507275

  18. Early-Onset Autoimmune Disease as a Manifestation of Primary Immunodeficiency

    PubMed Central

    Carneiro-Sampaio, Magda; Coutinho, Antonio

    2015-01-01

    Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-? pathway (in Aicardi–Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID. PMID:25999944

  19. Early Pliocene onset of modern Nordic Seas circulation related to ocean gateway changes.

    PubMed

    De Schepper, Stijn; Schreck, Michael; Beck, Kristina Marie; Matthiessen, Jens; Fahl, Kirsten; Mangerud, Gunn

    2015-01-01

    The globally warm climate of the early Pliocene gradually cooled from 4 million years ago, synchronous with decreasing atmospheric CO2 concentrations. In contrast, palaeoceanographic records indicate that the Nordic Seas cooled during the earliest Pliocene, before global cooling. However, a lack of knowledge regarding the precise timing of Nordic Seas cooling has limited our understanding of the governing mechanisms. Here, using marine palynology, we show that cooling in the Nordic Seas was coincident with the first trans-Arctic migration of cool-water Pacific mollusks around 4.5 million years ago, and followed by the development of a modern-like Nordic Seas surface circulation. Nordic Seas cooling precedes global cooling by 500,000 years; as such, we propose that reconfiguration of the Bering Strait and Central American Seaway triggered the development of a modern circulation in the Nordic Seas, which is essential for North Atlantic Deep Water formation and a precursor for more widespread Greenland glaciation in the late Pliocene. PMID:26507275

  20. Early Pliocene onset of modern Nordic Seas circulation related to ocean gateway changes

    NASA Astrophysics Data System (ADS)

    de Schepper, Stijn; Schreck, Michael; Beck, Kristina Marie; Matthiessen, Jens; Fahl, Kirsten; Mangerud, Gunn

    2015-10-01

    The globally warm climate of the early Pliocene gradually cooled from 4 million years ago, synchronous with decreasing atmospheric CO2 concentrations. In contrast, palaeoceanographic records indicate that the Nordic Seas cooled during the earliest Pliocene, before global cooling. However, a lack of knowledge regarding the precise timing of Nordic Seas cooling has limited our understanding of the governing mechanisms. Here, using marine palynology, we show that cooling in the Nordic Seas was coincident with the first trans-Arctic migration of cool-water Pacific mollusks around 4.5 million years ago, and followed by the development of a modern-like Nordic Seas surface circulation. Nordic Seas cooling precedes global cooling by 500,000 years; as such, we propose that reconfiguration of the Bering Strait and Central American Seaway triggered the development of a modern circulation in the Nordic Seas, which is essential for North Atlantic Deep Water formation and a precursor for more widespread Greenland glaciation in the late Pliocene.

  1. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease

    PubMed Central

    Caso, Francesco; Galozzi, Paola; Costa, Luisa; Sfriso, Paolo; Cantarini, Luca; Punzi, Leonardo

    2015-01-01

    The recent identification of genetic mutations leading to dysfunction of inflammatory and apoptotic pathways, has allowed to characterise a group of diseases, recognised as monogenic autoinflammatory syndromes. Among those, Blau syndrome (BS) and early-onset sarcoidosis (EOS) have been identified as familial and sporadic phenotypes of the same non-caseating granulomatous form. Both the diseases are caused by mutations in the CARD15/NOD2 gene, encoding the cytosolic NOD2 protein, one of the key molecules in the regulation of innate immunity. Clinical onset is typically located in the first years of life and phenotype is characterised by simultaneous or less articular, cutaneous and ocular non-caseating granulomatous inflammation, which can be variably associated with a heterogeneous systemic spectrum. The CARD15/NOD2 gene has also been identified as one of the genes linked to susceptibility to Crohn's disease (CD), a common polygenic inflammatory granulomatous bowel disease. The heightened nuclear factor-?B activity, found in the intestinal tissue of patients affected by CD, has probably a genetic cause related to several CARD15/NOD2 polymorphisms. Other substitutions in the CARD15/NOD2 gene have also been found in a recently described disorder, called NOD2-associated autoinflammatory disease, which shares several clinical characteristics with BS and EOS. This review attempts to describe these diseases on the basis of the most recent evidences. We described genetic and clinical aspects, mainly focusing on BS and EOS, the most representative diseases of autoinflammatory granulomatous diseases, with the ultimate purpose to expand their knowledge. PMID:26509073

  2. De novo deleterious genetic variations target a biological network centered on A? peptide in early-onset Alzheimer disease.

    PubMed

    Rovelet-Lecrux, A; Charbonnier, C; Wallon, D; Nicolas, G; Seaman, M N J; Pottier, C; Breusegem, S Y; Mathur, P P; Jenardhanan, P; Le Guennec, K; Mukadam, A S; Quenez, O; Coutant, S; Rousseau, S; Richard, A-C; Boland, A; Deleuze, J-F; Frebourg, T; Hannequin, D; Campion, D

    2015-09-01

    We hypothesized that de novo variants (DNV) might participate in the genetic determinism of sporadic early-onset Alzheimer disease (EOAD, onset before 65 years). We investigated 14 sporadic EOAD trios first by array-comparative genomic hybridization. Two patients carried a de novo copy number variation (CNV). We then performed whole-exome sequencing in the 12 remaining trios and identified 12 non-synonymous DNVs in six patients. The two de novo CNVs (an amyloid precursor protein (APP) duplication and a BACE2 intronic deletion) and 3/12 non-synonymous DNVs (in PSEN1, VPS35 and MARK4) targeted genes from a biological network centered on the Amyloid beta (A?) peptide. We showed that this a priori-defined genetic network was significantly enriched in amino acid-altering DNV, compared with the rest of the exome. The causality of the APP de novo duplication (which is the first reported one) was obvious. In addition, we provided evidence of the functional impact of the following three non-synonymous DNVs targeting this network: the novel PSEN1 variant resulted in exon 9 skipping in patient's RNA, leading to a pathogenic missense at exons 8-10 junction; the VPS35 missense variant led to partial loss of retromer function, which may impact neuronal APP trafficking and A? secretion; and the MARK4 multiple nucleotide variant resulted into increased Tau phosphorylation, which may trigger enhanced A?-induced toxicity. Despite the difficulty to recruit Alzheimer disease (AD) trios owing to age structures of the pedigrees and the genetic heterogeneity of the disease, this strategy allowed us to highlight the role of de novo pathogenic events, the putative involvement of new genes in AD genetics and the key role of A? network alteration in AD. PMID:26194182

  3. Elevated Expression of KiSS-1 in Placenta of Chinese Women with Early-Onset Preeclampsia

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    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

    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

  5. 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)

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

    2005-01-01

    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.

  6. Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

    PubMed Central

    Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Iamashita, Priscila; Silva, Filipi Nascimento; Costa, Luciano da Fontoura; Silva, Alexandre Valotta; Castro, Luiz Henrique Martins; Wen, Hung-Tzu

    2015-01-01

    Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to generate adaptive mechanisms, what has implications for epilepsy management and drug discovery. PMID:26011637

  7. Periodontitis associated with osteomalacia

    PubMed Central

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

    2014-01-01

    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

  8. Defining periodontal health

    PubMed Central

    2015-01-01

    Assessment of the periodontium has relied exclusively on a variety of physical measurements (e.g., attachment level, probing depth, bone loss, mobility, recession, degree of inflammation, etc.) in relation to various case definitions of periodontal disease. Periodontal health was often an afterthought and was simply defined as the absence of the signs and symptoms of a periodontal disease. Accordingly, these strict and sometimes disparate definitions of periodontal disease have resulted in an idealistic requirement of a pristine periodontium for periodontal health, which makes us all diseased in one way or another. Furthermore, the consequence of not having a realistic definition of health has resulted in potentially questionable recommendations. The aim of this manuscript was to assess the biological, environmental, sociological, economic, educational and psychological relationships that are germane to constructing a paradigm that defines periodontal health using a modified wellness model. The paradigm includes four cardinal characteristics, i.e., 1) a functional dentition, 2) the painless function of a dentition, 3) the stability of the periodontal attachment apparatus, and 4) the psychological and social well-being of the individual. Finally, strategies and policies that advocate periodontal health were appraised. I'm not sick but I'm not well, and it's a sin to live so well. Flagpole Sitta, Harvey Danger PMID:26390888

  9. Hypersexual Behavior in Frontotemporal Dementia: A Comparison with Early-Onset Alzheimer’s Disease

    PubMed Central

    Mendez, Mario F.; Shapira, Jill S.

    2013-01-01

    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

  10. The Environmental Factor: Driving the Onset and Early Evolution of High-Mass Stars and Clusters

    NASA Astrophysics Data System (ADS)

    Rivera-Ingraham, Alana; Marston, Anthony; Martin, Peter; Ristorcelli, Isabelle; Juvela, Mika

    2015-08-01

    While the process leading to the formation of low-mass stars is reasonably well established, the origin of their high-mass counterparts, and in particular, the link with the properties and evolution of the parental structures, remains poorly understood. The key role that high-mass stars and massive clusters play in driving the evolution of the ISM, from planetary to galactic scales, makes this study, however, particularly critical.Here we present the latest results from an ongoing Herschel-based project of high-mass star formation in the Outer Galaxy, and which aims to quantify the complex dependence between the final characteristics of young high-mass stars and the early evolution of their local environment.Datasets from the Herschel imaging survey of OB Young Stellar objects (HOBYS; PI. F. Motte) and the Herschel infrared Galactic Plane Survey (Hi-Gal; PI. S. Molinari) Key Programmes are used as a base to carry out an in-depth examination of the cloud physical characteristics, compact source population, and star formation history of those regions with the potential for (and on-going) high-mass star and cluster formation. Results from this study are compelling evidence for the requirement of local external processes, such as stellar feedback (e.g., Convergent Constructive Feedback model; Rivera-Ingraham et al. 2013), in order to counteract the limitations of gravity in the formation and evolution of dense and exotic environments. We will describe how such processes could drive the formation and evolution of the parental host, and therefore influence the final characteristics of the young high-mass stars and clusters (Rivera-Ingraham, et al. 2015a; 2015b, in prep). Our conclusions are further supported by an extensive independent analysis of filamentary properties as a function of Galactic environment (Rivera-Ingraham et al. 2015c; subm), and which we will present as part of the Galactic Cold Cores Key Programme (PI. M. Juvela).

  11. KP1 expression of ghost Pick bodies, amyloid P-positive astrocytes and selective nigral degeneration in early onset Picks disease.

    PubMed

    Kobayashi, K; Hayashi, M; Fukutani, Y; Miyazu, K; Shiozawa, M; Muramori, F; Aoki, T; Koshino, Y

    1999-01-01

    We present a patient with early-onset Pick's disease in which selective nigral degeneration, KP1 expression of ghost Pick bodies and amyloid P-positive astrocytes were found. We also review the literature on early-onset Pick's disease. A 34-year-old man showed personality change including stereotypical behavior. Muscle rigidity and spasticity developed later, and he died twelve years after the onset of his illness. The brain showed lobar cerebral atrophy prominent in the temporal lobe, and to a lesser degree in the prefrontal and orbitofrontal cortex. The substantia nigra displayed profound degeneration whereas the head of the caudate nucleus and the putamen were not so seriously affected because the neurons were preserved and only slight astrocytic proliferation was seen. Many Pick bodies were found in the hippocampal formation, and ballooned neurons (Pick cells) were dispersed throughout the cerebral cortex, subcortical grey matter and hippocampal formation. The affected white matter exhibited severe fibrillary gliosis, and numerous astrocytes positive for glial fibrillary acidic protein and microglial cells positive for CR3/43 were found in the atrophied cortical lesions. The intraneuronal Pick bodies expressed ubiquitin, neurofilament and tau, and KP1 distinctly stained ghost Pick bodies. Tau-positive astrocytes were found in the striatum, hippocampal formation, pontine tegmentum, substantia nigra and affected frontotemporal cortices. These astrocytes were also positive for amyloid P. Extensive search of the literature on early-onset Pick's disease disclosed only a few cases with selective nigral degeneration, and we failed to find any differences in duration, progression of the illness and the extent of subcortical gray matter involvement between cases of early-onset and presenile onset of Pick' s disease. We conclude that the striatopallidal and nigral system can be affected independently in Pick's disease and report new immunohistochemical findings. PMID:10505433

  12. 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

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

    2012-01-01

    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…

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  14. Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes.

    PubMed

    Silverman, Edwin K; Mosley, Jonathan D; Palmer, Lyle J; Barth, Matthew; Senter, Jody M; Brown, Alison; Drazen, Jeffrey M; Kwiatkowski, David J; Chapman, Harold A; Campbell, Edward J; Province, Michael A; Rao, D C; Reilly, John J; Ginns, Leo C; Speizer, Frank E; Weiss, Scott T

    2002-03-15

    Familial aggregation of chronic obstructive pulmonary disease (COPD) has been demonstrated, but linkage analysis of COPD-related phenotypes has not been reported previously. An autosomal 10 cM genome-wide scan of short tandem repeat (STR) polymorphic markers was analyzed for linkage to COPD-related phenotypes in 585 members of 72 pedigrees ascertained through severe, early-onset COPD probands without severe alpha1-antitrypsin deficiency. Multipoint non-parametric linkage analysis (using the ALLEGRO program) was performed for qualitative phenotypes including moderate airflow obstruction [forced expiratory volume at one second (FEV(1)) < 60% predicted, FEV(1)/FVC < 90% predicted], mild airflow obstruction (FEV(1) < 80% predicted, FEV(1)/FVC < 90% predicted) and chronic bronchitis. The strongest evidence for linkage in all subjects was observed at chromosomes 12 (LOD = 1.70) and 19 (LOD = 1.54) for moderate airflow obstruction, chromosomes 8 (LOD = 1.36) and 19 (LOD = 1.09) for mild airflow obstruction and chromosomes 19 (LOD = 1.21) and 22 (LOD = 1.37) for chronic bronchitis. Restricting analysis to cigarette smokers only provided increased evidence for linkage of mild airflow obstruction and chronic bronchitis to several genomic regions; for mild airflow obstruction in smokers only, the maximum LOD was 1.64 at chromosome 19, whereas for chronic bronchitis in smokers only, the maximum LOD was 2.08 at chromosome 22. On chromosome 12p, 12 additional STR markers were genotyped, which provided additional support for an airflow obstruction locus in that region with a non-parametric multipoint approach for moderate airflow obstruction (LOD = 2.13) and mild airflow obstruction (LOD = 1.43). Using a dominant model with the STR markers on 12p, two point parametric linkage analysis of all subjects demonstrated a maximum LOD score of 2.09 for moderate airflow obstruction and 2.61 for mild airflow obstruction. In smokers only, the maximum two point LOD score for mild airflow obstruction was 3.14. These observations provide suggestive evidence that there is a locus on chromosome 12p which contributes to susceptibility to early-onset COPD. PMID:11912177

  15. Diabetes aggravates periodontitis by limiting repair through enhanced inflammation

    PubMed Central

    Pacios, Sandra; Kang, Jun; Galicia, Johnah; Gluck, Kenneth; Patel, Hemal; Ovaydi-Mandel, Amy; Petrov, Sophia; Alawi, Faizan; Graves, Dana T.

    2012-01-01

    Periodontitis is the most common lytic bone disease and one of the first clinical manifestations of diabetes. Diabetes increases the risk of periodontitis. The aim of the present study was to examine mechanisms by which diabetes aggravates periodontitis. Ligature-induced periodontitis was examined in Goto-Kakizaki rats with type 2 diabetes. A tumor necrosis factor (TNF)-specific-inhibitor, pegsunercept, was applied to diabetic rats after the onset of periodontal disease. Interferon-? (IFN-?), TNF-?, interleukin-1 ? (IL-1?), fibroblast growth factor-2 (FGF-2), transforming growth factor beta-1 (TGF?-1), bone morphogenetic protein-2 (BMP-2), and BMP-6 were measured by real-time RT-PCR, and histological sections were examined for leukocyte infiltration and several parameters related to bone resorption and formation. Inflammation was prolonged in diabetic rats and was reversed by the TNF inhibitor, which reduced cytokine mRNA levels, leukocyte infiltration, and osteoclasts. In contrast, new bone and osteoid formation and osteoblast numbers were increased significantly vs. untreated diabetic animals. TNF inhibition in diabetic animals also reduced apoptosis, increased proliferation of bone-lining cells, and increased mRNA levels of FGF-2, TGF?-1, BMP-2, and BMP-6. Thus, diabetes prolongs inflammation and osteoclastogenesis in periodontitis and through TNF limits the normal reparative process by negatively modulating factors that regulate bone.—Pacios, S., Kang, J., Galicia, J., Gluck, K., Patel, H., Ovaydi-Mandel, A., Petrov, S., Alawi, F., Graves, D. T. Diabetes aggravates periodontitis by limiting repair through enhanced inflammation. PMID:22179526

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

    Butler, Blake E.; Lomber, Stephen G.

    2013-01-01

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

  18. Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated.

    PubMed Central

    Diebold, R J; Eis, M J; Yin, M; Ormsby, I; Boivin, G P; Darrow, B J; Saffitz, J E; Doetschman, T

    1995-01-01

    Transforming growth factor beta 1 (TGF beta 1)-null mice die fro complications due to an early-onset multifocal inflammatory disorder. We show here that cardiac cells are hyperproliferative and that intercellular adhesion molecule 1 (ICAM-1) is elevated. To determine which phenotypes are primarily caused by a deficiency in TGF beta 1 from those that are secondary to inflammation, we applied immunosuppressive therapy and genetic combination with the severe combined immunodeficiency (SCID) mutation to inhibit the inflammatory response. Treatment with antibodies to the leukocyte function-associated antigen 1 doubled longevity, reduced inflammation, and delayed heart cell proliferation. TGF beta 1-null SCID mice displayed no inflammation or cardiac cell proliferation, survived to adulthood, and exhibited normal major histocompatibility complex II (MHC II) and ICAM-1 levels. TGF beta 1-null pups born to a TGF beta 1-null SCID mother presented no gross congenital heart defects, indicating that TGF beta 1 alone does not play an essential role in heart development. These results indicate that lymphocytes are essential for the inflammatory response, cardiac cell proliferation, and elevated MHC II and ICAM-1 expression, revealing a vital role for TGF beta 1 in regulating lymphocyte proliferation and activation, which contribute to the maintenance of self tolerance. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8618872

  19. Early-Onset Subicular Microvascular Amyloid and Neuroinflammation Correlate With Behavioral Deficits in Vasculotropic Mutant APP Transgenic Mice

    PubMed Central

    Xu, Feng; Grande, Alicia M.; Robinson, John K.; Previti, Mary Lou; Vasek, Michael; Davis, Judianne; Van Nostrand, William E.

    2007-01-01

    Cerebral microvascular amyloid ? protein (A?) deposition and associated neuroinflammation are increasingly recognized as an important component leading to cognitive impairment in Alzheimer’s disease and related cerebral amyloid angiopathy (CAA) disorders. Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human A? precursor protein in brain (Tg-SwDI) accumulate abundant cerebral microvascular fibrillar amyloid deposits exhibiting robust neuroinflammation. In the present study, we sought to determine if the unique amyloid pathology of Tg-SwDI mice was associated with deficits in behavioral performance. Behavioral performance tests that assessed a variety of psychological functions, including overall activity, motor ability, balance and strength, anxiety, impulsivity, and learning were conducted on homozygous Tg-SwDI mice and similarly aged wild-type C57Bl/6 mice. Our results indicate that Tg-SwDI mice were impaired in the performance of the Barnes maze learning and memory task at 3, 9, and 12 months of age. While more widespread cerebral microvascular A? pathology was evident in older animals, the evaluation of the A? pathology in the 3 months old transgenic animals revealed specific accumulation of microvascular amyloid and markedly elevated numbers of reactive astrocytes and activated microglia restricted to the subiculum. These findings indicate that early-onset accumulation of subicular microvascular amyloid and accompanying neuroinflammation correlates with impaired performance in the learning and memory task in Tg-SwDI mice. PMID:17331655

  20. Early onset behavioral variant frontotemporal dementia due to the C9ORF72 hexanucleotide repeat expansion: psychiatric clinical presentations.

    PubMed

    Arighi, Andrea; Fumagalli, Giorgio G; Jacini, Francesca; Fenoglio, Chiara; Ghezzi, Laura; Pietroboni, Anna M; De Riz, Milena; Serpente, Maria; Ridolfi, Elisa; Bonsi, Rossana; Bresolin, Nereo; Scarpini, Elio; Galimberti, Daniela

    2012-01-01

    A hexanucleotide repeat expansion in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis or frontotemporal lobar degeneration with or without concomitant motor neuron disease phenotype and TDP-43 based pathology. Here, we report on three cases carrying the hexanucleotide repeat expansion with an atypical presentation consisting in the development of psychiatric symptoms. Patient #1, a 53 year old man with positive family history for dementia, presented with mood deflection, characterized by apathy, social withdraw, and irritability in the last two years. He was diagnosed with "mild cognitive impairment due to depressive syndrome" six months later and subsequently with Alzheimer's disease. Patient #2, a woman with positive family history for dementia, developed behavioral disturbances, aggressiveness, and swearing at 57 years of age. Patient #3 presented, in the absence of brain atrophy, with mystical delirium with auditory hallucinations at 44 years of age, and did not present neurological symptoms over a 7-year follow up. The description of these cases underlines that the hexanucleotide repeat expansion in chromosome 9 could be associated with early onset psychiatric presentations. PMID:22571983

  1. Functional deterioration from the premorbid period to 2 years after the first episode of psychosis in early-onset psychosis.

    PubMed

    Del Rey-Mejías, Ángel; Fraguas, David; Díaz-Caneja, Covadonga M; Pina-Camacho, Laura; Castro-Fornieles, Josefina; Baeza, Inmaculada; Espliego, Ana; Merchán-Naranjo, Jessica; González-Pinto, Ana; de la Serna, Elena; Payá, Beatriz; Graell, Montserrat; Arango, Celso; Parellada, Mara

    2015-12-01

    The aim of the study was to analyze changes in functional adjustment from childhood to 2 years after the first episode of psychosis (FEP) in patients with early-onset schizophrenia spectrum disorders (SSD) and affective psychoses (AFP) and a good or intermediate level of premorbid adjustment. We followed 106 adolescents (aged 12-17 years) with FEP for 2 years after recruitment. Premorbid adjustment in childhood was assessed in 98 patients with the childhood subscale of the Cannon-Spoor Premorbid Adjustment Scale (c-PAS). Global functioning was assessed 2 years after the FEP with the Children's Global Assessment Scale (c-GAS) or the Global Assessment of Functioning scale (GAF), as appropriate. Functional deterioration was defined as a downward shift in the level of functional adjustment from childhood to 2 years after the FEP. In patients with good or intermediate premorbid adjustment, functional deterioration was observed in 28.2 % (26.5 % of the AFP group, 29.4 % of the SSD group). Longer duration of untreated psychosis (Beta = 0.01; P = 0.01) and higher symptom severity at the FEP, as measured with the Clinical Global Impression Scale (Beta = 1.12; P = 0.02), significantly predicted the presence of functional deterioration, accounting for 21.4 % of the variance. Irrespective of diagnosis (SSD or AFP), almost one-third of adolescents with FEP and good or intermediate premorbid adjustment showed functional deterioration from the premorbid period to 2 years after the FEP. PMID:25726022

  2. FAM161A and TTC8 are Differentially Expressed in Non-Allelelic Early Onset Retinal Degeneration.

    PubMed

    Downs, Louise M; Aguirre, Gustavo D

    2016-01-01

    Ciliary genes FAM161A and TTC8 have been implicated in retinal degeneration (RD) in humans and in dogs. The identification of FAM161A and TTC8 mutations in canine RD is exciting as there is the potential to develop novel large animal models for RD. However, the disease phenotypes in the dog and the roles of abnormal genes in disease pathology have yet to be fully characterized. The present study evaluated the expression patterns of FAM161A and TTC8 during normal retinal development in dogs, and in three non-allelic, early onset canine RD models at critical time points of the disease: RCD1, XLPRA2 and ERD. Both genes were differentially expressed in RCD1 and ERD, but not in XLPRA2. These results add evidence to the hypothesis that (a) mutations in many retinal genes have a cascade effect on the expression of multiple, possibly unrelated genes and (b) a large number and wide range of genes probably contribute to RD in general. PMID:26427412

  3. A co-expression network analysis reveals lncRNA abnormalities in peripheral blood in early-onset schizophrenia.

    PubMed

    Ren, Yan; Cui, Yuehua; Li, Xinrong; Wang, Binhong; Na, Long; Shi, Junyan; Wang, Liang; Qiu, Lixia; Zhang, Kerang; Liu, Guifen; Xu, Yong

    2015-12-01

    Long non-coding RNAs (lncRNAs) are emerging as important regulators of gene expression and disease processes especially in neuropsychiatric disorders. To explore the potential regulatory roles of lncRNAs in schizophrenia, we performed an integrated co-expression network analysis on lncRNA and mRNA microarray profiles generated from the peripheral blood samples in 19 drug-naïve first-episode early-onset schizophrenia (EOS) patients and 18 demographically matched typically developing controls (TDCs). Using weighted gene co-expression network analysis (WGCNA), we showed that the lncRNAs were organized into co-expressed modules, and two lncRNA modules were associated with EOS. The mRNA networks were constructed and three disease-associated modules were identified. Gene Ontology (GO) analysis indicated that the mRNAs were highly enriched for mitochondrion and related biological processes. Moreover, our results revealed a significant correlation between lncRNAs and mRNAs using the canonical correlation analysis (CCA). Our results suggest that the convergent lncRNA alteration may be involved in the etiologies of EOS, and mitochondrial dysfunction participates in the pathological process of the disease. Our findings may shed light on the pathogenesis of schizophrenia and facilitate future diagnosis and therapeutic strategies. PMID:25967042

  4. Is the Predictability of New-Onset Postpartum Depression Better During Pregnancy or in the Early Postpartum Period? A Prospective Study in Croatian Women.

    PubMed

    Naki? Radoš, Sandra; Herman, Radoslav; Tadinac, Meri

    2016-01-01

    The researchers' aim was to examine whether it was better to predict new-onset postpartum depression (PPD) during pregnancy or immediately after childbirth. A prospective study conducted in Croatia followed women (N = 272) from the third trimester of pregnancy through the early postpartum period (within the first 3 postpartum days), to 6 weeks postpartum. Questionnaires on depression, anxiety, stress, coping, self-esteem, and social support were administered. Through regression analyses we showed that PPD symptoms could be equally predicted by variables from pregnancy (30.3%) and the early postpartum period (34.0%), with a small advantage of PPD prediction in the early postpartum period. PMID:25558954

  5. Nonsurgical periodontal treatment.

    PubMed

    Aimetti, Mario

    2014-01-01

    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

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

    PubMed Central

    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

    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

  7. Rare complication of ventriculoperitoneal shunt. Early onset of distal catheter migration into scrotum in an adult male: Case report and literature review

    PubMed Central

    Lee, Bryan S.; Vadera, Sumeet; Gonzalez-Martinez, Jorge A.

    2014-01-01

    Introduction The role of shunt placement is to divert cerebrospinal fluid from within the ventricles to an alternative location in the setting of hydrocephalus. One of the rare shunt complications is distal catheter migration, and various body sites have been reported, including the scrotum. Although cases of scrotal migration of distal catheter have been reported in pediatric patients, cases in adult patients are rare due to obliterated processus vaginalis. Furthermore, there has not been a case reported for scrotal migration in an adult at an early onset. Presentation of case 65-year-old male underwent shunt placement for normal-pressure hydrocephalus-like symptoms. On post-operative day seven patient developed right testicular edema, for which ultrasound was performed, revealing hydrocele along with the presence of distal catheter in the scrotum. On post-operative day nine patient underwent distal catheter trimming via laparoscopic approach with general surgery, with post-operative imaging showing satisfactory location of distal catheter in the peritoneal cavity. Discussion/Conclusion Early onset of distal catheter migration into scrotum in an adult male is a unique case, as most cases are reported in pediatric patients, and it is the first case reported in the English literature to have occurrence at an early onset during the peri-operative period. As our case demonstrates, early occurrence and detection of scrotal migration of the distal catheter prevent shunt malfunction. Prompt surgical management of catheter repositioning is therefore recommended to avoid the risk of further complications. PMID:25553524

  8. Periodontitis diagnostics using resonance Raman spectroscopy on saliva

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

    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.

