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Sample records for early onset progressive

  1. Early-onset childhood vitiligo is associated with a more extensive and progressive course.

    Science.gov (United States)

    Mu, Euphemia W; Cohen, Brandon E; Orlow, Seth J

    2015-09-01

    Vitiligo commonly presents in children, with half of all cases developing before 20 years of age. Although studies have characterized differences between pediatric and adult vitiligo, little is known about vitiligo presenting in early childhood. The purpose of this study was to compare clinical features of early-onset (vitiligo. This retrospective case series examined patients given a diagnosis of vitiligo in a pediatric dermatology practice at an academic medical center from 1990 to 2014. Characteristics of the early- and later-onset groups were compared by χ(2) and t test for categorical and continuous variables, respectively. Of the 208 children in the study, 31 had early-onset and 177 had later-onset disease. Early-onset vitiligo was associated with higher percentages of body surface area involvement and increased rates of disease progression during an average 1.9 years of follow-up. There were no significant differences between the 2 groups in repigmentation, vitiligo type, halo nevi, gender ratio, or personal and family history of autoimmune diseases. This was a retrospective, single-institution study. Patients given a diagnosis of vitiligo at younger ages tend to have more extensive and progressive disease. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Early onset cannabis use and progression to other drug use in a sample of Dutch twins

    NARCIS (Netherlands)

    Lynskey, M.T.; Vink, J.M.; Boomsma, D.I.

    2006-01-01

    One possible explanation of the commonly reported associations between early onset cannabis use and elevated risks of other illicit drug use is that early onset cannabis use increases access and availability to other drugs. It was this argument that in part motivated policy changes in the

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Identification of probable early-onset biomarkers for tuberculosis disease progression.

    Directory of Open Access Journals (Sweden)

    Jayne S Sutherland

    Full Text Available Determining what constitutes protective immunity to TB is critical for the development of improved diagnostics and vaccines. The comparison of the immune system between contacts of TB patients, who later develop TB disease (progressors, versus contacts who remain healthy (non-progressors, allows for identification of predictive markers of TB disease. This study provides the first comprehensive analysis of the immune system of progressors and non-progressors using a well-characterised TB case-contact (TBCC platform in The Gambia, West Africa. 22 progressors and 31 non-progressors were analysed at recruitment, 3 months and 18 months (time to progression: median[IQR] of 507[187-714] days. Immunophenotyping of PBMC, plasma cytokine levels and RT-MLPA analysis of whole blood-derived RNA was performed to capture key immune system parameters. At recruitment, progressors had lower PBMC proportions of CD4+ T cells, NKT cells and B cells relative to non-progressors. Analysis of the plasma showed higher levels of IL-18 in progressors compared to non-progressors and analysis of the RNA showed significantly lower gene expression of Bcl2 but higher CCR7 in progressors compared to non-progressors. This study shows several markers that may predict the onset of active TB at a very early stage after infection. Once these markers have been validated in larger studies, they provide avenues to prospectively identify people at risk of developing TB, a key issue in the testing of new TB vaccines.

  5. Serial Derotational Casting in Idiopathic and Non-Idiopathic Progressive Early-Onset Scoliosis.

    Science.gov (United States)

    Gussous, Yazeed M; Tarima, Sergey; Zhao, Shi; Khan, Safdar; Caudill, Angela; Sturm, Peter; Hammerberg, Kim W

    2015-05-01

    Serial derotational casting has been used as a definitive treatment or as delaying strategy in progressive idiopathic (IS) and non-idiopathic (NIS) early-onset scoliosis (EOS). Retrospective chart and radiographic review of patients who underwent serial casting for progressive EOS between 2005 and 2012 at a single institution. A total of 74 consecutive patients entered serial cast treatment. Twenty-eight were currently being casted, 30 completed cast treatment and were converted to thoracolumbosacral orthosis (TLSO), 9 were treated surgically, 6 were lost to follow-up, and 1 had no further treatment. The researchers diagnosed IS in 41 patients; 33 had NIS. At presentation the IS group had an average Cobb angle (CA) of 49° and a rib vertebral angle difference (RVAD) of 37°. The NIS group had a CA of 51° (p = .69) and RVAD of 37° (p = .94). In patients currently being casted, 19 IS patients had a decreased CA, from 47° to 27°. The 9 NIS patients had a decreased CA, from 62° to 57° (p = .0002). Cobb angle improvement was significantly better in IS (p = .0005). In the TLSO group the 17 IS patients had a decreased average CA, from 46° to 18°, after serial casting and the 13 NIS patients decreased CA from 42° to 32°. Patients with IS had better improvement in CA than the NIS group (p Casting initiated before age 2 years yielded better curve correction for IS (p casting than NIS patients. Casting in IS patients before age 24 months yielded better curve correction. Patients who required surgery had a higher age and Cobb angle at presentation than those who transitioned to a TLSO. The surgical group was observed for a similar duration of time and there was no significant statistical difference. Although RVAD is a predictor of progression in infantile IS, it did not show a predictive value in the response to casting of either the IS or NIS groups. Copyright © 2015 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  6. The Vertical Expandable Prosthetic Titanium Rib in the treatment of spinal deformity due to progressive early onset scoliosis.

    Science.gov (United States)

    Ramirez, Norman; Flynn, John M; Serrano, Jose Anibal; Carlo, Simon; Cornier, Alberto S

    2009-07-01

    The Vertical Expandable Prosthetic Titanium Rib (VEPTR) is a technique developed for the treatment of progressive early onset scoliosis. This vertically placed device uses distraction to indirectly elongate the spine and chest, stabilizing the progression of the spinal deformity while preserving spinal growth. Thoracic spine and chest wall deformity are usually correlated; therefore, elongation of the chest wall will increase the space available for the lung and improve respiratory mechanics in patients with early onset scoliosis. We conducted a retrospective study of 17 patients with early onset scoliosis treated with the VEPTR technique. The medical records, imaging studies, and follow-up physical examinations were evaluated. The patient population consisted of 17 primary VEPTR implantations and 33 expansion surgeries with a mean follow-up of 25 months. Our results show that there was an improvement in the coronal plane deformity between the presurgical and postsurgical Cobb angles, preoperative Cobb angle of 59 degrees (range 38-77) to postoperative 35 degrees (range 10-70), resulting in an average decrease of 59% in the Cobb angle (PVEPTR implantation is a safe and efficient method for the treatment of early onset scoliosis.

  7. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline

    DEFF Research Database (Denmark)

    Hardies, Katia; Cai, Yiying; Jardel, Claude

    2016-01-01

    with intractable epilepsy and tau pathology. We performed whole exome or genome sequencing in three independent sib pairs with early onset refractory seizures and progressive neurological decline, and identified novel segregating recessive SYNJ1 defects. A homozygous missense variant resulting in an amino acid...... function, our results provide evidence that a critical reduction of the dual phosphatase activity of SYNJ1 underlies a severe disorder with neonatal refractory epilepsy and a neurodegenerative disease course. These findings further expand the clinical spectrum of synaptic dysregulation in patients...

  8. Early-onset schizophrenia

    OpenAIRE

    Hojka Gregorič Kumperščak

    2013-01-01

    Early-onset schizophrenia is defined as schizophrenia with onset before the age of 18 years. While schizophrenia is a very rare disorder in childhood, it becomes increasingly common during adolescence and peaks in early adulthood. Even though childhood and adolescent schizophrenia lie on a continuum with adult schizophrenia and show roughly the same clinical picture, they both have some developmental specifics. They display greater symptom variability making the ...

  9. What is 'early onset dementia'?

    Science.gov (United States)

    Miyoshi, Koho

    2009-06-01

    There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelerated onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a 'presenile dementia'. Since the 1980s, 'senile dementia of Alzheimer type' (SDAT) and 'Alzheimer's disease' have been considered to belong to the same pathological entity and both are now known as 'dementia of Alzheimer's type (DAT)' or merely 'Alzheimer's disease'. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important

  10. Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes).

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    Oh, Annie; Pearce, Jacqueline W; Gandolfi, Barbara; Creighton, Erica K; Suedmeyer, William K; Selig, Michael; Bosiack, Ann P; Castaner, Leilani J; Whiting, Rebecca E H; Belknap, Ellen B; Lyons, Leslie A

    2017-03-21

    African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management.

  11. Spinster homolog 2 (spns2 deficiency causes early onset progressive hearing loss.

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    Jing Chen

    2014-10-01

    Full Text Available Spinster homolog 2 (Spns2 acts as a Sphingosine-1-phosphate (S1P transporter in zebrafish and mice, regulating heart development and lymphocyte trafficking respectively. S1P is a biologically active lysophospholipid with multiple roles in signalling. The mechanism of action of Spns2 is still elusive in mammals. Here, we report that Spns2-deficient mice rapidly lost auditory sensitivity and endocochlear potential (EP from 2 to 3 weeks old. We found progressive degeneration of sensory hair cells in the organ of Corti, but the earliest defect was a decline in the EP, suggesting that dysfunction of the lateral wall was the primary lesion. In the lateral wall of adult mutants, we observed structural changes of marginal cell boundaries and of strial capillaries, and reduced expression of several key proteins involved in the generation of the EP (Kcnj10, Kcnq1, Gjb2 and Gjb6, but these changes were likely to be secondary. Permeability of the boundaries of the stria vascularis and of the strial capillaries appeared normal. We also found focal retinal degeneration and anomalies of retinal capillaries together with anterior eye defects in Spns2 mutant mice. Targeted inactivation of Spns2 in red blood cells, platelets, or lymphatic or vascular endothelial cells did not affect hearing, but targeted ablation of Spns2 in the cochlea using a Sox10-Cre allele produced a similar auditory phenotype to the original mutation, suggesting that local Spns2 expression is critical for hearing in mammals. These findings indicate that Spns2 is required for normal maintenance of the EP and hence for normal auditory function, and support a role for S1P signalling in hearing.

  12. Spinster homolog 2 (spns2) deficiency causes early onset progressive hearing loss.

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    Chen, Jing; Ingham, Neil; Kelly, John; Jadeja, Shalini; Goulding, David; Pass, Johanna; Mahajan, Vinit B; Tsang, Stephen H; Nijnik, Anastasia; Jackson, Ian J; White, Jacqueline K; Forge, Andrew; Jagger, Daniel; Steel, Karen P

    2014-10-01

    Spinster homolog 2 (Spns2) acts as a Sphingosine-1-phosphate (S1P) transporter in zebrafish and mice, regulating heart development and lymphocyte trafficking respectively. S1P is a biologically active lysophospholipid with multiple roles in signalling. The mechanism of action of Spns2 is still elusive in mammals. Here, we report that Spns2-deficient mice rapidly lost auditory sensitivity and endocochlear potential (EP) from 2 to 3 weeks old. We found progressive degeneration of sensory hair cells in the organ of Corti, but the earliest defect was a decline in the EP, suggesting that dysfunction of the lateral wall was the primary lesion. In the lateral wall of adult mutants, we observed structural changes of marginal cell boundaries and of strial capillaries, and reduced expression of several key proteins involved in the generation of the EP (Kcnj10, Kcnq1, Gjb2 and Gjb6), but these changes were likely to be secondary. Permeability of the boundaries of the stria vascularis and of the strial capillaries appeared normal. We also found focal retinal degeneration and anomalies of retinal capillaries together with anterior eye defects in Spns2 mutant mice. Targeted inactivation of Spns2 in red blood cells, platelets, or lymphatic or vascular endothelial cells did not affect hearing, but targeted ablation of Spns2 in the cochlea using a Sox10-Cre allele produced a similar auditory phenotype to the original mutation, suggesting that local Spns2 expression is critical for hearing in mammals. These findings indicate that Spns2 is required for normal maintenance of the EP and hence for normal auditory function, and support a role for S1P signalling in hearing.

  13. Early Onset Werner Syndrome

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    Berna İmge Aydoğan

    2015-09-01

    Full Text Available Werner syndrome (WS is a rare autosomal recessive adult-onset progeroid disorder characterized by the early onset of aged-appearance and age-related metabolic disorders. Symptoms of premature aging usually first develop in the second-third decades of life. We report a 27-year-old female who was admitted to our clinic at the age of eighteen with hyperglycemia. She was diagnosed with diabetes and type 4 dyslipidemia at the age of seven. In her family history, her parents were first cousins and she had three healthy brothers. On her first physical examination; she had bird-like face appearance, global hair loss, beaked nose, short stature and she was overweight. She had global hair loss with gray and thin hair. Hoarseness of voice and hyperkeratosis of skin were observed. She had bilateral cataracts and moderate sensorineural hearing loss. On psychiatric examination, borderline mental retardation was detected. She had severe insulin resistance and hypertriglyceridemia despite levothyroxine, gemfibrozil, omega-3 and intensive insulin treatment. Routine lipid apheresis was performed to lower the triglyceride levels reaching 5256 mg/dL. She also had focal segmental glomerulosclerosis, hepatosteatosis, osteoporosis and epilepsy. Disease was accompanied by several congenital deformities, such as Rathke’s cleft cyst, angiomyolipoma and femoral neck hypoplasia. WS is a rare genetic disorder characterized by multiple endocrine manifestations as well as soft tissue changes. We present a case of early disturbances that were diagnosed before typical clinical signs and symptoms. We propose that WS should be kept in mind when type 2 diabetes and hyperlipidemia are diagnosed early in childhood. Turk Jem 2015; 19: 99-104

  14. Early onset dementia.

    Science.gov (United States)

    Fadil, Halim; Borazanci, Aimee; Ait Ben Haddou, Elhachmia; Yahyaoui, Mohamed; Korniychuk, Elena; Jaffe, Stephen L; Minagar, Alireza

    2009-01-01

    Dementia is characterized by a decline in cognitive faculties and occurrence of behavioral abnormalities which interfere with an individual's activities of daily living. Dementing disorders usually affect elderly individuals but may occur in individuals younger than 65 years (early-onset dementia or EOD). EOD is often misdiagnosed or its diagnosis is delayed due to the fact that it has a more varied differential diagnosis than late-onset dementia. EOD affects individuals at the height of their career and productivity and produces devastating consequences and financial loss for the patient's family as well as society. EOD is not uncommon and is diagnosed in up to a third of patients presenting with dementia. Most importantly, some of the causes of EOD are curable which makes the need for a specific and timely diagnosis crucial. The present chapter presents a systematic approach to the differential diagnosis of EOD and provides readers with the clinical and neuroimaging features of these disorders as well as important considerations for their diagnostic evaluation. Specifically, the nuances of assessing the history and examination are discussed with careful attention to the various methods of cognitive and behavioral evaluation. A step-wise approach to diagnostic testing is followed by a discussion of anatomical localization, which often aids in identifying specific etiologies. Finally, in order to organize the subject for the reader, the various etiologies are grouped under the general categories of vascular, infectious, toxic-metabolic, immune-mediated, neoplastic/metastatic, and neurodegenerative.

  15. Early-Onset Dementia

    DEFF Research Database (Denmark)

    Konijnenberg, Elles; Fereshtehnejad, Seyed-Mohammad; Kate, Mara Ten

    2017-01-01

    of this study was to investigate quality-of-care indicators in subjects with EOD from 3 tertiary memory clinics in 3 European countries. METHODS: We included 1325 newly diagnosed EOD patients, ages 65 years or younger, between January 1, 2007 and December 31, 2013, from the Danish Dementia Registry......BACKGROUND: Early-onset dementia (EOD) is a rare condition, with an often atypical clinical presentation, and it may therefore be challenging to diagnose. Specialized memory clinics vary in the type of patients seen, diagnostic procedures applied, and the pharmacological treatment given. The aim...... (Rigshospitalet, Copenhagen), the Swedish Dementia Registry ("SveDem", Karolinska University Hospital, Stockholm), and the Amsterdam Dementia Cohort (VU University Medical Center). RESULTS: The frequency of EOD among all dementia patients was significantly lower in Copenhagen (410, 20%) and Stockholm (284, 21...

  16. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    Science.gov (United States)

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

  17. Early onset type 2 diabetes

    DEFF Research Database (Denmark)

    Bo, A; Thomsen, R W; Nielsen, J S

    2017-01-01

    was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age-gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2......AIM: To examine the association between early onset of type 2 diabetes (DM) and clinical and behavioural risk factors for later diabetes complications. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic...... Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early-onset) with diagnosis age 46-55, 56-65 (average-onset = reference), 66-75, and >75 years (late-onset). Prevalence ratios (PRs) were computed using Poisson regression. RESULTS: Poor...

  18. Rapidly progressive young-onset dementia.

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    Kelley, Brendan J; Boeve, Bradley F; Josephs, Keith A

    2009-03-01

    To characterize a cohort of individuals who have experienced rapidly progressive dementia with onset before age 45. Very little data regarding the clinical features or clinical spectrum of rapidly progressive young-onset dementia (RP-YOD) is available, primarily consisting of case reports or small series. A search of the Mayo Clinic medical record was employed to identify patients who had onset before age 45 of rapidly progressive dementia. All available medical records, laboratory data, neuroimaging studies, and pathologic data were reviewed. Twenty-two patients met the predefined inclusion and exclusion criteria. Behavioral and affective disorders, cerebellar dysfunction, and visual and/or oculomotor dysfunction were common early clinical features within the cohort, as were clinical features often associated with Creutzfeldt-Jakob disease. Diagnostic testing identified an etiology in most patients. Presentations of RP-YOD result from a variety of etiologies and significant overlap in clinical features is observed. Clinical features often associated with Creutzfeldt-Jakob disease seem to be common within the entire cohort of RP-YOD patients. Diagnostic studies aided in establishing a diagnosis in most patients, however 5 had uncertain diagnoses despite exhaustive evaluation.

  19. Can VEPTR(®) control progression of early-onset kyphoscoliosis? A cohort study of VEPTR(®) patients with severe kyphoscoliosis.

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    Reinker, Kent; Simmons, James W; Patil, Vishwas; Stinson, Zachary

    2011-05-01

    Kyphoscoliosis is considered a relative contraindication to treatment with the Vertical Expandable Prosthetic Titanium Rib (VEPTR(®); Synthes Inc, Paoli, PA). Nevertheless, patients do present with early-onset kyphoscoliosis and thoracic insufficiency syndrome, and no suitable alternative treatments are currently available. However, it is unclear whether VEPTR(®) is reasonable for treating patients with kyphoscoliosis. We determined whether VEPTR(®) controls progression in patients with kyphoscoliosis and, if so, what methods might be used to improve control of deformity progression in these patients. We retrospectively reviewed 14 patients who had VEPTR(®) treatment of early-onset kyphoscoliosis. Degrees of kyphosis and scoliosis before, during, and after treatment were measured, and levels of instrumentation, thoracic dimensions, and complications were recorded. Minimum followup was 1.7 years (average, 5.8 years; range, 1.7-12.8 years). While scoliosis was stabilized, kyphosis increased a mean of 22° at last followup. Supple kyphosis became rigid during treatment. Proximal cradle cutout was a recurring problem. Distal anchors placed too proximally had inadequate lever arms to control kyphosis. Progression of kyphosis can be minimized during VEPTR(®) treatment by early extension of the construct to the second ribs bilaterally, distal extension of hybrid constructs to the pelvis, use of bilateral hybrid VEPTR(®) implants, and use of redesigned VEPTR(®) constructs that enhance fixation at the upper end. While our early results suggest these devices control progression of kyphosis, longer followup with more patients will be required to confirm the concept in these patients.

  20. Early onset sebaceous carcinoma

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    Kaltreider Sara A

    2011-09-01

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

  1. Quantitative Electroencephalographic Analysis Provides an Early-Stage Indicator of Disease Onset and Progression in the zQ175 Knock-In Mouse Model of Huntington's Disease

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    Fisher, Simon P.; Schwartz, Michael D.; Wurts-Black, Sarah; Thomas, Alexia M.; Chen, Tsui-Ming; Miller, Michael A.; Palmerston, Jeremiah B.; Kilduff, Thomas S.; Morairty, Stephen R.

    2016-01-01

    Study Objectives: Patients with Huntington's disease (HD) show a high prevalence of sleep disorders that typically occur prior to the onset of motoric symptoms and neurodegeneration. Our understanding of the pathophysiological alterations in premanifest HD is limited, hindering the ability to measure disease modification in response to treatment. We used a full-length knock-in HD model to determine early changes in the electroencephalogram (EEG) and sleep that may predict the onset and progression of the disease. Methods: A 10-month longitudinal study was designed to determine the effect of the HD mutation on the EEG and sleep/wake changes in heterozygous (HET) and homozygous (HOM) zQ175 mice and wild-type (WT) littermates from 8 to 48 w of age. Mice were instrumented with tethered headmounts to record EEG/electromyography signals. Telemeters were implanted to continuously measure locomotor activity (LMA) and body temperature (Tb). Sleep deprivation (SDep) was performed at 8, 12, 16, 24, 32, and 48 w of age. Results: The HD mutation disrupted the EEG field potential from 8–12 w in an age- and mutant huntington dose-dependent manner, prior to changes in sleep/wake states, LMA, and Tb. Prominent effects of the HD mutation on the EEG included a progressive reduction in low frequency power, a slowing of rapid eye movement peak theta frequency, and the emergence of state-dependent beta/gamma oscillations. There was no effect of genotype on the relative increase in nonrapid eye movement delta power or sleep time in response to SDep. Conclusions: The expression of the Huntington's disease (HD) mutation results in complex EEG alterations that occur prior to deficits in behavioral measures and are one of the earliest phenotypes uncovered in this mouse model. Despite these EEG changes, homeostatic responses to sleep loss were preserved in HET and HOM zQ175 mice. Greater insight into the localization and response of these EEG alterations to novel therapies may enable early

  2. Substance use progression from adolescence to early adulthood: effortful control in the context of friendship influence and early-onset use.

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    Piehler, Timothy F; Véronneau, Marie-Hélène; Dishion, Thomas J

    2012-10-01

    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 substance use and friends' substance use tended to be highly correlated and together were robust predictors of a problematic pattern of usage for all substances in early adulthood. In addition, the adolescent effortful control construct directly predicted progressions to problematic use of tobacco and marijuana, but not for alcohol. In the alcohol model, effortful control interacted with the construct of substance use lifestyle (based on adolescent alcohol use and friends' substance use) when predicting problematic alcohol use in early adulthood. Results held when comparing across genders and across ethnic groups. These findings emphasize the importance of addressing adolescent self-regulation in interventions designed to treat and prevent early-adult substance abuse.

  3. A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD machinery.

    Directory of Open Access Journals (Sweden)

    Kaisa Kyöstilä

    Full Text Available 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 (p(raw = 1.1x10(-7, p(genome = 7.5x10(-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

  4. Genetics Home Reference: early-onset glaucoma

    Science.gov (United States)

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

  5. Fusionless surgery in early-onset scoliosis.

    Science.gov (United States)

    Odent, T; Ilharreborde, B; Miladi, L; Khouri, N; Violas, P; Ouellet, J; Cunin, V; Kieffer, J; Kharrat, K; Accadbled, F

    2015-10-01

    Surgical treatment of early-onset scoliosis has greatly developed in recent years. Early-onset scoliosis covers a variety of etiologies (idiopathic, neurologic, dystrophic, malformative, etc.) with onset before the age of 5 years. Progression and severity threaten respiratory development and may result in respiratory failure in adulthood. Many surgical techniques have been developed in recent years, aiming to protect spinal and thoracic development. Present techniques are based on one of two main principles. The first consists in posterior distraction of the spine in its concavity (single growing rod, or vertical expandable prosthetic titanium rib [VEPTR]), or on either side (dual rod); this requires iterative surgery, for lengthening, unless motorized using energy provided by a magnetic system. The second option is to use spinal growth force to lengthen the assembly; these techniques (Luque Trolley, Shilla), using a sliding assembly, are known as growth guidance. These techniques are effective in controlling early scoliotic deformity, and to some extent restore spinal growth. However, they show a high rate of complications: infection, rod breakage, spinal fixation pull out and, above all, progressive spinal stiffness, reducing long-term efficacy. Respiratory gain is harder to assess, as thoracic expansion does not systematically improve respiratory function, particularly due to impaired compliance of the thoracic cage. Copyright © 2015. Published by Elsevier Masson SAS.

  6. Risk assessment in neonatal early onset sepsis.

    Science.gov (United States)

    Mukhopadhyay, Sagori; Puopolo, Karen M

    2012-12-01

    The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Early-Onset Neonatal Sepsis

    Science.gov (United States)

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

    2014-01-01

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

  8. Severe early onset ethylmalonic encephalopathy with West syndrome.

    Science.gov (United States)

    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.

  9. Substance Use Progression from Adolescence to Early Adulthood: Effortful Control in the Context of Friendship Influence and Early-Onset Use

    Science.gov (United States)

    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…

  10. Late Onset Streptococcus agalactiae Meningitis following Early Onset Septicemia: A Preventable Disease?

    Directory of Open Access Journals (Sweden)

    Kam Lun Hon

    2017-01-01

    Full Text Available We report a neonate who presented with early onset Streptococcus agalactiae or group B streptococcus (GBS septicemia within 24 hours of birth. After discharge at day 14, she went on to develop late onset GBS meningitis at 36 days of age. The infant was treated with intravenous antibiotics on both occasions and eventually discharged home with no apparent sequelae. We address issues associated with GBS infection in infancy including the demographics, risk factors, and the risk of late onset GBS meningitis following an early onset GBS infection. The major source of GBS in early onset GBS disease is maternal birth canal GBS colonization. On the other hand, nosocomial cross-infection is an important source of GBS in late onset disease. Penicillin remains the current treatment of choice for GBS infection. Given the rapid onset and progression within hours of birth and lack of an effective solution for preventing late onset GBS, administration of an effective GBS vaccine in pregnancy could provide a sensible and cost-effective solution in all settings.

  11. Late Onset Streptococcus agalactiae Meningitis following Early Onset Septicemia: A Preventable Disease?

    Science.gov (United States)

    Hon, Kam Lun; Chan, King Hang; Ko, Pak Long; So, King Woon; Leung, Alexander K C

    2017-01-01

    We report a neonate who presented with early onset Streptococcus agalactiae or group B streptococcus (GBS) septicemia within 24 hours of birth. After discharge at day 14, she went on to develop late onset GBS meningitis at 36 days of age. The infant was treated with intravenous antibiotics on both occasions and eventually discharged home with no apparent sequelae. We address issues associated with GBS infection in infancy including the demographics, risk factors, and the risk of late onset GBS meningitis following an early onset GBS infection. The major source of GBS in early onset GBS disease is maternal birth canal GBS colonization. On the other hand, nosocomial cross-infection is an important source of GBS in late onset disease. Penicillin remains the current treatment of choice for GBS infection. Given the rapid onset and progression within hours of birth and lack of an effective solution for preventing late onset GBS, administration of an effective GBS vaccine in pregnancy could provide a sensible and cost-effective solution in all settings.

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

    Science.gov (United States)

    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. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  13. Peri-implantitis - onset and pattern of progression.

    Science.gov (United States)

    Derks, Jan; Schaller, Dennis; Håkansson, Jan; Wennström, Jan L; Tomasi, Cristiano; Berglundh, Tord

    2016-04-01

    While information on the prevalence of peri-implantitis is available, data describing onset and progression of the disease are limited. A 9-year follow-up examination of 596 randomly selected implant-carrying individuals identified 62 patients with moderate/severe peri-implantitis. Longitudinal assessments of peri-implant marginal bone levels were used to construct a statistical model with bone loss as the dependent variable. A multilevel growth model estimated the pattern of bone loss for each implant/patient. Onset of peri-implantitis was determined by evaluating the cumulative percentage of implants/patients presenting with estimated bone loss at each year following prosthesis delivery. The analysis showed a non-linear, accelerating pattern of bone loss at the 105 affected implants. The onset of peri-implantitis occurred early, and 52% and 66% of implants presented with bone loss of >0.5 mm at years 2 and 3 respectively. A total of 70% and 81% of subjects presented with ≥1 implants with bone loss of >0.5 mm at years 2 and 3 respectively. It is suggested that peri-implantitis progresses in a non-linear, accelerating pattern and that, for the majority of cases, the onset occurs within 3 years of function. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Early-onset familial Alzheimer's disease (EOFAD).

    Science.gov (United States)

    Wu, Liyong; Rosa-Neto, Pedro; Hsiung, Ging-Yuek R; Sadovnick, A Dessa; Masellis, Mario; Black, Sandra E; Jia, Jianping; Gauthier, Serge

    2012-07-01

    Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.

  15. [Early-onset sarcoidosis/Blau syndrome].

    Science.gov (United States)

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

    2011-01-01

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

  16. Cockayne syndrome with early onset of manifestations.

    Science.gov (United States)

    Moyer, D B; Marquis, P; Shertzer, M E; Burton, B K

    1982-10-01

    The Cockayne syndrome is an autosomal recessive syndrome of growth failure and characteristic physical and pathological changes. Typically the disorder becomes manifest in the second year of life; growth and development are normal during the first year. We report presumably monozygotic twins with otherwise classic Cockayne syndrome but with a prenatal onset. Several previously described cases seem to represent a similar form of Cockayne syndrome with early onset of growth failure and development delay.

  17. Fatal early-onset neonatal sepsis due to Streptococcus pneumoniae.

    Science.gov (United States)

    Nallusamy, R

    1998-12-01

    Two cases of invasive early-onset neonatal pneumococcal sepsis are reported. One neonate was born at term with no risk factors and the other preterm at 35 weeks. Sepsis was not detected at birth for either of these babies and diagnosis was made at the stage of severe sepsis. A fatal outcome resulted despite treatment. Pneumococcal sepsis was confirmed after death in both these cases. Although maternal carriage was not documented in either case, the ages at presentation and progression suggested perinatal acquisition of infection. Early onset neonatal pneumococcal sepsis presents similarly as early onset neonatal Group B streptococcal (GBS) sepsis. Vaginal carriage of pneumococcus is rare but the micro-organism may have a higher invasion to colonisation ratio (attack rate) than GBS. Risk factors for invasive disease are similar to GBS.

  18. The link between early onset drinking and early onset alcohol-impaired driving in young males.

    Science.gov (United States)

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

    2014-05-01

    Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. The present study aimed to assess this link along with potentially confounding factors. The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population-based sample of 625 males at aged 16-19. Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving.

  19. Progression of Late-Onset Stargardt Disease

    NARCIS (Netherlands)

    Lambertus, S.; Lindner, M.; Bax, N.M.; Mauschitz, M.M.; Nadal, J.; Schmid, M.; Schmitz-Valckenberg, S.; Hollander, A.I. den; Weber, B.H.; Holz, F.G.; Wilt, G.J. van der; Fleckenstein, M.; Hoyng, C.B.

    2016-01-01

    Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy

  20. Genomes of early onset prostate cancer

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Korbel, Jan O.

    2017-01-01

    Purpose of review Prostate cancer is a disease of the elderly but a clinically relevant subset occurs early in life. In the current review, we discuss recent findings and the current understanding of the molecular underpinnings associated with early-onset prostate cancer (PCa) and the evidence...... supporting age-specific differences in the cancer genomes. Recent findings Recent surveys of PCa patient cohorts have provided novel age-dependent links between germline and somatic aberrations which points to differences in the molecular cause and treatment options. Summary Identifying the earliest...

  1. Follow up of intima-media thickness after severe early-onset preeclampsia

    NARCIS (Netherlands)

    Blaauw, Judith; Souwer, Esteban T D; Coffeng, Sophie M; Smit, Andries J; van Doormaal, Jasper J; Faas, Marijke M; van Pampus, Maria G

    2014-01-01

    OBJECTIVE: Early-onset preeclampsia is associated with premature cardiovascular disease. We previously demonstrated that femoral intima-media thickness (IMT) and markers of cardiovascular disease were increased in women 1 year after early-onset preeclampsia. The current study measured (progression

  2. A cluster analysis of early onset in common anxiety disorders.

    Science.gov (United States)

    Schat, A; van Noorden, M S; Noom, M J; Giltay, E J; van der Wee, N J A; de Graaf, R; Ten Have, M; Vermeiren, R R J M M; Zitman, F G

    2016-12-01

    Early onset is regarded as an important characteristic of anxiety disorders, associated with higher severity. However, previous findings diverge, as definitions of early onset vary and are often unsubstantiated. We objectively defined early onset in social phobia, panic disorder, agoraphobia, and generalised anxiety disorder, using cluster analysis with data gathered in the general population. Resulting cut-off ages for early onset were ≤22 (social phobia), ≤31 (panic disorder), ≤21 (agoraphobia), and ≤27 (generalised anxiety disorder). Comparison of psychiatric comorbidity and general wellbeing between subjects with early and late onset in the general population and an outpatient cohort, demonstrated that among outpatients anxiety comorbidity was more common in early onset agoraphobia, but also that anxiety- as well as mood comorbidity were more common in late onset social phobia. A major limitation was the retrospective assessment of onset. Our results encourage future studies into correlates of early onset of psychiatric disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Early onset preeclampsia in subsequent pregnancies correlates with early onset preeclampsia in first pregnancy.

    Science.gov (United States)

    Li, X L; Chen, T T; Dong, X; Gou, W L; Lau, S; Stone, P; Chen, Q

    2014-06-01

    Preeclampsia is a major complication of pregnancy and its occurrence in a first pregnancy is a major risk factor for recurrence in subsequent pregnancies. Whether the time of onset or the severity of preeclampsia in a first pregnancy is associated with the incidence of recurrent preeclampsia is not clear. We performed a retrospective study to analyse the incidence of recurrent preeclampsia and associations of the time of onset and the severity of preeclampsia between first preeclampsia and recurrent preeclampsia. Ninety-two women with previous preeclampsia who had a second pregnancy in a 4 year period were included. Data on the first and second pregnancies were obtained and included maternal age, maternal height and weight, gestation week at onset of preeclampsia and at delivery, blood pressure, proteinuria, interval between pregnancies and birth weights. Fifty-five women with previous preeclampsia developed recurrent preeclampsia (59.8%). The difference in the incidence of recurrent early and late onset preeclampsia was not significant different (65.3% versus 53.4%, p>0.05). The difference in the incidence of mild or severe disease in those who experienced recurrent preeclampsia was also not significant (59.6% versus 60%, p>0.05). The severity of preeclampsia in second pregnancy was not associated with the severity of preeclampsia in first pregnancy. However 93.7% women with previous early onset preeclampsia developed early onset preeclampsia in second pregnancy and 56.5% women with previous late onset preeclampsia developed early onset preeclampsia in second pregnancy. In addition, 76.2% women with previous mild preeclampsia developed severe preeclampsia in second pregnancy. The baby weight in recurrent preeclampsia was significantly decreased compared to that in first pregnancy with preeclampsia. Our data demonstrate that there was no association between the incidence of recurrent preeclampsia and the time of onset or severity of preeclampsia in first pregnancy

  4. Alzheimer's disease: a mathematical model for onset and progression.

    Science.gov (United States)

    Bertsch, Michiel; Franchi, Bruno; Marcello, Norina; Tesi, Maria Carla; Tosin, Andrea

    2017-06-01

    In this article we propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We regard brain neurons as a continuous medium and structure them by their degree of malfunctioning. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons and ii) neuron-to-neuron prion-like transmission. We model these two processes by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The second equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. Our numerical simulations are in good qualitative agreement with clinical images of the disease distribution in the brain which vary from early to advanced stages. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  5. Early-onset Hirayama disease in a female

    Directory of Open Access Journals (Sweden)

    Matthias Baumann

    2017-01-01

    Full Text Available Objectives: Hirayama disease is a rare myelopathy, occurring predominantly in males with onset in the teens. Methods and results: Here, we report a young female patient who developed the first signs of Hirayama disease at 10.5 years of age. Prior to onset, she had experienced a growth spurt and grew about 8 cm. The disease progressed over 3 years and the typical clinical, electrophysiological, and neuroimaging signs of Hirayama disease were found. After this period and achievement of her final height, no further progression was noticed. Conclusions: This case highlights that pediatric neurologists should be aware of Hirayama disease, which can also occur in girls in early adolescence.

  6. Risk Assessment in Neonatal Early-Onset Sepsis

    Science.gov (United States)

    Mukhopadhyay, Sagori; Puopolo, Karen M.

    2013-01-01

    The incidence of neonatal early-onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early-onset sepsis remains a potentially fatal condition, particularly among very low-birth weight infants. Clinical signs of neonatal infection are non-specific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk, and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures. PMID:23177799

  7. A cluster analysis of early onset in common anxiety disorders

    NARCIS (Netherlands)

    Schat, A.; van Noorden, M.S.; Noom, M. J.; Giltay, E.J.; van der Wee, N.J.A.; de Graaf, R.; ten Have, M.; Vermeiren, R.R.J.M.M.; Zitman, F.G.

    2016-01-01

    Early onset is regarded as an important characteristic of anxiety disorders, associated with higher severity. However, previous findings diverge, as definitions of early onset vary and are often unsubstantiated. We objectively defined early onset in social phobia, panic disorder, agoraphobia, and

  8. Factor analysis of symptom profile in early onset and late onset OCD.

    Science.gov (United States)

    Grover, Sandeep; Sarkar, Siddharth; Gupta, Gourav; Kate, Natasha; Ghosh, Abhishek; Chakrabarti, Subho; Avasthi, Ajit

    2017-10-02

    This study aimed to assess the factor structure of early and late onset OCD. Additionally, cluster analysis was conducted in the same sample to assess the applicability of the factors. 345 participants were assessed with Yale Brown Obsessive Compulsive Scale symptom checklist. Patients were classified as early onset (onset of symptoms at age ≤ 18 years) and late onset (onset at age > 18 years) OCD depending upon the age of onset of the symptoms. Factor analysis and cluster analysis of early-onset and late-onset OCD was conducted. The study sample comprised of 91 early onset and 245 late onset OCD subjects. Males were more common in the early onset group. Differences in the frequency of phenomenology related to contamination related, checking, repeating, counting and ordering/arranging compulsions were present across the early and late onset groups. Factor analysis of YBOCS revealed a 3 factor solution for both the groups, which largely concurred with each other. These factors were named as hoarding and symmetry (factor-1), contamination (factor-2) and aggressive, sexual and religious factor (factor-3). To conclude this study shows that factor structure of symptoms of OCD seems to be similar between early-onset and late-onset OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Psychosocial influences in onset and progression of late life disability.

    Science.gov (United States)

    Mendes de Leon, Carlos F; Rajan, Kumar B

    2014-03-01

    Disability in older age has been related to several psychosocial characteristics, including social networks, social engagement, and depression. However, the exact role of these characteristics in the disablement process remains uncertain. Data come from a population-based study of black and white adults aged ≥65 years (N = 5,306), with up to 9 yearly data on the primary outcome measure, activities of daily living (ADL) disability. We use a two-part regression model to simultaneously test the association between each psychosocial characteristic and both onset and progression of ADL disability, while controlling for demographic variables, education, and mode of interview in the first model and health status variables in the second model. Social networks were negatively associated with onset of ADL disability but not associated with progression. The association became non-significant after adjustment for health status. Social engagement was negatively associated with both onset and progression of disability, even after adjustment for health status. Depression was significantly associated with onset of disability after adjustment for health status but not with progression of disability. The results suggest a differential role for psychosocial characteristics in the disablement process, with generally stronger associations for transitions to onset of ADL disability than progression of ADL disability.

  10. Psychosocial Influences in Onset and Progression of Late Life Disability

    Science.gov (United States)

    2014-01-01

    Objectives. Disability in older age has been related to several psychosocial characteristics, including social networks, social engagement, and depression. However, the exact role of these characteristics in the disablement process remains uncertain. Method. Data come from a population-based study of black and white adults aged ≥65 years (N = 5,306), with up to 9 yearly data on the primary outcome measure, activities of daily living (ADL) disability. We use a two-part regression model to simultaneously test the association between each psychosocial characteristic and both onset and progression of ADL disability, while controlling for demographic variables, education, and mode of interview in the first model and health status variables in the second model. Results. Social networks were negatively associated with onset of ADL disability but not associated with progression. The association became non-significant after adjustment for health status. Social engagement was negatively associated with both onset and progression of disability, even after adjustment for health status. Depression was significantly associated with onset of disability after adjustment for health status but not with progression of disability. Discussion. The results suggest a differential role for psychosocial characteristics in the disablement process, with generally stronger associations for transitions to onset of ADL disability than progression of ADL disability. PMID:24389123

  11. The nosological status of early onset anorexia nervosa.

    Science.gov (United States)

    Cooper, P J; Watkins, B; Bryant-Waugh, R; Lask, B

    2002-07-01

    Although cases of early onset anorexia nervosa have been described, there has been no systematic comparison of early onset cases with classic cases of later onset, or with other forms of early onset eating disturbance. A consecutive series of patients referred to two specialist child and adolescent eating disorder services with a clinical diagnosis of eating disorder (N = 126) was systematically assessed using a child version of the Eating Disorder Examination (EDE) and the K-SADS interview. Of 86 patients with a diagnosis of eating disorder of early onset, 38 received a clinical diagnosis of anorexia nervosa (AN). The remainder were mainly diagnosed as having food avoidance emotional disorder (25 patients) and selective eating (17 patients). Six received other diagnoses (bulimia nervosa, or functional dysphasia). These 48 patients were combined to form a group of early onset non-AN eating disturbance. In terms of specific eating disorder psychopathology and general psychopathology, the early onset AN group was very similar to the late onset AN sample. When the two early onset groups were compared, there was a marked difference between them in terms of eating disorder psychopathology. A discriminant function analysis using the EDE information produced a clear discrimination, with the EDE restraint and shape concern subscales doing most of the discrimination work. The specific psychopathology of AN of early onset is very similar to that of classic adolescent onset AN. Other forms of early onset eating disorder do not evidence this specific psychopathology.

  12. Hippocampal volume in early onset depression

    Directory of Open Access Journals (Sweden)

    MacMaster Frank P

    2004-01-01

    Full Text Available Abstract Background Abnormalities in limbic structures have been implicated in major depressive disorder (MDD. Although MDD is as common in adolescence as in adulthood, few studies have examined youth near illness onset in order to determine the possible influence of atypical development on the pathophysiology of this disorder. Methods Hippocampal volumes were measured in 17 MDD subjects (age = 16.67 ± 1.83 years [mean ± SD]; range = 13 – 18 years and 17 age- and sex-matched healthy controls (16.23 ± 1.61 years [mean ± SD]; 13 – 18 years using magnetic resonance imaging (MRI. Results An analysis of covariance revealed a significant difference between MDD and control subjects (F = 8.66, df = 1, 29, P = 0.006. This was more strongly localized to the left hippocampus (P = 0.001 than the right hippocampus (P = 0.047. Conclusions Our findings provide new evidence of abnormalities in the hippocampus in early onset depression. However, our results should be considered preliminary given the small sample size studied.

  13. Early-onset vs. Late-onset Parkinson's disease: A Clinical-pathological Study.

    Science.gov (United States)

    Ferguson, Leslie Wayne; Rajput, Ali H; Rajput, Alexander

    2016-01-01

    Several studies have compared early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD) but most are not based on autopsy confirmed cases. We compared clinical and pharmacological profiles, time to reach irreversible Hoehn and Yahr (H&Y) Stage 3 and levodopa motor complications in autopsy confirmed EOPD and LOPD cases. At first clinic visit EOPD cases were younger but had longer disease duration and they died at a younger age (all pamantadine (p<0.05) and dopamine agonists (p<0.01) were higher in EOPD. While lifetime use of levodopa was similar in the two groups, levodopa was used for a significantly longer period by EOPD (p< 0.0001). EOPD had a higher cumulative incidence of dyskinesias (p<0.01), wearing-off (p<0.01), and on-off (p<0.01). However, the time to dyskinesia onset was similar in the two groups. The threshold to wearing-off was much longer in EOPD (p<0.01). H&Y stage profile at first visit was similar in the two groups. The duration from disease onset to reach irreversible H&Y stage 3 was significantly longer in EOPD. Our observations indicate that progression of PD is slower in EOPD and suggest that the pre-clinical interval in this group is longer. These findings can be used for case selection for drug trials and studies of the pathogenesis of PD.

  14. Early onset cerebellar ataxia with retained tendon reflexes : foot deformity in a first grade family member

    NARCIS (Netherlands)

    Schelhaas, HJ; Van der Hulst, M; Ippel, E; Prevo, RL; Hageman, G

    1999-01-01

    Early onset cerebellar ataxia with retained tendon reflexes (EOCA) is a clinical syndrome characterised by progressive cerebellar ataxia with an onset before the age of 25 years and a wide spectrum of associated features. It is distinguished from Friedreich's ataxia (FA) mainly by the preservation

  15. Childhood-onset HAM/TSP with progressive cognitive impairment.

    Science.gov (United States)

    Zorzi, Giovanna; Mancuso, Roberta; Nardocci, Nardo; Farina, Laura; Guerini, Franca Rosa; Ferrante, Pasquale

    2010-04-01

    HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy, usually with adult-onset. Very few cases of childhood-onset have been described, most presenting with progressive paraparesis and sphincteric disturbances as in the adult form. Here we report a young male with childhood-onset of HAM/TSP and progressive cognitive and behavioral disturbances. A serological screening revealed HTLV-I infection, confirmed by Western Immunoblotting analysis. Molecular characterization of amplified HTLV-I proviral DNA has been performed both in the patient and his mother by LTR sequence analysis, and HLA genotype inheritance was evaluated. Our case indicates the possibility that cognitive dysfunctions may be one manifestation of HTLV-I infection in childhood.

  16. Early-onset stargardt disease: phenotypic and genotypic characteristics

    NARCIS (Netherlands)

    Lambertus, S.; Huet, R.A.C. van; Bax, N.M.; Hoefsloot, L.H.; Cremers, F.P.M.; Boon, C.J.F.; Klevering, B.J.; Hoyng, C.B.

    2015-01-01

    OBJECTIVE: To describe the phenotype and genotype of patients with early-onset Stargardt disease. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-one Stargardt patients with age at onset onset, medical history, initial

  17. Clinical characteristics of early- and late-onset gout

    Science.gov (United States)

    Zhang, Bingqing; Fang, Weigang; Zeng, Xuejun; Zhang, Yun; Ma, Ya; Sheng, Feng; Zhang, Xinlei

    2016-01-01

    Abstract A retrospective cross-sectional study using data from an outpatient clinic in China was conducted to investigate the clinical features of early-onset gout patients. All patients diagnosed with gout were asked about clinical characteristics of their gout and comorbid diseases. Patients presenting with acute flares were asked about common triggers before the flare. “Early-onset” gout was defined as onset of gout before 40 years and “late-onset” as onset ≥40 years. Major joint involvement, flare frequency before presentation, the cumulative number of involved joints, proportions of tophi complications at presentation, flare triggers, as well as any metabolic, cardiovascular, cerebrovascular, and renal comorbidities, were compared between the 2 groups. A total of 778 gout patients were enrolled in this study, including 449 (57.7%) in the early-onset group and 329 (42.3%) in the late-onset group. Compared with the late-onset gout patients, the early-onset gout patients had a higher proportion of ankle/mid-foot involvement (62.8% vs 48.2%, P gout patients had fewer metabolic, cardiovascular, cerebrovascular, or renal complications. Early- and late-onset gout patients had different clinical features. Early-onset seems to be influenced more by lifestyle, while late-onset patients have more complications because of comorbidities. PMID:27893683

  18. Cataract in early onset and classic Cockayne syndrome.

    Science.gov (United States)

    Ferreira, R C; Roeder, E R; Bateman, J B

    1997-12-01

    To describe cataracts in classic and early onset Cockayne syndrome (CS). Classic CS typically has an onset after the first year of life; intrauterine growth failure and severe neurologic dysfunction from birth distinguishes the less common early onset CS from the classic form. A complete ophthalmic evaluation was performed in four affected patients, one with the early onset and three with classic CS. We report cataract in all patients and glaucoma in one, the latter never previously reported in CS. CS should be considered in babies with low birth weight and congenital cataract.

  19. Mechanisms of Epigenetic Regulation of Leukemia Onset and Progression

    OpenAIRE

    Ntziachristos, Panagiotis; Mullenders, Jasper; Trimarchi, Thomas; Aifantis, Iannis

    2013-01-01

    Over the past decade, it has become clear that both genetics and epigenetics play pivotal roles in cancer onset and progression. The importance of epigenetic regulation in proper maintenance of cellular state is highlighted by the frequent mutation of chromatin modulating factors across cancer subtypes. Identification of these mutations has created an interest in designing drugs that target enzymes involved in DNA methylation and posttranslational modification of histones. In this review, we ...

