Sample records for adult-onset obesity reveals

  1. Adult-onset obesity reveals prenatal programming of glucose-insulin sensitivity in male sheep nutrient restricted during late gestation.

    Philip Rhodes

    Full Text Available BACKGROUND: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. METHODS/PRINCIPAL FINDINGS: Pregnant sheep received adequate (1.0M; CE, n = 6 or energy restricted (0.7M diet during early (1-65 days; LEE, n = 6 or late (65-128 days; LEL, n = 7 gestation (term approximately 147 days. Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT and body composition determination by dual energy x-ray absorptiometry (DXA. All animals were then exposed to an obesogenic environment for 6-7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were 'lean' (1.5 years. Obesity revealed generalised metabolic 'inflexibility' and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulin(AUC (from 133 to 341 [s.e.d. 26] mins during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16]; LEL male vs. CE male, respectively. Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. CONCLUSIONS: This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and 'reveals' programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young

  2. Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D.

    Nguyen, K Hoa; Ande, Sudharsana R; Mishra, Suresh


    The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both, obesity-related abnormalities and m-PHB. Collectively, this data provides a proof-of-concept that obesity-associated abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D and reveals PHB as a potential susceptibility gene for T1D. PMID:26766792

  3. Ablation of NG2 proteoglycan leads to deficits in brown fat function and to adult onset obesity.

    Yunchao Chang

    Full Text Available Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O(2 consumption and CO(2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16 and peroxisome proliferator-activated receptor γ coactivator (PGC1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes.

  4. Adult-onset tic disorders

    Eapen, [No Value; Lees, AJ; Lakke, JPWF; Trimble, MR; Robertson, MM


    We report on 8 patients with adult-onset motor tics and vocalisations. Three had compulsive tendencies in childhood and 3 had a family history of tics or obsessive-compulsive behaviour. In comparison with DSM-classified, younger-onset Gilles de la Tourette syndrome, adult-onset tic disorders are mor

  5. Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma

    Pinja Ilmarinen; Tuomisto, Leena E.; Hannu Kankaanranta


    Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Genetic factors, atopy, and early respiratory tract infections are well-recognized factors predisposing to childhood-onset asthma. Adult-onset asthma is more often associated with obesity, smoking, depression, or other life-style or environmental factors, even though genetic factors and respiratory tract infections may also play a role in adult-onset disease. A...

  6. Adult onset sporadic ataxias: a diagnostic challenge

    Orlando Graziani Povoas Barsottini


    Full Text Available Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

  7. Adult onset xanthogranuloma presenting as laryngeal mass.

    Li, Shawn; Weidenbecher, Mark


    Histiocytic disorders can be classified according to the distribution pattern of the lesions and the organs involved. Non-Langerhans-cell histiocytosis is a rare group of diseases that have varied clinical presentations ranging from isolated masses to diffuse systemic eruptions. We discuss a patient who initially presented with a vocal cord lesion and was ultimately diagnosed with adult onset xanthogranuloma. PMID:26954863

  8. Adult-onset unilateral disabling pansclerotic morphea

    Adarshlata Singh


    Full Text Available Disabling pansclerotic morphea (DPM is a rare, severe, and mutilating form of morphea, involving the dermis, subcutaneous tissue, fat, muscle, and even bone. It is usually seen before the age of 14 years, with the patient complaining of arthralgia and stiffness at the time of onset. We report a case of unilateral adult-onset DPM with sparing of the face. Within a few months of onset, painful contracture deformities of the hand, elbow, and shoulder joints developed, impairing the patient′s normal daily activities. We are reporting this case because of the unusual presentation: DPM in an adult, with history of trauma in childhood and rapid onset of complications, is rare.

  9. Respiratory infections precede adult-onset asthma.

    Aino Rantala

    Full Text Available BACKGROUND: Respiratory infections in early life are associated with an increased risk of developing asthma but there is little evidence on the role of infections for onset of asthma in adults. The objective of this study was to assess the relation of the occurrence of respiratory infections in the past 12 months to adult-onset asthma in a population-based incident case-control study of adults 21-63 years of age. METHODS/PRINCIPAL FINDINGS: We recruited all new clinically diagnosed cases of asthma (n = 521 during a 2.5-year study period and randomly selected controls (n = 932 in a geographically defined area in South Finland. Information on respiratory infections was collected by a self-administered questionnaire. The diagnosis of asthma was based on symptoms and reversible airflow obstruction in lung function measurements. The risk of asthma onset was strongly increased in subjects who had experienced in the preceding 12 months lower respiratory tract infections (including acute bronchitis and pneumonia with an adjusted odds ratio (OR 7.18 (95% confidence interval [CI] 5.16-9.99, or upper respiratory tract infections (including common cold, sinusitis, tonsillitis, and otitis media with an adjusted OR 2.26 (95% CI 1.72-2.97. Individuals with personal atopy and/or parental atopy were more susceptible to the effects of respiratory infections on asthma onset than non-atopic persons. CONCLUSIONS/SIGNIFICANCE: This study provides new evidence that recently experienced respiratory infections are a strong determinant for adult-onset asthma. Reducing such infections might prevent onset of asthma in adulthood, especially in individuals with atopy or hereditary propensity to it.

  10. An unusual cause of adult onset cerebellar ataxia with hypogonadism

    Menon Ramshekhar


    Full Text Available We report an unusual case of sporadic adult onset cerebellar ataxia with hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and dysarthria along with complaints of non-development of secondary sexual characteristics and erectile dysfunction. There were complaints of intermittent diarrhea. Clinical examination revealed a pan-cerebellar syndrome with features of hypoandrogenism. No eye movement abnormalities were evident. There were signs of malabsorption. Investigations confirmed the presence of auto-antibodies found in celiac disease, and a duodenal biopsy confirmed the same. Hypoandrogenism was postulated to be due to hypergonadotropic hypogonadism which has been mentioned in a few patients of celiac disease. However, the pattern seen in our patient was of a hypogonadotropic hypogonadism. This is probably secondary to an autoimmune hypophysitis seen in some patients in the absence of other clinical manifestations. Autoantibody testing should be a diagnostic necessity in any adult with a sporadic cerebellar ataxia.

  11. Adult-onset Still's disease with vesiculopustules on the hands and feet.

    Lee, Jee Bum; Kim, Jae Wook; Lee, Shin Seok; Kim, Seong Jin; Won, Young Ho; Lee, Seung Chul


    Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology characterized by an evanescent rash, intermittent spiking high fever, arthralgia, and a variety of systemic features. We describe a 46-yr-old woman with Still s disease who presented with a 2-month history of a symmetrical vesiculopustular eruptions only on both hands and feet. Skin biopsy specimens of both vesicle and pustule revealed fibrin thrombi deposition in the small dermal vessels with litt...

  12. Adult-onset nemaline myopathy presenting as respiratory failure.

    Kelly, Emer


    Nemaline myopathy is a rare congenital myopathy that generally presents in childhood. We report a case of a 44-year-old man who presented with severe hypoxic hypercapnic respiratory failure as the initial manifestation of nemaline myopathy. After starting noninvasive ventilation, his pulmonary function test results improved substantially, and over the 4 years since diagnosis his respiratory function remained stable. There are few reported cases of respiratory failure in patients with adult-onset nemaline myopathy, and the insidious onset in this case is even more unusual. This case highlights the varied presenting features of adult-onset nemaline myopathy and that noninvasive ventilation improves respiratory function.

  13. Adult-onset bulbar ptosis in Joubert syndrome

    Burt B


    Full Text Available Benjamin Burt, Johanan Levine, Kim LeTexas Tech University, Department of Ophthalmology, Paul L Foster School of Medicine, El Paso, TexasAbstract: In this case report, we describe a case of adult-onset bulbar ptosis in a patient with Joubert syndrome. Joubert syndrome is a rare neurodevelopmental disorder with malformations in cerebellum and brainstem. Many ocular abnormalities have been noted in Joubert syndrome, but the association of this syndrome with adult-onset ptosis has not been described to date. This 24-year-old Joubert patient developed a cerebrospinal fluid cyst in her midbrain. She had signs of bilateral third nerve palsy and abducens palsy in the left eye. The bilateral central third nerve palsy causing functional blindness secondary to severe bilateral levator palsy was treated successfully with silicone sling frontalis suspension, as the seventh nerve nucleus was not involved.Keywords: Joubert syndrome, ptosis, diplopia, molar tooth formation, silicone sling implants

  14. Multimodal imaging of adult-onset foveomacular vitelliform dystrophy

    Grob, Seanna; Yonekawa, Yoshihiro; Eliott, Dean


    Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a clinically heterogeneous maculopathy that may mimic other conditions and be difficult to diagnose. It is characterized by late onset, slow progression and high variability in morphologic and functional alterations. Diagnostic evaluation should include careful ophthalmoscopy and imaging studies. The typical ophthalmoscopic findings are bilateral, asymmetric, foveal or perifoveal, yellow, solitary, round to oval elevated subretinal les...

  15. Etiopathogenesis and Therapeutic Approach to Adult Onset Acne.

    Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar


    Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14-17 years in females and 16-19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

  16. Season of Birth and Risk for Adult Onset Glioma

    Jimmy T. Efird


    Full Text Available Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive.

  17. Usual interstitial pneumonia in adult-onset still's disease

    Adult-onset still's disease (AOSD) is a multi-system inflammatory disorder of unknown origin, characterized by high spiking fevers, evanescent salmon colored rash, arthralgias or arthritis, hepatospleno-megaly, Iymphadenopathy and sore throat. It is not uncommon for AOSD to involve other organs, such as the liver, the kidney; the bone marrow and less often the lungs. Pulmonary involvement ranges from 30 to 40 % (0 to 53 %), the pulmonary manifestations of AOSD include pleurisy, acute pneumonitis and even the acute respiratory distress syndrome. We present a case of a patient with AOSD who developed an interstitial lung disease and reviewed the literature on it

  18. Clinical and MRI features of supratentorial gliomas with adult-onset epilepsy

    Although some patients with supratentorial gliomas develop epilepsy in their clinical course, the details of adult-onset epilepsy with gliomas have not been fully evaluated. This paper reports on 15 cases of supratentorial glioma with the sole symptom of adult-onset epilepsy and characterizes their clinical and MRI features. The patients, 5 males and 10 females, developed the first epilepsy at the mean age of 37 years. Generalized seizure was encountered in all cases and focal seizure alone was never seen. Seizure was satisfactorily controlled with anticonvulsants in all except 2 cases. The tumor was located in the frontal lobe (9 cases) or temporal lobe (6 cases). Histologically, there were 12 astrocytomas, 2 glioblastomas, and 1 oligoastrocytoma. Of these, 12 were benign gliomas. Surprisingly, CT scan and MRI revealed tumors larger than predicted. The abnormal intensity region was delineated most prominently on T2-weighted SE image and was broader on T2-weighted spin echo image than on T1-weighted spin echo and inversion recovery image. The authors conclude that gliomas presenting with epilepsy tend to be histologically benign, are predominantly seen in middle-aged women, and are located in the frontal and temporal lobes. Although a tumor may be large enough to be detected on CT scan or MRI, as in the present study, histological examination is needed to establish the diagnosis. Additionally, gliomas with equivocal abnormalities on CT and MRI do evolve despite further neurological deficits, so meticulous evaluation including stereotactic biopsy is the method of choice. Finally, T2-weighted SE image in the coronal plane is advocated for patients with adult-onset epilepsy to achieve accurate diagnosis and to initiate early treatment. (author)

  19. Adult Onset Still's Disease and Rocky Mountain Spotted Fever

    Paul Persad


    Full Text Available Adult Still's Disease was first described in 1971 by Bywaters in fourteen adult female patients who presented with symptoms indistinguishable from that of classic childhood Still's Disease (Bywaters, 1971. George Still in 1896 first recognized this triad of quotidian (daily fevers, evanescent rash, and arthritis in children with what later became known as juvenile inflammatory arthritis (Still, 1990. Adult Onset Still's Disease (AOSD is an inflammatory condition of unknown etiology characterized by an evanescent rash, quotidian fevers, and arthralgias. Numerous infectious agents have been associated with its presentation. This case is to our knowledge the first presentation of AOSD in the setting of Rocky Mountain Spotted Fever. Although numerous infectious agents have been suggested, the etiology of this disorder remains elusive. Nevertheless, infection may in fact play a role in triggering the onset of symptoms in those with this disorder. Our case presentation is, to our knowledge, the first case of Adult Onset Still's Disease associated with Rocky Mountain spotted fever (RMSF.

  20. Adult-onset Still's disease: current challenges and future prospects

    Siddiqui M


    Full Text Available Mariam Siddiqui,1 Michael S Putman,2 Anisha B Dua,11Department of Rheumatology, 2Department of Internal Medicine, The University of Chicago Medical Center, Chicago, IL, USA Abstract: Adult-onset Still's disease (AOSD – a multi-systemic inflammatory condition characterized by high fevers, polyarthritis, an evanescent rash, and pharyngitis – has been a challenging condition to diagnose expediently and treat effectively. Questions remain regarding the underlying pathophysiology and etiology of AOSD. Pathognomonic diagnostic tests and reliable biomarkers remain undiscovered. Over the past decade, important progress has been made. Diagnostic criteria employing glycosylated ferritin have improved specificity. More important, novel biologic therapies have offered important clues to AOSD's underlying pathophysiology. Cytokine-specific biologic therapies have been instrumental in providing more effective treatment for disease refractory to conventional treatment. While IL-1 therapy has demonstrated efficacy in refractory disease, novel therapies targeting IL-6 and IL-18 show great promise and are currently under investigation. Keywords: adult-onset Still's disease, biomarkers, therapeutics

  1. Adult onset glycogen storage disease type II (adult onset Pompe disease): report and magnetic resonance images of two cases

    Del Gaizo, Andrew [Emory University School of Medicine, Radiology Resident, Atlanta, GA (United States); Banerjee, Sima [Emory University School of Medicine, Musculoskeletal Radiology Department, Atlanta, GA (United States); Terk, Michael [Emory University School of Medicine, Radiology, Division of Musculoskeletal Imaging, Atlanta, GA (United States)


    Glycogen storage disease type II (GSDII), also referred to as Pompe disease or acid maltase deficiency, is a rare inherited condition caused by a deficiency in acid alpha-glucosidase (GAA) enzyme activity. The condition is often classified by age of presentation, with infantile and late onset variants (Laforet et al. J Neurology 55:1122-8, 2000). Late onset tends to present with progressive proximal muscle weakness and respiratory insufficiency (Winkel et al. J Neurology 252:875-84, 2005). We report two cases of biopsy confirmed adult onset GSDII, along with key Magnetic Resonance (MR) images. (orig.)

  2. Diagnosis of congenital and adult-onset hypothyroidism in cats.

    Greco, Deborah S


    Whereas hyperthyroidism is the most common endocrine disorder in the cat, hypothyroidism is the least common feline endocrine disorder. This is a the result of several factors including low index of suspicion, rarity of the naturally occurring hypothyroidism in cats, and a lack of species specific tests for endogenous TSH and antithyroglobulin antibodies. Nonetheless, hypothyroidism does occur in cats, especially in kittens and after radioactive treatment for hyperthyroidism. The clinician should become familiar with the common presentations of congenital and adult-onset hypothyroidism in cats. In addition, some of the tests specific to dogs (such as endogenous canine TSH) may be utilized to diagnose subclinical hypothyroidism in cats. Fortunately, the treatment of feline hypothyroidism with synthetic levothyroxine is both straightforward and effective. PMID:16584030

  3. A Study Of Sporadic Adult Onset Degenerative Cerebellar Ataxias

    Sinha K K


    Full Text Available Twenty-four cases of sporadic olivo-ponto-cerebellar atrophy (OPCA of adult onset were studied over a period of two years. Results suggest that this disorder has its usual onset in the 5th and 6th decade of life with a male: female ratio of 2:1. It manifests clinically with gait ataxia in all, dysarthria, other cerebellar signs and autonomic involvement in vast majority. There were features of basal ganglia involvement in some. No known identifiable environmental cause was found and genetically they are quite distinct from the known autosomal dominant spinocerebellar ataxias though sporadic occurrence in recessive inheritance or a de novo mutation could not be ruled out completely, but it is unlikely.

  4. Associated Markers for Adult-onset Allergic Asthma

    Martín Bedolla-Barajas


    Full Text Available The clinical behavior of asthma varies with age at onset. This study was undertaken to identify associated markers of adult-onset allergic asthma (age ≥20 years.This cross-sectional study compared two groups: 58 patients with asthma onset at <20years and 66 with onset at ≥20 years. They were compared depending on results of clinical history, and body mass index (BMI, aeroallergen sensitization, total serum IgE, eosinophil count, asthma control test, and asthma severity level.Ages at first asthma episode were 10.0 ± 6.6 and 33.4 ± 10.5 (p <0.001 in the <20 and≥20 group, respectively. BMI was higher in adult asthmatic subjects (29.8 versus 27.1, P=0.017, but BMI ≥30 kg/m2 was not associated with asthma onset in ≥20 years (odds ratio [OR] = 1.56, 95% confidence interval [CI] 0.759 to 3.211; p= 0.227. After multivariate analysis, allergic rhinitis and IgE ≥150 IU/mL were negatively correlated with asthma onset in ≥20 years old (OR adjusted [ORa] = 0.255, 95% CI 0.078 to 0.837,  P= 0.024, and ORa =0.385, 95% CI 0.175 to 0.849,  p= 0.018, respectively.Adult-onset allergic asthma was not different from early-onset asthma. 

  5. Adult-Onset Vanishing White Matter Disease Due to a Novel EIF2B3 Mutation

    La Piana, Roberta; Vanderver, Adeline; van der Knaap, Marjo; Roux, Louise; Tampieri, Donatella; Brais, Bernard; Bernard, Geneviève


    Objective To report a novel mutation in the gene EIF2B3 responsible for a late-onset form of vanishing white matter disease. Design Case report. Setting University teaching hospital. Patient A 29-year-old pregnant woman with a history of premature ovarian failure and hemiplegic migraines presented with a 10-week history of progressive confusion and headaches. Magnetic resonance imaging of the brain revealed a diffuse leukoencephalopathy. Results Sequencing of the exons and intron boundaries of EIF2B3 uncovered 2 missense mutations: c.260C>T (p.Ala87Val) and c.272G>A (p.Arg91His). To our knowledge, the latter missense mutation has never been previously reported. Conclusion This is the second report of adult-onset vanishing white matter disease due to mutations in EIF2B3 and the first report of the c.272G>A (p.Arg91His) missense mutation. PMID:22312164

  6. A mouse model of adult-onset anaemia due to erythropoietin deficiency.

    Yamazaki, Shun; Souma, Tomokazu; Hirano, Ikuo; Pan, Xiaoqing; Minegishi, Naoko; Suzuki, Norio; Yamamoto, Masayuki


    Erythropoietin regulates erythropoiesis in a hypoxia-inducible manner. Here we generate inherited super-anaemic mice (ISAM) as a mouse model of adult-onset anaemia caused by erythropoietin deficiency. ISAM express erythropoietin in the liver but lack erythropoietin production in the kidney. Around weaning age, when the major erythropoietin-producing organ switches from the liver to the kidney, ISAM develop anaemia due to erythropoietin deficiency, which is curable by administration of recombinant erythropoietin. In ISAM severe chronic anaemia enhances transgenic green fluorescent protein and Cre expression driven by the complete erythropoietin-gene regulatory regions, which facilitates efficient labelling of renal erythropoietin-producing cells. We show that the majority of cortical and outer medullary fibroblasts have the innate potential to produce erythropoietin, and also reveal a new set of erythropoietin target genes. ISAM are a useful tool for the evaluation of erythropoiesis-stimulating agents and to trace the dynamics of erythropoietin-producing cells. PMID:23727690

  7. Paraplegin mutations in sporadic adult-onset upper motor neuron syndromes.

    Brugman, F.; Scheffer, H.; Wokke, J.H.; Nillesen, W.M.; Visser, M. de; Aronica, E.; Veldink, J.H.; Berg, LH van den


    OBJECTIVE: To investigate the frequency of autosomal recessive paraplegin mutations in patients with sporadic adult-onset upper motor neuron (UMN) syndromes. METHODS: We analyzed the paraplegin gene in 98 Dutch patients with a sporadic adult-onset UMN syndrome. Inclusion criteria were a progressive

  8. Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

    de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.


    This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

  9. Comparing endophenotypes in adult-onset primary torsion dystonia.

    Bradley, David


    Adult-onset primary torsion dystonia (AOPTD) has an autosomal dominant pattern of inheritance with markedly reduced penetrance; the genetic causes of most forms of AOPTD remain unknown. Endophenotypes, markers of sub-clinical gene carriage, may be of use detecting non-manifesting gene carriers in relatives of AOPTD patients. The aim of this study was to compare the utility of the spatial discrimination threshold (SDT) and temporal discrimination threshold (TDT) as potential endophenotypes in AOPTD. Data on other published candidate endophenotypes are also considered. Both SDT and TDT testing were performed in 24 AOPTD patients and 34 of their unaffected first degree relatives; results were compared with normal values from a control population. Of the 24 AOPTD patients 5 (21%) had abnormal SDTs and 20 (83%) had abnormal TDTs. Of the 34 first degree relatives 17 (50%) had abnormal SDTs and 14 (41%) had abnormal TDTs. Discordant results on SDT and TDT testing were found in 16 (67%) AOPTD patients and 21 (62%) first degree relatives. TDT testing has superior sensitivity compared to SDT testing in AOPTD patients; although false positive TDTs are recognised, the specificity of TDT testing in unaffected relatives is not determinable. The high level of discordance between the two tests probably relates methodological difficulties with SDT testing. The SDT is an unreliable AOPTD endophenotype; TDT testing fulfils criteria for a reliable endophenotype with a high sensitivity.

  10. Anti-Interleukin-1 Agents in Adult Onset Still's Disease

    Cecilia Giampietro


    Full Text Available Interleukin 1β (IL-1β is emerging as a master mediator of adult onset Still’s disease (AOSD pathogenesis. This pleiotropic cytokine, whose expression is under the control of the inflammasome pathway, has a wide type of effects. As a key mediator of innate immunity is a potent pyrogen and facilitates neutrophilic proliferation and diapedesis into the inflamed tissues, which are key AOSD manifestations. The study of proinflammatory cytokines profiles in sera and pathological tissues of AOSD patients has shown elevated levels of IL-1β, these levels being highly correlated with disease activity and severity. These experimental evidences and the analogy with other autoinflammatory diseases that share with AOSD clinical and biological characteristics have suggested the blockade of IL-1β as a possible new therapeutic option for the AOSD, especially in conventional therapy resistant cases. Anakinra, the first anti-IL-1 agent put on the market, has demonstrated capable to induce a rapid response sustained over time, especially in systemic forms, where anti-TNFα failed to control symptoms. While a growing number of evidences supports the utilisation of anakinra in AOSD, a new generation of anti-IL1β antagonists is developing. Canakinumab and rilonacept, thanks to their higher affinity and longer half-life, could improve the management of this invalidating disease.

