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Sample records for age disease severity

  1. Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity

    PubMed Central

    Mischley, Laurie K.; Standish, Leanna J.; Weiss, Noel S.; Padowski, Jeannie M.; Kavanagh, Terrance J.; White, Collin C.; Rosenfeld, Michael E.

    2016-01-01

    Objectives. Oxidative stress contributes to Parkinson's disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman's rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P = 0.02, 95% CI: −13.96, −1.14) and the PRO-PD (P = 0.01, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.

  2. Sever's Disease

    MedlinePlus

    ... Are Reading Upsetting News Reports? What to Say Vaccines: Which Ones & When? Smart School Lunches Emmy-Nominated Video "Cerebral Palsy: Shannon's Story" 5 Things to Know About Zika & Pregnancy Sever's Disease KidsHealth > ...

  3. Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease.

    PubMed

    Dukart, Juergen; Mueller, Karsten; Villringer, Arno; Kherif, Ferath; Draganski, Bogdan; Frackowiak, Richard; Schroeter, Matthias L

    2013-01-01

    The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage.

  4. A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease

    PubMed Central

    Disson, Olivier; Brigitte, Madly; Guivel-Benhassine, Florence; Touret, Yasmina; Barau, Georges; Cayet, Nadège; Schuffenecker, Isabelle; Desprès, Philippe; Arenzana-Seisdedos, Fernando; Michault, Alain

    2008-01-01

    Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates. PMID:18282093

  5. International practice patterns by age and severity of lung disease in cystic fibrosis: data from the Epidemiologic Registry of Cystic Fibrosis (ERCF).

    PubMed

    Koch, C; McKenzie, S G; Kaplowitz, H; Hodson, M E; Harms, H K; Navarro, J; Mastella, G

    1997-08-01

    The Epidemiologic Registry of Cystic Fibrosis provides clinical profiles for more than 6,800 patients and descriptions of practice patterns across eight European countries. Preliminary cross-sectional analysis has been performed by age and pulmonary function as an assessment of disease severity. In general, pulmonary treatments including inhaled bronchodilators and rhDNase increased as lung disease became more severe. Use of a number of treatments, including mucolytic agents and inhaled corticosteroids, varied markedly from country to country. Several widely used therapies are not yet supported by controlled clinical trials, particularly in patients under 6 years of age. Nutritional intervention was more common in patients with advanced lung disease regardless of age. Patients with nasal polyps had less severe lung disease at each age than patients without polyps. It is clear that studies of early interventions are needed to determine the optimal types of treatments and the ages at which to begin treatment.

  6. Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice▿

    PubMed Central

    Rockx, Barry; Sheahan, Timothy; Donaldson, Eric; Harkema, Jack; Sims, Amy; Heise, Mark; Pickles, Raymond; Cameron, Mark; Kelvin, David; Baric, Ralph

    2007-01-01

    The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly. PMID:17507479

  7. Aging and liver disease

    PubMed Central

    Kim, Hee; Kisseleva, Tatiana; Brenner, David A.

    2016-01-01

    Purpose of review Aging is a condition in which a person gradually loses the ability to maintain homeostasis, due to structural alteration or dysfunction. Aging is a major risk factor for most chronic diseases. As the liver has a remarkable ability to regenerate, this review assessed the effect of aging on clinical liver disease with references to preclinical models when relevant to pathogenesis. Recent findings Aging has been shown to not only enhance vulnerability to acute liver injury but also increase susceptibility of the fibrotic response. Aging is associated with the severity and poor prognosis of various liver diseases including nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and liver transplantation. Summary Treatment of older patients with liver disease may require different or longer interventions. Transplantation of an older liver will be less tolerant of subsequent injury. Future studies are needed to understand more about the molecular mechanism of aging and contribute to the development of a noble treatment strategy that can block the progression of aging-induced liver diseases. PMID:25850346

  8. Smoking and periodontal disease severity.

    PubMed

    Martinez-Canut, P; Lorca, A; Magán, R

    1995-10-01

    This study was performed to assess the influence of smoking on periodontal disease severity. Data concerning periodontal status and smoking habits were collected from 889 periodontal patients: 340 male and 549 female, 21 to 76 years of age, 47.4% being non smokers and 52.6% smokers. Periodontal parameters, recorded by the same examiner (PMC), were: gingival recession (GR), Pocket depth (PD), Probing attachment level (PAL), and mobility (M). The influence of age, sex and tobacco consumption on these periodontal parameters was statistically evaluated using an analysis of variance (ANOVA) with covariates. A non-linear effect model was also fitted by taking the natural logarithms of the response variables (GR, PD, PAL) closer to biomedical phenomena. Mobility was analyzed by a chi2-test. The effect of smoking on periodontitis showed no association with age or with sex. Smoking, age and sex were shown to be statistically significant for periodontitis, by performing both univariate (t-test for equal means) and multivariate tests. p-values for smoking and periodontitis were: GR (p=0.000), PD (p=0.000), PAL (p=0.000) and M (P=0.015). Smoking one cigarette per day, up to 10, and up to 20, increased PAL by 0.5%, 5% and 10%, respectively. The impact of tobacco is comparable to the impact resulting from the factor of age in this sample, increasing PAL by 0.7% for each year of life. Comparison between smokers of less than 10 cigarettes per day (PAL mean 3.72 mm +/-0.86) and non-smokers (PAL mean 3.84 +/- 0.89) showed no differences in PAL (p=0.216), while comparison for smokers from 11 to 20 cigarettes (PAL mean 4.36 +/- 1.23) and for more than 20 cigarettes (PAL mean 4.50 +/- 1.04) demonstrated significant differences (p=0.000). These findings suggest that: (1) tobacco increases periodontal disease severity; (2) this effect is clinically evident above consumption of a certain quantity of tobacco.

  9. The Several Ages of Learning

    ERIC Educational Resources Information Center

    Bailey, Stephen

    1976-01-01

    Examines the various stages of human development (as outlined by Erik Erikson and others) with their psychological stresses of recurring crises of identity and expectation and explores some of the implications for education's best serving human needs. Focuses on early childhood, late adolescence, middle age, and old age. (JT)

  10. Endocrine Disease in Aged Horses.

    PubMed

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. PMID:27449391

  11. Epidemiology of respiratory syncytial virus in children in Cyprus during three consecutive winter seasons (2010-2013): age distribution, seasonality and association between prevalent genotypes and disease severity.

    PubMed

    Panayiotou, C; Richter, J; Koliou, M; Kalogirou, N; Georgiou, E; Christodoulou, C

    2014-11-01

    This study reports the epidemiology of respiratory syncytial virus (RSV) in hospitalized children in Cyprus over three successive seasons (2010-2013) and the association between prevalent genotypes and disease severity. RSV infections had a circulation pattern from December to March. Most RSV-positive children (83%) were aged <2 years. Genotyping of RSV isolates showed that during the first winter season of the study (2010-2011), the only RSV genotype circulating was GA2 (RSV-A), followed by genotype BA (RSV-B) in the next winter season with only few sporadic cases of GA2. During the last winter season of the study (2012-2013) the newly emerged RSV genotype ON1 (RSV-A) was virtually the only circulating genotype. Children infected with genotype ON1 suffered a significantly milder illness compared to infections with genotypes GA2 and BA with a higher percentage of BA-infected children requiring oxygen. Our findings are in contrast to the majority of published reports that suggest RSV-A causes more severe illness than RSV-B. Therefore, further investigation of the association between RSV genotypes and disease severity is required, as it might affect treatment strategies in the future.

  12. Epidemiology of respiratory syncytial virus in children in Cyprus during three consecutive winter seasons (2010-2013): age distribution, seasonality and association between prevalent genotypes and disease severity.

    PubMed

    Panayiotou, C; Richter, J; Koliou, M; Kalogirou, N; Georgiou, E; Christodoulou, C

    2014-11-01

    This study reports the epidemiology of respiratory syncytial virus (RSV) in hospitalized children in Cyprus over three successive seasons (2010-2013) and the association between prevalent genotypes and disease severity. RSV infections had a circulation pattern from December to March. Most RSV-positive children (83%) were aged <2 years. Genotyping of RSV isolates showed that during the first winter season of the study (2010-2011), the only RSV genotype circulating was GA2 (RSV-A), followed by genotype BA (RSV-B) in the next winter season with only few sporadic cases of GA2. During the last winter season of the study (2012-2013) the newly emerged RSV genotype ON1 (RSV-A) was virtually the only circulating genotype. Children infected with genotype ON1 suffered a significantly milder illness compared to infections with genotypes GA2 and BA with a higher percentage of BA-infected children requiring oxygen. Our findings are in contrast to the majority of published reports that suggest RSV-A causes more severe illness than RSV-B. Therefore, further investigation of the association between RSV genotypes and disease severity is required, as it might affect treatment strategies in the future. PMID:24476750

  13. Severe scurvy: an underestimated disease.

    PubMed

    Levavasseur, M; Becquart, C; Pape, E; Pigeyre, M; Rousseaux, J; Staumont-Sallé, D; Delaporte, E

    2015-09-01

    Scurvy is one of the oldest diseases in human history. Nowadays, although scurvy tends to become a forgotten disease in developed country, rare cases still occur, especially in people undergoing extreme diet, old people or children with poor diet and patients with malabsorption. We describe three cases of scurvy. The first case is a patient diagnosed with Crohn's disease, the second one is in a context of anorexia nervosa and drug addiction, and the third case is in a context of social isolation. Early recognition of scurvy can be difficult because symptoms may appear nonspecific and can mimic more common conditions. In any patient with spontaneous hematoma and purpura, in the context of nutritional disorder, scurvy should be systematically considered. As this disease can lead to severe complications, such as bone pain, heart failure or gastrointestinal symptoms, nothing should delay vitamin C supplementation, which is a simple and rapidly effective treatment. PMID:26081492

  14. Severe scurvy: an underestimated disease.

    PubMed

    Levavasseur, M; Becquart, C; Pape, E; Pigeyre, M; Rousseaux, J; Staumont-Sallé, D; Delaporte, E

    2015-09-01

    Scurvy is one of the oldest diseases in human history. Nowadays, although scurvy tends to become a forgotten disease in developed country, rare cases still occur, especially in people undergoing extreme diet, old people or children with poor diet and patients with malabsorption. We describe three cases of scurvy. The first case is a patient diagnosed with Crohn's disease, the second one is in a context of anorexia nervosa and drug addiction, and the third case is in a context of social isolation. Early recognition of scurvy can be difficult because symptoms may appear nonspecific and can mimic more common conditions. In any patient with spontaneous hematoma and purpura, in the context of nutritional disorder, scurvy should be systematically considered. As this disease can lead to severe complications, such as bone pain, heart failure or gastrointestinal symptoms, nothing should delay vitamin C supplementation, which is a simple and rapidly effective treatment.

  15. The sense of self is supported by several independent cognitive processes in Alzheimer's disease and self-reported age tracks cognitive impairment.

    PubMed

    Nizzi, Marie-Christine; Belin, Catherine; Maillet, Didier; Moroni, Christine

    2016-09-01

    Do patients with Alzheimer's disease loose themselves? The impact of dementia on the sense of self has been extensively studied over the past 15 years. However, most studies investigate only one marker of the self - such as mirror self-recognition or the use of the pronoun "I" - and do not track how this marker evolves in the course of the illness in comparison to other markers. This situation has resulted in fragmented findings rather than converging evidence for a coherent model of the self in dementia. In our two studies, we use a questionnaire to investigate four markers of the self simultaneously (self-knowledge, mirror self-recognition, the bodily distinction between self and other, and self-reported age) in the same 60 patients spread across three stages of Alzheimer's disease. This method allows us to determine whether these markers are impaired independently over the progression of the illness. Our results suggest that the sense of self relies on a complex structure supported by several independent cognitive processes that are impacted differently by the progression of dementia. In particular, despite the early deterioration of self-knowledge, patients at advanced stages of the disease seem to maintain a sense of self, rooted into mirror self-recognition and the bodily self. Furthermore, self-reported age predicts the level of cognitive impairment. We suggest that a better understanding of the stage at which each marker of the self breaks down can help clinicians support their patients better by targeting the preserved dimensions of their identity at any given point in the progression of their condition. PMID:27651016

  16. Disease-associated QT-shortage versus quinine associated QT-prolongation: age dependent ECG-effects in Ghanaian children with severe malaria

    PubMed Central

    2014-01-01

    Background While several anti-malarials are known to affect the electric conduction system of the heart, less is known on the direct effects of Plasmodium falciparum infection. Some earlier studies point to a direct impact of Plasmodium falciparum infection on the electric conduction system of the heart. The aim of this study was to analyse infection- and drug-induced effects on the electric conduction system. Methods Children aged 12 months to 108 months with severe malaria were included in Kumasi, Ghana. In addition to basic demographic, clinical, biochemical and parasitological, biochemical data were measured data upon hospitalization (day 0) and 12-lead electrocardiograms were recorded before (day 0) and after (day 1) initiation of quinine therapy as well as after 42 (±3) days. Results A total of 180 children were included. Most children were tachycardic on day 0 but heart rate declined on day 1 and during follow up. The corrected QT intervals were longest on day 1 and shortest on day 0. Comparison of QT intervals with day 42 (healthy status) after stratification for age demonstrated that in the youngest (<24 months) this was mainly due to a QT shortage on day 0 while a QT prolongation on day 1 was most pronounced in the oldest (≥48 months). Nearly one third of the participating children had measurable 4-aminoquinoline levels upon admission, but no direct effect on the corrected QT intervals could be shown. Conclusion Severe P. falciparum infection itself can provoke changes in the electrophysiology of the heart, independent of anti-malarial therapy. Especially in young - thus non immune - children the effect of acute disease associated pre-treatment QT-shortage is more pronounced than quinine associated QT-prolongation after therapy. Nevertheless, neither malaria nor anti-malarial induced effects on the electrophysiology of the heart were associated with clinically relevant arrhythmias in the present study population. PMID:24902591

  17. Stop Aging Disease! ICAD 2014

    PubMed Central

    Ilia, Stambler

    2015-01-01

    On November 1–2, 2014, there took place in Beijing, China, the first International Conference on Aging and Disease (ICAD 2014) of the International Society on Aging and Disease (ISOAD). The conference participants presented a wide and exciting front of work dedicated to amelioration of aging-related conditions, ranging from regenerative medicine through developing geroprotective substances, elucidating a wide range of mechanisms of aging and aging-related diseases, from energy metabolism through genetics and immunomodulation to systems biology. The conference further emphasized the need to intensify and support research on aging and aging-related diseases to provide solutions for the urgent health challenges of the aging society. PMID:25821637

  18. Cerebrovascular disease in ageing and Alzheimer's disease.

    PubMed

    Love, Seth; Miners, J Scott

    2016-05-01

    Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease. PMID:26711459

  19. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine.

  20. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine. PMID:26646495

  1. Autoimmune diseases and reproductive aging

    PubMed Central

    Bove, Riley

    2013-01-01

    As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation. PMID:23522436

  2. Modulating Human Aging and Age-Associated Diseases

    PubMed Central

    Fontana, Luigi

    2009-01-01

    Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80 percent of adults over 65 years of age have at least one chronic disease, and 50 percent have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of healthcare costs, constituting an important burden for our society. Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease. PMID:19364477

  3. COPD exacerbations by disease severity in England

    PubMed Central

    Merinopoulou, Evie; Raluy-Callado, Mireia; Ramagopalan, Sreeram; MacLachlan, Sharon; Khalid, Javaria Mona

    2016-01-01

    Objectives Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Methods Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions). Results From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85) for GOLD A to 2.51 (95% CI: 2.47–2.55) for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93) for GOLD A to 7.44 (95% CI: 7.31–7.61) for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84). Conclusion Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits. Better patient management to stabilize the disease progression could allow for an

  4. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

    Bürkle, Alexander; Caselli, Graziella; Franceschi, Claudio; Mariani, Erminia; Sansoni, Paolo; Santoni, Angela; Vecchio, Giancarlo; Witkowski, Jacek M; Caruso, Calogero

    2007-01-01

    On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. PMID:17683521

  5. Comorbidity in chronic obstructive pulmonary disease. Related to disease severity?

    PubMed Central

    Echave-Sustaeta, Jose M; Comeche Casanova, Lorena; Cosio, Borja G; Soler-Cataluña, Juan Jose; Garcia-Lujan, Ricardo; Ribera, Xavier

    2014-01-01

    Background and objective Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients. Patients and methods In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated. Results Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage. Conclusion COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity. PMID:25429213

  6. The role of Alzheimer’s and cerebrovascular pathology in mediating the effects of age, race, and apolipoprotein E genotype on dementia severity in pathologically confirmed Alzheimer’s disease

    PubMed Central

    Gavett, Brandon E.; John, Samantha E.; Gurnani, Ashita S.; Bussell, Cara A.; Saurman, Jessica L.

    2016-01-01

    Background Dementia severity can be modeled as the construct δ, representing the “cognitive correlates of functional status.” Objective We recently validated a model for estimating δ in the National Alzheimer’s Coordinating Center’s Uniform Data Set; however, δ’s association with neuropathology remains untested. Methods We used data from 727 decedents evaluated at Alzheimer’s Disease (AD) Centers nationwide. Participants spoke English, had no genetic abnormalities, and were pathologically diagnosed with AD as a primary or contributing etiology. Clinical data from participants’ last visit prior to death were used to estimate dementia severity (δ). Results A structural equation model using age, education, race, and apolipoprotein E (APOE) genotype (number of ε2 and ε4 alleles) as predictors and latent AD pathology and cerebrovascular disease (CVD) pathology as mediators fit the data well (RMSEA = 0.031; CFI = .957). AD pathology mediated the effects of age and APOE genotype on dementia severity. An older age at death and more ε2 alleles were associated with less AD pathology and, in turn, with less severe dementia. In contrast, more ε4 alleles were associated with more pathology and more severe dementia. Although age and race contributed to differences in CVD pathology, CVD pathology was not related to dementia severity in this sample of decedents with pathologically confirmed AD. Conclusions Using δ as an estimate of dementia severity fits well within a structural model in which AD pathology directly affects dementia severity and mediates the relationship between age and APOE genotype on dementia severity. PMID:26444761

  7. Insurance Status and the Risk of Severe Respiratory Syncytial Virus Disease in United States Preterm Infants Born at 32–35 Weeks Gestational Age

    PubMed Central

    Franklin, Jeremy A.; Anderson, Evan J.; Wu, Xionghua; Ambrose, Christopher S.; Simões, Eric A. F.

    2016-01-01

    Background. Database studies have identified that public health insurance status is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in US infants. However, these studies did not adjust for the presence of other risk factors and did not evaluate the risk in preterm infants. Methods. In this study, we evaluate the independent association between public insurance and severe RSV disease outcomes adjusting for other risk factors. The prospective, observational RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US clinical sites that enrolled preterm infants born at 32–35 wGA who had not received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100 infant-seasons of the RSV-associated endpoints of outpatient lower respiratory tract infection (LRI), emergency department (ED) visits, RSV hospitalizations (RSVHs), and intensive care unit admissions during peak RSV season (November–March) were compared for infants with private and public insurance. Results. Of 1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.20–3.45) were higher for subjects with public insurance, with a similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI, .93–2.78). Conclusions. Socioeconomic status, as evaluated by public versus private healthcare insurance, is a significant independent risk factor for ED use in US preterm infants and may contribute to increased RSVHs in this population. PMID:27704018

  8. Cognitive aging and Alzheimer's disease

    PubMed Central

    Vandenberghe, R; Tournoy, J

    2005-01-01

    Cognitive aging and clinically probable Alzheimer's disease can be discriminated by means of clinical and neuropsychological testing, and structural and functional imaging techniques. Research at the level of cognitive brain systems and at the molecular level provides exciting new insights into the relation between aging and neurodegeneration. The advances at the clinical and at the basic research levels are necessary if we wish to meet the formidable challenge that the increasing prevalence of Alzheimer's disease poses to the medical community. PMID:15937198

  9. Aging, frailty and age-related diseases.

    PubMed

    Fulop, T; Larbi, A; Witkowski, J M; McElhaney, J; Loeb, M; Mitnitski, A; Pawelec, G

    2010-10-01

    The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people. PMID:20559726

  10. Aging and dry eye disease.

    PubMed

    Ding, Juan; Sullivan, David A

    2012-07-01

    Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD.

  11. Aging and dry eye disease

    PubMed Central

    Ding, Juan; Sullivan, David A.

    2012-01-01

    Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD. PMID:22569356

  12. Association between Age and Severity to Leptospirosis in Children

    PubMed Central

    Guerrier, Gilles; Hie, Pauline; Gourinat, Ann-Claire; Huguon, Emilie; Polfrit, Yann; Goarant, Cyrille; D'Ortenzio, Eric; Missotte, Isabelle

    2013-01-01

    Background In endemic areas, leptospirosis is more common and more severe in adults compared with children. Reasons to explain this discrepancy remain unclear and limited data focusing on adolescents are available. The objective of the study was to describe disease spectrum and outcome differences in children and adolescents admitted for leptospirosis in a large at-risk population. Methods Clinical and laboratory data were obtained on hospitalized cases in New Caledonia from 2006 to 2012. Results Data of 60 patients <18 years of age (25 children under 14 and 35 adolescents aged 14 to 17) with confirmed leptospirosis were analyzed. Compared with children, adolescents presented more often with classic features of Weil disease (p = 0.02), combining hepatic and renal involvement with or without pulmonary participation. Jarisch-Herxheimer reactions were observed more often among adolescents (p<0.01). The overall case fatality rate was low (1 adolescent versus 0 children). Conclusion Severe leptospirosis in adolescents may be more likely to show adults' characteristics compared with children. Further studies are required to explore age-dependant host factors, including puberty-related physiological changes. PMID:24086780

  13. Elucidating novel disease mechanisms in severe asthma.

    PubMed

    Kim, Richard Y; Rae, Brittany; Neal, Rachel; Donovan, Chantal; Pinkerton, James; Balachandran, Lohis; Starkey, Malcolm R; Knight, Darryl A; Horvat, Jay C; Hansbro, Philip M

    2016-07-01

    Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases. PMID:27525064

  14. Elucidating novel disease mechanisms in severe asthma

    PubMed Central

    Kim, Richard Y; Rae, Brittany; Neal, Rachel; Donovan, Chantal; Pinkerton, James; Balachandran, Lohis; Starkey, Malcolm R; Knight, Darryl A; Horvat, Jay C; Hansbro, Philip M

    2016-01-01

    Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases. PMID:27525064

  15. The aging mouth: differentiating normal aging from disease.

    PubMed

    Lamster, Ira B; Asadourian, Lynda; Del Carmen, Tessa; Friedman, Paula K

    2016-10-01

    Aging is the physiologic change that occurs over time. In humans, this change occurs at different rates and are related to lifestyle, environment and genetics. It can be challenging to differentiate normal aging from disease. In the oral cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping and fracture lines, and a darker color. The pulp chamber and canals are reduced in size as a result of the deposition of secondary dentin. Coronal or root caries, however, represent disease. A limited amount of periodontal attachment loss occurs in association with aging, usually manifesting as recession on the buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the population, with the peak incidence being observed at 35-40 years of age. Changes to the mucosal tissue that occur with age include reduced wound-healing capacity. However, environmental factors, such as smoking, dramatically increase the risk of mucosal pathology. Reduced salivary gland function is often seen in association with medication usage, as well as with disorders such as diabetes mellitus. Both medication use and chronic disorders are more common in older adults. Masticatory function is of particular importance for older adults. Maintenance of a nutritionally complete diet is important for avoiding sarcopenia and the frailty syndrome. Successful oral aging is associated with adequate function and comfort. A reduced, but functional, dentition of 20 teeth in occlusion has been proposed as a measure of successful oral aging. Healthy oral aging is important to healthy aging from both biological and social perspectives. PMID:27501493

  16. Predicting global variation in infectious disease severity

    PubMed Central

    Jensen, Per M.; De Fine Licht, Henrik H.

    2016-01-01

    Background and objectives: Understanding the underlying causes for the variation in case-fatality-ratios (CFR) is important for assessing the mechanism governing global disparity in the burden of infectious diseases. Variation in CFR is likely to be driven by factors such as population genetics, demography, transmission patterns and general health status. We present data here that support the hypothsis that changes in CFRs for specific diseases may be the result of serial passage through different hosts. For example passage through adults may lead to lower CFR, whereas passage through children may have the opposite effect. Accordingly changes in CFR may occur in parallel with demographic transitions. Methodology: We explored the predictability of CFR using data obtained from the World Health Organization (WHO) disease databases for four human diseases: mumps, malaria, tuberculosis and leptospirosis and assessed these for association with a range of population characteristics, such as crude birth and death rates, median age of the population, mean body mass index, proportion living in urban areas and tuberculosis vaccine coverage. We then tested this predictive model on Danish historical demographic and population data. Results: Birth rates were the best predictor for mumps and malaria CFR. For tuberculosis CFR death rates were the best predictor and for leptospirosis population density was a significant predictor. Conclusions and implications: CFR predictors differed among diseases according to their biology. We suggest that the overall result reflects an interaction between the forces driving demographic change and the virulence of human-to-human transmitted diseases. PMID:26884415

  17. Resveratrol: A Focus on Several Neurodegenerative Diseases

    PubMed Central

    Tellone, Ester; Galtieri, Antonio; Russo, Annamaria; Giardina, Bruno; Ficarra, Silvana

    2015-01-01

    Molecules of the plant world are proving their effectiveness in countering, slowing down, and regressing many diseases. The resveratrol for its intrinsic properties related to its stilbene structure has been proven to be a universal panacea, especially for a wide range of neurodegenerative diseases. This paper evaluates (in vivo and in vitro) the various molecular targets of this peculiar polyphenol and its ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. What emerges is that, in the deep heterogeneity of the pathologies evaluated, resveratrol through a convergence on the protein targets is able to give therapeutic responses in neuronal cells deeply diversified not only in morphological structure but especially in their function performed in the anatomical district to which they belong. PMID:26180587

  18. Aging, inflammation, immunity and periodontal disease.

    PubMed

    Ebersole, Jeffrey L; Graves, Christina L; Gonzalez, Octavio A; Dawson, Dolph; Morford, Lorri A; Huja, Pinar Emecen; Hartsfield, James K; Huja, Sarandeep S; Pandruvada, Subramanya; Wallet, Shannon M

    2016-10-01

    The increased prevalence and severity of periodontal disease have long been associated with aging, such that this oral condition affects the majority of the adult population over 50 years of age. Although the immune system is a critical component for maintaining health, aging can be characterized by quantitative and qualitative modifications of the immune system. This process, termed 'immunosenescence', is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasia and autoimmunity, presumably reflecting the prolonged antigenic stimulation and/or stress responses that occur across the lifespan. Interestingly, the global reduction in the host capability to respond effectively to these challenges is coupled with a progressive increase in the general proinflammatory status, termed 'inflammaging'. Consistent with the definition of immunosenescence, it has been suggested that the cumulative effect of prolonged exposure of the periodontium to microbial challenge is, at least in part, a contributor to the effects of aging on these tissues. Thus, it has also been hypothesized that alterations in the function of resident immune and nonimmune cells of the periodontium contribute to the expression of inflammaging in periodontal disease. Although the majority of aging research has focused on the adaptive immune response, it is becoming increasingly clear that the innate immune compartment is also highly affected by aging. Thus, the phenomenon of immunosenescence and inflammaging, expressed as age-associated changes within the periodontium, needs to be more fully understood in this era of precision and personalized medicine and dentistry. PMID:27501491

  19. [Severe hereditary retinal diseases in childhood].

    PubMed

    Lorenz, B

    1996-01-01

    In dependence on the various statistics, hereditary causes are identified in up to 50% of the visually handicapped and blind school children. Most common are retinal disorders, which account for 15 to 55%. The most important diseases are briefly reviewed: Leber's congenital amaurosis, rod monochromacy, blue cone monochromacy, congenital stationary night blindness (CSNB), X-linked retinitis pigmentosa, Usher syndromes, Bardet-Biedl syndrome, juvenile neuronal ceroid lipofuscinosis Spielmeyer-Vogt, the various forms of albinism, exsudative vitreoretinopathies including Norrie's disease, as well as Stargardt's macular dystrophy, vitelliform macular dystrophy, and hereditary retinoblastoma. In addition to the clinical symptoms, general genetic principles are stressed, such as mode of inheritance, heterogeneity, expressivity, penetrance, age at manifestation, X-chromosomal gene inactivation, and variability. They all have to be taken into account to correctly establish the diagnosis, to identify family members at risk, and to provide adequate genetic counselling. An overview of the actual molecular genetics of the various retinal disorders is also given.

  20. [Severe hemolytic jaundice and Wilson's disease].

    PubMed

    Storck, D; Bareiss, P; Jesel, B; Warter, J

    1976-12-01

    The onset of spontaneous hemolytic jaundice in a young subject should lead to the search for Wilson's disease when clinical examination reveals cirrhosis. This hemolysis may evolve in the form of severe jaundice to a stage where the cirrhosis remains usually latent or well tolerated. The intervention of a toxic, allergic of infective factor liable to produce a hepatic lesion which frees a dose of copper sufficient to trigger off hemolysis, is discussed. The mechanism of the latter, that of the coagulation disorders observed, liver cell failure and widespread intravascular coagulation, are analysed in this paper and compared with data in the literature. The dramatic character of the case indicates that it is necessary to treat as a routine with penicillamine all homozygous forms of Wilson's disease.

  1. [Clinical management of severe ocular surface disease].

    PubMed

    Stoiber, J; Grabner, G

    2005-07-01

    Severe ocular surface diseases, such as Stevens-Johnson syndrome, ocular cicatricial pemphigoid or severe ocular burns may result in a significant loss of corneal stem cells, eventually leading to vision impairment or even corneal blindness. In case of unilateral involvement, limbal autografting, by means of transplanting limbal stem cells from the healthy fellow eye, has proved to be an effective procedure for restoring the integrity of the ocular surface. Limbal allografts may be performed in patients with bilateral disease, however, systemic immunosuppression is mandatory in these cases, with a long-term outcome that is frequently reduced compared to limbal autografts due to acute or chronic graft rejection. In recent years, amniotic membrane transplantation has been successfully employed as an additional tool in ocular surface reconstruction. The AlphaCor synthetic cornea, which is made of flexible acrylic may be considered as an alternative in patients with repeated corneal graft failures. Both limbal transplantation and the AlphaCor have been shown to be effective in eyes with an adequate tear film, but are most likely to fail in severe dry eyes or in patients with cicatrising diseases. Such conditions are the domain of keratoprostheses (KPros) with rigid optics, which certainly can be considered as the 'last resort' to restore vision in patients with profound corneal blindness not amenable to conventional corneal and limbal grafting. The osteo-odonto-keratoprosthesis according to Strampelli and modified by Falcinelli makes use of a "biological" support consisting of a longitudinal section of one of the patient's teeth that is also supported by the surrounding alveolar bone tissue. Compared to other devices favourable long-term results have been reported. In patients lacking any usable teeth, implantation of a keratoprosthesis with haptics made of Dacron (Pintucci-KPro) or tibial bone (Temprano-KPro) might be considered.

  2. RISK FACTORS FOR SEVERE HAND, FOOT AND MOUTH DISEASE.

    PubMed

    Owatanapanich, Somchai; Wutthanarungsan, Rochana; Jaksupa, Wipaporn; Thisyakorn, Usa

    2015-05-01

    We studied risk factors associated with severe hand, foot and mouth disease (HFMD) caused by enteroviruses among patients aged less than 15 years admitted to King Narai Hospital, Lopburi, Thailand during 2011-2013. Cases were divided into either mild or severe. Severe cases were those with encephalitis, meningitis, myocarditis, pneumonia, pulmonary edema or respiratory failure. Risk factors for severe infection were evaluated using univariate and multivariate logistic regression analysis. One hundred eighteen patients met the case definition of HFMD. Of these, 95 (80.5%) were classified as mild cases, and 23 (19.5%) as severe cases; there were 5 deaths (4.2%). Of the 23 severe cases, 9 were infected with coxsackievirus A16 (CA16), 8 with enterovirus 71 (EV71) and 4 with both EV71 and CA16. The most common presentations among the severe caseswere: seizures (74%), pneumonia (39%), encephalitis (39%), and meningitis (13%). The clinical manifestations significantly related to severe HFMD on univariate analysis were highest body temperature 39.00C, duration of fever 23 days, absence of skin lesions, diarrhea, dyspnea, seizures and hyperglycemia. The clinical manifestations significantly related to severe HFMD on both univariate and multivariate analyses were age less than 1 year, absence of oral lesions and drowsiness/lethargy. Clinicians should be aware of these factors. Early recognition of severe cases is important to increase the rates of successful outcomes and reduce mortality.

  3. RISK FACTORS FOR SEVERE HAND, FOOT AND MOUTH DISEASE.

    PubMed

    Owatanapanich, Somchai; Wutthanarungsan, Rochana; Jaksupa, Wipaporn; Thisyakorn, Usa

    2015-05-01

    We studied risk factors associated with severe hand, foot and mouth disease (HFMD) caused by enteroviruses among patients aged less than 15 years admitted to King Narai Hospital, Lopburi, Thailand during 2011-2013. Cases were divided into either mild or severe. Severe cases were those with encephalitis, meningitis, myocarditis, pneumonia, pulmonary edema or respiratory failure. Risk factors for severe infection were evaluated using univariate and multivariate logistic regression analysis. One hundred eighteen patients met the case definition of HFMD. Of these, 95 (80.5%) were classified as mild cases, and 23 (19.5%) as severe cases; there were 5 deaths (4.2%). Of the 23 severe cases, 9 were infected with coxsackievirus A16 (CA16), 8 with enterovirus 71 (EV71) and 4 with both EV71 and CA16. The most common presentations among the severe caseswere: seizures (74%), pneumonia (39%), encephalitis (39%), and meningitis (13%). The clinical manifestations significantly related to severe HFMD on univariate analysis were highest body temperature 39.00C, duration of fever 23 days, absence of skin lesions, diarrhea, dyspnea, seizures and hyperglycemia. The clinical manifestations significantly related to severe HFMD on both univariate and multivariate analyses were age less than 1 year, absence of oral lesions and drowsiness/lethargy. Clinicians should be aware of these factors. Early recognition of severe cases is important to increase the rates of successful outcomes and reduce mortality. PMID:26521518

  4. Ethnic Differences in Presentation and Severity of Alcoholic Liver Disease

    PubMed Central

    Durbin-Johnson, Blythe; Halsted, Charles H.; Medici, Valentina

    2015-01-01

    Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD. PMID:25702770

  5. Short report: Predictors of severe disease in melioidosis patients in Kuala Lumpur, Malaysia.

    PubMed

    Mohd Roslani, Ardita Dewi Roslani; Tay, Sun Tee; Puthucheary, Savithri D; Rukumani, Devi V; Sam, I-Ching

    2014-12-01

    The predictors of severe disease or death were determined for 85 melioidosis patients in Kuala Lumpur, Malaysia. Most of the patients were male, > 40 years old, and diabetic. Severe disease or death occurred in 28 (32.9%) cases. Lower lymphocyte counts and positive blood cultures were significant independent predictors of severe disease, but age, presentations with pneumonia, inappropriate empirical antibiotics, or flagellin types of the infecting isolates were not. Knowledge of local predictors of severe disease is useful for clinical management.

  6. Chronic kidney disease and premature ageing.

    PubMed

    Kooman, Jeroen P; Kotanko, Peter; Schols, Annemie M W J; Shiels, Paul G; Stenvinkel, Peter

    2014-12-01

    Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

  7. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  8. Telomere length variations in aging and age-related diseases.

    PubMed

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  9. Aging is a weak but relentless determinant of dementia severity

    PubMed Central

    Royall, Donald R.; Palmer, Raymond F.

    2016-01-01

    Structural Equation Models (SEM) can explicitly distinguish “dementia-relevant” variance in cognitive task performance (i.e., “δ” for dementia). In prior work, δ appears to uniquely account for dementia severity regardless of the cognitive measures used to construct it. In this study, we test δ as a mediator of age's prospective association with future cognitive performance and dementia severity in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). Age had adverse effects on future cognition, and these were largely mediated through δ, independently of education, ethnicity, gender, depression ratings, serum homo-cysteine levels, hemoglobin A1c, and apolipoprotein e4 status. Age explained 4% of variance in δ, and through it, 11-18% of variance in future cognitive performance. Our findings suggest that normative aging is a dementing condition (i.e., a “senility”). While the majority of variance in dementia severity must be independent of age, age's specific effect is likely to accumulate over the lifespan. Our findings also constrain age's dementing effects on cognition to the age-related fraction of “general intelligence” (Spearman's “g”). That has broad biological and pathophysiological implications. PMID:26930722

  10. Oral health of patients with severe rheumatic heart disease.

    PubMed

    Maharaj, Breminand; Vayej, Ahmed C

    2012-07-01

    In order to determine whether adequate attention is paid to the maintenance of good oral health in patients at risk of developing infective endocarditis, we studied 44 black patients with severe rheumatic heart disease before they had cardiac surgery. Plaque and gingival index scores were calculated and panoramic radiographs were done in all patients. There were 17 males and 27 females (mean age: 30.6 years). The plaque and gingival index scores were classified as poor in 31.8 and 54.6% of patients, respectively. Panoramic radiographic findings included caries in 56.8% of patients, peri-apical pathology in 18.1% and retained roots in 22.7% of patients. This study demonstrates that inadequate attention is paid to the maintenance of good oral health in patients with severe rheumatic heart disease. The oral and dental care of patients at risk of developing infective endocarditis needs to be improved. PMID:22836156

  11. Severe Spinal Injury in Hirayama Disease

    PubMed Central

    Quarracino, Cecilia; Aguirre, Florencia; Rugilo, Carlos A.; Negri, Luciana De

    2015-01-01

    Hirayama disease is a rare neurological disorder characterized by an insidious progressive subacute unilateral or bilateral weakness of the hands and forearm muscles leading to a painless amyotrophy. The disease primarily affects young men in the second to third decades of life. It has always been described as a second motor neuron disease, thus sparing the pyramidal and sensitive pathways. It usually has a slow progression course of 3 to 5 years followed by stabilization. Since its initial description by Keyzo Hirayama in 1959, most cases have been reported in Asia, particularly Japan and India, although the disease reportedly has worldwide distribution. PMID:26435801

  12. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process.