  20. Multisystem disorder in late-onset chronic progressive external ophthalmoplegia.

    Science.gov (United States)

    Pfeffer, Gerald; Sirrs, Sandra; Wade, N Kevin; Mezei, Michelle M

    2011-01-01

    Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial syndrome on a disease spectrum with Kearns-Sayre syndrome (KSS). Clinical presentation is variable and our experience suggested that phenotypic differences exist in CPEO with onset after age 20. This descriptive study is a retrospective chart review of 40 patients with late-onset CPEO. Clinical features, laboratory and neurophysiology results were reviewed. Multisystem dysfunction was very common in this series. Gastrointestinal dysfunction was more common than expected (60%) as was migraine headache (40%). Clinical characteristics on the KSS disease spectrum were uncommon in this series with only 2.5% having pigmentary retinopathy, 5% with cardiac conduction abnormality, and 22.5% having endocrinopathy (most often thyroid dysfunction rather than diabetes). Neurophysiology abnormalities included length-dependent axonal polyneuropathy in 44% (sometimes subclinical) and myopathic EMG changes in 26%. Exposure to sources of acquired mitochondrial toxicity including cigarette use and hepatitis C infection were more common than expected in this series. Phenotype was different in this late-onset series compared with previous reports in CPEO patients. In this series of late-onset patients, multi-organ dysfunction was more common than previously reported in CPEO, and some classical mitochondrial manifestations, such as pigmentary retinopathy were rare. We suggest that acquired mitochondrial toxicity may have a role in the pathogenesis of adult-onset CPEO.

  1. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    OpenAIRE

    2008-01-01

    textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized controlled intervention trial, we examined whether intervention-induced reductions in ADHD symptoms at age 9 mediated the reduced risk of tobacco use onset among these children at age 10...

  2. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

  3. Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

    NARCIS (Netherlands)

    A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)

    2008-01-01

    textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,

  4. Reproductive outcome after early-onset pre-eclampsia

    NARCIS (Netherlands)

    Schaaf, Jelle M.; Bruinse, Hein W.; van der Leeuw-Harmsen, Loes; Groeneveld, Els; Koopman, Corine; Franx, Arie; van Rijn, Bas B.

    2011-01-01

    Early-onset pre-eclampsia is an important cause of maternal and neonatal morbidity and mortality and is believed to have a significant impact on future maternal physical and psychological health. However, structured follow-up data of women with a history of early-onset pre-eclampsia are lacking.

  5. Attention Deficit Hyperactivity Disorder Symptoms Mediate Early-Onset Smoking

    NARCIS (Netherlands)

    Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.

    2009-01-01

    Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

  6. Nearwork in early-onset myopia.

    Science.gov (United States)

    Saw, Seang-Mei; Chua, Wei-Han; Hong, Ching-Ye; Wu, Hui-Min; Chan, Wai-Ying; Chia, Kee-Seng; Stone, Richard A; Tan, Donald

    2002-02-01

    To determine the relationship of nearwork and myopia in young elementary school-age children in Singapore. A cross-sectional study of 1005 school children aged 7 to 9 years was conducted in two schools in Singapore. Cycloplegic autorefraction, keratometry, and biometry measurements were performed. In addition, the parents completed a detailed questionnaire on nearwork activity (books read per week, reading in hours per day and diopter hours [addition of three times reading, two times computer use, and two times video games use in hours per day]). Other risk factors, such as parental myopia, socioeconomic status, and light exposure history, were assessed. In addition to socioeconomic factors, several nearwork indices were associated with myopia in these young children. The multivariate adjusted odds ratio of higher myopia (at least -3.0 D) for children who read more than two books per week was 3.05 (95% confidence interval [CI], 1.80-5.18). However, the odds ratios of higher myopia for children who read more than 2 hours per day or with more than 8 diopter hours (1.50; 95% CI, 0.87-2.55 and 1.04; 95% CI, 0.61-1.78, respectively) were not significant, after controlling for several factors. Children aged 7 to 9 years with a greater current reading exposure were more likely to be myopic. This association of reading and myopia in a young age cohort was greater than the strength of the reading association generally found in older myopic subjects. Whether these results identify an association of early-onset myopia with nearwork activity or other potentially confounding factors is discussed.

  7. Adverse Housing Conditions and Early-Onset Delinquency.

    Science.gov (United States)

    Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

    2017-09-01

    Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

  8. Differences between early and late onset adult depression

    DEFF Research Database (Denmark)

    Drachmann Bukh, Jens; Bock, Camilla; Vinberg, Maj

    2011-01-01

    Background: It is unclear, whether age-of-onset identifies subgroups of depression. Aim: To assess the clinical presentation of depression with onset in the early adult age (18-30 years) as compared to depression with later onset (31-70 years). Method: A total number of 301 patients with first......, t-tests for continuous parametric data and Mann-Whitney U-test for continuous nonparametric data. Logistic and multiple regression analyses were used to adjust the analyses for potentially confounding variables. Results: Patients with early onset of depression were characterised by a higher...

  9. Late Onset Streptococcus agalactiae Meningitis following Early Onset Septicemia: A Preventable Disease?

    OpenAIRE

    Hon, Kam Lun; Chan, King Hang; Ko, Pak Long; So, King Woon; Leung, Alexander K. C.

    2017-01-01

    We report a neonate who presented with early onset Streptococcus agalactiae or group B streptococcus (GBS) septicemia within 24 hours of birth. After discharge at day 14, she went on to develop late onset GBS meningitis at 36 days of age. The infant was treated with intravenous antibiotics on both occasions and eventually discharged home with no apparent sequelae. We address issues associated with GBS infection in infancy including the demographics, risk factors, and the risk of late onset GB...

  10. Alzheimer's disease: a mathematical model for onset and progression

    CERN Document Server

    Bertsch, Michiel; Marcello, Norina; Tesi, Maria Carla; Tosin, Andrea

    2015-01-01

    In this paper we propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We regard brain neurons as a continuous medium, and structure them by their degree of malfunctioning. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons; ii) neuron-to-neuron prion-like transmission. We model these two processes by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The second equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. Even though we deliberately neglect many aspects of the complexity of the brain and the disease, numerical simulations are in good qualitative agreement with clinical...

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

    Science.gov (United States)

    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.

  12. Clinical features of late-onset ankylosing spondylitis: comparison with early-onset disease.

    Science.gov (United States)

    Montilla, Carlos; Del Pino-Montes, Javier; Collantes-Estevez, Eduardo; Font, Pilar; Zarco, Pedro; Mulero, Juan; Gratacós, Jordi; Rodríguez, Carlos; Juanola, Xavier; Fernández-Sueiro, Jose Luis; Almodovar, Raquel

    2012-05-01

    Ankylosing spondylitis (AS) is generally observed in young patients but can occur later in life or in persons ≥ 50 years of age. Our objective was to characterize the clinical features of late-onset AS in a large multicenter national cohort. We studied late-onset AS in the National Registry of Spondyloarthritis of the Spanish Society of Rheumatology (REGISPONSER database) cohort (n = 1257), of whom 3.5% had onset at age ≥ 50 years versus a control group with onset at < 50 years. There were no differences between late-onset and early-onset AS according to sex and family history of spondyloarthropathies. Patients in the late-onset group more often showed involvement of the cervical spine (22.7% vs 9.7%; p = 0.03) and arthritis of the upper (13.6% vs 3.0%; p = 0.002) and lower limbs (27.3% vs 15.2%; p = 0.03) as first manifestations than did patients in the early-onset group. A higher percentage of mixed forms (axial and peripheral joint disease) during the course of the disease was also recorded in the late-onset group (50% vs 24%; p = 0.0001). Our study suggests that age at onset of AS affects the patients' presenting clinical form. Arthritis of the upper limbs requires a differential diagnosis with other conditions frequent in patients over 50 years of age, such as rheumatoid arthritis or crystal-induced arthropathy.

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

    Science.gov (United States)

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

    2010-01-01

    Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

  14. Novel GFAP Variant in Adult-onset Alexander Disease With Progressive Ataxia and Palatal Tremor.

    Science.gov (United States)

    Gass, Jennifer M; Cheema, Anvir; Jackson, Jessica; Blackburn, Patrick R; Van Gerpen, Jay; Atwal, Paldeep S

    2017-11-01

    Alexander disease is a rare neurodegenerative disease caused by variants in the glial fibrillary acidic protein gene (GFAP). This disorder can develop as an infantile, juvenile or adult-onset form and is characterized by several clinical features, including macrocephaly, seizures, ataxia, and bulbar/pseudobulbar signs. While the majority of these patients have the more progressive infantile form which causes severe leukodystrophy and early death; the less common adult form is more variable (ie, onset age, symptoms), with bulbar dysfunction as the primary feature. In our investigation, we describe a patient with progressive neuromuscular issues including dyspnea, dysphagia, dysarthria and progressive ataxia with palatal tremor. Through genetic testing, we determined that our patient has a novel variant in GFAP typical of Alexander disease.

  15. Early-onset Coronary Artery Disease: Clinical and Hereditary Aspects

    DEFF Research Database (Denmark)

    Christiansen, Morten Krogh

    2017-01-01

    the advances in genetic techniques has led to an increased understanding of the genetic background of CAD, which may potentially be translated into clinical use. The studies of this thesis aimed to investigate the burden of conventional risk factors and control in early-onset CAD (i.e. ... component of coronary atherosclerosis and underpin the need for risk factor optimization in early-onset CAD. Furthermore, our data support that yet identified common risk variants may have little clinical relevance in the clinical setting of early-onset CAD....

  16. Gambling onset and progression in a sample of at-risk gamblers from the general population.

    Science.gov (United States)

    Carneiro, Elizabeth; Tavares, Hermano; Sanches, Marcos; Pinsky, Ilana; Caetano, Raul; Zaleski, Marcos; Laranjeira, Ronaldo

    2014-05-30

    The goal of this study was to investigate gambling-related behavior, onset and progression in a sample of at-risk gamblers from the community. A national household survey was conducted in Brazil, covering individuals 14 years old or older. Subjects were screened for at-risk gambling, those testing positive answered a questionnaire about gambling progression, preferred games and DSM-IV pathological gambling criteria. Out of 3007 respondents, 118 were considered at-risk gamblers according to the Lie/Bet Questionnaire. According to the DSM-IV, 32.7% and 24.9% of those were considered problem and pathological gamblers, respectively. Early at-risk gamblers (onset prior to 20 years of age), were more likely to be male, to prefer non-commercially structured games, and to chase losses while gambling. Young pathological gamblers (under 35 years of age) progressed faster from regular to problem gambling (roughly 2 years) than mature pathological gamblers (12 years). Such findings had not been described before because previous reports focused mostly on clinical samples that lack young, male, early-onset gamblers. Gambling programs have not satisfactorily covered this segment of gamblers. Outreach strategies and early interventions should be provided to prevent these individuals from rapidly evolving into pathological gambling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. COMPARATIVE STUDY OF MATERNAL AND PERINATAL OUTCOME IN EARLY ONSET AND LATE ONSET PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Sreedevi Atluri

    2017-01-01

    Full Text Available BACKGROUND Preeclampsia is the leading cause of maternal and perinatal morbidity and mortality worldwide, the exact aetiology of which is still unknown. The concept of early and late pre-eclampsia depending on gestational age at onset is more modern and is widely accepted that these two entities have different aetiologies and should be considered as different forms of the disease. Even though the presenting features overlap, these two entities of preeclampsia differ by biochemical markers, maternal and foetal outcomes. Aim of the Study- This study compares early-onset preeclampsia and late-onset preeclampsia with respect to their clinical presentation, laboratory parameters, management options, maternal and foetal outcomes which gives us an idea that these two preeclampsia subtypes have different pathological processes and a need for varied clinical approach to prevent adverse outcomes. METHODS This is a prospective comparative study conducted in JSS Hospital, Mysore from November, 2014 to June, 2016. All Antenatal cases (both booked and unbooked with gestational age ≥20 weeks between 18 yrs. and 40 yrs. of age diagnosed as preeclampsia as per the inclusion and exclusion criteria attending the outpatient department or admitted were selected and divided in to two groups, early onset preeclampsia (EOP group if gestational age at onset of preeclampsia is before 34 weeks and late onset preeclampsia if gestational age at onset is at 34 weeks or later were observed until delivery and early postpartum period and babies till early neonatal period. RESULTS A total of 158 patients at >20 weeks of gestation with preeclampsia were enrolled for this study. Early-onset Preeclampsia (EOP and Late-onset Preeclampsia (LOP had 75 and 83 pre eclamptic women respectively. Early onset group had severe clinical picture with deranged laboratory findings (Thrombocytopenia, altered liver enzymes, lactic dehydrogenase (LDH levels, urea and creatinine levels compared to

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

    Science.gov (United States)

    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…

  19. Genetics Home Reference: early-onset primary dystonia

    Science.gov (United States)

    ... as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. ... Diagnosis & Management Resources Genetic Testing (1 link) ... Isolated Dystonia MedlinePlus Encyclopedia: Movement - uncontrolled or slow ...

  20. Normal gastric antral myoelectrical activity in early onset anorexia nervosa.

    OpenAIRE

    Ravelli, A M; Helps, B. A.; Devane, S P; Lask, B. D.; Milla, P J

    1993-01-01

    Anorexia, epigastric discomfort, nausea, and vomiting may result from disordered gastric motility and emptying. These features have been found in many adults with anorexia nervosa, but have never been investigated in early onset anorexia nervosa. In 14 patients with early onset anorexia nervosa (eight of whom had upper gastrointestinal tract symptoms), six children with other eating disorders, four children with non-ulcer dyspepsia, and 10 controls matched for age and sex, the non-invasive te...

  1. Hippocampal morphology and distinguishing late-onset from early-onset elderly depression.

    Science.gov (United States)

    Ballmaier, Martina; Narr, Katherine L; Toga, Arthur W; Elderkin-Thompson, Virginia; Thompson, Paul M; Hamilton, Liberty; Haroon, Ebrahim; Pham, Daniel; Heinz, Andreas; Kumar, Anand

    2008-02-01

    Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early- and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated. With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early- (N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups. Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early- and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late- compared to early-onset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1-CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late- but not early-onset depressed patients or comparison subjects. More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies.

  2. Early onset pregnancy induced hypertension/eclampsia in Benin ...

    African Journals Online (AJOL)

    Pregnancy induced hypertension/eclampsia is a major cause of maternal and perinatal morbidity and mortality in Nigeria. There have been very few studies focussed on early onset pregnancy induced hypertension/eclampsia in Nigerian women To determine the incidence, clinical features and outcome of cases of early ...

  3. Markers of neurodevelopmental impairments in early-onset psychosis

    Directory of Open Access Journals (Sweden)

    Petruzzelli MG

    2015-07-01

    Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy 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. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

  4. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    Science.gov (United States)

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.

  5. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    Science.gov (United States)

    2017-04-01

    variants of significant effect contributing to AD risk, however, with the advent of new genomic technologies such as high-throughput sequencing... technology , small family aggregates and isolated cases, particularly those with an extreme phenotype of the disorder (such as early onset) can be used . Thus... dementia and age at onset (AAO) among these individuals. For this study, we examined well-characterized EOAD families using WES to discover AD risk

  6. Early-onset dementias: diagnostic and etiological considerations

    OpenAIRE

    Masellis, Mario; Sherborn, Kayla; Neto, Pedro Rosa; Sadovnick, Dessa A; Hsiung, Ging-Yuek R.; Black, Sandra E.; Prasad, Sadhana; Williams, Meghan; Gauthier, Serge

    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 cerebrovascu...

  7. [Early outcome of vertical expandable prosthetic titanium rib technique in treating early-onset scoliosis].

    Science.gov (United States)

    Qiu, Yong; Sun, Xu; Wang, Bin; Ding, Qi; Zhu, Ze-zhang; Qian, Bang-ping; Yu, Yang; Zhu, Feng; Ma, Wei-wei

    2012-10-01

    To investigate the early outcome of vertical expandable prosthetic titanium rib (VEPTR) technique in treating early-onset scoliosis. This study recruited 11 early-onset scoliosis patients (8 boys and 3 girls) who received VEPTR treatment from December 2006 to July 2011 with a minimum follow-up of 12 months. The average age at initial surgery was (7 ± 3) years (range, 3.1 to 9.8 years). VEPTR device, either rib to rib or rib to lumbar, was implanted at initial surgery. During the regular post-operative follow-ups, expansion surgeries were scheduled at an interval of 6 to 12 months. Measurements of primary curve magnitude, apical vertebral translation, thoracic height and T(1)-S(1) height were performed on radiographs, and were compared between those of preoperatively, postoperatively, and at latest follow-up through paired-t tests. All patients had a mean follow-up of (32 ± 11) months. Totally 41 surgeries were performed, averagely 3.7 surgeries per patient; and 30 expansion surgeries were carried out, averagely 2.7 surgeries per patient. The average interval for each expansion surgery was 8 months. From preoperatively to latest follow-up, the Cobb angle of primary curves was averagely corrected from 78° ± 18° to 55° ± 11° (t = 4.931, P VEPTR instrumented, gains in thoracic height and T(1)-S(1) height per expansion surgery averaged (0.8 ± 0.3) cm and (1.8 ± 0.4) cm, respectively. Eight complications occurred in 6 patients, including rib cradle dislodgements, displayed infection, intraoperative pleura rupture and loosening of lumbar pedicle screws. VEPTR technique proves to be an effective way of preventing curve progression in early-onset scoliosis patients while allowing growth of spine and chest. Yet, indications for such a technique need to be strictly selected because of the relatively high complication rate.

  8. Depression in young adult psychiatric outpatients: delimiting early onset.

    Science.gov (United States)

    Ramirez, Adriana; Ekselius, Lisa; Ramklint, Mia

    2015-04-01

    The aim of this study was to examine differences in childhood, adolescent and adult onset of depression. Young psychiatric outpatients (n = 156) diagnosed with a lifetime depressive episode were divided into three groups according to age of onset of their first depressive episode: childhood (≤12 years, n = 21), adolescent (13-17 years, n = 58) and early adult onset (18-25 years, n = 77). Participants were assessed by diagnostic interviews and by questionnaires measuring previous life events and childhood developmental delays. Clinical characteristics and various risk factors were compared between groups. This clinical sample was dominated by women, with onset of their first depressive episode occurring during adolescence. Childhood onset was related to an increased number of depressive episodes, higher prevalence of personality disorders, more current social problems and more reported development delays during childhood regarding literacy learning, social skills and memory. They also reported more separation anxiety symptoms and neglect during childhood and more experiences of teenage pregnancies and abortions. Childhood onset of depression is associated with more severe symptoms, more psychosocial risk factors and childhood developmental delays. Because all onset groups shared many features, the results are inconclusive if there are distinct subgroups according to age of onset. © 2013 Wiley Publishing Asia Pty Ltd.

  9. Early-onset type 2 diabetes in Mexico.

    Science.gov (United States)

    García-García, Eduardo; Aguilar-Salinas, Carlos A; Tusié-Luna, Teresa; Rull-Rodrigo, Juan Antonio

    2002-06-01

    This review summarizes the clinical, metabolic and genetic characteristics of early-onset type 2 diabetes in Mexico. Early-onset type 2 diabetes is both a clinical challenge and a public health problem. It is calculated that almost 300,000 Mexican diabetics are diagnosed between the ages of 20 and 40. The large Mexican family structure and the high prevalence of the disease provide a unique opportunity to identify the genes and the metabolic abnormalities involved in this form of the disease. In a hospital-based population, our group found that insulin deficiency was the main defect in this form of diabetes. Mutations in the NHF-1 alpha or HNF-4 alpha genes or autoimmunity to the beta cell were found in a small proportion of cases, leaving unexplained the majority of cases. Also discussed are the epidemiologic and therapeutic implications of early-onset type 2 diabetes, and the possible role of genetic testing for prevention.

  10. Herpes viruses and periodontopathic bacteria in early-onset periodontitis.

    Science.gov (United States)

    Kamma, J J; Contreras, A; Slots, J

    2001-09-01

    This study examined the occurrence of human herpes viruses and suspected periodontopathic bacteria in early-onset periodontitis patients who experienced progressive disease in at least 2 periodontal sites during the maintenance phase of therapy. In each of 16 individuals (9 male and 7 female; mean age 33.1+/-2.6 years), subgingival plaque samples were collected from 2 deteriorating and 2 stable periodontitis sites. A nested polymerase chain reaction method determined the presence of human cytomegalovirus (HCMV), Epstein-Barr virus type 1 (EBV-1) and herpes simplex virus (HSV). A 16s rRNA polymerase chain reaction method identified Porphyromonas gingivalis, Dialister pneumosintes, Bacteroides forsythus and Actinobacillus actinomycetemcomitans. HCMV was detected in 59.4% of active and in 12.5% of stable sites (pperiodontitis sites showing herpesvirus co-infection and all but one site showing P. gingivalis and D. pneumosintes co-infection revealed bleeding upon probing. HCMV, EBV-1, HSV and herpesvirus co-infection, as well as P. gingivalis, D. pneumosintes and P. gingivalis-D. pneumosintes co-infection were statistically associated with active periodontitis. Herpesviruses are immunosuppressive and may set the stage for overgrowth of subgingival P. gingivalis, D. pneumosintes and other periodontopathic bacteria. Understanding the significance of herpesviruses in human periodontitis may allow for improved diagnosis, more specific therapy and, ultimately, disease prevention.

  11. Early-Onset Friedreich's Ataxia With Oculomotor Apraxia

    Directory of Open Access Journals (Sweden)

    Amene Saghazadeh

    2017-02-01

    Full Text Available Friedreich’s ataxia (FRDA is a rare autosomal recessive spinocerebellar ataxia which in the majority of cases is associated with a GAA-trinucleotide repeat expansion in the first intron of Frataxin gene located on chromosome 9. The clinical features include progressive gait and limb ataxia, cerebellar dysarthria, neuropathy, optic atrophy, and loss of vibration and proprioception. Ataxia with ocular motor apraxia type 1 (AOA1 is another autosomal recessive cerebellar ataxia which is associated with oculomotor apraxia, hypoalbuminaemia, and hypercholesterolemia. Here we describe two siblings (13- and 10-year-old display overlapping clinical features of both early-onset FRDA and AOA1. Almost all of laboratory test (including urinary analysis/culture, biochemistry, peripheral blood smear, C-reactive protein level, erythrocyte sedimentation rate-1h results were within the normal range for both patients. Due to the normal laboratory test results; we concluded that the diagnosis was more likely to be FRDA than AOA1. Therefore, neurologists should bear in mind that clinical presentations of FRDA may vary widely from the classical phenotype of gait and limb ataxia to atypical manifestations such as oculomotor apraxia.

  12. GST polymorphisms and early-onset coronary artery disease in ...

    African Journals Online (AJOL)

    Background. Glutathione S-transferases (GSTs) detoxify environmental agents which influence the onset and progression of disease. Dysfunctional detoxification enzymes are responsible for prolonged exposure to reactive molecules and can contribute to endothelial damage, an underlying factor in coronary artery disease ...

  13. Awareness of early-onset anorexia nervosa.

    Science.gov (United States)

    Karwautz, A; de Zwaan, M; Wöber-Bingöl, C; Wöber, C; Friedrich, M H

    1997-09-01

    The aim of the study was to determine whether physicians consider anorexia nervosa as a possible diagnosis in children and adolescents presenting various somatic symptoms including significant weight loss. Questionnaires were handed out to participants of a national general medical congress in Austria. The questionnaire included two case vignettes of children with anorexia nervosa and questions about diagnosis, differential diagnoses and management. Anorexia nervosa was considered as possible primary diagnosis in both cases by 3.8% of the respondents and 11.4% suspected a psychosomatic or psychiatric disorder as primary diagnosis in both cases. These findings demonstrate a limited awareness of anorexia nervosa and of a psychosomatic or psychiatric origin of somatic symptoms including weight loss in children and adolescents among physicians. Recognizing anorexia nervosa in an early stage and referring the patients for a psychiatric evaluation as soon as possible is a prerequisite for specialized treatment and might improve the long-term outcome of this severe disorder. Increased educational efforts are required to improve the knowledge among primary care physicians about eating disorders.

  14. Novel Therapy for the Treatment of Early-Onset Preeclampsia.

    Science.gov (United States)

    Ornaghi, Sara; Paidas, Michael J

    2017-03-01

    Preeclampsia is a multisystem disorder affecting 2% to 8% of pregnancies and a leading cause of maternal and perinatal morbidity and mortality worldwide. Recent investigations have improved our understanding of the pathogenesis of this potentially life-threatening disease, especially in its early-onset form of manifestation. Despite these advances, therapeutic options are still limited and no effective pharmacologic interventions are currently available. Ongoing lines of research indicate some potential novel treatments targeting specific pathogenic steps. In this article we provide an updated overview of the multiple therapeutic approaches under preclinical and clinical assessment for the treatment of early-onset preeclampsia.

  15. Early onset obsessive-compulsive disorder with and without tics.

    Science.gov (United States)

    de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

    2009-07-01

    Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

  16. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study.

    Science.gov (United States)

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation's knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. The analysis brings the theoretical framework of "two-eyed seeing" to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease.

  17. Early detection of emphysema progression

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Jacobs, Sander S. A. M.; Lo, Pechin Chien Pau

    2010-01-01

    Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... score. We applied the proposed algorithm on 27 patients with severe emphysema with CT scans acquired five time points, at baseline, after 3, after 12, after 21 and after 24 or 30 months. The results showed consistent emphysema progression with time and the overall progression score correlates...

  18. Early detection of emphysema progression

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Jacobs, Sander S A M; Lo, Pechin

    2010-01-01

    Emphysema is one of the most widespread diseases in subjects with smoking history. The gold standard method for estimating the severity of emphysema is a lung function test, such as forced expiratory volume in first second (FEV1). However, several clinical studies showed that chest CT scans offer...... emphysema progression from longitudinal chest CT scans. First, images are registered to a common system of coordinates and then local image dissimilarities are computed in corresponding anatomical locations. Finally, the obtained dissimilarity representation is converted into a single emphysema progression...

  19. Early Onset Marfan Syndrome: Atypical Clinical Presentation of Two Cases

    Directory of Open Access Journals (Sweden)

    Ozyurt Abdullah

    2015-06-01

    Full Text Available Early onset Marfan Syndrome (eoMFS is a rare, severe form of Marfan Syndrome (MFS. The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system.

  20. Early-onset Hirayama disease in a female

    OpenAIRE

    Matthias Baumann; Josef Finsterer; Gizewski, Elke R.; Wolfgang N Löscher

    2017-01-01

    Objectives: Hirayama disease is a rare myelopathy, occurring predominantly in males with onset in the teens. Methods and results: Here, we report a young female patient who developed the first signs of Hirayama disease at 10.5 years of age. Prior to onset, she had experienced a growth spurt and grew about 8 cm. The disease progressed over 3 years and the typical clinical, electrophysiological, and neuroimaging signs of Hirayama disease were found. After this period and achievement of her fina...

  1. Neutrophil CD64 in early-onset neonatal sepsis

    African Journals Online (AJOL)

    EL-HAKIM

    Gonzalez BE, Mercado CK, Johnson L,. Brodsky NL, Bhandari V. Early markers of late- onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med. 2003; 31: 60 –8. 6. Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed 2004; 89: F229-. 35. 7. Ng PC, Lam ...

  2. LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis.

    Science.gov (United States)

    Lévy, Eva; Stolzenberg, Marie-Claude; Bruneau, Julie; Breton, Sylvain; Neven, Bénédicte; Sauvion, Sylvie; Zarhrate, Mohammed; Nitschké, Patrick; Fischer, Alain; Magérus-Chatinet, Aude; Quartier, Pierre; Rieux-Laucat, Frédéric

    2016-07-01

    LRBA (lipopolysaccharide-responsive and beige-like anchor protein) deficiency associates immune deficiency, lymphoproliferation, and various organ-specific autoimmunity. To date, prevalent symptoms are autoimmune cytopenias and enteropathy, and lymphocytic interstitial lung disease. In 2 siblings from a consanguineous family presenting with early onset polyautoimmunity, we presumed autosomal recessive inheritance and performed whole exome sequencing. We herein report the first case of early-onset, severe, chronic polyarthritis associated with LRBA deficiency. A novel 1bp insertion in the LRBA gene, abolishing protein expression, was identified in this family. Among the 2 brothers homozygous for LRBA mutation, one developed Evans syndrome and deceased at age 8.5 from complications of severe autoimmune thrombocytopenia. His brother, who carried the same homozygous LRBA mutation, early-onset erosive polyarthritis associated with chronic, bilateral, anterior uveitis and early onset type 1 diabetes mellitus. This report widens the clinical spectrum of LRBA deficiency and, in lights of the variable phenotypes described so far, prompts us to screen for this disease in patients with multiple autoimmune symptoms in the family, including severe, erosive, polyarticular juvenile arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Familial risk assessment for early-onset coronary heart disease.

    Science.gov (United States)

    Scheuner, Maren T; Whitworth, William C; McGruder, Henraya; Yoon, Paula W; Khoury, Muin J

    2006-08-01

    We examined the performance of a familial risk assessment method that stratifies risk for early-onset coronary heart disease by considering the number of relatives with coronary disease, degree of relationship, lineage, and age at diagnosis. By using data from the HealthStyles 2003 survey, we assessed the associations between familial risk and early-onset coronary heart disease, diabetes, hypercholesterolemia, hypertension, and obesity. By using area under the curve statistics, we evaluated the discriminatory ability of various risk assessment models. Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years. After adjustment for demographics, strong and moderate risk were significantly associated with approximately a five- and twofold risk of early-onset coronary disease, respectively. After adjustment for demographics and personal history of cardiovascular disease, strong familial risk was also significantly associated with diabetes, hypercholesterolemia, hypertension, and obesity. A risk assessment model that included familial risk, demographics, and personal history of diabetes, hypercholesterolemia, hypertension, and obesity was most optimal with an area under the curve statistic of 87.2% Familial risk assessment can stratify risk for early-onset coronary heart disease. Several conditions associated with increased familial risk can be prevented. These results have important implications for risk assessment and risk-reducing interventions.

  4. Early-Onset Psychosis in Youth with Intellectual Disability

    Science.gov (United States)

    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…

  5. Is prophylaxis of early-onset group B streptococcal disease ...

    African Journals Online (AJOL)

    Background. Early-onset group B streptococcal (GBS) disease in neonates can be prevented by the use of intrapartum chemoprophylaxis. There are two prevention strategies, one based on risk factors and the other on culture screening for GBS. This study sought to establish whether GBS chemoprophylaxis is appropriate ...

  6. Functional neuroimaging in early-onset anorexia nervosa.

    Science.gov (United States)

    Lask, Bryan; Gordon, Isky; Christie, Deborah; Frampton, Ian; Chowdhury, Uttom; Watkins, Beth

    2005-01-01

    Previous neuroimaging studies in early-onset anorexia nervosa provide evidence of limbic system dysfunction. The current study adds support to the possibility by revealing a significant association between unilateral reduction of blood flow in the temporal region and impaired visuospatial ability, impaired visual memory, and enhanced speed of information processing. 2005 by Wiley Periodicals, Inc.

  7. Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

    Science.gov (United States)

    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…

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

    Science.gov (United States)

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

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset

  9. Late-Onset Metachromatic Leukodystrophy with Early Onset Dementia Associated with a Novel Missense Mutation in the Arylsulfatase A Gene.

    Science.gov (United States)

    Stoeck, Katharina; Psychogios, Marios Nikos; Ohlenbusch, Andreas; Steinfeld, Robert; Schmidt, Jens

    2016-01-01

    A 48-year-old male patient presented with personality changes and progressive memory loss over 2 years with initially suspected Hashimoto's encephalopathy. Strategy of diagnostic workup of early onset dementia included dementia from neurodegenerative, neuroinflammatory, metabolic/toxic, and psychiatric origin. The patient's neurological exam was normal. MRI revealed a leukencephalopathy, predominantly in the frontal periventricular white matter, without notable changes over 2 years. On neurophysiological examination, prolonged central conduction times and a sensorimotor polyneuropathy were noted. Neuropsychological impairment included disorientation in place and a reduced short time memory. Behavioral alterations were predominated by sudden mood changes and disinhibition. Cerebrospinal fluid was normal. Despite presence of thyroid autoantibodies, glucocorticosteroid treatment did not improve the dementia. A metachromatic leukodystrophy was diagnosed by decreased arylsulfatase-A activity in leucocytes/fibroblasts and identification of a compound heterozygous mutation in the ARSA gene: c.542T>G (exon 3) and the novel mutation c.1013T>C (exon 6). Pathogenic function was suggested by bioinformatic mutation search. In a patient with early onset dementia, strategic diagnostic workup including genetic assessment revealed an adult-onset metachromatic leukodystrophy with a novel mutation in the arylsulfatase A gene.

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

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

    Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: 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. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

  11. Early-onset androgenetic alopecia and endocrine disruptors

    Directory of Open Access Journals (Sweden)

    M. Guarrera

    2011-01-01

    Full Text Available Androgenetic alopecia (AGA is the most common acquired non scarring alopecia in humans caused by androgen hormones in the setting of a genetic predisposition. Usually AGA starts after puberty, but recently it has been observed also in adolescents. Their mean age was 13 years with a slight prevalence in males. The premature AGA may be caused by environmental, alimentary (meat and milk or cosmetics overexposure to sexual hormones or to endocrine disrupters (EDs. EDs are "exogenous substances that interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body causing adverse effects to human health" and they are able bind to the steroid hormone receptors. Early onset AGA may be linked to the well known phenomenon of early puberty caused in some cases by hormones contained in food or by environmental chemicals. Therefore it is likely that the EDs may play a role also in the pathogenesis of early-onset AGA.

  12. Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood.

    Science.gov (United States)

    Roduit, Caroline; Frei, Remo; Depner, Martin; Karvonen, Anne M; Renz, Harald; Braun-Fahrländer, Charlotte; Schmausser-Hechfellner, Elisabeth; Pekkanen, Juha; Riedler, Josef; Dalphin, Jean-Charles; von Mutius, Erika; Lauener, Roger Pascal; Hyvärinen, Anne; Kirjavainen, Pirkka; Remes, Sami; Roponen, Marjut; Dalphin, Marie-Laure; Kaulek, Vincent; Ege, Markus; Genuneit, Jon; Illi, Sabina; Kabesch, Micahel; Schaub, Bianca; Pfefferle, Petra Ina; Doekes, Gert

    2017-07-01

    Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking. To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases. The Protection Against Allergy Study in Rural Environments (PASTURE) is a European birth cohort where pregnant women were recruited between August 2002 and March 2005 and divided in 2 groups dependent on whether they lived on a farm. Children from this cohort with data on atopic dermatitis from birth to 6 years of age were included. Atopic dermatitis, defined as an itchy rash on typical locations from birth to 6 years. The latent class analysis was used to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases. We included 1038 children; of these, 506 were girls. The latent class analysis model with the best fit to PASTURE data separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early

  13. Intraspinal anomalies in early-onset idiopathic scoliosis.

    Science.gov (United States)

    Pereira, E A C; Oxenham, M; Lam, K S

    2017-06-01

    In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

  14. TPIT mutations are associated with early-onset, but not late-onset isolated ACTH deficiency.

    Science.gov (United States)

    Metherell, L A; Savage, M O; Dattani, M; Walker, J; Clayton, P E; Farooqi, I S; Clark, A J L

    2004-10-01

    Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder that is clinically and genetically heterogeneous. Patients are characterised by low or absent cortisol production secondary to low plasma ACTH despite normal secretion of other pituitary hormones and the absence of structural pituitary defects. Onset may occur in the neonatal period, but may first be observed in later childhood. Recently, mutations in the TPIT gene, a T-box factor selectively expressed in developing corticotroph cells, have been found in cases of early-onset IAD. Here we report the screening of the TPIT gene in seven patients with IAD, four of whom had neonatal onset. Genomic DNA was extracted and the sequences of the 8 TPIT exons and their intron/exon junctions were determined by automated sequencing. Two siblings with early-onset IAD were both compound heterozygotes for mutations in exons 2 and 6. The missense mutation (Met86Arg) in exon 2 within the T-box (or DNA binding domain) is predicted to disrupt DNA binding. A frameshift mutation in exon 6 (782delA) introduces a premature stop codon and is likely to lead to a non-functional truncated protein. No nucleotide changes were observed in exonic sequences in the other two early- or the three later-onset cases. Fifteen single nucleotide polymorphisms that were not predicted to change the TPIT transcript were also detected. These findings provide a further illustration of the genetic heterogeneity of IAD and are highly suggestive of one or more other genes being implicated in this disorder.

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

    Directory of Open Access Journals (Sweden)

    Shamshul Ansari

    2015-01-01

    Full Text Available 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.

  16. Complications of growth-sparing surgery in early onset scoliosis.

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    Akbarnia, Behrooz A; Emans, John B

    2010-12-01

    Review of available literature, authors' opinion. To describe complications associated with growth-sparing surgical treatment of early onset scoliosis (EOS). EOS has many potential etiologies and is often associated with thoracic insufficiency syndrome. The growth of the spine, thorax, and lungs are interrelated, and severe EOS typically involves disturbance of the normal development of all 3. Severe EOS may be treated during growth with surgical techniques, intended to preserve growth while controlling deformity, the most common of which are spinal "growing rods" (GR) or "vertical expandable prosthetic titanium rib" (VEPTR). Although presently popular, there is minimal long-term data on the outcome of growth-sparing surgical techniques on EOS. Review. Potential adverse outcomes of GR or VEPTR treatment of EOS include failure to prevent progressive deformity or thoracic insufficiency syndrome, an unacceptably short or stiff spine or deformed thorax, increased family burden of care, and potentially negative psychological consequences from repeated surgical interventions. Neither technique reliably controls all deformity over the entirety of growth period. Infections are common to both GR and VEPTR. Rod breakage and spontaneous premature spinal fusion beneath rods are troublesome complications in GR, whereas drift of rib attachments and chest wall scarring are anticipated complications in VEPTR treatment. Indications for GR and VEPTR overlap, but thoracogenic scoliosis and severe upper thoracic kyphosis are best treated by VEPTR and GR, respectively. Surgeons planning treatment of EOS should anticipate the many complications common to growth-sparing surgery, share their knowledge with families, and use complications as one factor in the complex decision as to when and whether to initiate the repetitive surgeries associated with GR or VEPTR in the treatment of severe EOS.

  17. Early onset of treatment effects with oral risperidone

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    Naber Dieter

    2007-01-01

    Full Text Available Abstract Background The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. Methods In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. Results Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. Conclusion Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration.

  18. Early and phasic cortical metabolic changes in vestibular neuritis onset.

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    Marco Alessandrini

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

  19. Early-onset dementias: diagnostic and etiological considerations.

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    Masellis, Mario; Sherborn, Kayla; Neto, Pedro; Sadovnick, Dessa A; Hsiung, Ging-Yuek R; Black, Sandra E; Prasad, Sadhana; Williams, Meghan; Gauthier, Serge

    2013-07-31

    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.

  20. The genetics of very early onset Alzheimer disease.

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    Filley, Christopher M; Rollins, Yvonne D; Anderson, C Alan; Arciniegas, David B; Howard, Katherine L; Murrell, Jill R; Boyer, Philip J; Kleinschmidt-DeMasters, Belte K; Ghetti, Bernardino

    2007-09-01

    This study was undertaken to clarify the genetics of very early onset Alzheimer disease (VEOAD), defined as AD beginning before age 35. Early onset AD (EOAD) is defined by onset of symptoms before age 65, and affected individuals may harbor a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein. VEOAD is exceedingly rare, and PSEN1 mutations have been implicated. We encountered a man with phenotypic frontotemporal dementia beginning at age 32 and a strong family history of an autosomal dominant dementia who was found at autopsy to have AD. Histologic and genetic analyses of the patient's brain were undertaken, and a review of all published VEOAD cases was performed. Histologic findings were diagnostic of advanced stage AD. Genetic evaluation of brain tissue identified an intronic PSEN1 polymorphism; no known pathogenic mutation was found. Literature review (1934 to 2007) disclosed 101 cases of VEOAD; the youngest age of dementia onset was 24 years. In all cases in which definitive genetic analysis was available, either a PSEN1 mutation or linkage to chromosome 14 was found. VEOAD can present with atypical clinical features, including findings suggestive of frontotemporal dementia. All reported cases of VEOAD with conclusive genetic analysis seem to be associated with PSEN1 mutations. Genetic testing in adults younger than 35 with dementia can identify the genetic defect and assist in diagnosis and family counseling.

  1. Different alterations of cerebral regional homogeneity in early-onset and late-onset Parkinson's disease

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    Ke Sheng

    2016-07-01

    Full Text Available AbstractObjective: Early-onset Parkinson’s disease (EOPD is distinct from late-onset PD (LOPD as it relates to the clinical profile and response to medication. The objective is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD and 37 age-matched normal control subjects. Regional homogeneity (ReHo approaches were employed using ANOVA with two factors: PD and age.Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen gyrus and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; however, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset.

  2. Genetic Determinism of Primary Early-Onset Osteoarthritis.

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

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Familial early onset sarcoidosis with bone cysts and erosions

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    Blank, Norbert; Max, Regina; Lorenz, Hanns-Martin [University of Heidelberg, Department of Internal Medicine V, Division of Rheumatology, Heidelberg (Germany); Autschbach, Frank [University of Heidelberg, Department of Pathology, Heidelberg (Germany); Libicher, Martin [University of Cologne, Department of Radiology, Cologne (Germany)

    2007-09-15

    Early onset sarcoidosis is a granulomatous disease which is characterized by synovitis, polyarthritis, skin and eye involvement. We report the skeletal features of one patient with a family history and clinical symptoms suggestive of early onset sarcoidosis (EOS) which was confirmed by skin biopsy. Radiographs reveal postarthritic deformities of the MCP joints, contractures, a coarsened trabecular pattern at the PIP joints and small bone cysts resembling osteitis cystoides multiplex. Similar lesions were described in radiographs of the older sister and an uncle of our patient. This is the first report demonstrating bone cysts and erosions which could be a diagnostic feature in this rare disease and may help to differentiate other rheumatoid disorders. (orig.)

  4. Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

    Science.gov (United States)

    Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

    2015-07-01

    Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. [Early-onset eating disorders: a review of the literature].

    Science.gov (United States)

    Poppe, I; Simons, A; Glazemakers, I; Van West, D

    2015-01-01

    The incidence of anorexia nervosa (AN) in adolescents has increased significantly in recent years. In several studies and in the media it has been suggested that AN has recently become more prevalent in the pre-adolescence. In view of the impact that an eating disorder can have on a child, it is important to diagnose and start treating the illness as early as possible. To review the literature on the characteristics and susceptibilities of patients with eating disorders because this information can be important for early diagnosis, prevention and identification of susceptibilities to early-onset eating disorders. We searched the literature for articles relating to early-onset eating disorders. We based our search on PubMed and on related relevant articles listed in the references. We selected 34 relevant articles published between 1987 and 2014. The literature lists characteristics and susceptibilities at various levels. Many types of factors are involved; examples of 'biological' factors are prior streptococcal infection, previous consultations with GP and a patients medical history; psychological factors include comorbidity, temperament, a particular personality profile, maturation-anxiety; environmental factors such as family history, family functioning and/or stressful events can play a role in the development of eating disorders. CONCLUSION The literature indicates that the early development of AN in children is related to a complex combination of etiological factors. However, there is a need for more research into this group of patients.

  6. Stabilization in early adult-onset myopia with corneal refractive therapy.

    Science.gov (United States)

    González-Méijome, José M; Carracedo, Gonzalo; Lopes-Ferreira, Daniela; Faria-Ribeiro, Miguel A; Peixoto-de-Matos, Sofia C; Queirós, António

    2016-02-01

    To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between -1.50 and -2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ) lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January-December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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    J Casey Olson

    Full Text Available 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

  8. Bilateral rib-to-pelvis technique for managing early-onset scoliosis.

    Science.gov (United States)

    Smith, John T

    2011-05-01

    Early-onset scoliosis describes progressive spinal deformity of varying etiologies in the growing child. The management of early-onset scoliosis is challenging, with many treatment options but no conclusive evidence for the best treatment method. We describe a bilateral percutaneous rib-to-pelvis technique, present our early experience with this technique in patients with early-onset scoliosis, identify adverse events, and determine whether these are comparable to those for other current techniques. The VEPTR(®) device is placed through three small incisions that allow for attachment of rib hooks bilaterally at the upper end and through pelvic hooks at the distal end, providing distraction forces to correct the deformity while allowing for growth. We retrospectively reviewed all 37 patients with early-onset scoliosis treated with the bilateral rib-to-pelvis VEPTR(®) technique from 2003 and 2009. Patients were evaluated for demographics, diagnosis, curve correction, and adverse events and divided into two groups: ambulatory and nonambulatory. The 18 ambulatory patients underwent 139 procedures and the 19 nonambulatory patients underwent 100 procedures. Average followups were 84 and 64 months in the ambulatory and nonambulatory groups, respectively. The rate of adverse events per procedure was 13%. Thirty-nine percent of ambulatory patients developed a marked crouched gait over time. The rate of adverse events in the nonambulatory group was 15%. This technique appears a reasonable alternative to growing rods for the management of early-onset scoliosis in nonambulatory children due to the low rate of adverse events. Due to the increased incidence of crouched gait, we have abandoned this technique in ambulatory children unless there is no option to attach the distal fixation to the spine.

  9. Differences of symptoms and standardized weight index between patients with early-onset and late-onset anorexia nervosa.

    Science.gov (United States)

    Matsumoto, H; Takei, N; Kawai, M; Saito, F; Kachi, K; Ohashi, Y; Takeuchi, H; Mori, N

    2001-07-01

    There have so far been no studies that directly compared clinical features between patients with early- and late-onset anorexia nervosa (AN). We identified 64 patients with DSM-III-R AN. We defined individuals as an early-onset group, who had an age of onset before 14 years (N = 31), and the remaining as a late-onset group (N = 33). The clinical symptoms, body weight and weight index, were compared between the two groups. Subjects were dichotomized into those with extremely low weight and those remaining. We compared the proportion of the patients with extremely low weight between the two groups. The rates of 'self-induced vomiting' and 'purging' were significantly lower in a group of patients with early-onset AN than in those with late-onset AN. There were significantly fewer subjects with extremely low weight in early-onset than in late-onset AN group. We found clear differences in clinical features between early- and late-onset AN groups.

  10. [46-OR] : Early and late onset preeclampsia versus small for gestational age risks in subsequent pregnancies

    NARCIS (Netherlands)

    Bernardes, Thomas P; Mol, Ben W; Ravelli, Anita C; van den Berg, Paul P; Stolk, Ronald P; Groen, Henk

    OBJECTIVES: Current literature suggests that early and late onset preeclampsia should be treated as distinct entities and that early onset preeclampsia shares pathophysiology aspects with intrauterine growth restriction. Our objective was to investigate whether 5th percentile small for gestational

  11. Treatment Outcome of Adolescent Inpatients With Early-Onset and Adolescent-Onset Disruptive Behavior.

    Science.gov (United States)

    de Boer, Sjoukje Berdina Beike; Boon, Albert Eduard; Verheij, Fop; Donker, Marianne Catharina Henriëtte; Vermeiren, Robert

    2017-04-01

    Unlike adolescents with adolescent-onset (AO) disruptive behavior, adolescents with early-onset (EO) disruptive behavior may not benefit from treatment. Using Symptom Checklist (SCL-90-R) ratings at admission and discharge of adolescent inpatients with EO (n = 85) and AO (n = 60) disruptive behavior treatment outcome was determined by (a) a change in mean scores and (b) the Reliable Change Index. For a subgroup, ratings on the Satisfaction Questionnaire Residential Youth Care for Parents (n = 83) were used to verify the treatment outcome. Inpatients with EO disruptive behavior had a higher risk of dropout (44.4%) from treatment than the AO group (24.7%). Among the treatment completers, both onset groups reported improvements on the SCL-90-R, with 26.9% recovering and 31.7% improving. Inpatients who reported improvement were mostly rated as improved by their parents (r = .33). As EO inpatients are more likely to drop out, interventions should aim at motivating youngsters to continue treatment, particularly given the poor outcome in this group. Treatment may benefit both groups because those EO youths who stayed in treatment improved to the same extent as AO inpatients. © 2016 Wiley Periodicals, Inc.