  11. Distinguishing adult-onset asthma from COPD: a review and a new approach

    Abramson MJ


    Full Text Available Michael J Abramson,1 Jennifer L Perret,2,3 Shyamali C Dharmage,2 Vanessa M McDonald,4 Christine F McDonald3 1School of Public Health and Preventive Medicine, Monash University, 2Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia; 3Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Australia; 4Priority Research Centre for Asthma and Respiratory Disease, University of Newcastle, Newcastle, Australia Abstract: Adult-onset asthma and chronic obstructive pulmonary disease (COPD are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene–environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2 cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes. Parenchymal destruction (emphysema in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset

  12. Memory Loss and Frontal Cognitive Dysfunction in a Patient with Adult-onset Neuronal Intranuclear Inclusion Disease.

    Araki, Kunihiko; Sone, Jun; Fujioka, Yusuke; Masuda, Michihito; Ohdake, Reiko; Tanaka, Yasuhiro; Nakamura, Tomohiko; Watanabe, Hirohisa; Sobue, Gen


    Neuronal intranuclear inclusion disease (NIID) is an uncommon progressive neurodegenerative disorder. Adult-onset NIID can result in prominent dementia. We herein describe the case of a 74-year-old man who presented with dementia, cerebellar ataxia, neuropathy, and autonomic dysfunction. Diffusion-weighted imaging showed hyperintensity of the corticomedullary junction. Fluid-attenuated inversion recovery images showed frontal-dominant white matter hyperintensity. NIID was diagnosed from the presence of intranuclear inclusions in a skin biopsy sample. Neuropsychological testing revealed memory loss and frontal cognitive dysfunction, especially in relation to language and executive functions. We were therefore able to confirm the association of NIID with cognitive dysfunction. PMID:27523009

  13. Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

    Kimmich, Okka


    Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects <50 years of age; 22 subjects >50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige\\'s syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1\\/61 (2%) control subjects, 27\\/32 (84%) patients with adult-onset primary torsion dystonia and 32\\/73 (44%) unaffected relatives [siblings (20\\/36; 56%), offspring (11\\/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.

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

    González-Méijome, José Manuel; Carracedo, Gonzalo; Ferreira, Daniela Patrícia Lopes; Ribeiro, Miguel António Faria; Matos, Sofia Cláudia Peixoto; Queirós, A.


    Purpose: To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Methods: 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 refra...

  15. Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα.

    Komatsu, Michiharu; Kimura, Takefumi; Yazaki, Masahide; Tanaka, Naoki; Yang, Yang; Nakajima, Takero; Horiuchi, Akira; Fang, Zhong-Ze; Joshita, Satoru; Matsumoto, Akihiro; Umemura, Takeji; Tanaka, Eiji; Gonzalez, Frank J; Ikeda, Shu-Ichi; Aoyama, Toshifumi


    SLC25A13 (citrin or aspartate-glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα. PMID:25533124

  16. [A case of adult-onset type II citrullinemia (CTLN2) triggered by an overseas travel].

    Yamasaki, Masayoshi; Shimada, Takuya; Hamaoka, Shima; Shibata, Masunari; Naito, Yutaka


    A 43-year-old male presented with abnormal behavior and consciousness disturbance on the day after traveling abroad and was admitted to our hospital. Laboratory tests showed hyperammonemia and hypercitrullinemia. The electro-encephalogram showed frontal dominant bilateral slow δ burst. He had a peculiar taste for nuts. But he didn't take nuts during the overseas travel for 3 days. The family history revealed that his younger brother died of a status epilepticus of unknown cause at the age of 29. These findings were compatible with hepatic encephalopathy due to adult-onset type II citrullinemia (CTLN2). Gene analysis provided a definite diagnosis of CTLN2. Diet and drug therapy have improved his condition. He is due to have liver transplantation which is the only established radical treatment for CTLN2 if his condition becomes worse. The present case shows that cessation of the habitual intake of nuts only for 3 days could lead to onset of CTLN2. PMID:25283831

  17. Case of adult-onset Coats' disease with epiretinal membrane treated with 25-gauge pars plana vitrectomy.

    Mino, Akiko; Mitamura, Yoshinori; Katome, Takashi; Semba, Kentaro; Egawa, Mariko; Naito, Takeshi


    We describe a case of untreated adult-onset Coats' disease with a proliferative epiretinal membrane (ERM) treated successfully with 25-gauge pars plana vitrectomy (25GPPV). A 26-year-old man presented with a 3-week history of decreased vision in his left eye. At the initial examination, the decimal best-corrected visual acuity (BCVA) was 0.7 in the left eye. Ophthalmoscopy revealed the typical appearance of Stage 2A Coats' disease but with a proliferative ERM in the posterior pole. The patient received 2 monthly intravitreal injections of 2.5 mg bevacizumab, 5 laser photocoagulations to the area of telangiectasia, and 1 session of cryoretinopexy. Nine months after the initial visit, a traction by the ERM on the parafoveal area developed causing macular edema which reduced the BCVA to 0.3. He underwent 25GPPV with the removal of the ERM. In addition, the peripheral telangiectasia was treated intraoperatively with both laser photocoagulation and cryoretinopexy. Postoperatively, the traction to the parafoveal area was released and the BCVA improved to 0.6 which remained stable during the follow-up period of 13 months. We conclude that 25GPPV combined with ERM peeling, laser photocoagulation, and cryoretinopexy can be effective for adult-onset Coats' disease associated with an ERM. PMID:25817290

  18. Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

    Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes


    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity. PMID:26175648

  19. Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature

    Sakoe Kumi


    Full Text Available Abstract Background Alexander disease (ALX is a rare neurological disorder characterized by white matter degeneration and cytoplasmic inclusions in astrocytes called Rosenthal fibers, labeled by antibodies against glial fibrillary acidic protein (GFAP. Three subtypes are distinguished according to age at onset: infantile (under age 2, juvenile (age 2 to 12 and adult (over age 12. Following the identification of heterozygous mutations in GFAP that cause this disease, cases of adult-onset ALX have been increasingly reported. Case Presentation We present a 60-year-old Japanese man with an unremarkable past and no family history of ALX. After head trauma in a traffic accident at the age of 46, his character changed, and dementia and dysarthria developed, but he remained independent. Spastic paresis and dysphagia were observed at age 57 and 59, respectively, and worsened progressively. Neurological examination at the age of 60 revealed dementia, pseudobulbar palsy, left-side predominant spastic tetraparesis, axial rigidity, bradykinesia and gaze-evoked nystagmus. Brain MRI showed tadpole-like atrophy of the brainstem, caused by marked atrophy of the medulla oblongata, cervical spinal cord and midbrain tegmentum, with an intact pontine base. Analysis of the GFAP gene revealed a heterozygous missense mutation, c.827G>T, p.R276L, which was already shown to be pathogenic in a case of pathologically proven hereditary adult-onset ALX. Conclusion The typical tadpole-like appearance of the brainstem is strongly suggestive of adult-onset ALX, and should lead to a genetic investigation of the GFAP gene. The unusual feature of this patient is the symmetrical involvement of the basal ganglia, which is rarely observed in the adult form of the disease. More patients must be examined to confirm, clinically and neuroradiologically, extrapyramidal involvement of the basal ganglia in adult-onset ALX.

  20. Sandhoff disease mimicking adult-onset bulbospinal neuronopathy.

    Thomas, P K; Young, E; King, R H


    A 32 year old male is described with an onset of upper limb postural tremor in adolescence followed by muscle cramps. Progressive proximal amyotrophy and weakness in the limbs developed late in the third decade. Examination disclosed, in addition, bilateral facial weakness and mild dysarthria. Enzyme studies revealed hexosaminidase A and B deficiency, indicating a diagnosis of Sandhoff disease. Intra-axonal membranocytoplasmic bodies were present in a rectal biopsy. The presentation, which resembled that of X-linked bulbospinal neuronopathy, widens the clinical spectrum for disorders related to G(M2) gangliosidosis. PMID:2795083

  1. Adult onset leukodystrophy with neuroaxonal spheroids: Clinical, neuroimaging and neuropathologic observations

    Freeman, Stefanie H.; Hyman, Bradley T.; Sims, Katherine B.; Hedley-Whyte, E. T.; Vossough, Arastoo; Frosch, Matthew P.; Schmahmann, Jeremy D.


    Pigmented orthochromatic leukodystrophy (POLD) and Hereditary diffuse leukoencephalopathy with spheroids HDLS are two adult onset leukodystrophies with neuroaxonal spheroids presenting with prominent neurobehavioral, cognitive, and motor symptoms. These are familial or sporadic disorders characterized by cerebral white matter degeneration including myelin and axonal loss, gliosis, macrophages, and axonal spheroids. We report clinical, neuroimaging and pathological correlations of four women a...

  2. Perceived stress and risk of adult-onset asthma and other atopic disorders

    Rod, N H; Kristensen, T S; Lange, Peter; Prescott, E; Diderichsen, Finn


    of adult-onset asthma, allergic rhinitis, atopic dermatitis, and asthma/bronchitis medication. METHODS: Participants (n = 9785) from the Copenhagen City Heart Study, Denmark, free of atopic disorders at baseline in 1981-1983 were asked questions on stress intensity and frequency. They were followed...

  3. [Adult-onset Hartnup disease presenting with neuropsychiatric symptoms but without skin lesions].

    Mori, E; Yamadori, A; Tsutsumi, A; Kyotani, Y


    Hartnup disease is an inborn abnormality of renal and intestinal transport involving the neutral amino acids. Intermittent pellagra-like rash, attacks of cerebellar ataxia and psychiatric disturbance are characteristic symptoms of this disease. We described here a patient with adult-onset Hartnup disease who presented unique neuropsychiatric symptoms but no dermatologic symptoms, and reported features of amino acids transport in this patient and his family. The patient, a man aged 37 years, was referred to us because of lasting daytime bruxism. He is the second child of healthy parents who are first cousin; his elder brother who has been mentally retarded became bed-ridden and died at 32 years of age. His younger brother is completely healthy. Although the patient's development in infancy has been slightly retarded, he completed compulsory 9-year education. At 29 years of age, he experienced episodes of diplopia, ataxic gait and insomnia, and at 33 years of age, of transient stupor. There had been no history of photosensitivity or dermatitis. On neurological examination, there were trunkal ataxia, increased muscular tone and decreased mental activity besides bruxism. These symptoms remained unchanged despite of several medications including trihexyphenidyl, diazepam, halloperidol, tiapride and sulpiride. Two months later, the patient became stuporous; bruxism and hypertonicity became exaggerated. Myerson's sign, sucking reflex and grasp reflex in both hand appeared. There was no dermal lesion. A cranial computed tomography revealed a small calcification in the right frontal subcortical region and a single photon emission tomography indicated possible bifrontal hypoperfusion. Electroencephalograms demonstrated non-specific slowing. Somatosensory evoked potentials and nerve conduction velocities were normal. There were constant indicanuria and amino-aciduria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2582682

  4. Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.

    Bradley, D


    Familial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16\\/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal

  5. Suppurative necrotizing granulomatous lymphadenitis in adult-onset Still’s disease: a case report

    Assimakopoulos Stelios F


    Full Text Available Abstract Introduction Lymphadenopathy is found in about 65% of patients with adult-onset Still’s disease and is histologically characterized by an intense, paracortical immunoblastic hyperplasia. Adult-onset Still’s disease has not been previously described as an etiology of suppurative necrotizing granulomatous lymphadenitis. Case presentation We describe a 27-year-old Greek man who manifested prolonged fever, abdominal pain, increased inflammatory markers, episodic skin rash and mesenteric lymphadenopathy histologically characterized by necrotizing granulomatous adenitis with central suppuration. Disease flares were characterized by systemic inflammatory response syndrome with immediate clinico-laboratory response to corticosteroids but the patient required prolonged administration of methylprednisolone at a dose of above 12mg/day for disease control. After an extensive diagnostic work-up, which ruled out any infectious, malignant, rheumatic or autoinflammatory disease the patient was diagnosed as having adult-onset Still’s disease. The patient is currently treated with 4mg of methylprednisolone, 100mg of anakinra daily and methotrexate 7.5mg for two consecutive days per week and exerts full disease remission for six months. Conclusion To the best of our knowledge this is the first report of suppurative necrotizing granulomatous lymphadenitis attributed to adult-onset Still’s disease. This case indicates that the finding of a suppurative necrotizing granulomatous lymphadenitis should not deter the consideration of adult-onset Still’s disease as a potential diagnosis in a compatible clinical context; however, the exclusion of other diagnoses is a prerequisite.

  6. Adult-Onset Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Normal Lactate: Case Report

    Özdem Ertürk


    Full Text Available Leukoencephalopathy with brain stem and spinal cord involvement and high lactate (LBSL is a recently described leukoencephalopathy with a genetically proven underlying defect. Clinical features are slowly progressive pyramidal, cerebellar and dorsal column dysfunction with childhood or rarely adult onset. The genetic basis of the disease was recently identified, which concerned mutations in the DARS2 gene encoding mitochondrial aspartly-tRNA synthetase. The disease has distinct magnetic resonance imaging findings including inhomogeneous cerebral white matter abnormalities and selective brain stem and spinal cord tract involvement. Additionally, there are usually increased lactate levels on magnetic resonance spectroscopy (MRS of the abnormal white matter. In this case report, we describe the clinical and radiological features of a patient with genetically proven adult-onset LBSL and normal lactate levels on MRS.

  7. Clinical value of serum ferritin level in the adult onset still disease

    Objective: To investigate the clinical value of serum ferritin level in the adult onset still disease. Methods: Twenty patients enrolled were all met Yamaguchi criteria for claasification of adult's Still disease,their clinical features and treatment were reviewed, and the levels of serum ferritin, blood sedimentation, C reactive protein were detected. Furthermore, the correlativity between serum ferritin and ESR, CRP was analysed. Results: Comparing with those of previous treatment, the levels of SF, ESR, CRP of post-treatment were notably lower (P<0.001). There is negative correlativity between serum ferritin and ESR, CRP (P<0.05). Conclusion: The serum ferritin will probably indicate the activity of disease. The detection of serum ferritin will be helpful to the treatment of adult onset Still disease. (authors)

  8. A population study of adult onset limb-girdle muscular dystrophy.

    Yates, J R; Emery, A E


    Complete ascertainment of adult onset limb-girdle muscular dystrophy in the Lothian Region of Scotland was attempted. Ten index cases were identified giving a prevalence of 1.3 per 100 000 (0.9 per 100 000 for cases where the diagnosis of muscular dystrophy was supported by both electromyographic and muscle biopsy findings). In these 10 sibships there had been 11 affected subjects, significantly less than the 16.5 cases expected for autosomal recessive inheritance. Excluding cases suspected o...

  9. Current social functioning in adult-onset schizophrenia and its relation with positive symptoms

    Kundu, Partha S.; Sinha, Vinod K.; Paul, Sarita E.; Pushpal Desarkar


    Background: In schizophrenia, relation exists between psychopathology and social functioning. Aim and Objectives: Determining relationship of positive symptoms with current social functioning in adult-onset (≥19 years) schizophrenia. Materials and Methods: Eighty schizophrenia patients [ICD-10-DCR], of both sexes (18-60 years), on follow-up for ≥6 months, with no change of diagnosis and without co-morbidities, having onset of illness ≥19 years of age, accompanied by informants having contact ...

  10. Predictive Medicine: Recombinant DNA Technology and Adult-Onset Genetic Disorders

    Hayden, Michael


    Genetic factors are of great importance in common adult-onset disorders such as atherosclerosis, cancer, and neuro-degenerative diseases. Advances in DNA technology now allow identification of persons at high-risk of developing some of these diseases. This advance is leading to predictive medicine. In some genetic disorders, such as those leading to atherosclerosis and cancer, identification of high-risk individuals allows intervention which alters the natural history of the disorder. In othe...

  11. Childhood psychosocial stressors and adult onset arthritis: Broad spectrum risk factors and allostatic load

    Von Korff, Michael; Alonso, Jordi; Ormel, Johan; Angermeyer, Matthais; Bruffaerts, Ronny; Fleiz, Clara; de Girolamo, Giovanni; Ronald C. Kessler; Kovess-Masfety, Viviane; Posada-Villa, Jose; Scott, Kate M.; Uda, Hidenori


    Neural, endocrine, and immune stress mediators are hypothesized to increase risks of diverse chronic diseases, including arthritis. Retrospective data from the World Mental Health Surveys (N = 18,309) were employed to assess whether adult onset of arthritis was associated with childhood adversities and early onset psychological disorder. Cox proportional hazard models assessed the association of number of childhood adversities and the presence of early onset psychological disorder with arthri...

  12. Intra-arterial Chemotherapy for Adult Onset Retinoblastoma in a 32-Year-Old Man.

    Magan, Tejal; Khoo, Chloe T L; Jabbour, Pascal M; Fuller, Dwain G; Shields, Carol L


    A 32-year-old man with active unilateral group D retinoblastoma that was recurrent following external beam radiotherapy was treated with intra-arterial chemotherapy, leading to tumor regression. Additional plaque radiotherapy and intravitreal chemotherapy were required for complete control. Final visual acuity was 20/40. In selected cases, adult-onset retinoblastoma can be managed with intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2016;53:e43-e46.]. PMID:27486894

  13. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

    Smelt, A H; Poorthuis, B J; Onkenhout, W; Scholte, H R; Andresen, B S; van Duinen, S G; Gregersen, N; Wintzen, A R


    Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade...... be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis....

  14. Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

    Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil


    OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database. PMID:27581317

  15. Niemann-Pick type C: focus on the adolescent/adult onset form.

    Di Lazzaro, Vincenzo; Marano, Massimo; Florio, Lucia; De Santis, Stefano


    Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment. PMID:26998855

  16. Adult-Onset Type 1 Diabetes and Pregnancy: Three Case Reports

    Barbara Bonsembiante


    Full Text Available From 5% to 10% of diabetic patients have type 1 diabetes. Here we describe three cases of adult-onset type 1 diabetes in pregnancy treated at our clinic between 2009 and 2012. Two patients came for specialist examination during pregnancy, the third after pregnancy. These women had no prior overt diabetes and shared certain characteristics, that is, no family diabetes history, age over 35, normal prepregnancy BMI, need for insulin therapy as of the early weeks of pregnancy, and high-titer anti-GAD antibody positivity. The patients had persistent diabetes after delivery, suggesting that they developed adult-onset type 1 diabetes during pregnancy. About 10% of GDM patients become pancreatic autoantibody positive and the risk of developing overt diabetes is higher when two or more autoantibodies are present (particularly GAD and ICA. GAD-Ab shows the highest sensitivity for type 1 diabetes prediction. We need to bear in mind that older patients might conceivably develop an adult-onset type 1 diabetes during or after pregnancy. So we suggest that women with GDM showing the described clinical features shall be preferably tested for autoimmunity. Pregnant patients at risk of type 1 diabetes should be identified to avoid the maternal and fetal complications and the acute onset of diabetes afterwards.

  17. Prognostic factors and outcomes of adult-onset hemophagocytic lymphohistiocytosis: a retrospective analysis of 34 cases

    Masafumi Oto


    Full Text Available Adult-onset hemophagocytic lymphohistiocytosis (HLH has features that are distinct from that of HLH in pediatric patients. The clinical records at the Japanese Red Cross Kumamoto Hospital were reviewed. We retrospectively analyzed 34 patients who fulfilled the diagnostic criteria of HLH-2004. The median age of patients was 60.0 (range 15-86. Underlying diseases were diagnosed in 17 patients. They consisted of malignant lymphoma (n=3, other neoplastic disease (n=3, viral infection (n=4, collagen vascular disease (n=3, Kikuchi’s disease (n=3 and drug (n=1. Underlying diseases were not diagnosed in 17 patients despite examination. The treatments were steroids (n=18, dexamethasone + cyclosporine A (CSA + etoposide (n=4, multidrug chemotherapy (n=2, steroids and CSA (n=3. Eleven patients died during observation. In a multivariate analysis, the significant predictor for death was age at onset (hazard ratio, 1.22; 95%CI, 1.02-1.44; P=0.027. Autopsy was performed in 4 cases, but the underlying disease remained unknown in 3 of those cases. Adult-onset HLH has high diversity and various outcomes. The mechanism of adult-onset HLH is not fully understood and further research is required.

  18. Dioxin (TCDD induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

    Mohan Manikkam

    Full Text Available Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

  19. The Need for Improved Detection and Management of Adult-Onset Hearing Loss in Australia

    Catherine M. McMahon


    Full Text Available Adult-onset hearing loss is insidious and typically diagnosed and managed several years after onset. Often, this is after the loss having led to multiple negative consequences including effects on employment, depressive symptoms, and increased risk of mortality. In contrast, the use of hearing aids is associated with reduced depression, longer life expectancy, and retention in the workplace. Despite this, several studies indicate high levels of unmet need for hearing health services in older adults and poor use of prescribed hearing aids, often leading to their abandonment. In Australia, the largest component of financial cost of hearing loss (excluding the loss of well-being is due to lost workplace productivity. Nonetheless, the Australian public health system does not have an effective and sustainable hearing screening strategy to tackle the problem of poor detection of adult-onset hearing loss. Given the increasing prevalence and disease burden of hearing impairment in adults, two key areas are not adequately met in the Australian healthcare system: (1 early identification of persons with chronic hearing impairment; (2 appropriate and targeted referral of these patients to hearing health service providers. This paper reviews the current literature, including population-based data from the Blue Mountains Hearing Study, and suggests different models for early detection of adult-onset hearing loss.

  20. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana


    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis. PMID:27021143

  1. Stroke prevention by direct revascularization for patients with adult-onset moyamoya disease presenting with ischemia.

    Kim, Tackeun; Oh, Chang Wan; Kwon, O-Ki; Hwang, Gyojun; Kim, Jeong Eun; Kang, Hyun-Seung; Cho, Won-Sang; Bang, Jae Seung


    . CONCLUSIONS Direct or combined revascularization for patients with adult-onset moyamoya disease presenting with ischemia can prevent further stroke. PMID:26636391

  2. Radiographic abnormalities of the wrist in adult-onset still disease: Comparison with juvenile chronic arthritis and rheumatoid arthritis

    Pericapitate involvement of the wrist has been described as characteristic of adult-onset Still disease, a relatively rare disorder that is often diagnosed by exclusion after extensive and frequently invasive tests. To evaluate the diagnostic value of carpal radiography in cases of adult-onset Still disease, a retrospective blinded analysis of 48 patients, 16 each with adult-onset Still disease, juvenile chronic arthritis, and rheumatoid arthritis, was performed. Pericapitate articular alterations without radiocarpal involvement were found to be frequent in the setting of adult-onset Still disease but distinctly unusual among patients with rheumatoid arthritis. In juvenile chronic arthritis, severe pericapitate involvement was frequent, but generally occurred in conjunction with radiocarpal joint abnormalities

  3. Predominance of Th1 cytokine in peripheral blood and pathological tissues of patients with active untreated adult onset Still's disease

    Chen, D; Lan, J; Lin, F.; Hsieh, T; Wen, M.