  13. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process. PMID:26655093

  14. SIRT3 regulates progression and development of diseases of aging

    PubMed Central

    Bomze, Howard M.; Hirschey, Matthew D.

    2015-01-01

    The mitochondrial sirtuin SIRT3 is a protein deacylase that regulates almost every major aspect of mitochondrial biology, including nutrient oxidation, ATP generation, reactive oxygen species detoxification, mitochondrial dynamics, and the mitochondrial unfolded protein response. Interestingly, mice lacking SIRT3 (SIRT3KO), either spontaneously or when crossed with mouse models of disease, develop several diseases of aging at an accelerated pace, such as cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, and thus might be a valuable model of accelerated aging. In this review we discuss SIRT3 functions in pathways involved in diseases of aging, how lack of SIRT3 might accelerate the aging process, and suggest that further studies on SIRT3 might help uncover important new pathways driving the aging process. PMID:26138757

  15. The Level of Cholesterol in COPD Patients with Severe and Very Severe Stage of the Disease

    PubMed Central

    Zafirova-Ivanovska, Beti; Stojkovikj, Jagoda; Dokikj, Dejan; Anastasova, Sasha; Debresliovska, Angela; Zejnel, Sead; Stojkovikj, Dragana

    2016-01-01

    BACKGROUND: High blood cholesterol is part of metabolic syndrome and can be caused by medical conditions or bad dietary habits. AIM: The aim of the study was to investigate the prevalence of hypercholesterolemia in privies diagnosed patients with the severe and very severe stage of COPD, which were stable. MATERIAL AND METHODS: We investigated 100 subjects, all of them smokers, with smoking status >10 years, stratified into two groups: with severe and very severe stage of the disease. It was clinical, randomized, cross-sectional study. Besides demographic parameters and functional parameters, body mass index, cholesterol, LDL, and HDL were investigated. RESULTS: In the group of patients with very severe COPD were recorded significantly higher average values of cholesterol (6.16 ± 1.5 vs. 5.61 ± 1.1, p = 0.039). As independent significant factors influencing cholesterol in the group with a very severe COPD were confirmed the age of the patients (p = 0.005), LDL (p = 0.004) and HDL (p = 0.002). In the group with severe COPD, only LDL was confirmed as an independent significant factor that has an impact on cholesterol (p < 0.0001). CONCLUSION: The results of our survey demonstrated a high level of blood cholesterol and LDL, and low level of blood HDL in both investigated group’s patients with COPD. PMID:27335600

  16. NK Cells in Healthy Aging and Age-Associated Diseases

    PubMed Central

    Camous, Xavier; Pera, Alejandra; Solana, Rafael; Larbi, Anis

    2012-01-01

    NK cells exhibit the highest cytotoxic capacity within the immune system. Alteration of their number or functionality may have a deep impact on overall immunity. This is of particular relevance in aging where the elderly population becomes more susceptible to infection, cancer, autoimmune diseases, and neurodegenerative diseases amongst others. As the fraction of elderly increases worldwide, it becomes urgent to better understand the aging of the immune system to prevent and cure the elderly population. For this, a better understanding of the function and phenotype of the different immune cells and their subsets is necessary. We review here NK cell functions and phenotype in healthy aging as well as in various age-associated diseases. PMID:23251076

  17. NK cells in healthy aging and age-associated diseases.

    PubMed

    Camous, Xavier; Pera, Alejandra; Solana, Rafael; Larbi, Anis

    2012-01-01

    NK cells exhibit the highest cytotoxic capacity within the immune system. Alteration of their number or functionality may have a deep impact on overall immunity. This is of particular relevance in aging where the elderly population becomes more susceptible to infection, cancer, autoimmune diseases, and neurodegenerative diseases amongst others. As the fraction of elderly increases worldwide, it becomes urgent to better understand the aging of the immune system to prevent and cure the elderly population. For this, a better understanding of the function and phenotype of the different immune cells and their subsets is necessary. We review here NK cell functions and phenotype in healthy aging as well as in various age-associated diseases.

  18. Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma.

    PubMed

    Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

    2015-09-01

    Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in previous research, scores on the Parenting Stress Index in mothers and fathers of the children with problematic severe asthma were low. Higher parenting stress was associated with higher levels of internalizing and externalizing behavioral problems in children (Child Behavior Checklist). Higher parenting stress in mothers was also associated with higher airway inflammation (FeNO). Thus, although parenting stress was suggested to be low in this group, higher parenting stress, especially in the mother, is associated with more airway inflammation and greater child behavioral problems. This indicates the importance of focusing care in this group on all possible sources of problems, i.e., disease exacerbations and behavioral problems in the child as well as parenting stress.

  19. Severe Primary Raynaud's Disease Treated with Rituximab

    PubMed Central

    Almoallim, Hani

    2016-01-01

    Raynaud's phenomenon refers to reversible spasms of the peripheral arterioles that can be primary Raynaud's phenomenon (PRP) or secondary Raynaud's phenomenon (SRP) to underlying connective tissue disease, both of which are characterized by a triphasic color response triggered by cold exposure or stress. PRP is typically a benign disease, whereas SRP may progress into digital ulcers and/or gangrene. Here, we report a case of a 55-year-old female diagnosed with PRP 7 years ago. Treatment with first-line agents, including calcium channel blocker, aspirin, and phosphodiesterase inhibitor, did not control her symptoms, which progressed to digital ulceration and gangrene. There were no symptoms of underlying autoimmune disease or malignancy, and autoimmune, serology, and immunology test results were normal; a biopsy of her left little finger was negative for vasculitis. Development to critical digital ischemia necessitated treatment with intravenous iloprost and heparin infusion followed by angioplasty, which led to a partial improvement. Due to persistent symptoms, rituximab therapy was initiated and two cycles induced a complete resolution of symptoms.

  20. Severe Primary Raynaud's Disease Treated with Rituximab.

    PubMed

    Shabrawishi, Mohammed; Albeity, Abdurahman; Almoallim, Hani

    2016-01-01

    Raynaud's phenomenon refers to reversible spasms of the peripheral arterioles that can be primary Raynaud's phenomenon (PRP) or secondary Raynaud's phenomenon (SRP) to underlying connective tissue disease, both of which are characterized by a triphasic color response triggered by cold exposure or stress. PRP is typically a benign disease, whereas SRP may progress into digital ulcers and/or gangrene. Here, we report a case of a 55-year-old female diagnosed with PRP 7 years ago. Treatment with first-line agents, including calcium channel blocker, aspirin, and phosphodiesterase inhibitor, did not control her symptoms, which progressed to digital ulceration and gangrene. There were no symptoms of underlying autoimmune disease or malignancy, and autoimmune, serology, and immunology test results were normal; a biopsy of her left little finger was negative for vasculitis. Development to critical digital ischemia necessitated treatment with intravenous iloprost and heparin infusion followed by angioplasty, which led to a partial improvement. Due to persistent symptoms, rituximab therapy was initiated and two cycles induced a complete resolution of symptoms. PMID:27651971

  1. Severe Primary Raynaud's Disease Treated with Rituximab

    PubMed Central

    Almoallim, Hani

    2016-01-01

    Raynaud's phenomenon refers to reversible spasms of the peripheral arterioles that can be primary Raynaud's phenomenon (PRP) or secondary Raynaud's phenomenon (SRP) to underlying connective tissue disease, both of which are characterized by a triphasic color response triggered by cold exposure or stress. PRP is typically a benign disease, whereas SRP may progress into digital ulcers and/or gangrene. Here, we report a case of a 55-year-old female diagnosed with PRP 7 years ago. Treatment with first-line agents, including calcium channel blocker, aspirin, and phosphodiesterase inhibitor, did not control her symptoms, which progressed to digital ulceration and gangrene. There were no symptoms of underlying autoimmune disease or malignancy, and autoimmune, serology, and immunology test results were normal; a biopsy of her left little finger was negative for vasculitis. Development to critical digital ischemia necessitated treatment with intravenous iloprost and heparin infusion followed by angioplasty, which led to a partial improvement. Due to persistent symptoms, rituximab therapy was initiated and two cycles induced a complete resolution of symptoms. PMID:27651971

  2. Parkinson's disease as a result of aging.

    PubMed

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-06-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field.

  3. Parkinson's disease as a result of aging

    PubMed Central

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-01-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field. PMID:25677794

  4. Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

    PubMed

    Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

    2009-09-01

    One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

  5. Curcumin, inflammation, ageing and age-related diseases.

    PubMed

    Sikora, E; Scapagnini, Giovanni; Barbagallo, Mario

    2010-01-17

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy between April 7 and 8th 2009. Here the lecture by Sikora with some input from the chairpersons Scapagnini and Barbagallo is summarized. Ageing is manifested by the decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha, encoded by genes activated by the transcription factor NF-kappaB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-kappaB-dependent inflammation. In this review we consider the possibility of the spice curcumin, a powerful antioxidant and anti-inflammatory agent possibly capable of improving the health status of the elderly.

  6. Age-at-onset in Huntington disease

    PubMed Central

    Orth, Michael; Schwenke, Carsten

    2011-01-01

    Background: In Huntington disease, the accurate determination of age-at-onset is critical to identify modifiers and therapies that aim to delay it. Methods: Retrospective data from the European Huntington’s Disease Network’s REGISTRY and PREDICT-HD, a longitudinal study in prodromal huntingtin gene expansion mutation carriers. Data (age, gender, CAG repeat length, parent affected, and Unified Huntington’s Disease Rating Scale motor score, total functional capacity) from at least three visits in 423 REGISTRY and 124 PREDICT-HD participants were included. Data based extrapolations of individual age-at-onset using generalized linear mixed models based on individual slopes of motor score or total functional capacity, and predictions using the Langbehn, or Ranen formula, were compared with clinicians’ estimates. Results: Concordance was best for the observed age-at-onset in PREDICT-HD and the calculated onset using the PREDICT-HD UHDRS longitudinal motor scores. This was superior to the REGISTRY data. For total functional capacity, the investigator’s estimate was 4 years before the data derived age-at-onset. The concordance of predictions of probability of age-at-onset is better with the observed age-at-onset in the PREDICT-HD data (difference in 25%tile -5 to 10 years) than the REGISTRY data (±20 years). Conclusions: Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It can be useful to 1) add in the manifest population motor score regression derived age-at-onset as additional motor onset and 2) add total functional capacity regression derived age-at-onset for the onset of functional impact of Huntington disease when patients are in mid- to late-stage. PMID:22453877

  7. Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

    PubMed Central

    Reddy, P. Hemachandra; Reddy, Tejaswini P.

    2012-01-01

    Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal models, postmortem brain studies of and clinical studies of aging and neurodegenerative diseases suggests that mitochondrial function is defective in aging and neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Several lines of research suggest that mitochondrial abnormalities, including defects in oxidative phosphorylation, increased accumulation of mitochondrial DNA defects, impaired calcium influx, accumulation of mutant proteins in mitochondria, and mitochondrial membrane potential dissipation are important cellular changes in both early and late-onset neurodegenerative diseases. Further, emerging evidence suggests that structural changes in mitochondria, including increased mitochondrial fragmentation and decreased mitochondrial fusion, are critical factors associated with mitochondrial dysfunction and cell death in aging and neurodegenerative diseases. This paper discusses research that elucidates features of mitochondria that are associated with cellular dysfunction in aging and neurodegenerative diseases and discusses mitochondrial structural and functional changes, and abnormal mitochondrial dynamics in neurodegenerative diseases. It also outlines mitochondria-targeted therapeutics in neurodegenerative diseases. PMID:21470101

  8. Brain aging, Alzheimer's disease, and mitochondria

    PubMed Central

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  9. Parkinson's Disease Severity and Use of Dopaminergic Medications

    PubMed Central

    Fang, John Y.; Pérez, Adriana; Christine, Chadwick W.; Leehey, Maureen; Aminoff, Michael J.; Boyd, James T.; Morgan, John C.; Dhall, Rohit; Nicholas, Anthony P; Bodis-Wollner, Ivan; Zweig, Richard M.; Goudreau, John L.

    2015-01-01

    Background The effects of dopaminergic therapy in Parkinson's disease (PD) can vary depending on the class of medication selected. Objective The aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD. Methods A non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life. Results The outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cogmeds and amantadine. Conclusion This observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy. PMID:25541182

  10. NAD+ and sirtuins in aging and disease.

    PubMed

    Imai, Shin-ichiro; Guarente, Leonard

    2014-08-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide. PMID:24786309

  11. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration.

  12. Neuroinflamm-aging and neurodegenerative diseases: an overview.

    PubMed

    Pizza, Vincenzo; Agresta, Anella; D'Acunto, Cosimo W; Festa, Michela; Capasso, Anna

    2011-08-01

    Neuroinflammation is considered a chronic activation of the immune response in the central nervous system (CNS) in response to different injuries. This brain immune activation results in various events: circulating immune cells infiltrate the CNS; resident cells are activated; and pro-inflammatory mediators produced and released induce neuroinflammatory brain disease. The effect of immune diffusible mediators on synaptic plasticity might result in CNS dysfunction during neuroinflammatory brain diseases. The CNS dysfunction may induce several human pathological conditions associated with both cognitive impairment and a variable degree of neuroinflammation. Furthermore, age has a powerful effect on enhanced susceptibility to neurodegenerative diseases and age-dependent enhanced neuroinflammatory processes may play an important role in toxin generation that causes death or dysfunction of neurons in neurodegenerative diseases This review will address current understanding of the relationship between ageing, neuroinflammation and neurodegenerative disease by focusing on the principal mechanisms by which the immune system influences the brain plastic phenomena. Also, the present review considers the principal human neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and psychiatric disorders caused by aging and neuroinflammation.

  13. Chronic kidney disease: a clinical model of premature aging.

    PubMed

    Stenvinkel, Peter; Larsson, Tobias E

    2013-08-01

    Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population.

  14. Does severity of dermatochalasis in aging affect corneal biomechanical properties?

    PubMed Central

    Atalay, Kurşat; Gurez, Ceren; Kirgiz, Ahmet; Serefoglu Cabuk, Kubra

    2016-01-01

    Purpose The aim of this study was to investigate the possibility of a relationship between corneal biomechanical properties and different grades of dermatochalasis. Patients and methods Patients were assigned to four groups according to the severity of their dermatochalasis: normal (Group 1), mild (Group 2), moderate (Group 3), and severe (Group 4). An Ocular Response Analyzer device was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated intraocular pressure (IOPcc). Results We found no significant differences in the mean values of the CH, CRF, and IOPcc of all groups (P=0.75, P=0.93, and P=0.11, respectively). However, CH and IOPcc were negatively correlated in Group 1, Group 2, and Group 3 patients (P=0.013, r=−0.49; P=0.015, r=−0.52; and P=0.011, r=−0.47, respectively), but this correlation was not apparent in the Group 4 patients (P=0.57, r=0.12). CRF and IOPcc were correlated, but only in Group 4 (P=0.001, r=0.66). Conclusion Severe dermatochalasis was associated with altered corneal biomechanical properties. Some of the important visual consequences of dermatochalasis and related diseases (such as floppy eyelid syndrome) can be understood by considering corneal biomechanical alterations. PMID:27274214

  15. Cardiac and Respiratory Disease in Aged Horses.

    PubMed

    Marr, Celia M

    2016-08-01

    Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older equids.

  16. So! What's aging? Is cardiovascular aging a disease?

    PubMed

    Lakatta, Edward G

    2015-06-01

    "Inside every old person is a young person wondering what happened." So, what is aging? Aging is a manifestation of progressive, time-dependent failure of molecular mechanisms that create disorder within a system of DNA and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere, universe). Continuous signaling, transmitted with different kinetics across each of these environments, confers a "mutual enslavement" that creates ordered functions among the components within the system. Accrual of this molecular disorder over time, i.e. during aging, causes progressive changes in the structure and function of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of signaling within the DNA environment system within the heart and arteries become disordered with advancing age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation and nitration phosphorylation, lead to altered misfolding and disordered molecular interactions. The stoichiometry and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is not executed by "professional" inflammatory cells (i.e. white blood cells), however, but by activation of renin-angiotensin-aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and

  17. So! What's aging? Is cardiovascular aging a disease?

    PubMed

    Lakatta, Edward G

    2015-06-01

    "Inside every old person is a young person wondering what happened." So, what is aging? Aging is a manifestation of progressive, time-dependent failure of molecular mechanisms that create disorder within a system of DNA and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere, universe). Continuous signaling, transmitted with different kinetics across each of these environments, confers a "mutual enslavement" that creates ordered functions among the components within the system. Accrual of this molecular disorder over time, i.e. during aging, causes progressive changes in the structure and function of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of signaling within the DNA environment system within the heart and arteries become disordered with advancing age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation and nitration phosphorylation, lead to altered misfolding and disordered molecular interactions. The stoichiometry and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is not executed by "professional" inflammatory cells (i.e. white blood cells), however, but by activation of renin-angiotensin-aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and

  18. Fluency in Parkinson's disease: disease duration, cognitive status and age.

    PubMed

    Brabo, Natalia Casagrande; Minett, Thais Soares C; Ortiz, Karin Zazo

    2014-05-01

    The objective of this study was to determine the frequency of occurrence and to characterize the typology of dysfluencies in individuals with Parkinson's disease (PD), including the variables age, gender, schooling, disease duration, score on the Hoehn and Yahr scale and cognitive status (score on Mini-Mental State Examination). A cross-sectional study of a sample comprising 60 adults matched for gender, age and schooling was conducted. Group I comprised 30 adults with idiopathic PD, and Group II comprised 30 healthy adults. For assessment of fluency of speech, subjects were asked to utter a narrative based on a sequence of drawings and a transcription of 200 fluent syllables was performed to identify speech dysfluencies. PD patients exhibited a higher overall number of dysfluencies in speech with a large number of atypical dysfluencies. Additionally, results showed an influence of the variables cognitive status, disease duration and age on occurrence of dysfluencies. PMID:24863510

  19. Growth factors, aging and age-related diseases.

    PubMed

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID:26883276

  20. Diagnosis by ultrasound of severe carotid artery disease in patients undergoing cardiopulmonary bypass operations.

    PubMed Central

    Lewis, R R; Beasley, M G; Ayoub, A; Deverall, P B; Yates, A K; Gosling, R G

    1980-01-01

    A non-invasive method using continuous wave Doppler shift ultrasound and spectral analysis was used as a screening test for severe carotid artery disease in patients undergoing cardiopulmonary bypass operations. One hundred and eighty-eight patients were examined before cardiac surgery (91 for ischaemic heart disease, 17 for ischaemic heart disease and valve replacement, 66 for valve replacement alone, and 14 for congenital abnormalities). The mean age of the 108 patients suffering from ischaemic heart disease was 54 years (+/- 8) and that of the 80 patients admitted either for valve replacement alone or for congenital abnormalities was 52 years (+/- 12). Five of the 108 patients suffering from ischaemic heart disease were found to have severe occlusive disease of the internal carotid artery by the ultrasound test, while the test was normal in the other two groups. Patients with severe carotid artery disease proceeded to carotid arteriography and endarterectomy before the planned heart operation. Images PMID:7397042

  1. Fatigue in inflammatory bowel diseases: relationship with age and disease activity.

    PubMed

    Pellino, Gianluca; Sciaudone, Guido; Caserta, Violetta; Candilio, Giuseppe; De Fatico, G Serena; Gagliardi, Silvana; Landino, Isabella; Patturelli, Marta; Riegler, Gabriele; Di Caprio, Ester Livia; Canonico, Silvestro; Gritti, Paolo; Selvaggi, Francesco

    2014-01-01

    A higher rate of patients suffering from inflammatory bowel diseases (IBD) are reported to experience the symptom of fatigue compared with general population. Fatigue can impair quality of life of IBD patients by limiting their daily functioning. However, this problem is poorly understood and addressed. Our aim was to investigate the impact of fatigue in IBD patients compared with controls, and to seek for relation between age and disease activity. IBD patients aged between 16 and 75 years observed at our Unit from June 2011 through June 2012 were evaluated for fatigue. Patients were asked to fill the fatigue impact scale (FIS) questionnaire. A cohort of age- and sex-matched patients observed for other-than-IBD diseases were prospectively enrolled to act as controls. Patients diagnosed with malignancies were excluded from evaluation. Each group included 16 patients, of whom half aged over 65 years. Fatigue was more severe in IBD patients than in controls (p = 0.02), irrespective of age and disease activity. IBD patients with moderate to severe disease activity showed worse fatigue compared with controls at any age (p < 0.0001). Young IBD patients with low disease activity showed a trend toward worse FIS score when compared with old IBD counterparts (p = 0.06). IBD significantly impacted on fatigue in our series. Considering IBD patients in remission, younger patients may experience worse fatigue. Further studies are needed to explore the effects of fatigue on quality of life and the potential of appropriate intervention strategies.

  2. Neuropharmacology of depression in aging and age-related diseases.

    PubMed

    Gareri, Pietro; De Fazio, Pasquale; De Sarro, Giovambattista

    2002-02-01

    Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and non-suicide mortality. Depression may be also caused by a various number of drugs currently administered; this is remarkable especially in elderly people, where polypathology is often associated with polypharmacotherapy. However, the pathogenesis of geriatric depression is not well understood; major depression may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. Some clinical observations also suggest that striato-frontal dysfunction is associated with late life depression. A number of hypotheses have been made, focusing that mood disturbances are probably linked to a disturbed central metabolism of monoamines 5-hydroxytryptamine, noradrenaline and dopamine; however most of this knowledge is derived from animal models. Parkinson's and Alzheimer's diseases are age-related diseases associated to decreased activity or brain lesions in the orbital frontal cortex and basal ganglia. These observations lead to the hypothesis that the dysfunction of one or more of the cortical basal ganglia-thalamic neuronal loops are involved in the pathophysiology of primary and secondary depression. This dysfunction may be mediated by decreased serotonin release and probably, also by reduction in serotonin receptors. Development of novel approaches such as dynamic brain imaging methods, together with indirect knowledge coming from the effects of new antidepressants, will increase the understanding of neurochemistry of depression in old age. PMID:12039452

  3. Remission of severe aphthous stomatitis of celiac disease with etanercept

    PubMed Central

    2013-01-01

    Celiac disease is a common autoimmune disease triggered by gluten-containing foods (wheat, barley and rye) in genetically predisposed individuals. We present a patient with celiac disease complicated by severe aphthous stomatitis resulting in impairing swallowing, chewing and speaking. This led to weight loss, psychosocial problems as well as inability to perform her work. A variety of topical and systemic medications used resulted in either no improvement or only partial alleviation of the patient’s symptoms. After informed consent, etanercept was initiated and resulted in complete remission of aphthous stomatitis, decrease in arthralgia and fatigue and considerable improvement in her quality of life. The use of newer biological agents for selected and severe manifestations of celiac disease may lead to improved morbidity in these patients, but more studies are needed to determine long-term efficacy as well as safety of these drugs in the mucosal and/or systemic complications of this disease. PMID:24365222

  4. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  5. Defining Disease Severity in Inflammatory Bowel Diseases: Current and Future Directions.

    PubMed

    Peyrin-Biroulet, Laurent; Panés, Julián; Sandborn, William J; Vermeire, Séverine; Danese, Silvio; Feagan, Brian G; Colombel, Jean-Frédéric; Hanauer, Stephen B; Rycroft, Beth

    2016-03-01

    Although most treatment algorithms in inflammatory bowel disease (IBD) begin with classifying patients according to disease severity, no formal validated or consensus definitions of mild, moderate, or severe IBD currently exist. There are 3 main domains relevant to the evaluation of disease severity in IBD: impact of the disease on the patient, disease burden, and disease course. These measures are not mutually exclusive and the correlations and interactions between them are not necessarily proportionate. A comprehensive literature search was performed regarding current definitions of disease severity in both Crohn's disease and ulcerative colitis, and the ability to categorize disease severity in a particular patient. Although numerous assessment tools for symptoms, quality of life, patient-reported outcomes, fatigue, endoscopy, cross-sectional imaging, and histology (in ulcerative colitis) were identified, few have validated thresholds for categorizing disease activity or severity. Moving forward, we propose a preliminary set of criteria that could be used to classify IBD disease severity. These are grouped by the 3 domains of disease severity: impact of the disease on the patient (clinical symptoms, quality of life, fatigue, and disability); measurable inflammatory burden (C-reactive protein, mucosal lesions, upper gastrointestinal involvement, and disease extent), and disease course (including structural damage, history/extension of intestinal resection, perianal disease, number of flares, and extraintestinal manifestations). We further suggest that a disease severity classification should be developed and validated by an international group to develop a pragmatic means of identifying patients with severe disease. This is increasingly important to guide current therapeutic strategies for IBD and to develop treatment algorithms for clinical practice. PMID:26071941

  6. Studying the role of dystrophin-associated proteins in influencing Becker muscular dystrophy disease severity.

    PubMed

    van den Bergen, J C; Wokke, B H A; Hulsker, M A; Verschuuren, J J G M; Aartsma-Rus, A M

    2015-03-01

    Becker muscular dystrophy is characterized by a variable disease course. Many factors have been implicated to contribute to this diversity, among which the expression of several components of the dystrophin associated glycoprotein complex. Together with dystrophin, most of these proteins anchor the muscle fiber cytoskeleton to the extracellular matrix, thus protecting the muscle from contraction induced injury, while nNOS is primarily involved in inducing vasodilation during muscle contraction, enabling adequate muscle oxygenation. In the current study, we investigated the role of three components of the dystrophin associated glycoprotein complex (beta-dystroglycan, gamma-sarcoglycan and nNOS) and the dystrophin homologue utrophin on disease severity in Becker patients. Strength measurements, data about disease course and fresh muscle biopsies of the anterior tibial muscle were obtained from 24 Becker patients aged 19 to 66. The designation of Becker muscular dystrophy in this study was based on the mutation and not on the clinical severity. Contrary to previous studies, we were unable to find a relationship between expression of nNOS, beta-dystroglycan and gamma-sarcoglycan at the sarcolemma and disease severity, as measured by muscle strength in five muscle groups and age at reaching several disease milestones. Unexpectedly, we found an inverse correlation between utrophin expression at the sarcolemma and age at reaching disease milestones.

  7. Age-related changes in brain support cells: Implications for stroke severity.

    PubMed

    Sohrabji, Farida; Bake, Shameena; Lewis, Danielle K

    2013-10-01

    Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells.

  8. Fatigue Severity among African Americans: Gender and Age Interactions.

    ERIC Educational Resources Information Center

    Song, Sharon; Jason, Leonard A.; Taylor, Renee R.; Torres-Harding, Susan R.; Helgerson, Jena; Witter, Elizabeth

    2002-01-01

    Investigated the relationship between fatigue, age, and gender among African Americans, Caucasians, and Latinos. Survey results found significant age and gender interactions among African Americans and Caucasians. African American women and older African American men had the highest fatigue rates. There was no significant difference in levels of…

  9. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    PubMed Central

    Schick, Tina; Altay, Lebriz; Viehweger, Eva; Hoyng, Carel B.; den Hollander, Anneke I.; Felsch, Moritz; Fauser, Sascha

    2016-01-01

    Background Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. Methods In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. Results Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). Conclusion The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was

  10. HLA and other gene associations with dengue disease severity.

    PubMed

    Stephens, H A F

    2010-01-01

    Large case control gene association studies have been performed on cohorts of dengue virus (DENV) infected patients identified in mainland Southeast Asia, South Asia and the Caribbean. Candidate genes that have shown statistically significant associations with DENV disease severity encode HLA molecules, cell receptors for IgG (FcGII), vitamin D and ICAM3 (DCSIGN or CD209), pathogen recognition molecules such as mannose binding lectin (MBL), blood related antigens including ABO and human platelet antigens (HPA1 and HPA2). In ethnic Thais with secondary infections a variety of HLA class I alleles (HLA-A 0203, 0207, A11, B 15, B 44, B 46, B 48, B 51, B 52), DCSIGN promoter polymorphisms and the AB blood group, independently associate with either susceptibility or resistance to dengue fever (DF) and the more severe dengue hemorrhagic fever (DHF). There is also evidence that some HLA associations with disease severity correlate with the DENV serotype inducing secondary infections. Taken together, there is now evidence that allelic variants of multiple gene loci involved in both acquired and innate immune responses contribute significantly to DENV disease outcome and severity. Further analysis of the genetic basis of severe DENV disease in different at risk populations may contribute to the development of new preventative and therapeutic interventions.

  11. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  12. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression. PMID:26827786

  13. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression.

  14. Prevalence of celiac disease in patients with severe food allergy.

    PubMed

    Pillon, R; Ziberna, F; Badina, L; Ventura, A; Longo, G; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Patano, G; Not, T; Berti, I

    2015-10-01

    The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.

  15. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    PubMed Central

    Licastro, Federico; Candore, Giuseppina; Lio, Domenico; Porcellini, Elisa; Colonna-Romano, Giuseppina; Franceschi, Claudio; Caruso, Calogero

    2005-01-01

    The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival

  16. Validation of the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI): characterizing disease severity and assessing responsiveness to clinical change

    PubMed Central

    Anyanwu, C.O.; Fiorentino, D.; Chung, L.; Dzuong, C.; Wang, Y.; Okawa, J.; Carr, K.; Propert, K.J.; Werth, V.P.

    2015-01-01

    Summary Background The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was developed for use in clinical trials and longitudinal patient assessment. Objectives To characterize disease severity using the CDASI and assess responsiveness of this instrument to clinically meaningful changes in disease activity. Methods Patients with cutaneous dermatomyositis at the University of Pennsylvania (UPenn, n = 93) and Stanford University (Stanford, n = 106) were prospectively evaluated using the CDASI, physician global assessment (PGA) Likert scales, and visual analog scale (VAS). Data was analyzed using logistic regression models and receiver operating characteristic curves to select cut-offs. Results Baseline CDASI activity scores for the patients evaluated at UPenn ranged from 0 to 47 (median 17), and baseline PGA VAS scores ranged from 0 to 9.6 (median 1.1). At UPenn a CDASI activity score of 19 differentiated mild from moderate and severe disease. At Stanford baseline CDASI scores ranged from 0 to 48 (median 21), baseline PGA VAS scores ranged from 0 to 9.7 (median 4.2) and CDASI activity scores of 14 or less characterized mild disease. When a 2 cm change in the PGA VAS was regarded as a clinically significant improvement, a 4-point (UPenn) or 5-point (Stanford) change in CDASI reflected a minimal clinically significant response. Conclusions The CDASI is a valid and responsive measure that can be used to characterize cutaneous dermatomyositis severity and detect improvement in disease activity. Variations in cutoffs may be due to differences in disease severity between the two populations or inter-rater variations in use of the external gold measures. PMID:25994337

  17. Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies

    PubMed Central

    George, Michaela F.; Briggs, Farren B.S.; Shao, Xiaorong; Gianfrancesco, Milena A.; Kockum, Ingrid; Harbo, Hanne F.; Celius, Elisabeth G.; Bos, Steffan D.; Hedström, Anna; Shen, Ling; Bernstein, Allan; Alfredsson, Lars; Hillert, Jan; Olsson, Tomas; Patsopoulos, Nikolaos A.; De Jager, Philip L.; Oturai, Annette B.; Søndergaard, Helle B.; Sellebjerg, Finn; Sorensen, Per S.; Gomez, Refujia; Caillier, Stacy J.; Cree, Bruce A.C.; Oksenberg, Jorge R.; Hauser, Stephen L.; D'Alfonso, Sandra; Leone, Maurizio A.; Boneschi, Filippo Martinelli; Sorosina, Melissa; van der Mei, Ingrid; Taylor, Bruce V.; Zhou, Yuan; Schaefer, Catherine

    2016-01-01

    Objective: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). Methods: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ≤5 vs >5 and MSSS of <2.5 vs ≥7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01. Results: A total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing. Conclusions: The largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments. PMID:27540591

  18. Linguistic Correlates of Asymmetric Motor Symptom Severity in Parkinson's Disease

    ERIC Educational Resources Information Center

    Holtgraves, Thomas; McNamara, Patrick; Cappaert, Kevin; Durso, Raymond

    2010-01-01

    Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N = 31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the…

  19. Antibody Response and Disease Severity in Healthcare Worker MERS Survivors

    PubMed Central

    Khalid, Imran; Ahmed, Waleed A.; Dada, Ashraf M.; Bayumi, Daniyah T.; Malic, Laut S.; Althawadi, Sahar; Ignacio, Kim; Alsalmi, Hanadi S.; Al-Abdely, Hail M.; Wali, Ghassan Y.; Qushmaq, Ismael A.; Alraddadi, Basem M.; Perlman, Stanley

    2016-01-01

    We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease. PMID:27192543

  20. Spotlight on memantine in moderate to severe Alzheimer's disease.

    PubMed

    McKeage, Kate

    2010-02-01

    Memantine (Axura, Ebixa, Namenda) is an uncompetitive, moderate-affinity NMDA receptor antagonist that is indicated for the treatment of moderate to severe Alzheimer's disease. In well designed trials in patients with moderate to severe Alzheimer's disease, oral memantine monotherapy improved outcomes in the area of functional ability more than placebo in one trial, but in a second trial, treatment differences did not reach significance. Memantine has a distinct mode of action compared with that of acetylcholinesterase (AChE) inhibitors, and in a well designed study, combination therapy with memantine plus donepezil improved outcomes more than donepezil plus placebo in all four domains (function, cognition, behaviour and global change). Memantine is generally well tolerated, with adverse events occurring with a similar incidence to that reported with placebo. In modelled cost-effectiveness analyses, memantine was dominant to no therapy in regard to cost per quality-adjusted life-year (QALY) gained, and the combination of memantine plus donepezil was dominant to donepezil therapy alone in regard to QALYs gained when treatment periods exceeded 1 year in patients with moderate to severe disease. Thus, in the management of patients with moderate to severe Alzheimer's disease, memantine provides an effective treatment option. To date, clinical trial support is greater for memantine use in combination with an AChE inhibitor, while more data are needed to confirm its efficacy as monotherapy.

  1. Influence of the Circadian System on Disease Severity

    PubMed Central

    Litinski, Mikhail; Scheer, Frank AJL; Shea, Steven A

    2009-01-01

    Synopsis The severity of many diseases varies across the day and night. For example, adverse cardiovascular incidents peak in the morning, asthma is often worse at night and temporal lobe epileptic seizures are most prevalent in the afternoon. These patterns may be due to the day/night rhythm in environment and behavior, and/or endogenous circadian rhythms in physiology. Furthermore, chronic misalignment between the endogenous circadian timing system and the behavioral cycles could be a cause of increased risk of diabetes, obesity, cardiovascular disease and certain cancers in shift workers. Here we describe the magnitude, relevance and potential biological basis of such daily changes in disease severity and of circadian/behavioral misalignment, and present how these insights may help in the development of appropriate chronotherapy. PMID:20161149

  2. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments

  3. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  4. [Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases].

    PubMed

    Fiessinger, J N; Aiach, M; Lagneau, P; Cormier, J M; Housset, E

    1975-04-20

    38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment.

  5. [Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases].

    PubMed

    Fiessinger, J N; Aiach, M; Lagneau, P; Cormier, J M; Housset, E

    1975-04-20

    38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment. PMID:176733

  6. Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease

    PubMed Central

    Reed, Berenice; Masoumi, Amirali; Elhassan, Elwaleed; McFann, Kim; Cadnapaphornchai, Melissa; Maahs, David; Snell-Bergeon, Janet; Schrier, Robert W.

    2013-01-01

    Renal cysts, pain and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance, and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log10. Serum Log10 vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively correlated with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD. PMID:20881939

  7. Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease.