  12. Study protocol: EXERcise and cognition in sedentary adults with early-ONset dementia (EXERCISE-ON).

    Science.gov (United States)

    Hooghiemstra, Astrid M; Eggermont, Laura H P; Scheltens, Philip; van der Flier, Wiesje M; Bakker, Jet; de Greef, Mathieu H G; Koppe, Peter A; Scherder, Erik J A

    2012-08-16

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

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

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    Hooghiemstra Astrid M

    2012-08-01

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

  14. A Japanese girl with an early-infantile onset vanishing white matter disease resembling Cree leukoencephalopathy.

    Science.gov (United States)

    Takano, Kyoko; Tsuyusaki, Yu; Sato, Mutsumi; Takagi, Mariko; Anzai, Rie; Okuda, Mitsuko; Iai, Mizue; Yamashita, Sumimasa; Okabe, Tetsuhiko; Aida, Noriko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Matsumoto, Naomichi; Osaka, Hitoshi

    2015-06-01

    Vanishing white matter disease (VWM)/childhood ataxia with central hypomyelination (CACH) is an autosomal recessive leukoencephalopathy caused by mutations in one of five genes, EIF2B1-5, encoding the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B). The classical phenotype is characterized by early childhood onset and chronic progressive neurological deterioration with cerebellar ataxia, spasticity, optic atrophy and epilepsy. However, the onset of disease varies from antenatal period to adulthood. Cree leukoencephalopathy (CLE) is a severe variant of VWM and caused by a homozygous mutation (R195H) in the EIF2B5 gene. The patient reported in this study developed lethargy, vomiting and seizure 3days after an oral poliovirus vaccination at the age of 4months. She presented with rapid neurological deterioration within a month of onset. Brain MRI showed abnormal white matter intensity. Whole-exome sequencing identified two heterozygous mutations in the EIF2B5 gene: a known mutation, c.584G>A (R195H, which is homozygous in CLE), and a novel mutation, c.1223T>C (I408T, which resides in the "I-patch"). Mutations in the "I-patch" encoded region of eIF2Bε may be related to an early-infantile onset phenotype. This patient exhibits an early-infantile onset and progressive disease course resembling CLE, suggesting a severe functional disruption of eIF2Bε caused by R195H as well as by I408T mutations. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Probable early-onset Alzheimer's disease in an apolipoprotein E2 homozygote.

    Science.gov (United States)

    Cole, Lauren; Belden, Christine; Jacobson, Sandra; Liebsack, Carolyn; Myers, Kent; Reninger, Cornelia; Berk, Camryn; Sabbagh, Marwan N

    2010-01-01

    To describe a case of early-onset Alzheimer's disease (AD) in an apolipoprotein (Apo) ε2/ε2 homozygote. Apo ε2/ε2 is the rarest of the ApoE genotypes, representing only 1.4% of the population. Cognitive decline in ApoE ε2 homozygotes has rarely been reported. We report a 58-year-old Apo ε2/ε2 female who meets clinical criteria for probable AD as confirmed by neuropsychological testing, positron emission/computed tomography scan, CSF analysis and genetic screening for known mutations. The clinical course is typical of AD, with progressive cognitive and functional decline. Clinically confirmed early-onset AD is atypical in ApoE2 homozygotes but can occur. Copyright © 2010 S. Karger AG, Basel.

  16. INFLAMMATORY BOWEL DISEASE WITH A VERY EARLY ONSET

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    E. A. Kornienko

    2016-01-01

    Full Text Available Inflammatory bowel disease (Crohn's disease and ulcerative colitis has a tendency to manifest at earlier age. In childhood (< 6 years of age it has an especially severe course and is characterized by high grade inflammation, predominantly in the colon, by complication and extra-intestinal autoimmune injury. At younger age, Crohn's disease and ulcerative colitis require more aggressive treatment with frequently poor results. From genetic point of view, monogenic mutations controlling the immune response are characteristic for these diseases with an early onset; therefore, they are frequently associated with primary immunodeficiency. This implies various immunologic deficits, such as breakdown of the epithelial barrier, phagocytic dysfunction and dysfunction of Т and В lymphocytes and regulatory Т cells. Depending on this, a number of primary immunodeficiencies are identified associated with monogenic mutations of more than 50 genes. There some age-related specific features at manifestation. Thus, defects in interleukin 10 and FOXP3 manifest in the first months of life, whereas severe combined immunodeficiencies and phagocytosis defects become evident somewhat later. Virtually all 24 children with very early onset of inflammatory bowel disease, whom we examined, had immunologic defects and one child had a XIAP gene mutation. After identification of a specific immunologic defect, one can understand the mechanism of the disease and suspect one or another genetic defect with subsequent reasonable assessment of mutations in candidate genes. Detection of immunologic and genetic defects in children with a very early onset of inflammatory bowel disease allows for choosing an adequate strategy of non-conventional treatment that may differ depending on the mechanism of the disease.

  17. Early-onset anorexia nervosa in girls with Asperger syndrome

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    Dudova I

    2015-07-01

    Full Text Available Iva Dudova, Jana Kocourkova, Jiri Koutek Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Eating disorders frequently occur in conjunction with autism spectrum disorders, posing diagnostic and therapeutic difficulties. The comorbidity of anorexia nervosa and Asperger syndrome is a significant clinical complication and has been associated with a poorer prognosis. The authors are presenting the cases of an eleven-year-old girl and a five-and-a-half-year-old girl with comorbid eating disorders and Asperger syndrome. Keywords: eating disorders, early-onset anorexia nervosa, autism spectrum disorders, Asperger syndrome, diagnostics, therapy

  18. Early onset neonatal sepsis: diagnostic dilemmas and practical management.

    Science.gov (United States)

    Bedford Russell, A R; Kumar, R

    2015-07-01

    Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Early Onset Childhood Obesity and Risk of Metabolic Syndrome

    Centers for Disease Control (CDC) Podcasts

    2017-10-09

    This podcast features Lorena Pacheco, a doctoral student at the University of California San Diego and one of the winners of PCD’s 2017 Student Research Paper Contest. Lorena answers questions about her winning research, which focuses on the relationship between early onset obesity as a risk factor for increased metabolic syndrome in Chilean children.  Created: 10/9/2017 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/9/2017.

  20. Long-term outcome in early-onset anorexia nervosa.

    Science.gov (United States)

    Walford, G; McCune, N

    1991-09-01

    Fifteen children who developed anorexia nervosa aged 13 years or less were followed up at least three years later (mean 5.3 years). Outcome measures included the Morgan & Russell Outcome Schedule and the PSE. The general outcome was good in seven, intermediate in four, and poor in four, one of whom had died. A high incidence of psychiatric symptoms at follow-up, which has been suggested in other studies, was not confirmed in the 11 subjects who completed the PSE. Where onset was very early (11 years and under) and where hospital stay was prolonged, outcome tended to be poor.

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

    Science.gov (United States)

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

    2014-06-06

    Alzheimer's disease (AD) is a progressive brain disorder that causes gradual and irreversible loss of higher brain functions and is the most common cause of dementia in the elderly, as assessed by autopsy and clinical series. Furthermore, it has an annual incidence of approximately 3% in the 65-74-year-old age group. This incidence rate doubles with every increment of 5 years above the age of 65. In Morocco, AD affects almost 30,000 individuals and this number will possibly increase to 75,000 by 2020 (projections of the World Health Organization (WHO)). Genetically, AD is caused by a mutation in one of at least 3 genes: presenilin 1 (PS1), presenilin 2 (PS2) and the amyloid precursor protein (APP). Most cases are late onset and apparently sporadic, most likely as a result of a combination of environmental and non-dominant genetic factors. In Morocco, the genes predisposing individuals to AD and predicting disease incidence remain elusive. The purpose of the present study was to evaluate the genetic contribution of mutations in PS1 and PS2 genes to familial early-onset AD cases and sporadic late-onset AD cases. Seventeen sporadic late-onset AD cases and eight familial early-onset AD cases were seen at the memory clinic of the University of Casablanca Neurology Department. These patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Direct sequencing of each exon in PS1 and PS2 genes was performed on genomic DNA of AD patients. Further, we identified 1 novel frameshift mutation in the PS1 gene and 2 novel frameshift mutations in the PS2 gene. Our mutational analysis reports a correlation between clinical symptoms and genetic factors in our cases of Early-Onset Alzheimer's Disease (EOAD). These putative mutations cosegregate with affected family members suggesting a direct mutagenic effect. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Sleep problems in early childhood and early onset of alcohol and other drug use in adolescence.

    Science.gov (United States)

    Wong, Maria M; Brower, Kirk J; Fitzgerald, Hiram E; Zucker, Robert A

    2004-04-01

    No prospective studies exist on the relationship between sleep problems early in life and subsequent alcohol use. Stimulated by the adult literature linking sleep problems to the subsequent onset of alcohol use disorders in some adults, we examined whether sleep problems in early childhood predicted the onset of alcohol and other drug use in adolescence and whether such a relationship was mediated by other known predictors of this relationship, namely, attention problems, anxiety/depression, and aggression in late childhood. This study is part of an ongoing longitudinal study of the development of risk for alcohol and other substance use disorders. Study participants were 257 boys from a community-recruited sample of high-risk families. Mothers' ratings of their children's sleep problems at ages 3 to 5 years significantly predicted an early onset of any use of alcohol, marijuana, and illicit drugs, as well as an early onset of occasional or regular use of cigarettes by age 12 to 14. Additionally, although sleep problems in early childhood also predicted attention problems and anxiety/depression in later childhood, these problems did not mediate the relationship between sleep problems and onset of alcohol and other drug use. This is, to our knowledge, the first study that prospectively examines the relationship between sleep problems and early onset of alcohol use, a marker of increased risk for later alcohol problems and alcohol use disorders. Moreover, early childhood sleep problems seem to be a robust marker for use of drugs other than alcohol. Implications for the prevention of early alcohol and other drug use are discussed.

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

    Science.gov (United States)

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

    2015-01-01

    Early onset deformity of the spine and chest wall (initiated 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.

  4. A case of early-onset radiation retinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Yoko; Den, Seika; Shimizu, Kazuhiro; Ikeda, Tsunehiko [Osaka Medical Coll., Takatsuki (Japan)

    2001-12-01

    We encountered a 27-year-old male early caused by radiation retinopathy five months after radiotherapy (51 Gy) for astrocytoma. The retinopathy was the proliferative retinopathy, with several dot and blot hemorrhages, hard and soft exudate, increased capillary permeability, macula edema and avasucular areas. So it was treated with panretial photocoagulation like diabetic retinopathy. Now hemorrhage, exudate, edema and avascular areas were improved. Photocoagulation treatment is effective to stop the progression of radiation retinopathy. Radiation retinopathy is sometimes early caused, therefore long-term follow up is recommended on starting radiotherapy. (author)

  5. Subacute sclerosing panencephalitis presenting as rapidly progressive young-onset dementia.

    Science.gov (United States)

    Chakor, Rahul Tryambak; Santosh, Nandanavana Subbareddy

    2013-07-01

    Onset of dementia before 65 years of age is termed as young-onset dementia (YOD). Very little literature exists regarding the clinical features and diagnoses of dementia in younger individuals. We present a case series of four patients of age 10 to 23 years with severe dementia within 18 months of clinical onset (rapidly progressive dementia). Three patients had generalised periodic complexes typical of subacute sclerosing panencephalitis (SSPE) on electroencephalogram (EEG). All patients had elevated cerebrospinal fluid (CSF) IgG measles antibodies. Our case series highlights that SSPE is an important cause of rapidly progressive YOD in developing countries like India.

  6. The External Limiting Membrane in Early-Onset Stargardt Disease

    Science.gov (United States)

    Lee, Winston; Nõupuu, Kalev; Oll, Maris; Duncker, Tobias; Burke, Tomas; Zernant, Jana; Bearelly, Srilaxmi; Tsang, Stephen H.; Sparrow, Janet R.; Allikmets, Rando

    2014-01-01

    Purpose. To describe pathologic changes of the external limiting membrane (ELM) in young patients with early-onset Stargardt (STGD1) disease. Methods. Twenty-six STGD1 patients aged younger than 20 years with confirmed disease-causing adenosine triphosphate–binding cassette, subfamily A, member 4 (ABCA4) alleles and 30 age-matched unaffected individuals were studied. Spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (AF), and color fundus photography (CFP) images, as well as full-field electroretinograms were obtained and analyzed for one to four visits in each patient. Results. The ELM in all patients exhibited a distinct thickening that was not observed in unaffected individuals. In addition, accumulations of reflective deposits were noted in the outer nuclear layer in every patient. Four patients exhibited a concave protuberance or bulging of a thickened and hyperreflective ELM band within the fovea containing preserved photoreceptors. Longitudinal SD-OCT data in several patients revealed the persistence of this ELM abnormality over a period of time (1–4 years). Furthermore, the edges of the inner segment ellipsoid band appeared to recede earlier than the ELM band in active lesions. Conclusions. Structural changes seen in the ELM of this cohort may reflect a gliotic response to cellular stress at the photoreceptor level in early-onset STGD1. PMID:25139735

  7. Expanding the definition of a positive family history for early-onset coronary heart disease.

    Science.gov (United States)

    Scheuner, Maren T; Whitworth, William C; McGruder, Henraya; Yoon, Paula W; Khoury, Muin J

    2006-08-01

    Assessing familial risk for early-onset coronary heart disease (CHD) is typically limited to first-degree relatives with early-onset CHD. To evaluate the impact of additional family history, we examined the associations between various family history definitions and early-onset CHD. By using the national HealthStyles 2003 survey data, we assessed associations between self-reported family history and personal history of early-onset CHD (diagnosed at or before age 60 years), adjusting for demographics, hypercholesterolemia, hypertension, and obesity. Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years; 4.4% had early-onset CHD. In addition to having at least one first-degree relative with early-onset CHD, other significant associations included having at least one first-degree relative with late-onset CHD, at least one second-degree relative with early-onset CHD, and two or more affected second-degree relatives regardless of age of onset of CHD. Early-onset stroke in at least one first-degree relative and, in women, having at least one first-degree relative with diabetes were also significantly associated with early-onset CHD. Family history beyond early-onset CHD in first-degree relatives is significantly associated with prevalent CHD diagnosed at or before age 60 years.

  8. Suicide in later life : A comparison between cases with early-onset and late-onset depression

    NARCIS (Netherlands)

    Voshaar, Richard C. Oude; Kapur, Nay; Bickley, Harriet; Williams, Alyson; Purandare, Nitin

    Background: Suicide rates are high in elderly people with depressive disorder. We compared behavioural, clinical and care characteristics of depressed elderly patients, aged 60 years and over at the time of death by suicide, with an early-onset depression (EOD, onset before 60 years) with those

  9. Prevalidation of liver slices as a model for the early onset of liver fibrosis to test anti-fibrotic drugs

    NARCIS (Netherlands)

    Westra, Inge; Groothuis, Genoveva; Olinga, Peter

    Liver fibrosis is the progressive accumulation of connective tissue that affects the normal function of the liver and will eventually lead to liver cirrhosis. The aim of this study is to prevalidate precision-cut liver slices (PCLS) as an in vitro model to investigate the early onset of liver

  10. Co-occurring problems of early onset persistent, childhood limited, and adolescent onset conduct problem youth.

    Science.gov (United States)

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

    2010-11-01

    It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems differentially co-develop with the EOP, CL and AO trajectories across the childhood and adolescent years. Using data from the Avon Longitudinal Study of Parents and Children, an epidemiological, longitudinal cohort of boys and girls, we estimated growth curves for parent-reported hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors conditional on trajectories of conduct problems (i.e., EOP, CL and AO) from ages 4 to 13 years. At ages 7-8 years, DSM-IV-based diagnoses of conduct disorder, oppositional-defiant disorder, attention deficit/hyperactivity disorder (ADHD), anxiety, depression were examined by conduct problems trajectory. Overall, the development of hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors mirrored the development of conduct problems, showing similar trajectories. Results indicated that the problems of EOP youth were persistent across domains, CL youth showed decreased behavior problems while increasing in prosocial behaviors, and AO youth increased in adjustment problems after 10 years of age. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

  11. Early-onset heroin use and its link to conduct disorder: Clinical and management challenges

    Directory of Open Access Journals (Sweden)

    Shobhit Jain

    2016-01-01

    Full Text Available Childhood substance abuse and delinquency often progress to harder substances and antisocial personality disorder and carries deleterious consequences for self, family and community at large. Early management of such cases poses several clinical and management challenges, as highlighted in the present case. The treatment seeking for this sub-population is very low in spite of community surveys showing a worrisome pattern of substance use among younger population. Further, very few specialty clinics and trained manpower exist in the country to manage early onset substance use. Whether conduct disorder be cause or consequence for drug use is debatable, in view of shared risk factors. The present case helps to understand need for comprehensive assessment for identifying risk factors and comorbid conditions. Only pharmacological management does not help, psychosocial management must be delivered. Several prevention strategies may also help if these risk factors are identified before progression to illicit substance use disorder.

  12. Evidence for allelic heterogeneity in familial early-onset Alzheimer's disease

    NARCIS (Netherlands)

    C.M. van Duijn (Cornelia); J. Hardy (John); A.M. Goate (Alison); M.N. Rossor (Martin); A. Vandenberghe (Anton); J-J. Martin (Jean-Jacques); M.J. Mullan; C. van Broeckhoven (Christine); A. Hofman (Albert)

    1991-01-01

    textabstractAge of onset was examined for 139 members of 30 families affected by early-onset AD. Most (77%) of the variance of age of onset derived from differences between rather than within families. The constancy of age of onset within families was also observed in an analysis restricted to

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

    Science.gov (United States)

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

    2010-05-01

    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.

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

    Science.gov (United States)

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

    2013-10-01

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

  15. Late onset progressive multifocal leukoencephalopathy in Hodgkin lymphoma.

    Science.gov (United States)

    Aamodt, Whitley W; Siegler, James E; Viaene, Angela N; Rubenstein, Michael N

    2017-09-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from infection of oligodendrocytes in the central nervous system with John Cunningham virus. Although PML is commonly diagnosed in immunocompromised patients with human immunodeficiency virus, it can also arise in other immunodeficient states. In this report, we present an unusual case of PML occurring 40years after chemoradiation therapy for Hodgkin lymphoma in a patient with normal total lymphocyte counts on annual surveillance. Although current guidelines recommend annual complete blood counts for patients in remission, this testing may be insufficient to monitor patients with chronic CD4+ lymphopenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Comparing Characteristics of Early-Onset Injection Drug Users to Those With Late-Onset Injection in Kermanshah, Iran.

    Science.gov (United States)

    Jorjoran Shushtari, Zahra; Noroozi, Alireza; Mirzazadeh, Ali; Ahounbar, Elahe; Hajbi, Ahmad; Najafi, Mohammad; Bazrafshan, Ali; Farhadi, Mohammad Hossin; Farhoudian, Ali; Higgs, Peter; Shahboulagh, Farahnaz Mohammadi; Waye, Katherine; Noroozi, Mehdi

    2017-05-12

    Characteristics and behaviors of early-onset injection drug users are under studied topics in Iran. This study aimed to identify and compare the demographic characteristics as well as the drug using behaviors of early-onset and late-onset injection drug users in Kermanshah, West Iran. In this cross-sectional study using snowball and convenience sampling, we recruited 450 people during the Fall of 2014 from two drop in centers in Kermanshah, Iran. We collected data through face-to-face interviews. Early-onset injection is defined as whether the person reported their first injection at 22 years of age or younger. Subsequently, late-onset injection is defined as 23 years of age or older. We compared the characteristics of the two groups through both univariate and multiple logistic analyses. Overall, 54% (CI 95%: 44.3%, 62.2%) were early injectors. After controlling for low socioeconomic status, initiation of drug use at a young age, multiple drug use and methamphetamine use were all significantly associated with a higher likelihood of early-onset injection. Additionally, early-onset injection was associated with recent syringe borrowing (OR = 2.6, p = 0.001), recent syringe lending (OR = 1.4, p = 0.01), recent cooker sharing (OR = 3.2, p = 0.01) and injecting two or more times a day (OR = 2.2, p = 0.04). Early-onset injectors were more likely to report a lower socioeconomic status, initiation of first drug use at a younger age, using methamphetamine alongside polydrug use, and engaging in higher risk taking behaviors like borrowing needles. With these associations, the study emphasizes the need for drug-prevention programs to focus on the transition to injection drug use at younger ages.

  17. Differences in impulsivity and sensation seeking between early- and late-onset alcoholics

    NARCIS (Netherlands)

    Dom, G.; Hulstijn, W.; Sabbe, B.G.C.

    2006-01-01

    The personality traits of impulsivity and sensation seeking have been proposed as important features of early-onset alcoholism. Early-onset (EOA, n = 62) and late-onset (LOA, n = 68 ) alcoholic inpatients were compared as to the severity of their substance use and related problems, and self-report

  18. Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

    Science.gov (United States)

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

    2008-01-01

    Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

  19. Structural brain abnormalities in early onset first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, A K; Baaré, W F C; Raabjerg Christensen, A M

    2007-01-01

    BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder, delusi...... already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis.......BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder......, delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed...

  20. Changes in cellular mechanical properties during onset or progression of colorectal cancer

    Science.gov (United States)

    Ciasca, Gabriele; Papi, Massimiliano; Minelli, Eleonora; Palmieri, Valentina; De Spirito, Marco

    2016-01-01

    Colorectal cancer (CRC) development represents a multistep process starting with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations confer a selective growth advantage to colonic epithelial cells that form first dysplastic crypts, and then malignant tumours and metastases. All these steps are accompanied by deep mechanical changes at the cellular and the tissue level. A growing consensus is emerging that such modifications are not merely a by-product of the malignant progression, but they could play a relevant role in the cancer onset and accelerate its progression. In this review, we focus on recent studies investigating the role of the biomechanical signals in the initiation and the development of CRC. We show that mechanical cues might contribute to early phases of the tumour initiation by controlling the Wnt pathway, one of most important regulators of cell proliferation in various systems. We highlight how physical stimuli may be involved in the differentiation of non-invasive cells into metastatic variants and how metastatic cells modify their mechanical properties, both stiffness and adhesion, to survive the mechanical stress associated with intravasation, circulation and extravasation. A deep comprehension of these mechanical modifications may help scientist to define novel molecular targets for the cure of CRC. PMID:27621568

  1. Assessment, Management, and Health Implications of Early-Onset Preeclampsia.

    Science.gov (United States)

    Phillips, Cathi; Boyd, Margaret

    2016-01-01

    Early-onset preeclampsia is a serious condition of pregnancy with the potential for adverse maternal and fetal health outcomes. A strong body of evidence supports the need for postpartum follow-up and health counseling, because these women and their offspring are at risk for future cardiovascular disease; nurses play a key role in this education. An understanding of the diagnosis, risk screening for, pathogenesis, and management of severe preeclampsia and its sequelae, such as intrauterine growth restriction and pulmonary edema, enables nurses to develop a comprehensive plan of care that will support women and their families through this challenging and dynamic complication of pregnancy. © 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  2. Pretreatment cardiometabolic status in youth with early-onset psychosis

    DEFF Research Database (Denmark)

    Jensen, Karsten G.; Correll, Christoph U.; Rudå, Ditte

    2017-01-01

    Objective: To describe pretreatment cardiometabolic constitution in children and adolescents with first-episode psychosis (FEP). Methods: Baseline cardiometabolic assessment was performed in youths aged 12-17 years with FEP entering the Tolerability and Efficacy of Antipsychotics (TEA) trial......: Comparing 113 youths with FEP (age ± SD = 15.74 ± 1.36 years, males = 30.1%, schizophrenia-spectrum disorders = 92.9%, antipsychoticnaive: n = 57) to 60 controls, patients had higher waist circumference (WC) zscores (1.13 ± 1.65 vs 0.42 ± 1.27, P =.018), cholesterol (4.10 ± 0.71 vs 3.79 ± 0.49 mmol/L, P...... cardiometabolic risk. Early age at onset predicted increased BMI and WC z scores, while diagnosis of schizophrenia and higher Clinical Global Impression-Severity score were associated with increased blood lipids. Conclusions: Youths with FEP had significantly greater WC and lipid abnormalities than matched...

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

    Science.gov (United States)

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

    2009-01-01

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

  4. Examining determinants of early and late age at onset in panic disorder: an admixture analysis.

    Science.gov (United States)

    Tibi, Lee; van Oppen, Patricia; Aderka, Idan M; van Balkom, Anton J L M; Batelaan, Neeltje M; Spinhoven, Philip; Penninx, Brenda W; Anholt, Gideon E

    2013-12-01

    Past research demonstrated that age at onset might account for different clinical and etiological characteristics in panic disorder (PD). However, prior research relied on arbitrary choices of age cut-offs. Using a data-driven validated method, this study aimed to examine differences between early and late onset PD in various determinants. Admixture analysis was used to determine the best fitting model of age at onset distribution in PD. Data was collected from 511 individuals (ages 18-65) with PD diagnoses, who participated in the Netherlands Study of Depression and Anxiety (NESDA). DSM-IV comorbidities and various measures of childhood adversities, suicidal behavior, anxiety and depressive symptoms were assessed. The best fitting cut-off score between early and late age at onset groups was 27 years (early age at onset ≤ 27 years). Univariate tests showed that participants with early onset PD were younger and more likely to be female. Early onset PD was associated with agoraphobia, higher frequency of childhood trauma and life events, and higher rates of suicide attempts as compared to late onset PD. Multivariate logistic regression analysis demonstrated that only current age, childhood trauma and agoraphobia remained significantly associated with early onset PD. Findings suggest that 27 years marks two onset groups in PD, which are slightly distinct. Early onset PD is independently associated with exposure to childhood trauma and increased avoidance. This highlights the importance of subtyping age of onset in PD. Clinical implications are further discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Factors influencing the onset and progression of pododermatitis in captive flamingos (Phoenicopteridae).

    Science.gov (United States)

    Wyss, F; Wenker, C; Hoby, S; Gardelli, B; Studer-Thiersch, A; von Houwald, F; Schumacher, V; Clauss, M; Doherr, M G; Häfeli, W; Furrer, S; Béchet, A; Robert, N

    2013-09-01

    Pododermatitis is a worldwide problem in captive flamingos. We performed an evaluation of different influence factors (age, sex, weight, origin, breeding status) and a comparison of foot lesions between several zoological institutions and the feet of free-ranging Greater flamingos (Phoenicopterus roseus). A scoring system was used to determine the prevalence and types of lesions and severity. Cracks and nodules developed as early as 3 months of age and papillomatous growths as early as 6 to 7 months of age in captivity. Nodules with ulceration occurred significantly more often in birds older than 31 years and heavier than 4 kg. The comparison of different institutions revealed that birds kept in enclosures with natural-floored water ponds had significantly less severe lesions than birds kept in concrete water ponds. None of the free-ranging flamingos, which live on a muddy underground, showed any lesion. This study demonstrates that flooring, weight and age are important in the onset and progression of pododermatitis in flamingos.

  6. Metastasis: an early event in cancer progression.

    Science.gov (United States)

    Hu, Yijun; Yu, Xiya; Xu, Guixia; Liu, Shanrong

    2017-05-01

    Metastasis is the leading cause of death for a majority of cancer patients, and thus the need to understand the biology of metastasis becomes increasingly acute. When metastasis is initiated in tumor progression remains obscure. Better understanding of mechanisms regulating acquisition of metastatic ability in tumor cells will provide novel therapeutic targets and prevention of metastasis in clinics accompanied with the treatment of the primary tumor might be helpful in reducing metastasis-related mortality. A literature search was performed in multiple electronic databases. Research papers from clinical reports to experimental studies on metastasis were analyzed. The article discusses tumor heterogeneity and genomic instability in the context of metastasis and tumor cell dissemination. And then we review biological mechanism of metastasis at an early stage in both intracellular (CSCs and CTCs) and extracellular (microenvironment) context. Finally, current development of anti-metastatic therapies is summarized. Metastasis could be initiated at an early point of tumor progression. Therefore, early intervention on metastasis should be applied among cancer patients in clinical settings.

  7. Magnesium sulphate can prolong pregnancy in patients with severe early-onset preeclampsia.

    Science.gov (United States)

    Ueda, Akihiko; Kondoh, Eiji; Kawasaki, Kaoru; Mogami, Haruta; Chigusa, Yoshitsugu; Konishi, Ikuo

    2016-10-01

    To assess whether long-term use of magnesium sulphate prolongs pregnancy in patients with severe early-onset preeclampsia. Retrospective cohort study included all singleton pregnancies with severe early-onset preeclampsia, expectantly managed in our institution between 2005 and 2013. Obstetric and perinatal outcomes were compared between patients managed using a current protocol that tolerates long-term (over 48 h) use of magnesium sulphate (long-term group, n = 26) and a historical control group (control group, n = 15) that underwent conventional treatment (up to 48 h use of magnesium sulphate). Long-term group showed significant prolongation of pregnancy compared with the control group (9.2 ± 7.9 versus 16.6 ± 9.3 d, log-rank test, p = 0.021), which was also observed in patients with severe preeclampsia occurring before 28 weeks' gestation (n = 11, 4.5 ± 5.2 versus 13.2 ± 6.8 d, log-rank test, p = 0.035). In contrast to a progressive decrease of platelet count in patients managed without magnesium sulphate, administration of magnesium sulphate for 7 d prevented the decrease of platelet count (p = 0.001). Thirty two percent of patients (13/41) experienced a major complication irrespective of duration of magnesium sulphate use. Long-term use of magnesium sulphate prolonged pregnancy in patients with severe early-onset preeclampsia and can help alleviate progression of preeclampsia.

  8. Maintaining Intestinal Health: The Genetics and Immunology of Very Early Onset Inflammatory Bowel DiseaseSummary

    Directory of Open Access Journals (Sweden)

    Judith R. Kelsen

    2015-09-01

    Full Text Available Inflammatory bowel disease (IBD is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD younger than 5 years of age represent a unique form of disease, termed very early onset IBD (VEO-IBD, which is phenotypically and genetically distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression, and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal inflammation and promote tissue repair. Here, we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation. Keywords: Inflammatory Bowel Disease, Very Early Onset Inflammatory Bowel Disease, Whole Exome Sequencing, Mucosal Immunology

  9. Early childhood predictors of early onset of smoking: a birth prospective study.

    Science.gov (United States)

    Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

    2013-10-01

    Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  11. Clinical correlates of first episode early onset psychosis in KwaZulu ...

    African Journals Online (AJOL)

    Background: The study of first episode early onset psychosis can yield many clues to understanding the early development of psychosis and guide interventions to decrease psychosis risk and improve outcome. The aim of the study was to investigate the socio-demographic profile and clinical correlates in early onset ...

  12. Key Goals and Indicators for Successful Aging of Adults with Early-onset Disability

    OpenAIRE

    LaPlante, Mitchell P.

    2013-01-01

    Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and indep...

  13. Early-onset Lyme carditis with concurrent disseminated erythema migrans.

    Science.gov (United States)

    Patel, Kinjan P; Farjo, Peter D; Juskowich, Joy J; Hama Amin, Ali; Mills, James D

    2017-01-01

    Lyme disease is an infection that is estimated to affect over 300,000 people in the United States annually. Typically, it presents with erythema migrans (EM), an annular rash at the site of tick attachment, within 3 to 30 days of inoculation. Untreated patients may progress to early disseminated disease. A further complication, Lyme carditis is rare but may occur several weeks later. It commonly manifests as a variable atrioventricular (AV) conduction block, with a high-grade AV block occurring in only 1% of untreated patients. This case demonstrates an unusually early presentation of Lyme carditis with complete heart block. A 21-year-old male was transferred from an outside emergency department (ED) for possible pacemaker placement due to symptomatic third-degree AV block. Four days earlier the patient presented to the outside ED with fever, chills, and unrecognized EM on his right neck. He was discharged with antipyretics, but no antibiotic therapy. On the day of transfer, he returned with persistent fevers, EM now on his trunk and upper extremities, lightheadedness, and substernal chest pressure. An electrocardiogram revealed the third-degree AV block leading to transfer. Upon arrival, the patient was promptly diagnosed with Lyme carditis. Pacemaker implantation was deferred, and intravenous (IV) ceftriaxone was initiated. Within 48 hours his third-degree AV block improved to a first-degree block. By this time, his EM had also resolved. He was discharged with oral doxycycline and a 30-day event monitor, which ultimately showed persistent first-degree AV block. This case reinforces a unique presentation of Lyme carditis. Disseminated EM and Lyme carditis may present concurrently within 2 weeks of tick attachment. Early recognition and treatment is important for preventing progression to disseminated infection. Lyme-associated AV block will reverse within 48 to 72 hours of initiating IV antibiotic therapy and will not require pacemaker implantation. Lyme carditis

  14. [Research progress on the etiology of delayed-onset hearing loss in children].

    Science.gov (United States)

    Wang, X Y; Huang, L H; Du, Y T

    2017-10-07

    Newborn hearing screening is an effective method for early detection of hearing loss, however, it is not able to detect delayed-onset hearing loss. By exploring the etiology of delayed-onset hearing loss in children, it can provide a clinical basis for early detection of delayed-onset hearing loss. Mutations in SLC26A4, mitochondrial, GJB2 and other genes, enlarged vestibular aqueduct, congenital cytomegalovirus infection, extracorporeal membrane oxygenation, and auditory neuropathy et al were more commonly reported risk factors. In this paper, the risk factors related to delayed-onset hearing loss, which are divided into 5 categories: genetic mutation, abnormal inner ear malformation, perinatal factors, auditory neuropathy and no identifiable cause, are reviewed and analyzed.

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

    Science.gov (United States)

    Atwood, Craig S; Bowen, Richard L

    2015-01-01

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

  16. Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension.

    Science.gov (United States)

    Veerbeek, Jan H W; Hermes, Wietske; Breimer, Anath Y; van Rijn, Bas B; Koenen, Steven V; Mol, Ben W; Franx, Arie; de Groot, Christianne J M; Koster, Maria P H

    2015-03-01

    Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been investigated whether these differences in CVD risk factors are already present at postpartum cardiovascular screening. We evaluated postpartum differences in CVD risk factors in 3 subgroups of patients with a history of hypertensive pregnancy. We compared the prevalence of common CVD risk factors postpartum among 448 women with previous early-onset preeclampsia, 76 women with previous late-onset preeclampsia, and 224 women with previous pregnancy-induced hypertension. Women with previous early-onset preeclampsia were compared with women with late-onset preeclampsia and pregnancy-induced hypertension and had significantly higher fasting blood glucose (5.29 versus 4.80 and 4.83 mmol/L), insulin (9.12 versus 6.31 and 6.7 uIU/L), triglycerides (1.32 versus 1.02 and 0.97 mmol/L), and total cholesterol (5.14 versus 4.73 and 4.73 mmol/L). Almost half of the early-onset preeclampsia women had developed hypertension, as opposed to 39% and 25% of women in the pregnancy-induced hypertension and late-onset preeclampsia groups, respectively. Our data show differences in the prevalence of common modifiable CVD risk factors postpartum and suggest that prevention strategies should be stratified according to severity and gestational age of onset for the hypertensive disorders of pregnancy. © 2015 American Heart Association, Inc.

  17. Early Onset Alzheimer’s Disease and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Marco Antonio Meraz-Ríos

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia in elderly adults. It is estimated that 10% of the world’s population aged more than 60–65 years could currently be affected by AD, and that in the next 20 years, there could be more than 30 million people affected by this pathology. One of the great challenges in this regard is that AD is not just a scientific problem; it is associated with major psychosocial and ethical dilemmas and has a negative impact on national economies. The neurodegenerative process that occurs in AD involves a specific nervous cell dysfunction, which leads to neuronal death. Mutations in APP, PS1, and PS2 genes are causes for early onset AD. Several animal models have demonstrated that alterations in these proteins are able to induce oxidative damage, which in turn favors the development of AD. This paper provides a review of many, although not all, of the mutations present in patients with familial Alzheimer’s disease and the association between some of these mutations with both oxidative damage and the development of the pathology.

  18. Early and Late Onset Side Effects of Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Francesco Borgia

    2018-01-01

    Full Text Available Photodynamic Therapy (PDT is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Early-onset arthritis in retired National Football League players.

    Science.gov (United States)

    Golightly, Yvonne M; Marshall, Stephen W; Callahan, Leigh F; Guskiewicz, Kevin

    2009-09-01

    Injury has been identified as a potential risk factor for osteoarthritis. However, no previous study has addressed playing-career injuries and subsequent osteoarthritis in a large sample of former athletes. The purpose of this study was to describe the prevalence and determinants of arthritis and osteoarthritis in retired professional football players. Self-reported arthritis prevalence and retrospectively-recalled injury history were examined in a cross-sectional survey of 2,538 retired football players. Football players reported a high incidence of injury from their professional playing days (52.8% reported knee injuries, 74.1% reported ligament/tendon injuries, and 14.2% reported anterior cruciate ligament tears). For those under 60 years, 40.6% of retired NFL players reported arthritis, compared with 11.7% of U.S. males (prevalence ratio = 3.5, 95% CI: 3.3 to 3.7). Within the retired NFL player cohort, osteoarthritis was more prevalent in those with a history of knee injury (prevalence ratio = 1.7, 95% CI: 1.5 to 1.9) and ligament/tendon injury (prevalence ratio = 1.6, 95% CI: 1.4 to 1.9). In males under the age of 60, arthritis is over 3 times more prevalent in retired NFL players than in the general U.S. population. This excess of early-onset arthritis may be due to the high incidence of injury in football.

  1. Psychosocial impact of early onset dementia among caregivers

    Directory of Open Access Journals (Sweden)

    Nathália R. S. Kimura

    2015-12-01

    Full Text Available Introduction: There is growing recognition of early onset dementia (EOD as a significant clinical and social problem because of its effects on physical and mental health of people with dementia (PWD and their caregivers. Objective: To analyze the psychosocial impact of EOD in family caregivers. Methods: The study design was qualitative. Nine EOD caregivers (7 women were recruited at a service for Alzheimer's disease and assessed using semi-structured interviews. Interpretative phenomenological analysis was used to analyze caregivers' reports. Results: Five themes emerged from the narratives: psychological and emotional impact; physical impact; financial and professional impact; social impact and need for support services. The majority of the caregivers of people with EOD perceived their emotional wellbeing as poor or extremely poor. Carers reported poor physical health, which tends to be longer-lasting than mental health problems. Two caregivers had to retire after the disclosure of the dementia diagnosis, and seven reduced their work loads because they had to look after PWD. Preserving the abilities of PWD is essential to maintain their self-esteem, dignity and sense of utility. For the caregivers, interventions and stimulating activities make PWD feel worthwhile and contribute to improving life. Conclusion: The caregivers of people with EOD assume the role of caregiver prematurely and need to balance this activity with other responsibilities. There is a need for more studies of EOD in order to improve understanding of the impact of this disease and to enable development of adequate services for PWD and their caregivers.

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

    Directory of Open Access Journals (Sweden)

    Dandan Tan

    Full Text Available 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.

  3. Late and early onset dementia: what is the role of vascular factors? A retrospective study.

    Science.gov (United States)

    Carotenuto, Anna; Rea, Raffaele; Colucci, Luisa; Ziello, Antonio Rosario; Molino, Ivana; Carpi, Sabrina; Traini, Enea; Amenta, Francesco; Fasanaro, Angiola Maria

    2012-11-15

    Neuropathology of Alzheimer's disease (AD) demonstrates that the common occurrence of vascular lesions and vascular factors is suggested to contribute significantly to the clinical progression of the disease. This study has assessed the presence of vascular brain lesions and risk factors in subjects with diagnosis of AD and their influence on the disease course both in Late Onset Dementia (LOD) and in Early Onset Dementia (EOD). MRI scans of 374 LOD and of 67 EOD patients were evaluated for the presence of vascular associated lesions and rated according to the age-related white matter changes (ARWMC) scale as "pure degenerative", "mixed" and "vascular" cases of dementia. Vascular risk factors burden (hypertension, diabetes, dyslipidemia, myocardial infarction) and disease progression were also assessed. 44% of LOD cases and 46% of EOD were classified as "mixed dementia cases". The vascular risk factors burden showed an increase from the pure degenerative to the pure vascular forms. Disease progression, calculated in two years using the Mini Mental State Evaluation (MMSE), Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scores, did not reveal differences among the three different classes of dementias. Vascular lesions are found in the majority of LOD cases and in about one half of EOD. This observation is consistent with the hypothesis of a synergistic effect of the degenerative and vascular factors on the development of cognitive dysfunction. The linear increase of the vascular burden supports the idea of a continuum spectrum between the pure degenerative and the pure vascular forms of adult-onset dementia disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Regression and progression of microalbuminuria in adolescents with childhood onset diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mi Kyung Son

    2015-03-01

    Full Text Available PurposeAlthough microalbuminuria is considered as an early marker of nephropathy in diabetic adults, available information in diabetic adolescents is limited. The aim of this study was to investigate prevalence and frequency of regression of microalbuminuria in type 1 (T1DM and type 2 diabetes mellitus (T2DM patients with childhood onset.MethodsOne hundred and nine adolescents (median, 18.9 years; interquartile range (IQR, 16.5-21.0 years with T1DM and 18 T2DM adolescents (median, 17.9 years; IQR, 16.8-18.4 years with repeated measurements of microalbuminuria (first morning urine microalbumin/creatinine ratios were included. The median duration of diabetes was 10.1 (7.8-14.0 years and 5.0 (3.5-5.6 years, respectively, and follow-up period ranged 0.5-7.0 years. Growth parameters, estimated glomerular filtration rate, glycosylated hemoglobin (HbA1c and lipid profiles were obtained after reviewing medical record in each subject.ResultsThe prevalence of microalbuminuria at baseline and evaluation were 21.1% and 17.4% in T1DM, and 44.4% and 38.9% in T2DM. Regression of microalbuminuria was observed in 13 T1DM patients (56.5% and 3 T2DM patients (37.5%, and progression rate was 10.5% and 20% in T1DM and T2DM respectively. In regression T1DM group, HbA1c at baseline and follow-up was lower, and C-peptide at baseline was higher compared to persistent or progression groups. In T2DM, higher triglyceride was observed in persistent group.ConclusionConsiderable regression of microalbuminuria more than progression in diabetes adolescents indicates elevated urinary microalbumin excretion in a single test does not imply irreversible diabetic nephropathy. Careful monitoring and adequate intervention should be emphasized in adolescents with microalbuminuria to prevent rapid progression toward diabetic nephropathy.

  5. Early Onset Squamous Cell Carcinoma In A Case Of Lichen Planus

    Directory of Open Access Journals (Sweden)

    Singh Shri Nath

    1998-01-01

    Full Text Available Lichen planus, which is a very common condition, is being presented. However, the uncommon feature in this cases is its early onset and equally early development of squamous cell carcinoma on a lesion on the right thigh.

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

    Science.gov (United States)

    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…

  7. Early onset Cockayne's syndrome: case reports with neuropathological and fibroblast studies.

    OpenAIRE

    Patton, M A; Giannelli, F; Francis, A J; Baraitser, M; Harding, B; Williams, A J

    1989-01-01

    Two patients with early onset Cockayne's syndrome are presented. In each case there was a striking failure of growth and developmental deterioration around six months of age. It has been suggested that early onset Cockayne's syndrome is a syndrome distinct from Cockayne's syndrome, but when the first patient died aged two years 10 months, examination of the brain showed a leucodystrohy with 'tigroid' demyelination similar to that reported in later onset cases of Cockayne's syndrome. Studies o...

  8. Heart rate variability and baroreceptor reflex sensitivity in early- versus late-onset preeclampsia

    OpenAIRE

    Thomas Michael Weber; Helmut Karl Lackner; Andreas Roessler; Ilona Papousek; Vassiliki Kolovetsiou-Kreiner; Miha Lucovnik; Karin Schmid-Zalaudek; Uwe Lang; Manfred Georg Moertl

    2017-01-01

    Objective To determine whether there are differences in autonomic nervous system function in early- versus late-onset preeclampsia. Methods Matched case-control study. Cases were defined as singleton pregnancies with preeclampsia at < 34+0 weeks of gestation (early-onset preeclampsia) and ≥ 34+0 weeks of gestation (late-onset preeclampsia). For each case in each of the preeclampsia subgroups, three „control”uncomplicated singleton pregnancies were matched by maternal age, height, and week of ...

  9. The association of with severe early-onset pre-eclampsia

    African Journals Online (AJOL)

    antibodies with early onset of severe pre-eclampsia before ... early-onset severe pre-eclampsia it is unlikely that they are .... HELLP syndrome. 33. 26. 3. 160/120. 12,6. 2,1. Preterm. Severe uncontrollable hypertension. ACA anticardiolipin antibody; LAC. lUpus anticoagulant; IUD - intra·uterine death; HELLP - haemolysis.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

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

    2013-01-01

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

  12. Child and Adolescent (Early Onset) Schizophrenia: A Review in Light of DSM-III-R.

    Science.gov (United States)

    Werry, John S.

    1992-01-01

    This review of studies of early onset schizophrenia examines the nosological similarity between adult and early onset schizophrenia, differential diagnosis, treatment, and the extent to which children and adolescents diagnosed as having schizophrenia using adult criteria have the characteristic adult correlates. The paper discusses gender…

  13. Strategy to prevent neonatal early-onset group B streptococcal (GBS) disease in the Netherlands

    NARCIS (Netherlands)

    Trijbels-Smeulders, MAJM; Adriaanse, AH; Gerards, LJ; Kimpen, JLL

    Early-onset group B streptococcal (GBS) infection can be prevented by intrapartum antibiotic prophylaxis. In the USA the effectiveness of this strategy was demonstrated after the introduction of formal guidelines in 1996. In Europe prevention strategies for early-onset GBS infection have not been

  14. Social Status of Adolescents with an Early Onset of Externalizing Behavior: The SNARE Study

    Science.gov (United States)

    Franken, Aart; Harakeh, Zeena; Veenstra, Rene; Vollebergh, Wilma; Dijkstra, Jan Kornelis

    2017-01-01

    This study investigated the social status (i.e., popularity, likeability, and friendships) of adolescents with an early onset of externalizing behavior (i.e., alcohol use, tobacco use, and antisocial behavior). Building on Moffitt's dual-taxonomy model, it was hypothesized that early onset adolescents were more popular, but not necessarily more…

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

    Science.gov (United States)

    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…

  16. Parental and Child Characteristics Related to Early-Onset Disordered Eating

    DEFF Research Database (Denmark)

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia

    2015-01-01

    characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies...

  17. Early-onset preeclampsia : Constitutional factors and consequences for future pregnancy outcome and cardiovascular health

    NARCIS (Netherlands)

    van Rijn, B.B.|info:eu-repo/dai/nl/304816582

    2008-01-01

    In this thesis, maternal constitutional factors related to long-term cardiovascular health and subsequent pregnancy outcome in women with early-onset preeclampsia is addressed. Aims of the thesis: To evaluate subsequent pregnancy outcome in women with a first pregnancy complicated by early-onset

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

    Science.gov (United States)

    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…

  19. Early gestational age at preeclampsia onset is associated with subclinical atherosclerosis 12 years after delivery.

    Science.gov (United States)

    Christensen, Martin; Kronborg, Camilla Skovhus; Carlsen, Rasmus Kirkeskov; Eldrup, Nikolaj; Knudsen, Ulla Breth

    2017-09-01

    Women with a history of preeclampsia have increased risk of cardiovascular disease later in life. However, it is unclear whether early gestational age at preeclampsia onset is associated with higher cardiovascular disease risk. This study aimed to test the association between gestational age at preeclampsia onset (including the early-onset/late-onset preeclampsia distinction) and subclinical atherosclerosis and arterial stiffness in age-matched women 12 years after index pregnancy. Eligible participants were identified in two Danish registries. Main outcome measures were carotid plaque presence, carotid intima-media thickness, aortic pulse wave velocity, and augmentation index adjusted for heart rate. Twenty-four women with previous early-onset preeclampsia, 24 with previous late-onset preeclampsia and 24 with previous normotensive pregnancies were included after matching on age (±2 years) and time since delivery (±1 year). In all outcome measures, the early-onset group had the highest percentage or mean value. In the adjusted analysis, the early-onset group significantly differed from the late-onset group in all outcome measures except aortic pulse wave velocity. The early-onset group also had significantly higher carotid intima-media thickness (average and left) compared with the normotensive group. Gestational age at preeclampsia onset as a continuous variable was significantly associated to both carotid plaque presence and carotid intima-media thickness (average and right). Gestational age at preeclampsia onset is negatively associated with markers of subclinical atherosclerosis 12 years after delivery. Potentially, gestational age at preeclampsia onset might be helpful in directing cardiovascular disease prevention after preeclampsia. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  20. Heterozygous mutation in OTX2 associated with early-onset retinal dystrophy with atypical maculopathy.

    Science.gov (United States)

    Abdalla-Elsayed, Maram Ea; Schatz, Patrik; Neuhaus, Christine; Khan, Arif O

    2017-01-01

    Heterozygous mutations in OTX2 have been associated with a range of ocular and pituitary abnormalities. We report a novel heterozygous deletion in OTX2 underlying early-onset retinal dystrophy with atypical maculopathy. Clinical examination included electroretinography and multimodal retinal imaging. Molecular genetic testing was composed of next-generation sequencing of a panel of retinal dystrophy genes. A now 17-year-old boy presented 12 years earlier with a history of progressively poor vision since birth, nyctalopia, and early-onset retinal dystrophy with atypical maculopathy. He also had bilateral microphthalmos and a slim prepubertal appearance; growth hormone levels were within normal ranges. Next-generation sequencing of a retinal dystrophy gene panel revealed a heterozygous deletion c.485delC (p.Pro162G.Infs*24) in exon 5 of OTX2. This second report of maculopathy associated with a heterozygous mutation in OTX2 confirms that mutations in OTX2 should be considered in the differential diagnosis of atypical hereditary maculopathy, with or without rod-cone dystrophy.