  9. Recessive Mutations in the ?3 (VI) Collagen Gene COL6A3 Cause Early-Onset Isolated Dystonia

    PubMed Central

    Zech, Michael; Lam, Daniel D.; Francescatto, Ludmila; Schormair, Barbara; Salminen, Aaro V.; Jochim, Angela; Wieland, Thomas; Lichtner, Peter; Peters, Annette; Gieger, Christian; Lochmüller, Hanns; Strom, Tim M.; Haslinger, Bernhard; Katsanis, Nicholas; Winkelmann, Juliane

    2015-01-01

    Isolated dystonia is a disorder characterized by involuntary twisting postures arising from sustained muscle contractions. Although autosomal-dominant mutations in TOR1A, THAP1, and GNAL have been found in some cases, the molecular mechanisms underlying isolated dystonia are largely unknown. In addition, although emphasis has been placed on dominant isolated dystonia, the disorder is also transmitted as a recessive trait, for which no mutations have been defined. Using whole-exome sequencing in a recessive isolated dystonia-affected kindred, we identified disease-segregating compound heterozygous mutations in COL6A3, a collagen VI gene associated previously with muscular dystrophy. Genetic screening of a further 367 isolated dystonia subjects revealed two additional recessive pedigrees harboring compound heterozygous mutations in COL6A3. Strikingly, all affected individuals had at least one pathogenic allele in exon 41, including an exon-skipping mutation that induced an in-frame deletion. We tested the hypothesis that disruption of this exon is pathognomonic for isolated dystonia by inducing a series of in-frame deletions in zebrafish embryos. Consistent with our human genetics data, suppression of the exon 41 ortholog caused deficits in axonal outgrowth, whereas suppression of other exons phenocopied collagen deposition mutants. All recessive mutation carriers demonstrated early-onset segmental isolated dystonia without muscular disease. Finally, we show that Col6a3 is expressed in neurons, with relevant mRNA levels detectable throughout the adult mouse brain. Taken together, our data indicate that loss-of-function mutations affecting a specific region of COL6A3 cause recessive isolated dystonia with underlying neurodevelopmental deficits and highlight the brain extracellular matrix as a contributor to dystonia pathogenesis. PMID:26004199

  10. Stress increases periodontal inflammation.

    PubMed

    Rivera, César; Monsalve, Francisco; Suazo, Iván; Becerra, Javiera

    2012-11-01

    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1-1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P?0.05, Mann-Whitney U-test) and increased the severity (P?0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  11. Evolution of volcanically-induced palaeoenvironmental changes leading to the onset of OAE1a (early Aptian, Cretaceous)

    NASA Astrophysics Data System (ADS)

    Keller, Christina E.; Hochuli, Peter A.; Giorgioni, Martino; Garcia, Therese I.; Bernasconi, Stefano M.; Weissert, Helmut

    2010-05-01

    During the Cretaceous, several major volcanic events occurred that initiated climate warming, altered marine circulation and increased marine productivity, which in turn often resulted in the widespread black shale deposits of the Oceanic Anoxic Events (OAE). In the sediments underlying the early Aptian OAE1a black shales, a prominent negative carbon isotope excursion is recorded. Its origin had long been controversial (e.g. Arthur, 2000; Jahren et al., 2001) before recent studies attributed it to the Ontong Java volcanism (Méhay et al., 2009; Tejada et al., 2009). Therefore the negative C-isotope excursion covers the interval between the time, when volcanic activity became important enough to be recorded in the C-isotope composition of the oceans to the onset of widespread anoxic conditions (OAE1a). We chose this interval at the locality of Pusiano (N-Italy) to study the effect of a volcanically-induced increase in pCO2 on the marine palaeoenvironment and to observe the evolving palaeoenvironmental conditions that finally led to OAE1a. The Pusiano section (Maiolica Formation) was deposited at the southern continental margin of the alpine Tethys Ocean and has been bio- and magnetostratigraphically dated by Channell et al. (1995). We selected 18 samples from 12 black shale horizons for palynofacies analyses. Palynofacies assemblages consist of several types of particulate organic matter, providing information on the origin of the organic matter (terrestrial/marine) and conditions during deposition (oxic/anoxic). We then linked the palynofacies results to high-resolution inorganic and organic C-isotope values and total organic carbon content measurements. The pelagic Pusiano section consists of repeated limestone-black shale couplets, which are interpreted to be the result of changes in oxygenation of bottom waters. Towards the end of the negative C-isotope excursion we observe enhanced preservation of the fragile amorphous organic matter resulting in increased total organic carbon values in the black shale as well as in the limestone intervals. This shows how a rising pCO2 triggered changes in climate and oceanography and resulted in an increasing oxygen-deficiency of the bottom waters that persisted even during the 'limestone intervals' before oxygen-depletion finally became a global phenomenon. References: Arthur, M.A., 2000, Volcanic contributions to the carbon and sulfur geochemical cycles and global change, in Sigurdsson, H., Houghton, B., McNutt, S.R., Rymer, H., and Stix, J., eds., Encyclopedia of Volcanoes, Academic Press, p. 1045-1056. Channell, J.E.T., Cecca, F., and Erba, E., 1995, Correlations of Hauterivian and Barremian (Early Cretaceous) stage boundaries to polarity chrons: Earth and Planetary Science Letters, v. 134, p. 125-140. Jahren, A.H., Arens, N.C., Sarmiento, G., Guerrero, J., and Amundson, R., 2001, Terrestrial record of methane hydrate dissociation in the Early Cretaceous: Geology, v. 29, p. 159-162. Méhay, S., Keller, C.E., Bernasconi, S.M., Weissert, H., Erba, E., Bottini, C., and Hochuli, P.A., 2009, A volcanic CO2 pulse triggered the Cretaceous Oceanic Anoxic Event 1a and a biocalcification crisis: Geology, v. 37, p. 819-822. Tejada, M.L.G., Suzuki, K., Junichiro, K., Rodolfo, C., J., M.J., Naohiko, O., Tatsuhiko, S., and Yoshiyuki, T., 2009, Ontong Java Plateau eruption as a trigger for the early Aptian oceanic anoxic event: Geology, v. 37, p. 855-858.

  12. Limited family structure and triple-negative breast cancer (TNBC) subtype as predictors of BRCA mutations in a genetic counseling cohort of early-onset sporadic breast cancers.

    PubMed

    Zugazagoitia, Jon; Pérez-Segura, Pedro; Manzano, Arancha; Blanco, Ignacio; Vega, Ana; Custodio, Ana; Teulé, Alex; Fachal, Laura; Martínez, Beatriz; González-Sarmiento, Rogelio; Cruz-Hernández, Juan Jesús; Chirivella, Isabel; Garcés, Vicente; Garre, Pilar; Romero, Atocha; Caldés, Trinidad; Díaz-Rubio, Eduardo; de la Hoya, Miguel

    2014-11-01

    Early-onset diagnosis is an eligibility criterion for BRCA1 and BRCA2 (BRCA) testing in sporadic breast cancer patients. Limited family structure has been proposed as a predictor of BRCA mutation status in this group of patients. An overwhelming amount of data supports a strong association between BRCA1 mutations and triple-negative breast cancer (TNBC). Here, we analyze the feasibility of using limited family structure and TNBC as predictors of BRCA mutation status in early-onset breast cancer patients attending genetic counseling units. We have conducted the study in a cohort of sporadic early-onset (?35 years) breast cancer patients (N = 341) previously selected for BRCA genetic testing in Academic Hereditary Cancer Clinics from Spain. A retrospective review of medical records available at the time of risk assessment allowed us classifying patients according to family structure and TNBC. In addition, BRCAPRO score was calculated for all patients. Association between categorical variables was investigated using the Fisher's exact test. Binary Logistic Regression Analysis was used for multivariate analysis. Limited family structure (OR 3.61, p = 0.013) and TNBC (OR 3.14, p = 0.013) were independent predictors of BRCA mutation status. Mutation prevalence in the subgroup of patients with at least one positive predictor was 14%, whereas it dropped to 3% in non-TNBCs with adequate family history (OR 5.31, 95% CI 1.38-23.89, p = 0.006). BRCAPRO correctly discerned between limited and adequate family structures. Limited family structure and TNBC are feasible predictors of BRCA mutation status in sporadic early-onset (?35 years) breast cancer patients attending genetic counseling units. The low prevalence of mutations observed in non-TNBCs with adequate family structure suggests that this subgroup of patients might be excluded from genetic testing. PMID:25342642

  13. Polymorphism on Chromosome 9p21.3 Is Associated with Severity and Early-Onset CAD in Type 2 Diabetic Tunisian Population

    PubMed Central

    Abid, Kaouthar; Mili, Donia; Kenani, Abderraouf

    2015-01-01

    Multiple association studies found that the human 9p21.3 chromosome locus is a risk factor for atherosclerosis. The purpose of this study was to investigate the association of the severity and early-onset of coronary artery disease with variant rs1333049 on chromosome 9p21.3 polymorphism and the impact of this variant on cardiovascular risk factors in type 2 diabetic patients. The study population consisted of a control CAD group (101 patients) and 273 consecutive type 2 diabetic patients. Severity and extent of coronary atherosclerosis were scored numerically using the Gensini scoring system. The diabetic population was divided into three groups according to Gensini score: Group 1: no stenosis; Group 2: moderate CAD; Group 3, severe CAD. The homozygous CC genotype of rs1333049 was significantly associated with CAD in Group 2 (OR: 1.36; p = 0.02) and Group 3 (OR: 5.77, p < 0.001) compared to Group 1 (OR: 0.18; p = 0.2) and control group (OR: 0.22; p = 0.21). Among diabetic patients with early-onset CAD, CC genotype carriers had significantly higher Gensini scores than non-CC genotype carriers (49 ± 21.3 versus 14.87 ± 25.22; p < 0.001). The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and severe CAD in type 2 diabetic Tunisian population. PMID:26417150

  14. Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease.

    PubMed

    Cornejo-Olivas, Mario R; Yu, Chang-En; Mazzetti, Pilar; Mata, Ignacio F; Meza, Maria; Lindo-Samanamud, Saul; Leverenz, James B; Bird, Thomas D

    2014-03-20

    Presenilin 1 (PSEN1) gene mutations are found in 30-70% of familial early-onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment were completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family. PMID:24495933

  15. Periodontal Disease and Systemic Health

    MedlinePLUS

    ... Often They Floss Their Teeth Study: Poor Oral Hygiene Habits May Increase Hypertension Risk Study: Alcohol Consumption ... Career Options in Periodontics In-Service Examination Dental Hygiene Educators Perio Resident Recruitment Periodontal Literature Review: The ...

  16. Periodontal Probe Improves Exams, Alleviates Pain

    NASA Technical Reports Server (NTRS)

    2008-01-01

    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.

  17. Manganese exposure among smelting workers: Relationship between blood manganese–iron ratio and early onset neurobehavioral alterations

    PubMed Central

    Cowan, Dallas M.; Zheng, Wei; Zou, Yan; Shi, Xiujuan; Chen, Jian; Rosenthal, Frank S.; Fan, Qiyuan

    2014-01-01

    A biomarker for detection of early onset neurobehavioral alterations in manganism remains unknown. The purpose of this study was to use a neurobehavioral test battery to identify subtle changes in Mn-induced motor and memory dysfunction and to relate the quantifiable neurological dysfunction to an established Mn-exposure index such as blood manganese–iron ratio (MIR). A total of 323 subjects were recruited to control (n = 106), low-exposure (122), and high-exposure (95) groups. The test battery consisted of standard testing procedures including the nine-hole and groove-type steadiness tester, Benton visual retention test, and Purdue pegboard coordination test. No significant health problems or clinically diagnosed neurological dysfunctions were observed. Benton test did not reveal any abnormal memory deficits among Mn-exposed smelters, nor did the groove and nine-hole tests detect any abnormality in dynamic and static steadiness in tested subjects. Purdue pegboard test showed a remarkable age-related decline in fine movement coordination among all study participants regardless of the Mn-exposure condition. Mn exposure significantly exacerbated this age-related deterioration. Statistical modeling revealed that the plasma and erythrocyte MIR (i.e., pMIR and eMIR, respectively) were associated with Purdue pegboard scores. Among all subjects whose MIR were above the cut-off value (COV), pMIR was significantly correlated with pegboard scores (r = ?0.261, p = 0.002), whereas for those subjects over the age of 40, the eMIR, but not pMIR, was associated with declined pegboard performance (r = ?0.219, p = 0.069). When both factors were taken into account (i.e., age > 40 and MIR > the COV), only pMIR was inversely associated with pegboard scores. Combining their usefulness in Mn-exposure assessment, we recommend that the blood Mn–Fe ratio may serve as a reasonable biomarker not only for assessment of Mn exposure but also for health risk assessment. PMID:19963104

  18. Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics.

    PubMed

    Kuhn, Pierre; Dheu, Céline; Bolender, Chantal; Chognot, Didier; Keller, Laurence; Demil, Houria; Donato, Lionel; Langer, Bruno; Messer, Jean; Astruc, Dominique

    2010-09-01

    In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance. PMID:20670228

  19. Association of interleukin-1 ? (–889) gene polymorphism in patients with generalized aggressive and chronic periodontitis

    PubMed Central

    Puri, Komal; Chhokra, Mehak; Dodwad, Vidya; Puri, Nikhil

    2015-01-01

    Background: There is a strong evidence that genetic as well as environmental factors affect the age of onset, severity and lifetime risk of developing periodontitis. The objective of the present study was to compare and to evaluate the association between interleukin (IL)-1?(-889) and gene polymorphisms in patients with generalized aggressive periodontitis, chronic periodontitis and healthy controls. Materials and Methods: A total of 60 Indian patients, with 20 aggressive periodontitis, 20 chronic periodontitis and 20 healthy controls were recruited for this study. From each patient, a volume of 2 ml of blood was collected by venipuncture in the ante-cubital fossa and was stored in sodium EDTA vacutainers and was used for genotyping assays with the polymerase chain reaction restriction fragment length polymorphism technique. Clinical parameters such as oral hygiene index, gingival index and clinical attachment loss (CAL) were evaluated for each patient. Genotype distribution between different groups were analyzed using Chi-square test. A P = 0.05 or less was set for significance. Results: The mean oral hygiene index was 3.7 ± 0.86 and 3.25 ± 0.30 for chronic and aggressive periodontitis cases respectively. The CAL was 4.29 ± 0.63 mm for chronic periodontitis and 6.44 ± 0.57 mm for aggressive periodontitis. Homozygous genotype 2,2 was more predominant in cases of aggressive periodontitis whereas in chronic periodontitis, heterozygous genotype 1,2 was more predominant when compared with others (P < 0.001). Odds ratio for aggressive versus chronic periodontitis was calculated as 6.2 (95% confidence interval 6.019-7.892). Conclusion: The results of the present study support a positive association between aggressive periodontitis and the presence of the IL-1?-889, allele 2 polymorphism in Indian patients. PMID:25709679

  20. Loss of functional connectivity is greater outside the default mode network in non-familial early-onset Alzheimer’s disease variants

    PubMed Central

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

    2015-01-01

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

  1. Clinical Value of NPHS2 Analysis in Early- and Adult-Onset Steroid-Resistant Nephrotic Syndrome

    PubMed Central

    Santín, Sheila; Tazón-Vega, Bárbara; Silva, Irene; Cobo, María Ángeles; Giménez, Isabel; Ruíz, Patricia; García-Maset, Rafael; Ballarín, José

    2011-01-01

    Summary Background and objectives To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. Design, setting, participants, & measurements Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. Results Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio = 2.65; P = 0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. Conclusions NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant. PMID:20947785

  2. Chronic Mild Stress Assay Leading to Early Onset and Propagation of Alzheimer's Disease Phenotype in Mouse Models.

    PubMed

    Cuadrado-Tejedor, Mar; García-Osta, Ana

    2016-01-01

    A comprehensive chronic mild stress (CMS) procedure is presented, which consists in the application of unpredictable mild stressors to animal models in a random order for several weeks. This assay can be applied to Alzheimer's disease (AD) mouse models, leading to accelerated onset and increased severity of AD phenotypes and signs, including memory deficits and the accumulation of amyloid-? and phospho-tau. These assays open the way towards advanced studies on the influence of sustained mild stress, stress responses and pathways on the onset and propagation of Alzheimer's disease. PMID:26235071

  3. Defensins in periodontal health.

    PubMed

    Bedi, Taran; Mahendra, Jaideep; Ambalavanan, N

    2015-01-01

    Defensins are abundant and widely distributed peptides in human and animal tissues that are involved in host defence. Defensins not only have the ability to strengthen the innate immune system but can also enhance the adaptive immune system by chemotaxis of monocytes, T-lymphocytes, dendritic cells and mast cells to the infection site. Defensins also improves the capacity of macrophage phagocytosis. A greater understanding of how these peptides act in the healthy, gingivitis and periodontitis conditions would definitely open new opportunities for identification, prevention and treatment of periodontal diseases. This discussion focuses on recent studies about biological function of defensins in human diseases and animal models. PMID:26481877

  4. 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)

    Clifford, S. M.

    1993-01-01

    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.

  5. Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse

    SciTech Connect

    Vanyukov, M.M.; Moss, H.B.; Tarter, R.E.

    1995-04-24

    An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA-1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA-1 repeat was found in males, but not females, with {open_quotes}long{close_quotes} alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. 22 refs., 1 fig., 3 tabs.

  6. Identification of novel genetic determinants in the high prevalence early-onset inflammatory bowel disease population in Scotland 

    E-print Network

    Limbergen, Johan Emiel van

    2010-01-01

    -control analysis, childhood onset IBD and CD was associated with asthma (p<0.0001 OR 1.7 (1.3-2.1) and (p=0.005 OR 2.5 (1.3-4.8), respectively). Inherited variation of NOD1/CARD4 was not a strong determinant of disease susceptibility in the Scottish population...

  7. QUANTITATIVE ANALYSIS OF PERIODONTAL PATHOGENS IN PERIODONTITIS AND GINGIVITIS.

    PubMed

    Scapoli, L; Girardi, A; Palmieri, A; Martinelli, M; Cura, F; Lauritano, D; Carinci, F

    2015-01-01

    Periodontal tissues surround the teeth and provide their attachment. Periodontal diseases include a mild and reversible form named gingivitis and periodontitis that is the main cause of tooth loss in adults. Gingivitis, that affects gums and coronal junctional epithelium, as well as periodontitis, that is characterized by loss of connective tissue attachment, are caused by a persistent inflammatory response promoted by alteration of periodontal biofilm. The aim of the study was to test whether the prevalence or relative amount of each species was associated with a particular clinical condition. Periodontal evaluation of 539 unrelated patients was performed by the Periodontal Screening and Recording (PSR) system. Subgingival samples were obtained from the site with the worst PSR score. A selection of eleven bacterial species was evaluated by quantitative real time PCR. Some bacterial species were found to be associated with all phases of periodontal disease, such as Tannerella forsythia, Treponema denticola, and Treponema lecithinolyticum, while other species were more specifically associated with periodontitis, such as Porphyromonas endodontalis and Porphyromonas gingivalis, or with gingivitis, such as Capnocytophaga ochracea and Campylobacter rectus. Quantitative and qualitative analyses helps to better understand the microbial changes associated with different stages of periodontal disease. PMID:26511188

  8. Self-reported periodontal disease in a Virginia twin population.

    PubMed

    Corey, L A; Nance, W E; Hofstede, P; Schenkein, H A

    1993-12-01

    To investigate the contribution of genetic factors in the etiology of periodontal disease, questionnaire data were collected on 4,908 twin pairs included in the population-based Virginia Twin Registry. A history of periodontal disease was reported in 420 individuals who were members of 116 monozygotic (MZ) and 233 dizygotic (DZ) twin pairs. The mean age at diagnosis in this sample was 31.4 +/- 0.7 years and was significantly earlier in females than males (30.1 vs. 33.0 years, P < 0.025). Proband-wise concordance rates were 0.38 for MZ and 0.16 for DZ twins. There were no differences in concordance rate between same and opposite-sexed dizygotic twins. These findings provide evidence that genetic factors make an important contribution to risk for adult-onset periodontal disease. PMID:8106947

  9. A longitudinal assessment of periodontal disease in 52 miniature schnauzers

    PubMed Central

    2014-01-01

    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

  10. Periodontal Plastic Surgery Procedures

    MedlinePLUS

    ... smile just the right look. Long Teeth/Exposed Roots Sometimes gum recession causes the tooth root to become exposed, which makes your teeth look ... including periodontal diseases. Gum graft surgery and other root coverage procedures are designed to cover exposed roots, ...

  11. Periodontics II: Course Proposal.

    ERIC Educational Resources Information Center

    Dordick, Bruce

    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…

  12. The role of germline mutations in the BRCA1/2 and mismatch repair genes in men ascertained for early-onset and/or familial prostate cancer.

    PubMed

    Maia, Sofia; Cardoso, Marta; Paulo, Paula; Pinheiro, Manuela; Pinto, Pedro; Santos, Catarina; Pinto, Carla; Peixoto, Ana; Henrique, Rui; Teixeira, Manuel R

    2016-01-01

    Prostate cancer (PrCa) is one of the most common cancers diagnosed worldwide and 5-10 % of all cases are estimated to be associated with inherited predisposition. Even though there is strong evidence that the genetic component is significant in PrCa, the genetic etiology of familial and early-onset disease is largely unknown. Although it has been suggested that men from families with hereditary breast/ovarian cancer (HBOC) and, more recently, with Lynch syndrome may have an increased risk for PrCa, the contribution of these syndromes to PrCa predisposition in families ascertained for early-onset and/or familial PrCa, independently of the presence of other cancers in the family, is uncertain. To quantify the contribution of genes associated with HBOC and Lynch syndromes to PrCa predisposition, we have tested for germline mutations 460 early-onset and/or familial PrCa patients. All patients were screened for the six mutations that are particularly common in Portugal and 38 of them were selected for complete sequencing of BRCA1/2 and/or MLH1, MSH2 and MSH6. Two patients were found to harbor the same MSH2 mutation and a third patient carried a Portuguese BRCA2 founder mutation. None of the alterations were identified in 288 control subjects. Furthermore, we reviewed the 62 PrCa diagnoses in all HBOC (n = 161) and Lynch syndrome (n = 124) families previously diagnosed at our department, and found five other BRCA2 mutation carriers and two additional MSH2 mutation carriers. The clinicopathological characteristics of mutation carriers are in concordance with earlier data suggesting an aggressive PrCa phenotype and support the hypothesis that mutation carriers might benefit from targeted screening according to the gene mutated in the germline. PMID:26289772

  13. Prevalence and risk factors of early onset of sexual intercourse in a random sample of a multiethnic adolescent population in French Guiana.

    PubMed

    Ayhan, Gülen; Martin, Loic; Levy-Loeb, Mathieu; Thomas, Stéphanie; Euzet, Géneviève; Van Melle, Astrid; Parriault, Marie-Claire; Basurko, Célia; Nacher, Mathieu

    2015-01-01

    French Guiana, a French overseas department in South America, has been classified epidemic for HIV. This territory is consisting of a very young population with almost 45% of them being younger than 20 years of age. Delaying the onset of first sexual intercourse (SI) is one of the major objectives to fight HIV infection in adolescents. The objective of this study is to identify the age of first SI and the risk factors of early onset. A behavioural surveillance survey among students living on the coastline and alongside the Maroni River was conducted in 2011/2012. A total of 1603 students filled out the survey. While 60% had already SI, the mean age of first intercourse was 12.1 years for boys and 13.9 years for girls. Accordingly, over 90% had a premature onset of SI. Risk factors are age, male gender, living alongside the Maroni River, another language than the French being mother tongue, not being religious, alcohol and cannabis consumption and a bad attitude towards condom use. Risk factors for girls are an older first sexual partner, having more than three lifetime sexual partners and condom rupture. Evidence-based implementation with respect of local and socio-demographic aspects is necessary to improve youths' appreciation of SI and related risk of sexual transmitted diseases. PMID:25782704

  14. Personalized medicine: an update of salivary biomarkers for periodontal diseases.

    PubMed

    Korte, Dina L; Kinney, Janet

    2016-02-01

    This article provides an up-to-date review of the more robust salivary biomarkers, as well as of panels of combinatorial markers and periodontal pathogens, that reveal high sensitivity and specificity for enhancing clinical decision-making in periodontal disease progression, risk and diagnosis. Periodontal diseases are complex and require an inflammatory response to bacterial pathogens in a susceptible host to stimulate tissue destruction. When used alone, traditional clinical assessments provide a diagnosis of periodontitis only after the biologic onset of the disease process, and are unable to substantiate disease activity or future risk. New technologies are becoming available that are capable of measuring combinations of inflammatory cytokines and proteinases for rapid chair-side testing. Utilizing saliva to identify and measure specific phenotypes and host-derived mediators will allow highly individualized diagnosis, prognosis and treatments for periodontal diseases. This personalized medicine approach will strengthen the power of the clinical oral examination and medical history assessments, providing patients with evidence-based, targeted risk care. PMID:26662480

  15. Bone resorption: an actor of dental and periodontal development?

    PubMed Central

    Gama, Andrea; Navet, Benjamin; Vargas, Jorge William; Castaneda, Beatriz; Lézot, Frédéric

    2015-01-01

    Dental and periodontal tissue development is a complex process involving various cell-types. A finely orchestrated network of communications between these cells is implicated. During early development, communications between cells from the oral epithelium and the underlying mesenchyme govern the dental morphogenesis with successive bud, cap and bell stages. Later, interactions between epithelial and mesenchymal cells occur during dental root elongation. Root elongation and tooth eruption require resorption of surrounding alveolar bone to occur. For years, it was postulated that signaling molecules secreted by dental and periodontal cells control bone resorbing osteoclast precursor recruitment and differentiation. Reverse signaling originating from bone cells (osteoclasts and osteoblasts) toward dental cells was not suspected. Dental defects reported in osteopetrosis were associated with mechanical stress secondary to defective bone resorption. In the last decade, consequences of bone resorption over-activation on dental and periodontal tissue formation have been analyzed with transgenic animals (RANKTg and Opg??? mice). Results suggest the existence of signals originating from osteoclasts toward dental and periodontal cells. Meanwhile, experiments consisting in transitory inhibition of bone resorption during root elongation, achieved with bone resorption inhibitors having different mechanisms of action (bisphosphonates and RANKL blocking antibodies), have evidenced dental and periodontal defects that support the presence of signals originating bone cells toward dental cells. The aim of the present manuscript is to present the data we have collected in the last years that support the hypothesis of a role of bone resorption in dental and periodontal development. PMID:26594180

  16. Periodontal regeneration using periodontal ligament stem cell-transferred amnion.

    PubMed

    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

    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

  17. Comparative bacteriology of juvenile periodontitis.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Palcanis, K G; Ranney, R R

    1985-01-01

    Statistical comparisons of the floras associated with juvenile periodontitis, severe periodontitis, and moderate periodontitis indicated that differences in the bacterial compositions of affected sites in these populations were not statistically significant. The subgingival flora of affected juvenile periodontitis sites was statistically significantly different from the adjacent supragingival flora and from the subgingival floras of people with healthy gingiva and of children with developing (experimental) gingivitis. However, the subgingival flora of affected juvenile periodontitis sites was not significantly different from the flora of sites with gingival index scores of 1 or 2 in adults with developing (experimental) gingivitis. Of 357 bacterial taxa among over 18,000 isolates, 54 non-treponemal species, 2 treponemal species, and mycoplasma were most associated with diseased periodontal sulci. These species comprised an increasing proportion of the flora during developing gingivitis and constituted over half of the cultivable flora of diseased sites. PMID:3988344