    PubMed

    Reed, Berenice Y; Masoumi, Amirali; Elhassan, Elwaleed; McFann, Kim; Cadnapaphornchai, Melissa A; Maahs, David M; Snell-Bergeon, Janet K; Schrier, Robert W

    2011-01-01

    Renal cysts, pain, and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD, we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD, with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log(10). Serum log(10) vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD. PMID:20881939

  8. Translocator protein (TSPO) role in aging and Alzheimer's disease.

    PubMed

    Repalli, Jayanthi

    2014-01-01

    Cellular damage and deregulated apoptotic cell death lead to functional impairment, and a main consequence of these events is aging. Cellular damage is initiated by different stress/risk factors such as oxidative stress, inflammation, and heavy metals. These stress/risk factors affect the cellular homeostasis by altering methylation status of several aging and Alzheimer's disease associated genes; these effects can be manifested immediately after exposure to stress and at later stages of life. However, when cellular damage exceeds certain threshold levels apoptosis is initiated. This review discusses the stress factors involved in cellular damage and the role and potential of TSPO-mediated cell death in aging as well as in Alzheimer's disease, which is also characterized by extensive cell death. Mitochondrial-mediated apoptotic death through the release of cytochrome c is regulated by TSPO, and increased expression of this protein is observed in both elderly people and in patients with Alzheimer's disease. TSPO forms and mediates opening of the mitochondrial membrane pore, mPTP and oxidizes cardiolipin, and these events lead to the leakage of apoptotic death mediators, such as cytochrome c, resulting in cell death. However, TSPO has many proposed functions and can also increase steroid synthesis, which leads to inhibition of inflammation and inhibition of the release of apoptotic factors, thereby decreasing cell damage and promoting cell survival. Thus, TSPO mediates apoptosis and decreases the cell damage, which in turn dictates the process of aging as well as the functionality of organs such as the brain. TSPO modulation with ligands in the Alzheimer's disease mouse model showed improvement in behavioral symptoms, and studies in Drosophila species showed increased cell survival and prolonged lifespan in flies after TSPO inhibition. These data suggest that since effects/signs of stress can manifest at any time, prevention through change in lifestyle and TSPO

  9. Severe phenotypes in two Tunisian families with novel XPA mutations: evidence for a correlation between mutation location and disease severity.

    PubMed

    Messaoud, O; Rekaya, M Ben; Ouragini, H; Benfadhel, S; Azaiez, H; Kefi, R; Gouider-Khouja, N; Mokhtar, I; Amouri, A; Boubaker, M S; Zghal, M; Abdelhak, S

    2012-03-01

    Xeroderma pigmentosum (XP) is a rare disorder characterized by a high skin sun-sensitivity predisposing to skin cancers at an early age. Among Tunisian XP patients with an intermediate skin phenotype, 92% presented neurological abnormalities related to XPA gene deficiency. Clinical variability of the XP-A phenotype is associated with a mutational heterogeneity. In the present study, two Tunisian families with severe dermatological and neurological XP phenotypes were investigated in order to determine clinical characteristics and genetic basis. Two Tunisian families with four XP affected children were examined in the Dermatology Department. Clinical features showed severe presentation of the disease. Coding regions of the XPA gene were analysed by direct sequencing. Results showed the presence of a novel mutation, p.E111X, in three patients belonging to the same family and presenting a very severe phenotype i.e. development of skin lesions and neurological signs before 1 year age. For the other patient, we identified a nonsense mutation, p.R207X, already identified in a Palestinian XP-A patient. Identification of novel causing mutations in Tunisian XP-A patients shows the genetic and mutational heterogeneity of the disease in Tunisia. Despite a relatively homogenous mutational spectrum, mutational heterogeneity for rare cases is observed because of the high rate of consanguinity.

  10. Severe Bronchopulmonary Dysplasia, Growth, Nutrition, and Adipokines at School Age

    PubMed Central

    Suursalmi, Piia; Korhonen, Päivi; Kopeli, Tarja; Nieminen, Riina; Luukkaala, Tiina; Moilanen, Eeva; Tammela, Outi

    2016-01-01

    This study evaluated nutrition and growth in relation to plasma adipokine levels in 21 very-low-birth-weight (VLBW) children with radiographic bronchopulmonary dysplasia (BPD), 19 VLBW controls, and 19 term controls with a median age of 11.3 years. We took anthropometric measurements; assessed plasma levels of adipsin, resistin, adiponectin, and leptin; and analyzed the children’s 3-day food records. Children with BPD had a smaller age-adjusted head circumference and more microcephaly but no other significant growth differences. Daily recommended nutritional intake levels were poorly met but did not differ between the groups. Leptin levels correlated positively with the body mass index standard deviation score in VLBW children. No other associations between adipokine concentrations and growth were found. There were negative correlations between leptin concentrations and fat intake, resistin levels and carbohydrate intake, and adiponectin, adipsin, and leptin levels and energy intake. PMID:27336010

  11. Severity of necrotizing enterocolitis: influence on outcome at 2 years of age.

    PubMed

    Walsh, M C; Kliegman, R M; Hack, M

    1989-11-01

    The long-term outcome of very low birth weight (VLBW) infants with necrotizing enterocolitis has been reported to be similar to that of other VLBW infants. To examine the influence of disease severity on outcome, the growth and neurodevelopment of survivors of necrotizing enterocolitis were evaluated when the babies were 20 months' corrected age. Between 1975 and 1983, 1506 VLBW infants were admitted to the hospital, and necrotizing enterocolitis developed in 84 (5.6%). Forty infants (48%) survived to be 20 months' corrected age, and complete follow-up data were available for 36. Survivors were classified by modified Bell's criteria into four groups by increasing severity of disease; 13 had mild necrotizing enterocolitis (stage IIA, IIB), and 23 had severe necrotizing enterocolitis (stage IIIA, IIIB). The 36 survivors were compared with 766 surviving VLBW infants without necrotizing enterocolitis. There were no perinatal or socioeconomic differences between groups. Compared with infants with stage II necrotizing enterocolitis at 20 months, infants with stage III necrotizing enterocolitis had a higher rate of subnormal body weight (39% vs 15%) and subnormal head circumference (30% vs 0%). Thirty-three percent of necrotizing enterocolitis survivors had significant neurodevelopmental impairment; the majority of impaired infants (10 of 12) were survivors of stage III necrotizing enterocolitis. These findings highlight the importance of continued evaluations for medical and neurodevelopmental sequelae.

  12. Detection of severe respiratory disease epidemic outbreaks by CUSUM-based overcrowd-severe-respiratory-disease-index model.

    PubMed

    Polanco, Carlos; Castañón-González, Jorge Alberto; Macías, Alejandro E; Samaniego, José Lino; Buhse, Thomas; Villanueva-Martínez, Sebastián

    2013-01-01

    A severe respiratory disease epidemic outbreak correlates with a high demand of specific supplies and specialized personnel to hold it back in a wide region or set of regions; these supplies would be beds, storage areas, hemodynamic monitors, and mechanical ventilators, as well as physicians, respiratory technicians, and specialized nurses. We describe an online cumulative sum based model named Overcrowd-Severe-Respiratory-Disease-Index based on the Modified Overcrowd Index that simultaneously monitors and informs the demand of those supplies and personnel in a healthcare network generating early warnings of severe respiratory disease epidemic outbreaks through the interpretation of such variables. A post hoc historical archive is generated, helping physicians in charge to improve the transit and future allocation of supplies in the entire hospital network during the outbreak. The model was thoroughly verified in a virtual scenario, generating multiple epidemic outbreaks in a 6-year span for a 13-hospital network. When it was superimposed over the H1N1 influenza outbreak census (2008-2010) taken by the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, it showed that it is an effective algorithm to notify early warnings of severe respiratory disease epidemic outbreaks with a minimal rate of false alerts.

  13. Fracture, aging and disease in bone

    SciTech Connect

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    fracture resistance, whereas regulating the level of the cytokine TGF-beta can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.

  14. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

    PubMed Central

    Grandgirard, Denis; Valente, Luca G.; Täuber, Martin G.; Leib, Stephen L.

    2016-01-01

    Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  15. Clinical presentation and management of severe Ebola virus disease.

    PubMed

    West, T Eoin; von Saint André-von Arnim, Amélie

    2014-11-01

    Clinicians caring for patients infected with Ebola virus must be familiar not only with screening and infection control measures but also with management of severe disease. By integrating experience from several Ebola epidemics with best practices for managing critical illness, this report focuses on the clinical presentation and management of severely ill infants, children, and adults with Ebola virus disease. Fever, fatigue, vomiting, diarrhea, and anorexia are the most common symptoms of the 2014 West African outbreak. Profound fluid losses from the gastrointestinal tract result in volume depletion, metabolic abnormalities (including hyponatremia, hypokalemia, and hypocalcemia), shock, and organ failure. Overt hemorrhage occurs infrequently. The case fatality rate in West Africa is at least 70%, and individuals with respiratory, neurological, or hemorrhagic symptoms have a higher risk of death. There is no proven antiviral agent to treat Ebola virus disease, although several experimental treatments may be considered. Even in the absence of antiviral therapies, intensive supportive care has the potential to markedly blunt the high case fatality rate reported to date. Optimal treatment requires conscientious correction of fluid and electrolyte losses. Additional management considerations include searching for coinfection or superinfection; treatment of shock (with intravenous fluids and vasoactive agents), acute kidney injury (with renal replacement therapy), and respiratory failure (with invasive mechanical ventilation); provision of nutrition support, pain and anxiety control, and psychosocial support; and the use of strategies to reduce complications of critical illness. Cardiopulmonary resuscitation may be appropriate in certain circumstances, but extracorporeal life support is not advised. Among other ethical issues, patients' medical needs must be carefully weighed against healthcare worker safety and infection control concerns. However, meticulous attention

  16. Clinical presentation and management of severe Ebola virus disease.

    PubMed

    West, T Eoin; von Saint André-von Arnim, Amélie

    2014-11-01

    Clinicians caring for patients infected with Ebola virus must be familiar not only with screening and infection control measures but also with management of severe disease. By integrating experience from several Ebola epidemics with best practices for managing critical illness, this report focuses on the clinical presentation and management of severely ill infants, children, and adults with Ebola virus disease. Fever, fatigue, vomiting, diarrhea, and anorexia are the most common symptoms of the 2014 West African outbreak. Profound fluid losses from the gastrointestinal tract result in volume depletion, metabolic abnormalities (including hyponatremia, hypokalemia, and hypocalcemia), shock, and organ failure. Overt hemorrhage occurs infrequently. The case fatality rate in West Africa is at least 70%, and individuals with respiratory, neurological, or hemorrhagic symptoms have a higher risk of death. There is no proven antiviral agent to treat Ebola virus disease, although several experimental treatments may be considered. Even in the absence of antiviral therapies, intensive supportive care has the potential to markedly blunt the high case fatality rate reported to date. Optimal treatment requires conscientious correction of fluid and electrolyte losses. Additional management considerations include searching for coinfection or superinfection; treatment of shock (with intravenous fluids and vasoactive agents), acute kidney injury (with renal replacement therapy), and respiratory failure (with invasive mechanical ventilation); provision of nutrition support, pain and anxiety control, and psychosocial support; and the use of strategies to reduce complications of critical illness. Cardiopulmonary resuscitation may be appropriate in certain circumstances, but extracorporeal life support is not advised. Among other ethical issues, patients' medical needs must be carefully weighed against healthcare worker safety and infection control concerns. However, meticulous attention

  17. Control of mitochondrial integrity in ageing and disease

    PubMed Central

    Szklarczyk, Radek; Nooteboom, Marco; Osiewacz, Heinz D.

    2014-01-01

    Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a ‘healthy’ population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria. PMID:24864310

  18. Understanding Vascular Diseases: Lessons From Premature Aging Syndromes.

    PubMed

    Ikeda, Yuichi; Kumagai, Hidetoshi; Motozawa, Yoshihiro; Suzuki, Jun-Ichi; Akazawa, Hiroshi; Komuro, Issei

    2016-05-01

    Early human mummies examined recently by computed tomography demonstrated a high prevalence of vascular calcification, a pathognomonic sign of atherosclerosis, which was correlated with estimated age at death. Early populations had little exposure to modern-day metabolic risk factors: these observations thus suggest that humans have an inherent age-dependent predisposition to atherosclerosis. Premature aging syndromes are extremely rare genetic disorders that exhibit clinical phenotypes resembling accelerated aging, including severe atherosclerosis, but those phenotypes are usually segmental. Controversy persists, therefore, regarding the extent to which the molecular mechanisms underlying premature aging syndromes overlap with those of physiological aging. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome are well-characterized premature aging syndromes. HGPS is caused by gain-of-function mutations in the LMNA gene, which result in the accumulation of a mutant nuclear protein, called "progerin," at the nuclear rim. In contrast, loss-of-function mutations in Werner syndrome ATP-dependent helicase (WRN) lead to Werner syndrome. Mesenchymal stem cells (MSCs), which can differentiate into vascular cells to maintain vascular homeostasis in response to injury, are severely affected in these syndromes. Mechanistically, either aberrant expression of progerin or loss of WRN protein in MSCs alters heterochromatin structure, resulting in premature senescence and exhaustion of functional MSCs in premature aging syndromes. Surprisingly, vascular cells and MSCs in elderly healthy individuals have shown progerin expression and decreased expression levels of WRN, respectively. Studying these rare genetic disorders could thus provide valuable insights into age-related vascular diseases that occur in the general population. PMID:26948039

  19. Striatal function in normal aging: Implications for Parkinson's disease

    SciTech Connect

    Sawle, G.V.; Colebatch, J.G.; Shah, A.; Brooks, D.J.; Marsden, C.D.; Frackowiak, R.S. )

    1990-12-01

    Central to several current theories of the etiology of Parkinson's disease is the premise that the nigrostriatal dopaminergic system degenerates with normal aging. Much of the evidence for this assertion has come from postmortem neurochemical studies. We have used L-6-({sup 18}F) fluoro-Dopa and positron emission tomography in 26 healthy volunteers (age range, 27-76 years) to examine striatal and frontal cortical tracer uptake. Data have been analyzed by using a graphical approach to calculate an influx constant (Ki) for L-6-({sup 18}F)fluoro-Dopa uptake into the caudate, putamen, and medial frontal cortex of each subject. In the population studied, there was no decline in Ki with age for any of these structures. A series of physiological measurements made on the older subjects also showed few significant changes with age. The positron emission tomographic findings demonstrate preservation of nigrostriatal dopaminergic function in normal aging. The pathological process causing Parkinson's disease may operate closer to the time of presentation than has been suggested.

  20. Coronary Artery Disease Severity and Cardiovascular Biomarkers in Patients with Peripheral Artery Disease.

    PubMed

    Hikita, Hiroyuki; Shigeta, Takatoshi; Kimura, Shigeki; Takahashi, Atsushi; Isobe, Mitsuaki

    2015-12-01

    Cardiovascular mortality in peripheral artery disease (PAD) patients is higher in critical limb ischemia (CLI) than in intermittent claudication (IC). We sought to evaluate differential characteristics of coronary artery disease (CAD) severity and prognostic biomarkers for cardiovascular events between CLI and IC patients. Coronary angiography was performed on 242 PAD patients (age 73 ± 8 years) with either CLI or IC. High-sensitivity troponin T (hs-TnT), eicosapentaenoic acid-arachidonic acid ratio (EPA/AA), and lipoprotein(a), as biomarkers for prognostic factors, were measured from blood samples. The study patients were divided into a CLI-group (n = 42) and IC-group (n = 200). The Gensini score as an indicator of coronary angiographic severity was higher in the CLI-group than in the IC-group (39.1 ± 31.2 vs. 8.5 ± 8.3, p < 0.0001). Hs-TnT and lipoprotein(a) values were higher in the CLI-group than in the IC-group (0.152 ± 0.186 ng/mL vs. 0.046 ± 0.091, p < 0.0001, 45.9 ± 23.3 mg/dL vs. 26.2 ± 27.7, p = 0.0002, respectively) and EPA/AA was lower in the CLI-group than in the IC-group (0.22 ± 0.11 vs. 0.38 ± 0.29, p = 0.0049, respectively). Greater CAD severity, higher hs-TnT, and lipoprotein(a), and lower EPA/AA were observed in the CLI-group, which may explain higher cardiovascular events in patients with CLI.

  1. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

    PubMed

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-04-01

    Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  2. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  3. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease.

    PubMed

    Lucero, Catherine; Brown, Robert S

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  4. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  5. CT Metrics of Airway Disease and Emphysema in Severe COPD

    PubMed Central

    Kim, Woo Jin; Silverman, Edwin K.; Hoffman, Eric; Criner, Gerard J.; Mosenifar, Zab; Sciurba, Frank C.; Make, Barry J.; Carey, Vincent; Estépar, Raúl San José; Diaz, Alejandro; Reilly, John J.; Martinez, Fernando J.; Washko, George R.

    2009-01-01

    Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV1 and percent predicted value of FEV1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = −0.28, p = 0.0001) and SRWA (r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. PMID:19411295

  6. Lycopene Deficiency in Ageing and Cardiovascular Disease

    PubMed Central

    Petyaev, Ivan M.

    2016-01-01

    Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed. PMID:26881023

  7. Splicing biomarkers of disease severity in myotonic dystrophy

    PubMed Central

    Nakamori, Masayuki; Sobczak, Krzysztof; Puwanant, Araya; Welle, Steve; Eichinger, Katy; Pandya, Shree; Dekdebrun, Jeannne; Heatwole, Chad R.; McDermott, Michael P.; Chen, Tian; Cline, Melissa; Tawil, Rabi; Osborne, Robert J.; Wheeler, Thurman M.; Swanson, Maurice; Moxley, Richard T.; Thornton, Charles A.

    2014-01-01

    Objective To develop RNA splicing biomarkers of disease severity and therapeutic response in myotonic dystrophy type 1 (DM1) and type 2 (DM2). Methods In a discovery cohort we used microarrays to perform global analysis of alternative splicing in DM1 and DM2. The newly identified splicing changes were combined with previous data to create a panel of 50 putative splicing defects. In a validation cohort of 50 DM1 subjects we measured the strength of ankle dorsiflexion (ADF) and then obtained a needle biopsy of tibialis anterior (TA) to analyze splice events in muscle RNA. The specificity of DM-associated splicing defects was assessed in disease controls. The CTG expansion size in muscle tissue was determined by Southern blot. The reversibility of splicing defects was assessed in transgenic mice by using antisense oligonucleotides (ASOs) to reduce levels of toxic RNA. Results Forty-two splicing defects were confirmed in TA muscle in the validation cohort. Among these, 20 events showed graded changes that correlated with ADF weakness. Five other splice events were strongly affected in DM1 subjects with normal ADF strength. Comparison to disease controls and mouse models indicated that splicing changes were DM-specific, mainly attributable to MBNL1 sequestration, and reversible in mice by targeted knockdown of toxic RNA. Splicing defects and weakness were not correlated with CTG expansion size in muscle tissue. Interpretation Alternative splicing changes in skeletal muscle may serve as biomarkers of disease severity and therapeutic response in myotonic dystrophy. PMID:23929620

  8. Severe maxillofacial renal osteodystrophy in two patients with chronic kidney disease.

    PubMed

    Lopes, Maria Luiza Diniz de Sousa; Albuquerque, Assis Filipe Medeiros; Germano, Adriano Rocha; Queiroz, Lélia Maria Guedes; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

    2015-09-01

    Renal osteodystrophy (ROD) is the bone pathology that occurs as an uncommon complication related to the several alterations in mineral metabolism present in patients with chronic kidney disease (CKD). This paper describes two cases of severe ROD affecting the maxilla and mandible and causing facial disfigurement of a young and a middle-aged female patient with CKD. Both patients had a history of secondary hyperparathyroidism, previously treated by surgery. The pathogenesis of the disease, as well as its clinical, imaging, and histopathological features, and management of the patient are discussed. PMID:25784153

  9. Developmental determinants in non-communicable chronic diseases and ageing.

    PubMed

    Bousquet, J; Anto, J M; Berkouk, K; Gergen, P; Antunes, J Pinto; Augé, P; Camuzat, T; Bringer, J; Mercier, J; Best, N; Bourret, R; Akdis, M; Arshad, S H; Bedbrook, A; Berr, C; Bush, A; Cavalli, G; Charles, M A; Clavel-Chapelon, F; Gillman, M; Gold, D R; Goldberg, M; Holloway, J W; Iozzo, P; Jacquemin, S; Jeandel, C; Kauffmann, F; Keil, T; Koppelman, G H; Krauss-Etschmann, S; Kuh, D; Lehmann, S; Carlsen, K C Lodrup; Maier, D; Méchali, M; Melén, E; Moatti, J P; Momas, I; Nérin, P; Postma, D S; Ritchie, K; Robine, J M; Samolinski, B; Siroux, V; Slagboom, P E; Smit, H A; Sunyer, J; Valenta, R; Van de Perre, P; Verdier, J M; Vrijheid, M; Wickman, M; Yiallouros, P; Zins, M

    2015-06-01

    Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

  10. Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA

    PubMed Central

    Rebolledo-Jaramillo, Boris; Su, Marcia Shu-Wei; Stoler, Nicholas; McElhoe, Jennifer A.; Dickins, Benjamin; Blankenberg, Daniel; Chiaromonte, Francesca; Nielsen, Rasmus; Holland, Mitchell M.; Paul, Ian M.; Nekrutenko, Anton; Makova, Kateryna D.

    2014-01-01

    The manifestation of mitochondrial DNA (mtDNA) diseases depends on the frequency of heteroplasmy (the presence of several alleles in an individual), yet its transmission across generations cannot be readily predicted owing to a lack of data on the size of the mtDNA bottleneck during oogenesis. For deleterious heteroplasmies, a severe bottleneck may abruptly transform a benign (low) frequency in a mother into a disease-causing (high) frequency in her child. Here we present a high-resolution study of heteroplasmy transmission conducted on blood and buccal mtDNA of 39 healthy mother–child pairs of European ancestry (a total of 156 samples, each sequenced at ∼20,000× per site). On average, each individual carried one heteroplasmy, and one in eight individuals carried a disease-associated heteroplasmy, with minor allele frequency ≥1%. We observed frequent drastic heteroplasmy frequency shifts between generations and estimated the effective size of the germ-line mtDNA bottleneck at only ∼30–35 (interquartile range from 9 to 141). Accounting for heteroplasmies, we estimated the mtDNA germ-line mutation rate at 1.3 × 10−8 (interquartile range from 4.2 × 10−9 to 4.1 × 10−8) mutations per site per year, an order of magnitude higher than for nuclear DNA. Notably, we found a positive association between the number of heteroplasmies in a child and maternal age at fertilization, likely attributable to oocyte aging. This study also took advantage of droplet digital PCR (ddPCR) to validate heteroplasmies and confirm a de novo mutation. Our results can be used to predict the transmission of disease-causing mtDNA variants and illuminate evolutionary dynamics of the mitochondrial genome. PMID:25313049

  11. Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA.

    PubMed

    Rebolledo-Jaramillo, Boris; Su, Marcia Shu-Wei; Stoler, Nicholas; McElhoe, Jennifer A; Dickins, Benjamin; Blankenberg, Daniel; Korneliussen, Thorfinn S; Chiaromonte, Francesca; Nielsen, Rasmus; Holland, Mitchell M; Paul, Ian M; Nekrutenko, Anton; Makova, Kateryna D

    2014-10-28

    The manifestation of mitochondrial DNA (mtDNA) diseases depends on the frequency of heteroplasmy (the presence of several alleles in an individual), yet its transmission across generations cannot be readily predicted owing to a lack of data on the size of the mtDNA bottleneck during oogenesis. For deleterious heteroplasmies, a severe bottleneck may abruptly transform a benign (low) frequency in a mother into a disease-causing (high) frequency in her child. Here we present a high-resolution study of heteroplasmy transmission conducted on blood and buccal mtDNA of 39 healthy mother-child pairs of European ancestry (a total of 156 samples, each sequenced at ∼20,000× per site). On average, each individual carried one heteroplasmy, and one in eight individuals carried a disease-associated heteroplasmy, with minor allele frequency ≥1%. We observed frequent drastic heteroplasmy frequency shifts between generations and estimated the effective size of the germ-line mtDNA bottleneck at only ∼30-35 (interquartile range from 9 to 141). Accounting for heteroplasmies, we estimated the mtDNA germ-line mutation rate at 1.3 × 10(-8) (interquartile range from 4.2 × 10(-9) to 4.1 × 10(-8)) mutations per site per year, an order of magnitude higher than for nuclear DNA. Notably, we found a positive association between the number of heteroplasmies in a child and maternal age at fertilization, likely attributable to oocyte aging. This study also took advantage of droplet digital PCR (ddPCR) to validate heteroplasmies and confirm a de novo mutation. Our results can be used to predict the transmission of disease-causing mtDNA variants and illuminate evolutionary dynamics of the mitochondrial genome.

  12. Polymorphisms Associated with Age at Onset in Patients with Moderate-to-Severe Plaque Psoriasis.

    PubMed

    Prieto-Pérez, Rocío; Solano-López, Guillermo; Cabaleiro, Teresa; Román, Manuel; Ochoa, Dolores; Talegón, María; Baniandrés, Ofelia; López-Estebaranz, José Luis; de la Cueva, Pablo; Daudén, Esteban; Abad-Santos, Francisco

    2015-01-01

    Psoriasis is a chronic skin disease in which genetics play a major role. Although many genome-wide association studies have been performed in psoriasis, knowledge of the age at onset remains limited. Therefore, we analyzed 173 single-nucleotide polymorphisms in genes associated with psoriasis and other autoimmune diseases in patients with moderate-to-severe plaque psoriasis type I (early-onset, <40 years) or type II (late-onset, ≥40 years) and healthy controls. Moreover, we performed a comparison between patients with type I psoriasis and patients with type II psoriasis. Our comparison of a stratified population with type I psoriasis (n = 155) and healthy controls (N = 197) is the first to reveal a relationship between the CLMN, FBXL19, CCL4L, C17orf51, TYK2, IL13, SLC22A4, CDKAL1, and HLA-B/MICA genes. When we compared type I psoriasis with type II psoriasis (N = 36), we found a significant association between age at onset and the genes PSORS6, TNF-α, FCGR2A, TNFR1, CD226, HLA-C, TNFAIP3, and CCHCR1. Moreover, we replicated the association between rs12191877 (HLA-C) and type I psoriasis and between type I and type II psoriasis. Our findings highlight the role of genetics in age of onset of psoriasis. PMID:26613086

  13. Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. Methods: Prospective cohort study of severe leptospi...

  14. Evidence for severe atherosclerotic changes in chronic hemodialysis patients: comparative autopsy study against cardiovascular disease patients without chronic kidney disease.

    PubMed

    Suzuki, Chigure; Nakamura, Satoko; Ishibashi-Ueda, Hatsue; Yoshihara, Fumiki; Kawano, Yuhei

    2011-02-01

    Atherosclerosis is a major cause of mortality and morbidity among hemodialysis patients, but whether it is more severe in hemodialysis patients than in cardiovascular disease patients without chronic kidney disease is unclear. We examined 46 autopsy patients who had undergone hemodialysis, and age and sex-matched 46 patients with cardiovascular disease and an eGFR of >60 mL/min/1.73 m(2). There was no difference in the prevalence of diabetes or hypertension between the groups. We divided the aorta into four segments: A, ascending artery to arch; B, descending artery to diaphragm; C, suprarenal; and D, infrarenal. We used the classification of the American Heart Association to evaluate atherosclerosis progression. Distribution was scored by the extent to which each segment was damaged: 0, none; 1, less than 1/3; 2, more than 1/3 to less than 2/3; 3, more than 2/3. Histological examination revealed that the progression score (P < 0.05) and distribution score (P<0.005) were more severe in the hemodialysis group, especially in segment A. Regression analysis showed that atherosclerosis of segment A was related to age, gender, dyslipidemia, smoking, hemodialysis therapy, and hemodialysis duration. In hemodialysis patients, atherosclerotic changes in the aorta were more severe than in cardiovascular disease patients with an eGFR of >60 mL/min/1.73 m(2). Aortic atherosclerosis was aggravated by traditional and chronic kidney disease-related risk factors.

  15. Evaluating the Impact of Breastfeeding on Rotavirus Antigenemia and Disease Severity in Indian Children

    PubMed Central

    Das, Sushmita; Sahoo, Ganesh Chandra; Das, Pradeep; Singh, Utpal Kant; Jaiswal, Anil Kumar; Singh, Prachi; Kumar, Ranjeet; Kumar, Rishikesh

    2016-01-01

    Objectives To evaluate the contribution of breastfeeding to Rotavirus (RV)-induced antigenemia and/or RNAemia and disease severity in Indian children (<2 yrs age). Methods Paired stool and serum samples were collected from (a) hospitalized infants with diarrhea (n = 145) and (b) healthy control infants without diarrhea (n = 28). Stool RV-antigen was screened in both groups by commercial rapid-test and enzyme immunoassay. The disease severity was scored and real-time-PCR was used for viral-load estimation. Serum was evaluated for RV-antigenemia by EIA and RV-RNAemia by RT-PCR. Data was stratified by age-group and breastfeeding status and compared. Results Presence of RV-antigenemia and RV-RNAemia was positively related with presence of RV in stool. Disease severity and stool viral-load was significantly associated with RV-antigenemia[(r = 0.74; CI:0.66 to 0.84; P<0.0001,R2 = 0.59) and (r = -0.55; CI:-0.68 to -0.39; P<0.0001,R2 = 0.31) respectively], but not with RV-RNAemia. There was significant reduction in RV-antigenemiarate in the breast-fed group compared to non-breastfed infants, especially in 0–6 month age group (P<0.001). Non-breastfed infants were at risk for RV-antigenemia with severe disease manifestations in form of high Vesikari scores correlating with high fever, more vomiting episodes and dehydration. Conclusion RV-antigenemia was common in nonbreastfed children with severe RV-diarrhea and correlated with stool RV-load and disease severity. PMID:26828823

  16. Cardiovascular disease and diabetes in people with severe mental illness.

    PubMed

    Hert, Marc De; Dekker, Jacqueline M; Wood, David; Kahl, Kai G; Möller, Hans-Jürgen

    2009-03-01

    Position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed to an increased risk of the modifiable coronary heart disease risk factors, obesity, smoking, diabetes, hypertension, and dyslipidaemia. Antipsychotic medication and possibly other psychotropic medication like antidepressants can induce weight gain and further increase the risk of adverse metabolic effects which may result in further increased incidence of cardiovascular disease. Patients have limited access to general healthcare with less opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. The European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published this statement aiming to improve the care of patients suffering from severe mental illness. The intention is to initiate co-operation and shared care between the different health care professionals and to increase the awareness of psychiatrists caring for patients suffering from severe mental illness to screen and treat increased cardiovascular risk factors and diabetes. PMID:23034198

  17. Relationship of Inflammatory Biomarkers with Severity of Peripheral Arterial Disease

    PubMed Central

    Toyofuku, Takahiro; Inoue, Yoshinori

    2016-01-01

    Objective. The pentraxin family, including high-sensitivity C-reactive protein (hs-CRP), serum amyloid P (SAP), and pentraxin 3 (PTX3), has been identified as playing a key role in inflammatory reactions such as in atherosclerosis and cardiovascular disease. In this study, we examined the relationship between peripheral arterial disease (PAD) and serum levels of pentraxins. Methods. This study was undertaken via a retrospective review of PAD patients with surgical intervention for lesions of the common femoral artery. We evaluated the preoperative patient conditions, hemodynamic status, such as ankle brachial index (ABI), and clinical ischemic conditions according to Rutherford classification. Preoperatively, we collected blood samples for determining the serum levels of hs-CRP, SAP, and PTX3. Results. Twelve PAD patients with common femoral arterial lesions were treated and examined. The hemodynamic severity of PAD was not negatively correlated with hs-CRP, SAP, or PTX3. The clinical severity evaluated by Rutherford classification was significantly positively correlated with the serum level of PTX3 (p = 0.019). Conclusion. We demonstrated that PTX3 might be a better marker of PAD than hs-CRP and SAP. Furthermore, PTX3 might be a prognostic marker to evaluate the severity of PAD. PMID:27559483

  18. Relationship of Inflammatory Biomarkers with Severity of Peripheral Arterial Disease.

    PubMed

    Igari, Kimihiro; Kudo, Toshifumi; Toyofuku, Takahiro; Inoue, Yoshinori

    2016-01-01

    Objective. The pentraxin family, including high-sensitivity C-reactive protein (hs-CRP), serum amyloid P (SAP), and pentraxin 3 (PTX3), has been identified as playing a key role in inflammatory reactions such as in atherosclerosis and cardiovascular disease. In this study, we examined the relationship between peripheral arterial disease (PAD) and serum levels of pentraxins. Methods. This study was undertaken via a retrospective review of PAD patients with surgical intervention for lesions of the common femoral artery. We evaluated the preoperative patient conditions, hemodynamic status, such as ankle brachial index (ABI), and clinical ischemic conditions according to Rutherford classification. Preoperatively, we collected blood samples for determining the serum levels of hs-CRP, SAP, and PTX3. Results. Twelve PAD patients with common femoral arterial lesions were treated and examined. The hemodynamic severity of PAD was not negatively correlated with hs-CRP, SAP, or PTX3. The clinical severity evaluated by Rutherford classification was significantly positively correlated with the serum level of PTX3 (p = 0.019). Conclusion. We demonstrated that PTX3 might be a better marker of PAD than hs-CRP and SAP. Furthermore, PTX3 might be a prognostic marker to evaluate the severity of PAD. PMID:27559483

  19. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome.

  20. Scurvy in pediatric age group – A disease often forgotten?

    PubMed Central

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-01-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009–2014) with search terms “scurvy” “vitamin C deficiency” “ascorbic acid deficiency” “scurvy and children” “scurvy and pediatric age group”. There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  1. Scurvy in pediatric age group - A disease often forgotten?

    PubMed

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-06-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009-2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated. PMID:25983516

  2. Scurvy in pediatric age group - A disease often forgotten?

    PubMed

    Agarwal, Anil; Shaharyar, Abbas; Kumar, Anubrat; Bhat, Mohd Shafi; Mishra, Madhusudan

    2015-06-01

    Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009-2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated.

  3. Severity of Anxiety Disorders in Patients with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Safa, Mitra; Fallah Tafti, Saeed; Talischi, Firrouzeh; Ghassem Boroujerdi, Fatemeh

    2015-01-01

    Objective: Patients with chronic physical diseases sometimes show increased loss of function; such patients need more care. Anxiety is a well-known symptom that is prevalent among chronic obstructive pulmonary disease patients that can prolong and increase the risk of hospitalization. The purpose of this study was to evaluate the severity of anxiety in the mentioned patients and to examine the presence of symptoms and appropriate treatment strategies to understand the role of psychological functions in physical patients. Methods : This was a cross sectional study conducted in Masih Daneshvari Hospital. One hundred forty- three patients entered into the project by accessible method and signed the informed consent; they filled demographic information and Hamilton anxiety and depression questionnaires. Data were analyzed by SPSS-16. Results : Of the participants, 68% were above 60 years of age; 78% were male; 89% were married; and 38% were self-employed. Also, among the participants, 51% were illiterate; 72% had history of smoking; 46% had history of substance abuse; and 49% had moderate to severe anxiety disorder. Moreover, of the patients with severe anxiety, 41.3% had severe muscle spasms; and severe sleeplessness was found in 38.5% of those with severe anxiety disorder. Severe anxiety related symptoms were found in 20.3% of the patients with severe anxiety disorder. Depressed mood was found in 27.3% of the patients with severe anxiety disorder. Severe physical and muscular signs were found in 35.7% of those with severe anxiety disorder. Conclusion : According to our findings, many chronic diseases such as chronic obstructive pulmonary disease may contain anxiety and depression which result in vulnerability. Therefore, evaluation of anxiety in such patients is of importance for alleviating the disease. PMID:26884790

  4. Bats as reservoirs of severe emerging infectious diseases.

    PubMed

    Han, Hui-Ju; Wen, Hong-ling; Zhou, Chuan-Min; Chen, Fang-Fang; Luo, Li-Mei; Liu, Jian-wei; Yu, Xue-Jie

    2015-07-01

    In recent years severe infectious diseases have been constantly emerging, causing panic in the world. Now we know that many of these terrible diseases are caused by viruses originated from bats (Table 1), such as Ebola virus, Marburg, SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), Nipah virus (NiV) and Hendra virus (HeV). These viruses have co-evolved with bats due to bats' special social, biological and immunological features. Although bats are not in close contact with humans, spillover of viruses from bats to intermediate animal hosts, such as horses, pigs, civets, or non-human primates, is thought to be the most likely mode to cause human infection. Humans may also become infected with viruses through aerosol by intruding into bat roosting caves or via direct contact with bats, such as catching bats or been bitten by bats.

  5. Why AMD is a disease of ageing and not of development: mechanisms and insights

    PubMed Central

    Sharma, Kaushal; Sharma, Neel Kamal; Anand, Akshay

    2014-01-01

    Ageing disorders can be defined as the progressive and cumulative outcome of several defective cellular mechanisms as well as metabolic pathways, consequently resulting in degeneration. Environment plays an important role in its pathogenesis. In contrast, developmental disorders arise from inherited mutations and usually the role of environmental factors in development of disease is minimal. Age related macular degeneration (AMD) is one such retinal degenerative disorder which starts with the progression of age. Metabolism plays an important role in initiation of such diseases of ageing. Cholesterol metabolism and their oxidized products like 7-ketocholesterol have been shown to adversely impact retinal pigment epithelium (RPE) cells. These molecules can initiate mitochondrial apoptotic processes and also influence the complements factors and expression of angiogenic proteins like VEGF etc. In this review we highlight why and how AMD is an ageing disorder and not a developmental disease substantiated by disrupted cholesterol metabolism common to several age related diseases. PMID:25071560

  6. [Car driving, cognitive aging and Alzheimer disease].