  1. A systematic review of the risks factors associated with the onset and natural progression of epilepsy.

    Science.gov (United States)

    Walsh, Stephanie; Donnan, Jennifer; Fortin, Yannick; Sikora, Lindsey; Morrissey, Andrea; Collins, Kayla; MacDonald, Don

    2017-07-01

    Epilepsy is a neurological condition that affects more than 50 million individuals worldwide. It presents as unpredictable, temporary and recurrent seizures often having negative physical, psychological and social consequences. To inform disease prevention and management strategies, a comprehensive systematic review of the literature on risk factors for the onset and natural progression of epilepsy was conducted. Computerized bibliographic databases for systematic reviews, meta-analyses, observational studies and genetic association studies published between 1990 and 2013 describing etiological risk factors for epilepsy was searched. The quality of systematic reviews was validated using the AMSTAR tool and articles were reviewed by two referees. A total of 16,958 articles went through stage one review of abstracts and titles. A total of 76 articles on genetic and non-genetic risk factors for the onset and progression of epilepsy met the eligibility criteria for data extraction. Dozens of risk factors were significantly associated with onset of epilepsy. Inconsistent levels of evidence for risk of onset included family history of epilepsy, history of febrile seizures, alcohol consumption, CNS and other infections, brain trauma, head injury, perinatal stroke, preterm birth and three genetic markers. Limited evidence showed that symptomatic epilepsy, focal seizures/syndromes, slow waves on EEG, higher seizure frequency, high stress or anxiety, and lack of sleep decreased the odds of seizure remission. High quality studies were rare and while a large body of work exists, relatively few systematic reviews were found. Copyright © 2016. Published by Elsevier B.V.

  2. Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort.

    Science.gov (United States)

    Heighton, Julia N; Brady, Lauren I; Newman, Matthew C; Tarnopolsky, Mark A

    2017-12-12

    Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. We evaluated the impact of sex and smoking status upon knee extension strength and the phenotypic spectrum of disease in a large cohort of adult-onset CPEO patients (N=116) using retrospective chart analysis. The CPEO patients showed significantly lower knee extension strength as compared to the age- and sex-matched control population (-37%, PCPEO (-26%, PCPEO patients. Copyright © 2017. Published by Elsevier B.V.

  3. Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

    Science.gov (United States)

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

    2012-08-01

    Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

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

    Science.gov (United States)

    Cutler, David J; Zwick, Michael E; Okou, David T; 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

    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. 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 (parchitecture 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.

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

    Directory of Open Access Journals (Sweden)

    David J Cutler

    Full Text Available 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.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.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.

  6. Working memory and FDG-PET dissociate early and late onset Alzheimer disease patients.

    Science.gov (United States)

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

    2005-05-01

    The aims of this study were to determine the influence of the onset of Alzheimer's disease (AD) on 1) memory and cerebral glucose metabolism, 2) the relationships between cognitive performance and cerebral glucose metabolism. Brain metabolism was measured by 18FDG-PET in 12 early onset AD patients (age 65), with comparable mean MMSE scores. Working memory, semantic memory and episodic memory were assessed. Cognitivo-metabolic correlations (CMC) and complementary interregional correlations were performed in order to identify specific neurocognitive processes within each group. Both AD groups performed poorly on all tasks, except digit span in the late onset group. The early onset group performed more poorly than the late onset one on both the digit span and Brown-Peterson Paradigm (BPP) tasks. Temporo-parietal hypometabolism was found in both groups, the left hemisphere being more affected than the right, especially in the early onset patients, who also showed specific left frontal hypometabolism. For the BPP task, the CMC principally involved left frontal areas in the early onset group, and the cerebellum in the late onset one. For the digit span task, they involved cerebellar and occipital regions in the latter. Regarding the digit span, the occipital and cerebellar involvement may have reflected an effective compensatory mechanism in the late onset patients, while high left supramarginal gyrus hypometabolism in the early onset patients may have explained their failure in this task. In the BPP task, the lower performance of the early onset group may have been due to a frontal lobe dysfunction, as suggested by 1) the hypometabolism of this region, 2) the CMC results, 3) the interregional correlations, which indicated greater disruption of the antero- posterior loop.

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

    Science.gov (United States)

    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.

  8. Diagnosis of Late Stage, Early Onset, Small Fiber Polyneuropathy

    Science.gov (United States)

    2016-10-01

    98%), cognitive concerns (88%), and headache (72%). Internal consistency and test-retest reliability of the questionnaire were excellent. Specific...Klein MM. Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics 2013;131:e1091-e1100. 3

  9. Social Anxiety and Onset of Drinking in Early Adolescence

    Science.gov (United States)

    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…

  10. Early Onset Optic Neuritis Following Measles-Rubella Vaccination

    Directory of Open Access Journals (Sweden)

    Siamak Moradian

    2008-12-01

    Full Text Available

    PURPOSE: To report two cases of optic neuritis with onset less than 24 hours following measles-rubella (MR vaccination. CASE REPORT: Two teenage patients developed acute optic neuritis 6 to 7 hours after MR booster vaccination. The first patient demonstrated bilateral papillitis and severe visual loss but improved significantly with pulse intravenous steroid therapy with methylprednisolone 500 mg/day. The second patient had unilateral retrobulbar optic neuritis and demonstrated excellent visual recovery without intervention. CONCLUSION: Acute optic neuritis is a rare complication of MR vaccination and may occur early after immunization.

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

    Science.gov (United States)

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

    2005-01-01

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

  2. Early-Onset Preeclampsia and the Prevalence of Postpartum Metabolic Syndrome

    NARCIS (Netherlands)

    Stekkinger, Eva; Zandstra, Mirjam; Peeters, Louis L. H.; Spaanderman, Marc E. A.

    2009-01-01

    OBJECTIVE: To determine the prevalence of the metabolic syndrome postpartum in women with a history of pregnancy complicated by early-onset vascular disorders compared with women with late-onset disorders. METHODS: In this retrospective cohort study 849 women with a history of pregnancy complicated

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

    Science.gov (United States)

    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…

  4. Progressive and accelerated disability onset by race/ethnicity and education among late midlife and older adults.

    Science.gov (United States)

    Latham, Kenzie

    2012-12-01

    This study explores the pace of severe disability onset with an emphasis on the role of race/ethnicity and education. More specifically, this research examines whether race/ethnicity and educational attainment are independent predictors of progressive and accelerated disability onset. Using the Health and Retirement Study (HRS) Waves 2 to 10 (1994-2010), a series of discrete-time Cox proportional hazards models with multiple competing events were created to ascertain whether respondents developed progressive or accelerated disability in subsequent waves. Black and Hispanic respondents were at an increased risk of developing progressive disability. Respondents without a high school degree were more likely to experience progressive or accelerated disability. Low educational attainment was a particularly strong predictor of accelerated disability onset and may represent an acute lack of resources over the life course. Race and ethnicity were important predictors of progressive disability onset, which may reflect racial/ethnic variations in the disabling process.

  5. Distributional cues and the onset bias in early word segmentation.

    Science.gov (United States)

    Babineau, Mireille; Shi, Rushen

    2014-12-01

    In previous infant studies on statistics-based word segmentation, the unit of statistical computation was always aligned with the syllabic edge, which had a consonant onset. The current study addressed whether the learning system imposes a constraint that favors word forms beginning with a consonant onset over those beginning with an onsetless sub-syllable, by examining infants' segmentation of vowel-initial non-words in French liaison. French-learning 20- and 24-month-old infants (N = 64) were familiarized with sentences containing variable liaison consonants preceding the same vowel-initial non-word (e.g., /n/onche, /z/onche, /r/onche, /t/onche), such that the distributional cues supported the sub-syllabic target (e.g., onche). After familiarization, we tested sub-syllabic statistical segmentation by presenting the vowel-initial target (e.g., onche) versus another non-familiarized vowel-initial word (e.g., èque). Another group of infants was tested with a consonant-initial mis-segmentation of the target (e.g., zonche) versus another non-familiarized consonant-initial word (e.g., zèque). Results showed that 20-month-olds failed to segment the vowel-initial targets, but they mis-segmented the targets as consonant-initial, indicating that the onset bias dominated over sub-syllabic statistics for word segmentation at this age. Twenty-four-month-olds showed ambiguous interpretations (i.e., both vowel-initial segmentation and consonant-initial mis-segmentation), suggesting that the use of statistics to segment sub-syllabic words was emerging while the onset bias continued to have an impact. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  6. Early recognition improves prognosis in elderly onset RA. .

    Science.gov (United States)

    Negoescu, Andra; Ostör, Andrew J K

    2014-01-01

    Although commonly diagnosed in the third to fifth decades of life, the incidence and prevalence of RA continue to increase up to the ninth decade. Age at onset is particularly relevant as the presentation may differ in elderly onset RA (EORA) compared with young onset RA (YORA). Patients with EORA frequently report a more acute presentation, especially if positive for rheumatoid factor (RF). Fever, fatigue and weight loss appear to be more common in EORA. Although small joints are most frequently involved in the RA population overall, there is common involvement of large joints in EORA and these proximal symptoms may mimic polymyalgia rheumatica (PMR). In YORA, approximately 80% of patients are seropositive for RF however a lower frequency has been reported in EORA. Anti-CCP antibodies have been detected in over 70% of patients with RA and are highly specific for RA. The value of anti-CCP antibodies is even higher in patients with an atypical presentation (e.g. PMR-like symptoms), or those who are RF negative. X-rays of the hands and feet should always be performed in patients with a suspected inflammatory arthritis. Baseline joint erosions are present in a similar proportion in patients with YORA and EORA. In the elderly, the differential diagnosis of RA is extensive as many conditions present in a similar way e.g. PMR, osteoarthritis, polyarticular gout, pseudogout and malignancy. Anti-CCP antibodies are very useful for identifying EORA patients with a polymyalgic onset. Ultrasonography or MRI can also be helpful in differentiating PMR from EORA.

  7. Early onset epileptic encephalopathy caused by de novo SCN8A mutations

    National Research Council Canada - National Science Library

    Ohba, Chihiro; Kato, Mitsuhiro; Takahashi, Satoru; Lerman‐Sagie, Tally; Lev, Dorit; Terashima, Hiroshi; Kubota, Masaya; Kawawaki, Hisashi; Matsufuji, Mayumi; Kojima, Yasuko; Tateno, Akihiko; Goldberg‐Stern, Hadassa; Straussberg, Rachel; Marom, Dafna; Leshinsky‐Silver, Esther; Nakashima, Mitsuko; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Miyake, Noriko; Tanaka, Fumiaki; Matsumoto, Naomichi; Saitsu, Hirotomo

    2014-01-01

    ... (target capture or whole-exome sequencing) for early onset epileptic encephalopathies (EOEEs). A total of 163 patients with EOEEs without mutations in known genes, including 6 with malignant migrating partial seizures in infancy...

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

    National Research Council Canada - National Science Library

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

    2008-01-01

    ... families with early-onset dementia clinically diagnosed as probable Alzheimer's disease. Results: In 4 index patients, we identified 4 missense PSEN1 mutations, namely, L286V, G378E, L381V, and L392V...

  9. Maternal serum copeptin concentrations in early- and late-onset pre-eclampsia

    Directory of Open Access Journals (Sweden)

    Abdullah Tuten

    2015-08-01

    Conclusion: Our results suggest that copeptin levels might be useful in the evaluation of the severity of pre-eclampsia. However, copeptin might be involved in early- rather than late-onset pre-eclampsia.

  10. Primary progressive multiple sclerosis developing in the context of young onset Parkinson's disease.

    Science.gov (United States)

    Sadnicka, Anna; Sheerin, Una-Marie; Kaplan, Charles; Molloy, Sophie; Muraro, Paolo A

    2013-01-01

    We report a patient with young onset Parkinson's disease (PD) and a heterozygous point mutation in parkin (c.1000C>T; p.Arg334Cys). After 8 years he developed pyramidal signs and reinvestigation demonstrated MRI and laboratory findings supportive of a diagnosis of multiple sclerosis (MS) with a primary progressive (PP) clinical course. This is a previously un-described association of young onset PD with PPMS. Imaging clearly dates the occurrence of each disease as chronologically separate phenomena. There is not currently evidence for shared causation or pathogenesis between the two neurological disorders but we will follow with interest the emerging genetic characterization of parkin in both PD and MS.

  11. Early onset mood disorders and first alcohol use in the general population.

    Science.gov (United States)

    Birrell, Louise; Newton, Nicola C; Teesson, Maree; Slade, Tim

    2016-08-01

    Mood disorders and alcohol use are common in the general population and often occur together. This study explored how early onset mood disorders relate to age of first alcohol use in the Australian general population. Discrete time survival analysis modelled the odds of first alcohol use among those with, versus without, an early onset DSM-IV mood disorders (major depression, dysthymia or bipolar disorder). Data came from the 2007 Australian National Survey of Mental Health and Wellbeing (N=8841). Early onset mood disorders as an overall class were not significantly related to the odds of first alcohol use in any given year. On examining the different types of mood disorders individually early onset bipolar disorder was a significant predictor of first alcohol use. The analysis then looked at interactions with time and found that after the age of 14 years the presence of an early onset mood disorder significantly increased the odds of first alcohol use by 32%. Retrospective recall was used to determine age of onset data which is subject to known biases and replication is recommended in some subgroup analysis due to smaller sample sizes. Mood disorders, particularly bipolar disorder, act as unique risk factors for first alcohol use in the general population and show significant interactions with developmental timing. The findings point to the potential utility of prevention programs that target alcohol use and mood disorders together from early adolescence. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Risk factors for early psychosis in PD:insights from the Parkinson's Progression Markers Initiative

    OpenAIRE

    ffytche, Dominic H.; Pereira, Joana B.; Ballard, Clive; Chaudhuri, K Ray; Weintraub, Daniel; Aarsland, Dag

    2017-01-01

    BACKGROUND: Parkinson's Disease (PD) psychosis refers to the spectrum of illusions, formed hallucinations and delusions that occur in PD. Visual hallucinations and illusions are thought to be caused by specific cognitive and higher visual function deficits and patients who develop such symptoms early in the disease course have greater rates of cognitive decline and progression to dementia. To date, no studies have investigated whether such deficits are found prior to the onset of PD psychosis...

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

    Directory of Open Access Journals (Sweden)

    K.A. Sagar

    2015-12-01

    Full Text Available 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.

  14. Magnetic resonance imaging studies in early onset bipolar disorder: an updated review.

    Science.gov (United States)

    Terry, Janine; Lopez-Larson, Melissa; Frazier, Jean A

    2009-04-01

    Over the past 5-10 years, advances in neuroimaging methods and study designs have begun to appear in the literature of early-onset bipolar disorder (onset before 18 years of age). This article contains an updated review of the literature regarding neuroimaging in youths with bipolar disorder (BPD), highlighting important new study designs and techniques. Overall, structural, functional (fMRI) and magnetic resonance spectroscopy (MRS) report consistent abnormalities in regions of the frontal lobe and limbic structures. Functional MRI and MRS studies also frequently report striatal and thalamic abnormalities in early-onset BPD. Future neuroimaging studies in youths with BPD should include longitudinal studies incorporating multimodal neuroimaging techniques.

  15. Final Height of Female Patients with Early-onset Anorexia Nervosa

    OpenAIRE

    Naoaki, Hori; Mikako, Inokuchi; Rie, SASAKI; Myong-sun, Choe; Hisako, Watanabe; Tomonobu, Hasegawa; Department of Pediatrics, Keio University School of Medicine

    2003-01-01

    We retrospectively studied the final height (FH) of female patients with early-onset anorexia nervosa (AN), and whether the FH was affected by transient undernutrition. Thirteen female patients with early-onset AN treated by the "Keio method", onset age 6.0-45.6 years, were enrolled in this study. All of them achieved FH. Subjects were classified into 3 groups: Therapy (Tx) with lagging-down group, Tx without lagging-down group, and Non-Tx group. Tx groups (Tx with lagging-down group and Tx w...

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

    Science.gov (United States)

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

    2013-01-01

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

  17. Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review.

    Science.gov (United States)

    McKay, Kyla A; Jahanfar, Shayesteh; Duggan, Tom; Tkachuk, Stacey; Tremlett, Helen

    2017-07-01

    Multiple sclerosis (MS) is a chronic disease of the central nervous system with an unidentified etiology. We systematically reviewed the literature on the possible risk factors associated with MS disease onset, relapses and progression from 1960 to 2012 by accessing six databases and including relevant systematic reviews, meta-analyses, case-control or cohort studies. The focus was on identifying modifiable risk factors. Fifteen systematic reviews and 169 original articles were quality assessed and integrated into a descriptive review. Best evidence, which included one or more prospective studies, suggested that lower exposure to sunlight and/or lower serum vitamin D levels were associated with an increased risk of developing MS onset and subsequent relapses, but a similar quality of evidence was lacking for disease progression. Prospective studies indicated that cigarette smoking may increase the risk of MS as well as accelerate disease progression, but whether smoking altered the risk of a relapse was largely unknown. Infections were implicated in both risk of developing MS and relapses, but data for progression were lacking. Specifically, exposure to the Epstein-Barr virus, particularly if this manifested as infectious mononucleosis during adolescence, was associated with increased MS risk. Upper respiratory tract infections were most commonly associated with an increase in relapses. Relapse rates typically dropped during pregnancy, but there was no strong evidence to suggest that pregnancy itself altered the risk of MS or affected long-term progression. Emerging research with the greatest potential to impact public health was the suggestion that obesity during adolescence may increase the risk of MS; if confirmed, this would be of major significance. Copyright © 2016. Published by Elsevier B.V.

  18. 1:4 matched case-control study on influential factor of early onset neonatal sepsis.

    Science.gov (United States)

    Jiang, Z; Ye, G-Y

    2013-09-01

    Bacteria, funghi, viruses and protozoa can lead to neonatal sepsis. Neonatal sepsis is the leading cause of infectious disease onset and death in many neonates. To explore the major risk factors of early-onset neonatal sepsis and provide a scientific basis for strategies of early-onset neonatal sepsis prevention. A 1:4 matched case-control study was adopted and 147 cases of early-onset neonatal sepsis were enrolled. Conditional logistic regression model was used to analyze the univariate and multivariate data to estimate the odds ratio (OR) and the 95% confidence interval (95% CI). Univariate analysis shows that the impact factors on the occurrence of early-onset neonatal sepsis include the following: Maternal age > 35, mother having fixed occupation, mother of urban residence, abnormal fetal position, fetal times, parity, caesarean section, premature rupture of membranes, amniotic fluid volume abnormalities, pregnancy-induced hypertension, placental abnormalities, fetal distress, newborn gender, low birth weight infants, neonatal Apgar scoring at one and five minutes, neonatal jaundice, wet lung, anemia, IVH, and premature infant. Multivariate logistic regression analysis showed that maternal age > 35 (OR = 4.835, OR 95% CI = 1.170-19.981), cesarean section (OR = 0.103, OR 95% CI = 0.041-0.258), premature rupture of membranes (OR = 0.207, OR 95% CI = 0.078-0.547), premature infants (OR = 0.059, OR 95% CI = 0.010-0.329) and newborn jaundice (OR = 0.092, OR 95% CI = 0.021-0.404) were the factors of early-onset neonatal sepsis. Early-onset neonatal sepsis could be affected by multi-factors, and targeted prevention may reduce the incidence of early-onset neonatal sepsis rates.

  19. Exploring reasons for late identification of children with early-onset hearing loss.

    Science.gov (United States)

    Fitzpatrick, Elizabeth M; Dos Santos, Johnny Cesconetto; Grandpierre, Viviane; Whittingham, JoAnne

    2017-09-01

    Several studies have shown that early identification of childhood hearing loss leads to better language outcomes. However, delays in the confirmation of hearing loss persist even in the presence of well-established universal newborn hearing screening programs (UNHS). The objective of this population-based study was to document the proportion of children who experienced delayed confirmation of congenital and early onset hearing loss in a UNHS program in one region of Canada. The study also sought to determine the reasons for delayed confirmation of hearing loss in children. Population level data related to age of first assessment, age of identification and clinical characteristics were collected prospectively for all children identified through the UNHS program. We documented the number of children who experienced delay (defined as more than 3 months) from initial audiologic assessment to confirmation of hearing loss. A detailed chart review was subsequently performed to examine the reasons for delay to confirmation. Of 418 children identified from 2003 to 2013, 182 (43.5%) presented with congenital or early onset hearing loss, of whom 30 (16.5%) experienced more than 3 months delay from initial audiologic assessment to confirmation of their hearing disorder. The median age of first assessment and confirmation of hearing loss for these 30 children was 3.7 months (IQR: 2.0, 7.6) and 13.8 months (IQR: 9.7, 26.1) respectively. Close examination of the factors related to delay to confirmation revealed that for the overwhelming majority of children, a constellation of factors contributed to late diagnosis. Several children (n = 22; 73.3%) presented with developmental/medical issues, 15 of whom also had middle ear dysfunction at assessment, and 9 of whom had documented family follow-up concerns. For the remaining eight children, additional reasons included ongoing middle ear dysfunction for five children, complicated by family follow-up concerns (n = 3) and mild

  20. The impact of early-onset cannabis use on functional brain correlates of working memory.

    Science.gov (United States)

    Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

    2010-08-16

    Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  1. Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

    Science.gov (United States)

    ... area? Other Names for This Condition EOMFC Salih CMD Salih congenital muscular dystrophy Salih myopathy titinopathy & early- ... a novel form of congenital muscular dystrophy (Salih cmd). Pediatr Cardiol. 2001 Jul-Aug;22(4):297- ...

  2. Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions.

    Science.gov (United States)

    Pifarré, Paula; Gutierrez-Mecinas, María; Prado, Judith; Usero, Lorena; Roura-Mir, Carme; Giralt, Mercedes; Hidalgo, Juan; García, Agustina

    2014-01-01

    In addition to detrimental inflammation, widespread axon degeneration is an important feature of multiple sclerosis (MS) pathology and a major correlate for permanent clinical deficits. Thus, treatments that combine immunomodulatory and neuroprotective effects are beneficial for MS. Using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a model of MS, we recently showed that daily treatment with the phosphodiesterase 5 (PDE5) inhibitor sildenafil at peak disease rapidly ameliorates clinical symptoms and neuropathology (Pifarre et al., 2011). We have now investigated the immunomodulatory and neuroprotective actions of sildenafil treatment from the onset of EAE when the immune response prevails and show that early administration of the drug prevents disease progression. Ultrastructural analysis of spinal cord evidenced that sildenafil treatment preserves axons and myelin and increases the number of remyelinating axons. Immunostaining of oligodendrocytes at different stages of differentiation showed that sildenafil protects immature and mature myelinating oligodendrocytes. Brain-derived neurotrophic factor (BDNF), a recognized neuroprotectant in EAE, was up-regulated by sildenafil in immune and neural cells suggesting its implication in the beneficial effects of the drug. RNA microarray analysis of spinal cord revealed that sildenafil up-regulates YM-1, a marker of the alternative macrophage/microglial M2 phenotype that has neuroprotective and regenerative properties. Immunostaining confirmed up-regulation of YM-1 while the classical macrophage/microglial activation marker Iba-1 was down-regulated. Microarray analysis also showed a notable up-regulation of several members of the granzyme B cluster (GrBs). Immunostaining revealed expression of GrBs in Foxp3+-T regulatory cells (Tregs) suggesting a role for these proteases in sildenafil-induced suppression of T effector cells (Teffs). In vitro analysis of

  3. Exercise and Early-Onset Alzheimer’s Disease: Theoretical Considerations

    Directory of Open Access Journals (Sweden)

    Astrid M. Hooghiemstra

    2012-04-01

    Full Text Available Background/Aims: Although studies show a negative relationship between physical activity and the risk for cognitive impairment and late-onset Alzheimer’s disease, studies concerning early-onset Alzheimer’s disease (EOAD are lacking. This review aims to justify the value of exercise interventions in EOAD by providing theoretical considerations that include neurobiological processes. Methods: A literature search on key words related to early-onset dementia, exercise, imaging, neurobiological mechanisms, and cognitive reserve was performed. Results/Conclusion: Brain regions and neurobiological processes contributing to the positive effects of exercise are affected in EOAD and, thus, provide theoretical support for exercise interventions in EOAD. Finally, we present the design of a randomized controlled trial currently being conducted in early-onset dementia patients.

  4. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

    Science.gov (United States)

    Musumeci, Giuseppe; Aiello, Flavia Concetta; Szychlinska, Marta Anna; Di Rosa, Michelino; Castrogiovanni, Paola; Mobasheri, Ali

    2015-01-01

    Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder. PMID:25785564

  5. Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression.

    Science.gov (United States)

    Musumeci, Giuseppe; Aiello, Flavia Concetta; Szychlinska, Marta Anna; Di Rosa, Michelino; Castrogiovanni, Paola; Mobasheri, Ali

    2015-03-16

    Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by "low-grade inflammation" in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder.

  6. Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

    Science.gov (United States)

    Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

    ♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

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

    Science.gov (United States)

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

    2012-01-01

    Context Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources Primary data. Study Selection Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Data Extraction Uniform statistical analysis scripts were run locally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36–1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21–1.33, n = 19 505) (P = .01). Conclusion These results highlight an increased genetic vulnerability to smoking in early-onset smokers. PMID:22868939

  8. Heart rate variability and baroreceptor reflex sensitivity in early- versus late-onset preeclampsia.

    Science.gov (United States)

    Weber, Thomas Michael; Lackner, Helmut Karl; Roessler, Andreas; Papousek, Ilona; Kolovetsiou-Kreiner, Vassiliki; Lucovnik, Miha; Schmid-Zalaudek, Karin; Lang, Uwe; Moertl, Manfred Georg

    2017-01-01

    To determine whether there are differences in autonomic nervous system function in early- versus late-onset preeclampsia. Matched case-control study. Cases were defined as singleton pregnancies with preeclampsia at preeclampsia) and ≥ 34+0 weeks of gestation (late-onset preeclampsia). For each case in each of the preeclampsia subgroups, three "control"uncomplicated singleton pregnancies were matched by maternal age, height, and week of gestation. Blood pressure and heart rate were measured continuously for 30 minutes in each participant. Baroreceptor reflex sensitivity (assessed using sequence technique), time and frequency domain heart rate variability measures, as SDNN, RMSSD, LFRRI, HFRRI and LF/HFRRI of R-R intervals, were compared between groups (ppreeclampsia (10 with early-onset and 14 with late-onset preeclampsia) and 72 controls were included in the study. SDNN, RMSSD and HFRRI were significantly higher in the late-onset preeclampsia group compared to gestational age matched controls (p = 0.033, p = 0.002 and p = 0.018, respectively). No significant differences in SDNN RMSSD and HFRRI between early-onset preeclampsia group and gestational age matched controls were observed (p = 0.304, p = 0.325 and p = 0.824, respectively). Similarly, baroreceptor reflex sensitivity was higher in late-onset preeclampsia compared to controls at ≥ 34 weeks (p = 0.037), but not different between early-onset preeclampsia compared to controls at preeclampsia compared to healthy pregnancies. This indicates a better autonomic nervous system mediated adaptation to preeclampsia related cardiovascular changes in late-onset disease.

  9. Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

    Science.gov (United States)

    Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

    2016-01-01

    This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

  10. Differentiating early-onset persistent versus childhood-limited conduct problem youth.

    Science.gov (United States)

    Barker, Edward D; Maughan, Barbara

    2009-08-01

    Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.

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

    Science.gov (United States)

    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…

  12. Preliminary findings demonstrating latent effects of early adolescent marijuana use onset on cortical architecture

    Directory of Open Access Journals (Sweden)

    Francesca M. Filbey

    2015-12-01

    Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

  13. Role of vitamin D in the onset, progression, and severity of multiple sclerosis.

    Science.gov (United States)

    Mesliniene, Sandra; Ramrattan, Laurie; Giddings, Stanley; Sheikh-Ali, Mae

    2013-01-01

    To review and assess the role of vitamin D in the onset, progression, and relapse of multiple sclerosis (MS), based on evidence acquired from the analysis of preclinical, observational, and interventional studies. All English language literature in MEDLINE (January 1969 through April 2012) was searched for observational and interventional studies on the dosage effect of vitamin D on the onset, progression, and relapse rate of MS. The medical subject heading (MeSH) terms used in the search included Vitamin D and Multiple Sclerosis. Additional publications and abstracts were identified from review articles and from the references cited in the previously found articles. In addition to the experimental studies, only those human studies that specified the population size, doses of vitamin D used, and the resulting effect on MS were considered. Vitamin D deficiency is very common among MS patients. Multiple preclinical studies have shown that vitamin D is a potent regulator of inflammation in MS. Most observational studies support an association between high vitamin D levels and a reduced risk of developing MS. However, conflicting results have been reported by observational studies on the correlation between vitamin D and MS severity and by interventional studies using vitamin D as a therapeutic agent for MS. Vitamin D deficiency in MS patients should be avoided. In addition, the risk of developing MS might be reduced by maintaining optimal vitamin D levels in the healthy population. Larger randomized interventional trials are needed to clarify the therapeutic effect of vitamin D in MS.

  14. Late- versus early-onset geriatric depression in a memory research center

    Directory of Open Access Journals (Sweden)

    Carol Dillon

    2009-10-01

    Full Text Available Carol Dillon1, Ricardo F Allegri2, Cecilia M Serrano1, Mónica Iturry1, Pablo Salgado1, Frank B Glaser1, Fernando E Taragano21Memory Research Center, Department of Neurology, Hospital General Abel Zubizarreta, GCBA Buenos Aires, Argentina; 2Department of Neuropsychology (SIREN, CEMIC University, Buenos Aires, ArgentinaObjective: To contrast early-onset (<60 years and late-onset (>60 years depression in geriatric patients by evaluating differences in cognition, vascular comorbidity and sociological risk factors. Both patient groups were compared with normal subjects.Materials and methods: We recruited 76 patients with depressive symptoms (37 late onset and 39 early onset and 17 normal controls matched by age and educational level. All subjects were assessed using a semistructured neuropsychiatric interview and an extensive neuropsychological battery. Vascular and sociological risk factors were also evaluated.Results: We found a significant variation in performance between depressive patients and normal controls in most cognitive functions, especially memory (P < 0.0001, semantic fluency (P < 0.0001, verbal fluency, and digit-symbol (P < 0.0001. Late-onset depression patients scored lower and exhibited more severe impairment in memory domains than early-onset depression patients (P < 0.05. Cholesterol levels and marital status were significantly (P < 0.05 different between the depressive groups. Both depressed groups (early- and lateonset were more inactive than controls (P < 0.05; odds ratio: 6.02.Conclusion: Geriatric depression may be a manifestation of brain degeneration, and the initial symptom of a dementia. It is important to consider this in the treatment of patients that exhibit late-onset depressive symptoms.Keywords: early- and late-onset depression, geriatrics, cognition

  15. Early-Onset Chronic Inflammatory Disease Associated with Maternal Microchimerism

    Directory of Open Access Journals (Sweden)

    Tomoaki Ishikawa

    2012-01-01

    Full Text Available Maternal microchimerism (mMc refers to the presence of a small population of cells originating from the mother. Whether mMc leads to autoimmune responses in children remains controversial. We describe here an 11-year-old boy with persistent fever and elevated levels of C-reactive protein from infancy onward. During infancy, the patient presented with high fever, skin rashes, and hepatic dysfunction. Careful examination including a liver biopsy failed to reveal the cause. At 4 years old, petechiae developed associated with thrombocytopenia and positive anti-dsDNA autoantibodies. Steroid pulse therapy was effective, but the effect of low-dose prednisone was insufficient. At age 9, an extensive differential diagnosis was considered especially for infantile onset autoinflammatory disorders but failed to make a definitive diagnosis. On admission, the patient exhibited short stature, hepatosplenomegaly, generalized superficial lymphadenopathy, and rashes. Laboratory findings revealed anemia, elevated levels of inflammation markers, and hypergammaglobulinemia. Serum complement levels were normal. Serum levels of IL-6 and B-cell activating factor were elevated. Viral infections were not identified. Although HLA typing revealed no noninherited maternal antigens in lymphocytes, female cells were demonstrated in the patient’s skin and lymph nodes, suggesting that maternal microchimerism might be involved in the pathogenesis of fever without source in infants.

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

    Directory of Open Access Journals (Sweden)

    Sabine G. Gebhardt-Henrich

    2015-11-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2015-11-27

    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.

  18. Phenotype Characteristics of Fellow Eyes in Patients With Early Onset of Neovascular Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Schick, T.; Ersoy, L.; Hoyng, C.B.; Kirchhof, B.; Liakopoulos, S.

    2015-01-01

    PURPOSE: To investigate phenotype characteristics of fellow eyes in patients with early onset of neovascular age-related macular degeneration (NVAMD). METHODS: Patients with new-onset unilateral NVAMD between 50 and 65 years (n = 57, early-onset choroidal neovascularization [CNV] group) or >80

  19. The role of temperament in the relationship between early onset of tobacco and cannabis use : The TRAILS study

    NARCIS (Netherlands)

    Creemers, Hanneke E.; Korhonen, Tellervo; Kaprio, Jaakko; Vollebergh, Wilma A. M.; Ormel, Johan; Verhulst, Frank C.; Huizink, Anja C.

    2009-01-01

    Background: While temperamental characteristics have been related to the onset of cannabis use, it is not clear at what point(s) along the trajectory from early onset of tobacco use (EOT) to early onset of cannabis use (EOC) these characteristics exert their impact. This study examined if (1)

  20. Differences between early and late-onset Alzheimer's disease in neuropsychological tests.

    Directory of Open Access Journals (Sweden)

    Francisca eSá

    2012-05-01

    Full Text Available Although patients with Alzheimer disease (AD share clinical and histological features regardless of age of onset, the hypothesis that early-onset AD constitutes a distinct subgroup prevails. Some authors suggest that early attention or language impairment constitute patterns of differentiation in terms of neuropsychological profile. However, investigations are not consensual in terms of cognitive domains affected in each group.Aim: To investigate whether there is early neuropsychological difference between two types of AD using the conventional dividing line of 65 years.Methods: We evaluated the results obtained in the Mini-Mental State Examination (MMSE and in a comprehensive neuropsychological battery – Battery of Lisbon for the Assessment of Dementia (BLAD, at a Dementia clinic in the University Hospital of Coimbra and a Memory Clinic. Consecutive patients with a clinical probable diagnosis of mild to moderate AD, using standard criteria (DSMIV and NINCDS-ADRDA, were selected. Statistical analysis was performed using Qui-square and U-Mann-Whitney, for categorical and non-categorical variables.Results: The sample included 280 patients: 109 with early-onset AD and 171 with a late-onset form. Groups were comparable in gender, education, severity of disease and MMSE. In BLAD, the early onset group had lower scores in Naming (p=0,025, Right-Left Orientation (p=0,029 and Praxis (p=0,001, and better performances in Orientation (p=0,001 and Visual Memory (p=0,022. After application of Bonferroni correction for multiple comparisons only Praxis and Orientation could differentiate the two groups.Discussion: The results are suggestive of dissociated profiles between early and late-onset AD. Younger patients have a major impairment in Praxis and a tendency for a great impairment in neocortical temporal functions. Late-onset form had a tendency for worse performances in Visual Memory and Orientation, suggesting a more localized disease to the limbic

  1. Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy

    DEFF Research Database (Denmark)

    Sarzi, Emmanuelle; Seveno, Marie; Angebault, Claire

    2016-01-01

    levels of steroid precursor pregnenolone in females, causing an early-onset vision loss, abolished by ovariectomy. In addition, steroid production in retina is also increased which, in conjunction with high circulating levels, impairs estrogen receptor expression and mitochondrial respiratory complex IV...... cohort and found that women undergo more severe visual loss at adolescence and greater progressive thinning of the retinal nerve fibres than males. Thus, we disclosed a gender-dependent effect on ADOA severity, involving for the first time steroids and Müller glial cells, responsible for RGC degeneration....

  2. Early-onset preeclampsia appears to discourage subsequent pregnancy but the risks may be overestimated.

    Science.gov (United States)

    Seeho, Sean K; Algert, Charles S; Roberts, Christine L; Ford, Jane B

    2016-12-01

    Early-onset preeclampsia is associated with adverse maternal and perinatal outcomes. For women who consider another pregnancy after one complicated by early-onset preeclampsia, the likelihood of recurrence and the subsequent pregnancy outcome for themselves and their babies are pertinent considerations. The purpose of this study was to determine the subsequent pregnancy rate after a nulliparous pregnancy that was complicated by early-onset preeclampsia and among those who have a subsequent pregnancy, the risk of recurrence by gestational week, and adverse pregnancy outcomes. This was a population-based record linkage cohort study. The study population included nulliparous women with a singleton pregnancy and early-onset preeclampsia (Early-onset in the index birth was further categorized as pregnancy outcomes that were assessed included the pregnancy rate, preeclampsia recurrence, and maternal and perinatal morbidity and mortality rates. The risk of preeclampsia necessitating delivery at each gestational week for women who were at risk was plotted, and the net gain or loss of gestational age when comparing the index with the subsequent pregnancy was calculated. Among 361,031 nulliparous women with singleton pregnancies, 1473 (0.4%) had early-onset preeclampsia. Women with early-onset preeclampsia in their first pregnancy had a lower subsequent pregnancy rate (59.7%) than women without preeclampsia (67.7%). Of the 758 women with a subsequent singleton birth, 256 (33.8%) experienced preeclampsia in the next pregnancy; 57 women (7.5%) with recurrent early-onset preeclampsia were included. Cumulative rates of preeclampsia in the subsequent pregnancy were higher at every gestation from 23 weeks gestation when the index birth was age in their subsequent pregnancy. The median overall increase in gestational age at delivery was 6 weeks (interquartile range, 4-8); among women with recurrent preeclampsia, the median increase was 5 weeks (interquartile range, 2-7). Women with

  3. Key goals and indicators for successful aging of adults with early-onset disability.

    Science.gov (United States)

    LaPlante, Mitchell P

    2014-01-01

    Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Rafaela Torres Portugal Leite

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Medial temporal atrophy in early and late-onset Alzheimer’s disease

    OpenAIRE

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

    2014-01-01

    Late-onset and early-onset Alzhemer’s disease (LOAD, EOAD) affect different neural systems and may be separate nosographic entities. The most striking differences is in the medial temporal lobe, severely affected in LOAD and relatively spared in EOAD. We assessed amygdalar morphology and volume in 18 LOAD and 18 EOAD patients and 36 aged-matched controls, and explored their relationship with hippocampal volume. 3D amygdalar shape was reconstructed with the Radial Atrophy Mapping technique, hi...

  7. A systematic review of the long-term outcome of early onset schizophrenia

    DEFF Research Database (Denmark)

    Clemmensen, Lars; Vernal, Ditte Lammers; Steinhausen, Hans-Christoph

    2012-01-01

    ABSTRACT: BACKGROUND: The current review analyzes the long-term outcome and prognosis of early onset schizophrenia based on previously published studies onset schizophrenia based on previously published studies in 1980. METHODS: A systematic search of articles published in the English-language...... and adolescence still carries a particularly poor prognosis. According to these aggregated data analyses, longer follow-up periods, male sex, and patients having been diagnosed before 1970 contribute predominantly to the rather poor course of EOS....

  8. Long term follow up of patients with early onset anorexia nervosa.

    OpenAIRE

    Bryant-Waugh, R; Knibbs, J; Fosson, A; Kaminski, Z; Lask, B

    1988-01-01

    A long term follow up (mean 7.2 years) of 30 children with anorexia nervosa (mean age at onset 11.7 years) was carried out. The outcome was good in only 18 (60%), 10 children remaining moderately to severely impaired and two died. Poor prognostic factors included early age at onset (less than 11 years), depression during the illness, disturbed family life and one parent families, and those in which one or both parents had been married before.

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

    Science.gov (United States)

    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

  10. Effect of early use of low-dose aspirin therapy on late-onset preeclampsia.

    Science.gov (United States)

    Lan, Patrick G; Gillin, Adrian G; Pelosi, Marilena; Tooher, Jane; Sandager, Puk; Hyett, Jon

    2018-01-24

    Low-dose aspirin (LDA) therapy has been found to be effective in preventing the development of early-onset preeclampsia. However, its effect on late-onset preeclampsia has not been described. Our study was aimed at determining if LDA therapy prescribed from early in pregnancy modified the severity of late-onset preeclampsia. A retrospective analysis of all women who were screened for early-onset preeclampsia at 11-13+6 weeks' gestation between April 2012 and October 2014 at our institution, and who subsequently developed late-onset preeclampsia. The treatment group consisted of women who were prescribed LDA therapy from early in pregnancy as a result of the screening. The control group consisted of women who did not receive LDA therapy. The aspirin group was associated with earlier delivery at 38.0 (37.5-38.5) weeks' gestation versus 39.0 (38.7-39.4) weeks' gestation for the nonaspirin group (p < .01). The aspirin group was also associated with lower absolute birth weight 2851 (2646-3055) versus 3215 (3068-3362) grams in the nonaspirin group (p < .01). However, when normalised for gestational age at delivery, the proportion of foetuses that were small for gestation age (< 10th centile) were not significantly different between the two groups [28% in aspirin group versus 23% in nonaspirin group; p = .62]. No other significant difference was noted. There was no difference in the clinical severity of late-onset preeclampsia between women screened as high risk for early-onset preeclampsia and subsequently prescribed LDA during their pregnancy, compared to women found to be at low risk and not prescribed LDA.

  11. Early nutrition and immunity - progress and perspectives

    DEFF Research Database (Denmark)

    Calder, PC; Krauss-Etschmann, S; de Jong, EC

    2006-01-01

    maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate...... immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune...

  12. VEPTR Implantation to Treat Children With Early-Onset Scoliosis Without Rib Abnormalities: Early Results From a Prospective Multicenter Study.

    Science.gov (United States)

    El-Hawary, Ron; Kadhim, Muayad; Vitale, Michael; Smith, John; Samdani, Amer; Flynn, John M

    2017-01-30

    Thoracoplasty and insertion of vertical expandable prosthetic titanium rib (VEPTR) for thoracic and spine distraction has been found to be effective in the treatment of early-onset scoliosis (EOS) with ribs anomalies and congenital vertebral anomalies. The aim of this study was to evaluate the efficacy of VEPTR in preventing further progression of scoliosis without impeding spinal growth in children with progressive EOS without rib abnormalities. This is a prospective, multicenter, observational cohort study. Erect radiographs were analyzed for coronal and sagittal curve and height measurements at preimplant, immediate postoperative, and at 2-year follow-up. Sixty-three patients met inclusion: 35 males and 28 females. Mean age at time of implantation was 6.1±2.4 years. Etiologies included congenital (n=6), neuromuscular (n=36), syndromic (n=4), and idiopathic (n=17). The mean follow-up was 2.2±0.4 years. Scoliosis (72±18 degrees) decreased after implant surgery (47±17 degrees) followed by slight increase at 2-year follow-up (57±18 degrees), PVEPTR was effective in treating EOS without rib abnormalities with 86% of patients having an improvement in scoliosis and 94% of patients having an increased spinal height as compared with preoperative values. This study proved that spine continues to grow after VEPTR instrumentation during the distraction phase. This amount of growth represents about 40% for T1-T12 and 31% for T1-S1 spine of the expected age-matched growth based on Dimeglio reference numbers. We find this growth important as it proves continuous spine growth with VEPTR treatment. Level II.

  13. Early onset necrotizing enterocolitis (NEC) in premature twins.

    Science.gov (United States)

    Afzal, B; Elberson, V; McLaughlin, C; Kumar, V H S

    2017-01-01

    Twin infants born at 34 week gestation had frank blood in stools on day three of life on mixed feeds of formula and maternal breast milk. Sepsis work up was negative in these relatively well appearing infants with pneumatosis in the colon on abdominal x-ray. Blood in stools recurred on reintroduction of breast milk in Twin A. Both infants recovered from episodes of bloody stools on amino-acid based formula and were thriving at discharge. Early necrotizing enterocolitis in both twins is rare and has not been reported. Cow's milk protein sensitivity, possibly from in-utero sensitization, could explain non-infectious colitis in these twins, precipitated by formula or breast milk after birth.

  14. [Alarming signs and symptoms in the early diagnostics of late onset Pompe disease: super omnia clinica].

    Science.gov (United States)

    Nikitin, S S; Kurbatov, S A; Bredelev, V A; Kovalchuk, M O

    2015-01-01

    Pompe disease (PD) is a rare autosomal recessive muscle lysosomal glycogenosis caused by a deficiency of acid-α-glucosidase. There are two main forms of the disease: aggressive infantile PD started within the first year of life with a severe enzyme deficiency and multiorgan involvement, and late onset PD (LOPD) with progressive signs and symptoms including predominant proximal, axial muscle weakness and respiratory insufficiency started at any time from 1 till 75 years and older. Usually due to physician's unawareness, most adults with PD are diagnosed with great delay. The typical features and early nonspecific signs in four patients, aged between 35 and 72 years, with confirmed LOPD are delineated and discussed in correspondence with the age of first signs, age development of muscle weakness, distribution and age of final diagnosis. The disorders for differential diagnosis and spectrum of conditions that expanded the possibility of PB are listed. The fluorometrically analyzed level of acid α-glucosidase from dried blood spots is considered to be the first choice diagnostic method for clinically suspected cases of LOPD.

  15. Nutritional Therapy in Very Early-Onset Inflammatory Bowel Disease: A Case Report.

    Science.gov (United States)

    Miller, Talya L; Lee, Dale; Giefer, Mathew; Wahbeh, Ghassan; Suskind, David L

    2017-08-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract caused by a dysregulated immune response to the fecal microbiota. Very early-onset inflammatory bowel disease (VEO-IBD) refers to a subgroup of pediatric patients with IBD diagnosed before 6 years of age. This subgroup is often characterized by increased severity, aggressive progression, strong family history of IBD, and often poor response to conventional treatments. Nutritional therapies have been utilized to treat IBD, but their role in VEO-IBD is unclear. Disease behavior in VEO-IBD is often different from disease in adolescents and adults, as it is often restricted to the colon and refractory to standard medical therapies. Up to 25% of VEO-IBD patients have an identified underlying immunodeficiency, which may impact response to therapy. While specific mutations in interleukin 10 (IL-10), the IL-10 receptor (IL-10R), and mutations in NCF2, XIAP, LRBA, and TTC7 have been identified in VEO-IBD, polymorphisms in these genes are also associated with increased risk of developing IBD in adolescence or adulthood. We describe two cases in which infants presenting with VEO-IBD achieved clinical remission using exclusive enteral nutrition, a formula-based diet which has been shown to induce remission in older children with active Crohn's disease.

  16. Do Growing Rods for Idiopathic Early Onset Scoliosis Improve Activity and Participation for Children?

    Science.gov (United States)

    Sewell, Mathew David; Platinum, Johnson; Askin, Geoffrey Noel; Labrom, Robert; Hutton, Mike; Chan, Daniel; Clarke, Andrew; Stokes, Oliver M; Molloy, Sean; Tucker, Stewart; Lehovsky, Jan

    2017-03-01

    To investigate whether growing rod surgery for children with progressive idiopathic early onset scoliosis (EOS) effects activity and participation, and investigate factors that may affect this. Multicenter retrospective cohort study using prospectively collected data on 60 children with idiopathic EOS and significant scoliosis (defined as a Cobb angle >40°). Thirty underwent brace treatment, and 30, growth rod surgery. Questionnaire and radiographic data were recorded at 1 year. The validated Activities Scale for Kids performance version (ASKp) questionnaire was used to measure activity and participation. In the brace group, Cobb angle increased from 60° to 68°. There was no change in ASKp score. In the operative group, Cobb angle decreased from 67° to 45°. ASKp decreased from 91 to 88 (P 40°), growth rod surgery was associated with a reduction in activity and participation and Cobb angle, whereas brace treatment was associated with an increase in Cobb angle and no change in activity and participation. Pain was the most important factor affecting activity and participation in both groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Differences in uterine artery blood flow and fetal growth between the early and late onset of pregnancy-induced hypertension.

    Science.gov (United States)

    Mitsui, Takashi; Masuyama, Hisashi; Maki, Jota; Tamada, Shoko; Hirano, Yumika; Eto, Eriko; Nobumoto, Etsuko; Hayata, Kei; Hiramatsu, Yuji

    2016-10-01

    We continuously measured bilateral uterine artery (UA) blood flow and compared differences in UA blood flow to investigate the differences in pathophysiology between early- and late-onset pregnancy-induced hypertension (PIH) and the usefulness of continuous monitoring of UA blood flow for the prediction of early-onset PIH. The subjects were 76 PIH patients. The mean pulsatility index of bilateral UA (UAPI), an early diastolic notch in the velocity waveform, and regression curves were retrospectively examined and compared between early- and late-onset groups and the groups with and without fetal growth restriction (FGR). Regression curves of the UAPI in the early-onset group persisted at +2.0 standard deviations or more from the second to third trimester, while the UAPI in the late-onset group stayed within the normal range. A significantly higher mean UAPI with a high frequency of an early diastolic notch was observed in the early-onset group compared with the late-onset group in all pregnancy trimesters. There was a significant difference in UA resistance between the mild and severe groups and between the FGR and non-FGR groups, but to a small extent compared with the onset period. There was a difference in pathophysiology between early- and late-onset PIH. Continuous monitoring of UA blood flow might be useful for the prediction of early-onset PIH if high UA resistance has been observed.