  18. Centipeda periodontii in human periodontitis.

    PubMed

    Rams, Thomas E; Hawley, Charles E; Whitaker, Eugene J; Degener, John E; van Winkelhoff, Arie J

    2015-09-01

    This study assessed the subgingival occurrence of the flagellated, Gram-negative, anaerobic rod Centipeda periodontii in chronic periodontitis and periodontal health/gingivitis with species-specific nucleic acid probes, and evaluated the in vitro resistance of subgingival isolates to therapeutic levels of amoxicillin, metronidazole, and doxycycline. Subgingival plaque biofilm specimens from 307 adults with chronic periodontitis, and 48 adults with periodontal health/localized gingivitis, were evaluated with digoxigenin-labeled, whole-chromosomal, DNA probes to C. periodontii ATCC 35019 possessing a 10(4) cell detection threshold. Fifty-two C. periodontii subgingival culture isolates were assessed on antibiotic-supplemented enriched Brucella blood agar for in vitro resistance to either amoxicillin at 2 µg/ml, metronidazole at 4 µg/ml, or doxycycline at 2 µg/ml. A significantly greater subgingival occurrence of C. periodontii was found in chronic periodontitis subjects as compared to individuals with periodontal health/gingivitis (13.4 vs. 0 %, P < 0.003), although high subgingival counts of the organism (? 10(6) cells) were rarely detected (1.3 % of chronic periodontitis subjects). In vitro resistance was not found to amoxicillin or metronidazole, and to doxycycline in only 2 (3.9 %) of the 52 C. periodontii clinical isolates studied. These findings indicate that C. periodontii is not a major constituent of the subgingival microbiome in chronic periodontitis or periodontal health/gingivitis. The potential contribution of C. periodontii to periodontal breakdown in the few chronic periodontitis subjects who yielded high subgingival levels of the organism remains to be delineated. C. periodontii clinical isolates were susceptible in vitro to therapeutic concentrations of three antibiotics frequently used in treatment of human periodontitis. PMID:25037463

  19. Assessment of Psychopatologic Traits in a Group of Patients with Adult Chronic Periodontitis: Study on 108 Cases and Analysis of Compliance during and after Periodontal Treatment

    PubMed Central

    Laforgia, Alessandra; Corsalini, Massimo; Stefanachi, Gianluca; Pettini, Francesco; Di Venere, Daniela

    2015-01-01

    Objectives: Although there is nowadays wide agreement on bacteria being the main etiologic agents of periodontal disease, their sole presence cannot damage periodontal tissues in all subjects. This suggests that an individual response and an adaptation to a certain quantity of bacterial biofilm can occur without the disease progressing and vice versa. Depression, stress and anxiety have not been confirmed yet as risk conditions but, in some observational studies, they have been identified as potential risk factors of periodontal disease. The current study aims at investigating the role which these psychological disorder have in the onset and progression of advanced stage periodontitis. Materials and methods: The case selection was carried out by means of clinical and radiological periodontal assessment involving a total of 108 subjects, both male and female, aged between 24 and 67. Patients were then divided in two groups of 54 patients each: the first group included patients with severe periodontal disease, the second group was formed by periodontally healthy subjects. Clinical assessment was performed by a sole examiner who selected and divided periodontopathic patients from non-periodontopathic ones. From the current study were excluded: patients with systemic pathologies; smokers; patients taking antidepressant drugs; pregnant women. Results: For what concerns depression, in the group of periodontopathic patients it was found that the 62.5% of them were depressed, against the 38.86% in the group of periodontally healthy subjects. For the other two psychological conditions taken into consideration, anxiety and stress, it emerged a different percentage of subjects with anxiety in the periodontal group (31.48%) against healthy controls (20.37%). Conclusions: For each of the psychological variables considered (depression, anxiety, stress), a significant correlation could be observed with periodontal disease, it can be therefore be suggested that the importance these disturbs have in the onset and progress of the dental disease which supports the existing available data in literature. The innovative aspect of this research was the focus on the assessment of compliance, monitoring the ability of periodontal patients to follow oral hygiene instructions aiming at the improving and keeping their own periodontal condition, even though this takes more time than the control group. PMID:26516312

  20. Lasers in periodontics

    PubMed Central

    Elavarasu, Sugumari; Naveen, Devisree; Thangavelu, Arthiie

    2012-01-01

    Laser is one of the most captivating technologies in dental practice since Theodore Maiman in 1960 invented the ruby laser. Lasers in dentistry have revolutionized several areas of treatment in the last three and a half decades of the 20th century. Introduced as an alternative to mechanical cutting device, laser has now become an instrument of choice in many dental applications. Evidence suggests its use in initial periodontal therapy, surgery, and more recently, its utility in salvaging implant opens up a wide range of applications. More research with better designs are a necessity before lasers can become a part of dental armamentarium. This paper gives an insight to laser in periodontics. PMID:23066266

  1. Bilingual language processing after a lesion in the left thalamic and temporal regions. A case report with early childhood onset

    SciTech Connect

    van Lieshout, P.; Renier, W.; Eling, P.; de Bot, K.; Slis, I. )

    1990-02-01

    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.

  2. Neutrophil activation and periodontal tissue injury.

    PubMed

    Herrmann, Jens Martin; Meyle, Jörg

    2015-10-01

    Neutrophilic polymorphonuclear leukocytes (PMNL) track, engage and eliminate foreign entities, including bacteria, fungi and subcellular particles. PMNL are the major host-cell line involved in the acute response during the early stages of infections, including those in the oral cavity. Rather short lived, they are among the fastest moving cells in the human body and travel great distances only to be immolated after encountering and neutralizing antigens. Although their role as the first line of host defense is well established, their role in chronic granulomatous inflammations, diseases and infections remains poorly understood, and many questions on the activation, motility, bactericidity and termination of PMNL in these conditions remain unanswered. This review aims to summarize our current understanding of the molecular mechanisms of PMNL activation and signaling events. Recent evidence indicates the presence of collateral tissue damage caused by poorly regulated PMNL pursuits of periodontal bacteria. Imbalances between the antigenic challenge and the primary host response may augment periodontal tissue breakdown. Thereafter, orchestrated regulation of the resolution of inflammation fails in the presence of a pathogenic periodontal biofilm. PMID:26252405

  3. Inflammatory Myofibroblastic Tumor Mimicking Apical Periodontitis.

    PubMed

    Adachi, Makoto; Kiho, Kazuki; Sekine, Genta; Ohta, Takahisa; Matsubara, Makoto; Yoshida, Takakazu; Katsumata, Akitoshi; Tanuma, Jun-Ichi; Sumitomo, Shinichiro

    2015-12-01

    Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis. PMID:26602450

  4. Are Persistent Early Onset Child Conduct Problems Predicted by the Trajectories and Initial Levels of Discipline Practices?

    ERIC Educational Resources Information Center

    Lorber, Michael F.; Slep, Amy M. Smith

    2015-01-01

    In the present investigation we focused on 2 broad sets of questions: Do parental overreactivity, laxness, and corporal punishment show evidence of normative change in early to middle childhood? Are persistently elevated child conduct problems (CPs) associated with deviations from normative changes in, as well as high initial levels of, discipline…

  5. On putative periodontal pathogens: an epidemiological perspective.

    PubMed

    Lopez, Rodrigo; Hujoel, Philippe; Belibasakis, Georgios N

    2015-01-01

    The current understanding on the role of microbiology on periodontitis causation is reviewed. An appraisal of the literature reveals several issues that have limited the attempts to investigate candidate periodontal pathogens as causes of periodontitis and confirms that only limited epidemiological evidence is available. Several aspects of the contemporary understanding on causal inference are discussed with examples for periodontitis. PMID:25874553

  6. Perilous periodontitis: a clinical study.

    PubMed

    Emmanuel, Roby V; Neelakantan, Shiba

    2011-12-01

    The aim of this study is to determine whether periodontitis in pregnant women could be a risk factor for pre term low birth weight. The oral hygiene status, periodontal status and periodontal treatment needs of mothers who birthed infants with normal birth weight and normal gestation period (group A) and mothers who birthed pre term low birth weight infants (group B) were assessed and compared. The clinical parameters used were Oral Hygiene Index--simplified (OHI-S), gingival bleeding index (GBI), probing pocket depth and Community Periodontal Index of Treatment Needs (CPITN). This article presents the study and its findings and draws conclusions as to the relationship between poor periodontal condition and pre term low birth weight. PMID:22216586

  7. Periodontal Dressing: A Review Article

    PubMed Central

    Baghani, Zahra; Kadkhodazadeh, Mahdi

    2013-01-01

    The purpose of this paper was to review the commercially available periodontal dressings, their physical and chemical properties, biocompatibility and therapeutic effects. Electronic search of scientific papers from 1956 to 2012 was carried out using PubMed, Scopus and Wiley InterScience search engines using the searched terms periodontal dressing, periodontal pack. Numerous in vitro and in vivo studies have evaluated various properties of periodontal dressings. Physical and chemical properties of dressings are directly related to their dimensional changes and adhesion properties. Their biocompatibility and therapeutic effect are among the other factors evaluated in the literature. Chlorhexidine is the most commonly used antibacterial agent in studies. In general, when comparing the advantages with the disadvantages, application of periodontal dressing seems to be beneficial. Numerous factors are involved in selection of an optimal dressing such as surgeon’s intention, required time for the dressing to remain on the surgery site and its dimensional changes. PMID:24578815

  8. Animals deficient in C2Orf71, an autosomal recessive retinitis pigmentosa-associated locus, develop severe early-onset retinal degeneration.

    PubMed

    Kevany, Brian M; Zhang, Ning; Jastrzebska, Beata; Palczewski, Krzysztof

    2015-05-01

    Genetic mapping was recently used to identify the underlying cause for a previously uncharacterized cohort of autosomal recessive retinitis pigmentosa cases. Genetic mapping of affected individuals resulted in the identification of an uncharacterized gene, C2Orf71, as the causative locus. However, initial homology searches failed to reveal similarities to any previously characterized protein or domain. To address this issue, we characterized the mouse homolog, BC027072. Immunohistochemistry with a custom polyclonal antibody showed staining localized to the inner segments (IS) of photoreceptor cells, as well as the outer segments (OS) of cone cells. A knockout mouse line (BC(-/-)) was generated and demonstrated that loss of this gene results in a severe, early-onset retinal degeneration. Histology and electron microscopy (EM) revealed disorganized OS as early as 3 weeks with complete loss by 24 weeks of age. EM micrographs displayed packets of cellular material containing OS discs or IS organelles in the OS region and abnormal retinal pigmented epithelium cells. Analyses of retinoids and rhodopsin levels showed <20% in BC(-/-) versus wild-type mice early in development. Electroretinograms demonstrated that affected mice were virtually non-responsive to light by 8 weeks of age. Lastly, RNAseq analysis of ocular gene expression in BC(-/-) mice revealed clues to the causes of the progressive retinal degenerations. Although its function remains unknown, this protein appears essential for normal OS development/maintenance and vision in humans and mice. RNAseq data are available in the GEO database under accession: GSE63810. PMID:25616964

  9. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease.

    PubMed

    Palmio, Johanna; Jonson, Per Harald; Evilä, Anni; Auranen, Mari; Straub, Volker; Bushby, Kate; Sarkozy, Anna; Kiuru-Enari, Sari; Sandell, Satu; Pihko, Helena; Hackman, Peter; Udd, Bjarne

    2015-11-01

    DNAJB6 is the causative gene for limb-girdle muscular dystrophy 1D (LGMD1D). Four different coding missense mutations, p.F89I, p.F93I, p.F93L, and p.P96R, have been reported in families from Europe, North America and Asia. The previously known mutations cause mainly adult-onset proximal muscle weakness with moderate progression and without respiratory involvement. A Finnish family and a British patient have been studied extensively due to a severe muscular dystrophy. The patients had childhood-onset LGMD, loss of ambulation in early adulthood and respiratory involvement; one patient died of respiratory failure aged 32. Two novel mutations, c.271T?>?A (p.F91I) and c.271T?>?C (p.F91L), in DNAJB6 were identified by whole exome sequencing as a cause of this severe form of LGMD1D. The results were confirmed by Sanger sequencing. The anti-aggregation effect of the mutant DNAJB6 was investigated in a filter-trap based system using transient transfection of mammalian cell lines and polyQ-huntingtin as a model for an aggregation-prone protein. Both novel mutant proteins show a significant loss of ability to prevent aggregation. PMID:26338452

  10. Early-onset Alzheimers and cortical vision impairment in a woman with valosin-containing protein disease associated with 2 APOE ?4/APOE ?4 genotype.

    PubMed

    Shamirian, Sharis; Nalbandian, Angèle; Khare, Manaswitha; Castellani, Rudolph; Kim, Ronald; Kimonis, Virginia E

    2015-01-01

    Hereditary inclusion body myopathy is a heterogeneous group of disorders characterized by rimmed vacuoles and by the presence of filamentous cytoplasmic and intranuclear inclusions. Inclusion body myopathy with Paget disease of bone and frontotemporal dementia is a progressive autosomal dominant disorder associated with a mutation in valosin-containing protein (VCP) with typical onset of symptoms in the 30s. APOE [Latin Small Letter Open E]4 is a major risk factor for late-onset Alzheimer disease, a progressive neurodegenerative disorder that affects memory, thinking, behavior, and emotion as a result of the excessive buildup and decreased clearance of ?-amyloid proteins resulting in the appearance of neuritic plaques and neurofibrillary tangles. In conclusion, we report a unique patient with an APOE [Latin Small Letter Open E]4/APOE [Latin Small Letter Open E]4 genotype and atypical VCP disease associated with early Alzheimer disease and severe vision impairment. Future studies will elucidate the interaction of VCP mutations and APOE [Latin Small Letter Open E]4 alleles in understanding common mechanisms in AD and VCP disease. PMID:23715207

  11. Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus

    SciTech Connect

    Sakura, Hiroshi; Eto, Kazuhiro; Ueno, Hirohisa; Yazaki, Yoshio; Kadowaki, Takashi ); Kadowaki, Hiroko; Simokawa, Kotaro; Akanuma, Yasuo ); Koda, Naoya; Fukushima, Yoshimitsu )

    1992-12-01

    Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. The authors isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, they identified a missense mutation substituting ariginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM). 12 refs., 3 figs., 2 tabs.

  12. A review of the mechanism for poor placentation in early-onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remodeling.

    PubMed

    Saito, Shigeru; Nakashima, Akitoshi

    2014-03-01

    Shallow trophoblast invasion and impaired vascular remodeling of spiral arteries have been recognized in early-onset preeclampsia. Placentation and vascular remodeling are multistep processes, and hypoxia, placental oxidative stress, excessive or atypical maternal immune response to trophoblasts, exaggerated inflammation, and increased production of anti-angiogenic factors such as the soluble form of the vascular endothelial growth factor (VEGF) receptor (sFlt-1) and soluble endoglin (sENG) may play a role in poor placentation in preeclampsia. Recent findings suggest that autophagy plays an important role in extravillous trophoblast (EVT) invasion and vascular remodeling under hypoxia, and sENG inhibits EVT invasion and vascular remodeling by the inhibition of autophagy under hypoxic conditions. In this review, we discuss the relationship between inadequate autophagy and poor placentation in preeclampsia. PMID:23969229

  13. Developmental regulation of early mouse embryogenesis. A. Onset of insulin and related growth factor binding. B. Expression of selected proto-oncogenes

    SciTech Connect

    Mattson, B.A.

    1987-01-01

    Experimental and clinical evidence suggest a role for insulin and related growth factors in fetal growth. It was therefore of interest to determine the onset of insulin binding to cells of early embryos. These studies are the first to demonstrate stage-specific insulin binding during mouse preimplantation embryogenesis. Insulin binding was detected at the morula, blastocyst, and blastocyst outgrowth stages using indirect immunofluorescence and light microscopic autoradiographic techniques. No evidence of insulin binding was seen on unfertilized oocytes, two-, four-, or eight-cell embryos. Results of competitive inhibition studies using unlabeled insulin-like growth factors (IGFs) suggest binding of /sup 125/I-insulin to type I IGF receptors as well. Further studies are needed to confirm the presence of an IGF receptor in preimplantation embryos.

  14. Homozygous NOTCH3 null mutation and impaired NOTCH3 signaling in recessive early-onset arteriopathy and cavitating leukoencephalopathy.

    PubMed

    Pippucci, Tommaso; Maresca, Alessandra; Magini, Pamela; Cenacchi, Giovanna; Donadio, Vincenzo; Palombo, Flavia; Papa, Valentina; Incensi, Alex; Gasparre, Giuseppe; Valentino, Maria Lucia; Preziuso, Carmela; Pisano, Annalinda; Ragno, Michele; Liguori, Rocco; Giordano, Carla; Tonon, Caterina; Lodi, Raffaele; Parmeggiani, Antonia; Carelli, Valerio; Seri, Marco

    2015-06-01

    Notch signaling is essential for vascular physiology. Neomorphic heterozygous mutations in NOTCH3, one of the four human NOTCH receptors, cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Hypomorphic heterozygous alleles have been occasionally described in association with a spectrum of cerebrovascular phenotypes overlapping CADASIL, but their pathogenic potential is unclear. We describe a patient with childhood-onset arteriopathy, cavitating leukoencephalopathy with cerebral white matter abnormalities presented as diffuse cavitations, multiple lacunar infarctions and disseminated microbleeds. We identified a novel homozygous c.C2898A (p.C966*) null mutation in NOTCH3 abolishing NOTCH3 expression and causing NOTCH3 signaling impairment. NOTCH3 targets acting in the regulation of arterial tone (KCNA5) or expressed in the vasculature (CDH6) were downregulated. Patient's vessels were characterized by smooth muscle degeneration as in CADASIL, but without deposition of granular osmiophilic material (GOM), the CADASIL hallmark. The heterozygous parents displayed similar but less dramatic trends in decrease in the expression of NOTCH3 and its targets, as well as in vessel degeneration. This study suggests a functional link between NOTCH3 deficiency and pathogenesis of vascular leukoencephalopathies. PMID:25870235

  15. Homozygous NOTCH3 null mutation and impaired NOTCH3 signaling in recessive early-onset arteriopathy and cavitating leukoencephalopathy

    PubMed Central

    Pippucci, Tommaso; Maresca, Alessandra; Magini, Pamela; Cenacchi, Giovanna; Donadio, Vincenzo; Palombo, Flavia; Papa, Valentina; Incensi, Alex; Gasparre, Giuseppe; Valentino, Maria Lucia; Preziuso, Carmela; Pisano, Annalinda; Ragno, Michele; Liguori, Rocco; Giordano, Carla; Tonon, Caterina; Lodi, Raffaele; Parmeggiani, Antonia; Carelli, Valerio; Seri, Marco

    2015-01-01

    Notch signaling is essential for vascular physiology. Neomorphic heterozygous mutations in NOTCH3, one of the four human NOTCH receptors, cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Hypomorphic heterozygous alleles have been occasionally described in association with a spectrum of cerebrovascular phenotypes overlapping CADASIL, but their pathogenic potential is unclear. We describe a patient with childhood-onset arteriopathy, cavitating leukoencephalopathy with cerebral white matter abnormalities presented as diffuse cavitations, multiple lacunar infarctions and disseminated microbleeds. We identified a novel homozygous c.C2898A (p.C966*) null mutation in NOTCH3 abolishing NOTCH3 expression and causing NOTCH3 signaling impairment. NOTCH3 targets acting in the regulation of arterial tone (KCNA5) or expressed in the vasculature (CDH6) were downregulated. Patient's vessels were characterized by smooth muscle degeneration as in CADASIL, but without deposition of granular osmiophilic material (GOM), the CADASIL hallmark. The heterozygous parents displayed similar but less dramatic trends in decrease in the expression of NOTCH3 and its targets, as well as in vessel degeneration. This study suggests a functional link between NOTCH3 deficiency and pathogenesis of vascular leukoencephalopathies. PMID:25870235

  16. Common Periodontal Diseases of Children and Adolescents

    PubMed Central

    Al-Kahtani, Salem; Al-Duhaimi, Saad

    2014-01-01

    Background. Since 2000, studies, experiments, and clinical observations revealed high prevalence of periodontal diseases among children and adolescents. Therefore, this paper was designed to provide an update for dental practitioners on epidemiology, microbiology, pathology, prevention, diagnosis, and treatment of periodontal diseases in children and adolescents. Methods. This paper reviews the current literature concerning periodontal diseases in pediatric dentistry. It includes MEDLINE database search using key terms: “periodontal diseases in children,” “Periodontal diseasesin adolescents,” “periodontal diseases risk factors,” “microbiology of periodontal diseases,” “classification of periodontal diseases,” “epidemiology of periodontal diseases,” and “treatment of periodontal diseases.” Articles were evaluated by title and/or abstract and relevance to pediatric dentistry. Sixty-five citations were selected by this method and by the references within the chosen articles. A review of the comprehensive textbooks on pediatric dentistry and periodontology was done. Some recommendations were based on the opinions of experienced researchers and clinicians, when data were inconclusive. PMID:25053946

  17. Cytokine production by non-stimulated peripheral blood NK cells and lymphocytes in early-onset severe pre-eclampsia without HELLP.

    PubMed

    Bueno-Sánchez, J C; Agudelo-Jaramillo, B; Escobar-Aguilerae, L F; Lopera, A; Cadavid-Jaramillo, A P; Chaouat, G; Maldonado-Estrada, J G

    2013-04-01

    Preeclampsia involves an exacerbated maternal inflammatory response that suggests a possible role of innate immunity. NK cells can promote this kind of response through cytokine production and the expression of activating or inhibitory receptors. The aims of the present study were to explore cytokine production by peripheral blood mononuclear cells, as well as cytotoxic ability and receptor expression for HLA-E and HLA-G molecules in peripheral natural killer (NK) cells of women with early-onset severe preeclampsia without HELLP (hemolysis, elevated liver enzyme levels and a low platelet count) syndrome. The expression of the ILT2, KIRDL4, NKG2A, and NKG2C receptors and of cytotoxic activity was measured in non-stimulated NK cells, whereas the intracellular expression of IL-4, IL-10, IL-13, IL-12, IFN?, TNF and VEGF, was assessed in non-stimulated peripheral blood mononuclear cells subsets using flow cytometry. Circulating soluble HLA-G was also determined by ELISA. The intracellular cytokines tested were significantly higher in NK cell subsets from severely preeclamptic women compared with the control group. On the other hand, the percentage of NK cells expressing NKG2A or NKG2C and the cytotoxic activity of NK cells were significantly higher in severely preeclamptic women. Furthermore, there was a significant correlation between urine protein concentration and soluble human leukocyte antigen G (soluble HLA-G) in serum. We conclude that patients with early-onset severe preeclampsia without HELLP syndrome have increased NK cell function related to cytokine production, cytotoxicity and expression of lectin-like receptors such as NKG2. PMID:23415844

  18. Functional characterization of a new human melanocortin-4 receptor homozygous mutation (N72K) that is associated with early-onset obesity.

    PubMed

    Delhanty, Patric J D; Bouw, Elise; Huisman, Martin; Vervenne, Resie M L; Themmen, Axel P N; van der Lely, Aart Jan; van den Akker, Erica L T

    2014-12-01

    The melanocortin 4 receptor (MC4R) is expressed in the hypothalamus and is essential for regulation of appetite and energy expenditure. MC4R dysfunction in humans causes hyperphagia, impaired satiety and obesity. We have identified a novel c.216C>A (N72 K) homozygous mutation in MC4R in a girl with severe obesity. The patient presented with early-onset obesity and hyperphagia indicating an effect of the homozygous mutation on her phenotype. In silico analyses indicate a damaging effect on receptor function, and the mutation is unusual in occurring in the first intra-cellular loop of the receptor. Site-directed mutagenesis was used to generate plasmid constructs expressing wild-type and mutant MC4R. These were transfected into HEK293 cells and assessed for cAMP responsiveness to ?-MSH. Cells expressing N-terminal HA and C-terminal GFP-tagged MC4R were assessed by immunofluorescence confocal microscopy and flow cytometry for correct cell-surface localization. The maximal response of the mutant MC4R to ?-MSH was decreased to 20 ± 1 % of the wild type receptor response, and the EC50 was increased from 16.5 ± 5.4 nM to 37.0 ± 8.3 nM. Localization of N- and C-terminally tagged MC4R by confocal microscopy and flow cytometry showed aberrant retention of the mutant receptor in the cytoplasm. Our data describe a rare homozygous inactivating mutation in the first intra-cellular loop of MC4R that markedly impairs its function and is associated with early-onset obesity and hyperphagia. PMID:25163632

  19. A Novel Variant in CDKN1C Is Associated With Intrauterine Growth Restriction, Short Stature, and Early-Adulthood-Onset Diabetes

    PubMed Central

    Kerns, Sarah L.; Andrew, Shayne; Geng, Juan; Guevara, Carolina; Guevara-Aguirre, Marco; Guo, Michael; Oddoux, Carole; Shen, Yiping; Zurita, Andres; Rosenfeld, Ron G.; Ostrer, Harry; Hwa, Vivian

    2014-01-01

    Context: CDKN1C, a cyclin-dependent kinase inhibitor and negative regulator of cellular proliferation, is paternally imprinted and has been shown to regulate ?-cell proliferation. CDKN1C mutations are associated with growth disorders, including Beckwith-Wiedemann syndrome and IMAGe syndrome. Objective: To investigate the genetic basis for a familial disorder characterized by intrauterine growth restriction, short stature, and early-adulthood-onset diabetes. Design, Setting, and Participants: Genomic DNA samples (15 affected and 26 unaffected from a six-generation pedigree) were analyzed by genome-wide single nucleotide polymorphism arrays, whole exome and Sanger sequencing, and multiplex ligation-dependent probe amplification. Main Outcome Measure(s): Subjects were assessed for height, weight, adrenal gland size, ACTH, diabetes status, and testis volume. Linkage and sequence analyses were performed, and the identified genetic variant was functionally evaluated in reconstitution studies. Results: The pedigree followed a paternally imprinted pattern of inheritance, and genetic linkage analysis identified a single significant 2.6-megabase locus on chromosome 11p15, within the imprinting center region 2. Multiplex ligation-dependent probe amplification did not detect copy number variants or methylation abnormalities. Whole exome sequencing revealed a single novel variant in the proliferating cell nuclear antigen-binding region of CDKN1C (c.842G>T, p.R281I) that co-segregated with affected status and, unlike variants found in IMAGe, did not entirely abrogate proliferating cell nuclear antigen binding. Clinical assessments revealed that affected individuals had low testicular volume but normal adrenal function. Conclusions: We report a novel CDKN1C mutation associated with features of IMAGe syndrome, but without adrenal insufficiency or metaphyseal dysplasia, and characterized by early-adulthood-onset diabetes. Our data expand the range of phenotypes observed with CDKN1C defects and suggest that CDKN1C mutations may represent a novel monogenic form of diabetes. PMID:25057881

  20. Relation of subclinical coronary artery atherosclerosis to cerebral white matter disease in healthy subjects from families with early-onset coronary artery disease.