    Objective: To determine the type 1 T helper (Th1)/type 2 T helper (Th2) balance in the peripheral blood (PB) and pathological tissues of patients with active untreated adult onset Still's disease (AOSD).

  4. Bartonella henselae infection presenting with a picture of adult-onset Still's disease.

    Durey, Areum; Kwon, Hea Yoon; Im, Jae-Hyoung; Lee, Sun Myoung; Baek, JiHyeon; Han, Seung Baik; Kang, Jae-Seung; Lee, Jin-Soo


    We report a patient with a clinical picture of suggestive for adult-onset Still's Disease (ASOD) due to Bartonella infection. A 42-year-old immunocompetent man was admitted with fever, rash, arthralgia and sore throat. As his clinical picture suggested ASOD except unusual skin manifestation, we treated him on steroid and ibuprofen. His fever and constitutional symptoms responded immediately within 24hrs of commencing therapy, yet rash and leukocytosis remained. Meanwhile, Bartonella infection was proved by culture of bone marrow. Minocyclin treatment started combined with hydroxychloroquine sulfate and the patient discharged with overall improvement. PMID:27000538

  5. Percentage of glycosylated serum ferritin remains low throughout the course of adult onset Still's disease

    Vignes, S; Le Moel, G.; Fautrel, B.; Wechsler, B; Godeau, P; Piette, J


    OBJECTIVE—To determine the evolution of levels of total serum ferritin and percentage of the glycosylated form in patients with adult onset Still's disease (AOSD) at the time of diagnosis and during follow up.
METHODS—All patients with AOSD were tested at the time of diagnosis and during follow up. Total serum ferritin levels were analysed by immunoassay, and the percentage of glycosylated ferritin was determined by methods using Sepharose-Con A.
RESULTS—14 patients (eight women, six men) wit...

  6. Relationship between neuropsychological impairment and grey and white matter changes in adult-onset myotonic dystrophy type 1.

    Baldanzi, Sigrid; Cecchi, Paolo; Fabbri, Serena; Pesaresi, Ilaria; Simoncini, Costanza; Angelini, Corrado; Bonuccelli, Ubaldo; Cosottini, Mirco; Siciliano, Gabriele


    Myotonic dystrophy type 1 (DM1) has a wide phenotypic spectrum and potentially may affect central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and 3T-MRI protocol. GM and WM changes were evaluated calculating brain parenchymal fraction (BPF), voxel-based morphometry (VBM), white matter lesion load (LL% and Fazekas scale) and tract based spatial statistical (TBSS). Patients showed main impairment in tests exploring executive and mnesic domains with visuo-spatial involvement, significantly related to BPF. VBM revealed clusters of widespread GM reduction and TBSS revealed areas of decreased fractional anisotropy (FA) and increased radial diffusivity (RD), mean diffusivity (MD) and axial diffusivity (AD) in patients compared to a group of matched healthy controls. Multiple regression analyses showed areas of significant negative relationship between left temporal atrophy and verbal memory, between RD and mnesic and visuo-spatial cognitive domains, and between AD and verbal memory. TBSS results indicate that the involvement of normal appearance WM, beyond the signal changes detected with conventional MR imaging (Fazekas scale and LL%), was associated with neuropsychological deficit. These data suggest that disrupted complex neuronal networks can underlie cognitive-behavioural dysfunctions in DM1. PMID:27437180

  7. A unique case of pica of adult onset with interesting psychosexual aspects

    Suddhendu Chakraborty


    Full Text Available Pica has been considered as the ingestion of inedible substances or atypical food combinations. Pica has been reported widely in pediatric age group and often found to be co existing with obsessive compulsive or major depressive disorder. Reports of pica in elderly age group are relatively uncommon and rarely does it have an adult onset. In this article we present a case of adult onset pica. A young lady with unusual sensation in her abdomen was found to consume iron nails over years and there was history of dyspareunia since her marriage three months back. On query it was known that the lady is having same sex relationship over years. There unique conglomeration of cultural, psychodynamic and physiological determinants which together is responsible for this unusual habit of this lady. Moreover the onset of the disease at a late age and different psychodynamic issues make the case all the more interesting. Whether the pica is an eating disorder or obsessive compulsive disorder is still controversial. Pica has been mentioned in Diagnostic and Statistical Manual IV TR. The present case report warrants the need to look into this entity more closely with regards to its occurrence and etiology.

  8. Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype

    Hawa, Mohammed I; Kolb, Hubert; Schloot, Nanette;


    autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (>200 WHO IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P <0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than......OBJECTIVESSpecific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non-insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes.RESEARCH DESIGN AND METHODSWe...... consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30-70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A).RESULTSOf 6,156 patients, 541...

  9. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah


    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  10. Chinese new immigrant mothers' perception about adult-onset non-communicable diseases prevention during childhood.

    Wang, Linda Dong Ling; Lam, Wendy Wing Tak; Wu, Joseph Tsz Kei; Fielding, Richard


    Many non-communicable diseases (NCDs) are largely preventable via behaviour change and healthy lifestyle, which may be best established during childhood. This study sought insights into Chinese new immigrant mothers' perceptions about adult-onset NCDs prevention during childhood. Twenty-three semi-structured interviews were carried out with new immigrant mothers from mainland China who had at least one child aged 14 years or younger living in Hong Kong. Interviews were audio taped, transcribed and analysed using a Grounded Theory approach. The present study identified three major themes: perceived causes of adult NCDs, beliefs about NCDs prevention and everyday health information practices. Unhealthy lifestyle, contaminated food and environment pollution were perceived as the primary causes of adult NCDs. Less than half of the participants recognized that parents had responsibility for helping children establish healthy behaviours from an early age to prevent diseases in later life. Most participants expressed helplessness about chronic diseases prevention due to lack of knowledge of prevention, being perceived as beyond individual control. Many participants experienced barriers to seeking health information, the most common sources of health information being interpersonal conversation and television. Participants' everyday information practice was passive and generally lacked awareness regarding early prevention of adult-onset NCDs. Updated understanding of this issue has notable implications for future health promotion interventions. PMID:24842077

  11. Obesity

    Obesity means having too much body fat. It is different from being overweight, which means weighing too ... what's considered healthy for his or her height. Obesity occurs over time when you eat more calories ...

  12. A rare case of occult abdominal tuberculosis with Poncet′s disease mimicking Adult onset Still′s disease

    Isha Sood


    Full Text Available A 50-year-old female presented with fever, symmetrical arthralgias, rash, painful oral ulcerations and alopecia since 8 weeks. Examination showed mild hepatospleenomegaly. Investigations revealed leucocytosis, neutrophilia, elevated sedimentation rate and raised ferritin levels (3850 ng/ml. Computerized tomography (CT abdomen showed hepatospleenomegaly, mild ascitis and mild bilateral pleural-effusion. After ruling out occult infections, tuberculosis, malignancies and autoimmune diseases by appropriate investigations, and due to raised ferritin levels, adult onset stills disease (AOSD was diagnosed. Patient responded to oral steroids initially, but after 7 days developed severe abdominal pain. Repeat CT showed multiple enlarged, necrotic and matted retroperitoneal lymph nodes with caseating granuloma on histopathology suggesting tuberculosis. Patient was given four-drug anti-tubercular treatment and she improved. Thus our patient of occult abdominal tuberculosis with reactive arthritis (Poncet′s disease presented with hyperferritinemia mimicking AOSD. We postulate that extreme hyperferritinemia can be seen in tuberculosis and tuberculosis must be conclusively ruled out before diagnosing AOSD in tropics.

  13. Response to immunotherapy in a patient with adult onset Leigh syndrome and T9176C mtDNA mutation.

    Chuquilin, Miguel; Govindarajan, Raghav; Peck, Dawn; Font-Montgomery, Esperanza


    Leigh syndrome is a mitochondrial disease caused by mutations in different genes, including ATP6A for which no known therapy is available. We report a case of adult-onset Leigh syndrome with response to immunotherapy. A twenty year-old woman with baseline learning difficulties was admitted with progressive behavioral changes, diplopia, headaches, bladder incontinence, and incoordination. Brain MRI and PET scan showed T2 hyperintensity and increased uptake in bilateral basal ganglia, respectively. Autoimmune encephalitis was suspected and she received plasmapheresis with clinical improvement. She was readmitted 4 weeks later with dysphagia and aspiration pneumonia. Plasmapheresis was repeated with resolution of her symptoms. Given the multisystem involvement and suggestive MRI changes, genetic testing was done, revealing a homoplasmic T9176C ATPase 6 gene mtDNA mutation. Monthly IVIG provided clinical improvement with worsening when infusions were delayed. Leigh syndrome secondary to mtDNA T9176C mutations could have an autoimmune mechanism that responds to immunotherapy. PMID:27408822

  14. Incidence of Adult-onset Asthma After Hypothetical Interventions on Body Mass Index and Physical Activity: An Application of the Parametric G-Formula

    Garcia-Aymerich, Judith; Varraso, Raphaëlle; Danaei, Goodarz; Camargo,, Carlos A.; Hernán, Miguel A.


    High body mass index (BMI) (calculated as weight (kg)/height (m)2) is associated with increased asthma risk, but uncertainty persists about the role of physical activity. We estimated the independent and joint associations of hypothetical interventions on BMI and physical activity with the risk of adult-onset asthma in 76,470 asthma-free women from the Nurses’ Health Study who were followed between 1988 and 1998. Information about asthma, BMI, physical activity, and other factors was updated every 2 years. We used the parametric g-formula to estimate the 10-year asthma risk in the following 4 scenarios: no intervention, 5% BMI reduction in a 2-year period for those who were overweight or obese, at least 2.5 hours/week of moderate-to-vigorous physical activity, and both of the previous 2 interventions. At baseline, women had a mean age of 55 (standard deviation, 7) years and a mean BMI of 25.4 (standard deviation, 4.8). Median time spent in physical activity was 0.7 hours/week. During follow-up, 1,146 women developed asthma. The 10-year asthma risk under no intervention was 1.5%. Compared with no intervention, the population risk ratios were 0.96 (95% confidence interval (CI): 0.93, 0.99) under the BMI intervention, 0.96 (95% CI: 0.81, 1.10) under the physical activity intervention, and 0.92 (95% CI: 0.78, 1.06) under the joint intervention. Interventions on BMI and physical activity may have a modest impact on the risk of adult-onset asthma in this population of US women. PMID:24107616

  15. Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation.

    Sampey, Brante P; Freemerman, Alex J; Zhang, Jimmy; Kuan, Pei-Fen; Galanko, Joseph A; O'Connell, Thomas M; Ilkayeva, Olga R; Muehlbauer, Michael J; Stevens, Robert D; Newgard, Christopher B; Brauer, Heather A; Troester, Melissa A; Makowski, Liza


    Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to "Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic

  16. Ranibizumab for choroidal neovascularization following atrophic involution of adult-onset foveomacular vitelliform dystrophy.

    Sebastian Martinez-Castillo


    Full Text Available Purpose: We report a case of adult-onset foveomacular vitelliform dystrophy (AOFVD complicated with atrophic involution and subsequent choroidal neovascularization (CNV and treated with intravitreal ranibizumab. Design: Case Report Methods: A 71-year-old woman diagnosed with AOFVD experienced a progression of the vitelliform lesion to the atrophic stage in her left eye immediately after cataract surgery. Best corrected visual acuity (BCVA decreased from 0.5 to 0.16. Ten months later, the patient was referred with new worsening of her visual acuity (0.05 and metamorphopsia. The spectral-domain optical coherence tomography (SD-OCT confirmed the presence of type 2 CNV next to the atrophic area. The patient was treated with 2 monthly injections of ranibizumab. Results: SD-OCT images improved significantly and her BCVA increased to 0.20 associated with subjective improvement of metamorphopsia. Conclusion: Ranibizumab may be effective for CNV in patients with AOFVD.

  17. Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity.

    Mohamed Abu-Farha

    Full Text Available Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1 was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4 was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent

  18. Malignant ventricular arrhythmia in a case of adult onset of spinal muscular atrophy (Kugelberg-Welander disease).

    Roos, M.; Sarkozy, A.; Chierchia, G.B.; Wilde, P.C.M. de; Schmedding, E.; Brugada, P.


    We present a case of a 43-year-old male patient with adult onset of spinal muscular atrophy (SMA). The patient first came to our attention with atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted. Four years later, the PM data log showed occurrence of frequent episodes of no

  19. The Long-Term Clinical Follow-Up and Natural History of Men with Adult-Onset Idiopathic Hypogonadotropic Hypogonadism

    Dwyer, Andrew A.; Hayes, Frances J.; Plummer, Lacey; Pitteloud, Nelly; Crowley, William F.


    Context and Objective: Adult-onset idiopathic hypogonadotropic hypogonadism (AHH) is a rare disorder characterized by an isolated failure of gonadotropin secretion occurring after an otherwise normal sexual maturation in men. This study aims to examine the etiology and long-term natural history of this disorder.

  20. A longitudinal study of adult-onset asthma incidence among HMO members

    Rosiello Richard A


    Full Text Available Abstract Background HMO databases offer an opportunity for community based epidemiologic studies of asthma incidence, etiology and treatment. The incidence of asthma in HMO populations and the utility of HMO data, including use of computerized algorithms and manual review of medical charts for determining etiologic factors has not been fully explored. Methods We identified adult-onset asthma, using computerized record searches in a New England HMO. Monthly, our software applied exclusion and inclusion criteria to identify an "at-risk" population and "potential cases". Electronic and paper medical records from the past year were then reviewed for each potential case. Persons with other respiratory diseases or insignificant treatment for asthma were excluded. Confirmed adult-onset asthma (AOA cases were defined as those potential cases with either new-onset asthma or reactivated mild intermittent asthma that had been quiescent for at least one year. We validated the methods by reviewing charts of selected subjects rejected by the algorithm. Results The algorithm was 93 to 99.3% sensitive and 99.6% specific. Sixty-three percent (n = 469 of potential cases were confirmed as AOA. Two thirds of confirmed cases were women with an average age of 34.8 (SD 11.8, and 45% had no evidence of previous asthma diagnosis. The annualized monthly rate of AOA ranged from 4.1 to 11.4 per 1000 at-risk members. Physicians most commonly attribute asthma to infection (59% and allergy (14%. New-onset cases were more likely attributed to infection, while reactivated cases were more associated with allergies. Medical charts included a discussion of work exposures in relation to asthma in only 32 (7% cases. Twenty-three of these (72% indicated there was an association between asthma and workplace exposures for an overall rate of work-related asthma of 4.9%. Conclusion Computerized HMO records can be successfully used to identify AOA. Manual review of these records is

  1. Obesity

    ... obese, follow an unhealthy diet, and have an eating disorder all at the same time. Sometimes, medical problems or treatments cause weight gain, including: Underactive thyroid (hypothyroidism) Medicines such ...

  2. Health-related quality of life in sporadic adult-onset ataxia.

    Abele, Michael; Klockgether, Thomas


    Despite progressive disability in sporadic adult-onset ataxia (SAOA), little is known about patients' assessment of their ataxic disorder and its impact on health-related quality of life (Hr-QoL). This study investigated Hr-QoL by means of the following self-administered scales: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Beck Depression Inventory (BDI), and the Medical Outcome Study Short Form (SF-36). Twenty-two unselected ataxia patients were included. Sleep-related complaints were found in 9 (41%) of 22 and symptoms of depression in 6 (38%) of 16 patients. Compared to a large german control group, SAOA patients had lower scores in all SF-36 dimensions except for bodily pain. The greatest impairment was found in the domain physical functioning, followed by the domains social functioning and role limitations (emotional problems). There was a significant negative correlation of all nonmotor SF-36 dimensions with the BDI score. Walking aid dependency was significantly correlated with poorer health status perception in several motor and nonmotor domains. In addition, impaired sleep quality was correlated with an impaired general health perception and with bodily pain. The study demonstrates a great impact of SAOA on Hr-QoL. Adequate treatment of depression, motor disability, and impaired sleep quality is essential to improve Hr-QoL in ataxic patients. PMID:17149704

  3. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    Naghia Ahmed


    Full Text Available Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.

  4. A rare presentation of adult onset Still’s disease in an elderly patient

    Mariya Apostolova


    Full Text Available Adult onset Still’s disease (AOSD is a rare inflammatory disorder of unknown etiology that usually affects young adults. Very few patients older than 70-year-old have been reported. Clinical features include quotidian fevers, arthralgias, arthritis, pharyngitis, lymphadenopathy and an evanescent rash. AOSD should be considered in the differential diagnosis of fever of unknown origin. Early diagnosis is often difficult since it is a diagnosis of exclusion and the presence of infectious, neoplastic and autoimmune conditions needs to be ruled out before the diagnosis is made. No specific laboratory tests are available to aid in the diagnosis of AOSD. As a result, a set of diagnostic criteria that define the clinical features of this condition, termed the Yamaguchi criteria, have been most commonly used to establish the diagnosis. We describe the case of a 72-year-old Caucasian male with past medical history significant for generalized anxiety disorder, depression, BPH, and hypertriglyceridemia, who presented to a tertiary institution complaining of profound generalized weakness and weight loss that started three weeks prior to presentation. Initial laboratory studies showed leukocytosis, elevated ESR, CRP, ferritin and liver dysfunction. Cultures, ANA and rheumatoid factor studies were negative. The patient underwent further extensive workup that excluded the presence of infectious, neoplastic and autoimmune disorders and was subsequently diagnosed with AOSD and new onset diabetes mellitus. For the management of AOSD he was started on prednisone with significant improvement in markers of inflammation, symptoms and level of function.

  5. Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

    Cardin, Velia


    Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

  6. The anti-obesity drug orlistat reveals anti-viral activity.

    Ammer, Elisabeth; Nietzsche, Sandor; Rien, Christian; Kühnl, Alexander; Mader, Theresa; Heller, Regine; Sauerbrei, Andreas; Henke, Andreas


    The administration of drugs to inhibit metabolic pathways not only reduces the risk of obesity-induced diseases in humans but may also hamper the replication of different viral pathogens. In order to investigate the value of the US Food and Drug Administration-approved anti-obesity drug orlistat in view of its anti-viral activity against different human-pathogenic viruses, several anti-viral studies, electron microscopy analyses as well as fatty acid uptake experiments were performed. The results indicate that administrations of non-cytotoxic concentrations of orlistat reduced the replication of coxsackievirus B3 (CVB3) in different cell types significantly. Moreover, orlistat revealed cell protective effects and modified the formation of multi-layered structures in CVB3-infected cells, which are necessary for viral replication. Lowering fatty acid uptake from the extracellular environment by phloretin administrations had only marginal impact on CVB3 replication. Finally, orlistat reduced also the replication of varicella-zoster virus moderately but had no significant influence on the replication of influenza A viruses. The data support further experiments into the value of orlistat as an inhibitor of the fatty acid synthase to develop new anti-viral compounds, which are based on the modulation of cellular metabolic pathways. PMID:25680890

  7. Obesity

    Morgen, Camilla Schmidt; Sørensen, Thorkild I A


    A new report provides compelling evidence of the high prevalence of overweight and obesity throughout the world. The prevalence has increased since 1980, but at different rates across ages, times and locations. Studies exploring the causes of these differences could aid development of effective...

  8. Prevalence of reticular pseudodrusen in newly presenting adult onset foveomacular vitelliform dystrophy.

    Wilde, C; Lakshmanan, A; Patel, M; Morales, M U; Dhar-Munshi, S; Amoaku, W M K


    PurposeTo report the association and prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting adult onset foveomacular vitelliform dystrophy (AFVD). To compare the strength of association with other pathologies resulting from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE) complex, including eyes with geographic atrophy (GA) and angioid streaks.MethodsRetrospective single-centre review of all consecutive newly presenting AFVD. Multimodal imaging with spectral domain optical coherence tomography, fundus photographs, red-free/blue light images, and fundus fluorescein angiograms were graded for the presence of RPD. For comparison, all consecutive newly presenting cases of GA and eyes with angioid streaks were studied.ResultsFifteen (15) patients were identified with AFVD (mean age of 77.3 years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD 3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0). This age difference did not reach statistical significance, P=0.1. Six (40%) had identifiable RPD; being a bilateral finding in 100% of patients. No males with AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable angioid streaks, with 4 (36.4%) having RPD.ConclusionRPD are a frequent finding in eyes with newly presenting AFVD; not being restricted to AMD, but a finding common among diseases where pathophysiological mechanisms involve damage to Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports the concept that they occur with high but variable frequencies in eyes with various pathologies. PMID:27034200

  9. Clinical characteristics of adult-onset actinic prurigo in Asians: A case series

    Khor Jia Ker


    Full Text Available Background: Actinic prurigo (AP is a chronic, pruritic skin condition caused by an abnormal reaction to sunlight. Aims: The aim of this study is to determine the clinical characteristics of AP in patients attending the National Skin Centre, Singapore, from 1 st January 1999 to 30 th June 2008. Methods: Cases of AP diagnosed from 1 st January 1999 to 30 th June 2008 were retrieved from the center′s electronic medical records and analyzed. Results: A total of 11 patients were diagnosed with AP. The mean age at diagnosis was 52 years. There were 9 (82% Chinese and 2 (18% Malay patients. Nine (82% were male and 2 (18% were female. The most commonly affected areas were the face, forearms, and hands (72%. Phototesting showed reduced minimal erythema dose (MED to ultraviolet A (UVA in 5 (46% patients, both UVA and ultraviolet B (UVB in 4 (36% patients and UVB in 1 (9% patient. Seven (64% patients reported partial improvement after treatment with a combination of topical corticosteroids and sunscreens. Four (36% patients received systemic therapy with partial response. Conclusion: Adult-onset AP is more common in the Asian population, with a male predominance. The face, forearms, and hands are the most commonly affected areas. The absence of mucosal involvement is also a distinguishing feature between the Asian and Caucasian population. Close to half of the patients have reduced MED to UVA on phototesting. The prognosis for AP is poor as it tends to run a chronic course with suboptimal response to treatment.

  10. Granulomas Formation in Lymph Nodes, Liver and Spleen in Adult-Onset Still’s Disease: A Case Report

    Assimakopoulos, Stelios F; Karamouzos, Vassilios; Papakonstantinou, Christos; Zolota, Vassiliki; Labropoulou-Karatza, Chryssoula; Gogos, Charalambos


    Tissue granulomas formation in adult-onset Still’s disease (AOSD) is extremely rare. We describe a case of AOSD associated with formation of granulomatous lesions in lymph nodes, liver and presumably spleen. The high dose steroid-dependent nature of our patient’s illness, characterized by disease relapses when methylprednisolone dose was reduced below 10 mg/d, was overwhelmed with institution of anakinra (100 mg/d). The histologic finding of granulomas formation in lymph nodes, liver or splee...