  18. Early Neoplastic Progression Is Complement Independent

    Directory of Open Access Journals (Sweden)

    Karin E. de Visser

    2004-11-01

    Full Text Available Infiltration of leukocytes into premalignant tissue is a common feature of many epithelial neoplasms and is thought to contribute to cancer development. However, the molecular and cellular regulatory mechanisms underlying activation of innate host responses to enhanced neoplastic cell proliferation are largely unknown. Considering the importance of the complement system in regulating inflammation during acute pathologic tissue remodeling, we examined the functional significance of complement component 3 (C3 as a regulator of inflammatory cell infiltration and activation during malignant progression by using a transgenic mouse model of multistage epithelial carcinogenesis, e.g., HPV16 mice. Whereas abundant deposition of C3 is a characteristic feature of premalignant hyperplasias and dysplasias coincident with leukocyte infiltration in neoplastic tissue, genetic elimination of C3 neither affects inflammatory cell recruitment toward neoplastic skin nor impacts responding pathways downstream of inflammatory cell activation, e.g., keratinocyte hyperproliferation or angiogenesis. Taken together, these data suggest that complementindependent pathways are critical for leukocyte recruitment into neoplastic tissue and leukocytemediated potentiation of tumorigenesis.

  19. Loss of Nfkb1 leads to early onset aging.

    Science.gov (United States)

    Bernal, Giovanna M; Wahlstrom, Joshua S; Crawley, Clayton D; Cahill, Kirk E; Pytel, Peter; Liang, Hua; Kang, Shijun; Weichselbaum, Ralph R; Yamini, Bakhtiar

    2014-11-01

    NF-κB is a major regulator of age-dependent gene expression and the p50/NF-κB1 subunit is an integral modulator of NF-κB signaling. Here, we examined Nfkb1-/- mice to investigate the relationship between this subunit and aging. Although Nfkb1-/- mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes. In addition, aged Nfkb1-/- animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+. In vitro, serially passaged primary Nfkb1-/- MEFs have more senescent cells than comparable Nfkb1+/+ MEFs. Also, Nfkb1-/- MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1-/- animals compared to Nfkb1+/+. Finally, in wildtype animals a substantial decrease in p50 DNA binding is seen in aged tissue compared to young. Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence. Moreover, loss of p50 DNA binding is a prominent feature of aged mice relative to young. These findings support the strong link between the NF-κB pathway and mammalian aging.

  20. Late adolescent outcome of early onset anorexia nervosa.

    Science.gov (United States)

    Jarman, F C; Rickards, W S; Hudson, I L

    1991-08-01

    Forty-three young female patients admitted consecutively to hospital with anorexia nervosa (AN) were re-evaluated in late adolescence an average of 4.3 years following initial presentation. Follow-up interviews were conducted individually by a paediatrician and a psychiatrist on 32 of the original 43 patients (mean age 18.3 years) with outcome assessed by multidimensional physical, menstrual, eating behaviour, psychosocial and global outcome criteria. Physical outcome, as assessed by validated indices of body adiposity, was within the normal range (3-97th percentiles) in 94% of the 32 patients seen at follow-up, although only 56% reported regular cyclical menstrual function. Good physical outcome, however, was not necessarily predictive of successful adjustment in other areas. Eating behaviour was unequivocally normal in only 25% of patients, with a majority still dieting, binging or vomiting with meals, Psychosocial adjustment was satisfactory in the majority of cases but varied widely. Univariate and multivariate statistical analysis identified higher premorbid and admission body mass index (BMI) percentiles, a family history of obesity and shorter duration of illness on admission as significant prognostic indicators of favourable physical outcome. Although girls who develop AN in early adolescence are generally thought to have a favourable long-term prognosis, health professionals need to be aware that these patients form a heterogeneous group and may have considerable ongoing physiologic and psychologic disturbance despite normalization of body mass.

  1. [Early onset of fingolimod-associated macular edema].

    Science.gov (United States)

    Schelenz, D; Kleiter, I; Schöllhammer, J; Rehrmann, J; Elling, M; Dick, H B; Kakkassery, V

    2017-06-26

    Fingolimod, a disease-modifying sphingosine 1‑phosphate receptor modulator, which was approved in Germany in 2011, decreases the relapse rate and reduces neuroinflammation in patients with relapsing-remitting multiple sclerosis. Macular edema is a well-known ocular side effect of fingolimod therapy. Specific intervals for ophthalmologic check-ups after starting fingolimod and definite treatment schedules for fingolimod-associated macular edema are, however, still lacking. We present a case of early fingolimod-associated macular edema in a 45-year-old female patient with relapsing-remitting multiple sclerosis. The patient complained about visual impairment 1 month after the start of fingolimod and visited an eye specialist. Funduscopic examination and imaging diagnostics revealed macular edema in both eyes. The treatment with fingolimod was immediately stopped. For therapy of macular edema topical application of nepafenac and oral acetazolamide were given. During the 6 months of treatment the macular edema completely disappeared and visual function recovered completely. At the time of diagnosis, it is fundamentally important to discuss the continuation of fingolimod administration with the attending neurologist and if necessary to discontinue the drug. Regular ophthalmologic check-ups at 4‑week intervals over a period of 3 months are meaningful after beginning fingolimod treatment. As before, it is still a key aspect to determine predictive opthalmologic and neurological factors before beginning treatment to evaluate which patients are at risk of fingolimod-associated macular edema.

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

    OpenAIRE

    Hooghiemstra Astrid M; Eggermont Laura HP; Scheltens Philip; van der Flier Wiesje M; Bakker Jet; de Greef Mathieu HG; Koppe Peter A; Scherder Erik JA

    2012-01-01

    Abstract Background Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to partic...

  3. Mutant TDP-43 within motor neurons drives disease onset but not progression in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ditsworth, Dara; Maldonado, Marcus; McAlonis-Downes, Melissa; Sun, Shuying; Seelman, Amanda; Drenner, Kevin; Arnold, Eveline; Ling, Shuo-Chien; Pizzo, Donald; Ravits, John; Cleveland, Don W; Da Cruz, Sandrine

    2017-06-01

    Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43Q331K mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons. Cre-recombinase-mediated excision of the TDP-43Q331K gene from motor neurons is shown to delay onset of motor symptoms and appearance of TDP-43-mediated aberrant nuclear morphology, and abrogate subsequent death of motor neurons. However, reduction of mutant TDP-43 selectively in motor neurons did not prevent age-dependent degeneration of axons and neuromuscular junction loss, nor did it attenuate astrogliosis or microgliosis. Thus, disease mechanism is non-cell autonomous with mutant TDP-43 expressed in motor neurons determining disease onset but progression defined by mutant acting within other cell types.

  4. Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes

    Science.gov (United States)

    Mathews, Clayton E.; Xue, Song; Posgai, Amanda; Lightfoot, Yaima L.; Li, Xia; Lin, Andrea; Wasserfall, Clive; Haller, Michael J.; Schatz, Desmond

    2015-01-01

    Most natural history models for type 1 diabetes (T1D) propose that overt hyperglycemia results after a progressive loss of insulin-secreting β-cell mass and/or function. To experimentally address this concept, we prospectively determined morning blood glucose measurements every other day in multiple cohorts (total n = 660) of female NOD/ShiLtJ mice starting at 8 weeks of age until diabetes onset or 26 weeks of age. Consistent with this notion, a majority of mice that developed diabetes (354 of 489 [72%]) displayed a progressive increase in blood glucose with transient excursions >200 mg/dL, followed by acute and persistent hyperglycemia at diabetes onset. However, 135 of the 489 (28%) diabetic animals demonstrated normal glucose values followed by acute (i.e., sudden) hyperglycemia. Interestingly, diabetes onset occurred earlier in mice with acute versus progressive disease onset (15.37 ± 0.3207 vs. 17.44 ± 0.2073 weeks of age, P < 0.0001). Moreover, the pattern of onset (i.e., progressive vs. acute) dramatically influenced the ability to achieve reversal of T1D by immunotherapeutic intervention, with increased effectiveness observed in situations of a progressive deterioration in euglycemia. These studies highlight a novel natural history aspect in this animal model, one that may provide important guidance for the selection of subjects participating in human trials seeking disease reversal. PMID:26216853

  5. Risk factors and early signs of pancreatic cancer in diabetes: screening strategy based on diabetes onset age.

    Science.gov (United States)

    Mizuno, Suguru; Nakai, Yousuke; Isayama, Hiroyuki; Yanai, Ayako; Takahara, Naminatsu; Miyabayashi, Koji; Yamamoto, Keisuke; Kawakubo, Kazumichi; Mohri, Dai; Kogure, Hirofumi; Sasaki, Takashi; Yamamoto, Natsuyo; Sasahira, Naoki; Hirano, Kenji; Tsujino, Takeshi; Ijichi, Hideaki; Tateishi, Keisuke; Akanuma, Masao; Tada, Minoru; Koike, Kazuhiko

    2013-02-01

    Diabetes mellitus (DM) has long been recognized as a risk factor for pancreatic cancer (PaC) and recently has attracted attention as a manifestation of PaC. Diabetes is expected to be a clue for the early detection of PaC; however, no effective screening strategy has been established. Forty diabetic patients with PaC were identified and compared with 120 diabetic patients without any malignancies. We analyzed risk factors for and early signs of PaC, focusing on the DM-onset age. As there were peaks at 40-45 years and 60-65 years in the distribution of DM-onset age, we analyzed the clinical characteristics of and risk factors for PaC according to DM-onset age: i.e., early-onset (early-onset DM, and in 33% of those with late-onset DM. The mean duration of DM in patients with early-onset DM with PaC was longer than that in the late-onset patients (26 vs. 9 years; P early-onset DM, while the onset age of DM (OR 1.12) and multiple diabetic patients in the family (OR 6.13) were risk factors in those with late-onset DM. Body weight loss and exacerbation of DM were seen 12 months prior to PaC diagnosis in both groups. Our study revealed specific risk factors for and similar early signs of PaC in early-onset and late-onset DM. Thus, we could develop a screening strategy, combining these risk factors specific for DM-onset age with early signs of disease.

  6. Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

    Science.gov (United States)

    Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

    2015-09-01

    Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Risk of early-onset prostate cancer associated with occupation in the Nordic countries

    DEFF Research Database (Denmark)

    Hughes Barry, Kathryn; Martinsen, Jan Ivar; Alavanja, Michael C. R.

    2017-01-01

    .g. firefighters) (SIR = 1.71, 95% confidence interval [CI]: 1.23-2.31) and military personnel (SIR = 1.97, 95% CI: 1.31-2.85). These SIRs were significantly higher than the SIRs for later-onset disease (for public safety workers, SIR = 1.10, 95% CI: 1.07-1.14 and for military personnel, SIR = 1.09, 95% CI: 1.......05-1.13; pheterogeneity = 0.005 and 0.002, respectively). Administrators and technical workers also demonstrated significantly increased risks for early-onset prostate cancer, but the SIRs did not differ from those of later-onset disease (pheterogeneity >0.05). While our early-onset finding for public safety workers...... was restricted to the post-PSA period, that for military personnel was restricted to the pre-PSA period. CONCLUSION: Our results suggest that occupational exposures, particularly for military personnel, may be associated with early-onset prostate cancer. Further evaluation is needed to explain these findings....

  8. A new definition of early age at onset in alcohol dependence.

    Science.gov (United States)

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

    2010-04-01

    The accurate cut-off of an early onset of alcohol dependence is unknown. The objectives of this analysis are (1) to confirm that ages at onset variability in alcohol dependence is best described as a two subgroups entity, (2) to define the most appropriate cut-off, and (3) to test the relevancy of such distinction. Data were drawn the Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This study focused on the 4782 adults with lifetime alcohol dependence. The best-fit model distinguished two subgroups of age at onset of alcohol dependence, with a cut-off point at 22 years. Subjects with an earlier onset of alcohol dependence (alcohol dependence is best defined as beginning before the age of 22 years. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  9. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

    Directory of Open Access Journals (Sweden)

    Giuseppe Musumeci

    2015-03-01

    Full Text Available Osteoarthritis (OA is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin, it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder.

  10. Early-onset group B streptococcal disease in the era of maternal screening.

    Science.gov (United States)

    Puopolo, Karen M; Madoff, Lawrence C; Eichenwald, Eric C

    2005-05-01

    With the widespread implementation of intrapartum antibiotic prophylaxis (IAP), the rate of early-onset neonatal sepsis and meningitis caused by Streptococcus agalactiae (group B streptococcus [GBS]) has decreased dramatically, especially in term infants. However, cases of GBS disease continue to occur despite IAP and incur significant morbidity and mortality. Inaccurate screening results, improper implementation of IAP, or antibiotic failure all may contribute to persistent disease. To determine if clinical, procedural, or microbiologic factors influenced persistent early-onset GBS disease (EOGBS) cases in a single large maternity service after the institution of a screening-based protocol for IAP. Retrospective review of all cases of culture-proven EOGBS at the Brigham and Women's Hospital (Boston, MA) from 1997 to 2003. Serotyping and surface protein analyses were performed on available disease isolates. A total of 67260 infants were live-born during this period. Twenty-five cases of EOGBS (0.37 of 1000 live births) were identified. The overall incidence of EOGBS progressively decreased with different approaches to IAP. Of the 25 cases identified after institution of a screening-based protocol, 17 (68%) occurred in term infants (1 death), and 8 (32%) occurred in preterm infants (3 deaths). Among the mothers of term infants, 14 of 17 (82%) had been screened GBS negative; 1 was GBS unknown. More than half of the mothers of term infants who had screened GBS negative (8 of 14) had intrapartum risk factors for neonatal infection but did not receive antibiotics before delivery. Ten of the 17 term infants were evaluated for infection because of clinical signs of illness, and the remainder were evaluated because of intrapartum sepsis risk factors. Of the mothers of preterm infants, by the time of delivery 3 of 8 had been documented as GBS positive, 2 of 8 had been documented GBS negative, and 3 of 8 remained unknown. Only 1 of 25 women received adequate IAP, but the

  11. Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Bieniek, M; Altmann, D R; Davies, G R; Ingle, G T; Rashid, W; Sastre-Garriga, J; Thompson, A J; Miller, D H

    2006-09-01

    The onset of multiple sclerosis is relapsing remitting or primary progressive. An improved understanding of the causes of early progressive disability in primary progressive multiple sclerosis (PPMS) could provide mechanistic targets for therapeutic intervention. Five magnetic resonance imaging (MRI) parameters that could potentially cause progressive disability were investigated in 43 patients with early PPMS and in 37 patients with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both grey matter and white matter; intrinsic abnormality in brain, both grey matter and white matter (measured by the magnetisation transfer ratio (MTR)); and atrophy of the upper cervical spinal cord. Both groups were also compared with controls. Patients with PPMS were older and more likely to be men. Both patient groups had atrophy of brain grey matter and white matter, and intrinsic abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2; controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of all five MRI parameters, age and sex. Grey matter and white matter of the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant in PPMS treatment trials.

  12. Magnetic resonance imaging studies in early-onset bipolar disorder: a critical review.

    Science.gov (United States)

    Frazier, Jean A; Ahn, Mary S; DeJong, Sandra; Bent, Eileen K; Breeze, Janis L; Giuliano, Anthony J

    2005-01-01

    Neuroimaging studies of early-onset bipolar disorder (BD) are important in order to establish a fuller understanding of the underlying pathophysiology of the illness. The advantages of studying BD in children and adolescents include the relative absence of some confounds present in adult-onset research, such as lengthy duration of illness and exposure to treatments, greater number of mood episodes, and the presence of substance abuse or dependence. Finally, studying youths with the disorder may enhance our knowledge about the neural mechanisms of affective dysregulation and may specifically elucidate whether there are abnormalities that are unique to the early-onset form of the illness. PubMed was used to identify peer-reviewed publications from the past 15 years (January 1990 to January 2005) that used brain-imaging techniques (anatomic, functional, and biochemical) to research early-onset BD. Eleven studies using anatomic magnetic resonance imaging (MRI), seven using magnetic resonance spectroscopy (MRS), and two using functional MRI (fMRI) were identified. Structural abnormalities were reported in total cerebral, white matter, superior temporal gyrus, putamen, thalamus, amygdala, and hippocampal volumes. Deficits in cortical gray matter were also reported. Using MRS, abnormalities were reported in the dorsolateral prefrontal cortex, anterior cingulate, and basal ganglia. One fMRI study found increased activation in the putamen and thalamus of BD youths compared to controls, and a second found abnormal prefrontal-subcortical activation in familial pediatric BD. Published MRI studies of early-onset BD are few. Nonetheless, extant data implicate abnormalities in brain regions thought to regulate mood and cognition. Synthesis of the findings into an overall model of anatomic and functional disruption is difficult due to the methodological variations among studies and the limitations of individual studies, such as the use of small sample sizes, the heterogeneity of

  13. MODERN APPROACHES TO CLINICAL AND LABORATORY DIAGNOSTICS OF RHEUMATOID ARTHRITIS EARLY ONSET

    Directory of Open Access Journals (Sweden)

    D. G. Rekalov

    2013-10-01

    Full Text Available Rheumatoid arthritis (RA leads not only to a rapid development of disability, but can influence the life of these patients. One-third of patients with rheumatoid arthritis may have signs of disability during the first 3 years of the onset of the disease, while mortality in patients with RA almost two times higher in comparison with the general population. Analysis of recent prospective studies on the progression of the pathological process and predicting of the long-term outcomes in RA clearly indicate the need for clinical evaluation and a comprehensive laboratory and instrumental diagnosis of the disease in the initial manifestations of the most followed by early adequate pathogenetic therapy. The purpose of this survey was to determine modern clinical aspects of diagnosis, the possibility of standard and specialized instrumental examinations in patients with eRA, followed by predicting long-term results. We studied 52 specialized publications on clinical classification and a modern laboratory and diagnostic tests for eRA. This review presents the data of the importance of differentiation of several stages of RA in relation to the time factor. The data on the sensitivity and specificity of the diagnostic classification and clinical criteria of eRA and an algorithm for the identification of the disease were presented. It was shown prognostic value of the main serological markers of RA, and the predictive value for early detection of antibodies to the circulating peptide as a marker of the severity of bone-destructive changes in patients with certain clinical manifestations. Antibodies to the circulating peptide (ACPA can be detected many years before the onset of RA. Study of anti-citrulline mutated vimentin (anti-MCV in patients with eRA can be applied as a marker of activity of the process and the subsequent possibility of use for predicting long-term results. This review presents the major diagnostic errors using standard instrumental

  14. The unique pathophysiology of early-onset severe preeclampsia: role of decidual T regulatory cells.

    Science.gov (United States)

    Quinn, Kristen H; Lacoursiere, D Yvette; Cui, Li; Bui, Jack; Parast, Mana M

    2011-09-01

    Immunological mechanisms play a pivotal role in the pathophysiology of preeclampsia. T regulatory cells (Treg cells, FoxP3(+)) suppress the cytotoxic T cell (CD8(+)) and natural killer (NK) cell response, thereby promoting immunological tolerance to the fetus. In peripheral blood, Treg cells are elevated during pregnancy, decrease throughout gestation, and are decreased in preeclampsia. To determine their role at the implantation site, we characterized the proportion of decidual Treg and CD8+ cells, and compared these with placental histology, villous sFlt expression, and chorionic trophoblast apoptotic index in normal and preeclamptic pregnancies. Decidua from first (n=5) and second (n=4) trimester terminations and chorioamniotic membranes, containing decidua, from term deliveries (n=14), early-onset (≤ 34 weeks) (n=12), and late-onset (>34 weeks) (n=14) severe preeclampsia were evaluated. Immunohistochemistry for CD3, CD8, and FoxP3 was performed: CD8(+) and FoxP3(+) cells were calculated as a proportion of CD3(+) cells. Placental tissue was evaluated for villous hypermaturity and sFlt staining. Chorioamniotic membranes were evaluated, via TUNEL assay, for chorionic trophoblast apoptosis. Decidual Treg cells were seen to peak in second trimester and decrease with advancing gestational age and were lower in early-onset (0.46%) compared with late-onset severe preeclampsia (3.34%) and term pregnancies (5.21%). The proportion of CD8(+) cells was higher in cases of severe preeclampsia. Early-onset severe preeclamptic cases had the highest sFlt score, placental insufficiency score, and apoptotic index. Our data suggest that early-onset severe preeclampsia has a unique pathophysiology involving defective immunoregulatory pathways, potentially causing vascular and trophoblast damage at the implantation site. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, Rick; Lawerman, Tjitske F.; Kuiper, Marieke J; Lunsing, Roelineke J; Burger, Huibert; Sival, Deborah A

    AIM: To determine whether ataxia rating scales are reliable disease biomarkers for early onset ataxia (EOA). METHOD: In 40 patients clinically identified with EOA (28 males, 12 females; mean age 15y 3mo [range 5-34y]), we determined interobserver and intraobserver agreement (interclass correlation

  16. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J.W.; Blankenstein, M.A.; Heijboer, A.C.; van Vugt, J.M.

    2011-01-01

    Objective: To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). Methods: PlGF concentration was retrospectively measured in first trimester

  17. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J. W. R.; Blankenstein, M. A.; Heijboer, A. C.; van Vugt, J. M. G.

    2011-01-01

    To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). PlGF concentration was retrospectively measured in first trimester serum specimens of 23

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

    Science.gov (United States)

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

    2012-01-01

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

  19. Neutrophil CD64 in early-onset neonatal sepsis | El-Mazary ...

    African Journals Online (AJOL)

    However, for neonatal sepsis, little is known about a group of molecules playing a central role in the innate immune system. Among them is the neutrophil CD64 which is expressed on neutrophil surface in many inflammatory conditions. Objective: To study the neutrophil CD64 expression in neonates with early onset sepsis ...

  20. Type IV Neonatal Early-Onset Group B Streptococcal Disease in a United States Hospital▿

    Science.gov (United States)

    Puopolo, Karen M.; Madoff, Lawrence C.

    2007-01-01

    Group B streptococcus (GBS) serotypes causing neonatal disease vary by geographic region. Surveillance at the Brigham and Women's Hospital in Boston, Massachusetts, revealed a case of neonatal early-onset sepsis caused by type IV GBS. Neonatal type IV disease occurs in the Middle East but has not recently been described in U.S. infants. PMID:17267636

  1. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy

    NARCIS (Netherlands)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velden, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2016-01-01

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized

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

    Science.gov (United States)

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

    2011-01-01

    Although longevity among older adults with intellectual disabilities is increasing, there is limited information on their premature aging related health characteristics and how it may change with increasing age. The present paper provides information of the institutional manager's perception on early onset aging and service preparation for this…

  3. Examining determinants of early and late age at onset in panic disorder: An admixture analysis

    NARCIS (Netherlands)

    Tibi, L.; van Oppen, P.; Aderka, I.M.; van Balkom, A.J.L.M.; Batelaan, N.M.; Spinhoven, P.; Penninx, B.W.J.H.; Anholt, G.E.

    2013-01-01

    Past research demonstrated that age at onset might account for different clinical and etiological characteristics in panic disorder (PD). However, prior research relied on arbitrary choices of age cut-offs. Using a data-driven validated method, this study aimed to examine differences between early

  4. Examining determinants of early and late age at onset in panic disorder : An admixture analysis

    NARCIS (Netherlands)

    Tibi, Lee; van Oppen, Patricia; Aderka, Idan M.; van Balkom, Anton J. L. M.; Batelaan, Neeltje M.; Spinhoven, Philip; Penninx, Brenda W.; Anholt, Gideon E.

    2013-01-01

    Past research demonstrated that age at onset might account for different clinical and etiological characteristics in panic disorder (PD). However, prior research relied on arbitrary choices of age cut-offs. Using a data-driven validated method, this study aimed to examine differences between early

  5. Early onset of cannabis use: Does personality modify the relation with changes in perceived parental involvement?

    NARCIS (Netherlands)

    Creemers, H.E.; Buil, J.M.; Van Lier, P.A.C.; Keijsers, L.; Meeus, W.; Koot, H.M.; Huizink, A.C.

    2015-01-01

    Background: The present study examined (1) the association between changes in perceived parental control and support from age 13 to 15 and early onset of cannabis use (before age 16), and (2) whether personality modifies the association between a decline in perceived parental control and support and

  6. Early onset of cannabis use: Does personality modify the relation with changes in perceived parental involvement?

    NARCIS (Netherlands)

    Creemers, Hanneke E.; Buil, J. Marieke; van Lier, Pot A. C.; Keijsers, Loes; Meeus, W.H.J.; Koot, Hans M.; Huizink, Anja C.

    2015-01-01

    Background The present study examined (1) the association between changes in perceived parental control and support from age 13 to 15 and early onset of cannabis use (before age 16), and (2) whether personality modifies the association between a decline in perceived parental control and support and

  7. Apathy and depressive mood in nursing home patients with early-onset dementia.

    NARCIS (Netherlands)

    Leontjevas, R.; Hooren, S. van; Waterink, W.; Mulders, A.

    2009-01-01

    The study explored whether apathy and depressive mood symptoms (DMS) are related to cognitive and functional features of dementia in 63 nursing home (NH) residents with early-onset dementia (EOD). All EOD residents from one NH (n = 41) and a random sample from another NH were assessed for depressive

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

    NARCIS (Netherlands)

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

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to

  9. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, R.; Lawerman, T. F.; Kuiper, M. J.; Geffen, van Joke; Lunsing, I. J.; Burger, H.; de Koning, T. J.; de Vries, J. J.; de Koning-Tijssen, M. A. J.; Sival, D. A.

    Objective: To determine observer-agreement and discriminantvalidity of ataxia rating scales.Background: In children and young adults, Early Onset Ataxia(EOA) is frequently concurrent with other Movement Disorders,resulting in moderate inter-observer agreement among MovementDisorder professionals. To

  10. Assessment of speech in early-onset ataxia : a pilot study

    NARCIS (Netherlands)

    Kuiper, Marieke J.; Brandsma, Rick; Lawerman, T.F.; Lunsing, Roelineke J.; Keegstra, Anne L.; Burger, Huibert; De Koning, Tom J.; Tijssen, Marina A. J.; Sival, Deborah A.

    2014-01-01

    AIM: The aim of the study was to determine whether paediatric ataxia speech subscores are reliably applicable for international early-onset ataxia (EOA) databases. If so, we reasoned that ataxia speech subscores should be associated with ataxia scores and involve high interobserver agreement,

  11. Reliability and discriminant validity of ataxia rating scales in early onset ataxia

    NARCIS (Netherlands)

    Brandsma, Rick; Lawerman, Tjitske F.; Kuiper, Marieke J.; Lunsing, Roelineke J.; Burger, Huibert; Sival, Deborah A.

    AIM To determine whether ataxia rating scales are reliable disease biomarkers for early onset ataxia (EOA). METHOD In 40 patients clinically identified with EOA (28 males, 12 females; mean age 15y 3mo [range 5-34y]), we determined interobserver and intraobserver agreement (interclass correlation

  12. Impaired contrast sensitivity at low spatial frequency in cannabis users with early onset.

    Science.gov (United States)

    Lalanne, Laurence; Ferrand-Devouge, Eglantine; Kirchherr, Sebastien; Rauch, Lucie; Koning, Estelle; Speeg, Claude; Laprevote, Vincent; Giersch, Anne

    2017-12-01

    The regular use of cannabis generates pronounced cognitive disorders, especially in users who begin before the age of 15-16. However, less is known about the impact of regular cannabis on visual function, especially in the case of early onset. Cannabinoid receptors (CB1) are expressed in areas of the visual system, like the thalamus and primary cortex, which might originate sensory disorders. Hence, we measured contrast sensitivity (CS) in three groups, i.e. cannabis users with late onset of cannabis use (after 16 years old), cannabis users with early onset". We used a constant method which allowed us to control for biased responses. Stimuli were presented at high and low spatial frequencies and in both static and dynamic conditions (8Hz). As contrast sensitivity is measured behaviorally based on an explicit response and could thus be impacted by attentional or vigilance disorders, participants' attention and vigilance were carefully monitored by means of the D2 test, CPT-AX for attention and pupillography for vigilance. Cannabis users with early onset were significantly impaired only at low spatial frequency. This effect was independent of response bias, vigilance and attention. These results show for the first time that early cannabis use impacts contrast sensitivity at low spatial frequency. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

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

    Science.gov (United States)

    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),…

  14. Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study

    NARCIS (Netherlands)

    Karas, Giorgos; Scheltens, Philip; Rombouts, Serge; Schijndel, van Ronald; Klein, Martin; Jones, Bethany; Flier, van der Wiesje; Vrenken, Hugo; Barkhof, Frederik

    2007-01-01

    Introduction Alzheimer’s disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different

  15. Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement

    NARCIS (Netherlands)

    Ossenkoppele, R.; Zwan, M.D.; Tolboom, N.; van Assema, D.M.E.; Adriaanse, S.F.; Kloet, R.W.; Boellaard, R.; Windhorst, A.D.; Barkhof, F.; Lammertsma, A.A.; Scheltens, P.; van der Flier, W.M.; van Berckel, B.N.M.

    2012-01-01

    Alzheimer's disease with early onset often presents with a distinct cognitive profile, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age and both in vivo fibrillary amyloid deposition and glucose

  16. Type IV neonatal early-onset group B streptococcal disease in a United States hospital.

    Science.gov (United States)

    Puopolo, Karen M; Madoff, Lawrence C

    2007-04-01

    Group B streptococcus (GBS) serotypes causing neonatal disease vary by geographic region. Surveillance at the Brigham and Women's Hospital in Boston, Massachusetts, revealed a case of neonatal early-onset sepsis caused by type IV GBS. Neonatal type IV disease occurs in the Middle East but has not recently been described in U.S. infants.

  17. Comparison of Percentile Weight Gain of Growth-Friendly Constructs in Early-Onset Scoliosis.

    Science.gov (United States)

    Harris, Liam R; Andras, Lindsay M; Sponseller, Paul D; Johnston, Charles E; Emans, John B; Skaggs, David L

    2018-01-01

    Multicenter retrospective cohort. To compare improvement in nutritional status seen in early-onset scoliosis (EOS) patients following treatment with various growth-friendly techniques, especially in underweight patients (10 years old and Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  18. CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

    NARCIS (Netherlands)

    Ozen, Ahmet; Comrie, William A; Ardy, Rico C; Domínguez Conde, Cecilia; Dalgic, Buket; Beser, Ömer F; Morawski, Aaron R; Karakoc-Aydiner, Elif; Tutar, Engin; Baris, Safa; Ozcay, Figen; Serwas, Nina K; Zhang, Yu; Matthews, Helen F; Pittaluga, Stefania; Folio, Les R; Unlusoy Aksu, Aysel; McElwee, Joshua J; Krolo, Ana; Kiykim, Ayca; Baris, Zeren; Gulsan, Meltem; Ogulur, Ismail; Snapper, Scott B; Houwen, Roderick H J|info:eu-repo/dai/nl/087887991; Leavis, Helen L|info:eu-repo/dai/nl/304820717; Ertem, Deniz; Kain, Renate; Sari, Sinan; Erkan, Tülay; Su, Helen C; Boztug, Kaan; Lenardo, Michael J

    2017-01-01

    BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary

  19. Early-onset periodontitis in Morocco is associated with the highly leukotoxic clone of Actinobacillus actinomycetemcomitans

    DEFF Research Database (Denmark)

    Haubek, Dorte; Ennibi, O.-K.; Poulsen, Knud

    2001-01-01

    A particular clone (JP2) of Actinobacillus actinomycetemcomitans with increased leukotoxin production has been isolated from individuals with early-onset periodontitis (EOP). The aim of this study was to determine the frequency of carriers of this clone and its association with EOP in Moroccan...

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

    Science.gov (United States)

    Chang, Zheng; Lichtenstein, Paul; Larsson, Henrik

    2012-01-01

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

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

    Science.gov (United States)

    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 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. © The Author(s) 2015.

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

    NARCIS (Netherlands)

    Hooghiemstra, A.M.; Eggermont, L.H.P.; Scheltens, P.; van der Flier, W.M.; Bakker, J.; de Greef, M.H.G.; Koppe, P.A.; Scherder, E.J.A.

    2012-01-01

    Background: Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial

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

    NARCIS (Netherlands)

    Hooghiemstra, Astrid M.; Eggermont, Laura H. P.; Scheltens, Philip; van der Flier, Wiesje M.; Bakker, Jet; de Greef, Mathieu H. G.; Koppe, Peter A.; Scherder, Erik J. A.

    2012-01-01

    Background: Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial

  4. [Associations between early-onset mental disorders and educational attainment in Belgium; a population study].

    Science.gov (United States)

    Bruffaerts, R P; Bonnewyn, A; Demyttenaere, K

    2010-01-01

    There is no sufficient knowledge on the association between early-onset mental disorders and subsequent school dropout on the level of the Belgian general population. To investigate the associations between early-onset mental disorders and subsequent school dropout. As part of the European Study on the Epidemiology of Mental Disorders of the World Mental Health Surveys of the World Health Organization, a representative random sample of non-institutionalised Belgians aged 18 or older (n = 1,043) were interviewed between April 2001 and June 2002. With the Composite International Diagnostic Interview (version 3.0), respondents were assessed for the presence and age of onset of 15 dsm-iv mental disorders. Logistic regression analyses were performed in order to investigate the association between mental disorders and subsequent failure to complete elementary and/or secondary education, failure to proceed to tertiary education (when holding a secondary education leaving certificate) and failure to completion of tertiary education. Mood disorders were significantly associated with premature termination of secondary education (or = 2.4). Anxiety disorders (or = 2.0), drug abuse disorders (or = 11.2), and drug dependence disorders (or = 19.4) were significantly associated with failure to proceed to tertiary education. The cumulative proportion of early school terminations attributable to earlyonset mental disorders was estimated at 6.3%. Early-onset mental disorders have a considerable impact on school termination prior to completion in Belgium.

  5. Apolipoprotein E genotype and concomitant clinical features in early-onset Alzheimer's disease

    NARCIS (Netherlands)

    Bronzova, J.; Duijn, C.M. van; Havekes, L.M.; Knijff, P. de; Broeckhoven, C. van; Hofman, A.

    1996-01-01

    We have studied the relationship between the apolipoprotein E gene (APOE) and the development of myoclonus, tremors, rigidity and seizures in 168 patients with probable early-onset Alzheimer's disease (AD). There was a statistically significantly lower risk of tremor for carriers of the ε4 allele of

  6. Apolipoprotein E genotype and concomitant clinical features in early-onset Alzheimer's disease.

    NARCIS (Netherlands)

    J.B. Bronzova (Juliana); C.M. van Duijn (Cornelia); L.M. Havekes; P. de Knijff (Peter); C. van Broeckhoven (Christine); A. Hofman (Albert)

    1996-01-01

    textabstractWe have studied the relationship between the apolipoprotein E gene (APOE) and the development of myoclonus, tremors, rigidity and seizures in 168 patients with probable early-onset Alzheimer's disease (AD). There was a statistically significantly lower risk of tremor for carriers of the

  7. Clinical features and mortality in patients with early-onset Alzheimer's disease.

    NARCIS (Netherlands)

    W.N. Samson; C.M. van Duijn (Cornelia); W.C.J. Hop (Wim); A. Hofman (Albert)

    1996-01-01

    textabstractIn a population-based study of 198 patients with probable early-onset Alzheimer's disease (AD), we studied the occurrence of extrapyramidal signs (tremors and rigidity), myoclonus, psychosis and seizures, as well as their predictive value for mortality. The presence of tremors was

  8. Three cases of severe early-onset eating disorder: are they cases of anorexia nervosa?

    Science.gov (United States)

    Nielsen, G B; Lausch, B; Thomsen, P H

    1997-01-01

    3 cases of early onset, severe eating disorder are described. These young children did not present a distorted body image even though they had suffered a great weight loss, were somatically distressed and in all other aspects fulfilled the criteria for anorexia nervosa. The criteria for anorexia nervosa are discussed for this group of young patients.

  9. Early onset vulvar Lichen Sclerosus in premenopausal women and oral contraceptives.

    Science.gov (United States)

    Günthert, Andreas R; Faber, Melanie; Knappe, Gabriele; Hellriegel, Simin; Emons, Günter

    2008-03-01

    For vulvar Lichen sclerosus (LS) immunological factors, genetic predisposition, and decreased 5 alpha-reductase activity have been discussed as aetiological factors. During the last decade an increase of LS in young women has been suspected. Aim of this study was to evaluate data of premenopausal women with early onset LS to find potential risk factors focussing on the use of oral contraceptives. We retrospectively analyzed the data of 40 premenopausal patients with early onset LS regarding use of oral contraceptives (OCPs), and first occurrence of LS. To compare these data in a case-control study we analyzed a matched control group of 110 healthy women. All our LS patients were using OCPs compared to 73 women (66.4%) in the control group. OCPs with anti-androgenic activity (chlormadinone acetate, cyproterone acetate, dienogest, and drospirenone) were used by 28 (70%) of the LS patients and by 35 (47.9%) of the 73 women using OCPs in the control group. Thus, the odds ratio for early onset LS for women using anti-androgenic OCPs was 2.53 (95% CI: 1.12-5.75). Our data suggest that disturbance of the androgen dependent growth of the vulvar skin by OCPs and especially by OCPs with anti-androgenic properties might trigger the early onset of LS in a subgroup of susceptible young women.

  10. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

    NARCIS (Netherlands)

    Milne, Anya N. A.; Carvalho, Ralph; Morsink, Folkert M.; Musler, Alex R.; de Leng, Wendy W. J.; Ristimäki, Ari; Offerhaus, G. Johan A.

    2006-01-01

    Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (

  11. Deficient maturation of aspects of attention and executive functions in early onset schizophrenia

    DEFF Research Database (Denmark)

    Jepsen, Jens Richardt M; Fagerlund, Birgitte; Pagsberg, Anne Katrine

    2010-01-01

    The few existing long-term, neuropsychological follow-up studies of early onset schizophrenia (EOS) patients have reported relative stability in some cognitive functions but abnormal developmental trajectories in verbal memory, set shifting, aspects of attention, and speed of information processing...

  12. Attention deficit-hyperactivity disorder and early-onset bipolar disorder: two facets of one entity?

    OpenAIRE

    Zepf, Florian D.

    2009-01-01

    Early-onset bipolar disorder (BD) and attention-deficithyperactivity disorder (ADHD) have recently been the subject of highly controversial debate, due to theories regarding underlying pathophysiological processes and a clinical overlap of symptoms. Epidemiological data, clinical aspect, neuroimaging, neurochemical, and genetic studies suggest that there may be a possible relationship between biological factors and clinical characteristic in the development of symptoms. However, longitudinal ...

  13. Early-onset neonatal group B streptococcus sepsis following national risk-based prevention guidelines.

    Science.gov (United States)

    Darlow, Brian A; Voss, Lesley; Lennon, Diana R; Grimwood, Keith

    2016-02-01

    Neonatal infection with group B streptococcus (GBS) is an important cause of infant mortality. Intrapartum antibiotics reduce early-onset GBS sepsis, but recommendations vary as to whether they should be offered following antenatal screening or based on risk factors alone. We aimed to determine the incidence of early-onset GBS sepsis in New Zealand five years after the publication of national risk-based GBS prevention guidelines. Prospective surveillance of early-onset GBS sepsis (defined as infection in the first 48 h of life) was undertaken between April 2009 and March 2011 through the auspices of the New Zealand Paediatric Surveillance Unit as part of a survey of infection presenting in the first week of life. There were 29 cases of confirmed early-onset GBS sepsis, including one case of meningitis, giving an incidence rate of 0.23 per 1000 (95% CI 0.16-0.33) live births. Three infants (10.3%) died. In 16 cases (55%), a maternal risk factor qualifying the mother for intrapartum antibiotics was present, but only five (31%) received this intervention. A retrospective review of the major hospital laboratory databases for this period identified two additional cases. A secondary sensitivity analysis taking account of these cases provided an estimated national incidence of 0.26 (95% CI 0.18-0.37) per 1000 live births. Ten years after a similar survey and five years after promoting a single, risk-based prevention protocol nationally, the incidence of early-onset GBS disease in New Zealand has more than halved, but opportunities remain to further reduce the rate. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  14. Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

    Science.gov (United States)

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

    2015-01-01

    After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

  15. Outdoor activity during class recess reduces myopia onset and progression in school children.

    Science.gov (United States)

    Wu, Pei-Chang; Tsai, Chia-Ling; Wu, Hsiang-Lin; Yang, Yi-Hsin; Kuo, Hsi-Kung

    2013-05-01

    The aim of this study was to investigate the effect of outdoor activity during class recess on myopia changes among elementary school students in a suburban area of Taiwan. Prospective, comparative, consecutive, interventional study. Elementary school students 7 to 11 years of age recruited from 2 nearby schools located in a suburban area of southern Taiwan. The children of one school participated in the interventions, whereas those from the other school served as the control group. The interventions consisted of performing a recess outside the classroom (ROC) program that encouraged children to go outside for outdoor activities during recess. The control school did not have any special programs during recess. Data were obtained by means of a parent questionnaire and ocular evaluations that included axial length and cycloplegic autorefraction at the beginning and after 1 year. Five hundred seventy-one students were recruited for this study, of whom 333 students participated in the interventional program, and 238 students were in the control school. At the beginning of the study, there were no significant differences between these 2 schools with regard to age, gender, baseline refraction, and myopia prevalence (47.75% vs. 49.16%). After 1 year, new onset of myopia was significantly lower in the ROC group than in the control group (8.41% vs. 17.65%; Pschool year proved to be a protective factor against myopia shift in nonmyopic subjects (P = 0.020 and P = 0.017, respectively). For myopic subjects, school year was the only variable significantly associated with myopia progression (P = 0.006). Outdoor activities during class recess in school have a significant effect on myopia onset and myopic shift. Such activities have a prominent effect on the control of myopia shift, especially in nonmyopic children. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by

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

    Directory of Open Access Journals (Sweden)

    Yi-Chu Liao

    Full Text Available 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.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.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.

  17. Premorbid risk factors for major depressive disorder: are they associated with early onset and recurrent course?

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  19. Early onset of delinquency and the trajectory of alcohol-impaired driving among young males.

    Science.gov (United States)

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

    2011-12-01

    Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis.

    Science.gov (United States)

    McWilliams, Robert R; Maisonneuve, Patrick; Bamlet, William R; Petersen, Gloria M; Li, Donghui; Risch, Harvey A; Yu, Herbert; Fontham, Elizabeth T H; Luckett, Brian; Bosetti, Cristina; Negri, Eva; La Vecchia, Carlo; Talamini, Renato; Bueno de Mesquita, H Bas; Bracci, Paige; Gallinger, Steven; Neale, Rachel E; Lowenfels, Albert B

    2016-02-01

    While pancreatic cancer (PC) most often affects older adults, to date, there has been no comprehensive assessment of risk factors among PC patients younger than 60 years. We defined early-onset PC (EOPC) and very-early-onset PC (VEOPC) as diagnosis of PC in patients younger than 60 and 45 years, respectively. We pooled data from 8 case-control studies, including 1954 patients with EOPC and 3278 age- and sex-matched control subjects. Logistic regression analysis was performed to identify associations with EOPC and VEOPC. Family history of PC, diabetes mellitus, smoking, obesity, and pancreatitis were associated with EOPC. Alcohol use equal to or greater than 26 g daily also was associated with increased risk of EOPC (odds ratio, 1.49; 95% confidence interval, 1.21-1.84), and there appeared to be a dose- and age-dependent effect of alcohol on risk. The point estimate for risk of VEOPC was an odds ratio of 2.18 (95% confidence interval, 1.17-4.09). The established risk factors for PC, including smoking, diabetes, family history of PC, and obesity, also apply to EOPC. Alcohol intake appeared to have an age-dependent effect; the strongest association was with VEOPC.

  1. Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis

    Science.gov (United States)

    McWilliams, Robert R; Maisonneuve, Patrick; Bamlet, William R; Petersen, Gloria M; Li, Donghui; Risch, Harvey; Yu, Herbert; Fontham, Elizabeth TH; Luckett, Brian; Bosetti, Cristina; Negri, Eva; La Vecchia, Carlo; Talamini, Renato; Bueno de Mesquita, H Bas; Bracci, Paige; Gallinger, Steven; Neale, Rachel E; Lowenfels, Albert B

    2015-01-01

    Objectives While pancreatic cancer (PC) most often affects older adults, to date, there has been no comprehensive assessment of risk factors among PC patients under age 60. Methods We defined early onset PC (EOPC) and very early onset PC (VEOPC) as diagnosis of PC under ages 60 and 45, respectively. We pooled data from eight case-control studies, including 1,954 patients with EOPC and 3,278 age- and sex-matched controls. Logistic regression analysis was performed to identify associations with EOPC and VEOPC. Results Family history of PC, diabetes mellitus, smoking, obesity, and pancreatitis were associated with EOPC. Alcohol use ≥26 g daily also was associated with increased risk for EOPC (OR 1.49, 95% CI 1.21-1.84), and there appeared to be a dose-and age-dependent effect of alcohol on risk. The point estimate for risk for VEOPC was OR 2.18, (95% CI 1.17-4.09). Conclusion The established risk factors for PC, including smoking, diabetes, family history of PC, and obesity also apply to EOPC. Alcohol intake appeared to have an age-dependent effect; the strongest association was with VEOPC. PMID:26646264

  2. Beginners' Progress in Early Arithmetic in the Swedish Compulsory School

    Science.gov (United States)

    Eriksson, Gota

    2008-01-01

    This article focuses on spontaneous knowledge-building in the field of "the arithmetic "of" the child." The aim is to investigate the conceptual progress of fifteen children during their early school years in the compulsory school. The study is based on the epistemology of radical constructivism and the methodology of…

  3. Kita driven expression of oncogenic HRAS leads to early onset and highly penetrant melanoma in zebrafish.

    Directory of Open Access Journals (Sweden)

    Cristina Santoriello

    2010-12-01

    Full Text Available Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed.Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period.This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens.

  4. Results of the spine-to-rib-cage distraction in the treatment of early onset scoliosis

    Directory of Open Access Journals (Sweden)

    Teli Marco

    2010-01-01

    Full Text Available Background: Growing rod systems have been used in the last 30 years for the treatment of early onset scoliosis (EOS with variable success rates. We report the results of treatment of EOS with a newly developed hybrid rod distraction system applied to the rib cage and spine with a nonfusion technique in a prospective multicenter clinical trial. Materials and Methods: A total of 22 patients affected by progressive EOS resistant to cast and/or brace treatment were enrolled from 2004 to 2005 after informed consent into a trial of surgical treatment with a single spine-to-rib growing rod instrumentation growing spine profiler (GSP. Curves> 60° Cobb in the frontal plane or bending < 50% were addressed with staged anterior annulotomy and fusion and posterior implantation of a GSP rod. Less severe and rigid curves were treated with posterior implantation of GSP only. The elongation of GSP was planned according to spinal growth. Patients were kept in a brace between elongations. Results: A total of 20 patients were available to follow-up with complete data. The mean follow up is 4.1 years. Mean age at time of initial surgery was 5 years (3-8. Nine patients had staged antero-posterior surgeries, 11 posterior only surgeries. Mean spinal growth was 1.9 cm (1.5-2.3 or 0.5 cm per year. Mean coronal Cobb′s angle correction was from 56° to 45°. Major complications affected 40% of patients and included rod failure in 6/20 and crankshaft in 5/20 (all in the anteroposterior surgery group. Conclusion: Treatment of EOS with spine-to-rib growing rod in the present form provides similar correction and complication rates to those published in the series considering traditional single or dual growing rod systems. Based on this, the authors recommend revision of the GSP design and a new clinical trial to test safety and efficacy.