    PubMed

    Kral, Brian G; Nyquist, Paul; Vaidya, Dhananjay; Yousem, David; Yanek, Lisa R; Fishman, Elliot K; Becker, Lewis C; Becker, Diane M

    2013-09-15

    White matter disease (WMD) of the brain is associated with incident stroke. Similarly, subclinical calcified coronary artery plaque has been associated with incident coronary artery disease (CAD) events. Although atherogenesis in both vascular beds may share some common mechanisms, the extent to which subclinical CAD is associated with WMD across age ranges in subjects with a family history of early-onset CAD remains unknown. We screened 405 apparently healthy participants in the Genetic Study of Atherosclerotic Risk for CAD risk factors and for the presence of noncalcified and calcified coronary plaque using dual-source multidetector cardiac computed tomographic angiography. The presence and volumes of WMD were assessed by 3-Tesla brain magnetic resonance imaging. Participants were 60% women, 36% African-American, mean age 51.6 ± 10.6 years. The overall prevalence of coronary plaque was 43.0%. Subjects with coronary plaque had significantly greater WMD volumes (median 1,222 mm³, interquartile range 448 to 3,871) compared with those without coronary plaque (median 551 mm³, interquartile range 105 to 1,523, p <0.001). In multivariate regression analysis, adjusting for age, gender, race, traditional risk factors, total brain volume, and intrafamilial correlations, the presence of coronary plaque was independently associated with WMD volume (p = 0.05). This study shows a significant association between WMD and noncalcified and calcified coronary plaque in healthy subjects, independent of age and risk factors. In conclusion, these findings support the premise of possible shared causal pathways in 2 vascular beds in families at increased risk for early-onset vascular disease. PMID:23742943

  1. Comprehensive Analysis of BRCA1, BRCA2 and TP53 Germline Mutation and Tumor Characterization: A Portrait of Early-Onset Breast Cancer in Brazil

    PubMed Central

    Carraro, Dirce Maria; Koike Folgueira, Maria Aparecida Azevedo; Garcia Lisboa, Bianca Cristina; Ribeiro Olivieri, Eloisa Helena; Vitorino Krepischi, Ana Cristina; de Carvalho, Alex Fiorini; de Carvalho Mota, Louise Danielle; Puga, Renato David; do Socorro Maciel, Maria; Michelli, Rodrigo Augusto Depieri; de Lyra, Eduardo Carneiro; Grosso, Stana Helena Giorgi; Soares, Fernando Augusto; de Souza Waddington Achatz, Maria Isabel Alves; Brentani, Helena; Moreira-Filho, Carlos Alberto; Brentani, Maria Mitzi

    2013-01-01

    Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22%) [7 in BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients. PMID:23469205

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

    SciTech Connect

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

    2010-03-16

    Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X-ray fluorescence imaging on cross sections of diseased and healthy teeth using a microbeam to explore the distribution of trace metals in cementum and adhering plaque. The comparison between diseased and healthy teeth indicates that there are elevated levels of zinc, copper and nickel in diseased teeth as opposed to healthy teeth. This preliminary correlation between elevated levels of trace metals in the cementum and plaque of diseased teeth suggests that metals may play a role in the progress of periodontitis.

  3. Substance Use Progression from Adolescence to Early Adulthood: Effortful Control in the Context of Friendship Influence and Early-Onset Use

    ERIC Educational Resources Information Center

    Piehler, Timothy F.; Veronneau, Marie-Helene; Dishion, Thomas J.

    2012-01-01

    In a sample of 998 ethnically diverse adolescents, a multiagent, multimethod approach to the measurement of adolescent effortful control, adolescent substance use, and friendship influence was used to predict escalations to early-adult tobacco, alcohol, and marijuana use by ages 22-23. Structural equation modeling revealed that adolescent…

  4. Gingival crevicular fluid as a source of biomarkers for periodontitis.

    PubMed

    Barros, Silvana P; Williams, Ray; Offenbacher, Steven; Morelli, Thiago

    2016-02-01

    In evaluating the pathogenesis of periodontal diseases, the diagnostic potential of gingival crevicular fluid has been extensively explored during the last twenty years, from initially just confirming health and disease states to more recently investigating it as a potential prognostic tool. As host susceptibility is a critical determinant in periodontal disease pathogenesis, the inflammatory mediator levels present in gingival crevicular fluid represent relevant risk indicators for disease activity. Considerable work has been carried out to identify the many different cytokine inflammatory pathways and microbial stimuli that are associated with periodontal disease pathogenesis. Now, 'omics' approaches aim to summarize how these pathways interact and probably converge to create critical inflammatory networks. More recently, gingival crevicular fluid metabolomics appears promising as an additional diagnostic method. Biofilm structure and the host inflammatory response to the microbial challenge may induce specific inflammatory signatures. Host genetics and epigenetics may also modulate microbial colonization, adding to the multiplicity of potential causal pathways. Omics analyses of gingival crevicular fluid, measuring microbial and host interactions in association with the onset and progression of periodontal diseases, still show the potential to expand the landscape for the discovery of diagnostic, prognostic and therapeutic markers. PMID:26662482

  5. Acute Phase Proteins and Their Role in Periodontitis: A Review

    PubMed Central

    Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-01-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-? and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  6. Clinical improvement and radiological progression in a girl with early onset scoliosis (EOS) treated conservatively – a case report

    PubMed Central

    Weiss, Hans-Rudolf

    2006-01-01

    Background Chêneau-Brace treatment of a certain standard reduces the rate of surgery, prevents progression and in a certain patient population leads to marked improvement of Cobb angle and cosmetic appearance. During the last two years a patient refusing surgery with a double major curvature of initially 60° showed a clear cosmetic improvement and a clear radiological progression at the same time. The findings of this patient have been reviewed in order to find out how cosmetic appearance and Cobb angle can develop differently. Methods The patient entered conservative treatment at the age of 13 years, premenarchial with Tanner II and a Cobb angle of 60° thoracic and 59° lumbar. The angle of trunk rotation (ATR; Scoliometer) was 13° thoracic and 13° lumbar. We have documented the findings of this patient (Surface topography, ATR, Cobb angles and angles of vertebral rotation (according to Raimondi) during the treatment period (27 Month) until 2 years after the onset of menarche. Results After a treatment time of 27 Month the Cobb angle increased to 74° thoracic and 65° lumbar. The angles of vertebral rotation according to Raimondi increased slightly from 26° thoracic and 28° lumbar to 30° thoracic and 28° lumbar. The ATR improved to 12° thoracic and 5° lumbar while Lateral deviation improved from 22,4 mm to 4,6 mm and average surface rotation improved from 10,6° to 6°. In the X-rays a reduction of decompensation was visible. The patient felt comfortable with the cosmetic result. Conclusion Conservative treatment may improve cosmetic appearance while the curve progresses radiologically. This could be explained by assuming that (1) the Rigo Chêneau brace is able to improve cosmetic appearance by changing the shape of the thorax when the curve itself is too stiff to be corrected by a brace, that (2) reduction of decompensation leads to significant cosmetical improvements or (3) that the patient gained weight and therefore the deformation is masked. However, the weight the patient gained cannot explain the cosmetical improvement in this case. Conservative treatment with a certain standard of quality seems a viable alternative for patients with Cobb angles of > 60° when surgical treatment is refused. Specialists in scoliosis management should be aware of the fact that curve progression can occur even if the clinical measurements show an improvement. PMID:16872503

  7. Preclinical diagnosis of American visceral leishmaniasis during early onset of human Leishmania (L.) infantum chagasi-infection

    PubMed Central

    Lima, Luciana Vieira do Rêgo; Ramos, Patrícia Karla Santos; Campos, Marliane Batista; dos Santos, Thiago Vasconcelos; Gomes, Claudia Maria de Castro; Laurenti, Márcia Dalastra; Corbett, Carlos Eduardo Pereira; Silveira, Fernando Tobias

    2014-01-01

    American visceral leishmaniasis (AVL) is an infectious disease, often with long-duration evolution, caused by Leishmania (L.) infantum chagasi. However, although the disease is considered the major clinical manifestation of the link between L. (L.) i. chagasi and the human immune response, we have recently identified five clinical–immunological profiles of infection in the Brazilian Amazon: three asymptomatic (Asymptomatic Infection — AI, Sub-clinical Resistant Infection — SRI, and Indeterminate Initial Infection — III), and two symptomatic ones [Symptomatic Infection — SI (?=?AVL) and Sub-clinical Oligosymptomatic Infection — SOI]. We confirm here the preclinical diagnosis of AVL through the IgM-antibody response in a case of an early infection (profile III) that evolved to the full disease after 6 weeks. PMID:25491437

  8. A Carapace-Like Bony ‘Body Tube’ in an Early Triassic Marine Reptile and the Onset of Marine Tetrapod Predation

    PubMed Central

    Chen, Xiao-hong; Motani, Ryosuke; Cheng, Long; Jiang, Da-yong; Rieppel, Olivier

    2014-01-01

    Parahupehsuchus longus is a new species of marine reptile from the Lower Triassic of Yuan’an County, Hubei Province, China. It is unique among vertebrates for having a body wall that is completely surrounded by a bony tube, about 50 cm long and 6.5 cm deep, comprising overlapping ribs and gastralia. This tube and bony ossicles on the back are best interpreted as anti-predatory features, suggesting that there was predation pressure upon marine tetrapods in the Early Triassic. There is at least one sauropterygian that is sufficiently large to feed on Parahupehsuchus in the Nanzhang-Yuan’an fauna, together with six more species of potential prey marine reptiles with various degrees of body protection. Modern predators of marine tetrapods belong to the highest trophic levels in the marine ecosystem but such predators did not always exist through geologic time. The indication of marine-tetrapod feeding in the Nanzhang-Yuan’an fauna suggests that such a trophic level emerged for the first time in the Early Triassic. The recovery from the end-Permian extinction probably proceeded faster than traditionally thought for marine predators. Parahupehsuchus has superficially turtle-like features, namely expanded ribs without intercostal space, very short transverse processes, and a dorsal outgrowth from the neural spine. However, these features are structurally different from their turtle counterparts. Phylogeny suggests that they are convergent with the condition in turtles, which has a fundamentally different body plan that involves the folding of the body wall. Expanded ribs without intercostal space evolved at least twice and probably even more among reptiles. PMID:24718682

  9. Néstor-Guillermo progeria syndrome: a novel premature aging condition with early onset and chronic development caused by BANF1 mutations.

    PubMed

    Cabanillas, Rubén; Cadiñanos, Juan; Villameytide, José A F; Pérez, Mercedes; Longo, Jesús; Richard, José M; Alvarez, Rebeca; Durán, Noelia S; Illán, Rafael; González, Daniel J; López-Otín, Carlos

    2011-11-01

    Progeria syndromes are rare disorders that involve premature aging. Mutations in BANF1 have been recently reported to cause a new hereditary progeroid syndrome that we now propose to call the Néstor-Guillermo progeria syndrome (NGPS). We describe herein the clinical features of the first two NGPS patients, who phenocopy features of classic progerias (i.e., Hutchinson-Gilford progeria syndrome or mandibuloacral dysplasia), such as aged appearance, growth retardation, decreased subcutaneous fat, thin limbs, and stiff joints. However, these NGPS patients have a distinctive phenotype. In their early adulthood (32 and 24 years of age), they have no signs of cardiovascular impairment, diabetes mellitus, or hypertriglyceridemia. In contrast, they suffer profound skeletal abnormalities that affect their quality of life. The observed differences are of utmost importance to patients and their families and palliation of osseous manifestations is a priority, given their relatively long lifespan. We define NGPS as a chronic progeria because of its slow clinical course and relatively long survival, despite its early onset. Understanding the differences between progeria syndromes might contribute to the development of treatment strategies for common skeletal conditions, as well as aging itself. PMID:21932319

  10. Relationship between diabetes and periodontal infection

    PubMed Central

    Llambés, Fernando; Arias-Herrera, Santiago; Caffesse, Raúl

    2015-01-01

    Periodontal disease is a high prevalent disease. In the United States 47.2% of adults ? 30 years old have been diagnosed with some type of periodontitis. Longitudinal studies have demonstrated a two-way relationship between diabetes and periodontitis, with more severe periodontal tissue destruction in diabetic patients and poorer glycemic control in diabetic subjects with periodontal disease. Periodontal treatment can be successful in diabetic patients. Short term effects of periodontal treatment are similar in diabetic patients and healthy population but, more recurrence of periodontal disease can be expected in no well controlled diabetic individuals. However, effects of periodontitis and its treatment on diabetes metabolic control are not clearly defined and results of the studies remain controversial. PMID:26185600

  11. Over-representation of the APOE*4 allele in autopsy confirmed early- and late-onset sporadic Alzheimer`s disease

    SciTech Connect

    Kamboh, M.I.; DeKosky, S.T.; Ferrell, R.E.

    1994-09-01

    Apolipoprotein E binds to {beta}-amyloid peptide in senile plaques and neurofibrillary tangles in Alzheimer`s disease (AD). Recent studies have identified the APOE*4 allele as a major predisposing genetic factor for late-onset familial AD as well as in sporadic AD. Most of these association studies are based on clinically diagnosed AD cases with little data available on autopsy confirmed, definite AD. To characterize the distribution of APOE polymorphism in autopsy confirmed sporadic AD cases, we determined APOE genotypes in 111 DNA samples (aged 51-101 years) extracted from brain tissues which were available from the University of Pittsburgh Alzheimer`s Disease Research Center. The APOE data was compared between the AD group and 3 samples of population controls from Western Pennsylvania consisting of a young cohort (N=473, aged 18-48 years), middle cohort (N=473, aged 42-50 years) and an old cohort (N=870, aged 65-90 years). The frequency of the APOE*4 allele was similar in the young and middle cohorts (0.12) and slightly lower in the old cohort (0.10). However, the frequency of the APOE*4 allele was three times higher in both early-onset (<65 years; 0.36) and late-onset ({ge}65 years; 0.38) sporadic AD cases compared to the control groups (p<0.0001). In the AD cohort the frequency of the APOE*4 allele was similar across all age groups (<65, 65-75, 76-85, 86+) and so was in men and women (0.40 vs. 0.37). The E*4 homozygosity was observed in 18% of AD cases compared to 1% in each of the three control groups. The E*4 heterozygosity was present in 50% of AD cases compared to 17% in the control old cohort and 22% in both the young and middle control cohorts. These data confirm that the APOE*4 allele is a major risk factor for AD regardless of age-at-diagnosis or family history.

  12. Delayed onset of the 2002 Indian monsoon

    NASA Astrophysics Data System (ADS)

    Flatau, M. K.; Flatau, P. J.; Schmidt, J.; Kiladis, G. N.

    2003-07-01

    We show that there is a set of dynamical predictors, which facilitate forecasting of a delayed monsoon onset. The main dynamical contributor is the early May propagation of the ``bogus onset Intraseasonal Oscillation'' which triggers a set of events precluding the climatological monsoon onset. We analyze in detail the 2002 monsoon onset and show that it followed a pattern described in our previous study. We notice that the 2003 monsoon onset followed very similar pattern and was delayed.

  13. Effects of early-onset radiofrequency electromagnetic field exposure (GSM 900 MHz) on behavior and memory in rats.

    PubMed

    Klose, Melanie; Grote, Karen; Spathmann, Oliver; Streckert, Joachim; Clemens, Markus; Hansen, Volkert W; Lerchl, Alexander

    2014-10-01

    Female Wistar rats, from an age of 14 days to 19 months, were exposed in the head region for 2 h per day, 5 days per week, to a GSM-modulated 900 MHz radiofrequency electromagnetic field (RF-EMF). The average specific absorption rates (SAR) in the brain were 0 (sham), 0.7, 2.5 and 10 W/kg. To ensure a primary exposure of the head region, rats were fixed in restraining tubes of different sizes according to their increasing body weight. During the experiment, a set of 4 behavioral and learning tests (rotarod, Morris water maze, 8-arm radial maze, open field) were performed 3 times in juvenile, adult and presenile rats. In these tests, no profound differences could be identified between the groups. Only presenile rats of the cage control group showed a lower activity in two of these tests compared to the other groups presumably due to the lack of daily handling. The rotarod data revealed on some testing days significantly longer holding times for the sham-exposed rat vs. the exposed rat, but these findings were not consistent. During the first year, body weights of sham-exposed and exposed rats were not different from those of the cage controls, and thereafter only marginally lower, so that the effect of stress as confounder was probably negligible. The results of this study do not indicate harmful effects of long-term RF-EMF exposure even when begun at an early age on subsequent development, learning skills and behavior in rats, even at relatively high SAR values. PMID:25251701

  14. Early-onset inflammatory responses in vivo to adenoviral vectors in the presence or absence of lipopolysaccharide-induced inflammation.

    PubMed

    Thorne, P S; McCray, P B; Howe, T S; O'Neill, M A

    1999-06-01

    Adenoviral vectors (Ad) have potential for use in pulmonary gene transfer for treating cystic fibrosis (CF). However, Ad may induce inflammation even in the absence of gene expression. Endotoxin from gram-negative bacteria in the airways of CF patients may also induce inflammation, and may further inhibit vector delivery and gene transfer. We used a mouse model to study the time course of Ad-induced lung inflammation and to assess additivity with lipopolysaccharide (LPS)-induced inflammatory responses. C3H/HeJ endotoxin-resistant (RES) mice hyporesponsive to inflammatory stimuli and normoresponsive C3HeB/FeJ endotoxin-sensitive (SEN) mice were studied to characterize inflammatory responses that follow intratracheal instillation of inactivated Ad, with or without simultaneous inhalation exposure to LPS. Instillation of 10(10) Ad particles dramatically increased bronchoalveolar lavage fluid (BALF) concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 at 3 to 6 h and induced profound neutrophilia, maximal at 12 to 24 h. SEN mice had tenfold greater responses than did RES mice at 6, 12, and 24 h. Mice exposed to Ad alone, LPS alone, or Ad + LPS had significant inflammation at the 3-h time point as demonstrated by BALF neutrophils, TNF-alpha, and IL-6. With all three treatments, SEN mice had a five- to 300-fold greater response than did RES mice. Importantly, Ad + LPS yielded no greater inflammatory response than LPS without Ad. These data demonstrate that replication-deficient Ad induce early inflammation and LPS-induced inflammation is not augmented by concurrent treatment with Ad. PMID:10340934

  15. Effects of diet on early stage cortical perception and discrimination of syllables differing in voice-onset time: A longitudinal ERP study in 3 and 6 month old infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influence of infant diet on early stage cortical processing of syllables was examined in 239 healthy infants who were breastfed (BF) or fed milk-based formula (MF) or soy formula (SF). Using an oddball paradigm, event-related potentials to consonant-vowel syllables differing in voice-onset time ...

  16. A SEL1L Mutation Links a Canine Progressive Early-Onset Cerebellar Ataxia to the Endoplasmic Reticulum–Associated Protein Degradation (ERAD) Machinery

    PubMed Central

    Kyöstilä, Kaisa; Cizinauskas, Sigitas; Seppälä, Eija H.; Suhonen, Esko; Jeserevics, Janis; Sukura, Antti; Syrjä, Pernilla; Lohi, Hannes

    2012-01-01

    Inherited ataxias are characterized by degeneration of the cerebellar structures, which results in progressive motor incoordination. Hereditary ataxias occur in many species, including humans and dogs. Several mutations have been found in humans, but the genetic background has remained elusive in dogs. The Finnish Hound suffers from an early-onset progressive cerebellar ataxia. We have performed clinical, pathological, and genetic studies to describe the disease phenotype and to identify its genetic cause. Neurological examinations on ten affected dogs revealed rapidly progressing generalized cerebellar ataxia, tremors, and failure to thrive. Clinical signs were present by the age of 3 months, and cerebellar shrinkage was detectable through MRI. Pathological and histological examinations indicated cerebellum-restricted neurodegeneration. Marked loss of Purkinje cells was detected in the cerebellar cortex with secondary changes in other cortical layers. A genome-wide association study in a cohort of 31 dogs mapped the ataxia gene to a 1.5 Mb locus on canine chromosome 8 (praw?=?1.1×10?7, pgenome?=?7.5×10?4). Sequencing of a functional candidate gene, sel-1 suppressor of lin-12-like (SEL1L), revealed a homozygous missense mutation, c.1972T>C; p.Ser658Pro, in a highly conserved protein domain. The mutation segregated fully in the recessive pedigree, and a 10% carrier frequency was indicated in a population cohort. SEL1L is a component of the endoplasmic reticulum (ER)–associated protein degradation (ERAD) machinery and has not been previously associated to inherited ataxias. Dysfunctional protein degradation is known to cause ER stress, and we found a significant increase in expression of nine ER stress responsive genes in the cerebellar cortex of affected dogs, supporting the pathogenicity of the mutation. Our study describes the first early-onset neurodegenerative ataxia mutation in dogs, establishes an ERAD–mediated neurodegenerative disease model, and proposes SEL1L as a new candidate gene in progressive childhood ataxias. Furthermore, our results have enabled the development of a genetic test for breeders. PMID:22719266

  17. Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol

    PubMed Central

    Cluver, Catherine A; Walker, Susan P; Mol, Ben W; Theron, Gerard B; Hall, David R; Hiscock, Richard; Hannan, N; Tong, S

    2015-01-01

    Introduction Pre-eclampsia is a major complication of pregnancy, globally responsible for 60?000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress. Methods and analysis We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40?mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6?weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6?weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies. Ethics and dissemination This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB0005239), and is registered with NHREC (ID 3649) and the Pan African Clinical Trial Registry (PACTR201504000771349). Data will be presented at international conferences and published in peer-reviewed journals. PMID:26510725

  18. [ANALYSIS OF THE ASSOCIATIONS BETWEEN ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM AND ARTERIAL HYPOTENSION IN PREMATURE INFANTS WITH EARLY ONSET BACTERIAL INFECTIONS].

    PubMed

    Kovaleva, E; Pokhylko, V; Chernyavskaya, Yu; Kalyuzka, E; Poltoropavlov, V

    2015-11-01

    The rate of neonatal sepsis is not reduced varying inversely proportional to the gestational age at birth, and may reach 60% in the most immature infants. The high mortality rate of this disease and adverse neurological effects are associated with the development of cardiovascular changes and shock. The main leadership role in the regulation of blood pressure and blood volume in the body plays a renin-angiotensin system. Synthesis of angiotensin-converting enzyme is regulated by the ACE gene. The aim of the study was to identify and analyze the associations between the development of arterial hypotension in premature infants and insertion-deletion (I/D) polymorphism of the ACE gene. We conducted a prospective cohort study, which included 118 prematurely born children with early onset bacterial infections (n=57 with clinical manifestations in the form of hypotension, n=61 without hypotension). Both groups were genotyped to determine the insertion-deletion polymorphism ACE gene. We compared the clinical, laboratory and instrumental parameters in premature infants with hypotension and II, ID, DD genotype of the ACE gene. Also an analysis of the associations between different genotypes of ACE gene and the development of arterial hypotension in prematurely born children was conducted. The distribution of neonates in relation to the three polymorphic variants of ACE gene with respect to I/D polymorphism was identical among the study groups. The study found that children with a variety of I/D polymorphic variants of ACE gene had no significant differences in hemodynamic parameters. The rate of hemodynamic support use did not differ in both groups. The study of the associations between the ACE gene polymorphism and major ultrasound, Doppler indices that characterized both systemic and organ hemodynamics, revealed no significant differences in mean values ??of all the criteria that have been studied. It can be concluded no effect of I/D polymorphism of ACE gene on the occurrence of hemodynamic disorders in premature born children with early onset bacterial infections. PMID:26656553

  19. Periodontitis and bone metabolism

    PubMed Central

    Barbato, Luigi; Francioni, Edoardo; Bianchi, Massimiliano; Mascitelli, Eleonora; Marco, Leila Brancato; Tonelli, Duvina Paolo

    2015-01-01

    Summary Periodontitis is a plaque induced disease characterized by tissue destruction. The extent of the alveolar bone loss depends on the host response stimulated by bacterial infection. Recently researchers have focused on the role of the immune system, of RANK/RANKL/OPG pathway and of cytokines network. Another recent field of interest is osteoimmunology that try to explain the relationship between immune and bone cells in activating bone resorption. Advances in the understanding of the pathogenic mechanisms allowed a better understanding of the relationship with other diseases like osteoporosis and also to hypothesize new therapies based on modulation of host response (host modulatory therapy - HMT). The purpose of this mini-review is to briefly discuss these topics. PMID:26604945

  20. Association of Periodontitis With Urinary Albumin Excretion in Korean Adults With Diabetes

    PubMed Central

    Han, Kyungdo; Nam, Ga Eun; Kim, Do Hoon; Park, Jun-Beom; Ko, Youngkyung; Roh, Yong Kyun; Cho, Kyung Hwan; Park, Yong Gyu

    2015-01-01

    Abstract Albuminuria and periodontitis are both commonly associated with systemic inflammation. However, the association between urinary albumin excretion (UAE) and periodontitis in patients with type 2 diabetes has not been fully investigated. This study aimed to investigate the association between UAE and periodontitis in Korean adults with type 2 diabetes. This study performed a cross-sectional analysis and used hierarchical multivariable logistic regression analysis models. Data from the 2012 Korean National Health and Nutrition Examination Survey were analyzed. A total of 547 patients, with type 2 diabetes without renal impairment, were included in this study. UAE was assessed using the urinary albumin to creatinine ratio (UACR). A community periodontal index greater than or equal to code 3 was used to define periodontitis. The risk of periodontitis tended to increase as UACR increased even after adjustment for potential confounders (P for trend in the odds ratios?=?0.05 in model 1; 0.02 in model 2; and 0.01 in model 3). In a subgroup analysis, the prevalence of periodontitis was significantly higher in the patients with albuminuria (UACR >30?mg/g) than in those without albuminuria among patients younger than 65 years (P?=?0.03), those with newly diagnosed diabetes (P?=?0.04), or those without obesity (P?=?.04). UAE was positively associated with the risk of periodontitis in Korean adults with type 2 diabetes. In the patients who were younger, were newly diagnosed with diabetes, or had normal body mass index, individuals with albuminuria were more likely to have a higher prevalence of periodontitis. Early identification of periodontitis may be helpful in Korean diabetic adults with increased UAE. PMID:26496329

  1. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

    PubMed

    Soenjaya, Y; Foster, B L; Nociti, F H; Ao, M; Holdsworth, D W; Hunter, G K; Somerman, M J; Goldberg, H A

    2015-09-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp(-/-) mice. PMID:26130257

  2. Subgingival periodontal pathogens associated with chronic periodontitis in Yemenis

    PubMed Central

    2014-01-01

    Background Subgingival microbial profile associated with periodontitis has been reported to significantly differ by geographical location. The purpose of this study was to assess the association between a panel of putative periodontal bacterial pathogens and chronic periodontitis among Yemenis. Methods Subgingival DNA samples were obtained from diseased and healthy sites of 20 non-smoking, moderate to severe chronic periodontitis subjects. Absolute counts (bacterial DNA copies per sample) and relative counts (% total bacteria) of seven periopathogenic species/genera representative of the red and orange complexes were determined using Taqman q-PCR assays. Results The q-PCR assays showed excellent linearity (R2?>?0.99) and a sensitivity of 100 copies/sample. The detection rate was 100% for all tested species/genera except for P. gingivalis and A. actinomycetemcomitans that were detected at 97.5% and 67.5%, respectively. The median log absolute counts were in the range of 2.41-6.53 copies per sample while median relative counts were in the range of 0.001-0.77%, both being highest for fusobacteria and lowest for A. actinomycetemcomitans. Significant interspecies correlations were observed. Adjusting for multiple comparisons (P?0.0063), only T. forsythia, T. denticola and P. micra maintained significant association with periodontal destruction. The latter species, however, showed the strongest association and was found in higher proportions at the periodontitis sites across all subjects (3.39 median fold increase). No significant differences were observed for P. gingivalis. Conclusions P. micra rather than P. gingivalis appears as a keystone pathogen in this Yemeni Sample. However, these findings need to be validated in a larger-scale study before they can be claimed to represent ethnic variations in pathogens’ association with periodontitis. PMID:24548674

  3. C-Reactive Protein in Peripheral Blood of Patients with Chronic and Aggressive Periodontitis, Gingivitis, and Gingival Recessions

    PubMed Central

    Podzimek, Stepan; Mysak, Jaroslav; Janatova, Tatjana; Duskova, Jana

    2015-01-01

    CRP is a plasma protein that reflects a measure of the acute phase response to inflammation and is one of the markers of choice in monitoring this response. CRP can be used for the prediction and early detection of periodontal disease. The aim of this study was to compare and evaluate the systemic levels of CRP in the peripheral blood samples of patients with chronic and aggressive periodontitis, gingivitis, and gingival recessions and compare them with periodontal clinical parameters. All patients (N = 158) were examined prior to the initiation of periodontal treatment. Patients were divided into four groups. Group A consisted of 26 patients with aggressive periodontitis, Group B consisted of 111 patients with chronic periodontitis, Group C consisted of 13 patients with gingivitis, and Group D consisted of 8 patients with gingival recessions. Our study results indicate that CRP levels increase subsequently with the severity of the periodontal disease and that the bleeding on probing index showed much better positive correlation with the CRP levels compared to the pocket depth index in both periodontitis patients groups, especially in aggressive periodontitis patients. PMID:26346216

  4. Maternal protein restriction induces early-onset glucose intolerance and alters hepatic genes expression in the peroxisome proliferator-activated receptor pathway in offspring

    PubMed Central

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin

    2015-01-01

    Aims/Introduction Maternal undernutrition during pregnancy and/or lactation can alter the offspring's response to environmental challenges, and thus increases the risk of the development of metabolic diseases at a later age. However, whether maternal protein restriction can modulate glucose metabolism in the early life of offspring is less understood. Furthermore, we explored the potential underlying mechanisms that illustrate this phenotype. Materials and Methods To test this hypothesis, we examined the offspring of C57BL/6J mice at weaning to determine the effects of feeding their mothers a low-protein diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time polymerase chain reaction were utilized to explore the altered hepatic genes expression. Results The offspring of dams fed a low-protein diet had a lower birthweight and bodyweight, impaired glucose tolerance, decreased insulin sensitivity, and decreased serum cholesterol at weaning. Using gene array experiments, 253 differentially expressed genes were identified in the liver tissues of the offspring between the two groups. Bioinformatic analyses showed that all differentially expressed genes were mapped to 11 pathways. We focused on the ‘peroxisome proliferator-activated receptor signaling pathway,’ because peroxisome proliferator-activated receptors have emerged as central regulators of glucose and lipid homeostasis. Quantitative real-time polymerase chain reaction was utilized for the validation of genes in the pathway. Conclusions A maternal low-protein diet during pregnancy and lactation promotes early-onset glucose intolerance in the offspring mice, and the altered hepatic genes expression in peroxisome proliferator-activated receptor signaling pathway could play role in regulating this phenomenon. PMID:25969711

  5. Communication of brain network core connections altered in behavioral variant frontotemporal dementia but possibly preserved in early-onset Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Daianu, Madelaine; Jahanshad, Neda; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Thompson, Paul M.