  11. Magnetic resonance characteristics of adult-onset Lhermitte-Duclos disease: An indicator for active cancer surveillance?

    Wei, Guangquan; Zhang, Wei; Li, Qinlong; KANG, XIAOWEI; Zhao, Haitao; LIU, XIANPING; Tang, Xing; Wu, Yuanming; HAN, JUNTAO; Yin, Hong


    Lhermitte-Duclos disease (LDD) is a rare, non-cancerous entity characterized by enlarged, abnormally developed cerebellar folia containing dysplastic cells. Symptomatic LDD is commonly observed in adults (adult-onset LDD, aLDD) as an isolated condition or associated with Cowden’s disease (CD). The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and the underlying pathological findings in 7 cases of aLDD, with emphasis on the association with CD and the ...

  12. Levodopa Responsiveness in Adult-onset Lower Limb Dystonia is Associated with the Development of Parkinson’s Disease

    Chang, Florence C. F.; Josephs, Keith A.


    Background Adult-onset primary lower limb dystonia (AOPLLD) has been reported as an early sign of Parkinson’s disease (PD) or Parkinson-plus syndrome in case series. No prior systematic analysis has assessed clinical clues predicting later development of PD or Parkinson-plus syndrome. Methods We identified patients with AOPLLD from medical records. We excluded patients who had not been diagnosed by a neurologist, and who had a pre-existing diagnosis of PD, psychogenic, or secondary dystonia. ...

  13. Effect of thyroxine on munc-18 and syntaxin-1 expression in dorsal hippocampus of adult-onset hypothyroid rats

    Y. Zhu


    Full Text Available Adult-onset hypothyroidism induces a variety of impairments on hippocampus- dependent neurocognitive functioningin which many synaptic proteins in hippocampus neurons are involved. Here, we observed the effect of adult-onset hypothyroidism on the expression of syntaxin-1 and munc-18 in the dorsal hippocampus and whether the altered proteins could be restored by levothyroxine (T4 treatment. All rats were separated into 4 groups randomly: hypothyroid group, 5μg T4/100 g body weight (BW treated group, 20 μg T4/100g BW treated group and control group. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and the levels of syntaxin-1 and munc-18 in hippocampus were assessed by immunohistochemistry and Western blot. Both analysis corroborated that syntaxin-1 in the hypothyroid group was significantly higher. Munc-18 was lower in four layers of CA3 and dentate gyrus by immunohistochemistry. After two weeks of treatment with 5 μg T4/100g BW for hypothyroidism, syntaxin-1 levels were completely restored, whereas the recovery of munc-18 only located in two of the four impaired layers. Twenty μg T4/100g BW treatment normalized munc-18 levels. These data suggested that adult-onset hypothyroidism induced increment of syntaxin-1 and decrement of munc-18 in the dorsal hippocampus, which could be restored by T4 treatment. Larger dosage of T4 caused more effective restorations.

  14. Early life factors associated with adult onset systemic lupus erythematosus (SLE in women

    Christine Gibson Parks


    the development of disease, but knowledge on specific risk factors is mostly limited to occupational exposures[1]. The developmental origins hypothesis has been proposed for many adult-onset, chronic inflammatory diseases, including systemic lupus erythematosus (SLE [2-6]. Exposures during and after gestation, including nutritional, infectious, chemical

  15. A Genome-wide Study Reveals Copy Number Variants Exclusive to Childhood Obesity Cases

    Joseph T. Glessner; Bradfield, Jonathan P.; Wang, Kai; Takahashi, Nagahide; Zhang, Haitao; Sleiman, Patrick M.; Mentch, Frank D.; Kim, Cecilia E; Hou, Cuiping; Thomas, Kelly A.; Garris, Maria L.; Deliard, Sandra; Frackelton, Edward C; Otieno, F. George; Zhao, Jianhua


    The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Genomic copy number variations (CNVs) have been strongly implicated in subjects with extreme obesity and coexisting developmental delay. To complement these previous studies, we addressed CNVs in common childhood obesity by examining children with a BMI in the upper 5th percentile but excluding any subject greater than three standard deviations from the mean in order to reduc...

  16. Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation

    Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D


    Objective: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Methods: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Results: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. Conclusions: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the

  17. Gene expression profiling of white adipose tissue reveals paternal transmission of proneness to obesity.

    Morita, Sumiyo; Nakabayashi, Kazuhiko; Kawai, Tomoko; Hayashi, Keiko; Horii, Takuro; Kimura, Mika; Kamei, Yasutomi; Ogawa, Yoshihiro; Hata, Kenichiro; Hatada, Izuho


    Previously, we found that C57BL/6J (B6) mice are more prone to develop obesity than PWK mice. In addition, we analyzed reciprocal crosses between these mice and found that (PWK × B6) F1 mice, which have B6 fathers, are more likely to develop dietary obesity than (B6 × PWK) F1 mice, which have B6 mothers. These results suggested that diet-induced obesity is paternally transmitted. In this study, we performed transcriptome analysis of adipose tissues of B6, PWK, (PWK × B6) F1, and (B6 × PWK) F1 mice using next-generation sequencing. We found that paternal transmission of diet-induced obesity was correlated with genes involved in adipose tissue inflammation, metal ion transport, and cilia. Furthermore, we analyzed the imprinted genes expressed in white adipose tissue (WAT) and obesity. Expression of paternally expressed imprinted genes (PEGs) was negatively correlated with body weight, whereas expression of maternally expressed imprinted genes (MEGs) was positively correlated. In the obesity-prone B6 mice, expression of PEGs was down-regulated by a high-fat diet, suggesting that abnormally low expression of PEGs contributes to high-fat diet-induced obesity in B6 mice. In addition, using single-nucleotide polymorphisms that differ between B6 and PWK, we identified candidate imprinted genes in WAT. PMID:26868178

  18. Gene expression profiling of white adipose tissue reveals paternal transmission of proneness to obesity

    Morita, Sumiyo; Nakabayashi, Kazuhiko; Kawai, Tomoko; Hayashi, Keiko; Horii, Takuro; Kimura, Mika; Kamei, Yasutomi; Ogawa, Yoshihiro; Hata, Kenichiro; Hatada, Izuho


    Previously, we found that C57BL/6J (B6) mice are more prone to develop obesity than PWK mice. In addition, we analyzed reciprocal crosses between these mice and found that (PWK × B6) F1 mice, which have B6 fathers, are more likely to develop dietary obesity than (B6 × PWK) F1 mice, which have B6 mothers. These results suggested that diet-induced obesity is paternally transmitted. In this study, we performed transcriptome analysis of adipose tissues of B6, PWK, (PWK × B6) F1, and (B6 × PWK) F1 mice using next-generation sequencing. We found that paternal transmission of diet-induced obesity was correlated with genes involved in adipose tissue inflammation, metal ion transport, and cilia. Furthermore, we analyzed the imprinted genes expressed in white adipose tissue (WAT) and obesity. Expression of paternally expressed imprinted genes (PEGs) was negatively correlated with body weight, whereas expression of maternally expressed imprinted genes (MEGs) was positively correlated. In the obesity-prone B6 mice, expression of PEGs was down-regulated by a high-fat diet, suggesting that abnormally low expression of PEGs contributes to high-fat diet-induced obesity in B6 mice. In addition, using single-nucleotide polymorphisms that differ between B6 and PWK, we identified candidate imprinted genes in WAT. PMID:26868178

  19. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    Kogelman, Lisette; Zhernakova, Daria V.; Westra, Harm-Jan; Cirera Salicio, Susanna; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja


    BACKGROUND: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about the...... porcine model to investigate the mechanisms involved in obesity using a systems genetics approach. METHODS: Using a selective gene expression profiling approach, we selected 36 animals based on a previously created genomic Obesity Index for RNA sequencing of subcutaneous adipose tissue. Differential...... expression analysis was performed using the Obesity Index as a continuous variable in a linear model. eQTL mapping was then performed to integrate 60 K porcine SNP chip data with the RNA sequencing data. Results were restricted based on genome-wide significant single nucleotide polymorphisms, detected...

  20. Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation

    Sampey, Brante P.; Freemerman, Alex J.; Zhang, Jimmy; Kuan, Pei-Fen; Galanko, Joseph A.; O'Connell, Thomas M; Ilkayeva, Olga R.; Muehlbauer, Michael J; Stevens, Robert D.; Newgard, Christopher B.; Brauer, Heather A.; Troester, Melissa A.; Makowski, Liza


    Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to “Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify pote...

  1. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension.

    Baserga, Mariana; Hale, Merica A; Wang, Zheng Ming; Yu, Xing; Callaway, Christopher W; McKnight, Robert A; Lane, Robert H


    Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number and predisposes toward renal insufficiency early in life and increased risk of adult-onset hypertension. In this study, we hypothesized that the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein in nephrogenesis, constitutes a mechanism through which UPI and subsequent glucocorticoid overexposure can decrease nephron number. We further hypothesized that UPI downregulates the key enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which converts corticosterone to inert 11-dehydrocorticosterone, thereby protecting both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) from the actions of corticosterone. Following bilateral uterine ligation on the pregnant rat, UPI significantly decreased renal COX-2, 11beta-HSD2, and GR mRNA and protein levels, but upregulated expression of MR at birth. At day 21 of life, 11beta-HSD2, GR, and also MR mRNA and protein levels were downregulated. UPI did not affect blood pressures (BP) at day 21 of life but significantly increased systolic BP in both genders at day 140. We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult-onset hypertension. PMID:17272666

  2. Association of ADAM33 gene polymorphisms with adult-onset asthma and its severity in an Indian adult population

    Priya Tripathi; Shally Awasthi; Rajendra Prasad; Nuzhat Husain; Subramaniam Ganesh


    ADAM33, a member of the ADAM (a disintegrin and metalloprotease) gene family, is an asthma susceptibility gene originally identified by positional cloning. In the present study, we investigated the possible association of five single-nucleotide polymorphisms (SNPs) in the ADAM33 (rs511898, rs528557, rs44707, rs597980 and rs2787094) with adult-onset asthma in an Indian population. The study included 175 patients with mild intermittent ($n = 44$), mild persistent ($n = 108$) or moderate persistent ($n = 23$) subgroups of asthma, and 253 nonasthmatic control individuals. SNPs were genotyped with the help of restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method, and data were analysed using chi-square test and logistic regression model. Bonferroni’s correction for multiple comparisons was applied for each hypothesis. Genotypes and allele frequencies of SNPs rs511898 and rs528557 were significantly associated with adult-onset asthma ($P = 0.010-\\lt 0.001$). A significant association of the homozygous mutant genotype and mutant alleles of SNPs rs2787094, rs44707 and rs597980 with the asthma was also observed ($P = 0.020-\\lt 0.001$). A positive association between asthma and haplotypes AGCCT, GGCCT, AGACT, GCAGT, GGACT, ACCCC and AGACC were also found ($P = 0.036-\\lt 0.001$, OR $= 2.07-8.49$). Haplotypes AGCGT, GCAGC, ACAGC, ACAGT, GGAGC and GGCGT appear to protect against asthma ($P = 0.013-\\lt 0.0001$, OR $= 0.34-0.10$). Our data suggest that ADAM33 gene polymorphisms serve as genetic risk factors for asthma in Indian adult population.

  3. Temporal discrimination thresholds in adult-onset primary torsion dystonia: an analysis by task type and by dystonia phenotype.

    Bradley, D


    Adult-onset primary torsion dystonia (AOPTD) is an autosomal dominant disorder with markedly reduced penetrance. Sensory abnormalities are present in AOPTD and also in unaffected relatives, possibly indicating non-manifesting gene carriage (acting as an endophenotype). The temporal discrimination threshold (TDT) is the shortest time interval at which two stimuli are detected to be asynchronous. We aimed to compare the sensitivity and specificity of three different TDT tasks (visual, tactile and mixed\\/visual-tactile). We also aimed to examine the sensitivity of TDTs in different AOPTD phenotypes. To examine tasks, we tested TDT in 41 patients and 51 controls using visual (2 lights), tactile (non-painful electrical stimulation) and mixed (1 light, 1 electrical) stimuli. To investigate phenotypes, we examined 71 AOPTD patients (37 cervical dystonia, 14 writer\\'s cramp, 9 blepharospasm, 11 spasmodic dysphonia) and 8 musician\\'s dystonia patients. The upper limit of normal was defined as control mean +2.5 SD. In dystonia patients, the visual task detected abnormalities in 35\\/41 (85%), the tactile task in 35\\/41 (85%) and the mixed task in 26\\/41 (63%); the mixed task was less sensitive than the other two (p = 0.04). Specificity was 100% for the visual and tactile tasks. Abnormal TDTs were found in 36 of 37 (97.3%) cervical dystonia, 12 of 14 (85.7%) writer\\'s cramp, 8 of 9 (88.8%) blepharospasm, 10 of 11 (90.1%) spasmodic dysphonia patients and 5 of 8 (62.5%) musicians. The visual and tactile tasks were found to be more sensitive than the mixed task. Temporal discrimination threshold results were comparable across common adult-onset primary torsion dystonia phenotypes, with lower sensitivity in the musicians.

  4. Diffusion tensor imaging of the cortico-ponto-cerebellar pathway in patients with adult-onset ataxic neurodegenerative disease

    Kitamura, Kaeko; Nakayama, Keiko; Yamada, Eiji; Inoue, Yuichi [Osaka City University Graduate School of Medicine, Department of Radiology, Osaka (Japan); Kosaka, Satoru; Shimada, Hiroyuki; Miki, Takami [Osaka City University Graduate School of Medicine, Department of Neurology, Osaka (Japan)


    We sought to determine whether diffusion-tensor imaging (DTI) can detect in vivo axonal damage in the corticopontocerebellar pathway of patients with adult-onset ataxic neurodegenerative disease. Conventional MRI and DTI were performed on 18 patients with adult-onset ataxic neurodegenerative disease and 28 age-matched control subjects. Fractional anisotropy (FA) and the mean diffusivity (MD) were measured in the ventral, central, and dorsal pons, middle cerebellar peduncle (MCP) and internal capsule to evaluate corticopontocerebellar projection. Changes in FA and MD values were compared between patients and controls. Clinical disability was assessed according to the International Cooperative Ataxia Rating Scale (ICARS). The relationship between DTI measurements and ICARS was studied. Follow-up MRI was performed in five patients approximately 1 year later. FA values were significantly lower in the ventral and central portions of the pons, MCP, and internal capsules than in these areas in control subjects (P < 0.05) with the lower FA values correlating with poorer ICARS (r > -0.57, P < 0.05). MD values were elevated in these areas, but the differences were smaller than for the FA values. No relationship was observed between the MD and ICARS. In the five patients who underwent the follow-up study, there were significant decreases between the initial study and the follow-up DTI study for FA in the MCP and internal capsule (P < 0.05). DTI can demonstrate a degenerated corticopontocerebellar pathway in patients, and FA values can be correlated with ataxia severity. DTI may be a clinically useful tool as a quantitative surrogate marker for monitoring disease progression. (orig.)

  5. Two Siblings with Adolescent/Adult Onset Niemann-Pick Disease Type C in Korea.

    Lee, Su-Yun; Lee, Hyung Jin; Kim, Seong Hwan; Jeong, Young Jin; Jin, Hee Kyung; Bae, Jae-Sung; Cheon, Sang-Myung; Kim, Jae Woo


    Niemann-Pick disease, type C (NP-C), is caused by NPC1 or NPC2 gene mutations. Progressive neurological, psychiatric, and visceral symptoms are characteristic. Here, we present cases of a brother (Case 1) and sister (Case 2) in their mid-20s with gait disturbance and psychosis. For the Case 1, neurological examination revealed dystonia, ataxia, vertical supranuclear-gaze palsy (VSGP), and global cognitive impairment. Case 2 showed milder, but similar symptoms, with cortical atrophy. Abdominal computed tomography showed hepatosplenomegaly in both cases. NPC1 gene sequencing revealed compound heterozygote for exon 9 (c.1552C>T [R518W]) and exon 18 (c.2780C>T [A927V]). Filipin-staining tests were also positive. When a young patient with ataxia or dystonia shows VSGP, NP-C should be considered. PMID:27366019

  6. Proteomics analysis of human skeletal muscle reveals novel abnormalities in obesity and type 2 diabetes

    Hwang, Hyonson; Bowen, Benjamin P; Lefort, Natalie; Flynn, Charles R; De Filippis, Elena A; Roberts, Christine; Smoke, Christopher C; Meyer, Christian; Højlund, Kurt; Yi, Zhengping; Mandarino, Lawrence J


    changes involving the use of proteomics was used here. RESEARCH DESIGN AND METHODS: Muscle biopsies were obtained basally from lean, obese, and type 2 diabetic volunteers (n = 8 each); glucose clamps were used to assess insulin sensitivity. Muscle protein was subjected to mass spectrometry......OBJECTIVE : Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Studies of insulin resistance usually are highly focused. However, approaches that give a more global picture of abnormalities in insulin resistance are useful in pointing out new...

  7. Adult-Onset Deletion of β-Catenin in (10kb)Dmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain.

    Kedlaya, Rajendra; Kang, Kyung Shin; Hong, Jung Min; Bettagere, Vidya; Lim, Kyung-Eun; Horan, Daniel; Divieti-Pajevic, Paola; Robling, Alexander G


    β-Catenin (βcat) is a major downstream signaling node in canonical Wingless-related integration site (Wnt) signaling pathway, and its activity is crucial for canonical Wnt signal transduction. Wnt signaling has recently been implicated in the osteo-anabolic response to PTH, a potent calcium-regulating factor. We investigated whether βcat is essential for the anabolic action of intermittent PTH by generating male mice with adult-onset deletion of βcat in a subpopulation of bone cells (osteocytes and late-stage osteoblasts), treating them with an anabolic regimen of PTH, and measuring the skeletal responses. Male (10kb)Dmp1-CreERt2 transgenic mice that also harbored floxed loss-of-function βcat alleles (βcat(f/f)) were induced for Cre activity using tamoxifen, then injected daily with human PTH 1-34 (30 μg/kg) or vehicle for 5 weeks. Mice in which βcat was deleted showed either total lack of bone mineral density (BMD) gain, or BMD loss, and did not respond to PTH treatment. However, bone mass measurements in the trabecular compartment of the femur and spine revealed PTH-induced bone gain whether βcat was deleted or not. PTH-stimulated increases in periosteal and cancellous bone formation rates were not impaired by βcat deletion, but resorption markers and cortical porosity were significantly increased in induced mice, particularly induced mice treated with PTH. These results suggest that βcat is required for net-positive BMD effects of PTH therapy but that the anabolic effects per se of PTH treatment might not require osteocytic/osteoblastic βcat. PMID:27253995

  8. Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge

    Perreault, Maude; Zulyniak, Michael A.; Britz-McKibbin, Philip; Mutch, David M.


    Objective To determine if metabolically healthy obese (MHO) individuals have a different metabolic response to a standardized diet compared to lean healthy (LH) and metabolically unhealthy obese (MUO) individuals. Methods Thirty adults (35–70 yrs) were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal). Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs) and derivatives, and fatty acids (FAs). Results The postprandial response (i.e., area under the curve, AUC) for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05). Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, γ-linolenic acid, arachidonic acid) showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA) and FAs (e.g., saturated myristic and palmitic acids) were found to correlate with glucose and insulin AUC. Conclusion MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals. PMID:26274804


    Banerjee, Pia; Cloughesy, Timothy; Pham, Jennifer; Cervantes, Sandra; Nghiemphu, Phioanh; Lai, Albert; Wellisch, David


    INTRODUCTION: Neurocognitive functioning and other aspects of quality of life have become increasingly important in the clinical care of patients with glioma. While regular monitoring of neurocognitive functioning with thorough evaluations would be ideal for patients, this is often impractical due to time, cost, and resource considerations. Instead, a measure of self-reported cognitive symptoms can be administered to identify the patients who perceive themselves to be experiencing cognitive difficulties, allowing for rapid detection of patients in need. Recently, a self-report measure of neurocognitive functioning was developed to target the cognitive domains affected by cancer treatments. However, to our knowledge, studies of this questionnaire in adults have only included adult survivors of childhood cancers. METHODS: In the present study, 299 patients with adult-onset WHO Grade II-IV glioma completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. This 25-item measure has four subscales representing different cognitive functions: Task Efficiency, Emotional Tolerance, Organization, and Memory. RESULTS: Overall scores, primary areas of concern, and relationships with medical characteristics were identified. Subtest scores were: Task Efficiency T score (M = 42.8, SD = 15.9), Emotional Tolerance T score (M = 51.6, SD = 11.7), Organization T score (M = 48.6, SD = 11.7), and Memory T score (M = 44.0, SD = 15.3), demonstrating task efficiency to be the cognitive function of greatest concern. Individual item responses were then analyzed, with 188 patients (61.6%) endorsing the highest ranked item: "I have difficulty recalling things I had previously learned" (M = 0.81, SD = 0.74). Chi-square tests, t-tests, and regression were also performed, and these analyses identified statistically significant effects of tumor laterality, radiochemotherapy, recurrence, and KPS score (p < .05), but not tumor grade, on each of the four subscale scores. CONCLUSION

  10. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole


    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington’s disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions. PMID:26863614

  11. A case of adult onset medulloblastoma during maintenance chemotherapy for anaplastic astrocytoma one year after radiotherapy.

    Takeshi, Nishimoto; Kazuhiko, Sugiyama; Koji, Iida; Toshikazu, Hidaka; Kaoru, Kurisu


    Multiple primitive intracranial tumors with different histological characteristics are uncommon. Although coexistence of a medulloblastoma with glial tumors has been reported in children, medulloblastoma is rarely found in adults, especially those older than 40 years of age. We present an extremely rare case of a medulloblastoma developing in a 40-year-old male undergoing maintenance chemotherapy for anaplastic astrocytoma for 21 months after radiotherapy. Initially, he complained of intractable epilepsy characterized by complex partial seizures. Magnetic resonance imaging (MRI) revealed a slightly enhanced mass lesion in the left insula region. He underwent subtotal removal of the tumor and it was histologically diagnosed as anaplastic astrocytoma. After 19 months of treatment with temozolomide (TMZ) and radiotherapy, he presented with vertigo and headache. A homogeneously enhanced mass had developed in the left cerebellar hemisphere. He received gross total resection of the second tumor, pathologically diagnosed as medulloblastoma. In conclusion, this is the first case report of an adult medulloblastoma coexisting with anaplastic astrocytoma. PMID:24101275

  12. Recurrent adult-onset hypophyseal Langerhans cell histiocytosis after radiotherapy: a case report

    Funk Ryan K


    Full Text Available Abstract Introduction Langerhans cell histiocytosis is a rare disease within the adult population, with very few cases reported as solitary hypophyseal lesions in adults. Of the reported cases, most have been treated successfully with surgery, radiotherapy, and/or chemotherapy. Radiotherapy has been thought to be curative at the relatively low dose of 20Gy. Here we report a case of recurrent hypophyseal Langerhans cell histiocytosis 9 months after radiotherapy with an interval period of symptomatic and radiographic response to therapy. Case presentation A 50-year-old Caucasian woman who had headaches, memory difficulties, and diabetes insipidus was found to have a 2.5cm suprasellar mass. Langerhans cell histiocytosis was diagnosed following stereotactic brain biopsy. Further workup revealed no other lesions. Initial radiation treatment succeeded in shrinking the tumor and relieving clinical symptoms temporarily; however, growth and recurrence of clinical symptoms was noted at 9 months. Re-irradiation was well tolerated and the patient had no acute side effects. Conclusion Isolated hypophyseal involvement by Langerhans cell histiocytosis in adults is a unique presentation of a rare disease. Although radiotherapy doses as low as 20Gy have been reported to offer control, this case demonstrates that higher doses may be warranted to ensure tumor control. With modern imaging and radiotherapy techniques higher doses should offer little increased more durable risk to surrounding critical structures.