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

    Science.gov (United States)

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

    2015-10-01

    The common and specific involvement of brain networks in clinical variants of Alzheimer's disease (AD) is not well understood. We performed task-free ("resting-state") functional imaging in 60 nonfamilial AD patients, including 20 early-onset AD (age at onset functional connectivity is greatest in networks outside the DMN in early-onset and nonamnestic AD variants and may thus be a better biomarker in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models

    NARCIS (Netherlands)

    Thangaratinam, Shakila; Allotey, John; Marlin, Nadine; Dodds, Julie; Cheong-See, Fiona; von Dadelszen, Peter; Ganzevoort, Wessel; Akkermans, Joost; Kerry, Sally; Mol, Ben W.; Moons, Karl G. M.; Riley, Richard D.; Khan, Khalid S.; Sundararajah, Raajkumar; Nejad, Avideah; Khan, Rehan; Burrell, Celia; Gupta, Manish; Oon, Vincent; Kadir, Rezan; Ramsey-Marcelle, Zeudi; Page, Louise; Thilaganathan, Baskaran; Martin, Bill; Bakour, Shagaf Haj; Morsi, Hassan; Churchill, David; O'Mahony, Fidelma; Powell, Karen; Srinivasan, Jayasree; Mohajer, Michele; Quenby, Siobhan; Thirumalaikumar, Lakshmi; Konje, Justin; Thornton, Jim; Bugg, George; Mackenzie, Shonag; Ullal, Aarti; Smith, Marie; Arya, Rita; Cunnigham, Simon; Walker, James; Simpson, Nigel; Page, Joanne; Oxby, Claire; Watkins, Karen; Tuffnell, Derek; Bober, S.; Wijesiriwardana, A.; Brandon, Helene; El-Badawy, Saif; Brigham, Sara; Shorinola, Lanre; Khunda, Aethele; Kalla, Shaku; Agha, Mohammed M. Abdullah; Poku, Stephen; Olawo, Ayo; Amu, Johnson; Banfield, Philip; Majoko, Franz; Alcide, Julia; Rajeswary, Jyothi; Salloum, Marwan; Rees, Alexandra; Oteri, Odiri; Ikhena, Sunday; Creswell, Janet; Dawood, Feroza; Agarwal, Umber

    2017-01-01

    Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in

  7. Prediction of complications in early-onset pre-eclampsia (PREP) : Development and external multinational validation of prognostic models

    NARCIS (Netherlands)

    Thangaratinam, Shakila; Allotey, John; Marlin, Nadine; Dodds, Julie; Cheong-See, Fiona; von Dadelszen, Peter; Ganzevoort, Wessel; Akkermans, Joost; Kerry, Sally; Mol, Ben W.; Moons, Karl G.M.; Riley, Richard D.; Khan, Khalid S.

    2017-01-01

    Background: Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. Method: Women with confirmed early onset pre-eclampsia were recruited from 53

  8. The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

    Science.gov (United States)

    Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

    2017-07-01

    To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

  9. [The relationship between accommodative accuracy at different near-work distances and early-onset myopia].

    Science.gov (United States)

    Yu, Q W; Zhang, P; Zhou, S B; Hu, Y; Ji, M X; Luo, Y C; You, H L; Yao, Z X

    2016-07-01

    To observe the accommodative accuracy of children with early-onset myopia at different near-work distances, and discuss the relationship between accommodative accuracy and early-onset myopia. This was a case-control study. Thirty-seven emmetropic children, 41 early-onset myopic children without correction, and 39 early-onset myopic children with spectacles, aged 7 to 13 years, were included. Measures of refractive errors and accommodative accuracy at four near-work distances, including 50 cm, 40 cm, 30 cm, and 20 cm, were made using the binocular fusion cross cylinder (FCC) of an automatic phoropter. Most candidates showed accommodative lags, including the children with emmetropia. The ratio of lags in all candidates at different near-work distances was 75.21% (50 cm), 87.18% (40 cm), 92.31% (30 cm), and 98.29% (20 cm), respectively. All accommodative accuracies became worse, and the accommodative lag ratio and values of FCC increased, along with the shortening of the distance. The difference in accommodative accuracy among groups was statistically significant at 30 cm (χ(2)=7.852, P= 0.020) and 20 cm (χ(2)=6.480, P=0.039). The values of FCC among groups were significantly different at 30 cm (F=3.626, P=0.030) and 20 cm (F=3.703, P=0.028), but not at 50 cm and 40 cm (P>0.05). In addition, the FCC values of 30 cm and 20 cm had a statistically significant difference between myopic children without correction [(1.25±0.44) D and (1.76±0.43) D] and emmetropic children [(0.95±0.52) D and (1.41±0.58) D] (P=0.012, 0.008). The correlation between diopters of myopia and accommodative accuracy at different nearwork distances was not statistically significant (P>0.05). However, the correlation between diopters of myopia and the accommodative lag value (FCC) at 20 cm was statistically significant (r=0.246, P=0.028). The closer the near-work distance is, the worse the accommodative accuracy is. This is more significant in early-onset myopia, especially myopia without

  10. Family physician consultation patterns indicate high risk for early-onset anorexia nervosa.

    Science.gov (United States)

    Lask, Bryan; Bryant-Waugh, Rachel; Wright, Fiona; Campbell, Mari; Willoughby, Kate; Waller, Glenn

    2005-11-01

    There is often a delay in the recognition of early-onset anorexia nervosa. The current study aimed to determine whether there are specific patterns in the frequency and content of family physician consultations that might predict its onset. Lifetime number and type of family physician consultations were recorded for three groups: (a) an index group comprising 19 girls with anorexia nervosa, onset under 14; (b) a clinical control group comprising 19 girls with an emotional disorder; and (c) a nonclinical group comprising 19 girls with no history of mental health problems. Both clinical groups had an elevated number of consultations, particularly in the 5 years before diagnosis. The index group had a significantly higher number of eating, weight, and shape consultations (especially in the year before diagnosis), whereas the clinical control group had a greater number of psychological consultations. A single consultation about eating behaviour or weight and shape concerns is a strong predictor of the subsequent emergence of anorexia nervosa.

  11. Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

    Science.gov (United States)

    Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

    2017-03-16

    To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Onset and early use of gestural communication in nonhuman great apes.

    Science.gov (United States)

    Schneider, Christel; Call, Josep; Liebal, Katja

    2012-02-01

    The early gesturing of six bonobos, eight chimpanzees, three gorillas, and eight orangutans was systematically documented using focal animal sampling. Apes' were observed during their first 20 months of life in an effort to investigate: (i) the onset of gesturing; (ii) the order in which signals of different sensory modalities appear; (iii) the extent to which infants make use of these modalities in their early signaling; and (iv) the behavioral contexts where signals are employed. Orangutans differed in important gestural characteristics to African ape species. Most notably, they showed the latest gestural onset and were more likely to use their early signals in food-related interactions. Tactile and visual signals appeared similarly early across all four species. In African apes, however, visual signaling gained prominence over time while tactile signaling decreased. These findings suggest that motor ability, which encourages independence from caregivers, is an important antecedent, among others, in gestural onset and development, a finding which warrants further investigation. © 2011 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. An analysis of expectant management in women with early-onset preeclampsia in China.

    Science.gov (United States)

    Chen, Q; Shen, F; Gao, Y F; Zhao, M

    2015-06-01

    Preeclampsia is a pregnancy-specific disorder and a leading cause of morbidity and mortality in both women and fetus. Although women with early severe preeclampsia are generally considered to require expedious delivery, expectant management may benefit for pregnancy prolongation. We performed a retrospective analysis of expectant management in early-onset preeclampsia, with or without fetal grow restriction (FGR) over a 6-year period, to investigate whether these women benefit from expectant management. Data including clinical parameters and liver and renal function from 186 nulliparous women with early-onset preeclampsia were analysed. In women with early-onset preeclampsia, 76.8% were delivered after 48 h and the median pregnancy prolongation was 8 days, whereas 23.2% were delivered within 48 h. There was no difference in maternal parameters, liver or renal functions between women in these two groups, regardless of the severity of preeclampsia. However, the stillbirth number was higher in preeclamptic women delivered after 48 h compared with those delivered within 48 h. Our study demonstrates that the decision for immediate delivery or expectant management was not associated with clinical parameter or laboratory biomarker of liver and renal function. However, the risk of stillbirth should still be taken into consideration when making the decision for immediate delivery or expectant management in the clinic.

  15. Early onset otitis media: risk factors and effects on the outcome of chronic suppurative otitis media.

    Science.gov (United States)

    Lasisi, Akeem O; Olayemi, Oladapo; Irabor, Achiaka E

    2008-07-01

    The onset of early otitis media (EOM), in the first few months of life has been reported to predict later chronic otitis media (CSOM), although the prevalence rates are increasing little is known about specific risk factors. In this survey we examined the hypothesis that higher risk factors is associated with the development of OM within 1 year compared to later onset and early onset otitis media (OM) has potential for negative outcome of CSOM. This is a survey of the age at onset of otorrhoea and associated risk factors in children with CSOM, in five sites spread in two sub-urban cities in two states in Nigeria. Questionnaires were administered on the informants followed by examination of the children. EOM was seen in 136/189 (70%) with CSOM, the age range was 1-150 months, mean of 59.25 (SD = 44.55). Of the 85 CSOM subjects with hearing loss, EOM accounted for 49 (57.7%) while 36 (42.4%) was later onset, On multivariate analysis (OR = 0.276, CI = 0.133-0.572, P = 0.001) revealing EOM was significant in the development of hearing loss however there was no correlation with the frequency of attack of otorrhoea (OR = 1.025, CI = 0.88-1.19, P = 0.75). Low socioeconomic status seen in 110/136 EOM (P = 0.000), allergy (P = 0.030) and number of people >10 in household (OR = 4.13, CI = 1.81-9.39, P = 0.001) constituted the significant risk for EOM compared to later onset. Bottlefeeding, adenoiditis/adenoid hypertrophy, indoor cooking and upper respiratory infection were not found to have statistical significance in early onset OM compared to later onset OM. This study found correlation between EOM and hearing loss and identified allergy, low social status and chronic exposure to overcrowding through increased number of children in the household significant risk factors for future research focus. This may help in controlling the prevalence of hearing loss accompanying CSOM.

  16. Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Karas, Giorgos [Vrije Universiteit Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Scheltens, Philip; Jones, Bethany [Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Department of Clinical Neurology, Amsterdam (Netherlands); Rombouts, Serge [Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Department of Clinical Physics and Informatics, Amsterdam (Netherlands); Schijndel, Ronald van [Vrije Universiteit Medical Center, Image Analysis Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Department of Clinical Physics and Informatics, Amsterdam (Netherlands); Klein, Martin [Vrije Universiteit Medical Center, Department of Medical Psychology, Amsterdam (Netherlands); Flier, Wiesje van der [Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands); Vrenken, Hugo [Vrije Universiteit Medical Center, Image Analysis Center, Amsterdam (Netherlands); Barkhof, Frederik [Vrije Universiteit Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Image Analysis Center, Amsterdam (Netherlands); Vrije Universiteit Medical Center, Alzheimer Center, Amsterdam (Netherlands)

    2007-12-15

    Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans. We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex. The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning. Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset. (orig.)

  17. Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Giulia Venturini

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

  18. Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization.

    Science.gov (United States)

    O'Grady, Gina L; Best, Heather A; Sztal, Tamar E; Schartner, Vanessa; Sanjuan-Vazquez, Myriam; Donkervoort, Sandra; Abath Neto, Osorio; Sutton, Roger Bryan; Ilkovski, Biljana; Romero, Norma Beatriz; Stojkovic, Tanya; Dastgir, Jahannaz; Waddell, Leigh B; Boland, Anne; Hu, Ying; Williams, Caitlin; Ruparelia, Avnika A; Maisonobe, Thierry; Peduto, Anthony J; Reddel, Stephen W; Lek, Monkol; Tukiainen, Taru; Cummings, Beryl B; Joshi, Himanshu; Nectoux, Juliette; Brammah, Susan; Deleuze, Jean-François; Ing, Viola Oorschot; Ramm, Georg; Ardicli, Didem; Nowak, Kristen J; Talim, Beril; Topaloglu, Haluk; Laing, Nigel G; North, Kathryn N; MacArthur, Daniel G; Friant, Sylvie; Clarke, Nigel F; Bryson-Richardson, Robert J; Bönnemann, Carsten G; Laporte, Jocelyn; Cooper, Sandra T

    2016-11-03

    This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase. Distinctive histopathology showed abundant internalized nuclei, myofibrillar disorganization, desmin-positive inclusions, and thickened Z-bands. PYROXD1 is a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins (FAD-binding) and catalyze pyridine-nucleotide-dependent (NAD/NADH) reduction of thiol residues in other proteins. Complementation experiments in yeast lacking glutathione reductase glr1 show that human PYROXD1 has reductase activity that is strongly impaired by the disease-associated missense mutations. Immunolocalization studies in human muscle and zebrafish myofibers demonstrate that PYROXD1 localizes to the nucleus and to striated sarcomeric compartments. Zebrafish with ryroxD1 knock-down recapitulate features of PYROXD1 myopathy with sarcomeric disorganization, myofibrillar aggregates, and marked swimming defect. We characterize variants in the oxidoreductase PYROXD1 as a cause of early-onset myopathy with distinctive histopathology and introduce altered redox regulation as a primary cause of congenital muscle disease. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

    Science.gov (United States)

    Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

    2014-04-30

    Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Possible role of glial cells in the onset and progression of Lyme neuroborreliosis

    Directory of Open Access Journals (Sweden)

    Jacobs Mary B

    2009-08-01

    Full Text Available Abstract Background Lyme neuroborreliosis (LNB may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. Methods We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS, and dorsal root nerves and ganglia (DRG. Results ELISA of the cerebrospinal fluid (CSF showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. Conclusion Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.

  1. Microscopic and macroscopic models for the onset and progression of Alzheimer's disease

    Science.gov (United States)

    Bertsch, Michiel; Franchi, Bruno; Carla Tesi, Maria; Tosin, Andrea

    2017-10-01

    In the first part of this paper we review a mathematical model for the onset and progression of Alzheimer’s disease (AD) that was developed in subsequent steps over several years. The model is meant to describe the evolution of AD in vivo. In Achdou et al (2013 J. Math. Biol. 67 1369-92) we treated the problem at a microscopic scale, where the typical length scale is a multiple of the size of the soma of a single neuron. Subsequently, in Bertsch et al (2017 Math. Med. Biol. 34 193-214) we concentrated on the macroscopic scale, where brain neurons are regarded as a continuous medium, structured by their degree of malfunctioning. In the second part of the paper we consider the relation between the microscopic and the macroscopic models. In particular we show under which assumptions the kinetic transport equation, which in the macroscopic model governs the evolution of the probability measure for the degree of malfunctioning of neurons, can be derived from a particle-based setting. The models are based on aggregation and diffusion equations for β-Amyloid (Aβ from now on), a protein fragment that healthy brains regularly produce and eliminate. In case of dementia Aβ monomers are no longer properly washed out and begin to coalesce forming eventually plaques. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: (i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons; (ii) neuron-to-neuron prion-like transmission. In the microscopic model we consider mechanism (i), modelling it by a system of Smoluchowski equations for the amyloid concentration (describing the agglomeration phenomenon), with the addition of a diffusion term as well as of a source term on the neuronal membrane. At the macroscopic level instead we model processes (i) and (ii) by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the

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

    Directory of Open Access Journals (Sweden)

    Vernooij-Dassen Myrra JFJ

    2010-03-01

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

  3. Early onset alcohol dependence with high density of family history is not "male limited".

    Science.gov (United States)

    Magnusson, Asa; Göransson, Mona; Heilig, Markus

    2010-03-01

    Based on classical adoption studies, early onset type II alcoholism was originally described as "male limited." We examined the possible expression of this subtype in present day alcohol-dependent women. Detailed systematic assessment was obtained from 200 treatment-seeking alcohol-dependent women and 189 healthy population controls. Women fulfilling type II alcoholism criteria had higher alcoholism severity as measured by The Alcohol Use Disorders Identification Test and markedly higher use of illicit drugs. Both alcoholism subtypes scored higher than normal on anxiety and impulsivity traits, but type II women scored markedly higher on aggression subscales than either of the other groups. Importantly, density of family history was markedly higher in type II women, suggesting a higher heritability. Despite its original description as male limited, early onset alcoholism with high density of family history is likely to be a valid construct in women. Its recognition has important implications for diagnosis, treatment, and research. Published by Elsevier Inc.

  4. IKs Gain- and Loss-of-Function In Early-Onset Lone Atrial Fibrillation

    DEFF Research Database (Denmark)

    Steffensen, Annette Buur; Refsgaard, Lena; Andersen, Martin Nybo

    2015-01-01

    INTRODUCTION: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.1), was the first ion channel dysfunction...... to be associated with familial AF. We hypothesized that early-onset lone AF is associated with a high prevalence of mutations in KCNQ1. METHODS AND RESULTS: We bidirectionally sequenced the entire coding sequence of KCNQ1 in 209 unrelated patients with early-onset lone AF (... the identified mutations functionally in a heterologous expression system. We found four non-synonymous KCNQ1 mutations (A46T, R195W, A302V, and R670K) in 4 unrelated patients (38, 31, 39, and 36 years, respectively). None of the mutations were present in the control group (n = 416 alleles). No other mutations...

  5. Reduced life expectancy seen in hereditary diseases which predispose to early-onset tumors

    OpenAIRE

    Evans DGR; Ingham SL

    2013-01-01

    D Gareth R Evans,1 Sarah Louise Ingham21Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester Foundation Trust, St Mary's Hospital, Manchester, UK; 2Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UKAbstract: There are several hereditary diseases that are a predisposition to early-onset tumors. These include syndromic conditions like neurofibromatosis 1 and 2, von Hippel–Lindau syndrome, Gorli...

  6. Homozygous partial genomic triplication of the parkin gene in early-onset parkinsonism.

    Science.gov (United States)

    Mata, Ignacio F; Alvarez, Victoria; Coto, Eliecer; Blazquez, Marta; Guisasola, Luis M; Salvador, Carlos; Kachergus, Jennifer M; Lincoln, Sarah J; Farrer, Matthew

    2005-06-03

    Autosomal recessive mutations in the parkin gene are the predominant cause of familial, early-onset parkinsonism; missense mutations involving one or a few nucleotides, exonic deletions and duplications have been described. Here we report a family with two affected brothers. Direct sequencing of parkin did not detect mutations, but semi-quantitative analysis identified a novel exonic rearrangement of exons 2-4. Both patients were homozygous for unique genomic triplications of the parkin gene.

  7. Job Loss After Diagnosis of Early-Onset Dementia: A Matched Cohort Study

    OpenAIRE

    Sakata, Nobuo; Okumura, Yasuyuki

    2017-01-01

    Early-onset dementia (EOD) affects the employment of patients and family members. To demonstrate how likely employees are to leave their jobs after an EOD diagnosis for themselves or a family member, we conducted a matched cohort study of 143 employees and 77 family members diagnosed with EOD using a claims database. We matched these participants to 5 controls each, and followed them for approximately 600 days. In the employee cohort, patients with EOD were more likely to leave their jobs tha...

  8. A case of probable non-familial early onset Alzheimer dementia in a Hispanic male

    OpenAIRE

    Ephrussi, Corey; Alweis, Richard

    2012-01-01

    Background: Early onset Alzheimer’s type dementia (EOAD) is usually familial and associated with mutations in the Presenilin-1 (PSEN1), Presenilin-2 (PSEN2) or amyloid precursor protein (APP) genes. It is rarely reported in patients of Hispanic descent. Case report: A 49-year-old Hispanic male developed significant cognitive impairment over a 4-year period. PET scan showed diminished metabolic activity in the posterior parietal/temporal lobes. Genetic testing revealed the presence of a PSEN1 ...

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

    Science.gov (United States)

    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…

  10. Case study: early-onset anorexia nervosa in a Chinese boy.

    Science.gov (United States)

    Lai, K Y; Pang, A H; Wong, C K

    1995-03-01

    In this case study of early-onset anorexia nervosa in a male patient from Hong Kong, clinical features are outlined and compared with those of their Western counterparts. Implications of being the only son in a traditional Chinese family and the process of acculturation and cultural conflicts of growing up in a Western-oriented society are put forward as significant psychodynamic factors in the etiology of his illness.

  11. Expectant management of early-onset severe preeclampsia. Literature review and treatment protocol

    Directory of Open Access Journals (Sweden)

    César Augusto Rendón

    2013-12-01

    Full Text Available The main goal of expectant management in women with severe preeclampsia (PE remote from term is to improve neonatal outcome, without compromising maternal health. Studies suggest that expectant management in early-onset preeclampsia may be associated with decreased neonatal morbidity, but also conclude that further studies are needed to assess maternal safety. The aim of this review is to assess the current issue evidence regarding the management of severe preeclampsia remote from term.

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

    Directory of Open Access Journals (Sweden)

    Sachin K. Gupta

    2013-10-01

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

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

    OpenAIRE

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

    2013-01-01

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

  14. Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis.

    Science.gov (United States)

    Okafuji, Ikuo; Nishikomori, Ryuta; Kanazawa, Nobuo; Kambe, Naotomo; Fujisawa, Akihiro; Yamazaki, Shin; Saito, Megumu; Yoshioka, Takakazu; Kawai, Tomoki; Sakai, Hidemasa; Tanizaki, Hideaki; Heike, Toshio; Miyachi, Yoshiki; Nakahata, Tatsutoshi

    2009-01-01

    Blau syndrome and its sporadic counterpart, early-onset sarcoidosis (EOS), share a phenotype featuring the symptom triad of skin rash, arthritis, and uveitis. This systemic inflammatory granulomatosis is associated with mutations in the NOD2 gene. The aim of this study was to describe the clinical manifestations of Blau syndrome/EOS in Japanese patients and to determine whether the NOD2 genotype and its associated basal NF-kappaB activity predict the Blau syndrome/EOS clinical phenotype. Twenty Japanese patients with Blau syndrome/EOS and NOD2 mutations were recruited. Mutated NOD2 was categorized based on its basal NF-kappaB activity, which was defined as the ratio of NF-kappaB activity without a NOD2 ligand, muramyldipeptide, to NF-kappaB activity with muramyldipeptide. All 9 mutations, including E383G, a novel mutation that was identified in 20 patients with Blau syndrome/EOS, were detected in the centrally located NOD region and were associated with ligand-independent NF-kappaB activation. The median age of the patients at disease onset was 14 months, although in 2 patients in Blau syndrome families (with mutations R334W and E383G, respectively) the age at onset was 5 years or older. Most patients with Blau syndrome/EOS had the triad of skin, joint, and ocular symptoms, the onset of which was in this order. Clinical manifestations varied even among familial cases and patients with the same mutations. There was no clear relationship between the clinical phenotype and basal NF-kappaB activity due to mutated NOD2. However, when attention was focused on the 2 most frequent mutations, R334W and R334Q, R334W tended to cause more obvious visual impairment. NOD2 genotyping may help predict disease progression in patients with Blau syndrome/EOS.

  15. Reduced life expectancy seen in hereditary diseases which predispose to early-onset tumors

    Directory of Open Access Journals (Sweden)

    Evans DGR

    2013-07-01

    Full Text Available D Gareth R Evans,1 Sarah Louise Ingham21Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester Foundation Trust, St Mary's Hospital, Manchester, UK; 2Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UKAbstract: There are several hereditary diseases that are a predisposition to early-onset tumors. These include syndromic conditions like neurofibromatosis 1 and 2, von Hippel–Lindau syndrome, Gorlin syndrome, multiple endocrine neoplasia, and familial adenomatous polyposis; and conditions which are usually not possible to diagnose clinically in a single individual, such as Lynch syndrome and BRCA1/2. Understanding of the mortality in hereditary cancer predisposing diseases is important for developing effective disease treatment programs. A number of studies have been undertaken to investigate the genetic predictors, prevalence and incidence, and treatment outcomes of these diseases; however, the majority examine only the most common of these diseases (eg, neurofibromatosis or BRCA, or look into postoperative survival. The mortality of individuals who are diagnosed with one of these hereditary diseases remains an area for investigation. This review is the first to attempt identification of studies investigating life expectancy in hereditary diseases which predispose to early-onset tumors.Keywords: mortality, survival, life expectancy, early-onset, tumors

  16. Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.

    Science.gov (United States)

    Mayoral, María; Merchán-Naranjo, Jessica; Rapado, Marta; Leiva, Marta; Moreno, Carmen; Giráldez, Marisa; Arango, Celso; Parellada, Mara

    2010-11-01

    The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls. NSS were assessed by means of the Neurological Evaluation Scale in a sample of 29 patients with Asperger syndrome (mean age = 12.86 ± 2.58 years), 30 patients with first-episode early-onset psychoses (mean age 14.17 ± 1.02 years) and 30 healthy controls (mean age 12.33 ± 2.69 years). Significant group differences were found between Asperger syndrome patients and healthy controls both in all the Neurological Evaluation Scale subscales and in the Neurological Evaluation Scale total score. There were no significant differences between both groups of patients in any of the Neurological Evaluation Scale scores. NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses. © 2010 Blackwell Publishing Asia Pty Ltd.

  17. Beyond mice: Emerging and transdisciplinary models for the study of early-onset myopathies.

    Science.gov (United States)

    Jagla, Krzysztof; Kalman, Benoit; Boudou, Thomas; Hénon, Sylvie; Batonnet-Pichon, Sabrina

    2017-04-01

    The use of the adapted models to decipher patho-physiological mechanisms of human diseases is always a great challenge. This is of particular importance for early-onset myopathies, in which pathological mutations often impact not only on muscle structure and function but also on developmental processes. Mice are currently the main animal model used to study neuromuscular disorders including the early-onset myopathies. However strategies based on simple animal models and on transdisciplinary approaches exploring mechanical muscle cell properties emerge as attractive, non-exclusive alternatives. These new ways provide valuable opportunities to improve our knowledge on how mechanical, biochemical, and genetic/epigenetic cues modulate the formation, organization and function of muscle tissues. Here we provide an overview of how single cell and micro-tissue engineering in parallel to non-mammalian, Drosophila and zebrafish models could contribute to filling gaps in our understanding of pathogenic mechanisms underlying early-onset myopathies. We also discuss their potential impact on designing new diagnostic and therapeutic strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Resource utilization associated with initial hospital stays complicated by early onset group B streptococcal disease.

    Science.gov (United States)

    Platt, R; Adelson-Mitty, J; Weissman, L; Zaleznik, D; Lee, M L; Baker, C J

    1999-06-01

    The epidemiology of early onset neonatal group B streptococcal (GBS) disease has changed appreciably, but there are no recent assessments of the in-hospital resource utilization it incurs. We performed a retrospective cohort study of infants delivered from 1987 through 1995 at Massachusetts' largest obstetrics hospital. A matched cohort design was used to assess care occurring after transfer to another acute care hospital. There were 135 cases of early onset neonatal GBS infection complicating 85,062 deliveries (1.6/1,000 births) in 9 years, with a substantial decline beginning in 1994, when maternal intrapartum chemoprophylaxis was widely introduced. Most (73%) infants had birth weights of 2500 g or more; 93% survived. Overall both the median and mean lengths of stay were 8 days longer for infants with GBS disease than for those without this infection (P 2500-g birth weight infants; no excess was evident for infants with birth weights of < 1500 g. There was a substantial excess length of stay and charges associated with early onset neonatal GBS disease, although this was less than previously reported.

  19. A comparative analysis of 4 curvature measurement methods in early-onset scoliosis.

    Science.gov (United States)

    Hwang, Jin-Ho; Hong, Jae-Young; Suh, Seung-Woo; Yang, Jae-Hyuk; Lee, Jae-Moon

    2012-09-15

    Observational study with 3 examiners. The aim of this study was to enhance the reproducibility and reliability of coronal curvature measurements in early-onset scoliosis. Previous reports show high variability of the Cobb method, especially on the measurement of the immature spine. A total of 115 whole-spine posteroanterior radiographs were collected to compare the reliability of the Cobb, lateral tangent, pedicle, and centroid methods in early-onset scoliosis. Radiographs were measured twice by each of the 3 examiners using the 4 measurement methods. Statistical analysis was performed to determine the inter- and intraobserver reliability. In this study, total inter- and intraobserver inter- and intraclass correlation coefficients (ICCs) in 115 radiographs were excellent in all methods (ICCs >0.961). However, mean absolute differences (MADs) in the lateral tangent method were less than 3.78°, which was higher than other methods (MADs 30°), total inter- and intraobserver ICCs gradually increased with increasing the severity of the deformity, whereas MADs of each severity group were similar despite their increased measurement scale. Particularly, interobserver ICCs and MADs of lateral tangent method were more than 0.474 and less than 3.76° with poor reliability, which showed high variability in the less deformed spine group (scoliosis regardless of severity. However, the other 3 methods showed lower ICCs and higher MAD values, which showed lowest reliability in the lateral tangent method. For improved treatment of early-onset scoliosis, we recommend the pedicle method for measuring curvature regardless of severity.

  20. Regional cerebral blood flow changes in early-onset anorexia nervosa before and after weight gain.

    Science.gov (United States)

    Komatsu, Hiroko; Nagamitsu, Shinichiro; Ozono, Shuichi; Yamashita, Yushiro; Ishibashi, Masatoshi; Matsuishi, Toyojiro

    2010-09-01

    To investigate the changes of regional cerebral blood flow (rCBF) in early-onset anorexia nervosa (AN) before and after weight gain, we examined resting rCBF using single photon emission computed tomography (SPECT) with [(123)I]iodoamphetamine ((123)I-IMP). Ten female children with AN (mean age 13.2 years old) participated in this study. SPECT examinations were performed in all patients twice at the beginning of treatment and after weight gain. The mean body mass index (BMI) was changed from 13.1 to 16.6 during 4 months treatment period. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Relatively increased rCBF in the bilateral parietal lobe and limbic lobe including the posterior cingulate cortex (PCC) were observed after weight gain in early-onset AN. There was no significant decrease in the rCBF after weight gain. A significant positive correlation was observed between BMI and rCBF in the right thalamus, right parietal lobe, and right cerebellum. These results suggested that weight gain during the process of recovery from early-onset AN might activate specific brain regions which are possibly relevant to the pathophysiological aspects of the disorder. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Pattern of birth in early-onset anorexia nervosa: an equatorial study.

    Science.gov (United States)

    Willoughby, Kate; Bowen, Rebecca; Lee, Ee-Lian; Pathy, Parvathy; Lask, Bryan

    2005-01-01

    Patients with anorexia nervosa (AN) born in the northern and southern hemispheres are more likely to be born during spring months than at any other time of the year. It has been hypothesized that environmental temperature at the time of conception may have a significant role in this pattern of findings. The current study aims to investigate the pattern of birth of early-onset AN patients in an equatorial region (Singapore), where there is little difference in environmental temperature throughout the year. Dates of birth were collected for 102 patients who were born in Singapore and diagnosed with early-onset AN. The patterns of birth were analyzed using chi-square analysis. There was no difference across the year in the birth patterns of patients with early-onset AN in Singapore, nor were there any differences between patients with restrictive and binge/purge AN. This lack of seasonal variation in the equator adds support to the "temperature at conception" hypothesis. 2004 by Wiley Periodicals, Inc.

  2. Metabolomics and first-trimester prediction of early-onset preeclampsia.

    Science.gov (United States)

    Bahado-Singh, Ray O; Akolekar, Ranjit; Mandal, Rupasri; Dong, Edison; Xia, Jianguo; Kruger, Michael; Wishart, David S; Nicolaides, Kypros

    2012-10-01

    To evaluate the use of metabolomics for the first-trimester detection of maternal metabolic dysfunction and prediction of subsequent development of early-onset preeclampsia (PE). This was a case-control study of maternal plasma samples collected at 11-13 weeks' gestation from 30 women who had subsequently developed PE requiring delivery before 34 weeks and 60 unaffected controls. Nuclear magnetic Resonance (NMR) spectroscopy was used to identify and quantify metabolomic changes in cases versus controls. Both genetic computing and standard statistical analyses were performed to predict the development of PE from the metabolite concentrations alone as well as the combination of metabolite concentrations with maternal characteristics and first-trimester uterine artery Doppler pulsatility index (PI). Significant differences between cases and controls were found for 20 metabolites. A combination of four of these metabolites (citrate, glycerol, hydroxyisovalerate, and methionine) appeared highly predictive of PE with an estimated detection rate of 75.9%, at a false-positive rate (FPR) of 4.9%. The predictive performance was improved by the addition of uterine artery Doppler PI and fetal crown-rump length (CRL) and with an estimated detection rate of 82.6%, at a FPR of 1.6%. A profound change in the first-trimester metabolite profile was noted in women who had subsequently developed early-onset PE. Preliminary algorithms appeared highly sensitive for first trimester prediction of early onset PE.

  3. Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer's Disease?

    Science.gov (United States)

    Harding, Alice; Robinson, Sarita; Crean, StJohn; Singhrao, Sim K

    2017-01-01

    A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P. gingivalis, to gain greater virulence. The initial process involves P. gingivalis disturbing neutrophil mediated innate immune responses in the healthy gingivae and then downregulating adaptive immune cell differentiation and development to invade, and subsequently, establish new dysbiotic bacterial communities. Immune responses affect the host in general and functionally via dietary adjustments caused by tooth loss. Studies from animals orally infected with P. gingivalis confirm this bacterium can transmigrate to distant organ sites (the brain) and contribute toward peripheral and intracerebral inflammation, and compromise vascular and microvascular integrity. In another study, P. gingivalis infection caused sleep pattern disturbances by altering glial cell light/dark molecular clock activity, and this, in turn, can affect the clearance of danger associated molecular patterns, such as amyloid-β, via the glymphatic system. Since P. gingivalis can transmigrate to the brain and modulate organ-specific inflammatory innate and adaptive immune responses, this paper explores whether better management of indigenous periodontal bacteria could delay/prevent the onset and/or progression of dementia.

  4. Transthyretin familial amyloid polyneuropathy (TTR-FAP) in Mallorca: a comparison between late- and early-onset disease.

    Science.gov (United States)

    Buades-Reinés, Juan; Raya-Cruz, Manuel; Gallego-Lezaún, Cristina; Ripoll-Vera, Tomás; Usón-Martín, Mercedes; Andreu-Serra, Hernán; Cisneros-Barroso, Eugenia

    2016-12-01

    The age of onset (AO) of hereditary ATTR amyloidosis (hATTR) is known to vary between populations, with differing characteristics reported according to AO in endemic/non-endemic foci. This was a retrospective study of patients with early AO (Mallorca. Data were collected on patient demographics, clinical disease manifestation, and physical symptoms. A total of 95 patients were analyzed, with mean follow-up of 9 years from diagnosis. The early AO group included 53 patients (33 male) and the late AO group included 42 patients (21 male). Neurologic involvement was the most common initial symptom, although it was significantly more frequent in the late AO vs. early AO group (p = 0.015). Autonomic involvement was observed in 26% of patients in the early AO group, but was rarely observed in the late AO group (5%). During follow up, cardiologic symptoms, renal involvement, and ophthalmologic symptoms were significantly more common in the late AO group (p < 0.05). This retrospective study demonstrates the variation in disease presentation and progression according to AO of hATTR at our Mallorcan center. © 2016 Peripheral Nerve Society.

  5. Predicting early onset of intoxication versus drinking—A population-based prospective study of Norwegian adolescents

    OpenAIRE

    Enstad, Frøydis; Pedersen, Willy; Nilsen, Wendy; von Soest, Tilmann

    2017-01-01

    Aims Recent research suggests that early onset of intoxication (EOI) may be of greater importance for a wide range of subsequent adverse outcomes than early drinking experiences without intoxication. However, research on antecedents of EOI is scarce. The present study identifies predictors of EOI and whether they differ from those of early onset of drinking (EOD). Methods Data was drawn from the prospective Tracking Opportunities and Problems (TOPP) study of Norwegian families (n = 382), whic...

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

    Science.gov (United States)

    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.

  7. Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Svati H Shah

    2009-01-01

    Full Text Available Neuropeptide Y (NPY is a strong candidate gene for coronary artery disease (CAD. We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families, we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004 in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72, family-based association of this block with CAD (p = 0.02, and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05, showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09; and (b GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02. A promoter SNP (rs16147 within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04. To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03. Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

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

    Directory of Open Access Journals (Sweden)

    Taha Ghada RA

    2011-07-01

    Full Text Available Abstract 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.

  9. The progressive creation of the early mother-child bonding

    OpenAIRE

    Traverso Koroleff, Pierina

    2012-01-01

    One of the research areas in mother-child health has focused on examining which are the signs inmothers' psychological functioning that would lead to a further disturbed development in an infant.The perspective of this paper has deviated from this research area. Natural observation of an infantduring his/her first year of life suggests that early mother-child affective bonding grows and strengthens progressively, even mother's behavior is not totally adequate. This article al so suggests that...

  10. Effect of early-onset preeclampsia on cardiovascular risk in the fifth decade of life.

    Science.gov (United States)

    Bokslag, Anouk; Teunissen, Pim W; Franssen, Constantijn; van Kesteren, Floortje; Kamp, Otto; Ganzevoort, Wessel; Paulus, Walter J; de Groot, Christianne J M

    2017-05-01

    Women with hypertensive disorders in pregnancy, in particular early-onset preeclampsia, are at increased risk of developing cardiovascular disease later in life. These women have a more than 2-fold increased risk of dying from cardiovascular diseases. Most studies have focused on identification of risk factors shortly after pregnancy. Less is known on the prevalence of risk factors or actual signs of cardiovascular disease 5-20 years later. The presence of hypertension or metabolic syndrome can be seen as an opportunity for preventive interventions to reduce the development of severe cardiovascular diseases like myocardial infarction and stroke. To assess cardiovascular risk factors and established cardiovascular disease in women after early-onset preeclampsia, in the fifth decade of life. As a consequence, we can assess whether there is still a window of opportunity for preventive measures and to establish in what proportion of women cardiovascular disease already has developed. In a prospective observational study, cardiovascular risk assessment was performed in women with early-onset preeclampsia (preeclampsia (n = 131) had significantly greater systolic and diastolic blood pressure, greater body mass index, more often had an abnormal lipid profile (lower high-density lipoprotein levels, higher triglycerides), greater glycated hemoglobin, and greater levels of albuminuria compared to controls (n = 56). None of the women with a history of early-onset preeclampsia was diagnosed with cardiovascular disease; 38.2% were diagnosed with hypertension; and 18.2% were diagnosed with metabolic syndrome. A total of 42% met the criteria for the window of opportunity for preventive measures. In women with a history of an uncomplicated pregnancy, no women were diagnosed with cardiovascular disease; 14.3% were diagnosed with hypertension; 1.8% with metabolic syndrome. In this cohort, 14.3% met the criteria for the window of opportunity for preventive measures. A large

  11. Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS.

    Directory of Open Access Journals (Sweden)

    Karen Ann Ribbons

    Full Text Available Multiple Sclerosis is more common in women than men and females have more relapses than men. In a large international cohort we have evaluated the effect of gender on disability accumulation and disease progression to determine if male MS patients have a worse clinical outcome than females.Using the MSBase Registry, data from 15,826 MS patients from 25 countries was analysed. Changes in the severity of MS (EDSS were compared between sexes using a repeated measures analysis in generalised linear mixed models. Kaplan-Meier analysis was used to test for sex difference in the time to reach EDSS milestones 3 and 6 and the secondary progressive MS.In relapse onset MS patients (n = 14,453, males progressed significantly faster in their EDSS than females (0.133 vs 0.112 per year, P<0.001,. Females had a reduced risk of secondary progressive MS (HR (95% CI = 0.77 (0.67 to 0.90 P = 0.001. In primary progressive MS (n = 1,373, there was a significant increase in EDSS over time in males and females (P<0.001 but there was no significant sex effect on the annualized rate of EDSS change.Among registrants of MSBase, male relapse-onset patients accumulate disability faster than female patients. In contrast, the rate of disability accumulation between male and female patients with primary progressive MS is similar.

  12. The role of oxidative stress in early-onset androgenetic alopecia.

    Science.gov (United States)

    Kaya Erdogan, Hilal; Bulur, Isıl; Kocaturk, Evin; Yildiz, Bahadir; Saracoglu, Zeynep Nurhan; Alatas, Ozkan

    2017-12-01

    Androgenetic alopecia (AGA) is the most common cause of alopecia in men. In the literature, although there are in vitro studies investigating the relationship between oxidative stress and AGA, any in vivo study does not exist. Our aim was to evaluate the oxidative stress status in male patients with early-onset AGA by measuring total oxidant levels (TOS), total antioxidant levels (TAS), and oxidative stress index (OSI). Our study included 33 male patients with early-onset AGA and 30 healthy men between ages of 18 and 30 years old. TAS and TOS measurements were taken, and OSI was calculated. When TAS, TOS, and OSI levels were compared between patient and control groups, there was no difference for TAS level, while TOS and OSI were significantly higher in patient group. In patient group, correlation between TAS, TOS, and OSI levels and age, and disease onset age and disease duration was evaluated. Highly significant negative correlation was determined between TAS level and both age and disease duration. When TAS, TOS, and OSI levels were assessed according to AGA stage, there was no significant difference between groups, while OSI level was significantly higher in patients with family history. We found increased oxidative stress in younger patients with early-onset AGA. There is need for further molecular studies on the role of oxidative stress in the etiopathogenesis of AGA. We also think that topical or systemic antioxidants can be promising in treatment of AGA, especially for young patients. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Richarda M de Voer

    2016-02-01

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

  14. POEMS syndrome with Guillan-Barre syndrome-like acute onset: a case report and review of neurological progression in 30 cases.

    Science.gov (United States)

    Isose, S; Misawa, S; Kanai, K; Shibuya, K; Sekiguchi, Y; Nasu, S; Fujimaki, Y; Noto, Y; Nakaseko, C; Kuwabara, S

    2011-06-01

    POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

  15. Problem drinking among Flemish students: beverage type, early drinking onset and negative personal & social consequences.

    Science.gov (United States)

    De Bruyn, Sara; Wouters, Edwin; Ponnet, Koen; Van Damme, Joris; Maes, Lea; Van Hal, Guido

    2018-02-12

    Although alcohol is socially accepted in most Western societies, studies are clear about its associated negative consequences, especially among university and college students. Studies on the relationship between alcohol-related consequences and both beverage type and drinking onset, however, are scarce, especially in a European context. The aim of this research was, therefore, twofold: (1) What is the relationship between beverage type and the negative consequences experienced by students? and (2) Are these consequences determined by early drinking onset? We will examine these questions within the context of a wide range of alcohol-related consequences. The analyses are based on data collected by the inter-university project 'Head in the clouds?', measuring alcohol use among students in Flanders (Belgium). In total, a large dataset consisting of information from 19,253 anonymously participating students was available. Negative consequences were measured using a shortened version of the Core Alcohol and Drug Survey (CADS_D). Data were analysed using negative binomial regression. Results vary depending on the type of alcohol-related consequences: Personal negative consequences occur frequently among daily beer drinkers. However, a high rate of social negative consequences was recorded for both daily beer drinkers and daily spirits drinkers. Finally, early drinking onset was significantly associated with both personal and social negative consequences, and this association was especially strong between beer and spirits drinking onset and social negative consequences. Numerous negative consequences, both personal and social, are related to frequent beer and spirits drinking. Our findings indicate a close association between drinking beer and personal negative consequences as well as between drinking beer and/or spirits and social negative consequences. Similarly, early drinking onset has a major influence on the rates of both personal and social negative consequences

  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

    NARCIS (Netherlands)

    de Graaf, R.; Radovanovic, M.; van Laar, M.; Fairman, B.; Degenhardt, L.; Aguilar-Gaxiola, S.; Bruffaerts, R.; De Girolamo, G.; Fayyad, J.; Gureje, O.; Haro, J.M.; Huang, Y.Q.; Kostychenko, S.; Lepine, J.P.; Matschinger, H.; Mora, M.E.M.; Neumark, Y.; Ormel, J.; Posada-Villa, J.; Stein, D.J.; Tachimori, H.; Wells, J.E.; Anthony, J.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)

  17. Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome.

    Science.gov (United States)

    Pan, Dao; Sciascia, Anthony; Vorhees, Charles V; Williams, Michael T

    2008-01-10

    Mucopolysaccharidosis type I (MPS I) is one of the most common lysosomal storage diseases with progressive neurological dysfunction. To characterize the chronological behavioral profiles and identify the onset of functional deficits in a MPS I mouse model (IDUA(-/-)), we evaluated anxiety, locomotor behavior, startle, spatial learning and memory with mice at 2, 4, 6 and 8 months of age. In automated open-field test, IDUA(-/-) mice showed hypoactivity as early as 2 months of age and altered anxiety starting from 6 months of age during the initial exploratory phase, even though normal habituation was observed at all ages. In the marble-burying task, the anxiety-like compulsive behavior was normal in IDUA(-/-) mice at almost all tested ages, but significantly reduced in 8-month old male IDUA(-/-) mice which coincided with the rapid death of IDUA(-/-) males starting from 7 months of age. In the Morris water maze, IDUA(-/-) mice exhibited impaired proficient learning only at 4 months of age during the acquisition phase. Spatial memory deficits were observed in IDUA(-/-) mice during both 1 and 7 days probe trials at 4 and 8 months of age. The IDUA(-/-) mice performed normally in a novel object recognition task at younger ages until 8 months old when reduced visual cognitive memory retention was noted in the IDUA(-/-) mice. In addition, 8-month-old IDUA(-/-) mice failed to habituate to repeated open-field exposure, suggesting deficits in non-aversive and non-associative memory. In acoustic startle assessment, significantly more non-responders were found in IDUA(-/-) mice, but normal performance was seen in those that did show a response. These results presented a temporal evaluation of phenotypic behavioral dysfunctions in IDUA(-/-) mice from adolescence to maturity, indicating the impairments, with different ages of onset, in locomotor and anxiety-like compulsive behaviors, spatial learning and memory, visual recognition and short-term non-associative memory retention

  18. Concordance of bioactive vs. total immunoreactive serum leptin levels in children with severe early onset obesity.

    Science.gov (United States)

    Stanik, Juraj; Kratzsch, Jürgen; Landgraf, Kathrin; Scheuermann, Kathrin; Spielau, Ulrike; Gausche, Ruth; Gasperikova, Daniela; Kiess, Wieland; Körner, Antje

    2017-01-01

    Leptin secreted from adipose tissue signals peripheral energy status to the brain. Monogenic leptin deficiency results in severe early onset obesity with hyperphagia. Recently, a similar phenotype of inactivating leptin mutations but with preserved immunoreactivity and hence normal circulating immunoreactive leptin has been reported. We aimed to evaluate the proportion of bioactive leptin serum levels (compared to immunoreactive leptin) as a biomarker for the screening of leptin gene mutations causing monogenic obesity. Furthermore, we aimed to compare the immunoreactive and bioactive leptin levels associations with parameters of insulin resistance and insulin secretion in obese children and adolescents. We measured bioactive and immunoreactive leptin levels by enzyme-linked immunosorbent assays in fasting serum samples of 70 children with severe (BMI SDS >3) non-syndromic obesity with onset childhood obesity cohort (n = 1204). Sanger sequencing of the leptin gene was performed in probands with proportion of bioactive/immunoreactive leptin severe early onset childhood obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin. Nevertheless, the bioactive leptin levels were stronger associated with selected insulin secretion/resistance indices than the immunoreactive leptin levels.

  19. Early-onset Alzheimer’s Disease: Nonamnestic Subtypes and Type 2 AD

    Science.gov (United States)

    Mendez, Mario F.

    2012-01-01

    Patients with Alzheimer’s disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ~4–5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer’s research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22–64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein E ε4 (APOE ε4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. PMID:23178565

  20. Frequency of LRRK2 mutations in early- and late-onset Parkinson disease.

    Science.gov (United States)

    Clark, L N; Wang, Y; Karlins, E; Saito, L; Mejia-Santana, H; Harris, J; Louis, E D; Cote, L J; Andrews, H; Fahn, S; Waters, C; Ford, B; Frucht, S; Ottman, R; Marder, K

    2006-11-28

    To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD). We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the 50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p risk factor in both early- and late-onset Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.

  1. Identifying anomalously early spring onsets in the CESM large ensemble project

    Science.gov (United States)

    Labe, Zachary; Ault, Toby; Zurita-Milla, Raul

    2017-06-01

    Seasonal transitions from winter to spring impact a wide variety of ecological and physical systems. While the effects of early springs across North America are widely documented, changes in their frequency and likelihood under the combined influences of climate change and natural variability are poorly understood. Extremely early springs, such as March 2012, can lead to severe economical losses and agricultural damage when these are followed by hard freeze events. Here we use the new Community Earth System Model Large Ensemble project and Extended Spring Indices to simulate historical and future spring onsets across the United States and in the particular the Great Lakes region. We found a marked increase in the frequency of March 2012-like springs by midcentury in addition to an overall trend towards earlier spring onsets, which nearly doubles that of observational records. However, changes in the date of last freeze do not occur at the same rate, therefore, causing a potential increase in the threat of plant tissue damage. Although large-scale climate modes, such as the Pacific Decadal Oscillation, have previously dominated decadal to multidecadal spring onset trends, our results indicate a decreased role in natural climate variability and hence a greater forced response by the end of the century for modulating trends. Without a major reduction in greenhouse gas emissions, our study suggests that years like 2012 in the US could become normal by mid-century.

  2. Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: a cohort study.