    PubMed

    Fabrigoule, Colette; Lafont, Sylviane

    2015-10-01

    Older drivers are more numerous on the roads. They are expert drivers, but with increasing age certain physiological changes can interfere with driving, which is a complex activity of daily living. Older drivers are involved in fewer accidents than younger drivers, but they have a higher accident rate per kilometer driven. The elderly are heavily represented in the balance sheet of road deaths, being motorists or pedestrians. This high mortality is largely explained by their physical frailty. In the presence of deficits, self-regulation of driving habits, changes/reductions or stopping in driving activity occur in the elderly. But cognitive deficits are associated with an increased risk of accidents. Among drivers with Alzheimer's disease, there is a heterogeneity of driving ability, making difficult the advisory role of a physician for driving. A protocol for physicians was developed to assess cognitive impairments that may affect driving in an elderly patient. The car plays an important role in the autonomy of the elderly and patient advice on stopping driving should take into account the risk/benefit ratio. PMID:26009241

  7. Celiac disease unmasked by acute severe iron deficiency anemia.

    PubMed

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  8. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  9. Severe hypercholesterolemia and liver disease in a 3-year old.

    PubMed

    Patel, Amol M; Brautbar, Ariel; Desai, Nirav K; Wilson, Don P

    2016-01-01

    Lipoprotein-X, which is composed of phospholipids and non-esterified cholesterol, is an abnormal lipoprotein with a density range similar to LDL-C. The two most common ways which lipoprotein-X accumulates is from reflux of bile salts into plasma or deficiency in lecithin cholesterol acyltransferase. This is a case of severe hypercholesterolemia and liver disease in a 3- year old male that presented with pruritus, pale stool, scleral ictus, and abdominal distention. He was diagnosed with primary sclerosing cholangitis which was confirmed by liver biopsy. Our patient was treated with steroids and immunomodulator therapy which was associated with significant reduction in cholestasis and LDL-C levels. Lipoprotein-X has several properties that make it anti-atherogenic, which raises the question if treatment for hypercholesterolemia should be initiated. PMID:27206954

  10. Linguistic Correlates of Asymmetric Motor Symptom Severity in Parkinson's Disease

    PubMed Central

    Holtgraves, Thomas; McNamara, Patrick; Cappaert, Kevin; Durso, Raymond

    2009-01-01

    Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N = 31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the participants were analyzed with the Linguistic Inquiry and Word Count (LIWC) program. Three measures of linguistic complexity – the proportion of verbs, proportion of function words, and sentence length – were found to be affected by symptom asymmetry. Greater left-side motor severity (and hence greater right hemisphere dysfunction) was associated with the production of significantly fewer verbs, function words, and shorter sentences. Hence, the production of linguistic complexity in a natural language context was associated with relatively greater right hemisphere involvement. The potential neurobiological mechanisms underlying this effect are discussed. PMID:19751960

  11. Environmental determinants of severity in sickle cell disease

    PubMed Central

    Tewari, Sanjay; Brousse, Valentine; Piel, Frédéric B.; Menzel, Stephan; Rees, David C.

    2015-01-01

    Sickle cell disease causes acute and chronic illness, and median life expectancy is reduced by at least 30 years in all countries, with greater reductions in low-income countries. There is a wide spectrum of severity, with some patients having no symptoms and others suffering frequent, life-changing complications. Much of this variability is unexplained, despite increasingly sophisticated genetic studies. Environmental factors, including climate, air quality, socio-economics, exercise and infection, are likely to be important, as demonstrated by the stark differences in outcomes between patients in Africa and USA/Europe. The effects of weather vary with geography, although most studies show that exposure to cold or wind increases hospital attendance with acute pain. Most of the different air pollutants are closely intercorrelated, and increasing overall levels seem to correlate with increased hospital attendance, although higher concentrations of atmospheric carbon monoxide may offer some benefit for patients with sickle cell disease. Exercise causes some adverse physiological changes, although this may be off-set by improvements in cardiovascular health. Most sickle cell disease patients live in low-income countries and socioeconomic factors are undoubtedly important, but little studied beyond documenting that sickle cell disease is associated with decreases in some measures of social status. Infections cause many of the differences in outcomes seen across the world, but again these effects are relatively poorly understood. All the above factors are likely to account for much of the pathology and variability of sickle cell disease, and large prospective studies are needed to understand these effects better. PMID:26341524

  12. Emphysematous pyelonephritis: the impact of urolithiasis on disease severity

    PubMed Central

    Myers, Frank; Chi, Thomas; Bagga, Herman S.; Taylor, Andrew G.; Stoller, Marshall L.

    2016-01-01

    Background Emphysematous pyelonephritis is a severe infection of the kidney associated with formation of gas in the renal parenchyma and/or collecting system. The purpose of this study was to evaluate outcomes of patients with emphysematous pyelonephritis in a contemporary cohort and to evaluate the impact of urolithiasis on disease severity. Methods A search of all imaging reports at University of California San Francisco (UCSF) for the term “emphysematous pyelonephritis” was undertaken from 2003–2014. Patients were included if there was clinical evidence of infection, no recent urologic instrumentation, and computerized tomography (CT) demonstrating gas in the renal parenchyma or collecting system. Clinical and laboratory variables were obtained from medical records. Results A total of 14 cases were identified. The majority of patients (57%) had gas confined to the collecting system. Three patients (21%) had gas in the renal parenchyma and 3 patients (21%) had gas extending into perirenal tissues. A total of 8 patients (57%) had concomitant urolithiasis. Seven patients (50%) were managed with antibiotic therapy alone while 6 patients (43%) required percutaneous drainage. No patients required immediate nephrectomy. There were no deaths. Patients with urolithiasis had less severe emphysematous pyelonephritis than patients without urolithiasis (P<0.05). Conclusions The majority of patients in this study had gas contained within the collecting system and were treated successfully with antibiotics alone. Percutaneous drainage was successfully utilized in patients with more advanced disease. No patients required emergent nephrectomy. Emphysematous pyelonephritis in patients with urolithiasis was less severe than in patients without urolithiasis. PMID:27785435

  13. Allergies and Disease Severity in Childhood Narcolepsy: Preliminary Findings

    PubMed Central

    Aydinoz, Secil; Huang, Yu-Shu; Gozal, David; Inocente, Clara O.; Franco, Patricia; Kheirandish-Gozal, Leila

    2015-01-01

    Introduction: Narcolepsy frequently begins in childhood, and is characterized by excessive daytime sleepiness, with the presence of cataplexy reflecting a more severe phenotype. Narcolepsy may result from genetic predisposition involving deregulation of immune pathways, particularly involving T helper 2 cells (Th2). Increased activation of Th2 cells is usually manifested as allergic conditions such as rhinitis, atopic dermatitis, and asthma. We hypothesized that the presence of allergic conditions indicative of increased Th2 balance may dampen the severity of the phenotype in children with narcolepsy. Methods: A retrospective chart review of childhood narcolepsy patients was conducted at three major pediatric sleep centers. Patients were divided into those with narcolepsy without cataplexy (NC−) and narcolepsy with cataplexy (NC+). Demographics, polysomnographic and multiple sleep latency test data, and extraction of information on the presence of allergic diseases such allergic rhinitis, atopic dermatitis, and asthma was performed. Results: There were 468 children identified, with 193 children in NC− group and 275 patients in the NC+ group. Overall, NC+ children were significantly younger, had higher body mass index, and had shorter mean sleep latencies and increased sleep onset rapid eye movement events. The frequency of allergic conditions, particularly asthma and allergic rhinitis, was markedly lower in NC+ (58/275) compared to NC− patients (94/193; P < 0.0001). Conclusion: Involvement of the immune system plays an important role in the pathophysiology of narcolepsy. Current findings further suggest that an increased shift toward T helper 2 cells, as indicated by the presence of allergic conditions, may modulate the severity of the phenotype in childhood narcolepsy, and reduce the prevalence of cataplexy in these patients. Citation: Aydinoz S, Huang YS, Gozal D, Inocente CO, Franco P, Kheirandish-Gozal L. Allergies and disease severity in childhood

  14. The association between periodontal disease parameters and severity of atherosclerosis

    PubMed Central

    Ketabi, Mohammad; Meybodi, Fatemeh Rashidi; Asgari, Mohammad Reza

    2016-01-01

    Background: Atherosclerosis is the most common cause for heart attack and stroke. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. The aim of this research was to determine the possible association between chronic periodontal disease and severity of atherosclerosis. Materials and Methods: Eighty-two subjects that were referred to Chamran Heart Hospital in Isfahan for angiography were involved in this study. Fifty-nine subjects had coronary artery obstruction (CAO) and 23 showed no obstruction after angiography. The severity of CAO was assessed. Periodontal parameters including pocket depth (PD), gingival recession (R), clinical attachment level (CAL), and bleeding on probing (BOP) of all subjects were recorded. The decayed-missing-filled (DMF) index of all subjects was also measured. For statistical analysis, Pearson correlation test, Chi-square, and independent t-test were used. Results: There were significant positive correlation between variables R, PD, CAL, decayed (D), missing (M), DMF, BOP, and degree of CAO. However, there were no significant differences between filling variable degree of CAO (left anterior descending, left circumflex, and right coronary artery). Independent t-test showed that the mean of variables R, PD, AL, D, M, and DMF in patients with obstructed arteries were significantly higher than subjects without CAO. But there were no significant differences between variable F in two groups. Conclusion: The results of this cross-section analytical study showed an association between periodontal disease and dental parameters with the severity of CAO measured by angiography. However, this association must not interpret as a cause and effect relationship. PMID:27274346

  15. Eyeblink classical conditioning differentiates normal aging from Alzheimer's disease.

    PubMed

    Woodruff-Pak, D S

    2001-01-01

    Eyeblink classical conditioning is a useful paradigm for the study of the neurobiology of learning, memory, and aging, which also has application in the differential diagnosis of neurodegenerative diseases expressed in advancing age. Converging evidence from studies of eyeblink conditioning in neurological patients and brain imaging in normal adults document parallels in the neural substrates of this form of associative learning in humans and non-human mammals. Age differences in the short-delay procedure (400 ms CS-US interval) appear in middle age in humans and may be caused at least in part by cerebellar cortical changes such as loss of Purkinje cells. Whereas the hippocampus is not essential for conditioning in the delay procedure, disruption of hippocampal cholinergic neurotransmission impairs acquisition and slows the rate of learning. Alzheimer's disease (AD) profoundly disrupts the hippocampaL cholinergic system, and patients with AD consistently perform poorly in eyeblink conditioning. We hypothesize that disruption of hippocampal cholinergic pathways in AD in addition to age-associated Purkinje cell loss results in severely impaired eyeblink conditioning. The earliest pathology in AD occurs in entorhinal cortical input to hippocampus, and eyeblink conditioning may detect this early disruption before declarative learning and memory circuits become impaired. A case study is presented in which eyeblink conditioning detected impending dementia six years before changes on other screening tests indicated impairment. Because eyeblink conditioning is simple, non-threatening, and non-invasive, it may become a useful addition to test batteries designed to differentiate normal aging from mild cognitive impairment that progresses to AD and AD from other types of dementia.

  16. The aging-disease false dichotomy: understanding senescence as pathology

    PubMed Central

    Gems, David

    2015-01-01

    From a biological perspective aging (senescence) appears to be a form of complex disease syndrome, though this is not the traditional view. This essay aims to foster a realistic understanding of aging by scrutinizing ideas old and new. The conceptual division between aging-related diseases and an underlying, non-pathological aging process underpins various erroneous traditional ideas about aging. Among biogerontologists, another likely error involves the aspiration to treat the entire aging process, which recent advances suggest is somewhat utopian. It also risks neglecting a more modest but realizable goal: to develop preventative treatments that partially protect against aging. PMID:26136770

  17. Vertebral degenerative disc disease severity evaluation using random forest classification

    NASA Astrophysics Data System (ADS)

    Munoz, Hector E.; Yao, Jianhua; Burns, Joseph E.; Pham, Yasuyuki; Stieger, James; Summers, Ronald M.

    2014-03-01

    Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists' scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist's score had a quadratic weighted Cohen's kappa of 0.64.

  18. Associations between pentraxin 3 and severity of coronary artery disease

    PubMed Central

    Liu, Hua; Guan, Shaofeng; Fang, Weiyi; Yuan, Fang; Zhang, Min; Qu, Xinkai

    2015-01-01

    Objective To investigate the associations between plasma levels of pentraxins 3 (PTX3) and C reactive protein (CRP) and the severity of coronary artery lesions. Design and methods 60 patients with coronary heart disease (CHD) who underwent coronary angiography (CAG) in our hospital were included. Plasma was collected during CAG. The coronary Gensini score was used to evaluate the severity of coronary artery lesions. Associations between Gensini scores and plasma levels of PTX3 and CRP were analysed. Patients with estimated glomerular filtration rate <60 mL/min/1.73 m2 were included in the chronic renal dysfunction subgroup. Results A linear correlation was observed between PTX3 and the Gensini score (r=0.513, p<0.001). One-way analysis of variance showed that PTX3 levels were significantly higher in patients with Gensini scores >90 compared with patients with scores of 46–90 or <45 (0–45:4.8±0.8, 46–90:6.7±1.2, >90:7.7±2.0, p<0.001). Stepwise multiple linear regression showed that PTX3 levels were significantly associated with Gensini score in patients with chronic renal dysfunction (p=0.012), while no significant association was found for CRP. Conclusions PTX3 levers were positively associated with the severity of coronary artery lesions. PTX3 is closely associated with the severity of coronary artery stenosis in patients with chronic renal dysfunction. PMID:25854969

  19. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    PubMed Central

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  20. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    PubMed

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.

  1. Switching between Abstract Rules Reflects Disease Severity but Not Dopaminergic Status in Parkinson's Disease

    ERIC Educational Resources Information Center

    Kehagia, Angie A.; Cools, Roshan; Barker, Roger A.; Robbins, Trevor W.

    2009-01-01

    This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses…

  2. Host demography influences the prevalence and severity of eelgrass wasting disease.

    PubMed

    Groner, Maya L; Burge, Colleen A; Couch, Courtney S; Kim, Catherine J S; Siegmund, Gregor-Fausto; Singhal, Sonia; Smoot, Samantha C; Jarrell, Ann; Gaydos, Joseph K; Harvell, C Drew; Wyllie-Echeverria, Sandy

    2014-02-19

    Many marine pathogens are opportunists, present in the environment, but causing disease only under certain conditions such as immunosuppression due to environmental stress or host factors such as age. In the temperate eelgrass Zostera marina, the opportunistic labyrinthulomycete pathogen Labyrinthula zosterae is present in many populations and occasionally causes severe epidemics of wasting disease; however, risk factors associated with these epidemics are unknown. We conducted both field surveys and experimental manipulations to examine the effect of leaf age (inferred from leaf size) on wasting disease prevalence and severity in Z. marina across sites in the San Juan Archipelago, Washington, USA. We confirmed that lesions observed in the field were caused by active Labyrinthula infections both by identifying the etiologic agent through histology and by performing inoculations with cultures of Labyrinthula spp. isolated from observed lesions. We found that disease prevalence increased at shallower depths and with greater leaf size at all sites, and this effect was more pronounced at declining sites. Experimental inoculations with 2 strains of L. zosterae confirmed an increased susceptibility of older leaves to infection. Overall, this pattern suggests that mature beds and shallow beds of eelgrass may be especially susceptible to outbreaks of wasting disease. The study highlights the importance of considering host and environmental factors when evaluating risk of disease from opportunistic pathogens.

  3. Chronic Respiratory Diseases of School-Age Children

    ERIC Educational Resources Information Center

    McGovern, John P.

    1976-01-01

    The author examines the problems of chronic respiratory disease in school-age children from a medical viewpoint, including recognition and diagnosis, commonly encountered diseases, their effect on participation in physical exercise, emotional factors, medication, and emergency care. (MB)

  4. Positive oxidative stress in aging and aging-related disease tolerance.

    PubMed

    Yan, Liang-Jun

    2014-01-01

    It is now well established that reactive oxygen species (ROS), reactive nitrogen species (RNS), and a basal level of oxidative stress are essential for cell survival. It is also well known that while severe oxidative stress often leads to widespread oxidative damage and cell death, a moderate level of oxidative stress, induced by a variety of stressors, can yield great beneficial effects on adaptive cellular responses to pathological challenges in aging and aging-associated disease tolerance such as ischemia tolerance. Here in this review, I term this moderate level of oxidative stress as positive oxidative stress, which usually involves imprinting molecular signatures on lipids and proteins via formation of lipid peroxidation by-products and protein oxidation adducts. As ROS/RNS are short-lived molecules, these molecular signatures can thus execute the ultimate function of ROS/RNS. Representative examples of lipid peroxidation products and protein oxidation adducts are presented to illustrate the role of positive oxidative stress in a variety of pathological settings, demonstrating that positive oxidative stress could be a valuable prophylactic and/or therapeutic approach targeting aging and aging-associated diseases.

  5. Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?

    PubMed

    Swerdlow, Russell H

    2007-10-01

    For 70 years after Alois Alzheimer described a disorder of tangle-and-plaque dementia, Alzheimer's disease was a condition of the relatively young. Definitions of Alzheimer's disease (AD) have, however, changed over the past 30 years and under the revised view AD has truly become an age-related disease. Most now diagnosed with AD are elderly and would not have been diagnosed with AD as originally conceived. Accordingly, younger patients that qualify for a diagnosis of AD under both original and current Alzheimer's disease constructs now represent an exceptionally small percentage of the diagnosed population. The question of whether pathogenesis of the "early" and "late" onset cases is similar enough to qualify as a single disease was previously raised although not conclusively settled. Interestingly, debate on this issue has not kept pace with advancing knowledge about the molecular, biochemical and clinical underpinnings of tangle-and-plaque dementias. Since the question of whether both forms of AD share a common pathogenesis could profoundly impact diagnostic and treatment development efforts, it seems worthwhile to revisit this debate.

  6. Functional capacity of Brazilian patients with Parkinson's disease (PD): relationship between clinical characteristics and disease severity.

    PubMed

    Barbieri, Fabio A; Rinaldi, Natalia M; Santos, Paulo Cezar R; Lirani-Silva, Ellen; Vitório, Rodrigo; Teixeira-Arroyo, Cláudia; Stella, Florindo; Gobbi, Lilian Teresa B

    2012-01-01

    The present study had three objectives: (a) to characterize the functional capacity of patients with PD, (b) to assess the relationship between the physical fitness components of functional capacity with clinical characteristics and disease severity, and (c) to compare the physical fitness components of functional capacity with clinical characteristics according to disease severity. The study included 54 patients with idiopathic PD who were distributed into two groups according to PD severity: unilateral group (n=35); and bilateral group (n=19). All patients underwent psychiatric assessment by means of the Hoehn and Yahr (HY) staging of PD, the Unified Parkinson's Disease Rating Scale (UPDRS), the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and The Mini-Mental State Examination (MMSE). The physical fitness components of functional capacity were evaluated over a 2-day period, using recommendations by the American Alliance for Health, Physical Education, Recreation and Dance, and the Berg Balance Scale (BBS). Pearson correlation coefficients and multiple regressions were calculated to test the correlation between functional capacity and clinical characteristics, and to predict clinical scores from physical performance, respectively. Clinical variables and physical component data were compared between groups using analysis of variance to determine the effects of disease severity. Patients with advanced disease showed low levels of functional capacity. Interestingly, patients with good functional capacity in one of the physical fitness components also showed good capacities in the other components. Disease severity is a major factor affecting functional capacity and clinical characteristics. Medical providers should take disease severity into consideration when prescribing physical activity for PD patients, since the relationship between functional capacity and clinical characteristics is dependent on disease severity. PMID:21963176

  7. Multiplicity of Infection and Disease Severity in Plasmodium vivax

    PubMed Central

    Pacheco, M. Andreína; Lopez-Perez, Mary; Vallejo, Andrés F.; Herrera, Sócrates; Arévalo-Herrera, Myriam; Escalante, Ananias A.

    2016-01-01

    Background Multiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared. Methodology/Principal Findings As part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7%) than P. falciparum (14.8%). Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections. Conclusion The association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired

  8. Incidence, severity, and prevention of infections in chronic granulomatous disease.

    PubMed

    Mouy, R; Fischer, A; Vilmer, E; Seger, R; Griscelli, C

    1989-04-01

    We retrospectively analyzed the frequency and nature of infections occurring in 48 patients with chronic granulomatous disease. The long-term use of trimethoprim-sulfamethoxazole and ketoconazole as a preventive therapy for infections has also been evaluated. Lymphadenitis, lung infections, dermatitis, enteral infections, and hepatic abscesses were the most frequent infections. Staphylococcus aureus, Salmonella, and Aspergillus were the main microorganisms encountered. Twelve patients died: five from lung aspergillosis, three from hepatic abscesses, two from pneumonopathy of unknown origin, one from salmonellosis, and one from another probable infection that could not be proved. The actuarial survival rate was 50% at 10 years of age, with a prolonged plateau thereafter. There was no difference in survival rates between patients with X-linked and those with autosomal recessive chronic granulomatous disease. The 8-year actuarial survival rate was significantly higher for patients born in 1978 or afterward than for patients born before 1978 (92.9% vs 70.5%). A retrospective analysis of the occurrence of bacterial and fungal infections in patients who received trimethoprim-sulfamethoxazole and ketoconazole as infection prophylaxis indicated that the former was effective against bacterial infections but that ketoconazole provided no protection against Aspergillus infections.

  9. Prevalence of COPD by disease severity in men and women in northern Vietnam.

    PubMed

    Lâm, Hoàng Th Formula See Text; Ekerljung, Linda; T Formula See Text Ng, Nguy Formula See Text N Văn; Rönmark, Eva; Larsson, Kjell; Lundbäck, Bo

    2014-09-01

    The prevalence of COPD and its risk factor pattern varies between different areas of the world. The aim of this study was to investigate the prevalence of COPD by disease severity in men and women and risk factors for COPD in northern Vietnam. From all 5782 responders to a questionnaire survey, a randomly selected sample of 1500 subjects was invited to a clinical follow-up study. The methods included a structured interview using a modified GA2LEN study questionnaire for registration of symptoms and possible determinants of disease. Spirometry was performed before and after bronchodilation. The age distribution of the sample was 23-72 years. Of 684 subjects attending, 565 completed acceptable spirometric measurements. The prevalence of COPD defined by the GOLD criteria was 7.1%; in men 10.9% and in women 3.9% (p = 0.002). Of those 3.4% had a mild disease, 2.8% a moderate and 0.9% a severe disease. In ages >50 years, 23.5% of men and 6.8% of women had COPD. Among smokers aged >60 years (all men), 47.8% had COPD. None of the women with COPD had been smokers. Increasing age, smoking and male sex were the dominating risk factors, although male sex lost its significance in a multivariate setting. The prevalence of COPD among adults in northern Vietnam was 7.1% and was considerably higher among men than women. The prevalence increased considerably with age. Increasing age and smoking, the latter among men only, were the most important determinants of COPD.

  10. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

    PubMed Central

    Conti, Valeria; Izzo, Viviana; Corbi, Graziamaria; Russomanno, Giusy; Manzo, Valentina; De Lise, Federica; Di Donato, Alberto; Filippelli, Amelia

    2016-01-01

    Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented. PMID:26903869

  11. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

    Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models. PMID:25364723

  12. Goal Disengagement Capacities and Severity of Disease across Older Adulthood: The Sample Case of the Common Cold

    ERIC Educational Resources Information Center

    Jobin, Joelle; Wrosch, Carsten

    2016-01-01

    This study examined age-related associations between goal disengagement capacities, emotional distress, and disease severity across older adulthood. Given that an age-related increase in the experience of stressors might render important goals unattainable, it is expected that goal disengagement capacities would predict a decrease in the severity…

  13. Can Serum Ferritin Level Predict Disease Severity in Patients with Crimean-Congo Hemorrhagic Fever?

    PubMed Central

    Metanat, Maliheh; Sharifi-Mood, Batool; Tabatabaei, Mehdi; Sarraf-Shirazi, Mohammad

    2013-01-01

    Objective: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral disease. Several factors have already been suggested to explain the pathogenesis as well as predict the disease severity. In our study we aim to investigate the role of serum ferritin level as a possible predicting factor of disease severity in these patients. Materials and Methods: We evaluated all patients with laboratory confirmed diagnosis of CCHF who were admitted to Boo-Ali Hospital of Zahedan from May 2011 to June 2012. Confirmation of the disease determined using the presence of anti- CCHFV IgM in the serum by enzyme-linked immunosorbent assay (ELISA) or by polymerase chain reaction(PCR). After ethical approval, patients were categorized into two groups of mild and severe disease according to disseminated intravascular coagulation (DIC) severity using the scoring system of International Society on Thrombosis and Hemostasis (ISTH). Serum ferritin levels were evaluated and compared between these two groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the optimal cutoff value of serum ferritin for predicting the disease severity. Results: A total of 42 patients (36 men, 6 women, age range: 17–78 years) were included in this study, of whom 38% had Persian and 62% had Baloch ethnicity. According to DIC severity score, 54.7% of the patients had severe disease and 45.3% had mild disease. The area under the ROC curve was 0.896 and 95% CI was 0.801–0.991 (p<0.0001). A cut-off point of 1060 ng/dL, had a sensitivity of 78.9%, a specificity of 87%, a positive predictive value of 6% and a negative predictive value of 100%. Positive and negative likelihood ratios for this serum ferritin level were 6.05 and 0.24, respectively. Conclusion: Increased serum ferritin level has a significant positive correlation with disease severity in patients with CCHF and can evaluate the prognosis of these patients with a high sensitivity and specificity. PMID:25610262

  14. Brain Molecular Aging, Promotion of Neurological Disease and Modulation by Sirtuin5 Longevity Gene Polymorphism

    PubMed Central

    Glorioso, Christin; Oh, Sunghee; Douillard, Gaelle Guilloux; Sibille, Etienne

    2010-01-01

    Mechanisms determining characteristic age of onset for neurological diseases are largely unknown. Normal brain aging associates with robust and progressive transcriptome changes (“molecular aging”), but the intersection with disease pathways is mostly uncharacterized. Here, using cross-cohort microarray analysis of four human brain areas, we show that neurological disease pathways largely overlap with molecular aging and that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5prom2) have older brain molecular ages. Specifically, molecular aging was remarkably conserved across cohorts and brain areas, and included numerous developmental and transcription-regulator genes. Neurological disease-associated genes were highly overrepresented within age-related genes and changed almost unanimously in pro-disease directions, together suggesting an underlying genetic “program” of aging that progressively promotes disease. To begin testing this putative pathway, we developed and used an age-biosignature to assess five candidate longevity gene polymorphisms association with molecular aging rates. Most robustly, aging was accelerated in cingulate, but not amygdala, of subjects carrying a SIRT5 promoter polymorphism (+9yrs, p=0.004), in concordance with cingulate-specific decreased SIRT5 expression. This effect was driven by a set of core transcripts (+24 yrs, p=0.0004), many of which were mitochondrial, including Parkinson’s disease genes, PINK1 and DJ1/PARK7, hence suggesting that SIRT5prom2 may represent a risk factor for mitochondrial dysfunction-related diseases, including Parkinson s, through accelerated molecular aging of disease-related genes. Based on these results we speculate that a “common mechanism” may underlie age of onset across several neurological diseases. Confirming this pathway and its regulation by common genetic variants would provide new strategies for predicting, delaying, and

  15. First Experimental In Vivo Model of Enhanced Dengue Disease Severity through Maternally Acquired Heterotypic Dengue Antibodies

    PubMed Central

    Ng, Jowin Kai Wei; Zhang, Summer Lixin; Tan, Hwee Cheng; Yan, Benedict; Maria Martinez Gomez, Julia; Tan, Wei Yu; Lam, Jian Hang; Tan, Grace Kai Xin; Ooi, Eng Eong; Alonso, Sylvie

    2014-01-01

    Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue

  16. First experimental in vivo model of enhanced dengue disease severity through maternally acquired heterotypic dengue antibodies.

    PubMed

    Ng, Jowin Kai Wei; Zhang, Summer Lixin; Tan, Hwee Cheng; Yan, Benedict; Martinez, Julia Maria; Tan, Wei Yu; Lam, Jian Hang; Tan, Grace Kai Xin; Ooi, Eng Eong; Alonso, Sylvie

    2014-04-01

    Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue

  17. Distinct Mechanisms of Impairment in Cognitive Ageing and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.

    2008-01-01

    Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…

  18. Polymerase Gamma Disease through the Ages

    ERIC Educational Resources Information Center

    Saneto, Russell P.; Naviaux, Robert K.

    2010-01-01

    The most common group of mitochondrial disease is due to mutations within the mitochondrial DNA polymerase, polymerase gamma 1 ("POLG"). This gene product is responsible for replication and repair of the small mitochondrial DNA genome. The structure-function relationship of this gene product produces a wide variety of diseases that at times, seems…

  19. Brain-water diffusion coefficients reflect the severity of inherited prion disease

    PubMed Central

    Hyare, H.; Wroe, S.; Siddique, D.; Webb, T.; Fox, N. C.; Stevens, J.; Collinge, J.; Yousry, T.; Thornton, J. S.

    2010-01-01

    Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases. GLOSSARY ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive subscale; ADC = apparent diffusion coefficient; ADL = Barthel Activities of Daily Living scale; BET = brain extraction tool; BPRS

  20. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  1. Relative adrenal insufficiency as a predictor of disease severity and mortality in severe septic shock

    PubMed Central

    Dalegrave, Daniele; Silva, Rafael Lockshin; Becker, Maicon; Gehrke, Lísia Varella; Friedman, Gilberto

    2012-01-01

    Objective To evaluate if cortisol responses to 250 µg of intravenously administered adrenocorticotropic hormone are related to disease severity and, hence, mortality. Methods This is a retrospective study in a medical-surgical intensive care unit of a university hospital. We studied 69 consecutive patients with septic shock over a 1-yr period; these patients underwent a short 250-µg adrenocorticotropic hormone test because they exhibited >6 hours of progressive hemodynamic instability requiring repeated fluid challenges and vasopressor treatment to maintain blood pressure. The test was performed by intravenously injecting 250 µg of synthetic adrenocorticotropic hormone and measuring cortisol immediately before injection, 30 minutes post-injection and 60 minutes post-injection. Results The mean APACHE II score was 22±7. The intensive care unit mortality rate at day 28 was 55%. Median baseline cortisol levels (19 [11-27] µg/dL versus 24 [18-34] µg/dL, p=0.047) and median baseline cortisol/albumin ratios (7.6 [4.6-12.3] versus 13.9 [8.8-18.5]; p=0.01) were lower in survivors than in non-survivors. Responders and non-responders had similar baseline clinical data and outcomes. The variables that were significantly correlated with outcome based on the area under the ROC curves (AUC) were APACHE II (AUC=0.67 [0.535 to 0.781]), baseline cortisol (µg/dl) (AUC=0.662 [0.536 to 0.773], peak cortisol (µg/dl) (AUC=0.642 [0.515 to 0.755]) and baseline cortisol/albumin (AUC=0.75 [0.621 to 0.849]). Conclusions Increased basal cortisol is associated with mortality and disease severity. Cortisol responses upon adrenocorticotropic hormone stimulation were not related to outcome. The cortisol/albumin ratio does not predict unfavorable outcomes better than total cortisol levels or help to improve the accuracy of the adrenocorticotropic hormone test. PMID:23917934

  2. Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity.

    PubMed

    Keogh, M J; Aribisala, B S; He, J; Tulip, E; Butteriss, D; Morris, C; Gorman, G; Horvath, R; Chinnery, P F; Blamire, Andrew M

    2015-10-01

    Neuroferritinopathy is an autosomal dominant adult-onset movement disorder which occurs due to mutations in the ferritin light chain gene (FTL). Extensive iron deposition and cavitation are observed post-mortem in the basal ganglia, but whether more widespread pathological changes occur, and whether they correlate with disease severity is unknown. 3D-T1w and quantitative T2 whole brain MRI scans were performed in 10 clinically symptomatic patients with the 460InsA FTL mutation and 10 age-matched controls. Voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) were subsequently performed. Clinical assessment using the Unified Dystonia Rating Scale (UDRS) and Unified Huntington's Disease Rating Scale (UHDRS) was undertaken in all patients. VBM detected significant tissue changes within the substantia nigra, midbrain and dentate together with significant cerebellar atrophy in patients (FWE, p < 0.05). Iron deposition in the caudate head and cavitation in the lateral globus pallidus correlated with UDRS score (p < 0.001). There were no differences between groups with VBR. Our data show that progressive iron accumulation in the caudate nucleus, and cavitation of the globus pallidus correlate with disease severity in neuroferritinopathy. We also confirm sub-clinical cerebellar atrophy as a feature of the disease. We suggest that VBM is an effective technique to detect regions of iron deposition and cavitation, with potential wider utility to determine radiological markers of disease severity for all NBIA disorders. PMID:26142024

  3. Taste bud homeostasis in health, disease, and aging.

    PubMed

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.

  4. Taste bud homeostasis in health, disease, and aging.

    PubMed

    Feng, Pu; Huang, Liquan; Wang, Hong

    2014-01-01

    The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. PMID:24287552

  5. The temporal patterns of disease severity and prevalence in schistosomiasis

    SciTech Connect

    Ciddio, Manuela; Gatto, Marino Casagrandi, Renato

    2015-03-15

    Schistosomiasis is one of the most widespread public health problems in the world. In this work, we introduce an eco-epidemiological model for its transmission and dynamics with the purpose of explaining both intra- and inter-annual fluctuations of disease severity and prevalence. The model takes the form of a system of nonlinear differential equations that incorporate biological complexity associated with schistosome's life cycle, including a prepatent period in snails (i.e., the time between initial infection and onset of infectiousness). Nonlinear analysis is used to explore the parametric conditions that produce different temporal patterns (stationary, endemic, periodic, and chaotic). For the time-invariant model, we identify a transcritical and a Hopf bifurcation in the space of the human and snail infection parameters. The first corresponds to the occurrence of an endemic equilibrium, while the latter marks the transition to interannual periodic oscillations. We then investigate a more realistic time-varying model in which fertility of the intermediate host population is assumed to seasonally vary. We show that seasonality can give rise to a cascade of period-doubling bifurcations leading to chaos for larger, though realistic, values of the amplitude of the seasonal variation of fertility.

  6. The temporal patterns of disease severity and prevalence in schistosomiasis

    NASA Astrophysics Data System (ADS)

    Ciddio, Manuela; Mari, Lorenzo; Gatto, Marino; Rinaldo, Andrea; Casagrandi, Renato

    2015-03-01

    Schistosomiasis is one of the most widespread public health problems in the world. In this work, we introduce an eco-epidemiological model for its transmission and dynamics with the purpose of explaining both intra- and inter-annual fluctuations of disease severity and prevalence. The model takes the form of a system of nonlinear differential equations that incorporate biological complexity associated with schistosome's life cycle, including a prepatent period in snails (i.e., the time between initial infection and onset of infectiousness). Nonlinear analysis is used to explore the parametric conditions that produce different temporal patterns (stationary, endemic, periodic, and chaotic). For the time-invariant model, we identify a transcritical and a Hopf bifurcation in the space of the human and snail infection parameters. The first corresponds to the occurrence of an endemic equilibrium, while the latter marks the transition to interannual periodic oscillations. We then investigate a more realistic time-varying model in which fertility of the intermediate host population is assumed to seasonally vary. We show that seasonality can give rise to a cascade of period-doubling bifurcations leading to chaos for larger, though realistic, values of the amplitude of the seasonal variation of fertility.

  7. Aging Stereotypes Must be Taken Into Account for the Diagnosis of Prodromal and Early Alzheimer Disease.

    PubMed

    Régner, Isabelle; Mazerolle, Marie; Alescio-Lautier, Béatrice; Clarys, David; Michel, Bernard; Paccalin, Marc; Piolino, Pascale; Rigalleau, François; Sambuchi, Nathalie; Huguet, Pascal

    2016-01-01

    Because of a dramatic increase of older people worldwide, screening for prodromal state of Alzheimer disease (AD) is a major societal challenge. Many individuals diagnosed with prodromal AD, do not convert to AD, some remaining stable and others reversing back to normal. We argue that an important source of this overdiagnosis comes from negative aging stereotypes (eg, the culturally shared beliefs that aging inescapably causes severe cognitive decline and diseases). Many laboratory studies show that such stereotypes impair memory performance in healthy older adults, producing inflated age differences. Research is needed to examine how aging stereotypes implicitly permeate neuropsychological testing and contribute to false positives.

  8. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... 64 have a heart attack. About half of women who have a heart attack before age 65 die within 8 years. Heart ... have another within 6 years. About half of women who have a heart attack will be disabled with heart failure within 6 ...