  13. Adult onset Leigh syndrome

    Pandit Lekha


    Full Text Available Leigh syndrome is a rare progressive mitochondrial disorder of oxidative metabolism. Though it has been reported in infancy and childhood, it is rarely described in adults. The authors describe a patient who had clinical and magnetic resonance imaging features diagnostic of Leigh syndrome, with supportive biochemical and muscle histochemistry evidence.

  14. Experiences of Racism and the Incidence of Adult-Onset Asthma in the Black Women’s Health Study

    Yu, Jeffrey; O’Connor, George T.; Brown, Timothy A.; Cozier, Yvette C.; Palmer, Julie R.; Rosenberg, Lynn


    Background: Chronic stress resulting from experiences of racism may increase the incidence of adult-onset asthma through effects on the immune system and the airways. We conducted prospective analyses of the relation of experiences of racism with asthma incidence in the Black Women’s Health Study, a prospective cohort of black women in the United States followed since 1995 with mailed biennial questionnaires. Methods: Among 38,142 participants followed from 1997 to 2011, 1,068 reported incident asthma. An everyday racism score was created based on five questions asked in 1997 and 2009 about the frequency in daily life of experiences of racism (eg, poor service in stores), and a lifetime racism score was based on questions about racism on the job, in housing, and by police. We used Cox regression models to derive multivariable incidence rate ratios (IRRs) and 95% CIs for categories of each racism score in relation to incident asthma. Results: The IRRs were 1.45 (95% CI, 1.19-1.78) for the highest compared with the lowest quartile of the 1997 everyday racism score (P for trend <.0001) and 1.44 (95% CI, 1.18-1.75) for the highest compared with the lowest category of 1997 lifetime racism. Among women who reported the same levels of racism in 1997 and 2009, the IRRs for the highest categories of everyday and lifetime racism were 2.12 (95% CI, 1.55-2.91) and 1.66 (95% CI, 1.20-2.30), respectively. Conclusions: Given the high prevalence of experiences of racism and asthma in black women in the United States, a positive association between racism and asthma is of public health importance. PMID:23887828

  15. Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer's disease.

    Oyinkan Sofola


    Full Text Available Abeta peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD, with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3 is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Abeta42 specifically in adult neurons, to avoid developmental effects. Abeta42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Abeta42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment rescued Abeta42 toxicity. Abeta42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Abeta42. The GSK-3-mediated effects on Abeta42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Abeta42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Abeta42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Abeta42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD.

  16. Incidence of Adult-onset Asthma After Hypothetical Interventions on Body Mass Index and Physical Activity: An Application of the Parametric G-Formula

    Garcia-Aymerich, Judith; Varraso, Raphaëlle; Danaei, Goodarz; Camargo, de, B.; Hernán, Miguel A.


    High body mass index (BMI) (calculated as weight (kg)/height (m)2) is associated with increased asthma risk, but uncertainty persists about the role of physical activity. We estimated the independent and joint associations of hypothetical interventions on BMI and physical activity with the risk of adult-onset asthma in 76,470 asthma-free women from the Nurses’ Health Study who were followed between 1988 and 1998. Information about asthma, BMI, physical activity, and other factors was updated ...

  17. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L

    Sheetal Patel; Seyed Monemian; Ayesha Khalid; Harvey Dosik


    Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron...

  18. Adult-Onset Deficiency in Growth Hormone and Insulin-Like Growth Factor-I Alters Oligodendrocyte Turnover in the Corpus Callosum

    Hua, Kun; Forbes, M. Elizabeth; Lichtenwalner, Robin J.; Sonntag, William E.; Riddle, David R.


    Growth hormone (GH) and insulin-like growth factor-I (IGF-I) provide trophic support during development and also appear to influence cell structure, function and replacement in the adult brain. Recent studies demonstrated effects of the GH/IGF-I axis on adult neurogenesis, but it is unclear whether the GH/IGF-I axis influences glial turnover in the normal adult brain. In the current study we used a selective model of adult-onset GH and IGF-I deficiency to evaluate the role of GH and IGF-I in ...

  19. When uncommon and common coalesce: adult onset Still's disease associated with breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).

    Dagan, A; Kogan, M; Shoenfeld, Y; Segal, G


    Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto-inflammatory disorder, while breast augmentation is a very common cosmetic procedure. We describe a case in which these two coalesce, AOSD, manifested with pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic, missing link, behind the development of AOSD following mammoplasty, is thought to be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We reviewed other cases of AOSD associated with breast mammoplasty published to date and the literature regarding AOSD and ASIA syndrome. The review is followed by a short debate of whether silicone implants should be explanted in similar, future cases. PMID:25604318

  20. Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes.

    Oberbach, Andreas; Blüher, Matthias; Wirth, Henry; Till, Holger; Kovacs, Peter; Kullnick, Yvonne; Schlichting, Nadine; Tomm, Janina M; Rolle-Kampczyk, Ulrike; Murugaiyan, Jayaseelan; Binder, Hans; Dietrich, Arne; von Bergen, Martin


    , RBP4, PEDF, GLN, and C18:2 showed the strongest correlation to changes in body fat mass. The combined serum proteomic and metabolomic profiling reveals a link between the complement system and obesity and identifies both novel (C3b, CLU, VDBP, and all metabolites) and confirms previously discovered markers (PEDF, RBP4, C3, ATIII, and SAP) of body fat mass changes. PMID:21823675

  1. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E. [Kings College Hospital, London (United Kingdom)


    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  2. Sequence analysis of three canine adipokine genes revealed an association between TNF polymorphisms and obesity in Labrador dogs.

    Mankowska, M; Stachowiak, M; Graczyk, A; Ciazynska, P; Gogulski, M; Nizanski, W; Switonski, M


    Obesity is an emerging health problem in purebred dogs. Due to their crucial role in energy homeostasis control, genes encoding adipokines are considered candidate genes, and their variants may be associated with predisposition to obesity. Searching for polymorphism was carried out in three adipokine genes (TNF, RETN and IL6). The study was performed on 260 dogs, including lean (n = 109), overweight (n = 88) and obese (n = 63) dogs. The largest cohort was represented by Labrador Retrievers (n = 136). Altogether, 24 novel polymorphisms were identified: 12 in TNF (including one missense SNP), eight in RETN (including one missense SNP) and four in IL6. Distributions of five common SNPs (two in TNF, two in RETN and one in IL6) were further analyzed with regard to body condition score. Two SNPs in the non-coding parts of TNF (c.-40A>C and c.233+14G>A) were associated with obesity in Labrador dogs. The obtained results showed that the studied adipokine genes are highly polymorphic and two polymorphisms in the TNF gene may be considered as markers predisposing Labrador dogs to obesity. PMID:26692319

  3. Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.

    Pruul, K; Kisand, K; Alnek, K; Metsküla, K; Reimand, K; Heilman, K; Peet, A; Varik, K; Peetsalu, M; Einberg, Ü; Tillmann, V; Uibo, R


    Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-β, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-β in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-β and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-β production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D. PMID:25980680

  4. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y. [Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima (Japan); Hayashi, Y. [Geriatric Health Service Facility Hidamari, Hiroshima (Japan)


    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  5. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  6. Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity

    Kwon Eun-Young


    Full Text Available Abstract Background Visceral white adipose tissue (WAT hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity. Results C57BL/6 J mice were fed a high-fat diet (HFD or normal diet (ND and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery after 2–4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9 and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14. Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages. Conclusions In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches

  7. Clinical Insights on Adult-onset Sporadic Ataxias%成人发病的散发性共济失调症临床诊疗



    Adult-onset sporadic ataxias are a group of disorders manifested predominantly with ataxia, due to a variety of the potential causes including intoxication, immune-mediation, vitamins deifciencies, infections, neurodegeneration, and even some hereditary conditions. The clinical spectrum of these disorders is diverse, and their diagnosis remains a challenge. Compared with hereditary ataxias, most ataxias in this group respond the treatment well, that means the signiifcance of timely and correct diagnosis. The advanced biochemical, immune and imaging tools will help the perception and management on those ataxias. Different categories of adult-onset sporadic ataxia were elucidated with the highlight on their clinical features, neuro-imagingand diagnostic criteria.%成人发病的散发性共济失调症是由多种原因所致,临床表现以共济失调为主要的多种疾病。致病原因包括中毒、免疫介导性、维生素缺乏、感染性疾病、变性病以及遗传性疾患等。散发性共济失调临床谱具有明显异质性,临床正确诊断极具挑战性。但相比于遗传性共济失调症,此类疾患多数治疗效果较好,及时、正确诊断尤为重要。现代生化、免疫以及影像学技术有助于此类疾患的认识和诊治。文中综述并讨论可致成人发病的散发性共济失调的不同疾病分类,并着重其临床和神经影像学表现及诊断标准。

  8. Iron Deficiency Anemia in Adult Onset Still's Disease with a Serum Ferritin of 26,387 μg/L

    Sheetal Patel


    Full Text Available Serum ferritin rises in the anemia of chronic inflammation reflecting increased iron storage and other changes mediated by inflammation. When iron deficiency coexists, the ferritin may not always decline into the subnormal range. We describe the rare interaction of iron deficiency with the extreme hyperferritinemia characteristic of adult onset Still's disease. The combination has clinical relevance and allows deductions about the presence of serum ferritin at 26,387 μg/L despite obvious iron depletion. The diagnosis of iron deficiency anemia was delayed and became fully obvious when her Still's disease remitted and serum ferritin decreased to 6.5 μg/L. The coexistence of iron deficiency should be considered when evaluating a patient with anemia of chronic inflammation even when the ferritin level is elevated several hundredfold. Further insights on ferritin metabolism in Still's disease are suggested by the likelihood that the patient's massive hyperferritinemia in the acute phase of Still's disease was almost entirely of the iron-free apoferritin form.

  9. Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice

    Sadler, Natalie C.; Angel, Thomas E.; Lewis, Michael P.; Pederson, Leeanna M.; Chauvigne-Hines, Lacie M.; Wiedner, Susan D.; Zink, Erika M.; Smith, Richard D.; Wright, Aaron T.


    High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD or if the mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar or elevated relative to standard diet (SD) mice, thereby IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, β-oxidation, and respiratory chain function at levels similar to or higher than SD mice.

  10. A methyl-seq analyses of rat offspring liver reveals maternal obesity-induced alterations in dna methylation status at weaning

    Exposure to maternal obesity (MO) increases the risk of obesity in adult-life. MO was induced in rats by overfeeding via total enteral nutrition. Male offspring from obese rats gain greater body weight, fat mass and develop insulin resistance when fed high fat diets. However the mechanisms underlyin...

  11. Adult Onset Langerhans’ Cell Histiocytosis

    Rahime İnci; Hamide Sayar; Mehmet Fatih İnci; Perihan Öztürk


    Langerhans’ cell histiocytosis (LCH) is a group of diseases of unknown cause resulting from abnormal proliferation of bone marrow-originated dendritic cells called histiocytes. The incidence is between 0.5-5.4 per million. More common in childhood, it is extremely rare in adults. In adults, pulmonary involvement with Langerhans’ cell histiocytosis usually occurs as a single-system disease. In this article, the clinical, radiological and histopathological findings of a 51-year-old male patient...

  12. Adult Onset Langerhans’ Cell Histiocytosis

    Rahime İnci


    Full Text Available Langerhans’ cell histiocytosis (LCH is a group of diseases of unknown cause resulting from abnormal proliferation of bone marrow-originated dendritic cells called histiocytes. The incidence is between 0.5-5.4 per million. More common in childhood, it is extremely rare in adults. In adults, pulmonary involvement with Langerhans’ cell histiocytosis usually occurs as a single-system disease. In this article, the clinical, radiological and histopathological findings of a 51-year-old male patient with both skin, bone and pulmonary involvement were presented and discussed with recent literature.

  13. [Adult-onset rare diseases].

    Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka


    The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.). PMID:24566697

  14. TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations

    Kim, Hyoun-Ah; Han, Jae Ho; Kim, Woo-Jung; Noh, Hyun Jin; An, Jeong-Mi; Yim, Hyunee; Jung, Ju-Yang; Kim, You-Sun; Suh, Chang-Hee


    S100A8/A9 has been suggested as a marker of disease activity in patients with adult-onset Still’s disease (AOSD). We evaluated the clinical significance of S100A8/A9 as a biomarker and its pathogenic role in AOSD. Blood samples were collected prospectively from 20 AOSD patients and 20 healthy controls (HCs). Furthermore, skin and lymph node biopsy specimens of AOSD patients were investigated for S100A8/A9 expression levels via immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) of active AOSD patients and HCs were investigated for S100A8/A9 cell signals. S100A8/A9, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than those of HCs. S100A8/A9 levels correlated positively with IL-1β, TNF-α and C-reactive protein. The inflammatory cells expressing S100A8/A9 were graded from one to three in skin and lymph node biopsies of AOSD patients. The grading for S100A8/A9 was more intense in the skin lesions with karyorrhexis, mucin deposition, and neutrophil infiltration. Like lipopolysaccharide (LPS), S100A8/A9 induced phosphorylation of p38 and c-Jun amino-terminal kinase (JNK) in PBMCs, suggesting that S100A8/A9 activates Toll-like receptor 4 signaling pathways. These findings suggest that S100A8/A9 may be involved in the inflammatory response with induction of proinflammatory cytokines and may serve as a clinicopathological marker for disease activity in AOSD. PMID:27537874

  15. Functional and Structural Analyses of CYP1B1 Variants Linked to Congenital and Adult-Onset Glaucoma to Investigate the Molecular Basis of These Diseases.

    Banerjee, Antara; Chakraborty, Subhadip; Chakraborty, Abhijit; Chakrabarti, Saikat; Ray, Kunal


    Glaucoma, the leading cause of irreversible blindness, appears in various forms. Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG). We investigated the molecular basis of the variable phenotypes resulting from the defects in CYP1B1 by using subclones of 23 CYP1B1 mutants reported in glaucoma patients, in a cell based system by measuring the dual activity of the enzyme to metabolize both retinol and 17β-estradiol. Most variants linked to POAG showed low steroid metabolism while null or very high retinol metabolism was observed in variants identified in PCG. We examined the translational turnover rates of mutant proteins after the addition of cycloheximide and observed that the levels of enzyme activity mostly corroborated the translational turnover rate. We performed extensive normal mode analysis and molecular-dynamics-simulations-based structural analyses and observed significant variation of fluctuation in certain segmental parts of the mutant proteins, especially at the B-C and F-G loops, which were previously shown to affect the dynamic behavior and ligand entry/exit properties of the cytochrome P450 family of proteins. Our molecular study corroborates the structural analysis, and suggests that the pathologic state of the carrier of CYP1B1 mutations is determined by the allelic state of the gene. To our knowledge, this is the first attempt to dissect biological activities of CYP1B1 for correlation with congenital and adult onset glaucomas. PMID:27243976

  16. Genetics of Childhood Obesity

    Grant, Struan F A; Jianhua Zhao


    Obesity is a major health problem and an immense economic burden on the health care systems both in the United States and the rest of the world. The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. Genome-wide association studies (GWAS) have revealed strongly associated genomic variants associated with most common ...

  17. Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects

    Soronen Jarkko


    Full Text Available Abstract Background To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. Methods Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 hours of intravenously maintained euglycemic hyperinsulinemia from 9 insulin-resistant and 11 insulin-sensitive females. Gene expression was measured using Affymetrix HG U133 Plus 2 microarrays and qRT-PCR. Microarray data and pathway analyses were performed with Chipster v1.4.2 and by using in-house developed nonparametric pathway analysis software. Results The most prominent difference in gene expression of the insulin-resistant group during hyperinsulinemia was reduced transcription of nuclear genes involved in mitochondrial respiration (mitochondrial respiratory chain, GO:0001934. Inflammatory pathways with complement components (inflammatory response, GO:0006954 and cytokines (chemotaxis, GO:0042330 were strongly up-regulated in insulin-resistant as compared to insulin-sensitive subjects both before and during hyperinsulinemia. Furthermore, differences were observed in genes contributing to fatty acid, cholesterol and triglyceride metabolism (FATP2, ELOVL6, PNPLA3, SREBF1 and in genes involved in regulating lipolysis (ANGPTL4 between the insulin-resistant and -sensitive subjects especially during hyperinsulinemia. Conclusions The major finding of this study was lower expression of mitochondrial respiratory pathway and defective induction of lipid metabolism pathways by insulin in insulin-resistant subjects. Moreover, the study reveals several novel genes whose aberrant regulation is associated with the obese insulin-resistant phenotype.

  18. Mass Spectrometry Imaging Reveals Elevated Glomerular ATP/AMP in Diabetes/obesity and Identifies Sphingomyelin as a Possible Mediator

    Satoshi Miyamoto


    Full Text Available AMP-activated protein kinase (AMPK is suppressed in diabetes and may be due to a high ATP/AMP ratio, however the quantitation of nucleotides in vivo has been extremely difficult. Via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI to localize renal nucleotides we found that the diabetic kidney had a significant increase in glomerular ATP/AMP ratio. Untargeted MALDI-MSI analysis revealed that a specific sphingomyelin species (SM(d18:1/16:0 accumulated in the glomeruli of diabetic and high-fat diet-fed mice compared with wild-type controls. In vitro studies in mesangial cells revealed that exogenous addition of SM(d18:1/16:0 significantly elevated ATP via increased glucose consumption and lactate production with a consequent reduction of AMPK and PGC1α. Furthermore, inhibition of sphingomyelin synthases reversed these effects. Our findings suggest that AMPK is reduced in the diabetic kidney due to an increase in the ATP/AMP ratio and that SM(d18:1/16:0 could be responsible for the enhanced ATP production via activation of the glycolytic pathway.

  19. Genetics of Childhood Obesity

    Jianhua Zhao


    Full Text Available Obesity is a major health problem and an immense economic burden on the health care systems both in the United States and the rest of the world. The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. Genome-wide association studies (GWAS have revealed strongly associated genomic variants associated with most common disorders; indeed there is general consensus on these findings from generally positive replication outcomes by independent groups. To date, there have been only a few GWAS-related reports for childhood obesity specifically, with studies primarily uncovering loci in the adult setting instead. It is clear that a number of loci previously reported from GWAS analyses of adult BMI and/or obesity also play a role in childhood obesity.

  20. Metabolite profiling of sex developmental steroid conjugates reveals an association between decreased levels of steroid sulfates and adiposity in obese girls.

    Lee, Su Hyeon; Kim, Shin Hye; Lee, Won-Yong; Chung, Bong Chul; Park, Mi Jung; Choi, Man Ho


    Free and conjugated steroids coexist in a dynamic equilibrium due to complex biosynthetic and metabolic processes. This may have clinical significance related to various physiological conditions, including sex development involving the reproductive system. Therefore, we performed quantitative profiling of 16 serum steroids conjugated with glucuronic and sulfuric acids using liquid chromatography-mass spectrometry (LC-MS). All steroid conjugates were purified by solid-phase extraction and then separated through a 3-μm particle size C18 column (150mm×2.1mm) at a flow rate of 0.3 mL/min in the negative ionization mode. The LC-MS-based analysis was found to be linear (r(2)>0.99), and all steroid conjugates had a limit-of-quantification (LOQ) of 10ng/mL, except for cholesterol sulfate and 17β-estradiol-3,17-disulfate (20ng/mL). The extraction recoveries of all steroid conjugates ranged from 97.9% to 110.7%, while the overall precision (% CV) and accuracy (% bias) ranged from 4.8% to 10.9% and from 94.4% to 112.9% at four different concentrations, respectively. Profiling of steroid conjugates corrected by adiposity revealed decreased levels of steroid sulfates (Psteroid conjugates and for understanding the pathophysiology and relative contributions of adiposity in childhood obesity. PMID:27154415

  1. Direct infusion MS-based lipid profiling reveals the pharmacological effects of compound K-reinforced ginsenosides in high-fat diet induced obese mice.

    Shon, Jong Cheol; Shin, Hwa-Soo; Seo, Yong Ki; Yoon, Young-Ran; Shin, Heungsop; Liu, Kwang-Hyeon


    The serum lipid metabolites of lean and obese mice fed normal or high-fat diets were analyzed via direct infusion nanoelectrospray-ion trap mass spectrometry followed by multivariate analysis. In addition, lipidomic biomarkers responsible for the pharmacological effects of compound K-reinforced ginsenosides (CK), thus the CK fraction, were evaluated in mice fed high-fat diets. The obese and lean groups were clearly discriminated upon principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) score plot, and the major metabolites contributing to such discrimination were triglycerides (TGs), cholesteryl esters (CEs), phosphatidylcholines (PCs), and lysophosphatidylcholines (LPCs). TGs with high total carbon number (>50) and low total carbon number (fat diet induced obesity in mice, respectively. When the CK fraction was fed to obese mice that consumed a high-fat diet, the levels of certain lipids including LPCs and CEs became similar to those of mice fed a normal diet. Such metabolic markers can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, changes in the levels of such metabolites can be employed to assess the risk of obesity and the therapeutic effects of obesity management. PMID:25744175

  2. Genomic analysis of hepatic Farnesoid X Receptor (FXR) binding sites reveals altered binding in obesity and direct gene repression by FXR

    Lee, Jiyoung; Seok, Sun Mi; Yu, Pengfei; Kim, Kyungsu; Smith, Zachary; Rivas-Astroza, Marcelo; Zhong, Sheng; Kemper, Jongsook Kim


    The nuclear bile acid receptor, Farnesoid X Receptor (FXR), is an important transcriptional regulator of liver metabolism. Despite recent advances in understanding its functions, how FXR regulates genomic targets and whether the transcriptional regulation by FXR is altered in obesity remain largely unknown. Here, we analyzed hepatic genome-wide binding sites of FXR in normal and dietary obese mice by chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. A total of 15,263 and 5,272 FXR...

  3. IL-2 immunotherapy reveals potential for innate beta cell regeneration in the non-obese diabetic mouse model of autoimmune diabetes.