    Science.gov (United States)

    Downs, Jenny; Torode, Ian; Wong, Kingsley; Ellaway, Carolyn; Elliott, Elizabeth J; Izatt, Maree T; Askin, Geoffrey N; Mcphee, Bruce I; Cundy, Peter; Leonard, Helen

    2016-06-01

    Scoliosis is a common comorbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood. After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12-0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06-0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16-1.03; p=0.06). With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome. © 2015 Mac Keith Press.

  3. Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

    Science.gov (United States)

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

    2013-06-01

    The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

  4. Late-onset myoclonic epilepsy in Down syndrome (LOMEDS: A spectrum of progressive myoclonic epilepsy — Case report

    Directory of Open Access Journals (Sweden)

    Chandra Mohan Sharma

    2016-01-01

    Full Text Available Cognitive decline and epilepsy are well recognized complication of Down syndrome (DS. Here, we intend to present a case of 28 year old male who presented with progressive mental regression, gait ataxia and myoclonic jerking especially on awakening in morning. His EEG was normal and karyotyping revealed trisomy of chromosome 21. Very few cases had been described in literature of late-onset myoclonic epilepsy in DS. This is first case report from India and our aim is to propose the inclusion of this entity in the spectrum of progressive myoclonic epilepsies but still more cases are yet to be found.

  5. Late-onset progressive visual loss in a man with unusual MRI findings: MS, Harding's, Leber's or Leber's Plus?

    LENUS (Irish Health Repository)

    Cawley, N

    2012-02-01

    Leber\\'s hereditary optic neuropathy (LHON) is a maternally inherited disorder, typically presenting in the second and third decade. We report the case of an elderly gentleman with significant vascular risk factors, presenting with slowly progressive, bilateral, visual loss with high signal lesions in the pericallosal and periventricular deep white matter on MRI brain studies. Possible diagnoses included late-onset MS, ischaemic optic neuropathies, a mitochondrial disorder or an overlap syndrome such as Harding\\'s disease.

  6. Recognising early onset neonatal sepsis: an essential step in appropriate antimicrobial use.

    Science.gov (United States)

    van Herk, Wendy; Stocker, Martin; van Rossum, Annemarie M C

    2016-07-05

    Early diagnosis and timely treatment of early onset neonatal sepsis (EOS) are essential to prevent life threatening complications. Subtle, nonspecific clinical presentation and low predictive values of biomarkers complicate early diagnosis. This uncertainty commonly results in unnecessary and prolonged empiric antibiotic treatment. Annually, approximately 395,000 neonates (7.9% of live term births) are treated for suspected EOS in the European Union, while the incidence of proven EOS varies between 0.01 and 0.53 per 1000 live births. Adherence to guidelines for the management of suspicion of EOS is poor. Pragmatic approaches to minimise overtreatment in neonates with suspected EOS, using combined stratified risk algorithms, based on maternal and perinatal risk factors, clinical characteristics of the neonate and sequential biomarkers are promising. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  7. Course of intelligence deficits in early onset, first episode schizophrenia: a controlled, 5-year longitudinal study

    DEFF Research Database (Denmark)

    Jepsen, Jens Richardt Møllegaard; Fagerlund, Birgitte; Pagsberg, Anne Katrine

    2010-01-01

    predominantly been characterized as relatively stable in these studies. However, comparisons of IQs from different test versions based on the different norms may not permit unequivocal interpretations. The objective of the current study was to compare the development of intelligence in EOS patients (N = 10......Only few prospective longitudinal studies have assessed the course of intelligence deficits in early onset schizophrenia (EOS), and these have used different age appropriate versions of Wechsler Intelligence Scales and age appropriate norms. The post-psychotic development of intelligence in EOS has......) from their first psychotic episode to 5 years of post onset with that of healthy controls (N = 35) and patients who at baseline had been diagnosed with other non-affective psychoses (N = 8). The same version of a Wechsler Intelligence Scale was administered at both baseline and follow-up assessments...

  8. Differences in anxiety among patients with early- versus late-onset Alzheimer's disease.

    Science.gov (United States)

    Kaiser, Natalie C; Liang, Li-Jung; Melrose, Rebecca J; Wilkins, Stacy S; Sultzer, David L; Mendez, Mario F

    2014-01-01

    The authors sought to evaluate the incidence and correlates of anxiety in early-onset Alzheimer's disease (EOAD) versus the more typical late-onset AD (LOAD). A group of 23 EOAD and 22 LOAD patients were compared by the Neuropsychiatric Inventory Anxiety subscale. Demographic and disease-related relationships with anxiety were evaluated, as well as types of anxiety symptoms that were endorsed. EOAD patients had significantly more anxiety symptoms than LOAD patients. Among those with EOAD, anxiety was associated with male gender, higher Mini-Mental State Exam score, and separation from caregivers. Among LOAD patients, anxiety was associated with psychotic and activating psychiatric symptoms. These results have implications for the management and alleviation of anxiety in AD.

  9. [Emergency Bypass Surgery for Progressive Cerebral Infarction Following Hemorrhagic Onset of Moyamoya Disease:A Case Report].

    Science.gov (United States)

    Hatakeyama, Junya; Yanagisawa, Toshiharu; Kudo, Erina; Togashi, Shuntaro; Shimizu, Hiroaki

    2016-10-01

    Progressive cerebral infarction in patients with hemorrhagic onset of moyamoya disease is rare, and a treatment strategy is not well established. Here, we report a case that was successfully treated with emergency bypass surgery. A 58-year-old woman presented with a sudden disturbance of consciousness and right-sided hemiparesis. Computed tomography(CT)showed intraventricular hemorrhage involving the head of the left caudate nucleus. Ventricular drainage was immediately performed, and the patient was treated conservatively. Magnetic resonance(MR)angiography revealed bilateral stenosis of the supraclinoid internal carotid artery(ICA), and arterial spin labeling(ASL)showed low signal intensity in the left cerebral hemisphere. The patient was diagnosed with hemorrhagic onset of moyamoya disease with cerebral infarction. Her neurological symptoms worsened on the 7th day after ictus despite medical treatment. MR imaging showed a new infarction in the left insular cortex. Based on the diagnosis of progressive stroke, emergency anastomoses between the superficial temporal artery and the middle and anterior cerebral arteries, along with encephalo-duro-myo-synangiosis, were performed. Her symptoms gradually improved following surgery, and 1 month later, she was able to regain independent function. Emergency bypass surgery may be the treatment of choice for patients with hemorrhagic onset of moyamoya disease presenting with progressive cerebral infarction, despite conservative treatments.

  10. Impulsivity in abstinent early- and late-onset alcoholics : differences in self-report measures and a discounting task

    NARCIS (Netherlands)

    Dom, G.; D'Haene, P.; Hulstijn, W.; Sabbe, B.G.C.

    2006-01-01

    Aims: To test the hypothesis that early-onset alcoholics (EOAs) can be differentiated from late-onset alcoholics (LOAs) by more severe substance-related problems and higher levels of impulsivity and aggression. Design and measurements: A cross-sectional patient survey with a community comparison

  11. Caregivers' perspectives on the pre-diagnostic period in early onset dementia: a long and winding road

    NARCIS (Netherlands)

    van Vliet, D.; de Vugt, M.E.; Bakker, C.; Koopmans, R.T.C.M.; Pijnenburg, Y.A.L.; Vernooij-Dassen, M.; Verhey, F.R.J.

    2011-01-01

    Background: Recognizing and diagnosing early onset dementia (EOD) can be complex and often takes longer than for late onset dementia. The objectives of this study are to investigate the barriers to diagnosis and to develop a typology of the diagnosis pathway for EOD caregivers. Methods:

  12. Early-onset alopecia and amyotrophic lateral sclerosis: a cohort study.

    Science.gov (United States)

    Fondell, Elinor; Fitzgerald, Kathryn C; Falcone, Guido J; O'Reilly, Eilis J; Ascherio, Alberto

    2013-10-01

    A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 46-81 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (1992-2008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk = 2.74, 95% confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (Ptrend = 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation.

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

    Science.gov (United States)

    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

  14. Thought and language disorders in very early onset schizophrenia, schizoaffective disorder and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Telma Pantano

    Full Text Available Abstract Background Thought and language disorders are main features of adults with schizophrenia and bipolar disorders however studies on such abnormalities are scant in young patients with very early onset psychosis (VEOS. The aim of the present study is to assess the relationship between language and thought disorders in patients with very early onset schizophrenia (SCZ, schizoaffective disorders (SCA and bipolar disorders (BD. Method Forty-one patients (18 SCZ, 16 BD, and 7 SCA with mean age less than 15 years old were assessed through a series of neurocognitive and psycholinguistic tests, including the Thought, Language and Communication Scale (TLC. Results SCZ group performed worse in all tests as well as the TLC, followed by SCA and BD groups respectively. Thought disorders were related to deficits in executive functioning and semantic processing, and the metaphors’ test was the best predictor of TLC functioning. Discussion TD in SCZ, SCA and BD are one of the most important features in patients with VEOS and that the evaluation of metaphor comprehension can be an important instrument in the early detection of this disorder.

  15. Early-Onset Alopecia and Amyotrophic Lateral Sclerosis: A Cohort Study

    Science.gov (United States)

    Fondell, Elinor; Fitzgerald, Kathryn C.; Falcone, Guido J.; O'Reilly, Éilis J.; Ascherio, Alberto

    2013-01-01

    A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 46–81 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (1992–2008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk = 2.74, 95% confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (Ptrend = 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation. PMID:23942216

  16. Early-onset severe obesity due to complete deletion of the leptin gene in a boy.

    Science.gov (United States)

    Ozsu, Elif; Ceylaner, Serdar; Onay, Huseyin

    2017-10-26

    Monogenic obesity results from single gene mutations. Extreme obesity starting at an early age, especially in infancy, which is associated with endocrinopathy and metabolic disturbances is key to the diagnosis of monogenic obesity. A 6-month-old boy was admitted to our clinic with severe obesity and food craving. He was born with a birth weight of 3400 g to first-cousin parents. He started to gain weight at an abnormal rate at the age of 2 months. He had hyperinsulinemia, dyslipidemia and grade 2 hepatosteatosis. He had a 7-year-old, healthy brother with a normal body weight. Because of severe early-onset obesity and abnormal food addiction, his leptin level was measured and found to be 0.55 ng/mL (normal range for his age and sex is 0.7-21 ng/mL). A LEP gene mutation was screened for and a gross leptin gene deletion was detected. To date, no report on a gross deletion of the LEP gene has been published in the literature. To the best of our knowledge, a gross deletion of the LEP gene has not been reported so far in the literature. Here we report a unique case with congenital leptin deficiency. Thus, clinicians should search for monogenic obesity in patients with early-onset severe obesity and endocrinopathy. Measuring the leptin level could aid clinicians to identify children with monogenic obesity.

  17. Pattern of birth in anorexia nervosa. I: Early-onset cases in the United Kingdom.

    Science.gov (United States)

    Watkins, Beth; Willoughby, Kate; Waller, Glenn; Serpell, Lucy; Lask, Bryan

    2002-07-01

    Previous studies suggest that adults with anorexia nervosa are more likely to be born in spring and early summer. This study examines whether this pattern of birth is true of early-onset anorexia nervosa, and whether there is a relationship between environmental temperature at assumed time of conception and a later diagnosis of anorexia nervosa. The population were children and adolescents with diagnoses of anorexia nervosa (N = 259) or "other eating disorders" (N = 149). Distribution of births across the year was compared between groups and relative to standard population norms. Temperature at assumed time of conception was taken from meteorological records. There was a significant preponderance of births among those with anorexia nervosa between April and June, compared with the other months of the year and with the "other eating disorders" group. Anorexia nervosa was also associated with higher environmental temperature at assumed time of conception. Among early-onset cases in the United Kingdom, patients with anorexia nervosa are more likely to be born between April and June, and to be conceived during warmer months. A tentative "temperature at conception" hypothesis is advanced to explain these findings and to generate further research.

  18. Successful scene encoding in presymptomatic early-onset Alzheimer’s disease

    Science.gov (United States)

    Quiroz, Yakeel T.; Willment, Kim Celone; Castrillon, Gabriel; Muniz, Martha; Lopera, Francisco; Budson, Andrew; Stern, Chantal E.

    2016-01-01

    Background Brain regions critical to episodic memory are altered during the preclinical stages of Alzheimer’s disease (AD). However, reliable means of identifying cognitively-normal individuals at higher risk to develop AD have not been established. Objective To examine whether fMRI can detect early functional changes associated with scene encoding in a group of presymptomatic Presenilin-1 (PSEN1) E280A mutation carriers. Methods Participants were 39 young, cognitively-normal individuals from an autosomal dominant early-onset AD kindred, located in Antioquia, Colombia. Participants performed an fMRI scene encoding task and a post-scan subsequent memory test. Results PSEN1 mutation carriers exhibited hyperactivation within medial temporal lobe regions during successful scene encoding (hippocampal formation, parahippocampal gyrus) compared to age-matched non-carriers. Conclusion Hyperactivation in medial temporal lobe regions during scene encoding is seen in individuals genetically-determined to develop AD years before their clinical onset. Our findings will guide future research with the ultimate goal of using functional neuroimaging in the early detection of preclinical AD. PMID:26401774

  19. Committee Opinion Summary No. 638: First-Trimester Risk Assessment for Early-Onset Preeclampsia.

    Science.gov (United States)

    2015-09-01

    Hypertensive disorders with adverse sequelae (including preterm birth, maternal morbidity and mortality, and long-term risk of maternal cardiovascular disease) complicate 5-10% of pregnancies. Early identification of pregnant women at risk of developing early-onset preeclampsia would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease. In practice, however, the effectiveness of such triage would be hindered by the low positive predictive value for early-onset preeclampsia reported in the literature. In spite of the modest predictive value of first-trimester preeclampsia risk assessment and the lack of data demonstrating improved clinical outcomes, commercial tests are being marketed for the prediction of preeclampsia in the first trimester. Taking a detailed medical history to evaluate for risk factors is currently the best and only recommended screening approach for preeclampsia; it should remain the method of screening for preeclampsia until studies show that aspirin or other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests.

  20. The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

    Science.gov (United States)

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

    2014-11-01

    Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. © The Author(s) 2014.

  1. Frequency of the apolipoprotein E epsilon 4 allele in a case-control study of early onset Parkinson's disease.

    Science.gov (United States)

    Whitehead, A S; Bertrandy, S; Finnan, F; Butler, A; Smith, G D; Ben-Shlomo, Y

    1996-10-01

    It has been suggested that Parkinson's disease and Alzheimer's disease may share a common or at least overlapping aetiology. The prevalence of dementia among cases of Parkinson's disease is known to be greater than expected in the general population. The frequency of the apolipoprotein epsilon 4 allele in a large case-control study of early onset Parkinson's disease has been examined. 215 patients and 212 population based controls were recruited from the Republic of Ireland between 1992 and 1994. Cases had to have disease onset at 55 years or younger and be born after 1925. The frequency of the epsilon 4 allele was almost identical between cases of Parkinson's disease (14.6%) and healthy controls (13.3%). There was no relation between epsilon 4 status and disease onset, disease duration, Hoehn and Yahr score, and disease progression. The frequency of the epsilon 4 allele was not increased among 10 patients with Parkinson's disease with dementia (10.0%) compared with the other patients without dementia (14.8%). There was no association between epsilon 4 allele status and either a history of smoking, family history of dementia, or Parkinson's disease, or being born in a rural area. The odds ratio for the ApoE epsilon 4 allele associated with Parkinson's disease was 1.10 (95% confidence interval (95% CI) 0.68-1.79), adjusting for age group, sex, and residential status. The pooled odds ratio from a meta-analysis of six studies of ApoE epsilon 4 status and Parkinson's disease was 0.94 (95% CI 0.69-1.27). The results from our study as well as the pooled meta-analysis exclude any important role for ApoE epsilon 4 status in the development of Parkinson's disease. Our results similarly do not support its role either in dementia associated with Parkinson's disease or disease prognosis.

  2. LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.

    Science.gov (United States)

    Musumeci, O; la Marca, G; Spada, M; Mondello, S; Danesino, C; Comi, G P; Pegoraro, E; Antonini, G; Marrosu, G; Liguori, R; Morandi, L; Moggio, M; Massa, R; Ravaglia, S; Di Muzio, A; Filosto, M; Tonin, P; Di Iorio, G; Servidei, S; Siciliano, G; Angelini, C; Mongini, T; Toscano, A

    2016-01-01

    A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Clinical presentation of early-onset Alzheimer's disease as a result of mutation in exon 12 of the PSEN-1 gene.

    Science.gov (United States)

    Klimkowicz-Mrowiec, Aleksandra; Bodzioch, M; Szczudlik, A; Slowik, A

    2014-12-01

    Mutations in the gene for presenilin 1 (PSEN-1) cause familial, early-onset Alzheimer's disease (EOAD). Diagnosis of EOAD is often a challenge because of the high frequency of atypical presentations. Clinical manifestation of EOAD may vary depending on underlying mutation; specific genetic mutations influence development of specific clinical phenotypes; however, intrafamilial phenotypic heterogeneity has also been noted in some pedigrees. We report a case of a 36-year-old woman presenting with progressive behavioral disturbances, dementia, involuntary movements, pyramidal signs, epilepsy, and a family history of early-onset dementia accompanied by involuntary movements. On genetic testing, the mutation at codon 424 (Leu→Arg) in PSEN-1 gene was identified. Our case describes a new phenotype of a known mutation of PSEN-1 at codon 424. © The Author(s) 2014.

  4. [Knowledge of Andalusian pediatricians and parents about early-onset tooth decay].

    Science.gov (United States)

    González, E; Pérez-Hinojosa, S; Alarcón, J A; Peñalver, M A

    2015-01-01

    To determine the level of knowledge of pediatricians and parents from Andalucía (southern Spain) about early-onset tooth decay, and to assess if pediatricians provide information to parents about pediatric oral care and visits to the pediatric dentist. A random sample of 113 pediatricians and 112 parents with children under 3 years of age received an anonymous questionnaire comprising 14 items for pediatricians and 16 items for parents, grouped into five blocks: visits to the dentist, oral hygiene, caries, nutritional habits, and treatment of caries. The chi-squared test was used to assess differences between groups. Pediatricians showed deficiencies in their knowledge about visits to the dentist and treatment of caries, however their level of knowledge on oral hygiene, tooth decay and nutritional habits were adequate. Parents showed a low level of knowledge in all aspects of the study, mainly about the treatment of tooth decay. There were no significant differences between pediatricians and parents in the knowledge about visits to the dentist, however pediatricians had more knowledge than the parents about hygiene, tooth decay, nutritional habits and treatment (P<0.001). Most of the parents indicated that pediatricians did not provide them detailed information on oral care, and about the possibility of visiting a pediatric dentist. Andalusian pediatricians should improve their knowledge about early-onset tooth decay, and provide more information to parents about the oral care and the possibility of visiting a pediatric dentist. Parents have a very low level of knowledge about early-onset tooth decay, and particularly about treatment. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  5. Racial differences in cancer risk among relatives of patients with early onset lung cancer.

    Science.gov (United States)

    Naff, Jessica L; Coté, Michele L; Wenzlaff, Angela S; Schwartz, Ann G

    2007-05-01

    Relatives of patients with early onset lung cancer are at increased risk for lung cancer, and this risk varies by race. This study evaluates whether first-degree relatives of patients with early onset lung cancer are at increased risk for cancer at sites other than lung. Family histories were ascertained from 673 lung cancer patients < 50 years of age identified from the Metropolitan Detroit Surveillance, Epidemiology and End Results program, and 773 age-, race-, and sex-matched control subjects were obtained via random-digit dialing. Data were collected for 3,556 case relatives (mothers, fathers, and siblings) and 3,943 control relatives, and unconditional logistic regression models using generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Among case relatives, African Americans were 2.44-fold more likely to have head and neck cancers and 1.86-fold more likely to have any tobacco-related cancer compared to white case relatives (95% CI, 1.04 to 5.69% and 95% CI, 1.25 to 2.76, respectively). African-American case relatives were at increased risk for head and neck cancers (OR, 13.42; 95% CI, 1.65 to 109.01), all tobacco-related cancers (OR, 3.77; 95% CI, 2.16 to 6.55), tobacco-related cancers other than lung (OR, 4.10; 95% CI, 1.56 to 10.79), and cancer at any site (OR, 1.45, 95% CI, 1.04 to 2.02) compared to African-American control relatives. These results can be used to counsel family members of patients with early onset lung cancer, and suggest target populations for preventive strategies, including smoking cessation and appropriate screening.

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

    Science.gov (United States)

    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 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.

  7. Nucleosynthesis in the early Galaxy: Progress and challenges.

    Science.gov (United States)

    Montes, Fernando

    2015-10-01

    Chemical imprints left by the first stars in the oldest stars of the Milky Way gives clues of the stellar nucleosynthesis responsible for the creation of elements heavier than iron. Recent progress in astronomical observations and in the modeling of the chemical evolution of the Galaxy have shown that multiple nucleosynthesis processes may operate at those early times. In this talk I will review some of that evidence along with the important role that nuclear reactions play in those processes. I will focus in progress in our understanding of the rapid neutron capture process (r-process) and in new results on nucleosynthesis in core-collapse supernovae and neutrino-driven winds that produce elements up to silver. I will show some examples of recent nuclear physics measurements addressing the need for better nuclear data and give an outlook of the remaining challenges and future plans to continue those measurements.

  8. Early Onset Obesity and Risk of Metabolic Syndrome Among Chilean Adolescents

    OpenAIRE

    Pacheco, Lorena Sonia; Blanco, Estela; Burrows, Raquel; Reyes, Marcela; Lozoff, Betsy; Gahagan, Sheila

    2017-01-01

    Introduction Obesity and metabolic syndrome (MetS) indicators have increased globally among the pediatric population. MetS indicators in the young elevate their risk of cardiovascular disease and metabolic disorders later in life. This study examined early onset obesity as a risk factor for MetS risk in adolescence. Methods A cohort of Chilean participants (N = 673) followed from infancy was assessed at age 5 years and in adolescence (mean age, 16.8 y). Adiposity was measured at both time poi...

  9. Management of early onset neonatal sepsis differs in the north and south of Scandinavia

    DEFF Research Database (Denmark)

    Drageset, Martin; Fjalstad, Jon Widding; Mortensen, Sven

    2017-01-01

    AIM: This study compared the management and outcomes of early-onset neonatal sepsis (EONS) in two tertiary neonatal units in Denmark and Norway. METHODS: We retrospectively studied all infants diagnosed with EONS between April 2010 and March 2013 and managed at Odense University Hospital, Denmark...... blood cultures had higher C-reactive protein levels than patients with negative blood cultures and higher sepsis-attributable mortality. Lumbar punctures were performed more frequently in Denmark. CONCLUSION: There were marginal differences in the management of EONS between units in Denmark and Norway...

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

    Science.gov (United States)

    Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

    2017-12-01

    To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

  12. Sibling Sex Ratio and Birth Order in Early-Onset Gender Dysphoric Adolescents

    OpenAIRE

    Schagen, Sebastian E. E.; Delemarre-Van De Waal, Henriette A; Blanchard, Ray; Cohen-Kettenis, Peggy T

    2011-01-01

    Several sibship-related variables have been studied extensively in sexual orientation research, especially in men. Sibling sex ratio refers to the ratio of brothers to sisters in the aggregate sibships of a group of probands. Birth order refers to the probands’ position (e.g., first-born, middle-born, last-born) within their sibships. Fraternal birth order refers to their position among male siblings only. Such research was extended in this study to a large group of early-onset gender dysphor...

  13. Probable Early-Onset Alzheimer's Disease in an Apolipoprotein E2 Homozygote

    OpenAIRE

    Cole, Lauren; Belden, Christine; Jacobson, Sandra; Liebsack, Carolyn; Myers, Kent; Reninger, Cornelia; Berk, Camryn; Sabbagh, Marwan N.

    2010-01-01

    Objective: To describe a case of early-onset Alzheimer's disease (AD) in an apolipoprotein (Apo) epsilon 2/epsilon 2 homozygote. Background: Apo epsilon 2/epsilon 2 is the rarest of the ApoE genotypes, representing only 1.4% of the population. Cognitive decline in ApoE epsilon 2 homozygotes has rarely been reported. Case Report/Methods: We report a 58-year-old Apo epsilon 2/epsilon 2 female who meets clinical criteria for probable AD as confirmed by neuropsychological testing, positron emissi...

  14. Influence of light exposure during early life on the age of onset of bipolar disorder

    DEFF Research Database (Denmark)

    Bauer, Michael; Glenn, Tasha; Alda, Martin

    2015-01-01

    of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Methods: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder...... positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Conclusions: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little...

  15. Validation study of the early onset schizophrenia diagnosis in the Danish Psychiatric Central Research Register

    DEFF Research Database (Denmark)

    Vernal, Ditte Lammers; Stenstrøm, Anne Dorte; Staal, Nina

    2018-01-01

    The objective of this study is to assess (1) the concordance and validity of schizophrenia register diagnoses among children and adolescents (early onset schizophrenia = EOS) in the Danish Psychiatric Central Research Register (DPCRR), and (2) the validity of clinical record schizophrenia diagnoses...... in inpatient settings, EOS diagnoses are reliable and valid for register-based research. Schizophrenia diagnosed in children and adolescents in outpatient settings were found to have a high number of false-positives, both due to registration errors and diagnostic practice. Utilizing this knowledge......, it is possible to reduce the number of false-positives in register-based research of EOS....

  16. Functional and Radiographic Outcomes Following Growth-Sparing Management of Early-Onset Scoliosis.

    Science.gov (United States)

    Johnston, Charles E; Tran, Dong-Phuong; McClung, Anna

    2017-06-21

    In this study, we sought to evaluate radiographic, functional, and quality-of-life outcomes of patients who have completed growth-sparing management of early-onset scoliosis. This prospective study involved patients with early-onset scoliosis who underwent growth-sparing treatment and either "final" fusion or observation for ≥2 years since the last lengthening procedure. Demographics, radiographic parameters, pulmonary function test (PFT) values, and scores of patient-reported assessments (Early-Onset Scoliosis Questionnaire [EOSQ] and Scoliosis Research Society [SRS]-30) were obtained. At the most recent follow-up, patients performed 2 additional functional outcome tests: step-activity monitoring and a treadmill exercise-tolerance test. Twelve patients were evaluated as "graduates" of growth-sparing management of early-onset scoliosis (mean of 37 months since the most recent surgery). The major scoliosis curve measurement averaged 88° before treatment and 47° at the most recent follow-up. T1-S1 height increased from a mean of 22.3 cm to 34.7 cm and T1-T12 height, from 13.3 to 22.3 cm. At the most recent follow-up, the mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) as a percentage of the predicted volume were 52.1% and 55.3%, respectively, and were essentially unchanged from the earliest PFT that patients could perform (FEV1 = 53.8% of predicted and FVC = 53.5% of predicted). There was no difference between graduates and controls with respect to activity time or total steps in step-activity monitoring, and in the exercise-tolerance test, graduates walked at the same speed but at a higher heart rate and at a significantly higher (p scoliosis appears to be spine elongation and maintenance of pulmonary function at a level that is no less than the percentage of normal at initial presentation. Functional testing and patient-reported outcomes at a mean of 3 years from the last surgery suggest that activity levels were generally equal

  17. Attention deficit-hyperactivity disorder and early-onset bipolar disorder: two facets of one entity?

    Science.gov (United States)

    Zepf, Florian D

    2009-01-01

    Early-onset bipolar disorder (BD) and attention-deficit-hyperactivity disorder (ADHD) have recently been the subject of highly controversial debate, due to theories regarding underlying pathophysiological processes and a clinical overlap of symptoms. Epidemiological data, clinical aspects neuroimaging, neurochemical, and genetic studies suggest that there may be a possible relationship between biological factors and clinical characteristics in the development of symptoms. However, longitudinal data supporting the hypothesis of a diagnostic shift from BD to ADHD symptoms and vice versa are currently not available. These would be essential to enable further investigations into whether these two disorders possibly represent two different aspects of an underlying common psychopathophysiological entity.

  18. A systematic review of the risks factors associated with the onset and natural progression of spina bifida.

    Science.gov (United States)

    Donnan, Jennifer; Walsh, Stephanie; Sikora, Lindsey; Morrissey, Andrea; Collins, Kayla; MacDonald, Don

    2017-07-01

    The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of spina bifida, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Searches of several health literature databases from inception to February 2013 were conducted by a health sciences librarian. A total of three meta-analyses that studied a risk factor for the onset of spina bifida were included. Pooled results showed that paternal exposure to Agent Orange (RR=2.02; 95% CI 1.48-2.74) and maternal obesity prior to pregnancy (OR=2.24; 95% CI 1.86-2.74) each increased the risk of having a child with spina bifida. Paternal exposure to organic solvents was also close to the limit of significance (OR=1.59; 95% CI 0.99-2.56). A total of 63 observational studies, encompassing hundreds of potential risk factors, were included for risk factors for the onset of disease. One meta-analysis and four observational studies examined the impact of genetic risk factors. Only specified mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were found to be linked to disease onset. One observational study evaluated a risk factor for the natural progression of disease. An extensive number of potential risk factors for the onset of spina bifida have been studied, though most lack sufficient evidence to confirm an association. Currently, strong evidence exists to suggest a causal association for maternal obesity prior to pregnancy, and paternal exposure to Agent Orange. Copyright © 2016. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available 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.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.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.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.

  20. Characteristics of early- and late-onset rapid eye movement sleep behavior disorder in China: a case-control study.

    Science.gov (United States)

    Zhou, Junying; Zhang, Jihui; Du, Lina; Li, Zhe; Li, Yun; Lei, Fei; Wing, Yun-Kwok; Kushida, Clete A; Zhou, Dong; Tang, Xiangdong

    2014-06-01

    To investigate demography and clinic and polysomnographic characteristics in Chinese rapid eye movement (REM) sleep behavior disorder (RBD) patients across onset ages. Ninety consecutive patients fulfilling the criteria for RBD were recruited for study in our sleep center. Patients were separated into early- and late-onset groups according to age when symptoms began (50 years, respectively). Ninety age- and gender-matched healthy subjects served as controls. All subjects were interviewed for their clinical history, completed an RBD questionnaire, and underwent an overnight video polysomnography assessment. Demographics, comorbidities, scores on the RBD questionnaire, sleep architecture, and EMG activity were compared between the patients and controls and between the early- and late-onset groups. Of all RBD patients, 63 were male, and mean age of RBD onset was 54.3±15.7 years. In 25 patients (28%), RBD was secondary and associated with neurodegenerative disease, narcolepsy or antidepressant use. Twenty-three patients (26%) had early-onset RBD and 67 (74%) were in the late-onset group. RBD patients had significantly more comorbidities, dreams and dream-enacting behaviors, and poorer sleep quality than did controls. The early-onset group had a high proportion of females (48%) and an increased proportion of cases associated with narcolepsy. The early-onset group also had fewer movements, lower EMG activity during REM sleep, and better sleep quality when compared to the late-onset group. EMG activity was positively correlated with age of onset. The mean follow-up time was 1.57±0.82 years, and four patients in the late-onset group were subsequently diagnosed with neurodegenerative diseases. Stratifying patients into early and late-onset RBD revealed different characteristics from those previously described as typical for RBD. EMG activity during REM sleep was positively correlated with age of onset. We suggest that it will be valuable to explore the relationship

  1. Quality of antenatal care as a risk factor for early onset neonatal infections in Rio de Janeiro, Brazil.

    Science.gov (United States)

    Mizumoto, B R; Moreira, B M; Santoro-Lopes, G; Cunha, A J; Santos, R M R dos; Pessoa-Silva, C L; Pinheiro, Azeredo A N; Ferreira, M; Leobons, M B; Hofer, Cristina Barroso

    2015-01-01

    Neonatal infection is a serious public health problem. The aim of this study was to assess the influence of the antenatal care on the risk of early-onset neonatal healthcare associated infection in two Brazilian maternities. Cohort study - Newborns admitted at two public neonatal intensive care units from 2008 to 2009 were included in the study. Data on antenatal and perinatal variables were collected from maternal prenatal cards and medical charts. Newborns were actively surveyed for early-onset neonatal healthcare associated infection, defined as a neonatal infection diagnosed within 48h after birth. Multiple logistic regression was used to assess variables independently associated with early-onset neonatal healthcare associated infection. 561 neonate-mother pairs were included in the study. Early-onset neonatal healthcare associated infection was diagnosed in 283 neonates (51%), an incidence rate of 43.5/1000 live births. Neonates whose mothers had less then six antenatal visits were under risk significantly higher for early-onset neonatal healthcare associated infection (OR=1.69, 95% CI=1.11-2.57), after adjusting for birth weight, membranes ruptured for >18h, maternal complications during delivery, maternal infection at admission, and hospital where patients received care. The risk of neonatal early-onset neonatal healthcare associated infection was significantly associated with insufficient number of antenatal care visits. Further studies assessing the quality of antenatal care and targeting its improvement are warranted. Copyright © 2015. Published by Elsevier Editora Ltda.

  2. Estimating the burden of early onset dementia; systematic review of disease prevalence.

    Science.gov (United States)

    Lambert, M A; Bickel, H; Prince, M; Fratiglioni, L; Von Strauss, E; Frydecka, D; Kiejna, A; Georges, J; Reynish, E L

    2014-04-01

    Dementia is more common in older age but a number of people develop symptoms at a younger age and are said to have early onset dementia (EOD). Those with EOD face different challenges to those with onset later in life. It has been difficult to quantify this disease burden. This is a systematic review of papers reporting on the prevalence of EOD. A search of Medline and Embase was performed. This was followed by a hand search of the references of these papers. Eleven suitable studies were included. All of the data was from more economically developed countries. The studies were heterogeneous in their design hindering direct comparison. The majority of the papers looked at all types of dementia although many gave a breakdown of the prevalence of different subgroups. A variety of diagnostic criteria was employed. Figures of 38 to 260 per 100,000 are quoted by papers looking at various different types of dementia together with an onset of between 30 and 64 or up to 420 per 100,000 for those aged 55-64. Prevalence rises as age approaches 65. Epidemiological data for prevalence rates for EOD are sparse. EOD remains a rare condition with low case numbers. Assimilation and comparison of results from existing studies is difficult due to methodological heterogeneity. Cross-national standardization of methodology should be a priority for future research in this area. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  3. Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update.

    Science.gov (United States)

    Raux, G; Guyant-Maréchal, L; Martin, C; Bou, J; Penet, C; Brice, A; Hannequin, D; Frebourg, T; Campion, D

    2005-10-01

    Autosomal dominant early onset Alzheimer's disease (ADEOAD) is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes have been identified. To further clarify the respective contribution of these genes to ADEOAD. 31 novel families were investigated. They were ascertained using stringent criteria (the occurrence of probable or definite cases of Alzheimer's disease with onset before 60 years of age in three generations). All cases fulfilled the NINCDS-ADRDA criteria for probable or definite Alzheimer's disease. The entire coding regions of PSEN1 and PSEN2 genes and exons 16 and 17 of APP gene were sequenced from genomic DNA RESULTS: PSEN1 mutations, including eight previously unreported mutations, were detected in 24 of the 31 families, and APP mutations were found in five families. In this sample, the mean ages of disease onset in PSEN1 and APP mutation carriers were 41.7 and 51.2 years, respectively. Combining these data with previously published data, yielding 65 ADEOAD families, 66% of the cases were attributable to PSEN1 mutations and 16% to APP mutations, while 18% remained unexplained.

  4. Early-Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome.

    Science.gov (United States)

    Barton, Michelle; Shen, Alex; O'Brien, Karel; Robinson, Joan L; Davies, H Dele; Simpson, Kim; Asztalos, Elizabeth; Langley, Joanne; Le Saux, Nicole; Sauve, Reginald; Synnes, Anne; Tan, Ben; de Repentigny, Louis; Rubin, Earl; Hui, Chuck; Kovacs, Lajos; Yau, Yvonne C W; Richardson, Susan E

    2017-04-01

    Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ≤7 days) or compared to late-onset disease (LOD, >7 days). All extremely low birth weight (ELBW, candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body.

  5. Cardiovascular Disease Risk Factors After Early-Onset Preeclampsia, Late-Onset Preeclampsia, and Pregnancy-Induced Hypertension

    NARCIS (Netherlands)

    Veerbeek, Jan H. W.; Hermes, Wietske; Breimer, Anath Y.; van Rijn, Bas B.|info:eu-repo/dai/nl/304816582; Koenen, Steven V.|info:eu-repo/dai/nl/239456742; Mol, Ben W.; Franx, Arie|info:eu-repo/dai/nl/157009939; de Groot, Christianne J. M.; Koster, Maria P. H.; Koster, M.P.H. (Wendy)|info:eu-repo/dai/nl/314064192

    Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been

  6. Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability

    Directory of Open Access Journals (Sweden)

    Antonio Giorgio

    2017-11-01

    Full Text Available Pediatric-onset multiple sclerosis (POMS may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15 in comparison with age- and disability-matched AOMS patients (n = 14 and to normal controls (NC, n = 20. We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space. POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

  7. Treatment of Early Onset Spinal Deformity (EOSD) with VEPTR: A Challenge for the Final Correction Spondylodesis: A Case Series.

    Science.gov (United States)

    Lattig, Friederike; Taurman, Rita; Hell, Anna K

    2012-08-18

    STUDY DESIGN:: Case Series. OBJECTIVE:: To describe the post VEPTR (vertical expandable prosthetic titanium rib) treatment changes in early onset spinal deformity (EOSD), which may influence the final correction spondylodesis. SUMMARY OF BACKGROUND DATA:: The VEPTR device, originally developed for the treatment of congenital rib cage malformation, is nowadays more widely used in the treatment of early onset spinal deformity. Up to now only a few reports describe the possible complications, which may occur with repeated lengthening procedures of the VEPTR thereby making the final spondylodesis more complicated and less satisfactory. METHODS:: X-Rays of five children treated for EOSD with two unilateral VEPTR (each rib to rib and rib to lumbar lamina) were analyzed for curve patterns and Cobb angles pre, during and at the end of VEPTR- treatment as well as after the final spondylodesis. Intraoperative observations during the sponylodesis, which influenced the possibilies of the curve correction, were documented. RESULTS:: All patients showed a marked decompensation of the frontal balance and a high degree of rigidity of the main curve as well as the compensatory curves after treatment with the VEPTR device. Due to this spontaneous autofusion of spinal segments, migration of the rib cradles and/or the laminar hook and a change of the curve patterns the final fusion had to be longer in all patients than the primary deformity would have intended. CONCLUSIONS:: If an EOSD is treated with VEPTR, the curve progression and in particular the development of a high thoracic hyperkyphosis or rotation of the main curve should be critically observed. Autofusion of ribs and vertebral bodies may make the final correction spondylodesis even more challenging and risky for the patient and the end result less satisfactory.

  8. A case of probable non-familial early onset Alzheimer dementia in a Hispanic male.

    Science.gov (United States)

    Ephrussi, Corey; Alweis, Richard

    2012-01-01

    Early onset Alzheimer's type dementia (EOAD) is usually familial and associated with mutations in the Presenilin-1 (PSEN1), Presenilin-2 (PSEN2) or amyloid precursor protein (APP) genes. It is rarely reported in patients of Hispanic descent. A 49-year-old Hispanic male developed significant cognitive impairment over a 4-year period. PET scan showed diminished metabolic activity in the posterior parietal/temporal lobes. Genetic testing revealed the presence of a PSEN1 gene mutation. Disparities in health care may account for an under-recognition of EOAD in the Hispanic population. Clinicians should test for EOAD in all patients with appropriate symptomatology, regardless of ethnicity. Early recognition and enrollment in clinical trials is vital to enhancing our understanding of the natural history and treatment of this condition.

  9. A case of probable non-familial early onset Alzheimer dementia in a Hispanic male

    Directory of Open Access Journals (Sweden)

    Corey Ephrussi

    2012-07-01

    Full Text Available Background: Early onset Alzheimer's type dementia (EOAD is usually familial and associated with mutations in the Presenilin-1 (PSEN1, Presenilin-2 (PSEN2 or amyloid precursor protein (APP genes. It is rarely reported in patients of Hispanic descent. Case report: A 49-year-old Hispanic male developed significant cognitive impairment over a 4-year period. PET scan showed diminished metabolic activity in the posterior parietal/temporal lobes. Genetic testing revealed the presence of a PSEN1 gene mutation. Conclusion: Disparities in health care may account for an under-recognition of EOAD in the Hispanic population. Clinicians should test for EOAD in all patients with appropriate symptomatology, regardless of ethnicity. Early recognition and enrollment in clinical trials is vital to enhancing our understanding of the natural history and treatment of this condition.

  10. Onset rivalry: brief presentation isolates an early independent phase of perceptual competition.

    Directory of Open Access Journals (Sweden)

    Olivia Carter

    2007-04-01

    Full Text Available When the left and right eyes are simultaneously presented with different images, observers typically report exclusive awareness of only one image. This phenomenon is termed binocular rivalry, reflecting the fact that the dominant image alternates every few seconds in a cycle of perceptual competition that continues indefinitely. Despite the apparent continuity in perceptual switching, we now demonstrate that the initial "onset" period is fundamentally different to all subsequent rivalry epochs. Using brief intermittent presentations, rivalry dominance shows strong biases such that the same target is perceived with each successive stimulus onset. These biases remain consistent within any given location, but vary across the visual field in a distribution that is stable over multiple weeks but highly idiosyncratic across observers. If the presentation exceeds approximately 1sec at any location, however, the very different and much more balanced alternations of sustained binocular rivalry become apparent. These powerful onset biases are observed with brief intermittent presentations at a single location or with continual smooth motion of the targets. Periods of adaptation to one of the rivaling targets induced local switches in dominance to the non-adapted target. However, these effects were generally limited to the spatial site of adaptation and had less influence over each subsequent cycle of the target. We conclude that onset rivalry is independent of sustained rivalry and cannot be explained by local regions of monocular dominance or memory of past perceptual history, but rather reflects low-level, spatially localized factors that are stable over periods of weeks. These findings suggest that brief presentation paradigms are inappropriate for their current use in studies of the mechanisms underlying sustained rivalry. However, brief presentations are ideal for investigating early stages of perceptual competition.

  11. Herlyn-Werner-Wunderlich syndrome: An "early" onset case report and review of Literature.

    Science.gov (United States)

    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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Impact of DNA testing for early-onset familial Alzheimer disease and frontotemporal dementia.

    Science.gov (United States)

    Steinbart, E J; Smith, C O; Poorkaj, P; Bird, T D

    2001-11-01

    DNA testing of persons at risk for hereditary, degenerative neurologic diseases is relatively new. Only anecdotal reports of such testing in familial Alzheimer disease (FAD) exist, and little is know about the personal and social impact of such testing. In a descriptive, observational study, individuals at 50% risk for autosomal dominant, early-onset FAD or frontotemporal dementia with parkinsonism linked to chromosome 17 underwent DNA testing for the genetic mutations previously identified in affected family members. Individuals were followed up for (1/2) to 3 years and were interviewed regarding attitudes toward the testing process and the impact of the results. Twenty-one (8.4%) of 251 persons at risk for FAD or frontotemporal dementia requested genetic testing. The most common reasons for requesting testing were concern about early symptoms of dementia, financial or family planning, and relief from anxiety. Twelve individuals had positive DNA test results, and 6 of these had early symptoms of dementia; 8 had negative results; and 1 has not yet received results. Of 14 asymptomatic individuals completing testing, 13 believed the testing was beneficial. Two persons reported moderate anxiety and 1 reported moderate depression. As expected, persons with negative test results had happier experiences overall, but even they had to deal with ongoing anxiety and depression. Thus far, there have been no psychiatric hospitalizations, suicide attempts, or denials of insurance. Genetic testing in early-onset FAD and frontotemporal dementia can be completed successfully. Most individuals demonstrate effective coping skills and find the testing to be beneficial, but long-term effects remain unknown.

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

    Science.gov (United States)

    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. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights

  14. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease

    NARCIS (Netherlands)

    Lindner, M.; Lambertus, S.; Mauschitz, M.M.; Bax, N.M.; Kersten, E; Luning, A.; Nadal, J.; Schmitz-Valckenberg, S.; Schmid, M.; Holz, F.G.; Hoyng, C.B.; Fleckenstein, M.

    2017-01-01

    Purpose: To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Methods: Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and

  15. 2014 CODEPEH recommendations: Early detection of late onset deafness, audiological diagnosis, hearing aid fitting and early intervention.

    Science.gov (United States)

    Núñez-Batalla, Faustino; Jáudenes-Casaubón, Carmen; Sequí-Canet, Jose Miguel; Vivanco-Allende, Ana; Zubicaray-Ugarteche, Jose

    2016-01-01

    The latest scientific literature considers early diagnosis of deafness as the key element to define the educational and inclusive prognosis of the deaf child, because it allows taking advantage of the critical period of development (0-4 years). Highly significant differences exist between deaf people who have been stimulated early and those who have received late or improper intervention. Early identification of late-onset disorders requires special attention and knowledge on the part of every childcare professional. Programs and additional actions beyond neonatal screening should be designed and planed to ensure that every child with a significant hearing loss is detected early. For this purpose, the CODEPEH would like to highlight the need for continuous monitoring of children's auditory health. Consequently, CODEPEH has drafted the recommendations included in the present document. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  16. Familial pathways to early-onset suicidal behavior: familial and individual antecedents of suicidal behavior.

    Science.gov (United States)

    Melhem, Nadine M; Brent, David A; Ziegler, Melissa; Iyengar, Satish; Kolko, David; Oquendo, Maria; Birmaher, Boris; Burke, Ainsley; Zelazny, Jamie; Stanley, Barbara; Mann, J John

    2007-09-01

    The authors sought to identify clinical predictors of new-onset suicidal behavior in children of parents with a history of mood disorder and suicidal behavior. In a prospective study of offspring of parents with mood disorders, 365 offspring (average age, 20 years) of 203 parents were followed for up to 6 years. Offspring with incident suicide attempts or emergency referrals for suicidal ideation or behavior ("incident events") were compared with offspring without such events on demographic and clinical characteristics. Multivariate analyses were conducted to examine predictors of incident events and predictors of time to incident event. Offspring of probands who had made suicide attempts, compared with offspring of parents with mood disorders who had not made attempts, had a higher rate of incident suicide attempts (4.1% versus 0.6%, relative risk=6.5) as well as overall suicidal events (8.3% versus 1.9%, relative risk=4.4). Mood disorder and self-reported impulsive aggression in offspring and a history of sexual abuse and self-reported depression in parents predicted earlier time to, and greater hazard of, an incident suicidal event. In offspring of parents with mood disorders, precursors of early-onset suicidal behavior include mood disorder and impulsive aggression as well as parental history of suicide attempt, sexual abuse, and self-reported depression. These results suggest that efforts to prevent the familial transmission of early-onset suicidal behavior by targeting these domains could reduce the morbidity of suicidal behavior in high-risk youths.

  17. Patterns of striatal functional connectivity differ in early and late onset Parkinson's disease.

    Science.gov (United States)

    Hou, Yanbing; Yang, Jing; Luo, Chunyan; Ou, Ruwei; Song, Wei; Liu, Wanglin; Gong, Qiyong; Shang, Huifang

    2016-10-01

    To map functional connectivity (FC) patterns of early onset Parkinson's disease (EOPD) and late onset PD (LOPD) in drug-naïve early stage. MRI was used to assess atrophy and resting-state FC focusing on striatal subregions of EOPD and LOPD in two subgroups of 18 patients matched for disease duration and severity, relative to age- and sex- matched healthy controls. Compared with controls, both PD subgroups showed FC alterations in cortico-striatal and cerebello-striatal loops but with different patterns in resting state. EOPD patients showed widespread increased FC between striatum and sensorimotor cortex, middle frontal gyrus, superior and inferior parietal lobules, superior and inferior temporal gyri, and cerebellum. While LOPD patients were evidenced with increased FC in cerebello-striatal circuit and decreased FC between orbitofrontal gyrus and striatum. In addition, Unified Parkinson's Disease Rating Scale part III scores were negatively correlated with the increased FC between the caudate nucleus and sensorimotor cortex (r = -0.571, p = 0.013) in EOPD patients, while negatively correlated with the increased FC between the putamen and cerebellum (r = -0.478, p = 0.045) in LOPD patients, suggesting that increased FC is here likely to reflect compensatory mechanism. FC changes in EOPD and LOPD share common features and have differences, which may suggest that the responses to defective basal ganglia are different between the two subtypes. Improved insights into the onset-related subtypes of PD and its disruptive FC pattern will be valuable for improving our understanding of the pathogenesis of the disease.