  9. Impairment of age estimation from faces in Alzheimer's disease.

    PubMed

    Moyse, Evelyne; Bastin, Christine; Salmon, Eric; Brédart, Serge

    2015-01-01

    A prerequisite for any function in social cognition is the perception and processing of social cues. Age estimation is a skill that is used in everyday life and is fundamental in social interactions. This study evaluated whether facial age estimation is impaired in patients with mild to moderate Alzheimer's disease (AD). The current age of faces is known to have an impact on age estimation, and therefore stimuli belonging to different age groups (young, middle-aged, and older adults' faces) were used. As expected, an impairment of age estimation from faces was observed in mild to moderate AD patients. However, the profile of impairment depended on the age of faces and stage of the disease. Mild AD patients presented difficulties mainly in assessing the age of middle-aged adults. In moderate disease stage, these difficulties also affected the age estimation of young adult faces. Interestingly, AD patients remained relatively good at estimating the age of older adults' faces, compared to healthy controls. PMID:25589725

  10. Age of the mother as a risk factor and timing of hypospadias repair according to severity

    PubMed Central

    Jorge, Juan Carlos; Pérez-Brayfield, Marcos Raymond; Torres, Camille M.; Piñeyro-Ruiz, Coriness; Torres, Naillil

    2016-01-01

    Background & Objectives Hypospadias is characterized by a displacement of the urethral opening in males that can change from the typical position within the glans penis to a subcoronal position (Type I), to anywhere along the ventral shaft (Type II), to penoscrotal, scrotal, or perineal positions (Type III). We and others have previously reported that age of the mother (≥ 40 years old) is a risk factor for having a child with hypospadias, but there is a scarcity of reports on whether such risk is higher for having a child with the mild (Type I) or the more severe forms (Types II and III). In addition, we aimed to assess the timing of hypospadias repair according to severity. Methods Parents of children with hypospadias were interviewed by using a series of questionnaires (n = 128 cases). Severity was confirmed in the clinic and age of the mother was self-reported. Number of surgeries, age of child by the first and the last intervention was also assessed. Ordered logistic regression and the Brant test were employed to calculate risk between mild (Type I) and severe cases (Types II and III), and the assumption of proportional odds, respectively. The Mann-Whitney U Test was used to compare number of surgeries and age by the last repair between mild and severe cases. One-way ANOVA was employed to compare age of the child at the time of first surgery across severities (Types I - III). Results Women ≥ 40 years of age are 3.89 times [95% CI: 1.20-12.64] at a higher risk for having a child with the more severe forms of the condition than younger women. Repair of Type I was accomplished with 1 intervention whereas more severe cases required 1 – 4 (2 ± 0.5) surgical interventions. The timing for hypospadias repair of Type I cases occurred at an average age of 16.2 ± 4.88 months, of Type II cases occurred at an average age of 20.3 ± 8.15 months whereas the average age of the first hypospadias repair among Type III cases was 12.68 ± 2.52 months. Number of surgeries

  11. Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

    PubMed Central

    Dewey, Daniel C.; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B.; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B.

    2014-01-01

    Objective To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Methods Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Interpretation Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. PMID:25082782

  12. Discover the network mechanisms underlying the connections between aging and age-related diseases.

    PubMed

    Yang, Jialiang; Huang, Tao; Song, Won-Min; Petralia, Francesca; Mobbs, Charles V; Zhang, Bin; Zhao, Yong; Schadt, Eric E; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named "GeroNet" to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to "response to decreased oxygen levels", "insulin signalling pathway", "cell cycle", etc. Based on subnetwork connectivity, we can correctly "predict" if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer's disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  13. Discover the network mechanisms underlying the connections between aging and age-related diseases

    PubMed Central

    Yang, Jialiang; Huang, Tao; Song, Won-min; Petralia, Francesca; Mobbs, Charles V.; Zhang, Bin; Zhao, Yong; Schadt, Eric E.; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named “GeroNet” to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to “response to decreased oxygen levels”, “insulin signalling pathway”, “cell cycle”, etc. Based on subnetwork connectivity, we can correctly “predict” if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer’s disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  14. Disease activity and severity in early inflammatory arthritis predict hand cortical bone loss

    PubMed Central

    Pye, Stephen R.; Adams, Judith E.; Ward, Kate A.; Bunn, Diane K.; Symmons, Deborah P. M.

    2010-01-01

    Objectives. To determine the influence of disease-related variables on hand cortical bone loss in women with early inflammatory arthritis (IA), and whether hand cortical bone mass predicts subsequent joint damage. Method. Adults aged ≥16 years with recent onset of IA were recruited to the Norfolk Arthritis Register between 1990 and 1998, and followed prospectively. At baseline, patients had their joints examined for swelling and tenderness and had CRP and disease activity 28-joint assessment score (DAS-28) measured. Radiographs of the hands were performed in a subgroup of patients at Year 1 and at follow-up, which were assessed using digital X-ray radiogrammetry (DXR). They were also evaluated for the presence of erosions using Larsen’s method. Linear mixed models were used to investigate whether disease-related factors predicted change in DXR–areal bone mineral density (BMDa). We also evaluated whether DXR–BMDa predicted the subsequent occurrence of erosive disease. Results. Two hundred and four women, mean (s.d.) age 55.1 (14.0) years, were included. Median follow-up between radiographs was 4 years. The mean within-subject change in BMDa was 0.024 g/cm2 equivalent to 1% decline per year. After adjustment for age, height and weight, compared with those within the lower tertile for CRP, those in the upper tertile had greater subsequent loss of bone. This was true also for DAS-28 and Larsen score. Among those without erosions on the initial radiograph (121), DXR–BMDa at baseline did not predict the new occurrence of erosions. Conclusion. Increased disease activity and severity are associated with accelerated bone loss. However, lower BMDa did not predict the new occurrence of erosive disease. PMID:20573690

  15. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

    PubMed Central

    Soler-Cataluna, J; Martinez-Garcia, M; Roman, S; Salcedo, E; Navarro, M; Ochando, R

    2005-01-01

    Background: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Methods: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Results: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). Conclusions: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital. PMID:16055622

  16. Quantifying Parkinson's disease finger-tapping severity by extracting and synthesizing finger motion properties.

    PubMed

    Sano, Yuko; Kandori, Akihiko; Shima, Keisuke; Yamaguchi, Yuki; Tsuji, Toshio; Noda, Masafumi; Higashikawa, Fumiko; Yokoe, Masaru; Sakoda, Saburo

    2016-06-01

    We propose a novel index of Parkinson's disease (PD) finger-tapping severity, called "PDFTsi," for quantifying the severity of symptoms related to the finger tapping of PD patients with high accuracy. To validate the efficacy of PDFTsi, the finger-tapping movements of normal controls and PD patients were measured by using magnetic sensors, and 21 characteristics were extracted from the finger-tapping waveforms. To distinguish motor deterioration due to PD from that due to aging, the aging effect on finger tapping was removed from these characteristics. Principal component analysis (PCA) was applied to the age-normalized characteristics, and principal components that represented the motion properties of finger tapping were calculated. Multiple linear regression (MLR) with stepwise variable selection was applied to the principal components, and PDFTsi was calculated. The calculated PDFTsi indicates that PDFTsi has a high estimation ability, namely a mean square error of 0.45. The estimation ability of PDFTsi is higher than that of the alternative method, MLR with stepwise regression selection without PCA, namely a mean square error of 1.30. This result suggests that PDFTsi can quantify PD finger-tapping severity accurately. Furthermore, the result of interpreting a model for calculating PDFTsi indicated that motion wideness and rhythm disorder are important for estimating PD finger-tapping severity. PMID:27032933

  17. [Mechanisms of the immune system ageing and some age-associated diseases].

    PubMed

    Witkowski, Jacek M

    2014-01-01

    In this paper the concept of homeostenosis (progressive reduction of ability to adapt producing loss of effectiveness) of the immune system is presented as a cause of the system ageing. In particular, the progression of immune system homeostenosis was shown to be associated with previous or ongoing chronic inflammatory diseases, including rheumatoid arthritis, type 2 diabetes, chronic kidney disease and Alzheimer's disease.

  18. Using Nutrition Against Aging and Degenerative Disease.

    ERIC Educational Resources Information Center

    Rokosz, Francis M.

    A review of historical and research literature presents various perspectives on the growing controversy surrounding the use of vitamin and mineral supplements to maintain good health and for preventive health care. Several points are made in opposition to many health professionals' opinions that most nutritional supplements are unnecessary.…

  19. The Impact of Obstructive Sleep Apnea on Nonalcoholic Fatty Liver Disease in Patients with Severe Obesity

    PubMed Central

    Benotti, Peter; Wood, G. Craig; Argyropoulos, George; Pack, Allan; Keenan, Brendan T.; Gao, Xiang; Gerhard, Glenn; Still, Christopher

    2016-01-01

    Objective Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD. Methods Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis. Results The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m2. On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD. Conclusions OSA severity and its accompanying hypoxia are associated with the severity of NAFLD. PMID:26880657

  20. Stone age diseases and modern AIDS

    PubMed Central

    Koch, Arthur L

    2008-01-01

    The great advantage of being a sexually transmitted disease is the ability to survive and specialize solely on a host species that is present in low numbers and widely distributed so that contact between infected and uninfected organisms by chance is rare. Pathogens of a sparse, but widely distributed host species, must either: i) have an alternative host; ii) be able to survive in a dormant state; or iii) be non-destructive to their host. For the pathogens of a diploid there is a particularly effective strategy, that of being sexually transmitted. Then the hosts' themselves transfer the pathogen. PMID:18687115

  1. Glycation: the angiogenic paradox in aging and age-related disorders and diseases.

    PubMed

    Roca, F; Grossin, N; Chassagne, P; Puisieux, F; Boulanger, E

    2014-05-01

    Angiogenesis is generally a quiescent process which, however, may be modified by different physiological and pathological conditions. The "angiogenic paradox" has been described in diabetes because this disease impairs the angiogenic response in a manner that differs depending on the organs involved and disease evolution. Aging is also associated with pro- and antiangiogenic processes. Glycation, the post-translational modification of proteins, increases with aging and the progression of diabetes. The effect of glycation on angiogenesis depends on the type of glycated proteins and cells involved. This complex link could be responsible for the "angiogenic paradox" in aging and age-related disorders and diseases. Using diabetes as a model, the present work has attempted to review the age-related angiogenic paradox, in particular the effects of glycation on angiogenesis during aging.

  2. Use of Metformin in Diseases of Aging

    PubMed Central

    Miles, John M.; Rule, Andrew D.; Borlaug, Barry A.

    2014-01-01

    Metformin is the most commonly prescribed medication for type 2 diabetes (T2DM) in the world. It has primacy in the treatment of this disease because of its safety record and also because of evidence for reduction in the risk of cardiovascular events. Evidence has accumulated indicating that metformin is safe in people with stage 3 chronic kidney disease (CKD-3). It is estimated that roughly one-quarter of people with CKD-3 and T2DM in the United States (well over 1 million) are ineligible for metformin treatment because of elevated serum creatinine levels. This could be overcome if a scheme, perhaps based on pharmacokinetic studies, could be developed to prescribe reduced doses of metformin in these individuals. There is also substantial evidence from epidemiological studies to indicate that metformin may not only be safe, but may actually benefit people with heart failure (HF). Prospective, randomized trials of the use of metformin in HF are needed to investigate this possibility. PMID:24752835

  3. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    DOE PAGES

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; et al

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). Amore » biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

  4. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    SciTech Connect

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; Perelson, Alan S.; Dahari, Harel

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver diseasemax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

  5. Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity?

    PubMed Central

    Duraković, Nadira; Krečak, Ivan; Perić, Zinaida; Milošević, Milan; Desnica, Lana; Pulanić, Dražen; Pusic, Iskra; Kušec, Vesna; Vrhovac, Radovan; Pavletic, Steven Z.; Nemet, Damir

    2016-01-01

    Aim To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. Methods This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician’s Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. Results YKL-40 levels were significantly higher in cGVHD patients than in controls (P = 0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P = 0.017). YKL-40 level significantly positively correlated with disease severity (P < 0.001; correlation coefficient 0.455), and activity estimated using Clinician’s Impression of Activity (P = 0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P = 0.085; correlation coefficient 0.296). Conclusion YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD. PMID:27374825

  6. Nutritional influences on epigenetics and age-related disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  7. Aging is not a disease: implications for intervention.

    PubMed

    Rattan, Suresh I S

    2014-06-01

    Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease management and treatment. Continuing the disease-oriented research and treatment approaches, as opposed to health-oriented and preventive strategies, are economically, socially and psychologically unsustainable.

  8. Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

    PubMed

    Dukart, Juergen; Kherif, Ferath; Mueller, Karsten; Adaszewski, Stanislaw; Schroeter, Matthias L; Frackowiak, Richard S J; Draganski, Bogdan

    2013-04-01

    The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.

  9. Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

    PubMed

    Tummala, Sudhakar; Roy, Bhaswati; Park, Bumhee; Kang, Daniel W; Woo, Mary A; Harper, Ronald M; Kumar, Rajesh

    2016-10-01

    Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc.

  10. Parkinson's disease and age: The obvious but largely unexplored link.

    PubMed

    Abdullah, Rashed; Basak, Indranil; Patil, Ketan S; Alves, Guido; Larsen, Jan Petter; Møller, Simon Geir

    2015-08-01

    Parkinson's disease is a chronic, progressive neurodegenerative disorder with increased prevalence in the aging population. It is estimated that approximately 1.5 million individuals in the US alone suffer from Parkinson's disease and with the extension of life expectancy this number is expected to rise dramatically within the next twenty-five years. The majority of Parkinson's disease cases are sporadic. But mutations in genes such as α-synuclein, Parkin, PINK1, DJ-1 and LRRK2, have been conclusively associated with both early- and late-onset of the disease. Although the genetics of Parkinson's disease is starting to become unraveled, the interplay between genetic and environmental factors is largely unknown as are the underlying mechanisms that trigger the disease as the brain ages. The risk of Parkinson's disease increases dramatically in individuals over the age of 60 and it is estimated that more than 1% of all seniors have some form of the condition. In this review, we will highlight some of the central proteins associated with Parkinson's disease and how they may be linked to processes and factors associated with age.

  11. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement.

    PubMed

    Candore, G; Caruso, C; Jirillo, E; Magrone, T; Vasto, S

    2010-01-01

    Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and age-related diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling age-related low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing.

  12. Quantitative characterization of disease severity in diseases with complex symptom profiles.

    PubMed

    Kondraske, George V; Stewart, R Malcolm

    2006-01-01

    A number of clinical and research situations arise that require the integration of complex, multi-dimensional, performance-related information to determine a single quantity such as "disease severity" or "risk level" (for subsequent development of a disease). This process is generally carried out either by relying on a subjective gestalt approach or by using rating scales that combine scores for component measures using an additive process without justification. Concepts from general systems performance theory have provided insights into this problem, teaching that a fundamentally multiplicative method of integrating components is often appropriate. In this paper, concepts and previous supportive experimental work are reviewed in the context of the quantitative characterization of disease severity. A Parkinson's disease study (n=114) is presented that mimics the "two-condition" situation encountered in the clinical trial of a new drug or other therapy. Traditional and performance theory-based composite scores are computed for each condition ("on" and "off" medications) and compared, with emphasis on the different quantitative "pictures" conveyed by each approach. It is concluded that performance theory based composites are not only more sensitive to therapeutic agents experimentally, but also have superior conceptual validity compared to traditional forms of single-number composites. PMID:17946592

  13. Outcomes of Combined Shelf Acetabuloplasty with Femoral Varus Osteotomy in Severe Legg-Calve-Perthes (LCP) Disease: Advanced Containment Method for Severe LCP Disease

    PubMed Central

    Lim, Kyung Sup

    2015-01-01

    Background Standard treatments may provide adequate containment in mild to moderate Legg-Calve-Perthes disease (LCPD), but they can be problematic in more severe cases. The purpose of this study was to report the results of combined shelf acetabuloplasty with femoral varus osteotomy in severe LCPD. Methods We reviewed 12 patients who had undergone combined shelf acetabuloplasty with femoral varus osteotomy. The indications for this type of operation were: (1) above 8 years of age at clinical onset; (2) massive femoral epiphysis involvement (Catterall group 4, lateral pillar C); (3) femoral head lateral subluxation on the anteroposterior radiograph; and (4) impending hinged abduction on preoperative magnetic resonance imaging or arthrography. The mean age was 9.3 years (range, 8 to 10.8 years). The patients were clinically evaluated with Iowa hip score and leg length discrepancy at the final follow-up. Radiographic outcome was assessed using the Stulberg classification to evaluate femoral head sphericity. The presence of osteoarthritis was evaluated by the Tonnis classification. Correlation analysis was conducted to analyze the preoperative factors that were strongly associated with patients' outcomes. Results The mean follow-up period was 10.1 years (range, 7.1 to 13.2 years). Functional grade was excellent in all patients at last follow-up (mean, 92; range, 82 to 99). The mean leg length discrepancy after skeletal maturity was 0.9 cm (range, 0 to 1.7 cm). There were no significant complications or need for additional surgery. Radiographically, 92% of patients reached satisfactory outcomes: Stulberg grade I, 0 cases; Stulberg grade II, 4 cases (34%); Stulberg III, 7 cases (58%), Stulberg IV, 1 case (8%); and Stulberg V, 0 cases. There was no osteoarthritis by Tonnis classification. Conclusions The surgical outcomes for combined shelf acetabuloplasty with femoral varus osteotomy in severe LCPD patients over 8 years old are comparable with other advanced surgical

  14. Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 2: social responsiveness.

    PubMed

    Rosado, B; González-Martínez, A; Pesini, P; García-Belenguer, S; Palacio, J; Villegas, A; Suárez, M-L; Santamarina, G; Sarasa, M

    2012-11-01

    Changes in social interactions with owners and other dogs are frequently observed in dogs with cognitive dysfunction syndrome (CDS). The aim of this work was to assess the effect of age and severity of CDS on social responsiveness. This is the second part of a 2-part report on spontaneous activity in pet dogs. A human interaction test and a mirror test were administered at baseline and 6 months later to assess social responses to humans and conspecifics, respectively, to four groups of privately-owned dogs: young (n=9), middle-aged (n=9), cognitively unimpaired aged (n=31), and cognitively impaired aged (n=36). The severity of cognitive impairment was considered in the last group and dogs were categorised as having either mild or severe CDS. The influence of the person and the mirror on locomotion and exploratory behaviour was also studied. Dogs were recorded in a testing room and the video recordings were subsequently analysed. Young dogs displayed more interactions involving physical contact with a person. Young and middle-aged dogs showed more vocalisations in response to social isolation. In contrast, aged animals spent more time in front of the mirror. Changes in social responsiveness associated with severe CDS included decreased response to social isolation and human interaction and increased time in front of the mirror, suggesting a deficit in habituation. Testing of spontaneous activity might help to characterise CDS in aged dogs, a condition increasingly diagnosed in veterinary clinics and a potentially useful natural model of Alzheimer's disease in humans. PMID:22578689

  15. Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

    PubMed

    McIntosh, Roger C; Ironson, Gail; Antoni, Michael; Fletcher, Mary Ann; Schneiderman, Neil

    2016-02-01

    Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network.

  16. Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

    PubMed

    McIntosh, Roger C; Ironson, Gail; Antoni, Michael; Fletcher, Mary Ann; Schneiderman, Neil

    2016-02-01

    Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network. PMID:26143246

  17. [Severe behavioral changes in a patient with Fahr's disease].

    PubMed

    Kümmer, Arthur; de Castro, Maila; Caramelli, Paulo; Cardoso, Francisco; Teixeira, Antônio Lúcio

    2006-09-01

    We report on a case of a 40 year-old man with Fahrs disease, defined by idiopathic bilateral basal ganglia calcification, who developed depressive disorder, motor and phonic tics, stereotyped behaviors such as punding and personality changes with significant social and familiar implications. We discuss about the psychopathology of Fahrs disease and the relevance of the basal ganglia in the determination of humans behavior. PMID:17119811

  18. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    PubMed Central

    Davalli, Pierpaola; Mitic, Tijana; Caporali, Andrea; Lauriola, Angela; D'Arca, Domenico

    2016-01-01

    The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. PMID:27247702

  19. Telomeres in aging and disease: lessons from zebrafish

    PubMed Central

    Carneiro, Madalena C.; de Castro, Inês Pimenta

    2016-01-01

    ABSTRACT Age is the highest risk factor for some of the most prevalent human diseases, including cancer. Telomere shortening is thought to play a central role in the aging process in humans. The link between telomeres and aging is highlighted by the fact that genetic diseases causing telomerase deficiency are associated with premature aging and increased risk of cancer. For the last two decades, this link has been mostly investigated using mice that have long telomeres. However, zebrafish has recently emerged as a powerful and complementary model system to study telomere biology. Zebrafish possess human-like short telomeres that progressively decline with age, reaching lengths in old age that are observed when telomerase is mutated. The extensive characterization of its well-conserved molecular and cellular physiology makes this vertebrate an excellent model to unravel the underlying relationship between telomere shortening, tissue regeneration, aging and disease. In this Review, we explore the advantages of using zebrafish in telomere research and discuss the primary discoveries made in this model that have contributed to expanding our knowledge of how telomere attrition contributes to cellular senescence, organ dysfunction and disease. PMID:27482813

  20. Cellular senescence in aging and age-related disease: from mechanisms to therapy

    PubMed Central

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2016-01-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy. PMID:26646499

  1. Cellular senescence in aging and age-related disease: from mechanisms to therapy.

    PubMed

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2015-12-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

  2. Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats.

    PubMed

    Garvey, Sean M; Dugle, Janis E; Kennedy, Adam D; McDunn, Jonathan E; Kline, William; Guo, Lining; Guttridge, Denis C; Pereira, Suzette L; Edens, Neile K

    2014-06-01

    Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several muscles in particular undergo progressive atrophy and degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling to characterize trends in metabolic changes between 15-month-old adult and 32-month-old aged Fischer 344 × Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, exhibits markedly fewer signs of atrophy. Both gastrocnemius and soleus muscles were analyzed, as well as plasma and urine. Compared to adult gastrocnemius, aged gastrocnemius showed evidence of reduced glycolytic metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels of citrate and nicotinamide adenine dinucleotide were reduced, consistent with mitochondrial abnormalities. Indicative of muscle atrophy, 3-methylhistidine and free amino acids were elevated in aged gastrocnemius. The monounsaturated fatty acids oleate, cis-vaccenate, and palmitoleate also increased in aged gastrocnemius, suggesting altered lipid metabolism. Compared to gastrocnemius, aged soleus exhibited far fewer changes in carbohydrate metabolism, but did show reductions in several glycolytic intermediates, fumarate, malate, and flavin adenine dinucleotide. Plasma biochemicals showing the largest age-related increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, and creatine. These changes suggest reduced insulin sensitivity in aged FBN rats. Altogether, these data highlight skeletal muscle group-specific perturbations of glucose and lipid metabolism consistent with mitochondrial dysfunction in aged FBN rats. PMID:24652515

  3. Sensitivity of spatiotemporal gait parameters in measuring disease severity in Friedreich ataxia.

    PubMed

    Milne, Sarah C; Hocking, Darren R; Georgiou-Karistianis, Nellie; Murphy, Anna; Delatycki, Martin B; Corben, Louise A

    2014-12-01

    Friedreich ataxia (FRDA) is an autosomal recessive disease with gait ataxia being the main source of morbidity. Mobility progressively declines, from initial symptom onset at approximately 10-15 years of age to being unable to ambulate 10-15 years later. Here, we sought to investigate the relationship between spatiotemporal gait parameters and clinical markers of disease severity. Thirteen people with FRDA walked along an 8.3-m GAITRite® mat six times each at their preferred fast and slow speeds. Relationships between spatiotemporal gait parameters and a range of clinical and disease characteristics were examined. Significant correlations were found between spatiotemporal gait characteristics at each of the walking speeds and Friedreich Ataxia Rating Scale (FARS) score and disease duration. During the fast-walking condition, gait speed and cadence decreased with an increase in disease duration and the FARS score. GAA1 repeat expansion negatively correlated with double-support percentage of the gait cycle in all speed conditions demonstrating a relationship between the genetic mutation and compensatory strategies for impaired dynamic balance. In all speed conditions, there were correlations between a range of spatiotemporal gait characteristics and the timed 25-ft walk test, a well-established measure of gait mobility. These findings suggest that spatiotemporal gait parameters are a sensitive measure of gait decline in individuals with FRDA and should be considered for inclusion in intervention studies whilst participants are still ambulant.

  4. The relationship between electrovestibulography and Parkinson's disease severity.

    PubMed

    Shoushtarian, Mehrnaz; Lithgow, Brian

    2007-01-01

    Parkinson's disease (PD) is the second largest neurodegenerative disorder worldwide. This disease results from the loss of dopamine producing neurons in parts of the basal ganglia of the brain. Previous studies have shown the involvement of the dopamine system in the basal ganglia in balance control. Sensations of balance in the body are detected by the vestibular apparatus. In this project, electrovestibulography (EVestG) has been used to measure neuronal activity of the vestibular apparatus and nuclei from Parkinson's patients. A wavelet based signal processing technique, a Neural Event Extraction Routine, has been used to extract biomarkers from these EVestG recordings. These measurements appear to be correlated with scores from mobility tests which indicate disease progression and mobility impairment in Parkinson's patients. PMID:18002471

  5. Lifestyle changes and beliefs regarding disease severity in patients with chronic hepatitis C.

    PubMed

    Castera, L; Constant, A; Bernard, P-H; de Ledinghen, V; Couzigou, P

    2006-07-01

    The aim of this prospective study was to investigate beliefs regarding disease severity and lifestyle changes following hepatitis C diagnosis in patients with chronic hepatitis C (CHC). One hundred and eighty-five consecutive CHC patients were interviewed by means of self-questionnaires exploring several aspects of their disease. Most patients (93%) identified cirrhosis and liver cancer as the two main complications of CHC. More than half of patients (59%) thought that CHC was always associated with a fatal outcome whereas 3% thought that they would stay healthy. HCV viral load was the most commonly reported factor associated with disease severity. Sex life changes were reported by 107 patients (58%) whereas dietary intake changes were reported by 88 patients (48%). In multivariate analysis, changes in sex life were associated with male gender [odds ratio (OR): 2.57, 95% CI: 1.30-5.08, P < 0.007], perceived disease severity (OR: 1.02, 95% CI: 1.00-1.03, P < 0.03) and anxiety (OR: 1.05, 95% CI: 1.01-1.08, P < 0.003), whereas changes in dietary intake were associated with age (OR: 1.04, 95% CI: 1.02-1.08, P < 0.003) and anxiety (OR: 1.04, 95% CI: 1.01-1.08, P < 0.006). Our results show the considerable impact of CHC diagnosis on patients' lifestyle. They emphasize the need for improving CHC patient counselling in order to avoid unnecessary sex life and dietary intake changes. PMID:16792542

  6. Severe asthma in school-age children: evaluation and phenotypic advances.

    PubMed

    Coverstone, Andrea; Bacharier, Leonard B; Fitzpatrick, Anne M

    2015-05-01

    Although the majority of children with asthma have a favorable clinical response to treatment with low to moderate doses of inhaled corticosteroids (ICS), a small subset of children have "severe" asthma characterized by ongoing symptoms and airway inflammation despite treatment with high doses of ICS and even oral corticosteroids. Although there is symptom heterogeneity in the affected children, children with severe asthma share the risk for adverse outcomes, including recurrent and potentially life-threatening exacerbations, which contribute to substantial economic burden. This article reviews current knowledge of severe asthma in school-age children (age 6-17 years) with a focus on recent literature published after January 2012. Clinical management approaches for children with severe asthma are discussed as well as current phenotyping efforts and emerging phenotypic-directed therapies that may be of benefit for subpopulations of children with severe asthma in the future.

  7. Axis II comorbidity in borderline personality disorder is influenced by sex, age, and clinical severity.

    PubMed

    Barrachina, Judith; Pascual, Juan C; Ferrer, Marc; Soler, Joaquim; Rufat, M Jesús; Andión, Oscar; Tiana, Thais; Martín-Blanco, Ana; Casas, Miquel; Pérez, Víctor

    2011-01-01

    Borderline personality disorder (BPD) is a severe psychiatric disorder that has a high clinical heterogeneity and frequent co-occurrence with other personality disorders (PDs). Although several studies have been performed to assess axis II comorbidity in BPD, more research is needed to clarify associated factors. The aim of this study was to determine the prevalence of co-occurrent axis II disorders in a large sample of patients with BPD and to investigate the influence of sex, age, and severity on this comorbidity. Data were collected from 484 patients with BPD through 2 semistructured interviews. We analyzed the frequency of axis II comorbidity and assessed differences regarding sex, age, and severity of BPD. About 74% of patients with BPD had at least 1 co-occurrent axis II disorder. The most common were paranoid, passive-aggressive, avoidant, and dependent PDs. Significant sex differences were found. Women presented more comorbidity with dependent PD, whereas men showed higher rates of comorbidity with antisocial PD. We also observed a significant positive correlation between age and the number of co-occurrent axis II disorders in women with BPD. Another finding was the positive correlation between BPD severity and the number of co-occurrent axis II disorders. These findings suggest that comorbidity with other axis II disorders and sex, age, and severity should be taken into account when developing treatment strategies and determining the prognosis of BPD.

  8. Role of Maternal Antibodies in Infants with Severe Diseases Related to Human Parechovirus Type 31

    PubMed Central

    Aizawa, Yuta; Watanabe, Kanako; Oishi, Tomohiro; Hirano, Harunobu; Hasegawa, Isao

    2015-01-01

    Human parechovirus type 3 (HPeV3) is an emerging pathogen that causes sepsis and meningoencephalitis in young infants. To test the hypothesis that maternal antibodies can protect this population, we measured neutralizing antibody titers (NATs) to HPeV3 and other genotypes (HPeV1 and HPeV6) in 175 cord blood samples in Japan. The seropositivity rate (>1:32) for HPeV3 was 61%, similar to that for the other genotypes, but decreased significantly as maternal age increased (p<0.001). Furthermore, during the 2014 HPeV3 epidemic, prospective measurement of NATs to HPeV3 in 45 patients with severe diseases caused by HPeV3 infection showed low NATs (<1:16) at onset and persistently high NATs (>1:512) until age 6 months. All intravenous immunoglobulin samples tested elicited high NATs to HPeV3. Our findings indicate that maternal antibodies to HPeV3 may help protect young infants from severe diseases related to HPeV3 and that antibody supplementation may benefit these patients. PMID:26485714

  9. Immune aging, dysmetabolism, and inflammation in neurological diseases

    PubMed Central

    Deleidi, Michela; Jäggle, Madeline; Rubino, Graziella

    2015-01-01

    As we age, the immune system undergoes a process of senescence accompanied by the increased production of proinflammatory cytokines, a chronic subclinical condition named as “inflammaging”. Emerging evidence from human and experimental models suggest that immune senescence also affects the central nervous system and promotes neuronal dysfunction, especially within susceptible neuronal populations. In this review we discuss the potential role of immune aging, inflammation and metabolic derangement in neurological diseases. The discovery of novel therapeutic strategies targeting age-linked inflammation may promote healthy brain aging and the treatment of neurodegenerative as well as neuropsychiatric disorders. PMID:26089771

  10. Atypical Pestivirus and Severe Respiratory Disease in Calves, Europe

    PubMed Central

    Lucente, Maria Stella; Mari, Viviana; Cirone, Francesco; Cordioli, Paolo; Camero, Michele; Sciarretta, Rossana; Losurdo, Michele; Lorusso, Eleonora; Buonavoglia, Canio

    2011-01-01

    In 2010, a HoBi-like pestivirus was isolated from clinically affected calves in Italy. This European virus reproduced a milder form of disease under experimental conditions and was genetically related to previously reported HoBi-like strains. Isolation of this novel virus from a clinical outbreak may have implications for cattle health and prophylactic programs. PMID:21801648

  11. Parameters of a severe disease course in ulcerative colitis

    PubMed Central

    Stallmach, Andreas; Nickel, Luisa; Lehmann, Thomas; Bokemeyer, Bernd; Bürger, Martin; Hüppe, Dietrich; Kruis, Wolfgang; Nikolaus, Susanna; Preiss, Jan C; Sturm, Andreas; Teich, Niels; Schmidt, Carsten

    2014-01-01

    AIM: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT). METHODS: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy. RESULTS: In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can

  12. Interleukin 15 Levels in Serum May Predict a Severe Disease Course in Patients with Early Arthritis

    PubMed Central

    González-Álvaro, Isidoro; Ortiz, Ana M.; Alvaro-Gracia, José María; Castañeda, Santos; Díaz-Sánchez, Belen; Carvajal, Inmaculada; García-Vadillo, J. Alberto; Humbría, Alicia; López-Bote, J. Pedro; Patiño, Esther; Tomero, Eva G.; Vicente, Esther F.; Sabando, Pedro; García-Vicuña, Rosario

    2011-01-01

    Background Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). Methodology and Results Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06–0.18]; p<0.001) or ACPA (0.34 [0.01–0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18–2.7; p = 0.007). Conclusions Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for

  13. Single photon emission computed tomography in Alzheimer's disease. Abnormal iofetamine I 123 uptake reflects dementia severity

    SciTech Connect

    Johnson, K.A.; Holman, B.L.; Mueller, S.P.; Rosen, T.J.; English, R.; Nagel, J.S.; Growdon, J.H.

    1988-04-01

    To determine whether abnormalities in regional cerebral functional activity estimated by iofetamine hydrochloride I 123 and single photon emission computed tomography can be detected in mild or moderate as well as severe cases of Alzheimer's disease (AD), we performed iofetamine I 123-single photon emission computed tomography in 37 patients with probable AD (nine patients with mild, 18 patients with moderate, and ten patients with severe dementia) and nine age-matched control subjects. Iofetamine I 123 uptake was measured in right and left frontal, temporal, parietal, and occipital cortices. Mean (right and left) iofetamine I 123 activity was lowest in the parietal region of patients with AD and was significantly reduced in the other three regions compared with control subjects. Only in the parietal region was lower relative iofetamine I 123 activity associated with an impaired level of patient function and with cognitive deficit.

  14. Comparison of Risk Factors and Disease Severity Between Old and Young Patients With Gastroesophageal Reflux Disease

    PubMed Central

    Lee, Shou-Wu; Lee, Teng-Yu; Lien, Han-Chung; Yeh, Hong-Zen; Chang, Chi-Sen; Ko, Chung-Wang

    2013-01-01

    Background Gastroesophageal reflux disease (GERD) tends to relapse and develop complications. The aim of the study was to compare the risk factors and disease severity of GERD in young and old patients. Methods Data from patients with GERD were collected between January and November 2009. The enrolled cases were assigned to the younger group if they were below 65 years, or the elderly group if 65 years or older. The general demographic data, lifestyle characteristics and endoscopic findings of the two groups were compared. Results Among all enrolled 111 patients, 78 and 33 patients were classified in the younger and elderly groups, respectively. The elderly group had significantly more men than the younger group did (72.7% vs 39.7%, P = 0.001). Lower rates of smoking (3% vs 6.4%, P = 0.029) and tea drinking (21.3% vs 34.6%, P = 0.001) were noted in the elderly patients, but similar rates of alcohol and coffee drinking. There were more severe esophagitis, esophagocardiac junction (ECJ) ulcers (21.2% vs. 2.6%, P = 0.003) and hiatal hernia (36.4% vs 16.9%, P = 0.025) in the elderly group. Conclusion Elderly GERD patients were more likely to be male, and having severe esophagitis, but lower rates of cigarette smoking and tea drinking, than those of younger patients.

  15. Obesity as a Risk and Severity Factor in Rheumatic Diseases (Autoimmune Chronic Inflammatory Diseases)

    PubMed Central

    Gremese, Elisa; Tolusso, Barbara; Gigante, Maria Rita; Ferraccioli, Gianfranco

    2014-01-01

    The growing body of evidence recognizing the adipose tissue (AT) as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low-grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the AT on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases. PMID:25426122

  16. Inflammatory markers of disease severity in acute pancreatitis.

    PubMed

    Papachristou, Georgios I; Whitcomb, David C

    2005-03-01

    To date, CRP remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinico-physiological scores and CRP provides good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data supporting the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than seven, IL-6 at the time of admission, and urine TAP, urine trypsinogen-2,and serum PMN-elastase at 24 hours (Box 1). These markers will only be able to help the clinician's predictive ability if they can be performed locally and if the results can be available in a timely manner. Future research should focus on markers such as procalcitonin, IL-8, IL-I ra, sTNFR,CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward.

  17. The impact of base excision DNA repair in age-related neurodegenerative diseases.

    PubMed

    Leandro, Giovana S; Sykora, Peter; Bohr, Vilhelm A

    2015-06-01

    The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited back-up DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases.

  18. MicroRNAs in age-related diseases.

    PubMed

    Dimmeler, Stefanie; Nicotera, Pierluigi

    2013-02-01

    Aging is a complex process that is linked to an increased incidence of major diseases such as cardiovascular and neurodegenerative disease, but also cancer and immune disorders. MicroRNAs (miRNAs) are small non-coding RNAs, which post-transcriptionally control gene expression by inhibiting translation or inducing degradation of targeted mRNAs. MiRNAs target up to hundreds of mRNAs, thereby modulating gene expression patterns. Many miRNAs appear to be dysregulated during cellular senescence, aging and disease. However, only few miRNAs have been so far linked to age-related changes in cellular and organ functions. The present article will discuss these findings, specifically focusing on the cardiovascular and neurological systems.