    2015-03-01

    Diffusion imaging and brain connectivity analyses can assess white matter deterioration in the brain, revealing the underlying patterns of how brain structure declines. Fiber tractography methods can infer neural pathways and connectivity patterns, yielding sensitive mathematical metrics of network integrity. Here, we analyzed 1.5-Tesla wholebrain diffusion-weighted images from 64 participants - 15 patients with behavioral variant frontotemporal dementia (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Using whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We evaluated the brain's networks focusing on the most highly central and connected regions, also known as hubs, in each diagnostic group - specifically the "high-cost" structural backbone used in global and regional communication. The high-cost backbone of the brain, predicted by fiber density and minimally short pathways between brain regions, accounted for 81-92% of the overall brain communication metric in all diagnostic groups. Furthermore, we found that the set of pathways interconnecting high-cost and high-capacity regions of the brain's communication network are globally and regionally altered in bvFTD, compared to healthy participants; however, the overall organization of the high-cost and high-capacity networks were relatively preserved in EOAD participants, relative to controls. Disruption of the major central hubs that transfer information between brain regions may impair neural communication and functional integrity in characteristic ways typical of each subtype of dementia.

  6. Trait and State Attributes of Insight in First Episodes of Early-Onset Schizophrenia and Other Psychoses: A 2-Year Longitudinal Study

    PubMed Central

    Parellada, Mara; Boada, Leticia; Fraguas, David; Reig, Santiago; Castro-Fornieles, Josefina; Moreno, Dolores; Gonzalez-Pinto, Ana; Otero, Soraya; Rapado-Castro, Marta; Graell, Montserrat; Baeza, Inmaculada; Arango, Celso

    2011-01-01

    Background: Increasing evidence supports the important role of illness state and individual characteristics in insight. Methods: Insight, as measured with the Scale to Assess Unawareness of Mental Disorder, over the first 2 years of early-onset first-episode psychosis and its correlations with clinical, socio-demographic, cognitive, and structural brain variables are studied. Results: (1) insight at 2 years is poorer in schizophrenia spectrum disorders (SSDs) than in subjects with other psychoses; (2) the more severe the psychosis, the worse the insight. In SSD, depressive symptoms, poorer baseline executive functioning, lower IQ, longer duration of untreated psychosis (DUP), and poorer premorbid infancy adjustment are associated with poorer insight; frontal and parietal gray matter (GM) reductions at baseline correlate with worse insight into having psychotic symptoms at 2 years; (3) insight into having a mental disorder (Scale to Assess Unawareness of Mental Disorder [SUMD]1) at 1 year, DUP, and baseline IQ are the most consistent variables explaining different aspects of insight at 2 years in SSD patients. IQ and SUMD1 at 1 year, together with left frontal and parietal GM volumes, explain 80% of the variance of insight into having specific psychotic symptoms in SSD patients (adjusted R2 = 0.795, F = 15.576, P < .001). Conclusion: Insight is a complex phenomenon that depends both on severity of psychopathology and also on disease and subject characteristics, such as past adjustment, IQ, DUP, cognitive functioning, frontal and parietal GM volumes, and age, gender, and ethnicity. PMID:20884756

  7. A rare association of early-onset inclusion body myositis, rheumatoid arthritis and autoimmune thyroiditis: a case report and literature review

    PubMed Central

    Clerici, Angelo Maurizio; Bono, Giorgio; Delodovici, Maria Luisa; Azan, Gaetano; Cafasso, Giuseppina; Micieli, Giuseppe

    2013-01-01

    Summary Sporadic inclusion body myositis (sIBM) is a slowly progressive, red-rimmed vacuolar myopathy leading to muscular atrophy and progressive weakness; it predominantly affects males older than fifty years, and is resistant to immunotherapy. It has been described in association with immuno-mediated thrombocytopenic purpura, multiple sclerosis, connective tissue disorders and, occasionally, rheumatoid arthritis. A 37-year-old man with longstanding rheumatoid arthritis and autoimmune thyroiditis with hypothyroidism was referred to us with slowly progressive, diffuse muscle weakness and wasting, which had initially involved the volar finger flexors, and subsequently also the ankle dorsiflexors and knee extensors. Needle electromyography showed typical myopathic motor unit potentials, fibrillation and positive sharp waves with normal nerve conduction studies. Quadriceps muscle biopsy was suggestive of sIBM. Considering data published in the literature, this case may be classified as an early-onset form. The patient was treated with long-term intravenous immunoglobulin and obtained a substantial stabilization of his muscle strength. PMID:24125563

  8. The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes.

    PubMed

    Macedo, Maria G; Anar, Burcu; Bronner, Iraad F; Cannella, Milena; Squitieri, Ferdinando; Bonifati, Vincenzo; Hoogeveen, André; Heutink, Peter; Rizzu, Patrizia

    2003-11-01

    Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently DJ-1 mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1L166P mutant protein shows a different elution profile as compared with DJ-1WT both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1L166P mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT-PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. This rapid turnover and the structural changes of DJ-1L166P mutant protein might be crucial in the disease pathogenesis. PMID:12952867

  9. A rare association of early-onset inclusion body myositis, rheumatoid arthritis and autoimmune thyroiditis: a case report and literature review.

    PubMed

    Clerici, A M; Bono, G; Delodovici, M L; Azan, G; Cafasso, G; Micieli, G

    2013-01-01

    Sporadic inclusion body myositis (sIBM) is a slowly progressive, red-rimmed vacuolar myopathy leading to muscular atrophy and progressive weakness; it predominantly affects males older than fifty years, and is resistant to immunotherapy. It has been described in association with immuno-mediated thrombocytopenic purpura, multiple sclerosis, connective tissue disorders and, occasionally, rheumatoid arthritis. A 37-year-old man with longstanding rheumatoid arthritis and autoimmune thyroiditis with hypothyroidism was referred to us with slowly progressive, diffuse muscle weakness and wasting, which had initially involved the volar finger flexors, and subsequently also the ankle dorsiflexors and knee extensors. Needle electromyography showed typical myopathic motor unit potentials, fibrillation and positive sharp waves with normal nerve conduction studies. Quadriceps muscle biopsy was suggestive of sIBM. Considering data published in the literature, this case may be classified as an early-onset form. The patient was treated with long-term intravenous immunoglobulin and obtained a substantial stabilization of his muscle strength. PMID:24125563

  10. A Case of Cauda Equina Syndrome in Early-Onset Chronic Inflammatory Demyelinating Polyneuropathy Clinically Similar to Charcot-Marie-Tooth Disease Type 1

    PubMed Central

    Lee, Seung Eun; Ha, Sam Yeol; Nam, Taek Kyun

    2014-01-01

    To present a case of cauda equina syndrome (CES) caused by chronic inflammatory demyelinating polyneuropathy (CIDP) which seemed clinically similar to Charcot-Marie-Tooth disease type1 (CMT1). CIDP is an immune-mediated polyneuropathy, either progressive or relapsing-remitting. It is a non-hereditary disorder characterized by symmetrical motor and sensory deficits. Rarely, spinal nerve roots can be involved, leading to CES by hypertrophic cauda equina. A 34-year-old man presented with low back pain, radicular pain, bilateral lower-extremity weakness, urinary incontinence, and constipation. He had had musculoskeletal deformities, such as hammertoes and pes cavus, since age 10. Lumbar spine magnetic resonance imaging showed diffuse thickening of the cauda equina. Electrophysiological testing showed increased distal latency, conduction blocks, temporal dispersion, and severe nerve conduction velocity slowing (3 m/s). We were not able to find genetic mutations at the PMP 22, MPZ, PRX, and EGR2 genes. The pathologic findings of the sural nerve biopsy revealed thinly myelinated nerve fibers with Schwann cells proliferation. We performed a decompressive laminectomy, intravenous IgG (IV-IgG) and oral steroid. At 1 week after surgery, most of his symptoms showed marked improvements except foot deformities. There was no relapse or aggravation of disease for 3 years. We diagnosed the case as an early-onset CIDP with cauda equine syndrome, whose initial clinical findings were similar to those of CMT1, and successfully managed with decompressive laminectomy, IV-IgG and oral steroid. PMID:25237436

  11. Young-Onset Dementia

    PubMed Central

    Kuruppu, Dulanji K; Matthews, Brandy R

    2014-01-01

    Young-onset dementia (YOD) is an neurological syndrome that affects behavior and cognition of patients younger than 65 years of age. Although frequently misdiagnosed, a systematic approach, reliant upon attainment of detailed medical history, collateral history from an informant, neuropsychological testing, laboratory studies, and neuroimaging, may facilitate earlier and more accurate diagnosis with subsequent intervention. The differential diagnosis of YOD is extensive and includes early-onset forms of adult neurodegenerative conditions including Alzheimer's disease, vascular dementia, frontotemporal dementia, Lewy body dementias, Huntington's disease, and prion disease. Late-onset forms of childhood neurodegenerative conditions may also present as YOD and include mitochondrial disorders, lysosomal storage disorders, and leukodystrophies. Potentially reversible etiologies including inflammatory disorders, infectious diseases, toxic/metabolic abnormalities, transient epileptic amnesia, obstructive sleep apnea, and normal pressure hydrocephalus also represent important differential diagnostic considerations in YOD. This review will present etiologies, diagnostic strategies, and options for management of YOD with comprehensive summary tables for clinical reference. PMID:24234358

  12. Childhood Onset Schizophrenia: Clinical Features, Course and Outcome

    ERIC Educational Resources Information Center

    Sood, Mamta; Kattimani, Shivanand

    2008-01-01

    Schizophrenia in children is diagnosed by using adult criteria. Based on the age of onset, patients with childhood onset schizophrenia (COS) are subdivided into those with very early onset (before age 12-14 years) and those with early onset (between 14-17 years). The prevalence of COS is reported to be 1 in 10,000 before the age of 12 years;…

  13. Effects of Periodontal Therapy on Rate of Preterm Delivery A Randomized Controlled Trial

    PubMed Central

    Offenbacher, Steven; Beck, James D.; Jared, Heather L.; Mauriello, Sally M.; Mendoza, Luisto C.; Couper, David J.; Stewart, Dawn D.; Murtha, Amy P.; Cochran, David L.; Dudley, Donald J.; Reddy, Michael S.; Geurs, Nicolaas C.; Hauth, John C.

    2010-01-01

    OBJECTIVE To test the effects of maternal periodontal disease treatment on the incidence of preterm birth (delivery before 37 weeks of gestation). METHODS The Maternal Oral Therapy to Reduce Obstetric Risk Study was a randomized, treatment-masked, controlled clinical trial of pregnant women with periodontal disease who were receiving standard obstetric care. Participants were assigned to either a periodontal treatment arm, consisting of scaling and root planing early in the second trimester, or a delayed treatment arm that provided periodontal care after delivery. Pregnancy and maternal periodontal status were followed to delivery and neonatal outcomes until discharge. The primary outcome (gestational age less than 37 weeks) and the secondary outcome (gestational age less than 35 weeks) were analyzed using a ?2 test of equality of two proportions. RESULTS The study randomized 1,806 patients at three performance sites and completed 1,760 evaluable patients. At baseline, there were no differences comparing the treatment and control arms for any of the periodontal or obstetric measures. The rate of preterm delivery for the treatment group was 13.1% and 11.5% for the control group (P=.316). There were no significant differences when comparing women in the treatment group with those in the control group with regard to the adverse event rate or the major obstetric and neonatal outcomes. CONCLUSION Periodontal therapy did not reduce the incidence of preterm delivery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, www.clinicaltrials.gov, NCT00097656. LEVEL OF EVIDENCE I PMID:19701034

  14. Lessons learned and unlearned in periodontal microbiology

    PubMed Central

    Teles, Ricardo; Teles, Flavia; Frias-Lopez, Jorge; Paster, Bruce; Haffajee, Anne

    2013-01-01

    Periodontal diseases are initiated by bacterial species living in polymicrobial biofilms at or below the gingival margin and progress largely as a result of the inflammation initiated by specific subgingival species. In the past few decades, efforts to understand the microbiota of periodontal diseases have led to an exponential increase in information about biofilms associated with periodontal health and disease. In fact, the oral microbiota is one of the best characterized microbiomes that colonize the human body. Despite this increased knowledge, one has to ask if our fundamental concepts of the etiology and pathogenesis of periodontal diseases have really changed. In this chapter we will review how our comprehension of the structure and function of the subgingival microbiota evolved over the years in search of lessons learned and unlearned in periodontal microbiology. More specifically, this review focuses on: 1) how the data obtained through molecular techniques has impacted our knowledge of the etiology of periodontal infections; 2) the potential role of viruses in the etiopathogenesis of periodontal diseases; 3) how concepts of microbial ecology have expanded our understanding of host microbial interactions that might lead to periodontal diseases; 4) the role of inflammation in the pathogenesis of periodontal diseases; and 5) the impact of these evolving concepts on treatment and preventive approaches to periodontal infections. We will conclude by reviewing how novel systems biology approaches promise to unravel new details of the pathogenesis of periodontal diseases and, hopefully, lead to a better understanding of periodontal disease mechanisms. PMID:23574465

  15. A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity

    PubMed Central

    Mencarelli, Monica; Zulian, Alessandra; Cancello, Raffaella; Alberti, Luisella; Gilardini, Luisa; Di Blasio, Anna Maria; Invitti, Cecilia

    2012-01-01

    Rare mutations in several genes have a critical role in the control of homeostatic mechanisms such as food-intake, energy balance and glucose metabolism. In this study, we performed a mutational screening in a 58-year-old woman presenting early-onset type 2 diabetes and central obesity. The entire coding regions of MC4R, MC3R, HNF1A, GCK and POMC (pro-opiomelanocortin) genes were analyzed by direct sequencing. A new missense mutation was identified within the POMC gene signal peptide sequence, resulting in a heterozygous substitution of an arginine for a glycine at codon 15 (p.A15G) that was excluded in 300 healthy normal weight controls. The mutation segregated in the family and was associated with overweight, type 2 diabetes, hypertension and coronary heart disease in the carriers. Functional studies demonstrated that POMC protein was not detectable in ?-TC3 cells transfected with A15G-POMC vector as well as in their culture media, despite POMC mRNA levels were comparable for amount and stability to those of wild-type-transfected cells. In silico RNA folding prediction indicated that the mutation gives rise to a different RNA secondary structure, suggesting that it might affect translation and protein synthesis. To the best of our knowledge, this is the first report addressing the functional consequences of a mutation in the signal peptide of POMC. These findings further support the hypothesis that POMC-derived peptides might have a role in the control of peripheral glucose metabolism and suggest that disruption of central POMC secretion might represent an additional link between type 2 diabetes and obesity. PMID:22643178

  16. Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control

    PubMed Central

    Bächle, Christina; Lange, Karin; Stahl-Pehe, Anna; Castillo, Katty; Scheuing, Nicole; Holl, Reinhard W.; Giani, Guido; Rosenbauer, Joachim

    2015-01-01

    Background This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control. Methods In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9) for symptoms of depression and severity of depressive symptoms (PHQ-9 score). Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c. Results A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation) was 5.3 (4.4) among women and 3.9 (3.6) among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (?women 3.8, p<0.001). However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (?men 0.14, p=0.006). Conclusions Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes. PMID:26121155

  17. Magnetostratigraphic evidence from the Cold Creek bar for onset of ice-age cataclysmic floods in eastern Washington during the early Pleistocene

    SciTech Connect

    Pluhar, Christopher J.; Bjornstad, Bruce N.; Reidel, Steve P.; Coe, Robert S.; Nelson, Paul B.

    2006-01-01

    This study provides a detailed magnetostratigraphy of sediments composing the Cold Creek cataclysmic flood bar in the Pasco Basin, Washington. Our interpretation suggests onset of Missoula floods or similar events prior to 1.1 myr, later than previously suggested by Bjornstad et al. [Bjornstad B.N., Fecht, K.R., Pluhar, C.J., 2001]. Long history of pre-Wisconsin, Ice Age cataclysmic floods: evidence from southeastern Washington State. [Journal of Geology 109 (6), 695-713]. Nonetheless these data suggest that Channeled Scabland features formed over a much longer timespan than commonly cited, that continental ice sheets of the early Pleistocene reached as far south as those of the late Pleistocene, and that similar physiography existed in eastern Washington and perhaps Montana to both generate and route Missoula-flood-like events. This study adds paleomagnetic polarity results from 213 new samples of silts and sands derived from nine new drill cores penetrating the Cold Creek cataclysmic flood bar to our previous database of 53 samples from four boreholes, resulting in a much more robust and detailed magnetostratigraphy. Rock magnetic studies on these sediments show pure magnetite to be the predominant remanence-carrying magnetic mineral, ruling out widespread remagnetization by secondary mineralization. The magnetostratigraphy at eastern Cold Creek bar is characterized by a normal polarity interval bracketed by reversed polarities. Equating the normal zone with the Jaramillo subchron (0.99-1.07 myr) affords the simplest correlation to the magnetic polarity timescale. Western Cold Creek bar was likely deposited during the Brunhes chron (0-0.78 myr) since it exhibits mainly normal polarities with only two thin reversed-polarity horizons that we interpret as magnetic excursions during the Brunhes.

  18. Multifactorial relationship of obesity and periodontal disease.

    PubMed

    Suresh, Snophia; Mahendra, Jaideep

    2014-04-01

    Obesity is a chronic disease of mutifactorial origin, where there is increase in body fat. Periodontitis is an inflammatory disease of tooth supporting tissues resulting in destruction of periodontal ligament and alveolar bone. Periodontitis and obesity are both chronic health problems and the literature supports this association. A hyperinflammatory state observed in obesity is proposed as a mechanism to explain this association. This low grade inflammation in obese subjects triggers the worsening of non transmissible chronic diseases like periodontitis. So the aim of this article is to get the overview of association between adipose tissue derived cytokines and periodontal disease. PMID:24959524

  19. Association of Periodontitis and Subsequent Depression

    PubMed Central

    Hsu, Chih-Chao; Hsu, Yi-Chao; Chen, Hsuan-Ju; Lin, Che-Chen; Chang, Kuang-Hsi; Lee, Chang-Yin; Chong, Lee-Won; Kao, Chia-Hung

    2015-01-01

    Abstract Periodontitis is a systemic and chronic inflammatory disease associated with multiple physical conditions. Distress and depression are other problems affecting the progression of periodontitis. However, the causal relationship between depression and periodontitis has not been adequately investigated. This aim of this study was to determine the association between periodontitis and the subsequent development of depression. We identified 12,708 patients with newly diagnosed periodontitis from 2000 to 2005 and 50,832 frequency-matched individuals without periodontitis. Both groups were followed until diagnosed with depression, withdrawal from the National Health Insurance program, or the end of 2011. The association between periodontitis and depressio was analyzed using Cox proportional hazard regression models. The incidence density rate of depression was higher in the periodontitis group than in the nonperiodontitis group, with an adjusted hazard ratio of 1.73 (95% confidence interval 1.58–1.89) when adjusting for sex, age, and comorbidity. Cox models revealed that periodontitis was an independent risk factor for depression in patients, except for comorbidities of diabetes mellitus (DM), alcohol abuse, and cancer. Periodontitis may increase the risk of subsequent depression and was suggested an independent risk factor regardless of sex, age, and most comorbidities. However, DM, alcohol abuse, and cancer may prevent the development of subsequent depression because of DM treatment, the paradoxical effect of alcohol, and emotional distress to cancer, respectively. Prospective studies on the relationship between periodontitis and depression are warranted. PMID:26705230

  20. Significance of maternal periodontal health in preeclampsia

    PubMed Central

    Desai, Khushboo; Desai, Parth; Duseja, Shilpa; Kumar, Santosh; Mahendra, Jaideep; Duseja, Sareen

    2015-01-01

    Objective: The aim of the present case–control study was to evaluate the association between maternal periodontitis and preeclampsia. Association studies between maternal periodontitis and elevated risk for preeclampsia have shown conflicting results. Periodontal maintenance is necessary to reduce the risk of adverse pregnancy outcomes like preeclampsia. Materials and Methods: Periodontal parameters [bleeding on probing, probing depth (PD), and clinical attachment level (CAL)] of 1320 women were assessed, followed by retrieval of their demographic and medical data from the medical records. Based on the medical records, 80 women were excluded from the study, leaving 1240 females as the eligible sample for the study. The women were divided into control group (1120 non-preeclamptic women who gave birth to infants with adequate gestational age) and case group (120 preeclamptic women). Logistic regression analysis revealed that primiparity and maternal periodontitis were the two significant variables causing preeclampsia. Further analysis was carried out by matching the two groups for primiparity to find the significance of maternal periodontitis. Maternal periodontitis was defined as PD ?4 mm and CAL ?3 mm at the same site in at least four teeth. Results: The results showed that maternal periodontitis (odds ratio 19.8) was associated with preeclampsia. Maternal periodontitis also remained associated with preeclampsia after matching for primiparity, which was another significant confounding factor in the study (odds ratio 9.33). Conclusion: Maternal periodontitis is a risk factor associated with preeclampsia, emphasizing the importance of periodontal care in prenatal programs. PMID:25992334

  1. The Effect of Non-surgical Periodontal Therapy on Hemoglobin A1c Levels in Persons with Type 2 Diabetes and Chronic Periodontitis: A Randomized Clinical Trial

    PubMed Central

    Engebretson, Steven P.; Hyman, Leslie G.; Michalowicz, Bryan S.; Schoenfeld, Elinor R.; Gelato, Marie C.; Hou, Wei; Seaquist, Elizabeth R.; Reddy, Michael S.; Lewis, Cora E.; Oates, Thomas W.; Tripathy, Devjit; Katancik, James A.; Orlander, Philip R.; Paquette, David W.; Hanson, Naomi Q.; Tsai, Michael Y.

    2014-01-01

    Importance Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. Objective To determine if non-surgical periodontal treatment reduces hemoglobin A1c (HbA1c) in persons with type 2 diabetes (DM) and moderate to advanced chronic periodontitis. Design, Setting and Participants The Diabetes and Periodontal Therapy Trial (DPTT) is a 6-month, single-masked, randomized, multi-center clinical trial. Participants had DM, were taking stable doses of medications, had HbA1c ?7% and <9%, and untreated periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with five academic medical centers. Intervention The treatment group (n=257) received scaling and root planing plus chlorhexidine oral rinse at baseline, and supportive periodontal therapy at three and six months. The control group (n=257) received no treatment for six months. Main Outcome Measure Difference in HbA1c change from baseline between groups at six months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose, and the Homeostasis Model Assessment (HOMA2). Results Enrollment was stopped early due to futility. At 6 months, the periodontal therapy group increased HbA1c 0.17% (1.0) (mean (SD)) compared to 0.11% (1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference = -0.05%; 95% Confidence Interval (CI): -0.23%, 0.12%; p=0.55). Probing depth, clinical attachment loss, bleeding on probing and gingival index measures improved in the treatment group compared to the control group at six months with adjusted between-group differences of 0.33mm (95% CI: 0.26, 0.39), 0.31mm (95% CI: 0.23, 0.39), 16.5% (95% CI: 12.9, 20.0) and 0.28 (95% CI: 0.21, 0.35), respectively; all p values <0.0001). Conclusions and Relevance Non-surgical periodontal therapy did not improve glycemic control in patients with DM and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering HbA1c. PMID:24346989

  2. Association between postmenopausal osteoporosis and experimental periodontitis.

    PubMed

    Luo, Kai; Ma, Souzhi; Guo, Jianbin; Huang, Yongling; Yan, Fuhua; Xiao, Yin

    2014-01-01

    To investigate the correlation between postmenopausal osteoporosis (PMO) and the pathogenesis of periodontitis, ovariectomized rats were generated and the experimental periodontitis was induced using a silk ligature. The inflammatory factors and bone metabolic markers were measured in the serum and periodontal tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme-linked immunosorbent assays, and immunohistochemistry. The bone mineral density of whole body, pelvis, and spine was analyzed using dual-energy X-ray absorptiometry and image analysis. All data were analyzed using SPSS 13.0 statistical software. It was found that ovariectomy could upregulate the expression of interleukin- (IL-)6, the receptor activator of nuclear factor- ?B ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10 expression in periodontal tissues, which resulted in progressive alveolar bone loss in experimental periodontitis. This study indicates that changes of cytokines and bone turnover markers in the periodontal tissues of ovariectomized rats contribute to the damage of periodontal tissues. PMID:24683547

  3. Properties of periodontal dressings.

    PubMed

    von Fraunhofer, J A; Argyropoulos, D C

    1990-01-01

    The physical properties of periodontal dressing materials, two chemically curing and one photocured, were examined. A modified penetrometer test showed that COEpak and PerioCare were similar in behavior, setting at 10-15 min post-mixing. Barricaid required 30 s of minimum light exposure to achieve curing. All materials absorbed water; both COEpak and PerioCare behaved similarly at 23 degrees C, but PerioCare absorbed far more water at 37 degrees C. Increased light exposure had little effect on Barricaid water sorption or solubility. There was no difference (p greater than 0.05) in the solubility of each material when immersed at 23 and 37 degrees C. When immersed in 0.9% KCl solution, Barricaid had no effect on solution conductivity or pH. COEpak and PerioCare increased conductivity slightly and the pH markedly. The adhesion of COEpak to a single tooth at one h was about 7 kg, but this decreased to about 6.5 kg at 24 h and to 5 kg at seven d. The adhesion of PerioCare was 2 kg at one h and 8.5 kg at 24 h, but it decreased to 7.5 kg at seven d. The adhesion of Barricaid was about 5 kg at one h, but it decreased to 3.5 kg at 24 h and to ca. 1.5 kg at seven d. The adhesion of Barricaid appears to involve mechanical locking and differs from that of COEpak and PerioCare. PMID:2376296

  4. Periodontal considerations in veneer cases.

    PubMed

    Peto, David

    2015-04-01

    Porcelain veneers are a minimally invasive technique to enhance patients' smiles. A crucial component in these cases is the supporting periodontal apparatus and its interaction with the restorations. This article addresses basic concepts such as biologic width, altered eruption patterns, appropriate gingival contouring and smile design to give practitioners the tools to diagnose, evaluate and treat cases successfully and predictably. PMID:25916012

  5. Investigation of allelic imbalances on chromosome 3p in nasopharyngeal carcinoma in Tunisia: high frequency of microsatellite instability in patients with early-onset of the disease.