  18. Pharmacotherapy effectiveness for clinical subgroups among children and adolescents with early onset schizophrenia.

    Science.gov (United States)

    Jerrell, Jeanette M; McIntyre, Roger S; Deroche, Chelsea B

    2017-03-01

    This study aims to determine the effectiveness of pharmacotherapies among children and adolescents diagnosed with early onset schizophrenia subgrouped according to their co-occurring psychiatric disorders. A retrospective cohort design was employed, using South Carolina's (USA) Medicaid claims dataset covering outpatient and inpatient medical services, between January, 1999 and December, 2013 to identify patients ≤17 years of age. Random effects regression analyses assessed differential changes in acute psychiatric service utilization over time across the 3 subgroups associated with antipsychotic, mood stabilizer, psychostimulant, or antidepressant pharmacotherapy. For patients with schizophrenia and comorbid mood disorders or emotional dysregulation (Cluster 1), or schizophrenia and severe cognitive impairments (Cluster 2), those treated with monotherapy second-generation antipsychotics (SGAs) over time demonstrated consistently lower use of acute psychiatric treatment services as did those coprescribed mood stabilizers, primarily lithium, or anticonvulsants. In all clusters, including the relatively homogenous subgroup of patients with early onset schizophrenia and few comorbid disorders, acute psychiatric service utilization was significantly higher and more variable over time for those prescribed multiple SGAs. Regardless of the specific constellation of symptoms and comorbid disorders targeted, the coprescription of multiple SGAs was not effective over time in stabilizing children and adolescents outside of acute care settings. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Focused Molding Using Adhesive Pads in Mehta Casting for Early-Onset Scoliosis.

    Science.gov (United States)

    Abraham, Roby; Sponseller, Paul D

    2014-11-01

    Prospective clinical series. To determine the effect of adhesive pads placed over the apex of scoliosis curves on curve correction 1) after the first cast and 2) after the final cast. Early-onset scoliosis is often effectively managed by serial casting. Properly localizing the apex of the molds with the cast in place is challenging. The authors explored the effectiveness of a novel technique: incorporation of adhesive pads placed over the major curve apex before Mehta casting. The 27 patients who received body casts (2000-2013) were divided into 2 groups: those without and with apical adhesive pads (5-6 layers of pads placed on the major curve's apex during casting): non-pad (NP) group (n = 12) and pad (P) group (n = 15), respectively. Groups were compared regarding the percentage of Cobb angle change from the first cast and curve correction to a Cobb angle of cast curve correction was 39% ± 18% and 56% ± 17% in the NP and P groups, respectively. Of the 26 patients out of a cast, 11 (42%) had a Cobb angle of casting were effective in increasing the amount of major curve correction from the first cast for idiopathic early-onset scoliosis and in decreasing curves to <25° at final follow-up. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

  20. Blau syndrome mutation of CARD15/NOD2 in sporadic early onset granulomatous arthritis.

    Science.gov (United States)

    Rosé, Carlos D; Doyle, Trudy M; McIlvain-Simpson, Gail; Coffman, Jessica E; Rosenbaum, James T; Davey, Michael P; Martin, Tammy M

    2005-02-01

    Patients with sporadic early-onset granulomatous arthritis are clinically identical to Blau syndrome, but without the family history. Blau syndrome is an autosomal dominant inherited disease and is known to be caused by mutations in the CARD15 gene (also called NOD2). We investigated the hypothesis that an individual with sporadic early onset granulomatous arthritis may have a Blau syndrome mutation in CARD15/NOD2. Our patient's genomic DNA isolated from a buccal swab sample was subjected to amplification to include the region of exon 4 from the CARD15/NOD2 gene that contains known mutations that cause Blau syndrome. This region was screened for mutations by direct DNA sequencing in both directions. One of the mutations in CARD15/NOD2 attributed to Blau syndrome was found in the DNA sample. The nucleotide change encodes an amino acid substitution from arginine to tryptophan at position 334 of the protein. This mutation has been found in some Blau syndrome pedigrees reported in the literature. These data suggest that sporadic granulomatous arthritis may in fact be the sporadic form of Blau syndrome, but arising from a spontaneous neomutation. This would explain the profound clinical identity and the lack of disease history in the parents.

  1. Early-Onset Central Diabetes Insipidus due to Compound Heterozygosity for AVP Mutations.

    Science.gov (United States)

    Bourdet, Karine; Vallette, Sophie; Deladoëy, Johnny; Van Vliet, Guy

    2016-01-01

    Genetic cases of isolated central diabetes insipidus are rare, are mostly due to dominant AVP mutations and have a delayed onset of symptoms. Only 3 consanguineous pedigrees with a recessive form have been published. A boy with a negative family history presented polyuria and failure to thrive in the first months of life and was diagnosed with central diabetes insipidus. Magnetic resonance imaging showed a normal posterior pituitary signal. A molecular genetic analysis of the AVP gene showed that he had inherited a previously reported mutation from his Lebanese father and a novel A>G transition in the splice acceptor site of intron 1 (IVS1-2A>G) from his French-Canadian mother. Replacement therapy resulted in the immediate disappearance of symptoms and in weight gain. The early polyuria in recessive central diabetes insipidus contrasts with the delayed presentation in patients with monoallelic AVP mutations. This diagnosis needs to be considered in infants with very early onset of polyuria-polydipsia and no brain malformation, even if there is no consanguinity and regardless of whether the posterior pituitary is visible or not on imaging. In addition to informing family counseling, making a molecular diagnosis eliminates the need for repeated imaging studies. © 2015 S. Karger AG, Basel.

  2. [Early-onset type 2 diabetes mellitus. The experience from a third level medical institution].

    Science.gov (United States)

    Lerman-Garber, Israel; Aguilar-Salinas, Carlos; Tusié-Luna, Teresa; Velásquez, Daniel; Lobato-Valverde, Marlette; Osornio-Flores, Melannie; Gómez-Pérez, Francisco J; Granados-Arreola, Julio; Villa, Antonio R; Velascoa, María Luisa; Rull-Rodrigo, Juan A

    2010-01-01

    Describe the clinical, metabolic and psychosocial characteristics observed among patients with early onset type 2 diabetes (T2DM). We included 80 consecutive patients with early onset T2DM. All had a medical record, completed a battery of questionnaires and had blood and urine tests. Mean age was 49 +/- 12 years, 57.5% were women, 76.2% had a family history of diabetes and 68.8% a personal history of obesity. Diabetes was diagnosed at the mean age of 32 +/- 6 years with a mean duration of 17 +/- 11 years. Most patients (66.2%) were on poor glycemic control (Alc > 9.0%) and 30% were depressed. Insulin was commonly needed (80% of the patients) and started on average 9 years after diagnosis Significant diabetes related complications were common (71.3% of patients). A longer diabetes duration was the variable most significantly associated with developing complications (p diabetic patients attending our clinic; they are characterized by a stronger family history of diabetes, a personal history of obesity and co-morbidities associated with metabolic syndrome. Longer disease course and poor glycemic control contribute to a high prevalence of diabetes related complications and high rates of mortality.

  3. A Survey on Current Practice of Management of Early Onset Neonatal Sepsis.

    Science.gov (United States)

    Dey, A C; Hossain, M I; Afroze, S; Dey, S K; Mannan, M A; Shahidullah, M

    2016-04-01

    It was a survey type of cross sectional study where the participants were from different teaching/referral hospital across the country and was done to gather information regarding current practice of management of neonatal sepsis among paediatricians and neonatologists and was conducted on the spot during a national conference of Bangladesh Perinatal Society in December 2013. Specialists in neonatology, paediatrics, and some other disciplines working in different institutes across the country were requested to respond. Out of 150 physicians, 92 (61.33%) were neonatologists. Physicians suspected early onset neonatal sepsis (EONS) when there is history suggestive of prolonged rupture of membrane (74.77%), prolonged labour (9.33%), chorioamnionitis (7.33%) and maternal fever (2%). Clinical sepsis is found commonly (53.33%) which is later proved by laboratory evidences such as Hb%, TC, DC PBF (peripheral blood film), C-reactive protein, chest X-ray etc. Injection Ampicillin and Gentamycin are still the first choice of antibiotics (61.3%). Preferred route was intravenous (95.3%). Antibiotics were given for 7-10 days by most of the physicians (48.77%). However there is lack of uniformity among the participants in regard to taking decision about antibiotics, the choice of first line and the subsequent options of antibiotics. So, neonatal sepsis is the most important cause of neonatal mortality in the community. Therefore a standard protocolized approach for diagnosis and management of Early Onset Neonatal Sepsis may prove critical which is currently not in practice uniformly.

  4. Candidate predisposing germline copy number variants in early onset colorectal cancer patients.

    Science.gov (United States)

    Brea-Fernandez, A J; Fernandez-Rozadilla, C; Alvarez-Barona, M; Azuara, D; Ginesta, M M; Clofent, J; de Castro, L; Gonzalez, D; Andreu, M; Bessa, X; Llor, X; Xicola, R; Jover, R; Castells, A; Castellvi-Bel, S; Capella, G; Carracedo, A; Ruiz-Ponte, C

    2017-05-01

    A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter. We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis. These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

  5. GATA2 is associated with familial early-onset coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Jessica J Connelly

    2006-08-01

    Full Text Available The transcription factor GATA2 plays an essential role in the establishment and maintenance of adult hematopoiesis. It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelial cells and smooth muscle cells. We have shown that GATA2 expression is predictive of location within the thoracic aorta; location is suggested to be a surrogate for disease susceptibility. The GATA2 gene maps beneath the Chromosome 3q linkage peak from our family-based sample set (GENECARD study of early-onset coronary artery disease. Given these observations, we investigated the relationship of several known and novel polymorphisms within GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significant association of two of these single nucleotide polymorphisms in an independent case-control sample set that was phenotypically similar to the GENECARD families. These observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary artery disease inheritance.

  6. Validity of hematologic parameters in identification of early and late onset neonatal infection.

    Science.gov (United States)

    Varsha; Rusia, Usha; Sikka, Meera; Faridi, M M A; Madan, Nishi

    2003-10-01

    This study was designed to evaluate the utility of hematological parameters and C-reactive protein (CRP) to formulate a sepsis screen to detect sepsis in early and late onset infection. Hundred and fifty neonates clinically suspected of bacterial infection, based on risk factors and/or clinical features were selected for the study. Blood was collected by venipuncture at the time of admission in all neonates. A total leukocyte count (TLC), differential leukocyte count (DLC), its derivatives [Total neutrophil count (TNC or T), ratio of immature to total neutrophil count (I/T), ratio of immature to mature neutrophil count (I/M)] and CRP were obtained. TLC = 10x10(9)/L, TNC = 8x10(9)/L, I/T = 0.16, I/M = 0.25 and CRP = 0.6 mg/dl were found to be good parameters in detection of sepsis. During the first three days of life leukopenia, neutropenia, elevated I/T ratio, elevated I/M ratio and CRP were good diagnostic aids while after 3 days of life CRP was the best single test. This emphasizes use of multiple indicators for detection of sepsis. Using these parameters a sepsis screen was formulated which detected >90% of proven early and late onset sepsis suggesting that other neonates with positive sepsis screen but blood culture negativity may have been truly infected.

  7. Longitudinal telomere shortening and early Alzheimer's disease progression in adults with down syndrome.

    Science.gov (United States)

    Jenkins, Edmund C; Marchi, Elaine J; Velinov, Milen T; Ye, Lingling; Krinsky-McHale, Sharon J; Zigman, Warren B; Schupf, Nicole; Silverman, Wayne P

    2017-08-30

    Telomere shortening was shown to parallel Alzheimer's disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T-lymphocyte interphases from individuals with Down syndrome (DS) with and without "mild cognitive impairment" (MCI-DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI-DS in this high-risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (N = 4 Female, N = 6 Male) developing MCI-DS. Cases were selected blind to telomere length from a sample of adults with DS previously enrolled in a prospective longitudinal study at 18-month intervals with clinical and telomere assessments: (1) MCI-DS group data were collected approximately three years prior to development of MCI-DS; (2) 18 months later; (3) when MCI-DS was first observed. These telomere measures were compared to those from another 10 adults with DS matched by sex and approximate age but without indications of MCI-DS (Controls). PNA (peptide nucleic acid) probes for telomeres together with a chromosome two centromere probe were used. Findings indicated telomere shortening over time for both Cases and Controls. Group differences emerged by 18-months prior to recognition of MCI-DS onset and completely non-overlapping distributions of telomere measures were observed by the time of MCI-DS onset. This study adds to accumulating evidence of the value of telomere length, as an early biomarker of AD progression in adults with Down syndrome. © 2017 Wiley Periodicals, Inc.

  8. Amyloid misfolding, aggregation, and the early onset of protein deposition diseases: insights from AFM experiments and computational analyses

    Directory of Open Access Journals (Sweden)

    Yuri L. Lyubchenko

    2015-05-01

    Full Text Available The development of Alzheimer's disease is believed to be caused by the assembly of amyloid β proteins into aggregates and the formation of extracellular senile plaques. Similar models suggest that structural misfolding and aggregation of proteins are associated with the early onset of diseases such as Parkinson's, Huntington's, and other protein deposition diseases. Initially, the aggregates were structurally characterized by traditional techniques such as x-ray crystallography, NMR, electron microscopy, and AFM. However, data regarding the structures formed during the early stages of the aggregation process were unknown. Experimental models of protein deposition diseases have demonstrated that the small oligomeric species have significant neurotoxicity. This highlights the urgent need to discover the properties of these species, to enable the development of efficient diagnostic and therapeutic strategies. The oligomers exist transiently, making it impossible to use traditional structural techniques to study their characteristics. The recent implementation of single-molecule imaging and probing techniques that are capable of probing transient states have enabled the properties of these oligomers to be characterized. Additionally, powerful computational techniques capable of structurally analyzing oligomers at the atomic level advanced our understanding of the amyloid aggregation problem. This review outlines the progress in AFM experimental studies and computational analyses with a primary focus on understanding the very first stage of the aggregation process. Experimental approaches can aid in the development of novel sensitive diagnostic and preventive strategies for protein deposition diseases, and several examples of these approaches will be discussed.

  9. Amyloid misfolding, aggregation, and the early onset of protein deposition diseases: insights from AFM experiments and computational analyses.

    Science.gov (United States)

    Lyubchenko, Yuri L

    2015-01-01

    The development of Alzheimer's disease is believed to be caused by the assembly of amyloid β proteins into aggregates and the formation of extracellular senile plaques. Similar models suggest that structural misfolding and aggregation of proteins are associated with the early onset of diseases such as Parkinson's, Huntington's, and other protein deposition diseases. Initially, the aggregates were structurally characterized by traditional techniques such as x-ray crystallography, NMR, electron microscopy, and AFM. However, data regarding the structures formed during the early stages of the aggregation process were unknown. Experimental models of protein deposition diseases have demonstrated that the small oligomeric species have significant neurotoxicity. This highlights the urgent need to discover the properties of these species, to enable the development of efficient diagnostic and therapeutic strategies. The oligomers exist transiently, making it impossible to use traditional structural techniques to study their characteristics. The recent implementation of single-molecule imaging and probing techniques that are capable of probing transient states have enabled the properties of these oligomers to be characterized. Additionally, powerful computational techniques capable of structurally analyzing oligomers at the atomic level advanced our understanding of the amyloid aggregation problem. This review outlines the progress in AFM experimental studies and computational analyses with a primary focus on understanding the very first stage of the aggregation process. Experimental approaches can aid in the development of novel sensitive diagnostic and preventive strategies for protein deposition diseases, and several examples of these approaches will be discussed.

  10. Psychological differences between early- and late-onset psoriasis: a study of personality traits, anxiety and depression in psoriasis.

    Science.gov (United States)

    Remröd, C; Sjöström, K; Svensson, A

    2013-08-01

    Onset of psoriasis may occur at any age. Early negative experiences often influence personality development, and may lead to physical disease, anxiety and depression in adulthood. Knowledge about onset of psoriasis and psychopathology is limited. To examine whether patients with early-onset psoriasis differ psychologically from patients with late-onset psoriasis, regarding personality traits, anxiety and depression. A descriptive cross-sectional study was conducted among 101 consecutively recruited outpatients with psoriasis. A psychosocial interview was performed followed by self-assessment of validated questionnaires: Swedish Universities Scales of Personality (SSP), Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory. Psoriasis severity was assessed by the Psoriasis Area and Severity Index. Patients with early-onset psoriasis (age personality traits: SSP-embitterment, -trait irritability, -mistrust and -verbal trait aggression. Our results indicate that early detection of psychological vulnerability when treating children and adolescents with psoriasis seems to be of great importance. Traits of psychological vulnerability and pessimistic personality traits were found to be significantly associated with the early onset of psoriasis, but not with disease duration in this study. These traits may be seen as a consequence of psoriasis, and/or as individual traits modulating and impairing clinical course and efforts to cope with psoriasis. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

  11. Delayed-onset adrenoleukodystrophy after cerebral contusion : progressive pattern of demyelination on serial MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Kwon Ha; Suh, Dae chul; Lee, Sang Ahm; Lee, Ho Kyu; Choi, Choong Gon; Yoo, Shi Joon [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-08-01

    We described serial MR findings in a 20-year-old male with adrenoleuko-dystrophy who presented progressive neurologic deterioration after cerebral contusion. On MR imaging, progressive demyelination was predominant in the white matter of the right temporal lobe as well as tn the parietalobe at the site of prior trauma and exteded into the contralateral hemisphere through the anterior commissure.

  12. Early-onset multisystem degeneration with central motor, autonomic and optic nerve disturbances: unusual Riley-Day syndrome or new clinical entity?

    Science.gov (United States)

    Schnitzler, A; Witte, O W; Kunesch, E; Freund, H J; Benecke, R

    1998-02-05

    We report a 21-year-old woman presenting with a slowly progressive tetraparesis, optic nerve atrophy on both sides, and autonomic disturbances since early childhood. The patient has been carefully followed up for 5 years with clinical and ancillary investigations. The results and the time course strongly suggest an underlying degenerative syndrome affecting parts of three major systems: autonomic, motor and visual. Some symptoms resemble familial dysautonomia (FD, Riley-Day syndrome), however, hallmarks of FD, such as absence of fungiform papillae of the tongue, abnormal reaction on intradermal histamine injection, absent tendon reflexes, are missing, and central motor disturbances have not been described in FD. We consider this syndrome a slowly progressive multisystemic degeneration with two unusual hitherto unreported features: the combination of affected systems (autonomic and motor systems, optic nerves), and the early onset.

  13. A porcine early-onset scoliosis model created using a posterior mini-invasive method: a pilot study.

    Science.gov (United States)

    Zheng, Xin; Sun, Xu; Qiu, Yong; Zhu, Ze-Zhang; Bin, Wang; Ding, Yi-Tao; Qian, Bang-Ping

    2014-12-01

    An animal study. To create a reliable porcine scoliosis model representative of early-onset scoliosis (EOS) without violation of the vertebral elements along the curve. To develop new nonfusion techniques for the treatment of EOS, a reliable large animal model with remarkable growth potential is required. However, a long tethering period which consumed the majority of the rapid growth phase or violation of the vertebral elements was thought to be essential in most of the previous models. Therefore, these models may be suboptimal for mimics of human EOS which was usually idiopathic type without vertebral anomalies. This study included 12 female Yorkshire pigs (aged, 5-6 wk; weight, 5-7 kg) in which scoliosis was created by posterior asymmetric tethering from T5 to L3. At the index surgery, 3 separate incisions were preformed, and ipsilateral rib tethering from the 10th to the 13th rib was performed while maintaining the vertebral elements along the maximal curve in a pristine state. Progressive deformity was documented with monthly radiographs. Frontal and sagittal profiles were assessed using the Cobb method. After an 8-week tethering period, the whole instrumentations were removed, and the pigs were observed for an additional 8-week period with serial radiographs to document the progression of the deformity. Of the 12 pigs enrolled in this study, 2 encountered substantial complications (1 developed a postoperative infection, and the other experienced prolonged postoperative weakness). Of the 10 available for analysis, all pigs developed rapidly progressive, structurally 3-dimensional, idiopathic-type curves with convex to the right in the lower thoracic spine. The mean coronal Cobb angle was 29 degrees immediately postoperatively and progressed to 65 degrees after the 8-week tethering period. Eight weeks after removal of the tether, the scoliosis continued to progress and averaged 68 degrees (range, 58-78 degrees). On the sagittal plane, a mean lordosis of 32

  14. Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer.

    Science.gov (United States)

    Coté, Michele L; Kardia, Sharon L R; Wenzlaff, Angela S; Ruckdeschel, John C; Schwartz, Ann G

    2005-06-22

    Evidence exists that lung cancer aggregates in families and recent findings of a chromosomal region linked to lung cancer susceptibility support a genetic component to risk. Family studies of early-onset lung cancer patients offer a unique opportunity to evaluate lifetime risk of lung cancer in relatives. To measure lung cancer aggregation and estimate lifetime risk among relatives of early-onset cases and population-based controls. Familial aggregation and cumulative risk estimates from interview data of incident cases and concurrently ascertained controls between 1990 and 2003 in metropolitan Detroit, Mich. The study included 7576 biological mothers, fathers, and siblings of 692 early-onset cases and 773 frequency-matched controls. One third of the population was black. Cumulative lifetime risk of lung cancer, stratified by race and smoking behavior in relatives of early-onset cases and controls. Smokers with a family history of early-onset lung cancer in a first-degree relative had a higher risk of developing lung cancer with increasing age than smokers without a family history. An increase in risk occurs after age 60 years in these individuals, with 17.1% (SE 2.4%) of white case relatives and 25.1% (SE 5.8%) of black case relatives diagnosed with lung cancer by age 70 years. Relatives of black cases were at statistically significant increased risk of lung cancer compared with relatives of white cases (odds ratio, 2.07, 95% confidence interval, 1.29-3.32) after adjusting for age, sex, pack-years, pneumonia, and chronic obstructive lung disease. First-degree relatives of black individuals with early-onset lung cancer have greater risk of lung cancer than their white counterparts, and these risks are further amplified by cigarette smoking. These data provide estimates of lung cancer risk that can be used to offer counseling to family members of patients with early-onset lung cancer.

  15. Early lessons from the recent-onset rheumatoid arthritis cohort ESPOIR.

    Science.gov (United States)

    Combe, Bernard; Rincheval, Nathalie

    2015-01-01

    ESPOIR is a French multicenter cohort of patients with undifferentiated arthritis enrolled within six months of symptom onset, naive to disease-modifying antirheumatic drugs and corticosteroid therapy, and either having rheumatoid arthritis (RA) or being at risk for progression to RA. The cohort is sponsored by the French Society for Rheumatology (Société française de rhumatologie [SFR]). Between December 2002 and March 2005, 813 patients were enrolled at 14 regional university hospitals, with the participation of a network of community-based rheumatologists. The objective was to establish a database on recent-onset inflammatory joint disease and, more specifically, on RA to serve for scientific research in the clinical, epidemiological, pathophysiological, and healthcare-cost fields. Ten years after enrolment were started, the cohort still has about 500 patients. The scientific committee has approved 104 clinical research projects, of which many are ongoing, and 54 original articles written by numerous French and international groups have been published. These projects cover a vast spectrum of topics including environmental factors, diagnosis, outcomes, prognosis, disease evaluation, imaging, genetics, biomarkers, costs, and RA management strategies. Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  16. Reduced Expression of FOXP3 and Regulatory T-Cell Function in Severe Forms of Early-onset Autoimmune Enteropathy

    NARCIS (Netherlands)

    Moes, Nicolette; Rieux-Laucat, Frederic; Begue, Bernadette; Verdier, Julien; Neven, Benedicte; Patey, Natacha; Torgerson, Troy T.; Picard, Capucine; Stolzenberg, Marie-Claude; Ruemmele, Corinne; Rings, Edmond Hhm; Casanova, Jean-Laurent; Piloquet, Hugues; Biver, Armand; Breton, Anne; Ochs, Hans D.; Hermine, Olivier; Fischer, Alain; Goulet, Olivier; Cerf-Bensussan, Nadine; Ruemmele, Frank M.

    BACKGROUND & AIMS: Little is known about the pathophysiology of early onset forms of autoimmune enteropathy (AIE). AIE has been associated with mutations in FOXP3-a transcription factor that controls regulatory T-cell development and function. We analyzed the molecular basis of neonatal or early

  17. Construct Validity and Reliability of the SARA Gait and Posture Sub-scale in Early Onset Ataxia

    NARCIS (Netherlands)

    Lawerman, Tjitske F.; Brandsma, Rick; Verbeek, Renate J.; van der Hoeven, Johannes H.; Lunsing, Roelineke J.; Kremer, Hubertus P. H.; Sival, Deborah A.

    2017-01-01

    Aim: In children, gait and posture assessment provides a crucial marker for the early characterization, surveillance and treatment evaluation of early onset ataxia (EOA). For reliable data entry of studies targeting at gait and posture improvement, uniform quantitative biomarkers are necessary.

  18. Cardiac acceleration at the onset of exercise: a potential parameter for monitoring progress during physical training in sports and rehabilitation.

    Science.gov (United States)

    Hettinga, Florentina J; Monden, Paul G; van Meeteren, Nico L U; Daanen, Hein A M

    2014-05-01

    There is a need for easy-to-use methods to assess training progress in sports and rehabilitation research. The present review investigated whether cardiac acceleration at the onset of physical exercise (HRonset) can be used as a monitoring variable. The digital databases of Scopus and PubMed were searched to retrieve studies investigating HRonset. In total 652 studies were retrieved. These articles were then classified as having emphasis on HRonset in a sports or rehabilitation setting, which resulted in 8 of 112 studies with a sports application and 6 of 68 studies with a rehabilitation application that met inclusion criteria. Two co-existing mechanisms underlie HRonset: feedforward (central command) and feedback (mechanoreflex, metaboreflex, baroreflex) control. A number of studies investigated HRonset during the first few seconds of exercise (HRonsetshort), in which central command and the mechanoreflex determine vagal withdrawal, the major mechanism by which heart rate (HR) increases. In subsequent sports and rehabilitation studies, interest focused on HRonset during dynamic exercise over a longer period of time (HRonsetlong). Central command, mechanoreflexes, baroreflexes, and possibly metaboreflexes contribute to HRonset during the first seconds and minutes of exercise, which in turn leads to further vagal withdrawal and an increase in sympathetic activity. HRonset has been described as the increase in HR compared with resting state (delta HR) or by exponential modeling, with measurement intervals ranging from 0-4 s up to 2 min. Delta HR was used to evaluate HRonsetshort over the first 4 s of exercise, as well as for analyzing HRonsetlong. In exponential modeling, the HR response to dynamic exercise is biphasic, consisting of fast (parasympathetic, 0-10 s) and slow (sympathetic, 1-4 min) components. Although available studies differed largely in measurement protocols, cross-sectional and longitudinal training studies showed that studies analyzing HRonset

  19. The Cache County Study on Memory in Aging: factors affecting risk of Alzheimer's disease and its progression after onset.

    Science.gov (United States)

    Tschanz, Joann T; Norton, Maria C; Zandi, Peter P; Lyketsos, Constantine G

    2013-12-01

    The Cache County Study on Memory in Aging is a longitudinal, population-based study of Alzheimer's disease (AD) and other dementias. Initiated in 1995 and extending to 2013, the study has followed over 5,000 elderly residents of Cache County, Utah (USA) for over twelve years. Achieving a 90% participation rate at enrolment, and spawning two ancillary projects, the study has contributed to the literature on genetic, psychosocial and environmental risk factors for AD, late-life cognitive decline, and the clinical progression of dementia after its onset. This paper describes the major study contributions to the literature on AD and dementia.

  20. Comparison of risk factors and perinatal outcomes in early onset and late onset preeclampsia: A cohort based study in Reunion Island.

    Science.gov (United States)

    Iacobelli, Silvia; Bonsante, Francesco; Robillard, Pierre-Yves

    2017-09-01

    Clinical differences, maternal risk factors and pregnancy outcomes of deliveries complicated by early- (deliverypregnancies). The overall preeclampsia rate in singleton pregnancies was 2.37%. Early- and late-onset preeclampsia rates were 0.75% and 1.5% respectively, and the trend for each type of disease was stable over time. In both form of preeclampsia, smoking during pregnancy was a protective factor and associated risk factors were: older age, primiparity, pre-existing diabetes, chronic hypertension, higher pre-pregnancy body mass index and obesity, infertility treatment, history of renal disease and hypercholesterolemia (all poffspring outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Incremental value of copeptin in suspected acute myocardial infarction very early after symptom onset.

    Science.gov (United States)

    Stallone, Fabio; Schoenenberger, Andreas W; Puelacher, Christian; Rubini Gimenez, Maria; Walz, Brigitte; Naduvilekoot Devasia, Allwin; Bergner, Michael; Twerenbold, Raphael; Wildi, Karin; Reichlin, Tobias; Hillinger, Petra; Erne, Paul; Mueller, Christian

    2016-09-01

    Patients presenting very early after chest pain onset may provide a diagnostic challenge even when using a high-sensitivity cardiac troponin (hs-cTnT). We hypothesized that in these patients the incremental value of copeptin in the early diagnosis of acute myocardial infarction (AMI) may be substantial. We aimed to investigate the incremental value of copeptin in a pre-specified subgroup analysis of patients presenting with suspected AMI to the emergency department within 2 hours of symptom onset in a multicenter study. Copeptin was measured in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis using all available clinical informations, including high-sensitivity cardiac troponin T (hs-cTnT). Overall, 2000 patients were enrolled, of whom 519 (26%) arrived within 2 hours of symptom onset. Of these, 102 patients (20%) had an AMI. The additional use of copeptin did not increase diagnostic accuracy as quantified by the area under the receiver-operating characteristic curve (AUC) of hs-cTnT (0.87 (95% confidence interval (CI): 0.83-0.90) for hs-cTnT alone to 0.86 (95% CI: 0.82-0.90) for the combination; p = NS). Copeptin (using 9 pmol/L as a cut-off) increased the negative predictive value (NPV) of hs-cTnT (using 14 ng/L as a cut-off) alone from 93% (95% CI: 90-95%) to 96% (95% CI: 93-98%). The NPV for the combination of hs-cTnT and copeptin was lower in patients arriving in the first 2 hours than in those arriving after 2 hours: 96% (95% CI: 93-98%) versus 99% (95% CI: 99-100%), respectively. The additional use of copeptin on top of hs-cTnT seems to lead to a small increase in NPV, but no increase in AUC. Routine use of copeptin in early presenters does not seem warranted. © The European Society of Cardiology 2016.

  2. Progressive Erosion of β-Cell Function Precedes the Onset of Hyperglycemia in the NOD Mouse Model of Type 1 Diabetes

    Science.gov (United States)

    Ize-Ludlow, Diego; Lightfoot, Yaima L.; Parker, Matthew; Xue, Song; Wasserfall, Clive; Haller, Michael J.; Schatz, Desmond; Becker, Dorothy J.; Atkinson, Mark A.; Mathews, Clayton E.

    2011-01-01

    OBJECTIVE A progressive decline in insulin responses to glucose was noted in individuals before the onset of type 1 diabetes. We determined whether such abnormalities occurred in prediabetic NOD mice—the prototypic model for human type 1 diabetes. RESEARCH DESIGN AND METHODS Morning blood glucose was measured every other day in a cohort of NOD females. Glucose tolerance and insulin secretion were measured longitudinally by intraperitoneal glucose tolerance tests in NOD/ShiLtJ and BALB/cJ mice 6 to 14 weeks of age. Arginine-stimulated insulin secretion and insulin sensitivity were assessed during intraperitoneal arginine or intraperitoneal insulin tolerance tests. RESULTS During prediabetes, NOD females displayed a progressive increase in glucose levels followed by an acute onset of hyperglycemia. First-phase insulin responses (FPIRs) during the intraperitoneal glucose tolerance test (IPGTT) declined before loss of glucose tolerance in NOD. The failure of FPIR could be detected, with a decline in peak insulin secretion during IPGTT. Arginine-stimulated insulin secretion remained unchanged during the study period. The decline in insulin secretion in NOD mice could not be explained by changes in insulin sensitivity. CONCLUSIONS There was an impressive decline in FPIR before changes in glucose tolerance, suggesting that impairment of FPIR is an early in vivo marker of progressive β-cell failure in NOD mice and human type 1 diabetes. We portend that these phenotypes in NOD mice follow a similar pattern to those seen in humans with type 1 diabetes and validate, in a novel way, the importance of this animal model for studies of this disease. PMID:21659497

  3. Early onset dementia: characteristics in a large cohort from academic memory clinics.

    Science.gov (United States)

    Picard, Candice; Pasquier, Florence; Martinaud, Olivier; Hannequin, Didier; Godefroy, Olivier

    2011-01-01

    To describe the characteristics of early-onset dementia (EOD) in a cohort from 3 memory clinics. We assessed all patients with dementia referred to the Academic Memory Clinics at Amiens, Lille, and Rouen University Medical Centers between 2005 and 2007. Patients aged less than 65 years at the time of onset of symptom were included in the EOD group, whereas older patients were included in the late-onset dementia (LOD) group. Three thousand four hundred and seventy-three patients (including 1932 women) were included and 811 (23.4%) were classified as EOD. The sex ratio was 1.12, whereas women were overrepresented in LOD (P=0.001). Patients with EOD were more frequently (P=0.001) living at home (87.3%), they had a lower educational level than the general population (P=0.0001) but were more educated (P=0.001). The current Mini Mental State Examination did not differ (P=0.3) between EOD (18.6±7.6) and LOD (18.9±6). The most common causes of EOD were Alzheimer's (22.3%) and vascular (15.9%) diseases and 4 pathologies that were significantly more frequent (P=0.001) than in the LOD group: frontotemporal dementia (9.7%), alcohol-related dementia (9.4%), traumatic brain injury (3.8%), and Huntington's disease (3%). EOD is characterized by specific features and different causes although Alzheimer's and vascular dementias remain the main causes of dementia in EOD.

  4. Slowly progressive hemiparesis in childhood as a consequence of Rasmussen encephalitis without or with delayed-onset seizures.

    Science.gov (United States)

    Bien, C G; Elger, C E; Leitner, Y; Gomori, M; Ran, B; Urbach, H; Wilken, B; Korn-Lubetzki, I

    2007-04-01

    Five young children developed slowly progressive hemiparesis as the initial manifestation of Rasmussen encephalitis (RE). Three have remained seizure free over an observational period of 1.3-1.9 years. In the remaining two patients, seizures occurred after 0.5 and 0.6 years respectively. We suggest that RE might be presently underdiagnosed and should be suspected in cases of new onset hemiparesis. In this series, three out of five patients showed oligoclonal bands on examination of cerebrospinal fluid (CSF) which represented additional diagnostic hints towards an immune-mediated condition. According to recently published formal diagnostic criteria, evidence of progressive cerebral hemiatrophy or bioptic identification of RE-typical inflammation confirms the diagnosis in such cases. Long-term immunotherapy is recommended in order to prevent further tissue loss and functional decline.

  5. The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

    DEFF Research Database (Denmark)

    Yde, C W; Olsen, B B; Meek, D

    2008-01-01

    Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC...... interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found...... regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.Oncogene advance online publication, 12 May 2008; doi:10.1038/onc.2008.146....

  6. Early energy deficit in Huntington disease: identification of a plasma biomarker traceable during disease progression.

    Directory of Open Access Journals (Sweden)

    Fanny Mochel

    Full Text Available Huntington disease (HD is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1H NMR spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA, valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide.

  7. A randomized controlled trial of two primary school intervention strategies to prevent early onset tobacco smoking.

    Science.gov (United States)

    Storr, Carla L; Ialongo, Nicholas S; Kellam, Sheppard G; Anthony, James C

    2002-03-01

    In this article, we examine the impact of two universal, grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence. The classroom-centered (CC) intervention was designed to reduce the risk for tobacco smoking by enhancing teachers' behavior management skills in first grade and, thereby, reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use. The family-school partnership (FSP) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents' child behavior management strategies. A cohort of 678 urban, predominately African-American, public school students were randomly assigned to one of three Grade 1 classrooms at entrance to primary school (age 6). One classroom featured the CC intervention, a second the FSP intervention, and the third served as a control classroom. Six years later, 81% of the students completed audio computer-assisted self-interviews. Relative to controls, a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms (26% versus 33%) (adjusted relative risk for CC/control contrast=0.57, 95% confidence interval (CI), 0.34-0.96; adjusted relative risk for FSP/control contrast=0.69, 95% CI, 0.50-0.97). Results lend support to targeting the early antecedent risk behaviors for tobacco smoking.

  8. Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of Contracture.

    Science.gov (United States)

    Lee, Younggun; Lee, Jung Hwan; Park, Hyung Jun; Choi, Young Chul

    2017-10-01

    The early diagnosis of LMNA-associated muscular dystrophy is important for preventing sudden arrest related to cardiac conduction block. However, diagnosing early-onset Emery-Dreifuss muscular dystrophy (EDMD) with later involvement of contracture and limb-girdle muscular dystrophy type 1B is often delayed due to heterogeneous clinical presentations. We aimed to determine the clinical features that contribute to a delayed diagnosis. We reviewed four patients who were recently diagnosed with LMNA-associated muscular dystrophy by targeted exome sequencing and who were initially diagnosed with nonspecific or other types of muscular dystrophy. Certain clinical features such as delayed contracture involvement and calf hypertrophy were found to contribute to a delayed diagnosis. Muscle biopsies were not informative for the diagnosis in these patients. Genetic testing of single or multiple genes is useful for confirming a diagnosis of LMNA-associated muscular dystrophy. Even EDMD patients could experience the later involvement of contracture, so clinicians should consider early genetic testing for patients with undiagnosed muscular dystrophy or laminopathy.

  9. Concordance of bioactive vs. total immunoreactive serum leptin levels in children with severe early onset obesity

    Science.gov (United States)

    Stanik, Juraj; Kratzsch, Jürgen; Landgraf, Kathrin; Scheuermann, Kathrin; Spielau, Ulrike; Gausche, Ruth; Gasperikova, Daniela; Kiess, Wieland

    2017-01-01

    Context Leptin secreted from adipose tissue signals peripheral energy status to the brain. Monogenic leptin deficiency results in severe early onset obesity with hyperphagia. Recently, a similar phenotype of inactivating leptin mutations but with preserved immunoreactivity and hence normal circulating immunoreactive leptin has been reported. Objective We aimed to evaluate the proportion of bioactive leptin serum levels (compared to immunoreactive leptin) as a biomarker for the screening of leptin gene mutations causing monogenic obesity. Furthermore, we aimed to compare the immunoreactive and bioactive leptin levels associations with parameters of insulin resistance and insulin secretion in obese children and adolescents. Patients and methods We measured bioactive and immunoreactive leptin levels by enzyme-linked immunosorbent assays in fasting serum samples of 70 children with severe (BMI SDS >3) non-syndromic obesity with onset obesity cohort (n = 1204). Sanger sequencing of the leptin gene was performed in probands with proportion of bioactive/immunoreactive leptin obesity, we did not identify leptin gene mutations leading to decreased proportion of bioactive leptin. Nevertheless, the bioactive leptin levels were stronger associated with selected insulin secretion/resistance indices than the immunoreactive leptin levels. PMID:28542631

  10. Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    Kh. S. Khaertynov

    2017-01-01

    Full Text Available Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS, as well as those with early onset of sepsis (EOS, had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted.

  11. Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis.

    Science.gov (United States)

    Khaertynov, Kh S; Boichuk, S V; Khaiboullina, S F; Anokhin, V A; Andreeva, A A; Lombardi, V C; Satrutdinov, M A; Agafonova, E A; Rizvanov, A A

    2017-01-01

    Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS), as well as those with early onset of sepsis (EOS), had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted.

  12. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum.

    Science.gov (United States)

    Campion, D; Dumanchin, C; Hannequin, D; Dubois, B; Belliard, S; Puel, M; Thomas-Anterion, C; Michon, A; Martin, C; Charbonnier, F; Raux, G; Camuzat, A; Penet, C; Mesnage, V; Martinez, M; Clerget-Darpoux, F; Brice, A; Frebourg, T

    1999-09-01

    To determine the prevalence of early-onset Alzheimer disease (EOAD) and of autosomal dominant forms of EOAD (ADEOAD), we performed a population-based study in the city of Rouen (426,710 residents). EOAD was defined as onset of disease at age <61 years, and ADEOAD was defined as the occurrence of at least three EOAD cases in three generations. Using these stringent criteria, we calculated that the EOAD and ADEOAD prevalences per 100,000 persons at risk were 41.2 and 5.3, respectively. We then performed a mutational analysis of the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) in 34 families with ADEOAD ascertained in France. In 19 (56%) of these families, we identified 16 distinct PSEN1 missense mutations, including 4 (Thr147Ile, Trp165Cys, Leu173Trp, and Ser390Ile) not reported elsewhere. APP mutations, including a novel mutation located at codon 715, were identified in 5 (15%) of the families. In the 10 remaining ADEOAD families and in 9 additional autosomal dominant Alzheimer disease families that did not fulfill the strict criteria for ADEOAD, no PSEN1, PSEN2, or APP mutation was identified. These results show that (1) PSEN1 and APP mutations account for 71% of ADEOAD families and (2) nonpenetrance at age <61 years is probably infrequent for PSEN1 or APP mutations.

  13. Low Prevalence and Clinical Effect of Vascular Risk Factors in Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Chen, Yaohua; Sillaire, Adeline Rollin; Dallongeville, Jean; Skrobala, Emilie; Wallon, David; Dubois, Bruno; Hannequin, Didier; Pasquier, Florence

    2017-01-01

    Determinants of early-onset Alzheimer's disease (EOAD) are not well known. In late-onset AD, vascular risk factors (VRFs) are associated with earlier clinical manifestation. The objective of this study was to assess the putative association between VRFs and EOAD. We studied participants with dementia meeting criteria for EOAD (recruited into the French CoMAJ prospective cohort study from 1 June 2009 to 28 February 2014) and age-, gender-matched controls (ratio 1:3, drawn randomly from the French MONA-LISA population-based survey between 2005 and 2007). Demographic data, VRFs, comorbidities, treatments, and APOE genotypes were compared in multivariable logistic regression analyses. We studied 102 participants with dementia (mean±standard deviation age: 59.5±3.8; women: 59.8%) and 306 controls. Compared with controls, EOAD participants had spent less time in formal education (9.9±2.9 versus 11.7±3.8 y; p dementia than in controls (50% versus 29.4%; p = 0.0002), as was the prevalence of depression (48% versus 32%; p testing should be considered more frequently in the context of EOAD.

  14. Mutations, associated with early-onset Alzheimer's disease, discovered in Asian countries.

    Science.gov (United States)

    Bagyinszky, Eva; Youn, Young Chul; An, Seong Soo A; Kim, SangYun

    2016-01-01

    Alzheimer's disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People's Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People's Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.

  15. Early-onset familial lewy body dementia with extensive tauopathy: a clinical, genetic, and neuropathological study.

    Science.gov (United States)

    Clarimón, Jordi; Molina-Porcel, Laura; Gómez-Isla, Teresa; Blesa, Rafael; Guardia-Laguarta, Cristina; González-Neira, Anna; Estorch, Montserrat; Ma Grau, Josep; Barraquer, Lluís; Roig, Carles; Ferrer, Isidre; Lleó, Alberto

    2009-01-01

    We describe a Spanish family in which 3 of 4 siblings had dementia with Lewy bodies, 2 of them starting at age 26 years and the other at 29 years. The father has recently been diagnosed with Lewy body disease, with onset at 77 years. Neuropathological examination of the brain of the index patient disclosed unusual features characterized by diffuse Lewy body disease and generalized neurofibrillary tangle pathology but with no amyloid deposits in any region. Moreover, Lewy body pathology colocalized with neurofibrillary tangles in most affected neurons. Mutation screening that included all coding exons of presenilin 1 (PSEN1), presenilin 2 (PSEN2), alpha-synuclein (SNCA), beta-synuclein (SNCB), microtubule-associated protein tau (MAPT), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and exons 16 and 17 of the amyloid precursor protein (APP) genes did not identify any mutation. Genome-wide single nucleotide polymorphism was performed in 4 family members and ruled out any pathogenic duplication or deletion in the entire genome. In summary, we report a unique family with pathologically confirmed early-onset dementia with Lewy bodies with widespread tau and alpha-synuclein deposition. The absence of mutations in genes known to cause Lewy body disease suggests that a novel locus or loci are implicated in this neurodegenerative disease.

  16. Early Onset of Sexual Intercourse and Parental Incarceration among African American Youth Living in Urban Public Housing.

    Science.gov (United States)

    Nebbitt, Von E; Voisin, Dexter R; Tirmazi, M Taqi

    2017-02-01

    Mass incarceration, substance use, and adolescent early onset of sex (e.g., initiate sexual intercourse at 13 years of age or younger) are social problems with disparate impacts on low-income African American communities. Two out of every five inmates in state and federal prisons are African American and the vast majority of these inmates are from low-income communities. Furthermore, this population experiences more severe consequences of substance use and abuse compared to other populations. In sum, African American youth endure the lion share of problems that mass incarceration and substance use leave in their wake. It is likely that the early onset of sex reported by African American youth in national data is related to mass incarceration and substance use in their communities. Using a sample of 142 African American youth, this paper assesses whether parental incarceration or substance, or both, are related to the likelihood of early onset of sex. Analytic procedures included chi-square and sequential logistic regression. The sample reported a mean age of 19 and 36% reported early onset of sex. Being male, paternal incarcerated, and maternal alcohol problems were associated with an increased likelihood of early onset of sex. Results point to a need for supportive services for the children of incarcerated parents, particularly those living in urban public housing developments.

  17. Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Cristino de Albuquerque

    2015-01-01

    Full Text Available The spinocerebellar ataxias (SCA are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7 is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

  18. Longitudinal follow-up to evaluate speech disorders in early-treated patients with infantile-onset Pompe disease.

    Science.gov (United States)

    Zeng, Yin-Ting; Hwu, Wuh-Liang; Torng, Pao-Chuan; Lee, Ni-Chung; Shieh, Jeng-Yi; Lu, Lu; Chien, Yin-Hsiu

    2017-05-01

    Patients with infantile-onset Pompe disease (IOPD) can be treated by recombinant human acid alpha glucosidase (rhGAA) replacement beginning at birth with excellent survival rates, but they still commonly present with speech disorders. This study investigated the progress of speech disorders in these early-treated patients and ascertained the relationship with treatments. Speech disorders, including hypernasal resonance, articulation disorders, and speech intelligibility, were scored by speech-language pathologists using auditory perception in seven early-treated patients over a period of 6 years. Statistical analysis of the first and last evaluations of the patients was performed with the Wilcoxon signed-rank test. A total of 29 speech samples were analyzed. All the patients suffered from hypernasality, articulation disorder, and impairment in speech intelligibility at the age of 3 years. The conditions were stable, and 2 patients developed normal or near normal speech during follow-up. Speech therapy and a high dose of rhGAA appeared to improve articulation in 6 of the 7 patients (86%, p = 0.028) by decreasing the omission of consonants, which consequently increased speech intelligibility (p = 0.041). Severity of hypernasality greatly reduced only in 2 patients (29%, p = 0.131). Speech disorders were common even in early and successfully treated patients with IOPD; however, aggressive speech therapy and high-dose rhGAA could improve their speech disorders. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  19. Time perspective and early-onset substance use: a model based on stress-coping theory.

    Science.gov (United States)

    Wills, T A; Sandy, J M; Yaeger, A M

    2001-06-01

    This research tested the relation of time perspective to early-onset substance use (tobacco, alcohol, and marijuana) with a sample of 454 elementary school students with a mean age of 11.8 years. An adaptation of the Zimbardo Time Perspective Inventory (P. G. Zimbardo & J. N. Boyd, 1999) was administered with measures derived from stress-coping theory. Independent effects showed future orientation inversely related to substance use and present orientation positively related to substance use. Structural modeling analysis indicated that the relation of time perspective measures to substance use was indirect, mediated through behavioral coping and anger coping. Proximal factors for substance use were negative affect, peer substance use, and resistance efficacy. Results are discussed with respect to epigenetic models and the role of executive functions in self-control ability.

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

    Directory of Open Access Journals (Sweden)

    Aksay SS

    2014-11-01

    Full Text Available Suna Su Aksay, Lucrezia Hausner, Lutz Frölich, Alexander Sartorius Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Abstract: Dementia-related behavioral disturbances are mostly treated with antipsychotics; however, the observed beneficial effects are modest and the risk of serious adverse effects high. We report the case of a 57-year-old woman with severe early-onset Alzheimer’s disease and severe agitation, whom we treated with electroconvulsive therapy (ECT. A significant clinical improvement was achieved over eight ECT sessions, which were tolerated well without cognitive worsening, and lasted approximately 3 months. Our case demonstrates the safe and effective use of ECT in pharmacotherapy-resistant severe agitation in Alzheimer’s disease. The risk–benefit profile of ECT for dementia-related agitation should be further investigated in clinical trials. Keywords: dementia, electroconvulsive therapy, cognition, emotional distress, disinhibition.