  19. Urinary symptoms: prevalence and severity in British men aged 55 and over.

    PubMed Central

    Hunter, D J; McKee, C M; Black, N A; Sanderson, C F

    1994-01-01

    OBJECTIVE--To measure the prevalence and severity of urinary symptoms among men aged 55 and over in the British population. DESIGN--Cross sectional population survey using a postal questionnaire. SETTING--North West Thames health region. SUBJECTS--1480 men aged 55 years and over randomly selected from 8 general practices. MAIN OUTCOME MEASURES--Self reported frequency and severity of urinary symptoms, their bothersomeness and previous prostate surgery. RESULTS--The response rate among eligible subjects was 78%. The prevalence of moderate and severe symptoms was 204 per 1000, rising from 160 per 1000 in the 55-59 age group to 259 per 1000 in the 70-74 age group and declining after the age of 80 to 119 per thousand in the 85+ age group. Twelve per cent of men reported previous prostate surgery, and the probability of having had surgery increases steadily with age. About a third of those undergoing surgery have recurrence or persistence of symptoms after surgery. Of men with moderate and severe symptoms, 27.9% reported that their symptoms were a medium or big problem, 36.9% reported that their symptoms interfered with their daily activities at least some of the time, and 43.1% were unhappy or 'felt terrible' about the prospect of a future with their current symptoms. CONCLUSION--The prevalence of urinary symptoms in men is lower than previously reported, although there is a substantial number of men who are bothered by, or who find their lives adversely effected by them. PMID:7830011

  20. Severe outbreak of disease in the southern chamois (Rupicapra pyrenaica) associated with border disease virus infection.

    PubMed

    Marco, Ignasi; Lopez-Olvera, Jorge Ramon; Rosell, Rosa; Vidal, Enric; Hurtado, Ana; Juste, Ramon; Pumarola, Marti; Lavin, Santiago

    2007-02-25

    An outbreak of a previously unreported disease affecting southern chamois (Rupicapra pyrenaica) in the central Pyrenees (NE Spain) was recorded in 2001 and 2002. There was a marked temporal distribution, most animals being found between February and June. After the outbreak, the population was found to have decreased by about 42%, most probably due to the disease. We examined 20 affected chamois. Clinical manifestations included depression, weakness and movement difficulties in all cases. Three chamois presented abnormal behaviour, with absence of flight reaction, and 16 showed different degrees of alopecia with skin hyperpigmentation. At necropsy cachexia was observed in all animals, four chamois had abscesses in different parts of the body, four had pneumonia, one had an extensive subcutaneous infection on the head and neck and one had severe orchitis. Microscopic lesions were found in the brain, mainly edema, gliosis, espongiosis, cariorrexis and neuronal multifocal necrosis. A perivascular mononuclear inflammatory infiltrate was present in three of them. Skin lesions included marked follicular atrophy, mild to moderate epidermal hyperplasia with orthokeratotic hyperkeratosis and follicular hyperkeratosis, and hypermelanosis. In 13 chamois there were haemosiderin deposits in the spleen, and in three individuals kidney "cloissone" was observed. Intraeritrocitic parasites were detected either by direct observation or PCR in 8 of 17 chamois. A pestivirus was isolated and detected by RT-PCR from 12 of 13 affected chamois and antigenic characterized as border disease virus by monoclonal antibodies. This is the first time a border disease virus has been associated with an outbreak of a high-mortality disease in a wild species.

  1. Falls Among Persons Aged ≥65 Years With and Without Severe Vision Impairment - United States, 2014.

    PubMed

    Crews, John E; Chou, Chiu-Fung; Stevens, Judy A; Saaddine, Jinan B

    2016-05-06

    In 2014, an estimated 2.8 million persons aged ≥65 years in the United States reported severe vision impairment* defined as being blind or having severe difficulty seeing, even with eyeglasses. Good vision is important for maintaining balance as well as for identifying low-contrast hazards, estimating distances, and discerning spatial relationships. Conversely, having poor vision increases the risk for falls (1,2). Falls among older adults are common and can cause serious injuries, disabilities, and premature death (1,3). To date, no state-level investigations have examined the annual prevalence of falls among persons with and without severe vision impairment. CDC analyzed data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) to estimate the state-specific annual prevalence of falls among persons aged ≥65 years with and without self-reported severe vision impairment. Overall, 46.7% of persons with, and 27.7% of older adults without, self-reported severe vision impairment reported having fallen during the previous year. The state-specific annual prevalence of falls among persons aged ≥65 years with severe vision impairment ranged from 30.8% (Hawaii) to 59.1% (California). In contrast, the prevalence of falls among persons aged ≥65 years without severe vision impairment ranged from 20.4% (Hawaii) to 32.4% (Alaska). Developing fall-prevention interventions intended for persons with severe vision impairment will help states manage the impact of vision impairment and falls on health care resources, and can inform state-specific fall prevention initiatives.

  2. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    PubMed

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  3. Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

    PubMed Central

    Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M.; Gaetano, Carlo

    2013-01-01

    Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. PMID:23989608

  4. Impact of severe disease caused by respiratory syncytial virus in children living in developed countries.

    PubMed

    Simoes, Eric A; Carbonell-Estrany, Xavier

    2003-02-01

    Among industrialized nations, the rate of rehospitalization in the United States for respiratory syncytial virus (RSV) is approximately 30 per 1000, exceptions being noted for American Indians and Alaskan natives, two ethnic groups who tend toward higher rates of RSV hospitalization. In distinction Japan reports an admission rate of 60 per 1000 for RSV disease. Yet Japan ranks considerably lower than many of its western counterparts in premature births. Whether an RSV subtype, a new viral genotype or some other unifying characteristic exists that might explain the severity of adenovirus, parainfluenza and RSV infections in this region of Asia remains to be determined. Outcomes trials in the United States, Canada, United Kingdom, Denmark and Japan all identified crowding and exposure to tobacco smoke as significant and independent risk factors for disease severity of RSV. The epidemiology of RSV is largely consistent throughout Europe, with peak outbreaks occurring in December and January. In Europe RSV accounts for 42 to 45% of hospital admissions for lower respiratory tract infections in children younger than 2 years of age, and inpatient populations tend to be younger and to experience greater disease severity. For RSV bronchiolitis lengths of stay in European hospitals range from a low of 4 days to a high of 10 days. The Infección Respiratoria Infantil por Virus Respiratorio Sincitial Study Group in Spain conducted 2 prospective observational studies in 14 and 26 neonatal units, respectively, on nonprophylaxed neonates to determine hospitalization rates for respiratory syncytial viral illness during 2 consecutive RSV seasons. Throughout each respiratory season the study group followed premature infants of < or =32 weeks gestational age at birth, representing an annual birth cohort of approximately 100 000 infants. A total of 584 infants who were < or =32 weeks gestational age in the first season and 999 in the second season were followed at monthly intervals

  5. Relationship of Age, Body Mass Index, Wrist and Waist Circumferences to Carpal Tunnel Syndrome Severity

    PubMed Central

    KOMURCU, Hatice Ferhan; KILIC, Selim; ANLAR, Omer

    2014-01-01

    Carpal tunnel syndrome (CTS) has a multifactorial etiology involving systemic, anatomical, idiopathic, and ergonomic characteristics. In this study, an investigation of the relationship between the CTS degree established by electrophysiological measurements in patients with clinical CTS prediagnosis, and age, gender, body mass index (BMI), hand wrist circumference, and waist circumference measurements has been done. On 547 patients included in the study, motor and sensory conduction examinations of the median and ulnar nerve were done on one or two upper extremities thought to have CTS. In terms of CTS severity, the patients were divided into four groups (normal, mild, medium, and severe CTS). A total of 843 electrophysiological examinations were done consisting of 424 on the right hand wrist and 419 on the left hand wrist. When the age group of 18–35 years is taken as the reference group, the CTS development risk independent of BMI has been found to have increased by a factor of 1.86 for ages 36–64 years, and by 4.17 for ages 65 years and higher after adjustment for BMI. With respect to normal degree CTS group, the BMI were significantly different in groups with mild, medium, and severe CTS. The waist circumferences of groups with mild, medium, and severe CTS severity were found to be significantly higher in comparison to the normal reference group. When this value was corrected with BMI and re-examined the statistically significant differences persisted. The study identified a significant relationship between the CTS severity and age, BMI, waist circumference. PMID:24257492

  6. Relationship of age, body mass index, wrist and waist circumferences to carpal tunnel syndrome severity.

    PubMed

    Komurcu, Hatice Ferhan; Kilic, Selim; Anlar, Omer

    2014-01-01

    Carpal tunnel syndrome (CTS) has a multifactorial etiology involving systemic, anatomical, idiopathic, and ergonomic characteristics. In this study, an investigation of the relationship between the CTS degree established by electrophysiological measurements in patients with clinical CTS prediagnosis, and age, gender, body mass index (BMI), hand wrist circumference, and waist circumference measurements has been done. On 547 patients included in the study, motor and sensory conduction examinations of the median and ulnar nerve were done on one or two upper extremities thought to have CTS. In terms of CTS severity, the patients were divided into four groups (normal, mild, medium, and severe CTS). A total of 843 electrophysiological examinations were done consisting of 424 on the right hand wrist and 419 on the left hand wrist. When the age group of 18-35 years is taken as the reference group, the CTS development risk independent of BMI has been found to have increased by a factor of 1.86 for ages 36-64 years, and by 4.17 for ages 65 years and higher after adjustment for BMI. With respect to normal degree CTS group, the BMI were significantly different in groups with mild, medium, and severe CTS. The waist circumferences of groups with mild, medium, and severe CTS severity were found to be significantly higher in comparison to the normal reference group. When this value was corrected with BMI and re-examined the statistically significant differences persisted. The study identified a significant relationship between the CTS severity and age, BMI, waist circumference. PMID:24257492

  7. Prevalence and Severity of Oral Diseases in the Africa and Middle East Region.

    PubMed

    Abid, A; Maatouk, F; Berrezouga, L; Azodo, C; Uti, O; El-Shamy, H; Oginni, A

    2015-07-01

    This review aims to determine the prevalence and severity of oral health diseases in the Africa and Middle East region (AMER). The profile of oral diseases is not homogeneous across the AMER. There are large disparities between groups. Reliable data are scarce. The prevalence and severity of oral diseases appear to be increasing in the African region, as does associated morbidity. There are substantial differences in inequalities in oral health. Dental caries prevalence is less severe in most African countries than in developed countries, but the high rate of untreated caries reflects the limited resources available and difficulties of access and affordability to essential oral health care services. The prevalence of gingival inflammation is very high in all age groups in several African countries. The prevalence of maxillofacial trauma has increased in many countries, with a wide variation of the incidence and high prevalence of traumatic dental injuries in primary and permanent teeth. Orofacial clefts are among the most common birth defects. Annual incidence of oral cancer is estimated as 25 cases per 100,000 people in Africa. Noma is a major public health problem for the Middle East and North African (MENA) region. Data about human immunodeficiency virus/AIDS are limited, particularly in the MENA region. According to the World Health Organization Regional Committee for Africa report, some fundamental key basic knowledge gaps need to be underlined. They include inequalities in oral health, low priority for oral health, lack of adequate funding, inadequate dental student training, obstacles to medical and dental research, and poor databases. There are very few effective public prevention and oral health promotion programs in the AMER. Universal health coverage is not achievable without scientific research on the effectiveness of health promotion interventions.

  8. Age impact on autoimmune thyroid disease in females

    NASA Astrophysics Data System (ADS)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  9. Age Alterations in Extent and Severity of Experimental Intranasal Infection with Chlamydophila pneumoniae in BALB/c Mice

    PubMed Central

    Little, C. Scott; Bowe, Andrew; Lin, Richard; Litsky, Jason; Fogel, Robert M.; Balin, Brian J.; Fresa-Dillon, Kerin L.

    2005-01-01

    The intracellular bacterium Chlamydophila (“Chlamydia”) pneumoniae is a pathogen for several respiratory diseases and may be a factor in the pathogenesis of chronic diseases of aging including atherosclerosis and Alzheimer's disease. We assessed whether aging is coupled with increased burden of infection in BALB/c mice after intranasal infection by C. pneumoniae. Six- and twenty-month-old BALB/c mice were infected intranasally with 5 × 104 inclusion forming units (IFU) or 5 × 105 IFU of C. pneumoniae. Lung, brain, and heart tissue were analyzed for infectious C. pneumoniae and for Chlamydophila antigen by immunohistochemistry. At both doses, aging was associated with a decreased proportion of animals that cleared infection from the lung and greater burden of infectious organism within the lung. We observed dose-dependent spread to the heart/ascending aorta in animals infected with C. pneumoniae. In mice given 5 × 104 IFU, spread to the heart by day 14 was only observed in old mice. By day 28, all animals inoculated with 5 × 104 IFU showed evidence of spread to the heart, although higher C. pneumoniae titers were observed in the hearts from old mice. In mice inoculated with 5 × 105 IFU, spread of C. pneumoniae to the heart was evident by day 14, with no discernible age effect. C. pneumoniae was also recovered from the central nervous system (brain and olfactory bulb) of all mice by day 28 postinfection, with higher C. pneumoniae titers in old animals than in young animals. Our results suggest that infection with C. pneumoniae may be more severe in old animals. PMID:15731073

  10. The Prevalence of Diabetes Mellitus in COPD Patients with Severe and Very Severe Stage of the Disease

    PubMed Central

    Stojkovikj, Jagoda; Zafirova-Ivanovska, Beti; Kaeva, Biserka; Anastasova, Sasha; Angelovska, Irena; Jovanovski, Smiljko; Stojkovikj, Dragana

    2016-01-01

    AIM: The aim of the study was to investigate the prevalence of diabetes mellitus in privies diagnosed chronic obstructive pulmonary disease (COPD) patients with severe and very severe disease, which ware stable. METHODS: We investigated 100 subjects, all of them smokers, with smoking status >10 years. They were stratified in two groups. It was clinical, randomized, cross sectional study. Besides demographic parameters, functional parameters, BMI, cholesterol, LDL and HDL, and the level of blood sugar was measured. RESULTS: The prevalence of diabetes mellitus in our survey in total number of COPD patients with severe and very severe stage was 21%. In the very severe group were recorded significantly higher average values of glycaemia compared with severe group (7.67 ± 3.7 vs. 5.62 ± 0.9, p = 0.018). In the group with severe COPD, it was not confirmed any factor with significant predictive effect on the values of glycaemia. As independent significant factors that affect blood glucose in a group of very severe COPD were confirmed cholesterol (p <0.0001) and HDL (p = 0.018). CONCLUSION: These results suggest that the presence of the COPD in patients itself is a factor that results in the clinical presentation of diabetes mellitus Type 2. PMID:27335596

  11. Risks of Death and Severe Disease in Patients With Middle East Respiratory Syndrome Coronavirus, 2012-2015.

    PubMed

    Rivers, Caitlin M; Majumder, Maimuna S; Lofgren, Eric T

    2016-09-15

    Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology. PMID:27608662

  12. In utero copper treatment for Menkes disease associated with a severe ATP7A mutation.

    PubMed

    Haddad, Marie Reine; Macri, Charles J; Holmes, Courtney S; Goldstein, David S; Jacobson, Beryl E; Centeno, Jose A; Popek, Edwina J; Gahl, Willam A; Kaler, Stephen G

    2012-09-01

    Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect. In an affected fetus whose parents found termination unacceptable and who understood the associated risks, we began in utero copper histidine treatment at 31.5 weeks gestational age. Copper histidine (900 μg per dose) was administered directly to the fetus by intramuscular injection (fetal quadriceps or gluteus) under ultrasound guidance. Percutaneous umbilical blood sampling enabled serial measurement of fetal copper and ceruloplasmin levels that were used to guide therapy over a four-week period. Fetal copper levels rose from 17 μg/dL prior to treatment to 45 μg/dL, and ceruloplasmin levels from 39 mg/L to 122 mg/L. After pulmonary maturity was confirmed biochemically, the baby was delivered at 35.5 weeks and daily copper histidine therapy (250 μg sc b.i.d.) was begun. Despite this very early intervention with copper, the infant showed hypotonia, developmental delay, and electroencephalographic abnormalities and died of respiratory failure at 5.5 months of age. The patient's ATP7A mutation (Q724H), which severely disrupted mRNA splicing, resulted in complete absence of ATP7A protein on Western blots. These investigations suggest that prenatally initiated copper replacement is inadequate to correct Menkes disease caused by severe loss-of-function mutations, and that postnatal ATP7A gene addition represents a rational approach in such circumstances.

  13. REST and stress resistance in ageing and Alzheimer's disease.

    PubMed

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X Shirley; Bennett, David A; Colaiácovo, Monica P; Yankner, Bruce A

    2014-03-27

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain. PMID:24670762

  14. REST and stress resistance in ageing and Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X. Shirley; Bennett, David A.; Colaiácovo, Monica P.; Yankner, Bruce A.

    2014-03-01

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.

  15. Neurological findings in Alzheimer's disease and normal aging.

    PubMed

    Galasko, D; Kwo-on-Yuen, P F; Klauber, M R; Thal, L J

    1990-06-01

    To determine the potential value of abnormal neurological findings as markers of Alzheimer's disease (AD) and their relationship to the stage of AD, we compared standardized neurological examinations in 135 community-dwelling patients with AD and 91 nondemented elderly individuals. After correcting for differences in age and education between the two groups, we found that rigidity, stooped posture, graphesthesia, neglect of simultaneous tactile stimuli (face-hand test), and snout, grasp, and glabella reflexes were present significantly more often in patients with AD than in control subjects. These findings increased in prevalence in patients with AD according to the severity of dementia. However, in a multivariate logistic regression model only the grasp reflex, graphesthesia, and the face-hand test were statistically significantly associated with the degree of cognitive impairment. Although abnormal neurological findings occur regularly in AD, they are too infrequent early in the course of AD to serve as diagnostic markers. Prospective studies are needed to determine whether patients with the early onset of extrapyramidal or other findings form a distinct subgroup of AD.

  16. Influence of age, previous health status, and severity of acute illness on outcome from intensive care.

    PubMed

    Le Gall, J R; Brun-Buisson, C; Trunet, P; Latournerie, J; Chantereau, S; Rapin, M

    1982-09-01

    Age, previous health status (HS), and severity of acute illness were assessed prospectively on 228 unselected patients admitted over 1 yr to the multidisciplinary ICU, to determine their influence on outcome. One hundred and fifty patients (66%) were discharged from the ICU, but the survival rate fell to 50% at 6 months, and was similar after 1 yr (49%). Over a 6-month period, there was improved HS in survivors which gradually leveled off. Compared to prior HS, the final HS was worsened in 37% of survivors. Three factors were important predictors of late survival: age under 50, good previous HS, and less than two visceral failures. We conclude that evaluation of ICU outcome should provide information on 6-month survival and HS and include important variables as age, previous HS, and severity of acute illness. PMID:7105766

  17. Comparison of disease-severity measures within severe and very severe COPD patients: results from a nationally representative chart review and patient survey

    PubMed Central

    Solem, Caitlyn T; Sun, Shawn X; Liu, Sizhu; Macahilig, Cynthia; Katyal, Monica; Gao, Xin; Shorr, Andrew F

    2014-01-01

    Objective This study aimed to compare spirometry- and risk + symptom-based classification systems to physician-based severity assessment and find which system is most predictive of patient-reported health status, as measured by the St George’s Respiratory Questionnaire for COPD (chronic obstructive pulmonary disease; SGRQ-C). Materials and methods In this chart review/patient survey, 99 physicians recruited patients with physician-assessed severe or very severe COPD who had recently experienced a moderate or severe exacerbation. A cross-tabulation was undertaken comparing physician report, spirometry (mild/moderate, forced expiratory volume in 1 second [FEV1] ≥50%; severe, 30% ≤ FEV1 <50%; very severe, FEV1 <30% predicted), and risk + symptom-based (A, low risk/fewer symptoms; B, low risk/more symptoms; C, high risk/fewer symptoms; D, high risk/more symptoms) severity systems. Analysis of covariance models were run for SGRQ-C, varying COPD-severity systems. Results Of 244 patients, 58.6% were severe and 34.8% very severe by physician report, 70% had FEV1 ≤50% at their most recent visit, and 86% fell into quadrant D. Spirometry and physician report had 57.4% agreement, with physicians often indicating higher severity. Physician report and risk + symptom agreement was high (81.2% severe/very severe and D). Physician-reported severity, risk + symptoms, exacerbations in the previous year, and symptoms were significant SGRQ-C predictors, while spirometry was not. Conclusion For recently exacerbating severe or very severe COPD patients, risk + symptoms more closely aligned with physician-reported severity and SGRQ-C versus spirometry. PMID:25284999

  18. Dementia Increases Severe Sepsis and Mortality in Hospitalized Patients With Chronic Obstructive Pulmonary Disease.

    PubMed

    Liao, Kuang-Ming; Lin, Tzu-Chieh; Li, Chung-Yi; Yang, Yea-Huei Kao

    2015-06-01

    Dementia increases the risk of morbidity and mortality in hospitalized patients. However, information on the potential effects of dementia on the risks of acute organ dysfunction, severe sepsis and in-hospital mortality, specifically among inpatients with chronic obstructive pulmonary disease (COPD), is limited. The observational analytic study was inpatient claims during the period from 2000 to 2010 for 1 million people who were randomly selected from all of the beneficiaries of the Taiwan National Health Insurance in 2000. In total, 1406 patients with COPD and dementia were admitted during the study period. Hospitalized patients with COPD and free from a history of dementia were randomly selected and served as control subjects (n = 5334). The patient groups were matched according to age (±3 years), gender, and the year of admission, with a control/dementia ratio of 4. Only the first-time hospitalization data for each subject was analyzed. Logistic regression models were used to calculate the odds ratio (OR) of outcome measures (acute organ dysfunction, severe sepsis, and mortality), controlling for confounding factors (age, sex, comorbidity, infection site, hospital level, and length of stay). In COPD patients with dementia, the incidence rate of severe sepsis and hospital mortality was 17.1% and 4.8%, respectively, which were higher than the controls (10.6% and 2.3%). After controlling for potential confounding factors, dementia was found to significantly increase the odds of severe sepsis and hospital mortality with an adjusted OR (OR) of 1.38 (95% confidence interval [CI] 1.10-1.72) and 1.69 (95% CI 1.18-2.43), respectively. Dementia was also significantly associated with an increased OR of acute respiratory dysfunction (adjusted OR 1.39, 95% CI 1.09-1.77). In hospitalized COPD patients, the presence of dementia may increase the risks of acute respiratory dysfunction, severe sepsis, and hospital mortality, which warrants the attention of health care

  19. Connective tissue diseases, multimorbidity and the ageing lung.

    PubMed

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients.

  20. Perspective: Does brown fat protect against diseases of aging?

    PubMed

    Mattson, Mark P

    2010-01-01

    The most commonly studied laboratory rodents possess a specialized form of fat called brown adipose tissue (BAT) that generates heat to help maintain body temperature in cold environments. In humans, BAT is abundant during embryonic and early postnatal development, but is absent or present in relatively small amounts in adults where it is located in paracervical and supraclavicular regions. BAT cells can 'burn' fatty acid energy substrates to generate heat because they possess large numbers of mitochondria in which oxidative phosphorylation is uncoupled from ATP production as a result of a transmembrane proton leak mediated by uncoupling protein 1 (UCP1). Studies of rodents in which BAT levels are either increased or decreased have revealed a role for BAT in protection against diet-induced obesity. Data suggest that individuals with low levels of BAT are prone to obesity, insulin resistance and cardiovascular disease, whereas those with higher levels of BAT maintain lower body weights and exhibit superior health as they age. BAT levels decrease during aging, and dietary energy restriction increases BAT activity and protects multiple organ systems including the nervous system against age-related dysfunction and degeneration. Future studies in which the effects of specific manipulations of BAT levels and thermogenic activity on disease processes in animal models (diabetes, cardiovascular disease, cancers, neurodegenerative diseases) are determined will establish if and how BAT affects the development and progression of age-related diseases. Data from animal studies suggest that BAT and mitochondrial uncoupling can be targeted for interventions to prevent and treat obesity and age-related diseases. Examples include: diet and lifestyle changes; specific regimens of mild intermittent stress; drugs that stimulate BAT formation and activity; induction of brown adipose cell progenitors in muscle and other tissues; and transplantation of brown adipose cells.

  1. Diseases of Old Age in Two Paintings by Rembrandt

    PubMed Central

    Weisz, George M.; Albury, William R.

    2015-01-01

    Two paintings of older men by Rembrandt (1609–1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person’s response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt’s own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject’s foot and the second involving the subject’s hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age. PMID:26886771

  2. Diseases of Old Age in Two Paintings by Rembrandt.

    PubMed

    Weisz, George M; Albury, William R

    2015-10-26

    Two paintings of older men by Rembrandt (1609-1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person's response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt's own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject's foot and the second involving the subject's hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age.

  3. Severity of brain injury following neonatal extracorporeal membrane oxygenation and outcome at age 5 years.

    PubMed

    Glass, P; Bulas, D I; Wagner, A E; Rajasingham, S R; Civitello, L A; Papero, P H; Coffman, C E; Short, B L

    1997-07-01

    Neurodevelopmental evaluation in childhood provides an opportunity to study complex neurological compensation following documented neonatal brain injury, and furnishes important clinical information which may have an impact on patient care. We studied 152 term children treated with extracorporeal membrane oxygenation (ECMO) as neonates and who received routine neonatal neuroimaging and comprehensive neurodevelopmental evaluation at age 5 years. The cohort was divided into four groups based on an independent neuroimaging score: No lesion, N=88; Mild lesion, N=38; Moderate lesion, N=12; and Severe lesion, N=14. Standardized testing at age 5 included complete neuropsychological assessment, neurological evaluation, and assessment of motor function. All testing was conducted without knowledge of the neuroimaging score. The occurrence of disability by severity of neuroimaging was: No lesion=10%; Mild=13%; Moderate=33%; Severe=57%. The relative risk within the ECMO population for disability at age 5 after moderate or severe neonatal lesion was 4.3 (CI=1.0 to 17.5) and 11.7 (CI=3.3 to 41.3), respectively. The remaining non-disabled children who had moderate to severe lesions functioned within normal limits. Severity of neonatal neuroimaging was inversely associated with IQ scores, pre-academic skills, and neuromotor function. The effect size was small but the rank order was predictable. Our data identify in 5-year-old children an impact of brain lesion severity demonstrated on routine neonatal neuroimaging. The results indicate potential compensation following moderate and severe lesions, and suggest a subtle but consistent influence of even mild neonatal brain injury.

  4. Emerging role of autophagy in kidney function, diseases and aging.

    PubMed

    Huber, Tobias B; Edelstein, Charles L; Hartleben, Björn; Inoki, Ken; Jiang, Man; Koya, Daisuke; Kume, Shinji; Lieberthal, Wilfred; Pallet, Nicolas; Quiroga, Alejandro; Ravichandran, Kameswaran; Susztak, Katalin; Yoshida, Sei; Dong, Zheng

    2012-07-01

    Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy. PMID:22692002

  5. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

    PubMed

    Maessen, Dionne E M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2015-06-01

    The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

  6. Estimation of plant disease severity visually, by digital photography and image analysis, and by hyperspectral imaging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reliable, precise and accurate estimates of disease severity are important for predicting yield loss, monitoring and forecasting epidemics, for assessing crop germplasm for disease resistance, and for understanding fundamental biological processes including co-evolution. In some situations poor qual...

  7. Cellular Senescence and the Biology of Aging, Disease, and Frailty.

    PubMed

    LeBrasseur, Nathan K; Tchkonia, Tamara; Kirkland, James L

    2015-01-01

    Population aging simultaneously highlights the remarkable advances in science, medicine, and public policy, and the formidable challenges facing society. Indeed, aging is the primary risk factor for many of the most common chronic diseases and frailty, which result in profound social and economic costs. Population aging also reveals an opportunity, i.e. interventions to disrupt the fundamental biology of aging could significantly delay the onset of age-related conditions as a group, and, as a result, extend the healthy life span, or health span. There is now considerable evidence that cellular senescence is an underlying mechanism of aging and age-related conditions. Cellular senescence is a process in which cells lose the ability to divide and damage neighboring cells by the factors they secrete, collectively referred to as the senescence-associated secretory phenotype (SASP). Herein, we discuss the concept of cellular senescence, review the evidence that implicates cellular senescence and SASP in age-related deterioration, hyperproliferation, and inflammation, and propose that this underlying mechanism of aging may play a fundamental role in the biology of frailty. PMID:26485647

  8. 326 Lung Age/Chronological Age Index as Indicator of Clinical Improvement or Severity in Asthma Patients

    PubMed Central

    Castrejon-Vázquez, Isabel; Vargas, Maria Eugenia; Sabido, Raúl Cicero; Tapía, Jorge Galicia

    2012-01-01

    Background Spirometry is a very useful clinical test to evaluate pulmonary function in asthma. However pulmonary function could be affected by the sex, time of clinical evolution, lung age (LA) and chronological age (CA). The aim of this study was to evaluate LA/CA as index of clinical improvement or severity in asthma patients. Methods The tenets of the Declaration of Helsinki were followed, and all patients gave their informed consent to participate in this study. Asthma severity was evaluated according with GINA classification. Spirometry was performed at the beginning of this study, at 46 days, 96 days, 192 days and after 8 months. Statistical analysis was performed using t test, 2-way ANOVA test, correlation and multiple regression models as well as ROC curves were also performed, a P < 0.05 was considered as significant. Results 70 asthma patients were included (22 male and 48 female), mean CA was 35-years old; mean LA was 48-years with a LA/CA index = 1.4, time of clinical evolution was 13 years. A LA/CA index = 1 (range 0.5 to 0.9) was observed in asymptomatic patients. LA/CA index over 1 were related with airway inflammation, and a LA/CA index more than 2 correlated with GINA step 3. Interestingly when we analyzed CA and LA, we observed that in female group more than 10 years of difference between CA and LA, (GINA Step2 and 3); while in male we observed (GINA Step1, Step2 and Step3). LA/CA index ≤ 1 was considered as normal. Conclusions LA/CA index is a good as clinical indicator of clinical improvement or severity in asthma patients in with excellent correlation of pulmonary function and age.

  9. Childhood Misfortune as a Threat to Successful Aging: Avoiding Disease

    ERIC Educational Resources Information Center

    Schafer, Markus H.; Ferraro, Kenneth F.

    2012-01-01

    Purpose: The purpose of this study was to examine whether childhood misfortune reduces the likelihood of being disease free in adulthood. Design and Methods: This article used a sample of 3,000+ American adults, aged 25-74, who were first interviewed in 1995 and reinterviewed in 2005. Logistic regression was used to estimate the odds of avoiding…

  10. Aged and Diseased Neurons Get Lost in Transport.

    PubMed

    Tamburrino, Anna; Decressac, Mickael

    2016-04-01

    The maintenance of nucleocytoplasmic compartmentalization is essential for proper cellular function. Recent studies from the Gage and the Hipp labs report impairments in transport across the nuclear envelope in models of normal and pathological neuronal senescence, providing a mechanistic link between cerebral aging and neurodegenerative diseases. PMID:26970902

  11. Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

    PubMed Central

    Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z. M.; Murray, Toby B. J.; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J.; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W.; Garden, O. James; Iredale, John P.; Uings, Iain J.; Liddle, John; Wright, Wayne L.; Dukes, George; Webster, Scott P.; Mole, Damian J.

    2016-01-01

    Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction. PMID:27669975

  12. Symptom cluster, healthcare use and mortality in patients with severe chronic obstructive pulmonary disease

    PubMed Central

    Park, Soo Kyung; Larson, Janet L

    2014-01-01

    Aims and objectives To examine how subgroups of patients with chronic obstructive pulmonary disease, identified by ratings of symptoms (dyspnoea, anxiety, depression and fatigue), affect healthcare use and mortality. Background People with chronic obstructive pulmonary disease often experience multiple symptoms. The importance of multiple symptoms and symptom clusters has received increased attention. However, little is known about symptom clusters and their effect on healthcare use and mortality in this population. Design Descriptive cross-sectional study. Methods This secondary data analysis used data from the National Emphysema Treatment Trial. Participants (n = 597) had severe chronic obstructive pulmonary disease. Descriptive and inferential statistics were used to analyse the data that were drawn from structured interviews, questionnaires and clinical measures. Results Three subgroup clusters emerged based on four symptom ratings. Mean age, proportion with higher education, proportion using oxygen, disease severity, exercise capacity and quality of life differed significantly between subgroups. Participants with high levels of symptoms used healthcare services more and were more likely to have died at the five-year follow-up than those with low levels of symptoms. Symptom cluster subgroups had more significant relationship with mortality than single symptoms. Conclusion Patients with high levels of symptoms require greater clinical attention. Relevance to clinical practice Understanding subgroups of patients, based on symptom ratings and their adverse effect on outcomes, may enable healthcare providers to assess multiple symptoms and identify subgroups of patients at risk of increased healthcare use and mortality. Targeting modifiable symptoms within the cluster may be more beneficial than focusing on a single symptom for certain health-related outcome. PMID:24460846

  13. Infectious disease burden and cognitive function in young to middle-aged adults.

    PubMed

    Gale, Shawn D; Erickson, Lance D; Berrett, Andrew; Brown, Bruce L; Hedges, Dawson W

    2016-02-01

    Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults. PMID:26598104

  14. Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

    PubMed

    Williams, K; Andrie, K; Cartoceti, A; French, S; Goldsmith, D; Jennings, S; Priestnall, S L; Wilson, D; Jutkowitz, A

    2016-07-01

    Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH.

  15. NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?

    PubMed Central

    Sahoo, Sanghamitra; Meijles, Daniel N.; Pagano, Patrick J.

    2016-01-01

    Reactive oxygen species (ROS) and oxidative stress have long been linked to aging and diseases prominent in the elderly such as hypertension, atherosclerosis, diabetes and atrial fibrillation (AF). NADPH oxidases (Nox) are a major source of ROS in the vasculature and are key players in mediating redox signalling under physiological and pathophysiological conditions. In this review, we focus on the Nox-mediated ROS signalling pathways involved in the regulation of ‘longevity genes’ and recapitulate their role in age-associated vascular changes and in the development of age-related cardiovascular diseases (CVDs). This review is predicated on burgeoning knowledge that Nox-derived ROS propagate tightly regulated yet varied signalling pathways, which, at the cellular level, may lead to diminished repair, the aging process and predisposition to CVDs. In addition, we briefly describe emerging Nox therapies and their potential in improving the health of the elderly population. PMID:26814203

  16. Female twins with severe Christmas disease (hemophilia B).

    PubMed

    Wollina, K; Bowen, D J; Syrbe, G; Zintl, F

    1993-11-15

    Hemophilia B is an X-linked bleeding disorder. We report on female twins, who were conspicious in prolonged bleeding after venipuncture as well as hematomas after intramuscular injections even in the first months of their life. Their father suffering from a severe hemophilia B deceased in 1992. Their mother, half-brother and grandmother from their father's side had no signs of bleeding disorders. Clotting analysis performed in both twins revealed a markedly prolonged partial thromboplastin time (> 100 s). The factor IX levels were below 2%. In order to detect mutations, a general screen using the polymerase chain reaction (PCR) followed by single strand conformation polymorphism (SSCP) analysis of the PCR products have been performed. PCR products have been cut into smaller fragments using restriction endonucleases (RE) for an in-depth SSCP screen. A general screen for gross abnormalities in the factor IX gene including deletions, insertions and rearrangements was performed by Southern blot analysis of RE-digests of genomic DNA using the factor IX cDNA as a hybridization probe. Furthermore, we screened for mutations in the CG dinucleotides comprising part of RE-recognition sequences (exon 1, 2, 3, 4, 5, and 8). By all methods applied herein, no mutations have been detected in these twins. On the basis of our results the hemophilia B of these twins might be explained by extreme non-random lyonization.

  17. Proteomic profiling reveals a severely perturbed protein expression pattern in aged skeletal muscle.

    PubMed

    O'Connell, Kathleen; Gannon, Joan; Doran, Philip; Ohlendieck, Kay

    2007-08-01

    Extended longevity is often accompanied by frailty and increased susceptibility to a variety of crippling disorders. One of the most striking features of human aging is sarcopenia, which is defined as the age-related decline in skeletal muscle mass and strength. Although various metabolic and functional defects in aging muscle fibres have been described over the last decade, it is not known whether a pathophysiological hierarchy exists within degenerative pathways leading to muscle wasting. Hence, in order to identify novel biomarkers of age-dependent skeletal muscle degeneration, we have here applied mass spectrometry-based proteomics for studying global muscle protein expression patterns. As a model system of sarcopenia, we have employed crude extracts from senescent rat gastrocnemius muscle, as compared to young adult tissue preparations. Using the highly sensitive protein dye Deep Purple for the analysis of the 2-D separated muscle proteome and peptide mass fingerprinting for the identification of individual protein spots, a differential expression pattern was observed for contractile proteins, metabolic factors, regulatory components and heat shock elements. A drastic increase was shown for alpha B-crystallin, myosin light chain MLC-1, phosphoglycerate kinase, adenylate kinase, triosephosphate isomerase, albumin, aconitase and nucleoside-diphosphate kinase in aged fibres. In contrast, the expression of pyruvate kinase, aldolase, creatine kinase, transferrin, alpha-tropomyosin and myosin light chain MLC-3 was decreased in old skeletal muscle. Comparative 2-D immunoblotting of selected candidate proteins has confirmed the effect of aging on the skeletal muscle proteome. These findings demonstrate a severely perturbed protein expression pattern in aged skeletal muscle, which reflects the underlying molecular alterations causing a drastic decline of muscle strength in the senescent organism. In the long-term, the systematic deduction of abnormal protein expression

  18. Optic Nerve Head Biomechanics in Aging and Disease

    PubMed Central

    Downs, J. Crawford

    2015-01-01

    This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. PMID:25819451

  19. Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

    PubMed Central

    Smith, J. A.; Leonardi, T.; Huang, B.; Iraci, N.; Vega, B.; Pluchino, S.