    PubMed

    Trimeche, Mounir; Braham, Hend; Ziadi, Sonia; Amara, Khaled; Hachana, Mohamed; Korbi, Sadok

    2008-08-01

    Tunisia is one of the world's intermediate risk areas for nasopharyngeal carcinoma (NPC). Loss of heterozygosity (LOH) on the short arm of chromosome 3 (3p) is the most frequent genetic change reported in NPC from endemic areas. In the present study, we investigate the incidence of LOH and microsatellite instability (MSI) on chromosome 3p in 49 microdissected primary NPC specimens and corresponding non-cancerous tissues from Tunisian patients using six microsatellite polymorphic markers. LOH at one or more markers was observed in 40 out of 48 informative cases (83.3%). The markers D3S1038 at 3p25.2-26.1 and D3S1076 at 3p21.1-21.2 have showed the highest frequency of LOH (51.3%), followed by D3S1067 at 3p14.3-21.1 (48.7%), D3S1568 at 3p21.3 (47.4%), D3S659 at 3p13 (15.3%), and D3S1228 at 3p14.1-14.2 (11%). Interestingly, MSI at one or more microsatellite markers was observed in 15 cases (31.2%). The highest frequency of MSI was presented by D3S1568 (18.4%), D3S1067 (17.9%), and D3S1038 (12.8%). With regard to clinicopathological features, LOH was found to be less common in young patients (under 25 years) than in adults (p=0.04), whereas MSI was found to be more frequent in patients under 45 years than in older patients (p=0.006). No significant correlation was found between LOH or MSI and the other clinicopathological features investigated including, gender, tumor size, lymph node metastasis, UICC clinical stage, and histological subtype. This study revealed different patterns of allelic imbalance on chromosome 3P in NPC between age groups in Tunisia, and suggests an alteration in the DNA mismatch repair machinery that may be, in part, responsible of the early age onset form of this disease in North African populations. More attention should be given to the mismatch repair system in the juvenile form of this disease in future studies. PMID:18206419

  6. Polymorphisms in migraine-associated gene, atp1a2, and ischemic stroke risk in a biracial population: the genetics of early onset stroke study.

    PubMed

    Harriott, Andrea M; Dueker, Nicole; Cheng, Yu-Ching; Ryan, Kathleen A; O'Connell, Jeffrey R; Stine, O Colin; McArdle, Patrick F; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J; Cole, John W

    2013-12-01

    In a recent meta-analysis migraine was associated with a two-fold increase in stroke risk. While the mechanism driving this association is unknown, one intriguing hypothesis is that migraineurs are genetically predisposed to developing ischemic stroke. Mutations in the ATP1A2 gene are implicated in familial hemiplegic migraine type II and increase the severity of ischemic brain injury in animal models. To further explore these observations, we assessed the association between ATP1A2 polymorphisms, migraine, and the risk of ischemic stroke in participants of the Genetics of Early-Onset Stroke Study, a population-based case-control study of ischemic stroke among men and women aged 15-49. Using responses to a headache symptoms questionnaire, subjects were classified as having no migraine, or migraine with or without visual aura. Evaluating a total of 134 ATP1A2 polymorphisms genotyped using a combination of Illumina platforms (Cardiovascular Gene-centric 50 K SNP Array and HumanOmni1-Quad_v1-0_B Bead Chip), only one polymorphism (rs2070704) demonstrated a nominally significant association with stroke in an age-, gender-, ethnicity-adjusted model (OR?=?0.83, 95% CI?=?0.71-0.98, p?=?0.025) and in a vascular risk factor model adjusting for age, gender, ethnicity, hypertension, diabetes, smoking, and myocardial infarction (OR?=?0.74, 95% CI?=?0.63-0.89, p?=?0.001). Ethnicity-stratified analyses demonstrated a significant association for rs2070704 among African-Americans (OR?=?0.68, 95% CI?=?0.53-0.90, p?=?0.005) but not Caucasians (OR?=?0.82, 95% CI?=?0.64-1.04, p?=?0.107). These associations were unchanged when migraine subtypes were included as co-variates. We did not observe an association between ATP1A2 polymorphisms and migraine. While our results do not demonstrate a strong relationship between ATP1A2 polymorphisms and migraine associated stroke risk, the results are hypothesis generating and indicate that an association between ATP1A2 polymorphisms and stroke risk may exist. Additional studies are required. PMID:23459313

  7. Novel Radiopaque UHMWPE Sublaminar Wires in a Growth-Guidance System for the Treatment of Early Onset Scoliosis: Feasibility in a Large Animal Study.

    PubMed

    Bogie, R; Roth, Ak; Faber, S; de Jong, Jja; Welting, Tjm; Willems, Pc; Arts, Jj; van Rhijn, Lw

    2014-09-29

    Study Design. In vivo analysis in an ovine model.Objective. To evaluate the feasibility of radiopaque UHMWPE sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility and growth potential.Summary of Background Data. Several growth-guidance systems have been developed for the treatment of early onset scoliosis (EOS). The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for EOS.Methods. Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHWMPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T11 and fixed to dual cobalt-chromiun rods. Four age-matched, unoperated animals were evaluated to serve as a control group. Radiographs were taken to measure growth of the instrumented segment. After 24 weeks, the animals were sacrificed and the spines were harvested for histological evaluation and high resolution peripheral quantitative computed tomography (HR-pQCT) analysis.Results. No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5-T11) in the intervention group (27± 2 mm), which was not significantly different to the control group, (30 ± 4mm, p = 0.42). HR-pQCT analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris.Conclusions. This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local tissue response to these wires was observed. PMID:25271492

  8. Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

    PubMed Central

    Buhimschi, Catalin S.; Bhandari, Vineet; Dulay, Antonette T.; Nayeri, Unzila A.; Abdel-Razeq, Sonya S.; Pettker, Christian M.; Thung, Stephen; Zhao, Guomao; Han, Yiping W.; Bizzarro, Matthew; Buhimschi, Irina A.

    2011-01-01

    Background Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. Methodology/Principal Findings We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n?=?3) versus GA-matched controls (n?=?3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1st-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (P<0.001). Western blot concurred in determining that EONS babies had conspicuous Hp&HpRP bands in cord blood (“switch-on pattern”) as opposed to non-EONS newborns who had near-absent “switch-off pattern” (P<0.001). Fetal Hp phenotype independently impacted Hp&HpRP. A Bayesian latent-class analysis (LCA) was further used for unbiased classification of all 180 cases based on probability of “antenatal IAI exposure” as latent variable. This was then subjected to 2nd-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (?20%) versus high (?70%) probability of IAI exposure. This approach reclassified ?30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Conclusions/Significance Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth. PMID:22028810

  9. Clinical application of CO2 laser in periodontal treatment

    NASA Astrophysics Data System (ADS)

    Hayase, Yasuhiro

    1994-09-01

    CO2 lasers in particular are expected to have many dental applications because the CO2 laser beam exhibits strong tissue transpirative actions, such as instant coagulation, carbonization, and vaporization, and because its wavelength at 10.6 micrometers is fully absorbed by water so that the ability to make precise incisions with a high degree of safety is excellent, without damaging the deep tissues. However, clinical application of the CO2 laser has been slowed since a fiber which can conduct the laser beam to the oral cavity has only recently developed. This new fiber is an extremely flexible fiber with a minimum bending radius of 20 mm and utilizes pulse wave modes that have improved the handling characteristics in the mouth, and this has enabled us to apply the CO2 laser to a variety of periodontal conditions. The aim of this study was to evaluate the effectiveness of CO2 lasers for the early treatment of inflammation and pain relief of acute periodontitis, curettage of periodontal pockets, healing after excision of gingiva, and early improvement of gingivitis.

  10. The association of periodontitis and metabolic syndrome

    PubMed Central

    Gurav, Abhijit N.

    2014-01-01

    Metabolic syndrome (MS) is a condition, which constitutes a group of risk factors that occur together and increase the risk for Coronary Artery Disease, Stroke and type 2 diabetes mellitus. This disorder is found prevalent in the industrialized societies of the world in epidemic proportions. Periodontitis is an oral disease of microbial origin characterized by loss of attachment apparatus of tooth, resulting in edentulism if untreated. Periodontitis has been attributed to produce a low grade systemic inflammatory condition. The link of periodontitis to various systemic disorders has led to the evolution of a new branch termed as “periodontal medicine.” Studies reviewed in the present paper have indicated a positive link between the MS and periodontitis and it is suggested that subjects displaying several components of MS should be submitted to periodontal examination. Present studies have displayed coherent relation between the two entities. This review will address the vicious association between MS and periodontitis, depicting the commonality of pathophysiological pathway between the two entities. Systematic reviews, meta-analysis addressing the concerned subject were screened. Whether the systematic periodontal therapy in individuals exhibiting MS has the potential to reduce the incidence of various adverse systemic complications remains a logical proposition. Further, longitudinal and controlled trials with a large population would be imperative to depict the robustness in the association between MS and periodontal disease in human subjects. PMID:24688553

  11. Initial periodontal screening and radiographic findings - A comparison of two methods to evaluate the periodontal situation

    PubMed Central

    2011-01-01

    Background The periodontal screening index (PSI) is an element of the initial dental examination. The PSI provides information on the periodontal situation and allows a first estimation of the treatment required. The dental panoramic tomography (DPT) indicates the proximal bone loss, thus also allowing conclusions on the periodontal situation. In this study, the results of both methods in determining the periodontal situation are compared. Methods The clinical examination covered DMF-T, QHI, and PSI scores at four proximal sites per tooth; the examining dentist was unaware of the radiographic finding. Based on the PSI scores, the findings were diagnosed as follows: score 0 - 2 "no periodontitis", score 3 and 4 "periodontitis". Independent of the locality and time of the clinical evaluation, two dentists examined the DPTs of the subjects. The results were classified as follows: no bone loss = "no periodontitis", and bone loss = "periodontitis". Results 112 male subjects (age 18 to 58, Ø 37.7 ± 8 years) were examined. Regarding the PSI, 17 subjects were diagnosed "no periodontitis" and 95 subjects "periodontitis". According to the evaluation of the DPTs, 70 subjects were diagnosed "no periodontitis" and 42 "periodontitis". A comparison of both methods revealed that the diagnosis "no periodontitis" corresponded in 17 cases and "periodontitis" in 42 cases (53%). In 47% (53 cases) the results were not congruent. The difference between both methods was statistically significant (p < 0.001; kappa = 0.194). Conclusion The present study shows that the initial assessment of the periodontal situation significantly depends on the method of evaluation. PMID:21235747

  12. Risk of Early Onset Substance Use among Students with and without Mild Academic Disabilities: Results of a Discrete-Time Survival Analysis

    ERIC Educational Resources Information Center

    Kepper, Annelies; Koning, Ina; Vollebergh, Wilma; Monshouwer, Karin

    2014-01-01

    This study investigated the age of onset of substance use among 536 students with mild academic disabilities and 906 students without academic disabilities, and the extent to which emotional, conduct, and hyperactivity problems explain the differences between these two groups. Using discrete-time survival analysis, the results of this study showed…

  13. Sex and the Self: The Impact of Early Sexual Onset on the Self-Concept and Subsequent Risky Behavior of African American Adolescents

    ERIC Educational Resources Information Center

    Houlihan, Amy E.; Gibbons, Frederick X.; Gerrard, Meg; Yeh, Hsiu-Chen; Reimer, Rachel A.; Murry, Velma M.

    2008-01-01

    A 5-year longitudinal study of African American adolescents, aged 10 to 12 at Time 1, used the prototype/willingness (prototype) model to examine the (social) cognitive effects of the onset of sexual behavior on self-concept. Structural equation modeling (SEM) showed that becoming sexually active was related to favorable changes in adolescents'…

  14. Neurobiology of Schizophrenia Onset

    PubMed Central

    Woo, Tsung-Ung W.

    2015-01-01

    The clinical symptoms and cognitive and functional deficits of schizophrenia typically begin to gradually emerge during late adolescence and early adulthood. Recent findings suggest that disturbances of a specific subset of inhibitory neurons that contain the calcium-binding protein parvalbumin (PV), which may regulate the course of postnatal developmental experience-dependent synaptic plasticity in the cerebral cortex, including the prefrontal cortex (PFC), may be involved in the pathogenesis of the onset of this illness. Specifically, converging lines of evidence suggest that oxidative stress, extracellular matrix (ECM) deficit and impaired glutamatergic innervation may contribute to the functional impairment of PV neurons, which may then lead to aberrant developmental synaptic pruning of pyramidal cell circuits during adolescence in the PFC. In addition to promoting the functional integrity of PV neurons, maturation of ECM may also play an instrumental role in the termination of developmental PFC synaptic pruning; thus, ECM deficit can directly lead to excessive loss of synapses by prolonging the course of pruning. Together, these mechanisms may contribute to the onset of schizophrenia by compromising the integrity, stability, and fidelity of PFC connectional architecture that is necessary for reliable and predictable information processing. As such, further characterization of these mechanisms will have implications for the conceptualization of rational strategies for the diagnosis, early intervention, and prevention of this debilitating disorder. PMID:23975845

  15. An update on periodontic-orthodontic interrelationships

    PubMed Central

    Dannan, Aous

    2010-01-01

    Talking about periodontic-orthodontic interrelationships is related primarily to the 1960s, where a generalized increase in salivary bacterial counts, especially Lactobacillus, had been shown after orthodontic band placement. The purpose of this article is to provide the dental practitioner with basic understanding of the interrelationship between periodontics and orthodontics by means of representing classical studies, and, to give an update on this topic by demonstrating the most recent opinions concerning periodontic-orthodontic interrelationships. Specific areas reviewed are the ability of orthodontic treatment to afford some degree of protection against periodontal breakdown, short-term and long-term effects of orthodontic treatment on the periodontium, and some mucogingival considerations. Topics considering orthodontic treatment in periodontally compromised patients were not included in this review. While past studies have shown that orthodontic treatment can positively affect the periodontal health, recent reviews indicate an absence of reliable evidence for the positive effects of orthodontic therapy on patients’ periodontal status. Periodontic-orthodontic interrelationships are still controversial issues. However, a standard language between the periodontist and the orthodontist must always be established to eliminate the existing communications barrier, and to improve the outcomes of the whole treatment. PMID:20922083

  16. Uncovering the molecular networks in periodontitis

    PubMed Central

    Trindade, Fábio; Oppenheim, Frank G.; Helmerhorst, Eva J.; Amado, Francisco; Gomes, Pedro S.; Vitorino, Rui

    2015-01-01

    Periodontitis is a complex immune-inflammatory disease that results from a preestablished infection in gingiva, mainly due to Gram-negative bacteria that colonize deeper in gingival sulcus and latter periodontal pocket. Host inflammatory and immune responses have both protective and destructive roles. Although cytokines, prostaglandins, and proteases struggle against microbial burden, these molecules promote connective tissue loss and alveolar bone resorption, leading to several histopathological changes, namely destruction of periodontal ligament, deepening of periodontal pocket, and bone loss, which can converge to attain tooth loss. Despite the efforts of genomics, transcriptomics, proteomics/peptidomics, and metabolomics, there is no available biomarker for periodontitis diagnosis, prognosis, and treatment evaluation, which could assist on the established clinical evaluation. Nevertheless, some genes, transcripts, proteins and metabolites have already shown a different expression in healthy subjects and in patients. Though, so far, ‘omics approaches only disclosed the host inflammatory response as a consequence of microbial invasion in periodontitis and the diagnosis in periodontitis still relies on clinical parameters, thus a molecular tool for assessing periodontitis lacks in current dental medicine paradigm. Saliva and gingival crevicular fluid have been attracting researchers due to their diagnostic potential, ease, and noninvasive nature of collection. Each one of these fluids has some advantages and disadvantages that are discussed in this review. PMID:24828325

  17. Relation between periodontitis and helicobacter pylori infection

    PubMed Central

    Zheng, Pei; Zhou, Weiying

    2015-01-01

    Objective: The correlation between periodontitis and Helicobacter pylori (H. pylori) infection in the mouth was analyzed. Method: 70 elderly patients with periodontitis treated at our hospital from January 2013 to December 2014 were recruited. Dental plaques and gargle were collected for H. pylori detection using PCR technique. Periodontal health status of the patients was recorded. 70 control cases with healthy periodontium were also included. The symptoms of H. pylori infection in the mouth were compared between the two groups, and the results were analyzed statistically. Results: The positive rate of urease C gene of H. pylori in the periodontitis group was 71.4%; the positive rate of cagA gene was 35.7%. The positive rate of urease C gene of H. pylori in the control group was 34.3% and that of cagA gene was 12.9%. The two groups did not show significant differences in these two indicators (P<0.05). The positive detection rate of urease C gene of H. pylori in subgingival plaques was higher than that in supragingival plaques, and the difference was of statistical significance (P<0.05). The positive detection rate of H. pylori in patients with moderate and severe periodontitis was obviously higher than that of patients with mild periodontitis (P<0.05). Conclusion: Periodontal health status of elderly people with periodontitis correlated with H. pylori infection in the stomach.

  18. Regulation of Regenerative Periodontal Healing by NAMPT

    PubMed Central

    Nokhbehsaim, Marjan; Keser, Sema; Jäger, Andreas; Jepsen, Søren

    2013-01-01

    Periodontitis is an inflammatory disease characterized by destruction of the tooth-supporting tissues. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of nicotinamide phosphoribosyltransferase (NAMPT) may be a pathomechanistic link between both diseases. Recently, increased levels of NAMPT have also been found in patients with periodontitis, irrespective of the presence of obesity. This in vitro study sought to examine the effects of NAMPT on the regenerative capacity of human periodontal ligament (PDL) cells and, thereby, periodontal healing. PDL cells treated with enamel matrix derivative (EMD), which was used to mimic regenerative healing conditions in vitro, were grown in the presence and absence of NAMPT for up to 14 d. EMD stimulated significantly (P < 0.05) the expression of growth factors and their receptors, matrix molecules, osteogenesis-associated factors, and wound closure and calcium accumulation. In the presence of NAMPT, all these stimulatory effects were significantly (P < 0.05) reduced. In conclusion, the beneficial effects of EMD on a number of PDL cell functions critical for periodontal regeneration are counteracted by NAMPT. Enhanced levels of NAMPT, as found in obesity and periodontal inflammation, may compromise the regenerative capacity of PDL cells and, thereby, periodontal healing in the presence of EMD. PMID:24288440

  19. Scope of photodynamic therapy in periodontics.

    PubMed

    Kumar, Vivek; Sinha, Jolly; Verma, Neelu; Nayan, Kamal; Saimbi, C S; Tripathi, Amitandra K

    2015-01-01

    Periodontal disease results from inflammation of the supporting structure of the teeth and in response to chronic infection caused by various periodontopathic bacteria. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. However, the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. Photodynamic therapy (PDT) is a powerful laser-initiated photochemical reaction, involving the use of a photoactive dye (photosensitizer) activated by light of a specific wavelength in the presence of oxygen. Application of PDT in periodontics such as pocket debridement, gingivitis, and aggressive periodontitis continue to evolve into a mature clinical treatment modality and is considered as a promising novel approach for eradicating pathogenic bacteria in periodontitis. PMID:26481895

  20. Arterial stiffness in periodontitis patients and controls.

    PubMed

    Houcken, W; Teeuw, W J; Bizzarro, S; Alvarez Rodriguez, E; Mulders, T A; van den Born, B-Jh; Loos, B G

    2016-01-01

    Increased arterial stiffness (AS) is an important indicator for atherosclerotic cardiovascular disease (ACVD). Epidemiologically, periodontitis and ACVD are associated. Therefore, we aimed to investigate AS in periodontitis patients and controls. In addition, we explored the effect of periodontal therapy on AS in a sub-group of cases. Pulse-wave velocity (PWV), a non-invasive chair-side function test for AS, was measured in periodontitis patients (n=57; mean age 46.6 years) and compared with a reference group (n=48; mean age 45.5 years). In addition, 45 cases (mean age 46.9 years) were 6 months followed after periodontal treatment, to explore a possible effect on arterial function. Periodontitis patients showed a significantly increased PWV compared with the reference group (8.01±0.20 vs 7.36±0.22?m?s(-1) respectively; P=0.029) and this remained significant after adjustments for ACVD risk factors (P=0.019). After periodontal therapy, no significant reduction in PWV was seen (8.00±1.8 to 7.82±1.6?m?s(-1); P=0.13), but systolic blood pressure (SBP) was significantly reduced (119.8±14.6 to 116.9±15.1?mm?Hg; P=0.040). It can be concluded that periodontitis is associated with increased AS. This confirms with a new parameter the association of periodontitis with ACVD. Although periodontal treatment did not lower AS significantly, a modest reduction of SBP after 6 months was observed. PMID:25972093

  1. Investigation of hemorheological parameters in periodontal diseases.

    PubMed

    Seringec, Nurten; Guncu, Guliz; Arihan, Okan; Avcu, Nihal; Dikmenoglu, Neslihan

    2015-10-28

    Periodontal diseases are frequently associated with cardiovascular diseases (CVD). On the other hand, occurrence of CVD has also been related with increased blood viscosity. This study was planned to investigate four main hemorheological parameters contributing to blood viscosity - hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity - and also some biochemical parameters (hs-CRP, fibrinogen, globulin etc.) in patients with periodontal disease. We hypothesized that poor periodontal health would be associated with deterioration of hemorheological properties. According to periodontal health status, subjects were divided into three groups as control (healthy), with plaque induced gingivitis and with chronic periodontitis. All groups included 15 males who had not received periodontal therapy in the last six months before the study, were non-smokers, had no systemic diseases and were not on any medication. Erythrocyte deformability and erythrocyte aggregation were measured with laser-assisted optical rotational cell analyzer (LORCA). Plasma viscosity was measured by a cone-plate viscometer. Data were analyzed with Kruskal-Wallis, Mann-Whitney U Test and Spearman Correlation Coefficient. Plasma viscosity (1.36 ± 0.01 mPa.s in the control group and 1.43 ± 0.02 mPa.s in the chronic periodontitis group, P?< ?0.01), erythrocyte aggregation tendency (aggregation index, amplitude and t½ were 58.82 ± 1.78% , 20.22 ± 0.40 au, 2.80 ± 0.25?s respectively in the control group, and 67.05 ± 1.47% , 22.19 ± 0.50 au, 1.84 ± 0.15?s in the chronic periodontitis group, P?< ?0.01), hs-CRP, fibrinogen and globulin levels were significantly higher, whereas HDL level was significantly lower in the chronic periodontitis group (P?< ?0.05) compared to the control group. All of these conditions may contribute to cardiovascular morbidity and mortality observed in people with periodontal disease, via increasing blood viscosity. PMID:25261434

  2. Magnetostratigraphic evidence of a mid-Pliocene onset of the Nihewan Formation e implications for early fauna and hominid occupation in the

    E-print Network

    Utrecht, Universiteit

    for early fauna and hominid occupation in the Nihewan Basin, North China Hong Ao a,*, Mark J. Dekkers b 29 November 2012 Keywords: Magnetostratigraphy Nihewan Formation Nihewan Fauna Hominid occupation crucial for our understanding of early fauna and hominid occupation and infilling history of the basin

  3. Coordinated Pediatric and Periodontal Dental Care of a Child with Down syndrome.

    PubMed

    Byrd, Gentry; Quinonez, Rocio B; Offenbacher, Steven; Keels, Martha Ann; Guthmiller, Janet M

    2015-01-01

    The purpose of this report was to describe the management of an eight-year-old Bulgarian male with Down syndrome presenting with periodontitis as a manifestation of systemic disease in the early mixed dentition. Treatment involved full-mouth mechanical debridement and extraction of hopeless teeth under general anesthesia followed by systemic antibiotics and chemical adjunctive therapy. Microbial culture and sensitivity testing aided in diagnosis and guided treatment decisions. This case report demonstrates a multidisciplinary approach in the management of aggressive periodontal disease in an internationally adopted pediatric patient with special health care needs. PMID:26314608

  4. Treatment with anti-C5aR mAb leads to early-onset clinical and mechanistic effects in the murine delayed-type hypersensitivity arthritis model.