    Yaiza Diaz-de-Durana

    Full Text Available Type-1 diabetes (T1D is an autoimmune disease targeting insulin-producing beta cells, resulting in dependence on exogenous insulin. To date, significant efforts have been invested to develop immune-modulatory therapies for T1D treatment. Previously, IL-2 immunotherapy was demonstrated to prevent and reverse T1D at onset in the non-obese diabetic (NOD mouse model, revealing potential as a therapy in early disease stage in humans. In the NOD model, IL-2 deficiency contributes to a loss of regulatory T cell function. This deficiency can be augmented with IL-2 or antibody bound to IL-2 (Ab/IL-2 therapy, resulting in regulatory T cell expansion and potentiation. However, an understanding of the mechanism by which reconstituted regulatory T cell function allows for reversal of diabetes after onset is not clearly understood. Here, we describe that Ab/IL-2 immunotherapy treatment, given at the time of diabetes onset in NOD mice, not only correlated with reversal of diabetes and expansion of Treg cells, but also demonstrated the ability to significantly increase beta cell proliferation. Proliferation appeared specific to Ab/IL-2 immunotherapy, as anti-CD3 therapy did not have a similar effect. Furthermore, to assess the effect of Ab/IL-2 immunotherapy well after the development of diabetes, we tested the effect of delaying treatment for 4 weeks after diabetes onset, when beta cells were virtually absent. At this late stage after diabetes onset, Ab/IL-2 treatment was not sufficient to reverse hyperglycemia. However, it did promote survival in the absence of exogenous insulin. Proliferation of beta cells could not account for this improvement as few beta cells remained. Rather, abnormal insulin and glucagon dual-expressing cells were the only insulin-expressing cells observed in islets from mice with established disease. Thus, these data suggest that in diabetic NOD mice, beta cells have an innate capacity for regeneration both early and late in disease

  4. Asthma and obesity

    Ulrik, Charlotte S


    PURPOSE OF REVIEW: Obesity has significant negative impact on asthma control and risk of exacerbations. The purpose of this review is to discuss recent studies evaluating the effects of weight reduction on asthma control in obese adults. RECENT FINDINGS: Clinical studies have shown that weight...... reduction in obese patients is associated with improvements in symptoms, use of controller medication, and asthma-related quality of life together with a reduction in the risk for severe exacerbations. Furthermore, several studies have also revealed improvements in lung function and airway responsiveness......: Weight reduction in obese adults with asthma leads to an overall improvement in asthma control, including airway hyperresponsiveness and inflammation. Weight reduction should be a cornerstone in the management of obese patients with asthma....

  5. Obesity and Asthma

    Juel, Caroline Trunk-Black; Ulrik, Charlotte Suppli


    Asthma is more prevalent in obese compared with normal weight subjects. Our aim has been to review current knowledge of the impact of obesity on asthma severity, asthma control, and response to therapy.Several studies have shown that overweight and obesity is associated with more severe asthma and...... impaired quality of life compared with normal weight individuals. Furthermore, obesity is associated with poorer asthma control, as assessed by asthma control questionnaires, limitations in daily activities, breathlessness and wheezing, use of rescue medication, unscheduled doctor visits, emergency...... department visits, and hospitalizations for acute asthma. Studies of the impact of a high body mass index (BMI) on response to asthma therapy have, however, revealed conflicting results. Most studies show that overweight and obesity is associated with less favorable response to asthma therapy with regard to...

  6. Molecular basis of adult-onset and chronic G sub M2 gangliosidoses in patients of Ashkenazi Jewish origin: Substitution of serine for glycine at position 269 of the. alpha. -subunit of. beta. -hexosaminidase

    Paw, B.H.; Kaback, M.M.; Neufeld, E.F. (Univ. of California, Los Angeles (USA))


    Chronic and adult-onset G{sub M2} gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of {beta}-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective {alpha}-subunit that failed to associate with the {beta}-subunit. The authors have now found a guanosine to adenosine transition at the 3{prime} end of exon 7, which causes substitution of serine for glycine at position 269 of the {alpha}-subunit. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly {yields} Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly {yields} Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic G{sub M2} gangliosidosis.

  7. Cultivating childhood obesity

    Greene-Martin, DeCleasha


    In recent years the levels of obesity in the United States has risen greatly especially amongst children. Doctors, psychologists, and other scientists have been studying the growing problem for years. Implications for childhood obesity not only have enormous physical consequences but emotional repercussions which can affect the child’s academic and social development. A number of factors have been identified as having an effect on these children; family life reveals the grocery store habits o...

  8. Obesity management

    Rates of obesity in the United States have increased dramatically over the past 30 years. Approximately 35% of children and 66% of adults are currently considered overweight or obese. Although obesity is seen in all ethnicities and economic classes, ethnic minorities and those of lower socioeconomic...

  9. Childhood Obesity

    Yuca, Sevil Ari, Ed.


    This book aims to provide readers with a general as well as an advanced overview of the key trends in childhood obesity. Obesity is an illness that occurs due to a combination of genetic, environmental, psychosocial, metabolic and hormonal factors. The prevalence of obesity has shown a great rise both in adults and children in the last 30 years.…

  10. Childhood Obesity

    Aydın, Ahmet; Koca, Fahrettin; Fıçıcıoğlu, Can; Çam, Halit; Mıkla, Şerare


    Management of childhood obesity and its early and late complications are among the most difficult problems confronted by pediatricians and practitioners The purpose of this review is to provide information for the evaluation and treatment of childhood obesity Key nbsp;words: nbsp;Child Obesity Etiology Management Complications

  11. Plastics derived endocrine disruptors (BPA, DEHP and DBP induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    Mohan Manikkam

    Full Text Available Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3 following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA, bis(2-ethylhexylphthalate (DEHP and dibutyl phthalate (DBP at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

  12. Childhood obesity treatment and prevention. Psychological perspectives of clinical approaches

    Maria Catena Quattropani; Teresa Buccheri


    Objective: This work focuses on clinical psychologist’ presence within childhood obesity prevention programmes in several countries. Method: The Authors collected articles considering psychological, biological and social aspects linked to childhood obesity. Results: Studies reveal that childhood obesity prevention programmes are based on biological, medical and educational aspects; clinical psychologists up until now have been engaged almost exclusively in the treatment of obesity. Conclusion...

  13. Obesity and gastrointestinal neoplasms

    Izabela Binkowska-Borgosz


    Full Text Available Being overweight or obese is a significant public health problem in the 21st century due to its scale, common existence and its cause-effect association with multiple diseases. Excessive accumulation of adipose tissue in humans is regarded as a major risk factor for development of cardiovascular and skeletal diseases. However, data from recent years have revealed that obesity is also strongly associated with increased risk of the majority of cancers in humans, including those originating from the gastrointestinal tract. During the last few year this association has been thoroughly proven and supported by several epidemiological analyses. The authors present i the current state of knowledge regarding key (pathomechanisms that link metabolism of human adipose tissue to development/progression of neoplasms (especially in the gastrointestinal tract, as well as ii the results of selected clinical studies in which the influence of obesity on risk of gastrointestinal cancer development has been addressed.

  14. Childhood Obesity

    Wilkinson, Justine; Howard, Simon


    Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to dis...

  15. Prepregnancy Obesity and Birth Outcomes.

    Averett, Susan L; Fletcher, Erin K


    Objective To investigate the association between prepregnancy obesity and birth outcomes using fixed effect models comparing siblings from the same mother. Methods A total of 7496 births to 3990 mothers from the National Longitudinal Survey of Youth 1979 survey are examined. Outcomes include macrosomia, gestational length, incidence of low birthweight, preterm birth, large and small for gestational age (LGA, SGA), c-section, infant doctor visits, mother's and infant's days in hospital post-partum, whether the mother breastfed, and duration of breastfeeding. Association of outcomes with maternal pre-pregnancy obesity was examined using Ordinary Least Squares (OLS) regression to compare across mothers and fixed effects to compare within families. Results In fixed effect models we find no statistically significant association between most outcomes and prepregnancy obesity with the exception of LGA, SGA, low birth weight, and preterm birth. We find that prepregnancy obesity is associated with a with lower risk of low birthweight, SGA, and preterm birth but controlling for prepregnancy obesity, increases in GWG lead to increased risk of LGA. Conclusions Contrary to previous studies, which have found that maternal obesity increases the risk of c-section, macrosomia, and LGA, while decreasing the probability of breastfeeding, our sibling comparison models reveal no such association. In fact, our results suggest a protective effect of obesity in that women who are obese prepregnancy have longer gestation lengths, and are less likely to give birth to a preterm or low birthweight infant. PMID:26515472

  16. Hormones and Obesity

    ... Balance › Hormones and Obesity Fact Sheet Hormones and Obesity March, 2010 Download PDFs English Espanol Editors Caroline Apovian, MD Judith Korner, MD, PhD What is obesity? Obesity is a chronic (long-term) medical problem ...

  17. Childhood Overweight and Obesity

    ... Childhood Obesity Facts The prevalence of obesity among low-income children aged 2 through 4 years, by state ... Obesity now affects 1 in 6 children and adolescents in the United States. Childhood Obesity Facts How ...

  18. Food reward, hyperphagia, and obesity

    Berthoud, Hans-Rudolf; Lenard, Natalie R.; Shin, Andrew C.


    Given the unabated obesity problem, there is increasing appreciation of expressions like “my eyes are bigger than my stomach,” and recent studies in rodents and humans suggest that dysregulated brain reward pathways may be contributing not only to drug addiction but also to increased intake of palatable foods and ultimately obesity. After describing recent progress in revealing the neural pathways and mechanisms underlying food reward and the attribution of incentive salience by internal stat...

  19. Adult-Onset Metachromatic Leukodystrophy: Two Cases

    Gaye Eryaşar


    Full Text Available Metachromatic Leukodystrophy(MLD is a lisosomal storage disorder which is characterized with arylsulphatase A deficiency. Enzyme deficiency results with demiyelination and storage of sulphatides in central nervous system.According to onset age;the disease has three major clinical forms as late infantile,juvenile and adult form. It is a rare disorder. For the patients who did not develop neurological findings bone marrow or hematopoietic stem cell transplantation may be effective as treatment.

  20. Childhood obesity.

    Han, Joan C; Lawlor, Debbie A; Kimm, Sue Y S


    Worldwide prevalence of childhood obesity has increased greatly during the past three decades. The increasing occurrence in children of disorders such as type 2 diabetes is believed to be a consequence of this obesity epidemic. Much progress has been made in understanding of the genetics and physiology of appetite control and from these advances, elucidation of the causes of some rare obesity syndromes. However, these rare disorders have so far taught us few lessons about prevention or reversal of obesity in most children. Calorie intake and activity recommendations need reassessment and improved quantification at a population level because of sedentary lifestyles of children nowadays. For individual treatment, currently recommended calorie prescriptions might be too conservative in view of evolving insight into the so-called energy gap. Although quality of research into both prevention and treatment has improved, high-quality multicentre trials with long-term follow-up are needed. Meanwhile, prevention and treatment approaches to increase energy expenditure and decrease intake should continue. Recent data suggest that the spiralling increase in childhood obesity prevalence might be abating; increased efforts should be made on all fronts to continue this potentially exciting trend. PMID:20451244

  1. 甲状腺激素对大鼠额叶乙酰胆碱的影响%Effect of thyroxine on acetylcholine level in the prefrontal cortex of rats with adult-onset hypothyroidism

    刘俊霞; 朱德发; 王芬; 王取南; 马维青


    Objective To study acetylcholine(Ach) level in prefrontal cortex of adult-onset hypothyroidism rats,and the difference of Ach after thyroid hormones treatment. Methods This animal study included control group (η=9) ,Hypothyroidism group (η= 8) and Hypothyroidism treated with T4(6 ug/100g body weight) group (n = 9 ) . The hypothyroidism models were replicated with 6-n-propyl-2-thiouracil ( PTU ). The levels of serum T3, T4 were assayed by radioimmunoassay method, and the level of acetylcholine ( Ach ) in prefrontal cortex was analyzed by the basic hydroxylamine colorimetric method. Results Compared to the control group,serum levels of T3 and T4 were significantly lower in the hypothyroid group (P <0.05)and similar in the T4-6 group and brain Ach level were significantly lower in prefrontal cortex in the hypothyroid than those of the control group ( P < 0. 05 ) and were not significantly different in the T4-6 group. Conclusion The level of Ach in the prefrontal cortex of adult-onset hypothyroidism is lower,Ach may be reversed by thyroid hormones replasement treatment in T4-6 group.%目的 研究成年期甲状腺功能减退症大鼠额叶内乙酰胆碱变化及甲状腺素替代治疗后的情况.方法 26只成年期雄性SD大鼠随机分为三组,用丙基硫氧嘧啶(PTU)建立成年期大鼠甲减模型,采用放射免疫法测定健康对照组、甲减组、甲状腺素替代治疗组(T4-6)大鼠的血清甲状腺激素水平;碱性羟胺比色法测定脑组织乙酰胆碱含量;用单因素方差分析比较三组之间各项指标差异.结果 与健康对照组相比,甲减组大鼠血清T3、T4水平显著减低、TSH水平增加(P<0.05);替代治疗后,血清T3、T4、TSH恢复至正常水平;甲减组大鼠额叶内乙酰胆碱含量降低(P<0.05),替代治疗后乙酰胆碱含量与对照组相比差异无统计学意义(P>0.05).结论 成年期甲减大鼠额叶内乙酰胆碱含量减少,甲状腺素替代治疗后乙酰胆碱含量恢复正常.

  2. Childhood obesity

    Heitmann, Berit L; Koplan, Jeffrey; Lissner, Lauren


    Despite progress toward assuring the health of today's young population, the 21(st) century began with an epidemic of childhood obesity. There is general agreement that the situation must be addressed by means of primary prevention, but relatively little is known about how to intervene effectively....... The evidence behind the assumption that childhood obesity can be prevented was discussed critically in this roundtable symposium. Overall, there was general agreement that action is needed and that the worldwide epidemic itself is sufficient evidence for action. As the poet, writer, and scholar...

  3. [Primary prevention of adult obesity. an interdisciplinary analysis].

    Hilbert, Anja; Ried, Jens; Schneider, Daniel; Juttner, Clemens; Sosna, Marc; Dabrock, Peter; Lingenfelder, Michael; Voit, Wolfgang; Rief, Winfried; Hebebrand, Johannes


    The primary prevention of adult obesity requires combined efforts by stakeholders at various societal levels, based on the knowledge from multiple disciplines. The goal of the present study was, therefore, to analyze current preventive approaches and delineate implications for future prevention research and practice by integrating knowledge from genetics, law, economics, psychology, and social ethics (Figure 1). Inconclusive evidence on the etiology of obesity, a complex, multifactorial condition, likely complicates prevention, contributing to a lack of specificity regarding target groups, focus, and techniques of prevention. Given the urgency and significance of the "obesity problem" that requires immediate and effective solutions, it is recommended that the various existing and developing prevention programs are evaluated to ensure orientation at current risk factor research. Results from genetic risk factor research can be used as a rationale to increase specificity of preventive measures regarding identification of high-risk groups, timing, and goals of prevention. Further, it is important to evaluate prevention programs for systematic application of behavior modification techniques and consideration of individual risk factors and resources to ensure promotion of long-term behavior change that leads to weight maintenance and a reduction of incidence rates of obesity in adults (Figure 3). Although the primary prevention of childhood obesity may lead to a reduction of incidence rates of obesity in adults, high rates of adult-onset obesity and the related medical and psychosocial sequelae in adulthood underscore the necessity of preventive efforts for adults. Concerning the environmental basis of obesity prevention, in many countries, the institutional and legal framework of preventive approaches requires further examination in order to improve funding, coordination between multiple stakeholders, and implementation of prevention in the health-care system. Evidence

  4. Childhood Obesity


    In this podcast, Dr. Tom Frieden, CDC Director, discusses the decrease in childhood obesity rates and what strategies have been proven to work to help our children grow up and thrive.  Created: 8/6/2013 by National Center for Injury Prevention and Control.   Date Released: 3/6/2014.

  5. Liver morphology in morbid obesity

    Andersen, T; Gluud, C


    Literature on liver morphology in untreated obesity reveals varying prevalences of various pathological findings. The purpose of this literature study was to summarize and evaluate the published observations and to discuss discrepant findings. A complete search was aimed at utilizing bibliographi...... of obesity, age, sex, alcohol consumption, diabetes mellitus) does not point towards a single causal factor. Co-influence of additional pathogenetic factors are likely in the development of liver changes in morbid obesity....... methods including a computerized survey. Forty-one original articles were included, comprising information on liver morphology in 1515 morbidly obese patients. Liver biopsy was considered normal in 12 per cent of the cases. The most frequent abnormality reported was fatty change, present in 80 per cent of...

  6. Obesity in children

    Canoy, Dexter; Bundred, Peter


    Obesity is the result of long-term energy imbalances, where daily energy intake exceeds daily energy expenditure. Obesity in children is associated with physical as well as psychosocial problems. Long-term adverse health consequences of childhood obesity may include increased risk for cardiovascular and metabolic disease in adulthood. Most obese adolescents stay obese as adults.

  7. Obesity in the new media: a content analysis of obesity videos on YouTube.

    Yoo, Jina H; Kim, Junghyun


    This study examines (1) how the topics of obesity are framed and (2) how obese persons are portrayed on YouTube video clips. The analysis of 417 obesity videos revealed that a newer medium like YouTube, similar to traditional media, appeared to assign responsibility and solutions for obesity mainly to individuals and their behaviors, although there was a tendency that some video categories have started to show other causal claims or solutions. However, due to the prevailing emphasis on personal causes and solutions, numerous YouTube videos had a theme of weight-based teasing, or showed obese persons engaging in stereotypical eating behaviors. We discuss a potential impact of YouTube videos on shaping viewers' perceptions about obesity and further reinforcing stigmatization of obese persons. PMID:21809934

  8. Obesity & osteoarthritis

    Lauren K King


    Full Text Available The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA, a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate of joint replacements as well as operative complications. Weight loss in OA can impart clinically significant improvements in pain and delay progression of joint structural damage. Further work is required to determine the relative contributions of mechanical and metabolic factors in the pathogenesis of OA.

  9. Prenatal Cocaine Exposure and Childhood Obesity at Nine Years

    LaGasse, Linda L.; Gaskins, Ronnesia B.; Bada, Henrietta S.; Shankaran, Seetha; Liu, Jing; Lester, Barry M.; Bauer, Charles R.; Higgins, Rosemary D.; Das, Abhik; Roberts, Mary


    Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI] ≥ 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcoho...


    Hendy Hendy


    Full Text Available Obesity has become a global issue. Previous studies in Bali reveal an increase in the proportionof obesity in adolescents. Obesity causes hypertension; hence there should also be an increase inthe prevalence of hypertension as well in Bali. Hypertension in obese adolescents could be causedby various factors, hence identification of the risks factors is crucial as a preventive approach.The aim of this study was to prove an association between obesity and hypertension in adolescents,and to look for the risk factors. We used an analitical cross sectional design conducted to 12-14years old samples. We took body weight, height, waist circumference, hip circumference, andblood pressure measurements with appropriate devices and asked for information regarding lifestyle and familial history by a questionnare filled in by the samples. The association of obeseadolescents with hypertension and their risk factors was analyzed by Chi-square and multivariatetests. A total of 225 subjects from Santo Yoseph junior high school students, west Denpasar,Bali, met the inclusion criteria. The proportion of obese subjects in this study was 25.7%. Wefound that proportion in familial history of obesity was greater in obese than non-obese subjects(70.7 % vs 41.3%. Logistic regression test revealed that obese subjects with hypertension had abody mass index (BMI > 30 with odds ratio of 7.3 (CI 95% = 1.8 to 28.8 and P = 0.005. Weconcluded that there was an association between obesity and adolescents with hypertension,and BMI > 30 could be a risk factor for obese adolescents with hypertension.

  11. Obesity and Cancer Risk

    ... may stimulate or inhibit cell growth. For example, leptin, which is more abundant in obese people, seems ... is known about the relationship between obesity and kidney cancer? Obesity has been consistently associated with renal ...

  12. Obesity hypoventilation syndrome (OHS)

    Obesity hypoventilation syndrome (OHS) is a condition in some obese people in which poor breathing leads to ... Maintain a healthy weight and avoid obesity. Use your CPAP or BiPAP treatment as your provider prescribed.

  13. Obesity Hypoventilation Syndrome

    ... page from the NHLBI on Twitter. What Is Obesity Hypoventilation Syndrome? Obesity hypoventilation (HI-po-ven-tih- ... NHLBI Research Featured in HBO Documentary Series on Obesity Hear people talk about their challenges and successes ...

  14. Obesity and Hispanic Americans

    ... and Data > Minority Population Profiles > Hispanic/Latino > Obesity Obesity and Hispanic Americans Among Mexican American women, 77 ... ss6304.pdf [PDF | 3.38MB] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  15. Obesity and African Americans

    ... Data > Minority Population Profiles > Black/African American > Obesity Obesity and African Americans African American women have the ... ss6304.pdf [PDF | 3.38MB] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  16. Obesity and Asian Americans

    ... and Data > Minority Population Profiles > Asian American > Obesity Obesity and Asian Americans Non-Hispanic whites are 60% ... youthonline . [Accessed 05/25/2016] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  17. Impaired decision making among morbidly obese adults.

    Brogan, Amy


    The Iowa Gambling Task (IGT) measures affective decision making and has revealed decision making impairments across a wide range of eating disorders. This study aimed to investigate affective decision making in severely obese individuals.

  18. Obesity Prevalence Maps

    ... Breastfeeding Micronutrient Malnutrition State and Local Programs Adult Obesity Prevalence Maps Recommend on Facebook Tweet Share Compartir Obesity Prevalence in 2015 Varies Across States and Territories ...