    2015-01-01

    Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs—or specific EV cargoes—are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases. PMID:24973266

  20. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.

    PubMed

    Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID:26872349

  1. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.

    PubMed

    Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging.

  2. Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease

    PubMed Central

    Dai, Dao-Fu; Chen, Tony; Johnson, Simon C.; Szeto, Hazel

    2012-01-01

    Abstract Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several “anti-aging” strategies that treat CVDs and improve healthy cardiac aging. PMID:22229339

  3. Impact of anthropometric measures and serum leptin on severity of gastroesophageal reflux disease.

    PubMed

    Abdelkader, N A; Montasser, I F; Bioumy, E E; Saad, W E

    2015-10-01

    The aim of this prospective study was to evaluate the impact of obesity, determined by different anthropometric measures, on clinical and endoscopic severity of GERD and the relation between serum leptin and clinical and endoscopic severity of GERD in Egyptian patients. The study was carried out at Ain Shams University Hospitals and Theodor Bilharz Research Institute, Cairo, Egypt. A total of 60 patients with clinically and endoscopically evident gastroesophageal reflux disease (GERD) were enrolled in this study as well as 20 healthy subjects matched for age and gender serving as the control group. Patients were divided according to their body mass index (BMI) into two groups: group 1 (n = 30): overweight and obese (BMI ≥ 25 and/or waist-to-height ratio [WHtR] ≥ 0.5) and group 2 (n = 30): normal weight (BMI ≥ 18 to < 25 and/or WHtR ≥ 0.4 to < 0.5). Upper gastrointestinal endoscopy, anthropometric measures, and symptom severity score questionnaire were done for all patients. Serum leptin hormone was assessed for patients and control groups.The evidence revealed statistically significant difference between the two groups in terms of different anthropometric measures (P < 0.00) except the height (P < 0.9), abdominal fat depot equations (P < 0.00), endoscopic findings according to Los Angeles classification (P < 0.001), symptom severity score (P < 0.00), and serum leptin hormone (43.96 ± 23.50 in group 1 vs. 7.5133 ± 8.18294 in group 2 and 6.98 ± 5.90 in the control group) (P = 0.00). Obesity in general and central (abdominal) obesity specifically has significant impact on clinical and endoscopic severity of GERD. Increased leptin hormone level is associated with clinical and endoscopic severity of GERD. Future trial on larger number of patients is emphasized.

  4. Severe Aortic Stenosis Associated with Unicommissural Unicuspid Aortic Valve in a Middle Aged Male

    PubMed Central

    Kwon, Hee-Jin; Kim, Song Soo; Sun, Byung Joo; Jin, Sun Ah; Kim, Jun-Hyung; Lee, Jae-Hwan; Choi, Siwan; Jeong, Jin-Ok; Seong, In-Whan

    2016-01-01

    Unicuspid aortic valve (UAV) is an extremely rare form of congenital aortic valvular abnormality. Although UAV shows similar clinical characteristics to bicuspid aortic valve, the clinical symptoms develop at earlier age and progress at a faster pace in UAV. In this report, we are presenting a 42-year-old male with severe aortic stenosis associated with unicommissural UAV. The patients underwent a successful Bentall operation. PMID:27721957

  5. The Biology of Proteostasis in Aging and Disease

    PubMed Central

    Labbadia, Johnathan; Morimoto, Richard I.

    2015-01-01

    Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases. PMID:25784053

  6. The Immunoproteasome in oxidative stress, aging, and disease.

    PubMed

    Johnston-Carey, Helen K; Pomatto, Laura C D; Davies, Kelvin J A

    2015-01-01

    The Immunoproteasome has traditionally been viewed primarily for its role in peptide production for antigen presentation by the major histocompatibility complex, which is critical for immunity. However, recent research has shown that the Immunoproteasome is also very important for the clearance of oxidatively damaged proteins in homeostasis, and especially during stress and disease. The importance of the Immunoproteasome in protein degradation has become more evident as diseases characterized by protein aggregates have also been linked to deficiencies of the Immunoproteasome. Additionally, there are now diseases defined by mutations or polymorphisms within Immunoproteasome-specific subunit genes, further suggesting its crucial role in cytokine signaling and protein homeostasis (or "proteostasis"). The purpose of this review is to highlight our growing understanding of the importance of the Immunoproteasome in the management of protein quality control, and the detrimental impact of its dysregulation during disease and aging. PMID:27098648

  7. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model

    PubMed Central

    Bebee, Thomas W.; Dominguez, Catherine E.; Samadzadeh-Tarighat, Somayeh; Akehurst, Kristi L.; Chandler, Dawn S.

    2012-01-01

    Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease associated with low levels of the essential survival motor neuron (SMN) protein. Reduced levels of SMN is due to the loss of the SMN1 gene and inefficient splicing of the SMN2 gene caused by a C>T mutation in exon 7. Global analysis of the severe SMNΔ7 SMA mouse model revealed altered splicing and increased levels of the hypoxia-inducible transcript, Hif3alpha, at late stages of disease progression. Severe SMA patients also develop respiratory deficiency during disease progression. We sought to evaluate whether hypoxia was capable of altering SMN2 exon 7 splicing and whether increased oxygenation could modulate disease in a severe SMA mouse model. Hypoxia treatment in cell culture increased SMN2 exon 7 skipping and reduced SMN protein levels. Concordantly, the treatment of SMNΔ7 mice with hyperoxia treatment increased the inclusion of SMN2 exon 7 in skeletal muscles and resulted in improved motor function. Transfection splicing assays of SMN minigenes under hypoxia revealed that hypoxia-induced skipping is dependent on poor exon definition due to the SMN2 C>T mutation and suboptimal 5′ splice site. Hypoxia treatment in cell culture led to increased hnRNP A1 and Sam68 levels. Mutation of hnRNP A1-binding sites prevented hypoxia-induced skipping of SMN exon 7 and was found to bind both hnRNP A1 and Sam68. These results implicate hypoxic stress as a modulator of SMN2 exon 7 splicing in disease progression and a coordinated regulation by hnRNP A1 and Sam68 as modifiers of hypoxia-induced skipping of SMN exon 7. PMID:22763238

  8. [The relationship between the polymorphism of immunity genes and both aging and age-related diseases].

    PubMed

    Ruan, Qing-Wei; Yu, Zhuo-Wei; Bao, Zhi-Jun; Ma, Yong-Xing

    2013-07-01

    Aging is acommon, progressive and irreversible state of multi-cell dysfunction. Immune aging mainly includes the declines of regenerative capacity and lymphoid lineage differentiation potential, the hyporesponsive to infection and vaccination, the hyperresponsive in the context of inflammatory pathology, and the increased risk of autoimmunity. The dysfunction of aged immune system accelerates the occurrence of aging and age-related diseases. The mutation of immunity genes that affect immune responses accelerates or slows aging process and age-related diseases. The frequencies of acquired immunity genes, such as immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased in the longevity populations. The increased susceptibility of immune inflammatory response, morbidity and mortality in the elderly is often associated with decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-β1 haplotype cnd10T/C, cnd25G/G, -988C/C, -800G/A, low proinflammatory fator TNFa level related extended TNF-A genotype -1031C/C, -863C/A, -857C/C, IL-6-174 CC and IFN-γ+874 T allele as well. The innate immunity genes, such as highly expressed anti-inflammatory +896 G KIR4 allele, CCR5Δ32 variant, -765 C Cox-2 allele, -1708 G and 21 C 5-Lox alleles are detected in centenarians. In age-related diseases, a higher CMV-specific IgG antibody level in elderly individuals is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH 402 His allele indicate high mortality in the elderly. In the present study, we review the advances in the polymorphism and haplotype of innate and adoptive immunity genes, and their association with both aging and age-related diseases. To strengthen the analysis of extended haplotypes, epigenetic studies of immunity genes and genetic study of

  9. The Influence of Polymorphisms in Disease Severity in β-Thalassemia.

    PubMed

    Mohammdai-Asl, Javad; Ramezani, Abolfazl; Norozi, Fatemeh; Alghasi, Arash; Asnafi, Ali Amin; Jaseb, Kaveh; Saki, Najmaldin

    2015-10-01

    β-Thalassemia is a genetic disorder with a continuum of mild to severe clinical manifestations and requirement of transfusion at different stages of life. The cause(s) of this variety is not clear but genetic alterations could be a potential factor. In this review, the correlation between polymorphisms and different clinical manifestations, including the need for transfusion, was investigated. Relevant articles published in pubmed database from 1982 onwards were studied and compiled. The articles all contained the keywords β-thalassemia, genetic modifiers, and mutations. Certain polymorphisms and mutations could dictate the severity of symptoms as well as their onset. A significant number of the mentioned genetic alterations appear in beta-globin gene cluster and affect gamma chain. Therefore, hemoglobin F production rate is increased and can affect thalassemia symptoms and can relieve β-thalassemia symptoms. A number of polymorphisms in catalase and glutathione S transferase genes have also been shown to modify the severity of disease and response to treatment. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients, especially in young ages or before birth to take proper measures in advance and eventually ameliorate the symptoms in the long run. PMID:26143597

  10. Mass spectrometric analysis of protein tyrosine nitration in aging and neurodegenerative diseases.

    PubMed

    Yeo, Woon-Seok; Kim, Young Jun; Kabir, Mohammad Humayun; Kang, Jeong Won; Ahsan-Ul-Bari, Md; Kim, Kwang Pyo

    2015-01-01

    This review highlights the significance of protein tyrosine nitration (PTN) in signal transduction pathways, the progress achieved in analytical methods, and the implication of nitration in the cellular pathophysiology of aging and age-related neurodegenerative diseases. Although mass spectrometry of nitrated peptides has become a powerful tool for the characterization of nitrated peptides, the low stoichiometry of this modification clearly necessitates the use of affinity chromatography to enrich modified peptides. Analysis of nitropeptides involves identification of endogenous, intact modification as well as chemical conversion of the nitro group to a chemically reactive amine group and further modifications that enable affinity capture and enhance detectability by altering molecular properties. In this review, we focus on the recent progress in chemical derivatization of nitropeptides for enrichment and mass analysis, and for detection and quantification using various analytical tools. PTN participates in physiological processes, such as aging and neurodegenerative diseases. Accumulation of 3-nitrotyrosine has been found to occur during the aging process; this was identified through mass spectrometry. Further, there are several studies implicating the presence of nitrated tyrosine in age-related diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PMID:24889964

  11. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  12. Parabiosis for the study of age-related chronic disease

    PubMed Central

    Eggel, Alexander; Wyss-Coray, Tony

    2014-01-01

    Summary Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago. In view of this tremendous achievement, it can seem as if progress has slowed, and we have been unable to impact the most devastating diseases of our time. Chronic diseases of age such as cardiovascular disease, diabetes, osteoarthritis, or Alzheimer’s disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which mimics aspects of the naturally occurring shared blood supply in conjoined twins in humans and certain animals, may just have the power to be such a transformative experimental paradigm. Forgotten and now shunned in many countries, it has contributed to major breakthroughs in tumor biology, endocrinology, and transplantation research in the past century, and a set of new studies in the US and Britain report stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited especially if one is to study complex age-related, chronic disorders. PMID:24496774

  13. Three-dimensional quantitative imaging of telomeres in buccal cells identifies mild, moderate, and severe Alzheimer's disease patients.

    PubMed

    Mathur, Shubha; Glogowska, Aleksandra; McAvoy, Elizabeth; Righolt, Christiaan; Rutherford, Jaclyn; Willing, Cornelia; Banik, Upama; Ruthirakuhan, Myuri; Mai, Sabine; Garcia, Angeles

    2014-01-01

    Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's disease (AD) patients and cognitively normal age and gender-matched controls, we have for the first time examined changes in the 3D nuclear telomeric architecture of buccal cells among levels of AD severity based on five 3D parameters: i) telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data indicate that matched controls have significantly different 3D telomere profiles compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct profiles were also evident for each AD severity group. An increase in telomere number and aggregation concomitant with a decrease in telomere length from normal to severe AD defines the individual stages of the disease (p < 0.0001).

  14. The microbiota and microbiome in aging: potential implications in health and age-related diseases.

    PubMed

    Zapata, Heidi J; Quagliarello, Vincent J

    2015-04-01

    Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.

  15. An Acoustic Study of the Relationships among Neurologic Disease, Dysarthria Type, and Severity of Dysarthria

    ERIC Educational Resources Information Center

    Kim, Yunjung; Kent, Raymond D.; Weismer, Gary

    2011-01-01

    Purpose: This study examined acoustic predictors of speech intelligibility in speakers with several types of dysarthria secondary to different diseases and conducted classification analysis solely by acoustic measures according to 3 variables (disease, speech severity, and dysarthria type). Method: Speech recordings from 107 speakers with…

  16. Chloroquine resistance of Plasmodium falciparum is associated with severity of disease in Nigerian children.

    PubMed

    Olumese, P E; Amodu, O K; Björkman, A; Adeyemo, A A; Gbadegesin, R A; Walker, O

    2002-01-01

    Chloroquine resistance of Plasmodium falciparum in vitro was significantly higher in isolates from patients with severe malaria than those with uncomplicated disease. This association may be due to either progression of uncomplicated to severe disease following chloroquine failure or increased virulence of chloroquine-resistant parasites. The implication of this for antimalarial treatment policy is discussed. PMID:12497979

  17. New insights into brain BDNF function in normal aging and Alzheimer disease.

    PubMed

    Tapia-Arancibia, Lucia; Aliaga, Esteban; Silhol, Michelle; Arancibia, Sandor

    2008-11-01

    The decline observed during aging involves multiple factors that influence several systems. It is the case for learning and memory processes which are severely reduced with aging. It is admitted that these cognitive effects result from impaired neuronal plasticity, which is altered in normal aging but mainly in Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus, cerebral cortex) and are considered as genuine molecular mediators of functional and morphological synaptic plasticity. Modification of BDNF and/or the expression of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal aging and Alzheimer disease. Interestingly, recent findings show that some physiologic or pathologic age-associated changes in the central nervous system could be offset by administration of exogenous BDNF and/or by stimulating its receptor expression. These molecules may thus represent a physiological reserve which could determine physiological or pathological aging. These data suggest that boosting the expression or activity of these endogenous protective systems may be a promising therapeutic alternative to enhance healthy aging.

  18. Discussion on calculation of disease severity index values from scales with unequal intervals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    When estimating severity of disease, a disease interval (or category) scale comprises a number of categories of known numeric values – with plant disease this is generally the percent area with symptoms (e.g., the Horsfall-Barratt (H-B) scale). Studies in plant pathology and plant breeding often use...

  19. Endoscopic evaluation of celiac disease severity and its correlation with histopathological aspects of the duodenal mucosa

    PubMed Central

    Bonatto, Mauro W.; Kotze, Luiz; Orlandoski, Marcia; Tsuchyia, Ricardo; de Carvalho, Carlos A.; Lima, Doryane; Kurachi, Gustavo; Orso, Ivan R.B.; Kotze, Lorete

    2016-01-01

    Background and study aims: Celiac disease (CD) is a chronic systemic autoimmune disorder affecting genetically predisposed individuals, triggered and maintained by the ingestion of gluten. Triggered and maintained by the ingestion of gluten, celiac disease is a chronic systemic autoimmune disorder affecting genetically predisposed individuals. Persistent related inflammation of the duodenal mucosa causes atrophy architecture detectable on esophagogastroduodenoscopy (EGD) and histopathology. We investigated the association between endoscopic features and histopathological findings (Marsh) for duodenal mucosa in celiac disease patients and propose an endoscopic classification of severity. Patients and methods: Between January 2000 and March 2010, an electronic database containing 34,540 EDGs of patients aged > 14 years was searched for cases of CD. Out of 109 cases, 85 met the inclusion criteria: conventional EGD combined with chromoendoscopy, zoom and biopsy. EGD types 0, I and II corresponds to Marsh grades 0, 1 and 2, respectively, while EGD type III corresponds to Marsh grade 3 and 4. Results: Five patients (5.8 %) were EGD I but not Marsh grade 1; 25 patients (29.4 %) were EGD II, 4 of whom (16 %) were classified as Marsh grade 2; and 55 patients (64.7 %) were EGD III, 51 (92.7 %) of whom were classified as Marsh grades 3 and 4. The Spearman correlation coefficient (r = 0.33) revealed a significant association between the methods (P = 0.002). Conclusions: Changes in the duodenal mucosa detected on EGD were significantly and positively associated with histopathologic findings. The use of chromoendoscopy in addition to conventional EGD enhances changes in the duodenal mucosa and permits diagnosis of CD, even in routine examinations. The proposed endoscopic classification is practical and easily reproducible and provides valuable information regarding disease extension. PMID:27556094

  20. Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in Aging Populations.

    PubMed

    Fragoso, Carlos A Vaz

    2016-01-01

    Current epidemiologic practice evaluates COPD based on self-reported symptoms of chronic bronchitis, self-reported physician-diagnosed COPD, spirometry confirmed airflow obstruction, or emphysema diagnosed by volumetric computed chest tomography (CT). Because the highest risk population for having COPD includes a predominance of middle-aged or older persons, aging related changes must also be considered, including: 1) increased multimorbidity, polypharmacy, and severe deconditioning, as these identify mechanisms that underlie respiratory symptoms and can impart a complex differential diagnosis; 2) increased airflow limitation, as this impacts the interpretation of spirometry confirmed airflow obstruction; and 3) "senile" emphysema, as this impacts the specificity of CT-diagnosed emphysema. Accordingly, in an era of rapidly aging populations worldwide, the use of epidemiologic criteria that do not rigorously consider aging related changes will result in increased misidentification of COPD and may, in turn, misinform public health policy and patient care. PMID:26629987

  1. The Marmoset as a Model of Aging and Age-Related Diseases

    PubMed Central

    Tardif, Suzette D.; Mansfield, Keith G.; Ratnam, Rama; Ross, Corinna N.; Ziegler, Toni E.

    2013-01-01

    The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16.5 years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change—for example, reduced neurogenesis, β-amyloid deposition in the cerebral cortex, loss of calbindin D28k binding, and evidence of presbycusis—appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age. PMID:21411858

  2. Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age.

    PubMed

    Smith, W J; Stewart, J; Pfaus, J G

    1997-05-01

    Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce a general excitement and autonomic arousal in rats that increases their sensitivity to external incentives. Such stimulation can facilitate a variety of behaviors, including feeding, aggression, sexual activity, parental behavior, and drug taking if the appropriate stimuli exist in the environment. However, the ability of tail pinch to induce general arousal and incentive motivation appears to diminish with age. Here we report on the ability of tail pinch to induce Fos immunoreactivity within several brain regions as a function of age. Young (2-3 months) and middle-aged (12-13 months) male rats were administered either five tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n = 4 per stimulation condition). Rats were sacrificed 75 min following the onset of stimulation, and their brains were prepared for immunocytochemical detection of Fos protein. Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches. In contrast to young rats, middle-aged rats had significantly less Fos induced by one and five tail pinches in the mPOA, PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos immunoreactivity was not found within the medial prefrontal cortex, nucleus accumbens, striatum, lateral septum, or locus coeruleus in either young or old rats. Tail pinch appears to activate regions of the brain known to be involved in behavioral responses to both incentive cues and stressors. The lower level of cellular reactivity to tail pinch in middle-aged rats suggests a diminished neural responsiveness to

  3. Strain Variation and Disease Severity in Congenital Cytomegalovirus Infection: In Search of a Viral Marker.

    PubMed

    Arav-Boger, Ravit

    2015-09-01

    The wide spectrum of congenital cytomegalovirus (CMV) disease and known differences in the biology and in vitro growth of CMV strains continue to drive studies in search for specific viral genetic determinants that may predict severity of congenital CMV disease. Several CMV genes have been studied in detail in congenitally infected children, but the complexity of the viral genome and differences in the definition of symptomatic disease versus asymptomatic CMV infection continue to raise questions related to what constitutes a pathogenic CMV strain.

  4. Chronic depression as a model disease for cerebral aging.

    PubMed

    Bewernick, Bettina H; Schlaepfer, Thomas E

    2013-03-01

    Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The "neurogenesis hypothesis of depression" posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression. Stress, neuroinflammation, dysfunctional insulin regulation, oxidative stress, and alterations in neurotrophic factors possibly contribute to the development of depression. The influence of antidepressant therapies, namely pharmacotherapy and neuroprotectants, on cellular plasticity are summarized. A dysfunction of complex neuronal networks as a consequence of neural degeneration in neuropsychiatric diseases has led to the application of deep brain stimulation. We discuss the way depression seen in the light of the neurogenesis hypothesis can be used as a model disease for cerebral aging. A common pathological mechanism in depression and cerebral aging-a dysfunction of neuroprotection and neurogenesis-is discussed. This has implications for new treatment methods.

  5. Mitochondrial DNA mutations in ageing and disease: implications for HIV?

    PubMed

    Payne, Brendan A I; Gardner, Kristian; Chinnery, Patrick F

    2015-01-01

    Mitochondrial DNA (mtDNA) mutations cause neurological and multisystem disease. Somatic (acquired) mtDNA mutations are also associated with degenerative diseases and with normal human ageing. It is well established that certain nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drugs cause inhibition of the mtDNA polymerase, pol γ, leading to a reduction in mtDNA content (depletion). Given this effect of NRTI therapy on mtDNA replication, it is plausible that NRTI treatment may also lead to increased mtDNA mutations. Here we review recent evidence for an effect of HIV infection or NRTI therapy on mtDNA mutations, as well as discussing the methodological challenges in addressing this question. Finally, we discuss the possible implications for HIV-infected persons, with particular reference to ageing.

  6. Benefits from dietary polyphenols for brain aging and Alzheimer's disease.

    PubMed

    Rossi, L; Mazzitelli, S; Arciello, M; Capo, C R; Rotilio, G

    2008-12-01

    Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

  7. Patient-Based Transcriptome-Wide Analysis Identify Interferon and Ubiquination Pathways as Potential Predictors of Influenza A Disease Severity

    PubMed Central

    Hoang, Long Truong; Tolfvenstam, Thomas; Ooi, Eng Eong; Khor, Chiea Chuen; Naim, Ahmand Nazri Mohamed; Ho, Eliza Xin Pei; Ong, Swee Hoe; Wertheim, Heiman F.; Fox, Annette; Van Vinh Nguyen, Chau; Nghiem, Ngoc My; Ha, Tuan Manh; Thi Ngoc Tran, Anh; Tambayah, Paul; Lin, Raymond; Sangsajja, Chariya; Manosuthi, Weerawat; Chuchottaworn, Chareon; Sansayunh, Piamlarp; Chotpitayasunondh, Tawee; Suntarattiwong, Piyarat; Chokephaibulkit, Kulkanya; Puthavathana, Pilaipan; de Jong, Menno D.; Farrar, Jeremy; van Doorn, H. Rogier; Hibberd, Martin Lloyd

    2014-01-01

    Background The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. Methodology/Principal Findings Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. Conclusion/Significances The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients. PMID:25365328

  8. Principles and practice of hormetic treatment of aging and age-related diseases.

    PubMed

    Rattan, Suresh Is

    2008-02-01

    Aging is characterized by stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. Studies on the beneficial biological effects of repeated mild heat shock on human cells in culture, and other studies on the anti-aging and life-prolonging effects of proxidants, hypergravity, irradiation and ethanol on cells and organisms suggest that hormesis as an antiaging and gerontomodulatory approach has a promising future. Its clinical applications include prevention and treatment of diabetes, cataract, osteoporosis, dementia and some cancers.

  9. Neurovascular and neurometabolic derailment in aging and Alzheimer's disease

    PubMed Central

    Lourenço, Cátia F.; Ledo, Ana; Dias, Cândida; Barbosa, Rui M.; Laranjinha, João

    2015-01-01

    The functional and structural integrity of the brain requires local adjustment of blood flow and regulated delivery of metabolic substrates to meet the metabolic demands imposed by neuronal activation. This process—neurovascular coupling—and ensued alterations of glucose and oxygen metabolism—neurometabolic coupling—are accomplished by concerted communication between neural and vascular cells. Evidence suggests that neuronal-derived nitric oxide (•NO) is a key player in both phenomena. Alterations in the mechanisms underlying the intimate communication between neural cells and vessels ultimately lead to neuronal dysfunction. Both neurovascular and neurometabolic coupling are perturbed during brain aging and in age-related neuropathologies in close association with cognitive decline. However, despite decades of intense investigation, many aspects remain poorly understood, such as the impact of these alterations. In this review, we address neurovascular and neurometabolic derailment in aging and Alzheimer's disease (AD), discussing its significance in connection with •NO-related pathways. PMID:26074816

  10. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  11. Predicting charges for inpatient medical rehabilitation using severity, DRG, age, and function.

    PubMed Central

    McGinnis, G E; Osberg, J S; DeJong, G; Seward, M L; Branch, L G

    1987-01-01

    We examined the effectiveness of using diagnosis related groups (DRGs), Severity of Illness Index (SII), age and function at admission to predict inpatient charges for medical rehabilitation. Data from our sample of 199 indicate that DRGs alone explained approximately 12 per cent of the variation in charges for inpatient rehabilitation while SII explained 26 per cent of the variation. SII, DRG, and age together yielded the highest regression coefficient, accounting for nearly 39 per cent of the variation in total charges; SII and age accounted for 36 per cent of the variation. Within DRG categories, SII was the only important predictor of inpatient charges accounting for 23 per cent of the variation in charges among stroke patients (DRG 014) and 28 per cent of the variation in charges among hip fracture patients (DRG 210). Function at admission was not a useful predictor of inpatient rehabilitation charges within DRGs. These results suggest that SII and age may be useful in developing a DRG-based prospective payment system for inpatient medical rehabilitation. PMID:3109268

  12. Senescence in chronic liver disease: Is the future in aging?

    PubMed

    Aravinthan, Aloysious D; Alexander, Graeme J M

    2016-10-01

    Cellular senescence is a fundamental, complex mechanism with an important protective role present from embryogenesis to late life across all species. It limits the proliferative potential of damaged cells thus protecting against malignant change, but at the expense of substantial alterations to the microenvironment and tissue homeostasis, driving inflammation, fibrosis and paradoxically, malignant disease if the process is sustained. Cellular senescence has attracted considerable recent interest with recognition of pathways linking aging, malignancy and insulin resistance and the current focus on therapeutic interventions to extend health-span. There are major implications for hepatology in the field of fibrosis and cancer, where cellular senescence of hepatocytes, cholangiocytes, stellate cells and immune cells has been implicated in chronic liver disease progression. This review focuses on cellular senescence in chronic liver disease and explores therapeutic opportunities.

  13. APOL1 Risk Alleles are Associated with More Severe Arteriosclerosis in Renal Resistance Vessels with Aging and Hypertension

    PubMed Central

    Hughson, Michael D; Hoy, Wendy E; Mott, Susan A; Puelles, Victor G; Bertram, John F; Winkler, Cheryl L; Kopp, Jeffrey B

    2016-01-01

    The increased risk of end-stage kidney disease (ESKD) among hypertensive African Americans is partly related to APOL1 allele variants. Hypertension-associated arterionephrosclerosis consists of arteriosclerosis, glomerulosclerosis, and cortical fibrosis. The initial glomerulosclerosis, attributed to preglomerular arteriosclerosis and ischemia, consists of focal global glomerulosclerosis (FGGS), but in biopsy studies, focal segmental glomerulosclerosis (FSGS) is found with progression to ESKD, particularly in African Americans. This is a study of arterionephrosclerosis in successfully APOL1 genotyped autopsy kidney tissue of 159 African Americans (61 no risk alleles, 68 one risk allele, 30 two risk alleles) and 135 whites aged 18–89 years from a general population with no clinical renal disease. Glomerulosclerosis was nearly exclusively FGGS with only three subjects having FSGS-like lesions that were unrelated to APOL1 risk status. For both races, in multivariable analysis, the dependent variables of arteriosclerosis, glomerulosclerosis, and cortical fibrosis were all significantly related to the independent variables of older age (P < 0.001) and hypertension (P < 0.001). A relationship between APOL1 genotype and arteriosclerosis was apparent only after 35 years of age when, for any level of elevated blood pressure, more severe arteriosclerosis was found in the interlobular arteries of 14 subjects with two APOL1 risk alleles when compared to African Americans with none (n = 37, P = 0.02) or one risk alleles (n = 35, P = 0.02). With the limitation of the small number of subjects contributing to the positive results, the findings imply that APOL1 risk alleles recessively augment small vessel arteriosclerosis in conjunction with age and hypertension. FSGS was not a significant finding, indicating that in the early stages of arterionephrosclerosis, the primary pathologic influence of APOL1 genotype is vascular rather than glomerular. PMID:27610422

  14. Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease

    PubMed Central

    Bohnen, Nicolaas I.; Kotagal, Vikas; Müller, Martijn L.T.M; Koeppe, Robert A; Scott, Peter J.H.; Albin, Roger L.; Frey, Kirk A; Petrou, Myria

    2014-01-01

    Background There is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied. Objective To investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations. Methods Cross-sectional study. Patients with PD (n=148; age 65.6±7.4 years, Hoehn and Yahr stage 2.4±0.6, with (n=15) and without (n=133) comorbid type II DM, underwent [11C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [11C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates. Results There were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (−0.98±1.01) compared to the non-diabetics (−0.36±0.91; F=7.78, P=0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F=8.39, P<0.0001). Conclusion Diabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than diseasespecific neurodegenerations. PMID:25454317

  15. Bleeding symptoms and laboratory correlation in patients with severe von Willebrand disease.

    PubMed

    Metjian, A D; Wang, C; Sood, S L; Cuker, A; Peterson, S M; Soucie, J M; Konkle, B A

    2009-07-01

    Type 3 von Willebrand disease (VWD) is a rare bleeding disorder with markedly decreased or absent von Willebrand factor (VWF) protein, accompanied by a parallel decrease in VWF function and factor VIII (FVIII) activity. The goal of this study was to describe the population of patients enrolled in the USA Centers for Disease Control Universal Data Collection (UDC) study with type 3 VWD, defined as a VWF:Ag of <10%, and to correlate bleeding symptoms with VWF and FVIII levels. Data on 150 patients were analysed. Almost all patients experienced bleeding episodes (98%) and required blood and/or factor product treatment (92%). While oral mucosal bleeding (the site of first bleed in 54%) was most common, subsequent muscle and joint bleeds were also seen (28%, 45%, respectively), and intracranial haemorrhage occurred in 8% of individuals. Mean age of first bleed was lower in those with either a FVIII < or =5% or a VWF:Ag <1%. Univariate marginal model analysis showed lower levels of FVIII and VWF:Ag both predicted a higher risk of joint bleeding. Longitudinal multivariate analysis found a lower FVIII level (P = 0.03), increasing age (P < 0.0001), history of joint bleeding (P = 0.001), higher body mass index (BMI) (P < 0.0001), and use of home infusion (P = 0.02) were all negatively associated with joint mobility. Low levels of VWF:Ag (P = 0.003) and male sex (P = 0.007) were also negatively associated with joint function. This study documents the strong bleeding phenotype in severe VWD and provides data to help target therapy, including prophylaxis, for patients most at risk of bleeding complications.

  16. Beyond and behind the fingerprints of oxidative stress in age-related diseases: Secrets of successful aging.

    PubMed

    Polidori, M Cristina; Scholtes, Marlies

    2016-04-01

    Several years after the first publication of the definition of oxidative stress by Helmut Sies, this topic is still focus of a large body of attention and research in the field of aging, neurodegeneration and disease prevention. The conduction of clinical and epidemiological research without a solid biochemical rationale has led to largely frustrating results without being able to disprove the oxidative stress hypothesis. The present work is dedicated to Helmut Sies and describes the successful scientific approach to bench-to-bedside (-to-behavior) oxidative stress clinical research. PMID:27095215

  17. Graves' Disease Pharmacotherapy in Women of Reproductive Age.

    PubMed

    Prunty, Jeremy J; Heise, Crystal D; Chaffin, David G

    2016-01-01

    Graves' disease is an autoimmune disorder in which inappropriate stimulation of the thyroid gland results in unregulated secretion of thyroid hormones resulting in hyperthyroidism. Graves' disease is the most common cause of autoimmune hyperthyroidism during pregnancy. Treatment options for Graves' disease include thioamide therapy, partial or total thyroidectomy, and radioactive iodine. In this article, we review guideline recommendations for Graves' disease treatment in women of reproductive age including the recent guideline from the American College of Obstetricians and Gynecologists. Controversy regarding appropriate thioamide therapy before, during, and after pregnancy is reviewed. Surgical and radioactive iodine therapy considerations in this patient population are also reviewed. In patients who may find themselves pregnant during therapy or develop Graves' disease during their pregnancy, consideration should be given to the most appropriate treatment course for the mother and fetus. Thioamide therapy should be used with either propylthiouracil or methimazole at appropriate doses that target the upper range of normal to slightly hyperthyroid to avoid creating hypothyroidism in the fetus. Consideration should also be given to the adverse effects of thioamide, such as agranulocytosis and hepatotoxicity, with appropriate patient consultation regarding signs and symptoms. Individuals who wish to breastfeed their infants while taking thioamide should receive the lowest effective dose. Surgery should be reserved for extreme cases and limited to the second trimester, if possible. Radioactive iodine therapy may be used in nonpregnant individuals, with limited harm to future fertility. Radioactive iodine therapy should be withheld in pregnant women and those who are actively breastfeeding. Clinicians should keep abreast of developments in clinical trials and evidence-based recommendations regarding Graves' disease in reproductive-age women for any changes in evidence

  18. Circulating miR-21 and miR-29a as Markers of Disease Severity and Etiology in Cholestatic Pediatric Liver Disease

    PubMed Central

    Goldschmidt, Imeke; Thum, Thomas; Baumann, Ulrich

    2016-01-01

    Circulating microRNAs have been investigated as markers of disease severity in a variety of conditions. We examined whether circulating miR-21 and miR-29a could serve as markers of hepatic fibrosis and disease etiology in children with various liver diseases. Circulating miR-21 and miR-29a were determined in 58 children (21 female, age 0.1–17.8 (median 9.8) years)) with chronic liver disease and compared to histological grading of hepatic fibrosis. 22 healthy children served as controls for circulating miRNAs. Levels of circulating miR-21 appeared to be age-dependent in healthy children. Children with biliary atresia had significantly higher levels of miR-21 compared both to healthy controls and to age-matched children with other cholestatic liver disease. Circulating miR-29a levels in biliary atresia children did not differ from healthy controls, but tended to be higher than in age-matched children with other cholestatic liver disease. Neither miR-21 nor miR-29a correlated well with hepatic fibrosis. Circulating miR-21 and miR-29a levels can potentially serve as non-invasive diagnostic markers to differentiate biliary atresia from other cholestatic disease in infancy. They do not appear suitable as non-invasive markers for the degree of hepatic fibrosis in an unselected cohort of children with various liver diseases. The discriminating effect regarding neonatal cholestasis should be followed up in a prospective longitudinal study. PMID:26927196

  19. Severe hypoxaemia can predict unfavourable clinical outcomes in individuals with pulmonary embolism aged over 40 years

    PubMed Central

    Souza, Caio Simoes; Resende, Fernanda Simoes Seabra; Rodrigues, Marcelo Palmeira

    2014-01-01

    INTRODUCTION Acute pulmonary embolism (APE) is an urgent clinical condition that can progress in a wide variety of ways. Therefore, we sought to develop an easy-to-apply algorithm, to be based on readily available clinical indicators, effective in predicting unfavourable outcomes. METHODS This was a retrospective cohort study based on systematically collected data in a database. The study included 102 patients with APE who were admitted to a tertiary care hospital. The following outcomes were defined as unfavourable shock, the need for mechanical ventilation, the use of thrombolytics, and death. Logistic regression analysis was used to explore variables significantly associated with outcome and to calculate post-test probabilities. RESULTS The prevalence of unfavourable outcomes was 25.5% (26 of the 102 patients with APE). The risk of an unfavourable outcome was reduced to 7.0% for patients with APE who were aged ≤ 40 years. In patients with APE who were aged > 40 years, the presence of hypoxaemia (i.e. peripheral oxygen saturation < 90%) alone increased the risk of an unfavourable outcome to 57.0%. A recent history of trauma and the presence of pre-existing lung or heart disease were significantly associated with unfavourable outcomes. The inclusion of those variables in the logistic regression model increased the post-test risk of an unfavourable outcome to 65.0%–86.0%. CONCLUSION Advanced age (i.e. > 40 years), the presence of hypoxaemia, a recent history of trauma and the presence of pre-existing lung or heart disease are risk factors for unfavourable outcome in patients with APE. PMID:25273933

  20. Mineral metabolism disturbances are associated with the presence and severity of calcific aortic valve disease*

    PubMed Central

    Yang, Zhen-kun; Ying, Chen; Zhao, Hong-yan; Fang, Yue-hua; Chen, Ying; Shen, Wei-feng

    2015-01-01

    Objective: We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease (CAVD) in patients with normal or mildly impaired renal function. Methods: We measured serum levels of calcium, phosphate, alkaline phosphatase (AKP), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OHD), and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis (AVSc) (n=164) or stenosis (AVS) (n=96) and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. Results: Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels (all P<0.001). Similarly, osteocalcin, procollagen I N-terminal peptide, and β-isomerized type I collagen C-telopeptide breakdown products were significantly increased stepwise from the control group to patients with AVS (all P<0.001). In patients with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were negatively, related to trans-aortic peak flow velocity and mean pressure gradient. After adjusting for relevant confounding variables, increased serum levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD were independently associated with the presence and severity of CAVD. Conclusions: This study suggests an association between mineral metabolism disturbance and the presence and severity of CAVD in patients with normal or mildly impaired renal function. Abnormal bone turnover may be a potential mechanism. PMID:25990053

  1. Rotavirus diarrhea in Bangladeshi children: correlation of disease severity with serotypes.

    PubMed Central

    Bern, C; Unicomb, L; Gentsch, J R; Banul, N; Yunus, M; Sack, R B; Glass, R I

    1992-01-01

    To improve the understanding of the relative importance of serotypes of rotavirus in dehydrating diarrhea, we examined the correlation of clinical characteristics and disease severity with serotype in 2,441 diarrheal episodes among children younger than 2 years of age in rural Bangladesh. Of 764 rotavirus-associated episodes, a single G type (serotype 1, 2, 3, or 4) was determined by oligonucleotide probe in 485 (63%), while 233 episodes were nontypeable. Episodes with G types 2 and 3 were associated with more-severe dehydration than episodes associated with G type 1 or 4 or with nontypeable rotavirus. Episodes did not differ by G type in prevalence of vomiting, copious diarrhea, fever, abdominal pain, or length of treatment center stay. Rotavirus reinfections were detected in seven children, with homologous reinfection (G type 2) in one. Twelve children with diarrhea who died had rotavirus detected in stool specimens within 30 days of death. Children who died were more likely to be malnourished than were surviving children with rotavirus diarrhea. Of 40 specimens tested by polymerase chain reaction, 29 (72.5%) were P type 1, 9 (22.5%) were P type 2, 1 (2.5%) was P type 3, and 1 (2.5%) was nontypeable. One severely symptomatic diarrheal episode was associated with P type 3 rotavirus, a serotype usually found in asymptomatic nursery infections. Although G types 2 and 3 were associated with more-severe dehydration than other serotypes, the differences do not appear to be of major clinical importance. Effective vaccines should protect against all four major G types. PMID:1333490

  2. Pantomime and Imitation of Limb Gestures in Relation to the Severity of Alzheimer's Disease

    ERIC Educational Resources Information Center

    Parakh, Rupa; Roy, Eric; Koo, Ean; Black, Sandra

    2004-01-01

    The present study was designed to investigate the relationship between performance of limb gestures and the severity of Alzheimer's disease (AD). Apraxia tends to occur at later stages of AD, and the severity of apraxia has been shown to vary with the severity of AD dementia. Participants were 19 mild (including 9 with no cognitive impairment and…

  3. Use of the Hayling Task to Measure Inhibition of Prepotent Responses in Normal Aging and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Belleville, Sylvie; Rouleau, Nancie; Van der Linden, Martial

    2006-01-01

    This study measures the effect of Alzheimer's disease (AD) and normal aging on the inhibition of prepotent responses. AD patients, normal aged controls, and young subjects were tested with the Hayling task, which measures the ability to inhibit a semantically constrained response, and with the Stroop procedure. AD patients showed a severe deficit…

  4. Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease

    PubMed Central

    Desbois, Anne Claire; Addimanda, Olga; Bertrand, Anne; Deroux, Alban; Pérard, Laurent; Depaz, Raphael; Hachulla, Eric; Lambert, Marc; Launay, David; Subran, Benjamin; Ackerman, Felix; Mariette, Xavier; Cohen, Fleur; Marie, Isabelle; Salvarini, Carlo; Cacoub, Patrice; Saadoun, David

    2016-01-01

    Abstract To report the safety and efficacy of anti-tumor necrosis factor α (TNFα) therapy in severe and refractory neuro-Behçet disease (NBD) patients. Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24–60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFα (infliximab 5 mg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months. Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1–6). The median Rankin score was 2 (1–4) at the initiation of anti-TNFα versus 1 (0–4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases. TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population. PMID:27281066

  5. Augmentation of Autoantibodies by Helicobacter pylori in Parkinson's Disease Patients May Be Linked to Greater Severity.