    PubMed

    Atkinson, Sara M; Nansen, Anneline; Usher, Pernille A; Sondergaard, Bodil-Cecilie; Mackay, Charles R; Friedrichsen, Birgitte; Chang, Chih-Chuan; Tang, Renhong; Skov, Søren; Haase, Claus; Hornum, Lars

    2015-11-01

    Blockade of the complement cascade at the C5a/C5a receptor (C5aR)-axis is believed to be an attractive treatment avenue in rheumatoid arthritis (RA). However, the effects of such interventions during the early phases of arthritis remain to be clarified. In this study we use the murine delayed-type hypersensitivity arthritis (DTHA) model to study the very early effects of a blocking, non-depleting anti-C5aR mAb on joint inflammation with treatment synchronised with disease onset, an approach not previously described. The DTHA model is a single-paw inflammatory arthritis model characterised by synchronised and rapid disease onset driven by T-cells, immune complexes and neutrophils. We show that a reduction in paw swelling, bone erosion, cartilage destruction, synovitis and new bone formation is apparent as little as 60?h after administration of a single dose of a blocking, non-depleting anti-mouse C5aR mAb. Importantly, infiltration of neutrophils into the joint and synovium is also reduced following a single dose, demonstrating that C5aR signalling during the early stage of arthritis regulates neutrophil infiltration and activation. Furthermore, the number of T-cells in circulation and in the draining popliteal lymph node is also reduced following a single dose of anti-C5aR, suggesting that modulation of the C5a/C5aR axis results in effects on the T cell compartment in inflammatory arthritis. In summary, these data demonstrate that blockade of C5aR leads to rapid and significant effects on arthritic disease development in a DTHA model strengthening the rationale of C5aR-blockade as a treatment strategy for RA, especially during the early stages of arthritis flare. PMID:25915570

  5. Periodontal disease and diabetes mellitus

    PubMed Central

    NEGRATO, Carlos Antonio; TARZIA, Olinda; JOVANOVI?, Lois; CHINELLATO, Luiz Eduardo Montenegro

    2013-01-01

    Periodontal disease (PD) is one of the most commonly known human chronic disorders. The relationship between PD and several systemic diseases such as diabetes mellitus (DM) has been increasingly recognized over the past decades. Objective: The purpose of this review is to provide the reader with knowledge concerning the relationship between PD and DM. Many articles have been published in the english and Portuguese literature over the last 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of DM, PD and different clinical criteria were applied to determine the prevalence, extent and severity of PD, levels of glycemic control and diabetes-related complications. Methods: This paper provides a broad overview of the predominant findings from research conducted using the BBO (Bibliografia Brasileira de Odontologia), MEDLINE, LILACS and PubMed for Controlled Trials databases, in english and Portuguese languages published from 1960 to October 2012. Primary research reports on investigations of relationships between DM/DM control, PD/periodontal treatment and PD/DM/diabetes-related complications identified relevant papers and meta-analyses published in this period. Results: This paper describes the relationship between PD and DM and answers the following questions: 1- The effect of DM on PD, 2- The effects of glycemic control on PD and 3- The effects of PD on glycemic control and on diabetes-related complications. Conclusions: The scientific evidence reviewed supports diabetes having an adverse effect on periodontal health and PD having an adverse effect on glycemic control and on diabetes-related complications. Further research is needed to clarify these relationships and larger, prospective, controlled trials with ethnically diverse populations are warranted to establish that treating PD can positively influence glycemic control and possibly reduce the burden of diabetes-related complications. PMID:23559105

  6. The application of Periodontal Screening and Recording (PSR) in a military population.

    PubMed

    Covington, Lemuel L; Breault, Lawrence G; Hokett, Steven D

    2003-08-15

    Periodontal Screening and Recording trade mark (PSR) is a diagnostic screening tool for the early detection of periodontal disease. The purposes of this study are to utilize PSR to estimate the periodontal health status of a representative military population and to compare the results with other studies of varying populations. When used to evaluate the periodontal health of a randomly-selected military population, PSR demonstrated the following: (1) males and females had a similar prevalence of being designated PSR+ (having PSR Code 3 score in two or more sextants or a PSR Code 4 score in at least one sextant), (2) Blacks and Hispanics had a similar prevalence of PSR+, and (3) both groups were twice as likely to be PSR+ as were Caucasians. Although income did not appear to be a significant predictor of PSR+, PSR+ did appear to be inversely proportional to education levels. When comparing PSR scores by sextant, the following was noted: (1) the maxillary central sextant was the most disease-free, (2) the mandibular central sextant most often presented with calculus, (3) mucogingival defects were observed more frequently in maxillary posterior sextants, and (4) the maxillary right sextant demonstrated the most destruction from periodontal disease. PMID:12937595

  7. The Impact of Periodontitis in the Preterm Birth and Body Size of Newborns

    PubMed Central

    Lauren, Muhametaj; Minire, Alilaj; Maldi, Xhelili; Mirton, Muhametaj; Aferdita, Manaj

    2012-01-01

    Background: Increasing evidence suggests that maternal gingivitis and periodontitis may be a risk factor for preterm birth and other adverse pregnancy outcomes. Objective: To assess the relationship between periodotitis and preterm birth. Methods: A retrospective study which included 230 pregnant women, and the delivery follow up to determine the correlation between periodontitis and preterm birth. Results: The study indicates that periodontal infection can lead to placental-fetal exposure and, when coupled with a fetal inflammatory response, can lead to preterm delivery. Periodontitis is correlated with preterm birth, so early diagnosis and a careful treatment are very important issues. Results: In 2009 at the Neurology Clinic CCUS have treated 34 patients who passed the committee for recommendation to interferon therapy (25 women and 9 men). The diagnosis of multiple sclerosis is safe based on the criteria of international panel in 2000. EDSS Average score for men was 1.8, 1.9 for women, the total EDSS score was 1.8. The gender ratio is 3:1 in women than in men. Sixteen patients received interferon by the Commission for multiple sclerosis, the Federal Ministry of Health and their therapy was initiated at the clinic. Conclusion: Periodontitis is one of the main causes of preterm-premature rupture of membranes and a proper treatment is the best solution for this pathology. PMID:23922515

  8. Protein Biomarkers of Periodontitis in Saliva

    PubMed Central

    Taylor, John J.

    2014-01-01

    Periodontitis is a chronic inflammatory condition of the tissues that surround and support the teeth and is initiated by inappropriate and excessive immune responses to bacteria in subgingival dental plaque leading to loss of the integrity of the periodontium, compromised tooth function, and eventually tooth loss. Periodontitis is an economically important disease as it is time-consuming and expensive to treat. Periodontitis has a worldwide prevalence of 5–15% and the prevalence of severe disease in western populations has increased in recent decades. Furthermore, periodontitis is more common in smokers, in obesity, in people with diabetes, and in heart disease patients although the pathogenic processes underpinning these links are, as yet, poorly understood. Diagnosis and monitoring of periodontitis rely on traditional clinical examinations which are inadequate to predict patient susceptibility, disease activity, and response to treatment. Studies of the immunopathogenesis of periodontitis and analysis of mediators in saliva have allowed the identification of many potentially useful biomarkers. Convenient measurement of these biomarkers using chairside analytical devices could form the basis for diagnostic tests which will aid the clinician and the patient in periodontitis management; this review will summarise this field and will identify the experimental, technical, and clinical issues that remain to be addressed before such tests can be implemented. PMID:24944840

  9. Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer's Disease

    PubMed Central

    Singhrao, Sim K.; Harding, Alice; Poole, Sophie; Kesavalu, Lakshmyya; Crean, StJohn

    2015-01-01

    Periodontal disease (PD) and Alzheimer's disease (AD) are inflammatory conditions affecting the global adult population. In the pathogenesis of PD, subgingival complex bacterial biofilm induces inflammation that leads to connective tissue degradation and alveolar bone resorption around the teeth. In health, junctional epithelium seals the gingiva to the tooth enamel, thus preventing bacteria from entering the gingivae. Chronic PD involves major pathogens (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) which have an immune armoury that can circumvent host's immune surveillance to create and maintain an inflammatory mediator rich and toxic environment to grow and survive. The neurodegenerative condition, AD, is characterised by poor memory and specific hallmark proteins; periodontal pathogens are increasingly being linked with this dementing condition. It is therefore becoming important to understand associations of periodontitis with relevance to late-onset AD. The aim of this review is to discuss the relevance of finding the keystone periodontal pathogen P. gingivalis in AD brains and its plausible contribution to the aetiological hypothesis of this dementing condition. PMID:26063967

  10. Periodontal Bioengineering: A Discourse in Surface Topographies, Progenitor Cells and Molecular Profiles

    NASA Astrophysics Data System (ADS)

    Dangaria, Smit J.

    2011-12-01

    Stem/progenitor cells are a population of cells capable of providing replacement cells for a given differentiated cell type. We have applied progenitor cell-based technologies to generate novel tissue-engineered implants that use biomimetic strategies with the ultimate goal of achieving full regeneration of lost periodontal tissues. Mesenchymal periodontal tissues such as cementum, alveolar bone (AB), and periodontal ligament (PDL) are neural crest-derived entities that emerge from the dental follicle (DF) at the onset of tooth root formation. Using a systems biology approach we have identified key differences between these periodontal progenitors on the basis of global gene expression profiles, gene cohort expression levels, and epigenetic modifications, in addition to differences in cellular morphologies. On an epigenetic level, DF progenitors featured high levels of the euchromatin marker H3K4me3, whereas PDL cells, AB osteoblasts, and cementoblasts contained high levels of the transcriptional repressor H3K9me3. Secondly, we have tested the influence of natural extracellular hydroxyapatite matrices on periodontal progenitor differentiation. Dimension and structure of extracellular matrix surfaces have powerful influences on cell shape, adhesion, and gene expression. Here we show that natural tooth root topographies induce integrin-mediated extracellular matrix signaling cascades in tandem with cell elongation and polarization to generate physiological periodontium-like tissues. In this study we replanted surface topography instructed periodontal ligament progenitors (PDLPs) into rat alveolar bone sockets for 8 and 16 weeks, resulting in complete attachment of tooth roots to the surrounding alveolar bone with a periodontal ligament fiber apparatus closely matching physiological controls along the entire root surface. Displacement studies and biochemical analyses confirmed that progenitor-based engineered periodontal tissues were similar to control teeth and uniquely derived from pre-implantation green fluorescent protein (GFP)-labeled progenitors. Together, these studies illustrate the capacity of natural extracellular surface topographies to instruct PDLPs to fully regenerate complex cellular and structural morphologies of tissues once lost to disease. We suggest that our strategy could be used for the replantation of teeth lost due to trauma or as a novel approach for tooth replacement using tooth-shaped replicas.

  11. Radiologic Assessment of the Periodontal Patient.

    PubMed

    Korostoff, Jonathan; Aratsu, Ali; Kasten, Brian; Mupparapu, Mel

    2016-01-01

    Periodontal examination involves evaluation of soft and hard tissue parameters to gauge gingival inflammatory changes and quantify attachment loss. Conventional radiographs are vital components of this process and can be used to assess the presence of calculus and other local factors to establish a diagnosis, prognosis, and periodontal treatment plan. The 2-dimensional nature of these images limits their utility. The advent of high-resolution cone beam computed tomography (CBCT) offers 3-dimensional images that might overcome these limitations. We discuss the use of conventional radiographic techniques as well as CBCT for evaluating, diagnosing, and treatment planning patients presenting for periodontal and/or implant therapy. PMID:26614950

  12. The antioxidant master glutathione and periodontal health

    PubMed Central

    Bains, Vivek Kumar; Bains, Rhythm

    2015-01-01

    Glutathione, considered to be the master antioxidant (AO), is the most-important redox regulator that controls inflammatory processes, and thus damage to the periodontium. Periodontitis patients have reduced total AO capacity in whole saliva, and lower concentrations of reduced glutathione (GSH) in serum and gingival crevicular fluid, and periodontal therapy restores the redox balance. Therapeutic considerations for the adjunctive use of glutathione in management of periodontitis, in limiting the tissue damage associated with oxidative stress, and enhancing wound healing cannot be underestimated, but need to be evaluated further through multi-centered randomized controlled trials. PMID:26604952

  13. [Immunological behavior (IgG, IgM, IgA) and total complement (CH50) of newborns infants with risk factors for early onset sepsis. Comparative analysis of newborns with and without infection].

    PubMed

    Ceccon, M E; Diníz, E M; Carneiro-Sampaio, M M; Arslanian, C; Diogo, C L; Ramos, J L; Vaz, F A

    1998-01-01

    Immunological behavior (IgG, IgM, IgA) and total Complement (CH50) of newborns infants with risk factors for early onset sepsis. Comparative analysis between newborns with and without infection. Rev. Hosp. Clín. Fac. Med. S. Paulo, 53(6): 303-310, 1998. The objective of this study was to verify the immunological behavior of the newborn infant in front of an infection. We studied 60 newborn infants that had risk factors for early onset sepsis (premature rupture membranes, clinic amnionitis or tract urinary infection) from de immunological and infection point of view. They were classified into three gestational age groups: < 34 weeks, between 34 and 36 6/7 weeks and > or = 37 weeks. Sepsis diagnosis was done through clinical and laboratorial data and we also included the followings exams: Immunological types (IgG, IgM, IgA) and total complement (CH50) obtained from the newborn at birth and on the fifth day of life. We could verify that 15 newborns (25%) presented early sepsis. There was a statistical association between perinatal asfixia and infection in the group with gestational age < 34 weeks and this same group presented statistical association between infection and death. The serical levels of IgG and CH50 were directly related to the gestational age and there were significant statistical differences between levels of IgG, IgM and total Complement between infected and not infected newborns within the same group os gestional age. We observed that the infection was associated to low levels of IgG and CH50, at birth and on the fifth day, mainly in the group of infected newborns with gestional age < 34 weeks, being this group, therefore, the one that would mostly benefit from an immunological support in front of and infection. PMID:10413946

  14. Severe Periodontitis Is Inversely Associated with Coffee Consumption in the Maintenance Phase of Periodontal Treatment

    PubMed Central

    Machida, Tatsuya; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Takeuchi, Noriko; Maruyama, Takayuki; Mizutani, Shinsuke; Kataoka, Kota; Kawabata, Yuya; Morita, Manabu

    2014-01-01

    This cross-sectional study addressed the relationship between coffee consumption and periodontitis in patients during the maintenance phase of periodontal treatment. A total of 414 periodontitis patients in the maintenance phase of periodontal treatment completed a questionnaire including items related to coffee intake and underwent periodontal examination. Logistic regression analysis showed that presence of moderate/severe periodontitis was correlated with presence of hypertension (Odds Ratio (OR) = 1.99, p < 0.05), smoking (former, OR = 5.63, p < 0.01; current, OR = 6.81, p = 0.076), number of teeth present (OR = 0.89, p < 0.001), plaque control record ?20% (OR = 1.88, p < 0.05), and duration of maintenance phase (OR = 1.07, p < 0.01). On the other hand, presence of severe periodontitis was correlated with smoking (former, OR = 1.35, p = 0.501; current, OR = 3.98, p < 0.05), coffee consumption (?1 cup/day, OR = 0.55, p < 0.05), number of teeth present (OR = 0.95, p < 0.05), and bleeding on probing ? 20% (OR = 3.67, p < 0.001). There appears to be an inverse association between coffee consumption (?1 cup/day) and prevalence of severe periodontitis in the maintenance phase of periodontal treatment. PMID:25338270

  15. Periodontal Bacteria and Prediabetes Prevalence in ORIGINS: The Oral Infections, Glucose Intolerance, and Insulin Resistance Study.

    PubMed

    Demmer, R T; Jacobs, D R; Singh, R; Zuk, A; Rosenbaum, M; Papapanou, P N; Desvarieux, M

    2015-09-01

    Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P = 0.23. Higher colonization levels of specific periodontal microbiota are associated with higher prediabetes prevalence among diabetes-free adults. PMID:26082387

  16. Ontong Java volcanism initiated long-term climate warming that caused substantial changes in terrestrial vegetation several tens of thousand years before the onset of OAE1a (Early Aptian, Cretaceous)

    NASA Astrophysics Data System (ADS)

    Keller, Christina E.; Hochuli, Peter A.; Giorgioni, Martino; Garcia, Therese I.; Bernasconi, Stefano M.; Weissert, Helmut

    2010-05-01

    During Cretaceous times, several intense volcanic episodes are proposed as trigger for episodic climate warming, for changes in marine circulation patterns and for elevated marine productivity, which resulted in the widespread black shale deposits of the Oceanic Anoxic Events (OAE). In the sediments underlying the early Aptian OAE1a black shales, a prominent negative carbon isotope excursion is recorded. Its origin had long been controversial (e.g. Arthur, 2000; Jahren et al., 2001) before recent studies attributed it to the Ontong Java volcanism (Méhay et al., 2009; Tejada et al., 2009). Volcanic outgassing results in an increased pCO2 and should lead to a rise in global temperatures. We therefore investigated if the volcanically-induced increase in pCO2 at the onset of OAE1a in the early Aptian led to a temperature rise that was sufficient to affect terrestrial vegetation assemblages. In order to analyse changes in terrestrial palynomorph assemblages, we examined 15 samples from 12 black shale horizons throughout the early Aptian negative C-isotope spike interval of the Pusiano section (Maiolica Formation; N-Italy). These sediments were deposited at the southern continental margin of the alpine Tethys Ocean and have been bio- and magnetostratigraphically dated by Channell et al. (1995). In order to obtain a continuous palynological record of the negative C-isotope spike interval and the base of OAE1a, we combined this pre-OAE1a interval of Pusiano with the OAE1a interval of the nearby Cismon section (Hochuli et al., 1999). The sporomorph assemblages at the base of this composite succession feature abundant bisaccate pollen, which reflects a warm-temperate climate. Rather arid conditions are inferred from low trilete spore percentages. Several tens of thousand years before the onset of OAE1a, C-isotope values started to decrease. Some thousand years later, bisaccate pollen began to decrease, whereas an increase of Classopollis spp. and Araucariacites spp. percentages indicate a rise in temperatures. Maximum temperatures (suggested by a dominance of Classopollis spp.) were only reached after the most negative inorganic C-isotope values and after the onset of OAE1a. Our study shows that the volcanically-induced increase in pCO2, which ultimately led to OAE1a caused a substantial climate warming that seriously affected terrestrial vegetation. References: Arthur, M.A., 2000, Volcanic contributions to the carbon and sulfur geochemical cycles and global change, in Sigurdsson, H., Houghton, B., McNutt, S.R., Rymer, H., and Stix, J., eds., Encyclopedia of Volcanoes, Academic Press, p. 1045-1056. Channell, J.E.T., Cecca, F., and Erba, E., 1995, Correlations of Hauterivian and Barremian (Early Cretaceous) stage boundaries to polarity chrons: Earth and Planetary Science Letters, v. 134, p. 125-140. Hochuli, P.A., Menegatti, A.P., Weissert, H., Riva, A., Erba, E., and Silva, I.P., 1999, Episodes of high productivity and cooling in the early Aptian Alpine Tethys: Geology, v. 27, p. 657-660. Jahren, A.H., Arens, N.C., Sarmiento, G., Guerrero, J., and Amundson, R., 2001, Terrestrial record of methane hydrate dissociation in the Early Cretaceous: Geology, v. 29, p. 159-162. Méhay, S., Keller, C.E., Bernasconi, S.M., Weissert, H., Erba, E., Bottini, C., and Hochuli, P.A., 2009, A volcanic CO2 pulse triggered the Cretaceous Oceanic Anoxic Event 1a and a biocalcification crisis: Geology, v. 37, p. 819-822. Tejada, M.L.G., Suzuki, K., Junichiro, K., Rodolfo, C., J., M.J., Naohiko, O., Tatsuhiko, S., and Yoshiyuki, T., 2009, Ontong Java Plateau eruption as a trigger for the early Aptian oceanic anoxic event: Geology, v. 37, p. 855-858.

  17. Quorum Sensing Inhibition, Relevance to Periodontics

    PubMed Central

    Yada, Sudheer; Kamalesh, B; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored. PMID:25709373

  18. Potential for Stem Cell-Based Periodontal Therapy.

    PubMed

    Bassir, Seyed Hossein; Wisitrasameewong, Wichaya; Raanan, Justin; Ghaffarigarakani, Sasan; Chung, Jamie; Freire, Marcelo; Andrada, Luciano C; Intini, Giuseppe

    2016-01-01

    Periodontal diseases are highly prevalent and are linked to several systemic diseases. The goal of periodontal treatment is to halt the progression of the disease and regenerate the damaged tissue. However, achieving complete and functional periodontal regeneration is challenging because the periodontium is a complex apparatus composed of different tissues, including bone, cementum, and periodontal ligament. Stem cells may represent an effective therapeutic tool for periodontal regeneration due to their plasticity and their ability to regenerate different tissues. This review presents and critically analyzes the available information on stem cell-based therapy for the regeneration of periodontal tissues and suggests new avenues for the development of more effective therapeutic protocols. PMID:26058394

  19. Isolated cleft lip with generalized aggressive periodontitis: A rare entity

    PubMed Central

    Metgud, Renuka; Kumar, Ajay; Bhat, Kishore

    2015-01-01

    Oro-facial clefts are one of the most common birth defects and may be associated with other genetic anomalies. Aggressive periodontitis is a rare condition that progresses rapidly, but affects only a small percentage of the population. Most of the cases of aggressive periodontitis are familial. Even though, literature has documented the association of various genetic disorders with aggressive periodontitis, the aggressive periodontitis in patients with isolated cleft lip (CL) have never been addressed. Here, we report a rare case of isolated CL with generalized aggressive periodontitis. The concomitant presentation of isolated CL with aggressive periodontitis in an individual has clinical significance for multi-disciplinary care. PMID:25810600

  20. Enamel Pearls Implications on Periodontal Disease

    PubMed Central

    Zenóbio, Elton Gonçalves; Vieira, Thaís Ribeiral; Bustamante, Roberta Paula Colen; Gomes, Hayder Egg; Shibli, Jamil Awad; Soares, Rodrigo Villamarin

    2015-01-01

    Dental anatomy is quite complex and diverse factors must be taken into account in its analysis. Teeth with anatomical variations present an increase in the rate of severity periodontal tissue destruction and therefore a higher risk of developing periodontal disease. In this context, this paper reviews the literature regarding enamel pearls and their implications in the development of severe localized periodontal disease as well as in the prognosis of periodontal therapy. Radiographic examination of a patient complaining of pain in the right side of the mandible revealed the presence of a radiopaque structure around the cervical region of lower right first premolar. Periodontal examination revealed extensive bone loss since probing depths ranged from 7.0?mm to 9.0?mm and additionally intense bleeding and suppuration. Surgical exploration detected the presence of an enamel pearl, which was removed. Assessment of the remaining supporting tissues led to the extraction of tooth 44. Local factors such as enamel pearls can lead to inadequate removal of the subgingival biofilm, thus favoring the establishment and progression of periodontal diseases. PMID:26491574

  1. Generalized Aggressive Periodontitis and Its Treatment Options: Case Reports and Review of the Literature

    PubMed Central

    Roshna, T.; Nandakumar, K.

    2012-01-01

    Generalized aggressive periodontitis results in rapid destruction of the periodontium and can lead to early tooth loss in the affected individuals if not diagnosed early and treated appropriately. The diagnostic features of the disease are characteristic, but the clinical presentation and patterns of destructions may vary between patients. Successful management of the disease is challenging especially if diagnosed at advanced stages of the disease, but not impossible with the current therapeutic choices for the disease. A vast array of treatment modalities is available which can be employed in the treatment of generalized aggressive periodontitis with varying success rates, but a definite guideline for the management is yet to be formulated. However, with the exponential rate of developments in periodontal research, regenerative therapy, tissue engineering, and genetic technologies, the future seems promising in regard to options at managing the disease. This paper attempts to describe the clinical and radiographic diagnostic features and the current treatment options along with a suggested protocol for comprehensive management of generalized aggressive periodontitis patients with case reports and a brief review. PMID:22291715

  2. Proteomic profiling of host-biofilm interactions in an oral infection model resembling the periodontal pocket

    PubMed Central

    Bao, Kai; Belibasakis, Georgios N.; Selevsek, Nathalie; Grossmann, Jonas; Bostanci, Nagihan

    2015-01-01

    Periodontal infections cause inflammatory destruction of the tooth supporting tissues. We recently developed a dynamic, in vitro periodontal organotypic tissue model in a perfusion bioreactor system, in co-culture with an 11-species subgingival biofilm, which may recapitulate early events during the establishment of periodontal infections. This study aimed to characterize the global proteome regulations in this host-biofilm interaction model. Semi-quantitative shotgun proteomics were applied for protein identification and quantification in the co-culture supernatants (human and bacterial) and the biofilm lysates (bacterial). A total of 896 and 3363 proteins were identified as secreted in the supernatant and expressed in the biofilm lysate, respectively. Enriched gene ontology analysis revealed that the regulated secreted human tissue proteins were related to processes of cytoskeletal rearrangement, stress responses, apoptosis, and antigen presentation, all of which are commensurate with deregulated host responses. Most secreted bacterial biofilm proteins derived from their cytoplasmic domain. In the presence of the tissue, the levels of Fusobacterium nucleatum, Actinomyces oris and Campylobacter rectus proteins were significantly regulated. The functions of the up-regulated intracellular (biofilm lysate) proteins were associated with cytokinesis. In conclusion, the proteomic overview of regulated pathways in this host-biofilm interaction model provides insights to the early events of periodontal pathogenesis. PMID:26525412

  3. Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood

    PubMed Central

    Breivik, Torbjørn; Gundersen, Yngvar; Murison, Robert; Turner, Jonathan D; Muller, Claude P; Gjermo, Per; Opstad, Kristian

    2015-01-01

    Background and Objective: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Material and Methods: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Results: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1? in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Conclusion: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis. PMID:25713634

  4. Detection and diagnosis of periodontal conditions amenable to prevention

    PubMed Central

    2015-01-01

    Gingivitis and chronic periodontitis are highly prevalent chronic inflammatory diseases. Gingivitis affects the majority of people, and advanced periodontitis is estimated to affect 5-15% of adults. The detection and diagnosis of these common diseases is a fundamentally important component of oral health care. All patients should undergo periodontal assessment as part of routine oral examination. Periodontal screening using methods such as the Basic Periodontal Examination/Community Periodontal Index or Periodontal Screening Record should be performed for all new patients, and also on a regular basis as part of ongoing oral health care. If periodontitis is identified, full periodontal assessment is required, involving recording of full mouth probing and bleeding data, together with assessment of other relevant parameters such as plaque levels, furcation involvement, recession and tooth mobility. Radiographic assessment of alveolar bone levels is driven by the clinical situation, and is required to assess bone destruction in patients with periodontitis. Risk assessment (such as assessing diabetes status and smoking) and risk management (such as promoting smoking cessation) should form a central component of periodontal therapy. This article provides guidance to the oral health care team regarding methods and frequencies of appropriate clinical and radiographic examinations to assess periodontal status, to enable appropriate detection and diagnosis of periodontal conditions. PMID:26390822

  5. A Novel Splice-Site Mutation in ALS2 Establishes the Diagnosis of Juvenile Amyotrophic Lateral Sclerosis in a Family with Early Onset Anarthria and Generalized Dystonias

    PubMed Central

    Vu, Anthony; Azim, Saad; Silver, David L.; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E. Shyong; Yeo, Gene W.; Khor, Chiea Chuen

    2014-01-01

    The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes. PMID:25474699

  6. The onset of the Early Eocene Climatic Optimum, including the K/X event, at Branch Stream, Clarence Valley, New Zealand

    NASA Astrophysics Data System (ADS)

    Slotnick, B. S.; Dickens, G. R.; Hollis, C. J.; Crampton, J. S.; Strong, P.; Dallanave, E.; Philips, A.

    2014-12-01

    The Early Eocene Climatic Optimum (EECO), lasting from ~53-50 Ma, has been characterized as the warmest sustained interval through the Cenozoic. It was comprised of a broad temperature maximum with elevated atmospheric pCO2, noticeable shifts in carbon cycling, and a variety of faunal and floral changes. This included one, and likely additional, brief (<200 kyr) intervals of extreme warming, the K/X event. At least for the most prominent events, the long-term drop in ?13C and short-term Carbon Isotope Excursions (CIEs) have been coupled to massive fluxes of 13C-depleted carbon into the exogenic system and global climate change. However, much about EECO remains unknown because of a lack of detailed and coupled proxy records; we are currently generating useful records to better characterize lithological and geochemical signatures of EECO. Here, we help rectify this problem by presenting a new lithologic and carbon isotopic record for a ~84-m-thick section of early Eocene upper slope calcareous-rich sediments, now lithified and exposed along Branch Stream, New Zealand. Comparison of new carbon isotopic and lithologic records of this greatly expanded section to nearby Mead Stream identifies multiple negative CIEs in short succession and generally more marl during lowermost EECO (~53.3-51.7 Ma), with the most prominent of these equating to the K/X event. The early Eocene lithologic and ?13C records at Branch and Mead Streams are remarkably similar to each other, with the following distinctions: sequences at Branch Stream are thicker and generally have a wider range of ?13C across CIEs. Both expanded sections are marked by terrigenous dilution, best explained by enhanced seasonal precipitation, elevated greenhouse-gas concentrations, and likely global warming. These data indicate lowermost EECO can be described as a time with a general ?13C low superimposed by a series of short-term climate perturbations.

  7. Toward a Clinical Definition of Early Osteoarthritis: Onset of Patient-Reported Knee Pain Begins on Stairs. Data From the Osteoarthritis Initiative

    PubMed Central

    Hensor, Elizabeth M A; Dube, Bright; Kingsbury, Sarah R; Tennant, Alan; Conaghan, Philip G

    2015-01-01

    Objective Early detection of osteoarthritis (OA) would increase the chances of effective intervention. We aimed to investigate which patient-reported activity is first associated with knee pain. We hypothesized that pain would occur first during activities requiring weight bearing and knee bending. Methods Data were obtained from the Osteoarthritis Initiative (OAI), a multicenter, longitudinal prospective observational cohort of people who have or are at high risk of OA. Participants completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; Likert scale) annually for up to 7 years. Rasch analysis was used to rank the WOMAC pain questions (activities) in order of affirmation as the pain score increased from 0. For each total WOMAC score category (0–20) we selected 25 individuals at random based on their maximum score across all visits. Fit to the Rasch model was assessed in this subset; stability of question ranking over successive visits was confirmed in the full OAI. Results WOMAC data on 4,673 people were included, with 491 selected for subset analysis. The subset data showed good fit to the Rasch model (?2 = 43.31, P = 0.332). In the full OAI, the “using stairs” question was the first to score points as the total pain score increased from 0 (baseline logit score ± 95% confidence interval ?4.74 ± 0.07), then “walking” (?2.94 ± 0.07), “standing” (?2.65 ± 0.07), “lying/sitting” (?2.00 ± 0.08), and finally “in bed” (?1.32 ± 0.09). This ordering was consistent over successive visits. Conclusion Knee pain is most likely to first appear during weight-bearing activities involving bending of the knee, such as using stairs. First appearance of this symptom may identify a group suitable for early intervention strategies. PMID:25074673

  8. Mixed Red-Complex Bacterial Infection in Periodontitis

    PubMed Central

    Suzuki, N.; Yoneda, M.; Hirofuji, T.