  19. Obesity in Malaysia.

    Ismail, M N; Chee, S S; Nawawi, H; Yusoff, K; Lim, T O; James, W P T


    This study was undertaken to assess the recent data on Malaysian adult body weights and associations of ethnic differences in overweight and obesity with comorbid risk factors, and to examine measures of energy intake, energy expenditure, basal metabolic rate (BMR) and physical activity changes in urban and rural populations of normal weight. Three studies were included (1) a summary of a national health morbidity survey conducted in 1996 on nearly 29 000 adults > or =20 years of age; (2) a study comparing energy intake, BMR and physical activity levels (PALs) in 409 ethnically diverse, healthy adults drawn from a population of 1165 rural and urban subjects 18-60 years of age; and (3) an examination of the prevalence of obesity and comorbid risk factors that predict coronary heart disease and type 2 diabetes in 609 rural Malaysians aged 30-65 years. Overweight and obesity were calculated using body mass index (BMI) measures and World Health Organization (WHO) criteria. Energy intake was assessed using 3-d food records, BMR and PALs were assessed with Douglas bags and activity diaries, while hypertension, hyperlipidaemia and glucose intolerance were specified using standard criteria. The National Health Morbidity Survey data revealed that in adults, 20.7% were overweight and 5.8% obese (0.3% of whom had BMI values of >40.0 kg m(-2)); the prevalence of obesity was clearly greater in women than in men. In women, obesity rates were higher in Indian and Malay women than in Chinese women, while in men the Chinese recorded the highest obesity prevalences followed by the Malay and Indians. Studies on normal healthy subjects indicated that the energy intake of Indians was significantly lower than that of other ethnic groups. In women, Malays recorded a significantly higher energy intake than the other groups. Urban male subjects consumed significantly more energy than their rural counterparts, but this was not the case in women. In both men and women, fat intakes (%) were

  20. Comprehensive Survey of miRNA-mRNA Interactions Reveals That Ccr7 and Cd247 (CD3 zeta) are Posttranscriptionally Controlled in Pancreas Infiltrating T Lymphocytes of Non-Obese Diabetic (NOD) Mice

    Macedo, Claudia; Sakamoto-Hojo, Elza T.; Donadi, Eduardo A.; Passos, Geraldo A.


    In autoimmune type 1 diabetes mellitus (T1D), auto-reactive clones of CD4+ and CD8+ T lymphocytes in the periphery evolve into pancreas-infiltrating T lymphocytes (PILs), which destroy insulin-producing beta-cells through inflammatory insulitis. Previously, we demonstrated that, during the development of T1D in non-obese diabetic (NOD) mice, a set of immune/inflammatory reactivity genes were differentially expressed in T lymphocytes. However, the posttranscriptional control involving miRNA interactions that occur during the evolution of thymocytes into PILs remains unknown. In this study, we postulated that miRNAs are differentially expressed during this period and that these miRNAs can interact with mRNAs involved in auto-reactivity during the progression of insulitis. To test this hypothesis, we used NOD mice to perform, for the first time, a comprehensive survey of miRNA and mRNA expression as thymocytes mature into peripheral CD3+ T lymphocytes and, subsequently, into PILs. Reconstruction of miRNA-mRNA interaction networks for target prediction revealed the participation of a large set of miRNAs that regulate mRNA targets related to apoptosis, cell adhesion, cellular regulation, cellular component organization, cellular processes, development and the immune system, among others. The interactions between miR-202-3p and the Ccr7 chemokine receptor mRNA or Cd247 (Cd3 zeta chain) mRNA found in PILs are highlighted because these interactions can contribute to a better understanding of how the lack of immune homeostasis and the emergence of autoimmunity (e.g., T1D) can be associated with the decreased activity of Ccr7 or Cd247, as previously observed in NOD mice. We demonstrate that these mRNAs are controlled at the posttranscriptional level in PILs. PMID:26606254


    Ogunbode, A.M.; A A Fatiregun; Ogunbode, O.O.


    Obesity is becoming of interest as a non-communicable disease. There is however a dearth of information on obesity in this environment, as literature in developing countries is limited. Review of health risks of obesity is useful in order to increase the pool of available information in Nigeria and to draw attention to obesity and its attendant health risks.

  2. Managing childhood obesity

    The prevalence of childhood obesity has steadily increased over the last decades, with approximately 35% of children aged 6-19 classified as overweight or obese. Recently, a plateau in the increasing rates of obesity has been observed. Despite this leveling off, overweight and obese children are hea...

  3. Genetics of Obesity.

    Srivastava, Apurva; Srivastava, Neena; Mittal, Balraj


    Numerous classical genetic studies have proved that genes are contributory factors for obesity. Genes are directly responsible for obesity associated disorders such as Bardet-Biedl and Prader-Willi syndromes. However, both genes as well as environment are associated with obesity in the general population. Genetic epidemiological approaches, particularly genome-wide association studies, have unraveled many genes which play important roles in human obesity. Elucidation of their biological functions can be very useful for understanding pathobiology of obesity. In the near future, further exploration of obesity genetics may help to develop useful diagnostic and predictive tests for obesity treatment. PMID:27605733

  4. Childhood obesity treatment and prevention. Psychological perspectives of clinical approaches

    Maria Catena Quattropani


    Full Text Available Objective: This work focuses on clinical psychologist’ presence within childhood obesity prevention programmes in several countries. Method: The Authors collected articles considering psychological, biological and social aspects linked to childhood obesity. Results: Studies reveal that childhood obesity prevention programmes are based on biological, medical and educational aspects; clinical psychologists up until now have been engaged almost exclusively in the treatment of obesity. Conclusions: There is a clear need to consider psychological aspects (emotional, cognitive and relational related to the childhood obesity’s causes and involve psychologists in its prevention projects. Keywords: childhood obesity, overweight, multidisciplinary approach, clinical psychology, prevention, treatment

  5. The role of nurses in the prevention and management of obesity.

    Lazarou, Chrystalleni; Kouta, Christiana

    This paper examines the current scientific knowledge on the relationship between diet and obesity, and considers the implications for nursing practice. It focuses on the main nutritional elements that have been identified as significant in the prevention and management of obesity. Research findings reveal the important role of specific dietary habits and patterns and their influence on obesity; particularly on childhood obesity. This paper discusses the nursing implications in relation to the prevention and management of obesity. PMID:20622760

  6. Unraveling the genetics of human obesity.

    David M Mutch


    Full Text Available The use of modern molecular biology tools in deciphering the perturbed biochemistry and physiology underlying the obese state has proven invaluable. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes (Prader-Willi and Bardet-Biedl previously assumed to be controlled by a single gene are, conversely, regulated by multiple elements. Finally, the application of comprehensive profiling technologies coupled with creative statistical analyses has revealed that interactions between genetic and environmental factors are responsible for the common obesity currently challenging many Westernized societies. As such, an improved understanding of the different "types" of obesity not only permits the development of potential therapies, but also proposes novel and often unexpected directions in deciphering the dysfunctional state of obesity.

  7. Learning from state surveillance of childhood obesity.

    Longjohn, Matt; Sheon, Amy R; Card-Higginson, Paula; Nader, Philip R; Mason, Maryann


    Data on childhood obesity collected by the Centers for Disease Control and Prevention helped reveal the nation's epidemic of overweight and obese children. But more information is needed. Collecting body mass index (BMI)-the widely accepted measurement of childhood weight status-at the state and local levels can be instrumental in identifying and tracking obesity trends, designing interventions to help overweight children, and guiding broader policy solutions. Approximately thirty states have enacted or proposed BMI surveillance laws and regulations. Arkansas stands out as the state with the highest-quality surveillance data. Innovative strategies being pursued in a number of other states should be explored for broader dissemination. PMID:20194988

  8. Immunometabolism in Obese Asthmatics: Are We There Yet?

    Lisa G. Wood


    Full Text Available Obesity is now recognised as a worldwide epidemic. The recent International Association for the Study of Obesity/International Obesity Taskforce (IASO/IOTF analysis estimates that approximately 1.0 billion adults are currently overweight and a further 475 million are obese. Obesity has huge psychosocial impact with obese children and adolescents facing discrimination and stigmatization in many areas of their lives leading to body dissatisfaction, low self-esteem and depression. Indeed, obesity is recognised as an important risk factor for the development of several chronic diseases such as hypertension, cancer, asthma and metabolic syndrome. Chronic low grade systemic inflammation is considered as a hallmark of obesity and may possibly explain the link between obesity and chronic disease, in particular the increased incidence, prevalence and severity of asthma in obese individuals. There is now strong evidence for infiltration of immune and inflammatory cells into adipose tissue that drives systemic inflammation and subsequent end organ damage. In addition to adipocytes, the key adipose tissue resident immune cells are macrophages and mast cells. Immunometabolism, as an emerging field of investigation, explores the pivotal role of these immune cells in translating immunological changes to metabolic effects in obesity. Abundance of free fatty acids, along with other inflammatory cytokines shift the balance of metabolic homeostasis to pro-inflammatory status by influencing the development of inflammatory cell lineage, which, further exhibits distinct functional phenotypes. There is emerging evidence for macrophage activation and functional polarization of an anti-inflammatory M2 phenotype towards a pro-inflammatory M1 phenotype of macrophages in obese adipose tissue. Similarly, studies in both obese humans and murine models reveal the pathognomic presence of an increased number of mast cells in visceral adipose tissue. These suggest a possible

  9. Obesity and Anesthesia

    ... Apnea and Anesthesia Smoking and Anesthesia Outpatient Surgery Obesity and Anesthesia More than one-third of Americans ... Sleep Apnea, a chronic medical problem common with obesity, can present with serious breathing problems before, during, ...

  10. Obesity hypoventilation syndrome (OHS)

    ... this page: // Obesity hypoventilation syndrome (OHS) To use the sharing features on this page, please enable JavaScript. Obesity hypoventilation syndrome (OHS) is a condition in some ...

  11. Reducing Childhood Obesity

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  12. Obesity and health (image)

    Obesity increases a person's risk of illness and death due to diabetes, stroke, heart disease, hypertension, high cholesterol, and kidney and gallbladder disease. Obesity may increase the risk for some types of ...

  13. Obesity: Pathophysiology and Intervention

    Yi Zhang


    Full Text Available Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

  14. Obesity in children

    ... regular menstrual periods. Obese children often have low self-esteem. They are more likely to be teased or ... EA, et al. Best practice updates for pediatric/adolescent weight loss surgery. Obesity (Silver Spring). 2009 May; ...

  15. Overweight and Obesity Statistics

    ... the full list of resources ​​. Overweight and Obesity Statistics Page Content About Overweight and Obesity Prevalence of ... adults age 20 and older [ Top ] Physical Activity Statistics Adults Research Findings Research suggests that staying active ...

  16. Economics, Policy, and Obesity

    Loureiro, Maria L.; Nayga, Rodolfo M.


    The US population now leads the world in obesity rates. The estimated societal cost of the overweight and obesity issue exceeds $115 billion. Policy may play a role if economically justifiable but conflicting interests exist.

  17. Reducing Childhood Obesity

    ... Navigation Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... page please turn Javascript on. The We Can! childhood obesity-prevention program involves parents, caregivers, and community leaders ...

  18. Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse

    Nikpay, Majid; Šeda, Ondrej; Tremblay, Johanne; Petrovich, Milan; Gaudet, Daniel; Kotchen, Theodore A.; Cowley, Allen W.; Hamet, Pavel


    Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58 000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and cof...

  19. Obesity in Children

    Arteburn, David E


    The prevalence of childhood obesity has increased dramatically during the past decades all over the world. The majority of obesity in adulthood has its origins in childhood which makes obesity a pediatric concern and the period when interventions should be done. Obesity is associated with increased morbidity and mortality in adult life and several adverse consequences in childhood like insulin resistance, type 2 diabetes, dyslipidemia, polycystic ovarian syndrome, pulmonary and orthopedic dis...

  20. Thinking Evolutionarily About Obesity

    Genné-Bacon, Elizabeth A.


    Obesity, diabetes, and metabolic syndrome are growing worldwide health concerns, yet their causes are not fully understood. Research into the etiology of the obesity epidemic is highly influenced by our understanding of the evolutionary roots of metabolic control. For half a century, the thrifty gene hypothesis, which argues that obesity is an evolutionary adaptation for surviving periods of famine, has dominated the thinking on this topic. Obesity researchers are often not aware that there i...

  1. The obesity epidemic

    Kollar, Lenka; Epifano, Evienne; McKneight, Molly; Miskovich, Jeff; Moore, Heather


    The incidence of chronic, noncommunicable diseases, such as heart disease, is increasing at an alarming rate on the global scale. The growing prevalence of overweight and obesity have led to an upsurge in cases of diabetes and other obesity-related diseases. About 18 million people die every year from heart disease, of which diabetes and obesity are major predisposing factors. Worldwide, more than 1.1 billion adults are overweight, 312 million of which are obese. The number of children that a...

  2. Obesity and ARDS

    Hibbert, Kathryn; Rice, Mary; Malhotra, Atul


    Obesity prevalence continues to increase globally, with figures exceeding 30% of some populations. Patients who are obese experience alterations in baseline pulmonary mechanics, including airflow obstruction, decreased lung volumes, and impaired gas exchange. These physiologic changes have implications in many diseases, including ARDS. The unique physiology of patients who are obese affects the presentation and pathophysiology of ARDS, and patients who are obese who have respiratory failure p...

  3. Obesity and Diabetes:

    Diamant, Allison L.; Babey, Susan H.; Wolstein, Joelle; Jones, Malia


    The prevalence of both diabetes and obesity has grown significantly in California. Six million adults are obese and an additional 9.3 million are overweight. Obesity is a significant risk factor for diabetes; more than two million adults have been diagnosed with diabetes in California. Obesity and diabetes disproportionately affect people of color, the poor and those with the least education in California. Policy and environmental changes that promote and encourage physical activity and healt...

  4. Environmental Perturbations: Obesity

    Shore, Stephanie A.


    Obesity currently affects about one third of the U.S. population, while another one third is overweight. The importance of obesity for certain conditions such as heart disease and type 2 diabetes is well appreciated. The effects of obesity on the respiratory system have received less attention and are the subject of this chapter. Obesity alters the static mechanic properties of the respiratory system leading to a reduction in the functional residual capacity (FRC) and the expiratory reserve v...

  5. Digging deeper into obesity

    Ahima, Rexford S.


    The growing problem of obesity is associated with multiple morbidities, including increased risk of diabetes, hypertension, heart disease, sleep apnea, and cancer. Obesity promotes disability, decreases productivity, and shortens life span. Although much attention has been focused on diet and exercise, these strategies alone are not effective in preventing obesity and maintaining weight loss. Moreover, the development of pharmacological approaches for obesity treatment has been dogged by poor...

  6. Canine and feline obesity

    Sandøe, Peter; Palmer, Clare; Corr, Sandra;


    Recent years have seen a drastic increase in the rates of overweight and obesity among people living in some developed nations. There has also been increased concern over obesity in companion animals. In the latest article in Veterinary Record's series on One Health, Peter Sandøe and colleagues...... argue that the relationship between obesity in people and in companion animals is closer and more complex than previously thought, and that obesity should be treated as a One Health problem....


    Şahin, Aynur; Doğru, Hatice Yılmaz


    Obesity is one of the serious condition that commonly effects health in modern age. It was reported that obesity was three-fold increased in the last three decades. According to the statement by World Health Organisation in 2005, 700 million people will be estimated obese in 2015. While neuraxial anesthesia is a commonly used technique in the worldwide, the process may have difficulties in obese patients. In this review, the pathophysiological changes and challenges in neuraxial anesthesia ...

  8. Obesity and gastric balloon

    Yasawy, Mohammed I; Al-Quorain, Abdulaziz A.; Anas M Hussameddin; Yasawy, Zakia M.; Al-Sulaiman, Raid M.


    Background: The obesity epidemic, which is among the most common nutritional disorders, is rising rapidly worldwide. It leads to several health problems such as metabolic disorders, stroke, and even cancer. Efforts to control obesity with exercise and diet have a limited value in obese patients and different approaches to do this have been tried. In this paper, we share our experience with bioenteric intragastric balloon (BIB) in treating obesity: Its safety, tolerability, and its efficacy in...

  9. Obesity and metabolic inflammation

    Xu, Haiyan


    Obesity epidemics affect 35.7% of adults and approximately 17% of children in the United States. Obesity has been associated with several health disorders, such as type 2 diabetes, cardiovascular diseases, fatty liver disease, and certain forms of cancer. Medical costs associated with obesity were estimated at $147 billion in 2008. Chronic tissue inflammation, particularly in adipose tissue, has been considered as a key underlying mechanism for the development of obesity-related metabolic syn...

  10. Obesity and renal hemodynamics

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.


    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  11. Childhood environment and obesity

    US children are at risk for developing childhood obesity. Currently, 23% of children ages 2–5 are overweight or obese, i.e., at or above the 85th percentile. This prevalence becomes even higher as children age, with 34% of children ages 6–11 being overweight or obese. Ethnic minority children are at...

  12. The Complexity of Obesity

    Gray, Katti


    With Americans fatter and more malnourished than ever--almost two-thirds of the population is considered overweight or obese compared with 56 percent in the late 1980s and early 1990s, and people of color and the poor are the most obese of all--federal and university researchers and outreach workers from various anti-obesity organizations aim to…

  13. Asthma and obesity

    Juel, Caroline Trunk-Black; Ali, Zarqa; Nilas, Lisbeth;


    Obesity is a major health problem, and obesity is associated with a high incidence of asthma and poor asthma control. The aim of the present paper is to systematically review the current knowledge of the effect on overall asthma control of weight reduction in overweight and obese adults with asthma....

  14. Obesity and respiratory diseases

    Christopher Zammit


    Full Text Available Christopher Zammit, Helen Liddicoat, Ian Moonsie, Himender MakkerSleep and Ventilation Unit, Department of Respiratory Medicine, North Middlesex University Hospital, London, UKAbstract: The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ producing systemic inflammation and effecting central respiratory control. Obesity plays a key role in the development of obstructive sleep apnea and obesity hypoventilation syndrome. Asthma is more common and often harder to treat in the obese population, and in this study, we review the effects of obesity on airway inflammation and respiratory mechanics. We also discuss the compounding effects of obesity on chronic obstructive pulmonary disease (COPD and the paradoxical interaction of body mass index and COPD severity. Many practical challenges exist in caring for obese patients, and we highlight the complications faced by patients undergoing surgical procedures, especially given the increased use of bariatric surgery. Ultimately, a greater understanding of the effects of obesity on the respiratory disease and the provision of adequate health care resources is vital in order to care for this increasingly important patient population.Keywords: obesity, lung function, obstructive sleep apnea, obesity hypoventilation syndrome, anesthesia

  15. Childhood Obesity: An Overview

    Reilly, John J.


    This article reviews recent research evidence, largely from systematic reviews, on a number of aspects of childhood obesity: its definition and prevalence; consequences; causes and prevention. The basis of the body mass index (BMI) as a means of defining obesity in children and adolescents is discussed: a high BMI for age constitutes obesity. In…

  16. Zinc metabolism in genetically obese mice

    Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from lean controls. In the present studies the absorption, retention and tissue distribution of zinc was compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When administered 0.1 and 1 umole 65Zn by stomach tube and killed after 4 h, fasted 10 week old obese mice had 2.7 and 2.2 times more radioactivity in their carcasses, respectively, than age-matched lean mice. Higher levels of 65Zn were also present in the intestinal mucosa of obese mice. To eliminate possible differences in the effects of fasting and gastric emptying rates between the phenotypes, zinc absorption and retention were determined according to the method of Heth and Hoekstra. Analysis of data revealed that obese and lean mice absorbed 43 and 18% of the oral dose, respectively. Also, the rate of 65Zn excretion between 2 and 6 days post-treatment was similar for obese and lean mice. After 6 days obese mice had significantly lower levels of radioisotope in skin, muscle plus bone, spleen and testes and higher levels of 65Zn in liver, small intestine and adipose tissue compared to tissues from lean mice. These results demonstrate increased absorption, altered tissue distribution and similar excretion of zinc in ob/ob mice

  17. Challenges in obesity research.

    Palou, Andreu; Bonet, M Luisa


    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. PMID:24010755

  18. Challenges in obesity research

    Andreu Palou


    Full Text Available Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity.

  19. Obesity and gastrointestinal diseases.

    Fujimoto, Ai; Hoteya, Shu; Iizuka, Toshiro; Ogawa, Osamu; Mitani, Toshifumi; Kuroki, Yuichiro; Matsui, Akira; Nakamura, Masanori; Kikuchi, Daisuke; Yamashita, Satoshi; Furuhata, Tsukasa; Yamada, Akihiro; Nishida, Noriko; Arase, Koji; Hashimoto, Mitsuyo; Igarashi, Yoshinori; Kaise, Mitsuru


    The prevalence of obesity in the Japanese population has been increasing dramatically in step with the Westernization of lifestyles and food ways. Our study demonstrated significant associations between obesity and a number of gastrointestinal disorders in a large sample population in Japan. We demonstrated that reflux esophagitis and hiatal hernia were strongly related to obesity (BMI > 25) in the Japanese. In particular, obesity with young male was a high risk for these diseases. On the other hand, it has been reported that obesity is also associated with Barrett's esophagus and colorectal adenoma; however, obesity was not a risk factor for these diseases in our study. The difference of ethnicity of our subjects may partly explain why we found no data to implicate obesity as a risk factor for Barrett's esophagus. Arterial sclerosis associated with advanced age and hyperglycemia was accompanied by an increased risk of colorectal adenoma. PMID:23781242

  20. Obesity: an emerging disease.

    Ogunbode, A M; Ladipo, Mma; Ajayi, I O; Fatiregun, A A


    Obesity is rapidly becoming an emerging disease in developing countries due to the increasing westernization of societies and change in the lifestyle. The etiology of obesity is said to be multifactorial, with a combination of genetic and environmental factors. Literature has been extensively reviewed to provide a broad overview of obesity. Data for this review were obtained from original articles, review articles and textbooks. Internet search engines were also employed. The years searched were from 1993 to 2008. Obesity, classified in terms of the body mass index and the waist-hip ratio, has several associated co-morbidities such as diabetes mellitus, hypertension, degenerative osteoarthritis and infertility. In Nigeria, there is limited information on obesity. A literature review on obesity is necessary to improve the knowledge about obesity in developing countries, its prevention and its management. PMID:22248935

  1. Endoscopic Devices for Obesity.

    Sampath, Kartik; Dinani, Amreen M; Rothstein, Richard I


    The obesity epidemic, recognized by the World Health Organization in 1997, refers to the rising incidence of obesity worldwide. Lifestyle modification and pharmacotherapy are often ineffective long-term solutions; bariatric surgery remains the gold standard for long-term obesity weight loss. Despite the reported benefits, it has been estimated that only 1% of obese patients will undergo surgery. Endoscopic treatment for obesity represents a potential cost-effective, accessible, minimally invasive procedure that can function as a bridge or alternative intervention to bariatric surgery. We review the current endoscopic bariatric devices including space occupying devices, endoscopic gastroplasty, aspiration technology, post-bariatric surgery endoscopic revision, and obesity-related NOTES procedures. Given the diverse devices already FDA approved and in development, we discuss the future directions of endoscopic therapies for obesity. PMID:27115879

  2. OPEN about obesity

    Lissner, L; Troiano, R P; Midthune, D;


    OBJECTIVE: Obesity-related under-reporting of usual dietary intake is one of the most persistent sources of bias in nutrition research. The aim of this paper is to characterize obese and non-obese individuals with respect to reporting errors observed with two common dietary instruments, using...... energy and protein recovery biomarkers as reference measures. POPULATION AND METHODS: This report employs data from the Observing Protein and Energy Nutrition (OPEN) study. Analyses are based on stratified samples of 211 (57 obese) men and 179 (50 obese) women who completed 24-h recalls (24HR), food...... frequency questionnaires (FFQ), doubly labelled water (DLW) and urinary nitrogen (UN) assessments. RESULTS: In obese and non-obese subgroups, FFQ yielded lower energy and protein intake estimates than 24HR, although biomarker-based information indicated under-reporting with both dietary instruments. Gender...

  3. Orexin: Pathways to obesity resistance?

    Butterick, Tammy A.; Billington, Charles J.; Kotz, Catherine M.; Nixon, Joshua P.


    Obesity has increased in prevalence worldwide, attributed in part to the influences of an obesity-promoting environment and genetic factors. While obesity and overweight increasingly seem to be the norm, there remain individuals who resist obesity. We present here an overview of data supporting the idea that hypothalamic neuropeptide orexin A (OXA; hypocretin 1) may be a key component of brain mechanisms underlying obesity resistance. Prior work with models of obesity and obesity resistance i...

  4. Pediatric Obesity: Looking into Treatment

    Marcella Malavolti; Paolo De Cristofaro; Angelo Pietrobelli; Simone Rugolotto


    Prevalence of pediatric obesity continues to rise worldwide. Increasing the number of health care practitioners as well as pediatricians with expertise in obesity treatment is necessary. Because many obese patients suffer obesity-associated cardiovascular, metabolic and other health complications that could increase the severity of obesity, it is fundamental not only to identify the child prone to obesity as early as possible, but to recognize, treat and monitor obesity-related diseases durin...

  5. Progressive obesity leads to altered ovarian gene expression in the Lethal Yellow mouse: a microarray study

    Brannian John


    Full Text Available Abstract Background Lethal yellow (LY; C57BL/6J Ay/a mice exhibit adult-onset obesity, altered metabolic regulation, and early reproductive senescence. The present study was designed to test the hypothesis that obese LY mice possess differences in expression of ovarian genes relative to age-matched lean mice. Methods 90- and 180-day-old LY and lean black (C57BL/6J a/a mice were suppressed with GnRH antagonist (Antide®, then stimulated with 5 IU eCG. cRNA derived from RNA extracts of whole ovarian homogenates collected 36 h post-eCG were run individually on Codelink Mouse Whole Genome Bioarrays (GE Healthcare Life Sciences. Results Fifty-two genes showed ≥ 2-fold differential (p Cyp51, and steroidogenic acute regulatory protein (Star. Fewer genes showed lower expression in LY mice, e.g. angiotensinogen. In contrast, none of these genes showed differential expression in 90-day-old LY and black mice, which are of similar body weight. Interestingly, 180-day-old LY mice had a 2-fold greater expression of 11beta-hydroxysteroid dehydrogenase type 1 (Hsd11b1 and a 2-fold lesser expression of 11beta-hydroxysteroid dehydrogenase type 2 (Hsd11b2, differences not seen in 90-day-old mice. Consistent with altered Hsd11b gene expression, ovarian concentrations of corticosterone (C were elevated in aging LY mice relative to black mice, but C levels were similar in young LY and black mice. Conclusion The data suggest that reproductive dysfunction in aging obese mice is related to modified intraovarian gene expression that is directly related to acquired obesity.

  6. The sociology of obesity.

    Rosengren, Annika; Lissner, Lauren


    The current obesity epidemic is largely driven by environmental factors, including nutritional transition towards refined and fatty foods with the growing production of energy-dense food at relatively low cost, increased access to motor vehicles, mechanisation of work and sedentary lifestyles. These influences in modern society are modified by individual characteristics. Ultimately, energy intake in excess of caloric expenditure causes obesity, but why this occurs in some but not all individuals is not known. Obesity is more prevalent in the lower socioeconomic classes but even so, there is a varying relation of socioeconomic status with obesity between countries at different stages of development and, even in the Western world, socioeconomic gradients with respect to obesity are both heterogeneous and in transition. Potential mechanisms for an effect of obesity on subsequent social status have been proposed, the most obvious being related to the stigmatisation experienced by the obese. Obesity seems to be causally related to mood disturbances, whereas there is no conclusive evidence that the reverse is true. When considering psychological aspects of obesity, depressive symptoms are more likely to be consequences, rather than causes of obesity. PMID:18230907

  7. [The pharmacotherapy of obesity].

    Budai, Kinga Anna; Mirzahosseini, Arash; Noszál Béla; Tóth, Gergő


    Obesity is considered the most concerning and blatantly visible--yet most neglected--public health problem by the WHO. The steadily increasing number of overweight and obese people has reached 2.3 billion and 700 million worldwide, respectively. Obesity is a complex condition, one that presents serious health risks with respect to type 2 diabetes, ischemic heart disease, and hypertension, therefore controlling the global obesity epidemic decreases not only health problems, but also expenditure. The underlying cause of obesity is a metabolic disorder of genetic, central nervous system or endocrine etiology that manifests in increased nutritional intake and/or decreased physical activity ultimately leading to excessive lipogenesis. The natural treatment of obesity, that is often advised, is comprised of healthy lifestyle choices, namely low-calorie diet and exercise. However, the pharmaceutic treatment of obesity is just as important; having a better compliance rate, anti-obesity drugs also improve quality of life and patient-care outcome concerning accompanying diseases. In most countries only one drug is currently available against obesity: orlistat, which is a specific and irreversible lipase inhibitor. One of the reasons for the scarce number of anti-obesity drugs is the complex pathomechanism involved in obesity. Interference with the intricate biochemical processes that govern alimentation may lead to widespread adverse effects. The advances of the field however, have prompted novel drug leads. In the past few years FDA has approved new drugs for the treatment of obesity, recently liraglutide in 2014. The approval of drug combinations, such as phentermine/topiramate and bupropion/naltrexone are also noteworthy, the components of which have been previously approved, but not necessarily for obesity as main indication. Furthermore, there are many anti-obesity drug candidates currently in clinical phase trials, with promisingly modest adverse effect profiles; hence

  8. Obesity and pregnancy

    Andreasen, Kirsten Riis; Andersen, Malene Lundgren; Schantz, Anne Louise


    , hypertensive disorders, and thromboembolic complications. Complications associated with obesity in labor are augmentation, early amniotomy, cephalopelvic disproportion, cesarean section, and perioperative morbidity. Complications associated with obesity in children are macrosomia, shoulder dystocia, small......BACKGROUND: As obesity is an increasing problem among fertile women, it is crucial that specialists involved in the treatment of these women be aware of the risks of complications and know how to deal with them. Complications associated with obesity in pregnancy are gestational diabetes mellitus...... for gestational age, late fetal death, and congenital malformations, especially neural tube defects. OBJECTIVE: The aim was to review the potential complications associated with obesity and pregnancy. RESULTS: Obesity is associated with a higher risk of all reviewed complications except small for gestational age....

  9. Obesity and asthma

    Sivapalan, Pradeesh; Diamant, Zuzana; Ulrik, Charlotte Suppli


    PURPOSE OF REVIEW: Obesity has significant impact on asthma incidence and manifestations. The purpose of the review is to discuss recent observations regarding the association between obesity and asthma focusing on underlying mechanisms, clinical presentation, response to therapy and effect of...... weight reduction. RECENT FINDINGS: Clinical and epidemiological studies indicate that obese patients with asthma may represent a unique phenotype, which is more difficult to control, less responsive to asthma medications and by that may have higher healthcare utilization. A number of common comorbidities...... have been linked to both obesity and asthma, and may, therefore, contribute to the obese-asthma phenotype. Furthermore, recently published studies indicate that even a modest weight reduction can improve clinical manifestations and outcome of asthma. SUMMARY: Compared with normal-weight patients, obese...

  10. Obesity and pregnancy

    Andreasen, Kirsten Riis; Andersen, Malene Lundgren; Schantz, Anne Louise


    BACKGROUND: As obesity is an increasing problem among fertile women, it is crucial that specialists involved in the treatment of these women be aware of the risks of complications and know how to deal with them. Complications associated with obesity in pregnancy are gestational diabetes mellitus......, hypertensive disorders, and thromboembolic complications. Complications associated with obesity in labor are augmentation, early amniotomy, cephalopelvic disproportion, cesarean section, and perioperative morbidity. Complications associated with obesity in children are macrosomia, shoulder dystocia, small for...... gestational age, late fetal death, and congenital malformations, especially neural tube defects. OBJECTIVE: The aim was to review the potential complications associated with obesity and pregnancy. RESULTS: Obesity is associated with a higher risk of all reviewed complications except small for gestational age....

  11. Anesthetizing the obese child

    Mortensen, Anette; Lenz, Katja; Abildstrøm, Hanne;


    obese child has an increased risk of perioperative complications especially related to airway management and ventilation. There is a significantly increased risk of difficult mask ventilation and perioperative desaturation. Furthermore, obesity has an impact on the pharmacokinetics of most anesthetic......The prevalence of childhood obesity is increasing. The focus of this review is the special anesthetic considerations regarding the perioperative management of obese children. With obesity the risk of comorbidity such as asthma, obstructive sleep apnea, hypertension, and diabetes increases. The...... drugs. This has important implications on how to estimate the optimal drug dose. This article offers a review of the literature on definition, prevalence and the pathophysiology of childhood obesity and provides suggestions on preanesthetic evaluation, airway management and dosage of the anesthetic...

  12. Obesity and obstetric anaesthesia.

    Mace, H S; Paech, M J; McDonnell, N J


    Obesity is increasing in the population as a whole, and especially in the obstetric population, among whom pregnancy-induced physiological changes impact on those already present due to obesity. In particular, changes in the cardiovascular and respiratory systems during pregnancy further alter the physiological effects and comorbidities of obesity. Obese pregnant women are at increased risk of diabetes, hypertensive disorders of pregnancy, ischaemic heart disease, congenital malformations, operative delivery postpartum infection and thromboembolism. Regional analgesia and anaesthesia is usually preferred but may be challenging. Obese pregnant women appear to have increased morbidity and mortality associated with caesarean delivery and general anaesthesia for caesarean delivery in particular, and more anaesthesia-related complications. This article summarises the physiological and pharmacological implications of obesity and pregnancy and describes the issues surrounding the management of these women for labour and delivery. PMID:21823371

  13. [Obesity and gastrointestinal motility].

    Lee, Joon Seong


    Gastrointestinal (GI) motility has a crucial role in the food consumption, digestion and absorption, and also controls the appetite and satiety. In obese patients, various alterations of GI motility have been investigated. The prevalence of GERD and esophageal motor disorders in obese patients are higher than those of general population. Gastric emptying of solid food is generally accelerated and fasting gastric volume especially in distal stomach is larger in obese patients without change in accommodation. Contractile activity of small intestine in fasting period is more prominent, but orocecal transit is delayed. Autonomic dysfunction is frequently demonstrated in obese patients. These findings correspond with increased appetite and delayed satiety in obese patients, but causes or results have not been confirmed. Therapeutic interventions of these altered GI motility have been developed using botulinum toxin, gastric electrical stimulation in obese patients. Novel agents targeted for GI hormone modulation (such as ghrelin and leptin) need to be developed in the near future. PMID:16929152

  14. The relationship between dental caries and obesity among primary school children aged 5 to 14 years

    Yao Yingshui; Ren Xiaohua; Song Xiuli; He Lianping; Jin Yuelong; Chen Yan; Lu Wei; Guo Daoxia; Ding Lingling; Tang Hui; Wei Ningkai; Qiu Shenwei; Li Chaopin


    Background: Previous study revealed that the link between dental caries and obesity has been controversial. The purpose of this research is to investigate the association between dental caries and obesity among primary school children in Wannan area, China. Methods: A cross-sectional study was designed to collect the routine health screening data for primary school children aged 5-14 years inWannan area,China, Overweight and obesity status were determined using the International Obesity Task ...

  15. Prevalence of educational inequalities in obesity between 1970 and 2003 in France.

    Singh-Manoux, Archana; Gourmelen, Julie; Lajnef, Mohamed; Sabia, Séverine; Sitta, Rémi; Menvielle, Gwenn; Melchior, Maria; Nabi, Hermann; Lanoe, Jean-Louis; Guéguen, Alice; Lert, France


    International audience This paper examines trends in obesity rates and education-related absolute and relative inequalities in obesity over the last 40 years in France. Data are drawn from the French Decennial Health Surveys of 1970, 1980, 1991 and 2003. The difference in obesity rates between the least- and most-educated, the Slope Index of Inequality, is used to estimate absolute inequalities in obesity. The ratio of the corresponding rates, the Relative Index of Inequality, reveals the ...

  16. Current mapping of obesity

    Carmen Pérez Rodrigo


    Obesity is a major risk factor for non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases, and cancers. The worldwide prevalence of obesity has almost doubled between 1980 and 2008. In some regions, such as Europe, the Eastern Mediterranean and the Americas, more than 50% of women are overweight. Tonga, Nauru and the Cook Islands show the highest prevalence of obesity worldwide, above 60% in men and in women. China and the United States are the countries that experienced ...

  17. Obesity: A multifactorial disease

    Marianna Ntokou


    Full Text Available Obesity represents one of the most serious global health issues with approximately 310 million people presently affected. Main cause of it’s development is the increase of energy intake in regard to energy expenditure.Aim: The aim of the present study was to review the literature about the causes and treatment of obesity, as well as the anthropometrical measurements used for the assessment of obesity. The method οf this study included bibliography research from both the review and the research literature, mainly in the “pub med data base” which referred to the causes and treatment of obesity, as well as the anthropometrical measurements used for the assessment of obesity. Results: The prevalence of obesity has increased markedly, throughout the world. Although the etiology of obesity has not been fully understood yet, however it seems to be a multifactorial disease for which are responsible a great deal of psychological, environmental, genetic and behavioral factors. The most common anthropometrical measurement that is used for assessment of obesity is Body Mass Index (BMI and is calculated by the following equation: ΒΜΙ=Weight/Height2. A value of ΒΜΙ ≥ 30 kg/m2 equals obesity. Another simple test used to measure obesity is Waist to Hip Ratio, which measures abdominal adiposity. Values greater than 0,95 should be treated seriously as they normally indicate body fatness. The majority of studies show that life-style modification in conjunction with a well-balanced nutrition and regular physical exercise consist the cornerstone for the treatment and prevention of obesity.Conclusions: Obesity is a disease that can be preventable through modification of way of living. The development of proper strategy prevention capable to change attitudes, to promote nutrition and physical activity should be the primary goal of every community and government.

  18. Gut Microbiota and Obesity

    Wolf, Kyle J.; Lorenz, Robin G.


    The current obesity epidemic clearly has many causes, including the impact of our modern world on both our diet and our lifestyle/physical activity. Although many interventions have been recommended, the prevalence of obesity continues to rise and has forced a re-evaluation of the potential interventions that could have an impact. In recent years it has been definitively shown that microbiota in the gastrointestinal tract are altered in obese individuals. Recent data provide a potential mecha...

  19. Obesity: Pathophysiology and Intervention

    Yi Zhang; Ju Liu; Jianliang Yao; Gang Ji; Long Qian; Jing Wang; Guansheng Zhang; Jie Tian; Yongzhan Nie; Yi Edi. Zhang; Gold, Mark S.; Yijun Liu


    Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pat...

  20. Obesity and respiratory diseases

    Christopher Zammit; Helen Liddicoat; Ian Moonsie; et al


    Christopher Zammit, Helen Liddicoat, Ian Moonsie, Himender MakkerSleep and Ventilation Unit, Department of Respiratory Medicine, North Middlesex University Hospital, London, UKAbstract: The obesity epidemic is a global problem, which is set to increase over time. However, the effects of obesity on the respiratory system are often underappreciated. In this review, we will discuss the mechanical effects of obesity on lung physiology and the function of adipose tissue as an endocrine organ produ...

  1. Challenges in obesity research

    Andreu Palou; Luisa Bonet, M.


    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors -often interrelated and many of them still unknown or poorly understood- can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regard...

  2. Genetic Factors of Obesity

    Mazura, Ivan; Ochoa-Rebato, E.

    Budapest: Eötvös University Press, 2010 - (Bodzsár, E.; Susanne, C.), s. 119-140. (Biennial Books of the EAA. 6). ISBN 978-963-88941-0-6 R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : aetiology of obesity * genetic factors * obesity genes * polymorphism * obesity -associated syndromes Subject RIV: EB - Genetics ; Molecular Biology

  3. DBS for Obesity

    Ruth Franco; Fonoff, Erich T; Pedro Alvarenga; Antonio Carlos Lopes; Euripides C Miguel; Manoel J. Teixeira; Durval Damiani; Clement Hamani


    Obesity is a chronic, progressive and prevalent disorder. Morbid obesity, in particular, is associated with numerous comorbidities and early mortality. In patients with morbid obesity, pharmacological and behavioral approaches often have limited results. Bariatric surgery is quite effective but is associated with operative failures and a non-negligible incidence of side effects. In the last decades, deep brain stimulation (DBS) has been investigated as a neurosurgical modality to treat variou...

  4. Obesity, Inflammation, and Cancer.

    Deng, Tuo; Lyon, Christopher J; Bergin, Stephen; Caligiuri, Michael A; Hsueh, Willa A


    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity. PMID:27193454

  5. Controversies in Obesity Treatment

    Majid Karandish


    Full Text Available The markedly high prevalence of obesity contributes to the increased incidence of chronic diseases, such as diabetes, hypertension, sleep apnea, and heart disease. Because of high prevalence of obesity in almost all countries, it has been the focus of many researches throughout the world during the recent decades. Along with increasing researches, new concepts and controversies have been emerged. The existing controversies on the topic are so deep that some researches argue on absolutely philosophical questions such as “Is obesity a disease?” or “Is it correct to treat obesity?” These questions are based on a few theories and real data that explain obesity as a biological adaptation and also the final results of weight loss programs. Many people attempt to lose weight by diet therapy, physical activity and lifestyle modifications. Importantly, weight loss strategies in the long term are ineffective and may have unintended consequences including decreasing energy expenditure, complicated appetite control, eating disorders, reducing self-esteem, increasing the plasma and tissue levels of persistent organic pollutants that promote metabolic complications, and consequently, higher risk of repeated cycles of weight loss and weight regain. In this review, major paradoxes and controversies on obesity including classic obesity paradox, pre-obesity; fat-but-fit theory, and healthy obesity are explained. In addition, the relevant strategies like “Health at Every Size” that emphasize on promotion of global health behaviors rather than weight loss programs are explained.

  6. Update on obesity surgery

    Dan Eisenberg; Andrew J Duffy; Robert L Bell


    The prevalence of obesity in the United States has reached epidemic proportions. With more than 30 million Americans clinically obese, the younger population has also been affected. Surgical therapy should be offered to the severely obese patient who is refractory to nonsurgical therapy, as established by the 1991 NIH Consensus Conference on Gastrointestinal Surgery for Severe Obesity. Surgery is currently the most effective therapy for weight loss. It is far more effective than any other treatment modality, both in terms of the amount of weight loss and in terms of durability in maintaining weight loss.

  7. What Are Overweight and Obesity?

    ... the NHLBI on Twitter. What Are Overweight and Obesity? Español The terms "overweight" and "obesity" refer to ... disease risk. Rate This Content: NEXT >> Featured Video Obesity happens one pound at a time. So does ...

  8. Obesity and academic performances in adolescents

    Nina Herlina


    Full Text Available Background Adolescence is a phase of dynamic development in human life, marked by rapid physical growth, in addition to mental, emotional, and social development. Adolescent obesity has been related to metabolic disease, in addition to psychological disorders, which may lead to a negative impact on academic performances. Objective To assess academic performances in adolescents with obesity Methods A cross-sectional study was conducted in Junior High School No. 14 in Bandung from December 2010 to July 2011. Subjects were aged 12 to 14 years, and were divided into two groups: obese or good nutritional status. Statistical analysis using Fisher’s exact test was performed to assess the association of obesity and academic performances. T-test was used to compare subjects’ mean mathematics and Eenglish performances in the two groups. Results There were 240 students who met the inclusion criteria. Since there were 40 obese subjects in the first group, we randomized the remaining students to obtain 40 subjects with good nutritional status for the second group. Bbest academic performances in mathematics and Eenglish was obtained mostly by subjects in the good nutrition group (38/40 and 39/40, respectively. Statistical analysis revealed a significant association of lower performances in mathematics (mean difference -2.8; 95%CI -5 to -0.6; P=0.043 and English (mean difference -1.9; 95%CI -3.5 to -0.2; P=0.001 to obesity. We also found a significant association of better mathematics (P=0.001 and English performances (P=0.004 to the father’s occupation. Additional English lessons were not associated with higher English performances in the obese group (mean difference 0.2; 95%CI -2.9 to 3.2; P=0.885. Conclusion Obese adolescents tend to have poorer academic performances compared to those with good nutritional status. [Paediatr Indones. 2013;53:12-5.

  9. The relation between childhood obesity and adenotonsillar hypertrophy.

    Daar, Ghaniya; Sarı, Kamran; Gencer, Zeliha Kapusuz; Ede, Hüseyin; Aydın, Reha; Saydam, Levent


    symptoms is prominent especially in children under 7 years of age, but its impact on the development of childhood obesity is still controversial. Our results revealed a possible relation between adenotonsillar hypertrophy and obesity rates. Further studies on larger populations should be planned to better define the real impact of adenotonsillar hypertrophy in obese children. PMID:25876003

  10. "Obesity is the New Major Cause of Cancer": Connections Between Obesity and Cancer on Facebook and Twitter.

    Kent, Erin E; Prestin, Abby; Gaysynsky, Anna; Galica, Kasia; Rinker, Robin; Graff, Kaitlin; Chou, Wen-Ying Sylvia


    Social media interactions can inform public health risk perceptions. While research has examined the risk relationships between obesity and cancer, public attitudes about their associations remain largely unknown. We explored how these constructs were discussed together on two social media platforms. Publicly accessible Facebook and Twitter posts from a 2-month period in 2012 containing references to obesity ("obese/obesity," "overweight," and "fat") and cancer-related words were extracted (N = 3702 posts). Data cleaning yielded a final set of 1382 posts (Facebook: N = 291; Twitter: N = 1091). Using a mixed-methods approach, themes were inductively generated, and sentiment valence, structural elements, and epistemic stance were coded. Seven relational themes emerged: obesity is associated with cancer (n = 389), additional factors are associated with both obesity and cancer (n = 335), obesity causes cancer (n = 85), cancer causes obesity (n = 6), obesity is not linked to cancer (n = 13), co-occurrence (n = 492), and obesity is valued differently than cancer (n = 60). Fifty-nine percent of posts focused on an associative or causal link between obesity and cancer. Thirty-one percent of posts contained positive and/or negative sentiment. Facebook was more likely to contain any sentiment, but Twitter contained proportionately more negative sentiment. Concurrent qualitative analysis revealed a dominance of individual blame for overweight/obese persons and more support and empathy for cancer survivors. Our study reflects wide recognition of the evidence linking obesity to increased risk of cancer, a diverse set of factors perceived to be dually associated with both conditions and differing attribution of responsibility. We demonstrate that social media monitoring can provide an important gauge of public health risk perception. PMID:25865399