    2013-01-01

    The red complex, which includes Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia (formerly Bacteroides forsythus), are recognized as the most important pathogens in adult periodontal disease. These bacteria are usually found together in periodontal pockets, suggesting that they may cause destruction of the periodontal tissue in a cooperative manner. This article discusses the interspecies pathogenic interactions within the red complex. PMID:23533413

  9. INTERLEUKIN-6 GENE POLYMORPHISM MODULATES THE RISK OF PERIODONTAL DISEASES.

    PubMed

    Scapoli, L; Girardi, A; Palmieri, A; Martinelli, M; Cura, F; Lauritano, D; Pezzetti, F; Carinci, F

    2015-01-01

    Gingivitis and periodontitis are the two main periodontal diseases. Both are characterized by inflammation of the tissues surrounding the teeth but while tissue damages observed in gingivitis are mild and reversible, destruction caused by periodontitis is deeper and irreversible. Periodontal diseases and levels of degeneration of tissues surrounding teeth depend on several interacting endogenous and exogenous factors. Polymorphisms of genes encoding molecules that modulate the immune response and tissue homeostasis are the main causes of individual susceptibility to periodontal diseases. The aim of this study was to investigate IL6, IL10 and VDR gene polymorphisms in a large number of subjects affected by either gingivitis or chronic periodontitis. The sample included 750 Italian patients. We found that the rs1800795 SNP located in the IL6 gene promoter was strongly associated with the occurrence of both gingivitis and periodontitis. Indeed, homozygous individuals with variant allele appeared less-susceptible to both gingivitis OR=0.47 (95% C.I. 0.27-0.82) and periodontitis OR=0.36 (95% C.I. 0.21-0.64). No evidence of association between periodontal diseases and IL10 or VDR polymorphisms was obtained. This data confirmed the role of IL6 in susceptibility to periodontitis among the Italian population. The evidence that IL6 polymorphisms are also involved in gingivitis has implications in periodontal disease pathogenesis and reduces the appeal of IL6 as a periodontitis biomarker. PMID:26511189

  10. The role of adipokines in periodontal infection and healing.

    PubMed

    Deschner, J; Eick, S; Damanaki, A; Nokhbehsaim, M

    2014-12-01

    Periodontitis is a chronic inflammatory disease of the periodontium, which is caused by pathogenic bacteria in combination with other risk factors. The bacteria induce an immunoinflammatory host response, which can lead to irreversible matrix degradation and bone resorption. Periodontitis can be successfully treated. To achieve regenerative periodontal healing, bioactive molecules, such as enamel matrix derivative (EMD), are applied during periodontal surgery. Recently, it has been shown that obesity is associated with periodontitis and compromised healing after periodontal therapy. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic link. Adipokines are bioactive molecules that are secreted by the adipose tissue, and that regulate insulin sensitivity and energy expenditure, but also inflammatory and healing processes. It has also been demonstrated that visfatin and leptin increase the synthesis of proinflammatory and proteolytic molecules, whereas adiponectin downregulates the production of such mediators in periodontal cells. In addition, visfatin and leptin counteract the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on periodontal cells. Since visfatin and leptin levels are increased and adiponectin levels are reduced in obesity, these adipokines could be a pathomechanistic link whereby obesity and obesity-related diseases enhance the risk for periodontitis and compromised periodontal healing. Recent studies have also revealed that adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on systemic diseases. PMID:25052571

  11. Diagnostic Accuracy of CBCT for Aggressive Periodontitis.

    PubMed

    Mohan, Ranjana; Mark, Ruhi; Sing, Ipsa; Jain, Ankita

    2014-01-01

    Cone beam computed tomography (CBCT) is an indispensable diagnostic imaging tool for dento-alveolar examination. CBCT scanning has become a valuable imaging modality in the field of Periodontology for the detection of very small osseous defects. A patient reported to the department of Periodontology with a complaint of loose teeth. Clinical and direct digital radiographic (DDR) examination revealed advanced periodontal destruction, but failed to diagnose the morphology of generalized osseous defects, around all the surfaces of each tooth. CBCT images were obtained for detailed examination of each and every osseous defect around all the teeth. Patient was then diagnosed with generalized aggressive periodontitis. Flap surgery was performed in order to eliminate the periodontal pockets, exposing and degranulating the osseous defects. Actual measurements of surgically exposed osseous defects were compared with that seen in CBCT images and found to be exactly identical. CBCT has proved to be as accurate in measuring osseous defects as direct measurements with a periodontal probe. Buccal and lingual periodontal defects that could not be diagnosed by conventional radiography can be identified with CBCT. PMID:25191628

  12. Treatment modalities and evaluation models for periodontitis.

    PubMed

    Tariq, Mohammad; Iqbal, Zeenat; Ali, Javed; Baboota, Sanjula; Talegaonkar, Sushama; Ahmad, Zulfiqar; Sahni, Jasjeet K

    2012-07-01

    Periodontitis is the most common localized dental inflammatory disease related with several pathological conditions like inflammation of gums (gingivitis), degeneration of periodontal ligament, dental cementum and alveolar bone loss. In this perspective, the various preventive and treatment modalities, including oral hygiene, gingival irrigations, mechanical instrumentation, full mouth disinfection, host modulation and antimicrobial therapy, which are used either as adjunctive treatments or as stand-alone therapies in the non-surgical management of periodontal infections, have been discussed. Intra-pocket, sustained release systems have emerged as a novel paradigm for the future research. In this article, special consideration is given to different locally delivered anti-microbial and anti inflammatory medications which are either commercially available or are currently under consideration for Food and Drug Administration (FDA) approval. The various in vitro dissolution models and microbiological strain investigated to impersonate the infected and inflamed periodontal cavity and to predict the in vivo performance of treatment modalities have also been thrashed out. Animal models that have been employed to explore the pathology at the different stages of periodontitis and to evaluate its treatment modalities are enlightened in this proposed review. PMID:23373002

  13. Spatiotemporally Controlled Microchannels of Periodontal Mimic Scaffolds

    PubMed Central

    Park, C.H.; Kim, K.H.; Rios, H.F.; Lee, Y.M.; Giannobile, W.V.; Seol, Y.J.

    2014-01-01

    Physiologic bioengineering of the oral, dental, and craniofacial complex requires optimized geometric organizations of fibrous connective tissues. A computer-designed, fiber-guiding scaffold has been developed to promote tooth-supporting periodontal tissue regeneration and functional restoration despite limited printing resolution for the manufacture of submicron-scaled features. Here, we demonstrate the use of directional freeze-casting techniques to control pore directional angulations and create mimicked topographies to alveolar crest, horizontal, oblique, and apical fibers of natural periodontal ligaments. For the differing anatomic positions, the gelatin displayed varying patterns of ice growth, determined via internal pore architectures. Regardless of the freezing coordinates, the longitudinal pore arrangements resulted in submicron-scaled diameters (~50 µm), along with corresponding high biomaterial porosity (~90%). Furthermore, the horizontal + coronal ((x??y?) freezing orientation facilitated the creation of similar structures to major fibers in the periodontal ligament interface. This periodontal tissue-mimicking microenvironment is a potential tissue platform for the generation of naturally oriented ligamentous tissues consistent with periodontal ligament neogenesis. PMID:25216511

  14. Treatment modalities and evaluation models for periodontitis

    PubMed Central

    Tariq, Mohammad; Iqbal, Zeenat; Ali, Javed; Baboota, Sanjula; Talegaonkar, Sushama; Ahmad, Zulfiqar; Sahni, Jasjeet K

    2012-01-01

    Periodontitis is the most common localized dental inflammatory disease related with several pathological conditions like inflammation of gums (gingivitis), degeneration of periodontal ligament, dental cementum and alveolar bone loss. In this perspective, the various preventive and treatment modalities, including oral hygiene, gingival irrigations, mechanical instrumentation, full mouth disinfection, host modulation and antimicrobial therapy, which are used either as adjunctive treatments or as stand-alone therapies in the non-surgical management of periodontal infections, have been discussed. Intra-pocket, sustained release systems have emerged as a novel paradigm for the future research. In this article, special consideration is given to different locally delivered anti-microbial and anti inflammatory medications which are either commercially available or are currently under consideration for Food and Drug Administration (FDA) approval. The various in vitro dissolution models and microbiological strain investigated to impersonate the infected and inflamed periodontal cavity and to predict the in vivo performance of treatment modalities have also been thrashed out. Animal models that have been employed to explore the pathology at the different stages of periodontitis and to evaluate its treatment modalities are enlightened in this proposed review. PMID:23373002

  15. Rheumatoid Arthritis and Periodontal Disease. An Update.

    PubMed

    Venkataraman, Archana; Almas, Khalid

    2015-01-01

    A review of the epidemiological, pathological and immunological relationships between two chronic inflammatory diseases: rheumatoid arthritis (RA) and periodontal disease (PD). RA is a chronic inflammatory disease of the joints, characterized by loss of connective tissue and mineralized structures, the so-called "synovial membrane." Periodontitis is the inflammatory destruction of the periodontal attachment and alveolar bone. While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are similar. And it is possible that individuals manifesting both PD and RA may suffer from a unifying underlying systemic deregulation of the inflammatory response. There is an overproduction of a variety of cytokines and MMPs that appears to be common in both diseases. Oral health parameters should be more closely monitored in patients with RA, an autoimmune disease. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Interventions to prevent, minimize or treat periodontitis in arthritis patients will definitely promise a better quality of life for these patients. PMID:26521325

  16. Non-Surgical Chemotherapeutic Treatment Strategies for the Management of Periodontal Diseases

    PubMed Central

    Krayer, Joe W.; Leite, Renata S.; Kirkwood, Keith L.

    2011-01-01

    Synopsis Periodontal diseases are initiated by subgingival periodontal pathogens in susceptible periodontal sites. The host immune response towards periodontal pathogens helps to sustain periodontal disease and eventual alveolar bone loss. Numerous adjunctive therapeutic strategies have evolved to manage periodontal diseases. Systemic and local antibiotics, antiseptics, and past and future host immune modulatory agents are reviewed and discussed to facilitate the dental practitioner’s appreciation of this ever-growing field in clinical periodontics. PMID:20103470

  17. Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.

    PubMed

    Taylor, Adam; Sheng, Kuo-Ching; Herrero, Lara J; Chen, Weiqiang; Rulli, Nestor E; Mahalingam, Suresh

    2013-01-01

    Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) and Ross River virus (RRV), are able to cause significant inflammatory pathologies ranging from arthritis to encephalitis. Following symptomatic infection with arthritis-associated alphaviruses, patients often experience severe joint pain, affecting distal and small joints, which can last six months or longer. Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug (DMARD), was used to treat patients experiencing chronic rheumatic symptoms following infection with CHIKV. Here, the effect of MTX on Ross River virus disease (RRVD) in mice was examined to better understand its therapeutic potential for alphaviral-induced musculoskeletal disease and to further our knowledge of the development of alphaviral pathologies. Using a mouse model, we analyzed the effect of MTX on RRVD. RRV disease pathogenesis in response to MTX treatment was determined by measuring levels of proinflammatory factors, cellular infiltrates, viral titer and histological analysis of infected tissues. RRV-infected mice receiving MTX treatment rapidly developed musculoskeletal disease, which correlated with a significant influx of inflammatory cell infiltrates into the skeletal muscle tissue. Although no difference was observed in the level of proinflammatory cytokines and chemokines, the viral load increased at early time points post infection in the serum and quadriceps of MTX treated mice, possibly contributing to disease pathogenesis. Results suggest that MTX treatment of acute RRVD in mice provides no therapeutic benefit and underline the importance of inflammatory monocytes in alphaviral induced arthritides. PMID:23951095

  18. Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

    PubMed Central

    Cag, Yasemin; Ozturk-Engin, Derya; Defres, Sylviane; Kaya, Selcuk; Larsen, Lykke; Poljak, Mario; Barsic, Bruno; Argemi, Xavier; Sørensen, Signe Maj; Bohr, Anne Lisbeth; Tattevin, Pierre; Gunst, Jesper Damsgaard; Baštáková, Lenka; Jereb, Matjaž; Johansen, Isik Somuncu; Karabay, Oguz; Pekok, Abdullah Umut; Sipahi, Oguz Resat; Chehri, Mahtab; Beraud, Guillaume; Shehata, Ghaydaa; Del Vecchio, Rosa Fontana; Maresca, Mauro; Karsen, Hasan; Sengoz, Gonul; Sunbul, Mustafa; Yilmaz, Gulden; Yilmaz, Hava; Sharif-Yakan, Ahmad; Kanj, Souha Shararah; Parlak, Emine; Pehlivanoglu, Filiz; Korkmaz, Fatime; Komur, Suheyla; Kose, Sukran; Ulug, Mehmet; Bolukcu, Sibel; Coskuner, Seher Ayten; Ince, Nevin; Akkoyunlu, Yasemin; Halac, Gulistan; Sahin-Horasan, Elif; Tireli, Hulya; Kilicoglu, Gamze; Al-Mahdawi, Akram; Nemli, Salih Atakan; Inan, Asuman; Senbayrak, Seniha; Stahl, Jean Paul; Vahaboglu, Haluk

    2015-01-01

    Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome. PMID:25779579

  19. Disruption of hypothalamic leptin signaling in mice leads to early-onset obesity, but physiological adaptations in mature animals stabilize adiposity levels

    PubMed Central

    Ring, Laurence E.; Zeltser, Lori M.

    2010-01-01

    Distinct populations of leptin-sensing neurons in the hypothalamus, midbrain, and brainstem contribute to the regulation of energy homeostasis. To assess the requirement for leptin signaling in the hypothalamus, we crossed mice with a floxed leptin receptor allele (Leprfl) to mice transgenic for Nkx2.1-Cre, which drives Cre expression in the hypothalamus and not in more caudal brain regions, generating LeprNkx2.1KO mice. From weaning, LeprNkx2.1KO mice exhibited phenotypes similar to those observed in mice with global loss of leptin signaling (Leprdb/db mice), including increased weight gain and adiposity, hyperphagia, cold intolerance, and insulin resistance. However, after 8 weeks of age, LeprNkx2.1KO mice maintained stable adiposity levels, whereas the body fat percentage of Leprdb/db animals continued to escalate. The divergence in the adiposity phenotypes of Leprdb/db and LeprNkx2.1KO mice with age was concomitant with increased rates of linear growth and energy expenditure in LeprNkx2.1KO mice. These data suggest that remaining leptin signals in LeprNkx2.1KO mice mediate physiological adaptations that prevent the escalation of the adiposity phenotype in adult mice. The persistence of severe adiposity in LeprNkx2.1KO mice, however, suggests that compensatory actions of circuits regulating growth and energy expenditure are not sufficient to reverse obesity established at an early age. PMID:20592471

  20. Periodontal Diseases and Dental Caries in Children with Type 1 Diabetes Mellitus

    PubMed Central

    Novotna, Marta; Podzimek, Stepan; Broukal, Zdenek; Lencova, Erika; Duskova, Jana

    2015-01-01

    Type 1 diabetes mellitus is a chronic metabolic disease of an autoimmune origin with early manifestation predominantly in the childhood. Its incidence has been rising in most European countries. Diabetes has been intensively studied by all branches of medicine. There were a number of studies investigating oral consequences of diabetes; however, unambiguous conclusions were drawn only for the relationship between diabetes and periodontal impairment. Many studies confirmed higher plaque levels and higher incidence of chronic gingivitis both in adults and in children with diabetes. Juvenile periodontitis is rare both in healthy subjects and in those with type 1 diabetes. Yet certain findings from well-conducted studies, for example, differences in oral microflora or the impact of metabolic control of diabetes on periodontal health, indicate a higher risk of periodontitis in children with type 1 diabetes. As for the association of diabetes and dental caries, the results of the studies are inconsistent. However, it was found that some risk factors for dental caries are either more or less prevalent in the diabetic population. Despite an extensive research in this area we have to acknowledge that many questions have remained unanswered. There is a need for continued, thorough research in this area. PMID:26347009

  1. Pathogenicity of the highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans and its geographic dissemination and role in aggressive periodontitis

    PubMed Central

    Haubek, Dorte; Johansson, Anders

    2014-01-01

    For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA) and cytolethal distending toxin (Cdt). LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are colonized with the JP2 clone, are likely to share this clone with several family members because the clone is transmitted through close contacts. This is a challenge to the clinicians. The patients need intense monitoring of their periodontal status as the risk for developing severely progressing periodontal lesions are relatively high. Furthermore, timely periodontal treatment, in some cases including periodontal surgery supplemented by the use of antibiotics, is warranted. Preferably, periodontal attachment loss should be prevented by early detection of the JP2 clone of A. actinomycetemcomitans by microbial diagnostic testing and/or by preventive means. PMID:25206940

  2. A colitis locus on chromosome 2 impacting the severity of early-onset disease in mice deficient in GPX1 and GPX2

    PubMed Central

    Esworthy, R. Steven; Kim, Byung-Wook; Larson, Garrett P.; Yip, M.L. Richard; Smith, David D.; Li, Min; Chu, Fong-Fong

    2012-01-01

    Background Genetic background has a profound effect on inflammatory bowel disease. The Gpx1 and Gpx2 double knockout (GPX1/2-DKO) mice on a mixed C57BL/6 (B6) and 129S1/SvimJ (129) background had spontaneous ileocolitis. The DKO mice on a B6 background had mild ileocolitis. We characterized the 129 DKO mice to identify a genetic locus affecting disease severity. Methods We backcrossed B6;129 DKO mice to 129 and analyzed for ileocolitis penetrance and severity at N5, N7 and N10. By correlating disease severity with single-nucleotide polymorphism (SNP) markers, we identified a colitis locus. Results As early as 9 days of age, 129 DKO N5 and N10 mice showed disease signs and morbidity. The N10 DKO mice had the severest colitis with nearly complete penetrance and high morbidity compared with other generations or backgrounds. 129 DKO mice had elevated colonic KC and SAA3 expression, shorter colon length, and cecal E. coli overgrowth compared to B6 DKO mice. Analysis of the B6 loci in 129 N5, N7 and N10 cohorts pointed to a region of chromosome 2: 119 Mbp contributing to mild symptoms. Conclusions GPX1/2-DKO mice on 129 genetic background have the most aggressive colitis compared to B6;129 and B6 colonies. A B6 locus significantly contributing the resistance resides on chromosome 2: 119 Mbp. This region coincides with cytokine-deficiency-induced-colitis-susceptibility, Cdcs3, identified in the resistant B6 and sensitive C3H/HeJBir (C3Bir) with IL-10 deficiency. A three-way SNP analysis between 129, B6 and C3Bir locus points the major candidate genes to B2m, Dnajc17, Duox2, Pla2g4b, Pla2g4e, Pla2g4f and Slc30a4. PMID:20872835

  3. Psidium guajava Linn. leaf extract affects hepatic glucose transporter-2 to attenuate early onset of insulin resistance consequent to high fructose intake: An experimental study

    PubMed Central

    Mathur, R.; Dutta, Shagun; Velpandian, T.; Mathur, S.R.

    2015-01-01

    Background: Insulin resistance (IR) is amalgam of pathologies like altered glucos metabolism, dyslipidemia, impaired glucose tolerance, non-alcoholic fatty liver disease, and associated with type-II diabetes and cardiometabolic diseases. One of the reasons leading to its increased and early incidence is understood to be a high intake of processed fructose containing foods and beverages by individuals, especially, during critical developmental years. Objective: To investigate the preventive potential of aqueous extract of Psidium guajava leaves (PG) against metabolic pathologies, vis-à-vis, IR, dyslipidemia, hyperleptinemia and hypertension, due to excess fructose intake initiated during developmental years. Materials and Methods: Post-weaning (4 weeks old) male rats were provided fructose (15%) as drinking solution, ad libitum, for 8 weeks and assessed for food and water/fructose intake, body weight, fasting blood sugar, mean arterial pressure, lipid biochemistry, endocrinal (insulin, leptin), histopathological (fatty liver) and immunohistochemical (hepatic glucose transporter [GLUT2]) parameters. Parallel treatment groups were administered PG in doses of 250 and 500 mg/kg/d, po × 8 weeks and assessed for same parameters. Using extensive liquid chromatography-mass spectrometry protocols, PG was analyzed for the presence of phytoconstituents like Myrecetin, Luteolin, Kaempferol and Guavanoic acid and validated to contain Quercetin up to 9.9%w/w. Results: High fructose intake raised circulating levels of insulin and leptin and hepatic GLUT2 expression to promote IR, dyslipidemia, and hypertension that were favorably re-set with PG. Although PG is known for its beneficial role in diabetes mellitus, for the first time we report its potential in the management of lifelong pathologies arising from high fructose intake initiated during developmental years. PMID:25829790

  4. Probiotics in periodontal health and disease

    PubMed Central

    Chatterjee, Anirban; Bhattacharya, Hirak; Kandwal, Abhishek

    2011-01-01

    Macfarlane Burnett stated in 1962 that “By the late twentieth century, we can anticipate the virtual elimination of infectious diseases as a significant factor in social life”. Probiotics have become of interest to researchers in recent times. Time has come to shift the paradigm of treatment from specific bacteria elimination to altering bacterial ecology by probiotics. The development of resistance to a range of antibiotics by some important pathogens has raised the possibility of a return to the pre-antibiotic dark ages. Here, probiotics provide an effective alternative way, which is economical and natural to combat periodontal disease. Thus, a mere change in diet by including probiotic foods may halt, retard, or even significantly delay the pathogenesis of periodontal diseases, promoting a healthy lifestyle to fight periodontal infections. PMID:21772717

  5. Application of ozone in the treatment of periodontal disease

    PubMed Central

    Srikanth, Adusumilli; Sathish, Manthena; Sri Harsha, Anumolu Venkatanaga

    2013-01-01

    Gingivitis and periodontitis are most common inflammatory diseases of supporting tissues of teeth. Role of microbial etiology and host response in progression of gingival and periodontal diseases has been well established. Because of the beneficial biological effects of ozone, due to its antimicrobial and immunostimulating effect, it is well indicated in the treatment of gingival and periodontal diseases. The objective of this article is to provide a general review about clinical applications of ozone in treatment of periodontal diseases and to summarize the available in vitro and in vivo studies in Periodontics in which ozone has been used. PMID:23946585

  6. Iatrogenic Damage to the Periodontium Caused by Periodontal Treatment Procedures

    PubMed Central

    Latheef, P; Sirajuddin, Syed; Gundapaneni, Veenadharini; MN, Kumuda; Apine, Ashwini

    2015-01-01

    Periodontitis is an inflammatory disease affecting the periodontium i.e. the tissues that surround and support the teeth. Periodontitis manifests as progressive loss of the alveolar bone around the teeth, and if left untreated, can cause loosening and subsequent loss of teeth. Periodontitis is initiated by microorganisms that adhere to and grow on the tooth's surfaces, besides an over -aggressive immune response against these microorganisms. The primary goal of periodontal therapy is to preserve the natural dentition by accomplishing and preserving a healthy functional periodontium. Many treatment modalities have been introduced to improve the therapeutic result of periodontal treatment which may also damage the periodontiumiatrogenically. PMID:26312087

  7. Genetic influences in caries and periodontal diseases.

    PubMed

    Hassell, T M; Harris, E L

    1995-01-01

    Deciphering the relative roles of heredity and environmental factors ("nature vs. nurture") in the pathogenesis of dental caries and diseases of the periodontium has occupied clinical and basic researchers for decades. Success in the endeavor has come more easily in the case of caries; the complex interactions that occur between host-response mechanisms and putative microbiologic pathogens in periodontal disease have made elucidation of genetic factors in disease susceptibility more difficult. In addition, during the 30-year period between 1958 and 1987, only meager resources were targeted toward the "nature" side of the nature/nurture dipole in periodontology. In this article, we present a brief history of the development of genetic epistemology, then describe the three main research mechanisms by which questions about the hereditary component of diseases in humans can be addressed. A critical discussion of the evidence for a hereditary component in caries susceptibility is next presented, also from a historical perspective. The evolution of knowledge concerning possible genetic ("endogenous", "idiotypic") factors in the pathogenesis of inflammatory periodontal disease is initiated with an analysis of some foreign-language (primarily German) literature that is likely to be unfamiliar to the reader. We identify a turning point at about 1960, when the periodontal research community turned away from genetics in favor of microbiology research. During the past five years, investigators have re-initiated the search for the hereditary component in susceptibility to common adult periodontal disease; this small but growing body of literature is reviewed. Recent applications of in vitro methods for genetic analyses in periodontal research are presented, with an eye toward a future in which persons who are at risk--genetically predisposed--to periodontal disease may be identified and targeted for interventive strategies. Critical is the realization that genes and environment do not act independently of each other; the appearance or magnitude of heritability may differ with various environments. PMID:8664422

  8. Host response mechanisms in periodontal diseases

    PubMed Central

    SILVA, Nora; ABUSLEME, Loreto; BRAVO, Denisse; DUTZAN, Nicolás; GARCIA-SESNICH, Jocelyn; VERNAL, Rolando; HERNÁNDEZ, Marcela; GAMONAL, Jorge

    2015-01-01

    Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts (OCLs). This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as a stage that presents a significantly host immune and inflammatory response to the microbial challenge that determine of susceptibility to develop the destructive/progressive periodontitis under the influence of multiple behavioral, environmental and genetic factors. PMID:26221929

  9. MC1R genotype as a predictor of early-onset melanoma, compared with self-reported and physician-measured traditional risk factors: an Australian case-control-family study

    PubMed Central

    2013-01-01

    Background Melanocortin-1 receptor (MC1R) gene variants are very common and are associated with melanoma risk, but their contribution to melanoma risk prediction compared with traditional risk factors is unknown. We aimed to 1) evaluate the separate and incremental contribution of MC1R genotype to prediction of early-onset melanoma, and compare this with the contributions of physician-measured and self-reported traditional risk factors, and 2) develop risk prediction models that include MC1R, and externally validate these models using an independent dataset from a genetically similar melanoma population. Methods Using data from an Australian population-based, case-control-family study, we included 413 case and 263 control participants with sequenced MC1R genotype, clinical skin examination and detailed questionnaire. We used unconditional logistic regression to estimate predicted probabilities of melanoma. Results were externally validated using data from a similar study in England. Results When added to a base multivariate model containing only demographic factors, MC1R genotype improved the area under the receiver operating characteristic curve (AUC) by 6% (from 0.67 to 0.73; P?early-onset melanoma than was pigmentation characteristics. Physician-measured nevi and previous non-melanoma skin cancer were also strong predictors. There might be modest benefit to measuring MC1R genotype for risk prediction even if information about traditional self-reported or clinically measured pigmentation characteristics and nevi is already available. PMID:24134749

  10. Evaluation of genetic variations in miRNA-binding sites of BRCA1 and BRCA2 genes as risk factors for the development of early-onset and/or familial breast cancer.

    PubMed

    Erturk, Elif; Cecener, Gulsah; Polatkan, Volkan; Gokgoz, Sehsuvar; Egeli, Unal; Tunca, Berrin; Tezcan, Gulcin; Demirdogen, Elif; Ak, Secil; Tasdelen, Ismet

    2014-01-01

    Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intron- exon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3'UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/ BRCA2 and to identify specific 3'UTR variants that may be risk factors for cancer development. The 3'UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs c.*1287C>T (rs12516) (BRCA1) and c.*105A>C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3'UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism c.*1287C>T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP c.*1287C>T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population. PMID:25339023

  11. New anesthetic technique in