    PubMed

    Suwarnalata, Gunasekaran; Tan, Ai Huey; Isa, Hidayah; Gudimella, Ranganath; Anwar, Arif; Loke, Mun Fai; Mahadeva, Sanjiv; Lim, Shen-Yang; Vadivelu, Jamuna

    2016-01-01

    Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity. PMID:27100827

  6. Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease: An Observational Study.

    PubMed

    Desbois, Anne Claire; Addimanda, Olga; Bertrand, Anne; Deroux, Alban; Pérard, Laurent; Depaz, Raphael; Hachulla, Eric; Lambert, Marc; Launay, David; Subran, Benjamin; Ackerman, Felix; Mariette, Xavier; Cohen, Fleur; Marie, Isabelle; Salvarini, Carlo; Cacoub, Patrice; Saadoun, David

    2016-06-01

    To report the safety and efficacy of anti-tumor necrosis factor α (TNFα) therapy in severe and refractory neuro-Behçet disease (NBD) patients.Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24-60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFα (infliximab 5 mg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months.Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1-6). The median Rankin score was 2 (1-4) at the initiation of anti-TNFα versus 1 (0-4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases.TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population.

  7. Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

    PubMed Central

    Pereira, Isabela Resende; Vilar-Pereira, Glaucia; da Silva, Andrea Alice; Lannes-Vieira, Joseli

    2014-01-01

    Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease. PMID:24937048

  8. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases.

    PubMed

    Suksuphew, Sarawut; Noisa, Parinya

    2015-03-26

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer's disease, Parkinson's disease, and Huntington's disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients.

  9. Metabolite mapping reveals severe widespread perturbation of multiple metabolic processes in Huntington's disease human brain.

    PubMed

    Patassini, Stefano; Begley, Paul; Xu, Jingshu; Church, Stephanie J; Reid, Suzanne J; Kim, Eric H; Curtis, Maurice A; Dragunow, Mike; Waldvogel, Henry J; Snell, Russell G; Unwin, Richard D; Faull, Richard L M; Cooper, Garth J S

    2016-09-01

    Huntington's disease (HD) is a genetically-mediated neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein (Htt) through lengthening of its polyglutamine tract, thus initiating a cascade that ultimately leads to premature death. However, neurodegeneration typically manifests in HD only in middle age, and mechanisms linking the causative mutation to brain disease are poorly understood. Brain metabolism is severely perturbed in HD, and some studies have indicated a potential role for mutant Htt as a driver of these metabolic aberrations. Here, our objective was to determine the effects of HD on brain metabolism by measuring levels of polar metabolites in regions known to undergo varying degrees of damage. We performed gas-chromatography/mass spectrometry-based metabolomic analyses in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine matched controls. In each patient, we measured metabolite content in representative tissue-samples from eleven brain regions that display varying degrees of damage in HD, thus identifying the presence and abundance of 63 different metabolites from several molecular classes, including carbohydrates, amino acids, nucleosides, and neurotransmitters. Robust alterations in regional brain-metabolite abundances were observed in HD patients: these included changes in levels of small molecules that play important roles as intermediates in the tricarboxylic-acid and urea cycles, and amino-acid metabolism. Our findings point to widespread disruption of brain metabolism and indicate a complex phenotype beyond the gradient of neuropathologic damage observed in HD brain. PMID:27267344

  10. Coexistence of sickle cell disease and severe congenital neutropenia: first impressions can be deceiving.

    PubMed

    Wali, Yasser; Beshlawi, Ismail; Fawaz, Naglaa; Alkhayat, Aisha; Zalabany, Mahmoud; Elshinawy, Mohamed; Al-Kindi, Salam; Al-Rawas, Abdul Hakim A; Klein, Christoph

    2012-09-01

    We report an Omani family in whom the propositus had a rare coexistence of sickle cell disease and severe congenital neutropenia associated with a mutation in ELANE. In contrast to his siblings with sickle cell disease, the severity of HbSS-associated complications such as painful crises and acute chest syndrome was significantly reduced. His course of the disease had markedly worsened after initiating G-CSF therapy. These clinical observations suggest that neutropenia may ameliorate inflammatory responses and thus display a modulating factor with respect to the clinical course of sickle cell disease.

  11. Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe

    PubMed Central

    Traverso, C E; Walt, J G; Kelly, S P; Hommer, A H; Bron, A M; Denis, P; Nordmann, J-P; Renard, J-P; Bayer, A; Grehn, F; Pfeiffer, N; Cedrone, C; Gandolfi, S; Orzalesi, N; Nucci, C; Rossetti, L; Azuara-Blanco, A; Bagnis, A; Hitchings, R; Salmon, J F; Bricola, G; Buchholz, P M; Kotak, S V; Katz, L M; Siegartel, L R; Doyle, J J

    2005-01-01

    Background: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. Methods: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated. Results: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated €86 for each incremental step ranging from €455 per person year for stage 0 to €969 per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease. Conclusions: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources. PMID:16170109

  12. Alzheimer’s Disease: Diagnosis and Treatment Across the Spectrum of Disease Severity

    PubMed Central

    Neugroschl, Judith; Wang, Sophia

    2012-01-01

    Alzheimer’s disease exists along a spectrum, from early memory changes to functional dependence and death. Using a case illustration, we review the evaluation and diagnosis of mild cognitive impairment and the diagnosis and management of Alzheimer’s disease at each stage, including the management of both cognitive and behavioral/psychiatric aspects of the disease and end-stage and end-of-life care. PMID:21748748

  13. Ages of celiac disease: From changing environment to improved diagnostics

    PubMed Central

    Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro

    2011-01-01

    From the time of Gee’s landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic “gluten infection”. The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed. PMID:21990947

  14. Human stem cells as targets for the aging and diseases of aging processes.

    PubMed

    Trosko, James E

    2003-03-01

    While many theories have been proposed for the aging process, and many debates on the matter of aging and the diseases of aging being either the result of the same or independent processes, most have not considered humans as a hierarchical system made up of cybernetically interacting levels of organization. To understand the aging process and the diseases of aging, one must view the human as the result of the total genomic DNA in the single fertilized egg that proliferates, differentiates and develops into an individual of about 100 trillion cells, organized by different cell types (pluri-potent stem cells, progenitor stem cells, terminally differentiated cells) into multiple tissue, organ and organ systems which interact with each other via endogenous factors and with exogenous factors. Our hypothesis is that both aging and diseases of aging are dependent of the normal functioning of the pluri-potent stem cell pool. Specifically, the concept involves the cybernetic feedback between the 'quantity' of the stem cell pool in each tissue niche with the 'quality' of the stem cells in the pool. The process of gap junctional inter-cellular communication (GJIC), which has been implicated in the evolution from the single cell organism to the multi-cellular organisms, requiring growth control, differentiation, apoptosis, adaptive response capability of differentiated cells and senescence, is speculated to be a shared mechanism in stem cell biology and in many chronic disease processes (teratogenesis; carcinogenesis, atherogenesis, diabetigenesis, etc.). Specifically, stem cells are assumed to be 'immortal' until induced to express their connexin genes and have functional GJIC, at which time they can differentiate and become 'mortal'. As long as the stem cells are communicating with their differentiated daughters via some extra-cellular soluble negative growth factor, the homeostatic control of their growth and differentiation is maintained for the organism. However, if the

  15. Aging, Neurodegenerative Disease, and Traumatic Brain Injury: The Role of Neuroimaging

    PubMed Central

    Levine, Brian

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease. PMID:25192426

  16. Prevalence of comorbidities according to predominant phenotype and severity of chronic obstructive pulmonary disease

    PubMed Central

    Camiciottoli, Gianna; Bigazzi, Francesca; Magni, Chiara; Bonti, Viola; Diciotti, Stefano; Bartolucci, Maurizio; Mascalchi, Mario; Pistolesi, Massimo

    2016-01-01

    Background In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD). Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH), ischemic heart disease, heart failure, peripheral vascular disease (PVD), diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema) and severity (mild and severe diseases) were determined by clinical and functional parameters. Methods A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide %) and sputum characteristics. Comorbidities were assessed by objective medical records. Results Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively). IAH prevailed significantly in predominant airway disease, osteoporosis prevailed significantly in predominant emphysema, and ischemic heart disease and PVD prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly in predominant airway phenotype of COPD and mild COPD severity. Conclusion Specific comorbidities prevail in different phenotypes of COPD; this fact may be relevant to identify patients at risk for specific, phenotype-related comorbidities. The highest prevalence of comorbidities in patients with mild disease indicates that these patients should be investigated for coexisting diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD. The simple method employed to phenotype and

  17. Prevalence of comorbidities according to predominant phenotype and severity of chronic obstructive pulmonary disease

    PubMed Central

    Camiciottoli, Gianna; Bigazzi, Francesca; Magni, Chiara; Bonti, Viola; Diciotti, Stefano; Bartolucci, Maurizio; Mascalchi, Mario; Pistolesi, Massimo

    2016-01-01

    Background In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD). Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH), ischemic heart disease, heart failure, peripheral vascular disease (PVD), diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema) and severity (mild and severe diseases) were determined by clinical and functional parameters. Methods A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide %) and sputum characteristics. Comorbidities were assessed by objective medical records. Results Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively). IAH prevailed significantly in predominant airway disease, osteoporosis prevailed significantly in predominant emphysema, and ischemic heart disease and PVD prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly in predominant airway phenotype of COPD and mild COPD severity. Conclusion Specific comorbidities prevail in different phenotypes of COPD; this fact may be relevant to identify patients at risk for specific, phenotype-related comorbidities. The highest prevalence of comorbidities in patients with mild disease indicates that these patients should be investigated for coexisting diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD. The simple method employed to phenotype and

  18. The role of DNA methylation in aging, rejuvenation, and age-related disease.

    PubMed

    Johnson, Adiv A; Akman, Kemal; Calimport, Stuart R G; Wuttke, Daniel; Stolzing, Alexandra; de Magalhães, João Pedro

    2012-10-01

    DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-L-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation.

  19. The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

    PubMed Central

    Johnson, Adiv A.; Akman, Kemal; Calimport, Stuart R.G.; Wuttke, Daniel; de Magalhães, João Pedro

    2012-01-01

    Abstract DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation. PMID:23098078

  20. Management of the aging risk factor for Parkinson's disease.

    PubMed

    Phillipson, Oliver T

    2014-04-01

    The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression.

  1. A mitochondrial superoxide theory for oxidative stress diseases and aging.

    PubMed

    Indo, Hiroko P; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K St; Majima, Hideyuki J

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.

  2. Severe Anemia and Helicobacter Pylori Infection in school age Children; A case reports

    PubMed Central

    Gheibi, Sh; Noroozi, M; Hejazi, S; Karamyyar, M; Farrokh-Eslamlou, H

    2016-01-01

    Background Iron-deficiency anemia is a widespread public health problem with major consequences for human health especially, children. However, in a fraction of patients an underlying cause is never found during routine investigation. Recent studies have suggested an association between Helicobacter pylori (H. Pylori) infection and iron-deficiency anemia. Case presentation Here is reported four school aged children (two male, two female) with refractory severe iron-deficiency anemia associated H. Pylori gastritis. Mean age of the patients was 13.62 years old and they were admitted with chief complaints of abdominal, chest pain weakness, headache and respiratory distress. Mean hemoglobin level in patients was 6.2 g/dl with persistence to iron therapy. After the diagnosis and therapy of H. pylori infection, clinical complaints, hemoglobin level and iron profiles were being normal and they gained weight. Conclusion This study suggests screening of H. pylori infection and appropriate treatment in any case of refractory moderate to severe iron-deficiency anemia, especially with clinical manifestations of gastrointestinal tract in children. PMID:27222704

  3. A Cost-Effectiveness Analysis of Surgery for Middle-Aged Men with Severe Obstructive Sleep Apnea Intolerant of CPAP

    PubMed Central

    Tan, Kelvin B.; Toh, Song Tar; Guilleminault, Christian; Holty, Jon-Erik C.

    2015-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Conventional OSA therapy necessitates indefinite continuous positive airway pressure (CPAP). Although CPAP is an effective treatment modality, up to 50% of OSA patients are intolerant of CPAP. We explore whether surgical modalities developed for those intolerant of CPAP are cost-effective. Methods: We construct a lifetime semi-Markov model of OSA that accounts for observed increased risks of stroke, cardiovascular disease, and motor vehicle collisions for a 50-year-old male with untreated severe OSA. Using this model, we compare the cost-effectiveness of (1) no treatment, (2) CPAP only, and (3) CPAP followed by surgery (either palatopharyngeal reconstructive surgery [PPRS] or multilevel surgery [MLS]) for those intolerant to CPAP. Results: Compared with the CPAP only strategy, CPAP followed by PPRS (CPAP-PPRS) adds 0.265 quality adjusted life years (QALYs) for an increase of $2,767 (discounted 2010 dollars) and is highly cost effective with an incremental cost-effectiveness ratio (ICER) of $10,421/QALY for a 50-year-old male with severe OSA. Compared to a CPAP-PPRS strategy, the CPAP-MLS strategy adds 0.07 QALYs at an increase of $6,213 for an ICER of $84,199/QALY. The CPAP-PPRS strategy appears cost-effective over a wide range of parameter estimates. Conclusions: Palatopharyngeal reconstructive surgery appears cost-effective in middle-aged men with severe OSA intolerant of CPAP. Further research is warranted to better define surgical candidacy as well as short-term and long-term surgical outcomes. Commentary: A commentary on this article appears in this issue on page 509. Citation: Tan KB, Toh ST, Guilleminault C, Holty JE. A cost-effectiveness analysis of surgery for middle-aged men with severe obstructive sleep apnea intolerant of CPAP. J Clin Sleep Med 2015;11(5):525–535. PMID:25700871

  4. Predictors of severe disease in a hospitalized population of children with acute viral lower respiratory tract infections.

    PubMed

    Pedraza-Bernal, Angela M; Rodriguez-Martinez, Carlos E; Acuña-Cordero, Ranniery

    2016-05-01

    Although predictors of severe viral acute lower respiratory infections (ALRIs) in children have been reported, there have been few research studies performed in low- and middle-income countries (LMIC). The aim of the present study was to determine predictors of disease severity in a population of Colombian children <5 years of age with ALRI. In a prospective cohort study, we determined independent predictors of severe ALRI in a hospitalized population of children under 5 years old with ALRI during a 1-year period. We included both underlying disease conditions and the infecting respiratory viruses as predictor variables of severe disease. We defined severe disease as the necessity of pediatric intensive care unit admission. Of a total of 1,180 patients admitted with a diagnosis of ALRI, 416 (35.3%) were included because they were positive for any kind of respiratory virus. After controlling for potential confounders, it was found that a history of pulmonary hypertension (RR 3.62; CI 95% 2.38-5.52; P < 0.001) and a history of recurrent wheezing (RR 1.77; CI 95% 1.12-2.79; P = 0.015) were independent predictors of severe disease. The present study shows that respiratory viruses are significant causes of ALRI in infants and young children in Colombia, a typical tropical LMIC, especially during the rainy season. Additionally, the results of the present study show that clinical variables such as a history of pulmonary hypertension and a history of recurrent wheezing are more relevant for predicting ALRI severity than the infecting respiratory viruses.

  5. Predictors of severe disease in a hospitalized population of children with acute viral lower respiratory tract infections.

    PubMed

    Pedraza-Bernal, Angela M; Rodriguez-Martinez, Carlos E; Acuña-Cordero, Ranniery

    2016-05-01

    Although predictors of severe viral acute lower respiratory infections (ALRIs) in children have been reported, there have been few research studies performed in low- and middle-income countries (LMIC). The aim of the present study was to determine predictors of disease severity in a population of Colombian children <5 years of age with ALRI. In a prospective cohort study, we determined independent predictors of severe ALRI in a hospitalized population of children under 5 years old with ALRI during a 1-year period. We included both underlying disease conditions and the infecting respiratory viruses as predictor variables of severe disease. We defined severe disease as the necessity of pediatric intensive care unit admission. Of a total of 1,180 patients admitted with a diagnosis of ALRI, 416 (35.3%) were included because they were positive for any kind of respiratory virus. After controlling for potential confounders, it was found that a history of pulmonary hypertension (RR 3.62; CI 95% 2.38-5.52; P < 0.001) and a history of recurrent wheezing (RR 1.77; CI 95% 1.12-2.79; P = 0.015) were independent predictors of severe disease. The present study shows that respiratory viruses are significant causes of ALRI in infants and young children in Colombia, a typical tropical LMIC, especially during the rainy season. Additionally, the results of the present study show that clinical variables such as a history of pulmonary hypertension and a history of recurrent wheezing are more relevant for predicting ALRI severity than the infecting respiratory viruses. PMID:26403374

  6. Searching for the birthplaces of open clusters with ages of several billion years

    NASA Astrophysics Data System (ADS)

    Acharova, I. A.; Shevtsova, E. S.

    2016-01-01

    We discuss the possibility of finding the birthplaces of open clusters (OC) with ages of several billion years. The proposed method is based on the comparison of the results of the chemical evolution modeling of the Galactic disk with the parameters of the cluster. Five OCs older than 7 Gyr are known: NGC6791, BH176, Collinder 261, Berkeley 17, and Berkeley 39. The oxygen and iron abundances in NGC6791 and the oxygen abundance in BH176 are twice the solar level, the heavy-element abundances in other clusters are close to the corresponding solar values. According to chemical evolution models, at the time of the formation of the objects considered the regions where the oxygen and iron abundances reached the corresponding levels extended out to 5 kpc from the Galactic center.At present time theOCs considered are located several kpc from the Galactic center. Some of these clusters are located extremely high, about 1 kpc above the disk midplane, i.e., they have been subject to some mechanism that has carried them into orbits uncharacteristic of this type of objects. It follows from a comparison with the results of chemical evolution that younger clusters with ages of 4-5 Gyr, e.g., NGC1193,M67, and others, may have formed in a broad range of Galactocentric distances. Their large heights above the disk midplane is sufficient to suggest that these clusters have moved away from their likely birthplaces. Clusters are carried far away from the Galactic disk until the present time: about 40 clusters with ages from 0 to 2 Gyr are observed at heights ranging from 300 to 750 pc.

  7. Minireview: Genetic basis of heterogeneity and severity in sickle cell disease

    PubMed Central

    Habara, Alawi

    2016-01-01

    Sickle cell disease, a common single gene disorder, has a complex pathophysiology that at its root is initiated by the polymerization of deoxy sickle hemoglobin. Sickle vasoocclusion and hemolytic anemia drive the development of disease complications. In this review, we focus on the genetic modifiers of disease heterogeneity. The phenotypic heterogeneity of disease is only partially explained by genetic variability of fetal hemoglobin gene expression and co-inheritance of α thalassemia. Given the complexity of pathophysiology, many different definitions of severity are possible complicating a full understanding of its genetic foundation. The pathophysiological complexity and the interlocking nature of the biological processes underpinning disease severity are becoming better understood. Nevertheless, useful genetic signatures of severity, regardless of how this is defined, are insufficiently developed to be used for treatment decisions and for counseling. PMID:26936084

  8. Link between sewage-derived nitrogen pollution and coral disease severity in Guam.

    PubMed

    Redding, Jamey E; Myers-Miller, Roxanna L; Baker, David M; Fogel, Marilyn; Raymundo, Laurie J; Kim, Kiho

    2013-08-15

    The goals of this study were to evaluate the contribution of sewage-derived N to reef flat communities in Guam and to assess the impact of N inputs on coral disease. We used stable isotope analysis of macroalgae and a soft coral, sampled bimonthly, as a proxy for N dynamics, and surveyed Porites spp., a dominant coral taxon on Guam's reefs, for white syndrome disease severity. Results showed a strong influence of sewage-derived N in nearshore waters, with δ(15)N values varying as a function of species sampled, site, and sampling date. Increases in sewage-derived N correlated significantly with increases in the severity of disease among Porites spp., with δ(15)N values accounting for more than 48% of the variation in changes in disease severity. The anticipated military realignment and related population increase in Guam are expected to lead to increased white syndrome infections and other coral diseases.

  9. Age and disease-related structural changes in the retinal pigment epithelium

    PubMed Central

    Bonilha, Vera L

    2008-01-01

    As the retinal pigment epithelium (RPE) ages, a number of structural changes occur, including loss of melanin granules, increase in the density of residual bodies, accumulation of lipofuscin, accumulation of basal deposits on or within Bruch’s membrane, formation of drusen (between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane), thickening of Bruch’s membrane, microvilli atrophy and disorganization of the basal infoldings. Although these changes are well known, the basic mechanisms involved in them are frequently poorly understood. These age-related changes progress slowly and vary in severity in different individuals. These changes are also found in age-related macular degeneration (AMD), a late onset disease that severely impacts the RPE, but they are much more pronounced than during normal aging. However, the changes in AMD lead to severe loss of vision. Given the many supporting functions which the RPE serves for the retina, it is important to decipher the age-related changes in this epithelium in order to understand age-related changes in vision. PMID:19668732

  10. Age-related carbon dioxide reactivity in children after moderate and severe traumatic brain injury.

    PubMed

    Maa, Tensing; Yeates, Keith Owen; Moore-Clingenpeel, Melissa; O'Brien, Nicole F

    2016-07-01

    OBJECTIVE The objective of this study is to assess carbon dioxide reactivity (CO2R) in children following traumatic brain injury (TBI). METHODS This prospective observational study enrolled children younger than 18 years old following moderate and severe TBI. Thirty-eight mechanically ventilated children had daily CO2R testing performed by measuring changes in their bilateral middle cerebral artery flow velocities using transcranial Doppler ultrasonography (TCD) after a transient increase in minute ventilation. The cohort was divided into 3 age groups: younger than 2 years (n = 12); 2 to 5 years old (n = 9); and older than 5 years (n = 17). RESULTS Children younger than 2 years old had a lower mean CO2R over time. The 2-5-year-old age group had higher mean CO2R than younger patients (p = 0.01), and the highest CO2R values compared with either of the other age groups (vs > 5 years old, p = 0.046; vs < 2 years old, p = 0.002). Having a lower minimum CO2R had a statistically significant negative effect on outcome at discharge (p = 0.0413). Impaired CO2R beyond Postinjury Day 4 trended toward having an effect on outcome at discharge (p = 0.0855). CONCLUSIONS Abnormal CO2R is prevalent in children following TBI, and the degree of impairment varies by age. No clinical or laboratory parameters were identified as risk factors for impaired CO2R. Lower minimum CO2R values are associated with worse outcome at discharge.

  11. Ocular Surface Disease and Dacryoadenitis in Aging C57BL/6 Mice

    PubMed Central

    McClellan, Andrew J.; Volpe, Eugene A.; Zhang, Xiaobo; Darlington, Gretchen J.; Li, De-Quan; Pflugfelder, Stephen C.; de Paiva, Cintia S.

    2015-01-01

    Dry eye in humans displays increased prevalence in the aged and in women. Here, we investigated the ocular surfaces and lacrimal glands of aged mice of both sexes. We surveyed three different ages [young, middle-aged (6 to 9 months), and elderly] by investigating severity markers of dry eye disease (DED). We observed an age-dependent dry eye phenotype as early as 6 to 9 months: increased corneal surface irregularity, increased corneal barrier disruption, conjunctival CD4+ T-cell infiltration, and loss of mucin-filled goblet cells. Expression of interferon-γ, IL-17 mRNA transcripts was increased in the conjunctiva and IL-17A, matrix metallopeptidase 9, and chemokine ligand 20 in the corneas of elderly mice. Elderly male mice develop more of a skewed response of type 1 T helper cell, whereas female mice have a bias toward type 17 T helper cell in the conjunctiva. In the lacrimal gland, an increase in CD4+ and CD8+ T cells and B cells and a decrease in activated dendritic cells were observed. Adoptive transfer of CD4+ T cells isolated from elderly mice transferred DED into young immunodeficient recipients, which was more pronounced from male donors. Our findings show the development of DED in aging mice. Pathogenic CD4+ T cells that develop with aging are capable of transferring DED from older mice to naive immunodeficient recipients. Taken together, our results indicate that age-related autoimmunity contributes to development of DED with aging. PMID:24389165

  12. Picture priming in normal aging and Alzheimer's disease.

    PubMed

    Ballesteros, Soledad; Reales, José M; Mayas, Julia

    2007-05-01

    The present study investigated age invariance for naming pictures and whether implicit memory is spared in Alzheimer's disease (AD). During the study phase, young adults, AD patients, and older controls were shown outlines of familiar pictures. After a distracter task, implicit memory was assessed incidentally. The results showed similar visual priming for the three groups, although young adults responded faster than the two older groups. Moreover, the number of errors was smaller for studied than for non-studied pictures. This pattern of results was repeated across the three groups, although AD patients produced more errors than young adults and older controls, and there were no differences between these latter groups. These results confirmed previous visual and haptic findings showing unimpaired perceptual priming in normal aging and AD patients when implicit memory is assessed using identification tasks. These results are interpreted from a cognitive neuroscience perspective. PMID:17425893

  13. Picture priming in normal aging and Alzheimer's disease.

    PubMed

    Ballesteros, Soledad; Reales, José M; Mayas, Julia

    2007-05-01

    The present study investigated age invariance for naming pictures and whether implicit memory is spared in Alzheimer's disease (AD). During the study phase, young adults, AD patients, and older controls were shown outlines of familiar pictures. After a distracter task, implicit memory was assessed incidentally. The results showed similar visual priming for the three groups, although young adults responded faster than the two older groups. Moreover, the number of errors was smaller for studied than for non-studied pictures. This pattern of results was repeated across the three groups, although AD patients produced more errors than young adults and older controls, and there were no differences between these latter groups. These results confirmed previous visual and haptic findings showing unimpaired perceptual priming in normal aging and AD patients when implicit memory is assessed using identification tasks. These results are interpreted from a cognitive neuroscience perspective.

  14. Proteostasis and the Aging Proteome in Health and Disease

    PubMed Central

    2014-01-01

    The maintenance of the proteome is essential to preserve cell functionality and the ability to respond and adapt to the changing environment. This is regulated by the proteostasis network, a dedicated set of molecular components comprised of molecular chaperones and protein clearance mechanisms, regulated by cell stress signaling pathways, that prevents the toxicity associated with protein misfolding and accumulation of toxic aggregates in different subcellular compartments and tissues. The efficiency of the proteostasis network declines with age and this failure in protein homeostasis has been proposed to underlie the basis of common age-related human disorders. The current advances in the understanding of the mechanisms and regulation of proteostasis and of the different types of digressions in this process in aging have turned the attention toward the therapeutic opportunities offered by the restoration of proteostasis in age-associated degenerative diseases. Here, we discuss some of the unresolved questions on proteostasis that need to be addressed to enhance healthspan and to diminish the pathology associated with persistent protein damage. PMID:24833584

  15. Genome maintenance and transcription integrity in aging and disease

    PubMed Central

    Wolters, Stefanie; Schumacher, Björn

    2013-01-01

    DNA damage contributes to cancer development and aging. Congenital syndromes that affect DNA repair processes are characterized by cancer susceptibility, developmental defects, and accelerated aging (Schumacher et al., 2008). DNA damage interferes with DNA metabolism by blocking replication and transcription. DNA polymerase blockage leads to replication arrest and can gives rise to genome instability. Transcription, on the other hand, is an essential process for utilizing the information encoded in the genome. DNA damage that interferes with transcription can lead to apoptosis and cellular senescence. Both processes are powerful tumor suppressors (Bartek and Lukas, 2007). Cellular response mechanisms to stalled RNA polymerase II complexes have only recently started to be uncovered. Transcription-coupled DNA damage responses might thus play important roles for the adjustments to DNA damage accumulation in the aging organism (Garinis et al., 2009). Here we review human disorders that are caused by defects in genome stability to explore the role of DNA damage in aging and disease. We discuss how the nucleotide excision repair system functions at the interface of transcription and repair and conclude with concepts how therapeutic targeting of transcription might be utilized in the treatment of cancer. PMID:23443494

  16. Musculoskeletal Disease in Aged Horses and Its Management.

    PubMed

    van Weeren, Paul René; Back, Willem

    2016-08-01

    Musculoskeletal disorders are the most prevalent health problem in aging horses. They are not life threatening, but are painful and an important welfare issue. Chronic joint disease (osteoarthritis) and chronic laminitis are the most prevalent. Treating osteoarthritis in the elderly horse is similar to treating performance horses, but aims at providing a stable situation with optimal comfort. Immediate medical treatment of flare-ups, long-term pain management, and adaptation of exercise and living conditions are the mainstays of treatment. Laminitis in the geriatric horse is related often to pituitary pars intermedia dysfunction, which may be treated with additional pergolide. PMID:27449390

  17. Evidence for age susceptibility of cattle to Johne's disease.

    PubMed

    Windsor, Peter A; Whittington, Richard J

    2010-04-01

    Calf rearing programs for the control of bovine Johne's disease (BJD) in dairy farms have been widely adopted globally and are based on evidence that the most significant risk factor for developing the disease is exposure of young calves to infectious doses of the causative organism Mycobacterium avium subsp. paratuberculosis (Mptb). Hygienic calf rearing practices aim to break the transmission cycle of Mptb by removing neonatal calves from their dams within 12h of birth and segregating replacement heifers from the herd until they are 12 months of age. But compliance with these interventions is difficult for many producers and delaying the removal of calves from their dams and earlier return of heifers to the herd are common practices. However, would changing these practices increase the risk of animals contracting BJD? Evidence for age susceptibility of calves and young adults to Mptb is reviewed. The experimental studies selected for inclusion in an analysis of the evidence were those designed specifically to address the issue and were confined to examination of 140 cattle in experiments conducted by eight groups of workers between the years 1938 and 2006. Approximately 75% of calves <6 months of age, 50% of those aged between 6 and 12 months, and just less than 20% of cattle >12 months old developed lesions indicative of BJD infection when exposed to any of the tested routes of Mptb infection. No direct evidence was found to support the commonly held view that calf removal from the dam for a maximum period of 12h is preferable to 24h. However the studies did show that if exposure to infection occurs at birth, then the risk of infection progressing to BJD is high, particularly in a highly contaminated environment or if the dam is infected.

  18. Age and Adaptive Functioning in Children and Adolescents with ASD: The Effects of Intellectual Functioning and ASD Symptom Severity

    ERIC Educational Resources Information Center

    Hill, Trenesha L.; Gray, Sarah A. O.; Kamps, Jodi L.; Enrique Varela, R.

    2015-01-01

    The present study examined the moderating effects of intellectual functioning and ASD symptom severity on the relation between age and adaptive functioning in 220 youth with autism spectrum disorder (ASD). Regression analysis indicated that intellectual functioning and ASD symptom severity moderated the relation between age and adaptive…

  19. Age differences in emotional responses to daily stress: The role of timing, severity, and global perceived stress

    PubMed Central

    Scott, Stacey B.; Sliwinski, Martin J.; Blanchard Fields, Fredda

    2013-01-01

    Research on age differences in emotional responses to daily stress has produced inconsistent findings. Guided by recent theoretical advances in aging theory (Charles, 2010) that emphasize the importance of context for predicting when and how age is related to affective well-being, the current study examined age differences in emotional responses to everyday stressors. The present study examines how three contextual features (e.g., timing of exposure, stressor severity, global perceived stress [GPS]) moderate age differences in emotional experience in an ecological momentary assessment study of adults aged 18–81 (N=190). Results indicated older adults’ negative affect (NA) was less affected by exposure to recent stressors than younger adults, but that there were no age differences in the effects of stressor exposure three to six hours afterward. Higher levels of GPS predicted amplified NA responses to daily stress, and controlling for GPS eliminated age differences in NA responses to stressors. No age differences in NA responses as a function of stressor severity were observed. In contrast, older age was associated with less of a decrease in PA when exposed to recent stressors or with more severe recent stressors. There were no age differences in the effect of previous stressor exposure or severity on PA, nor any interactions between momentary or previous stress and GPS on PA. Together, these results support the notion that chronic stress plays a central role in emotional experience in daily life. Implications of these results for emotion theories of aging are discussed. PMID:24364410

  20. Chronic hepatitis C: an age wave of disease burden.

    PubMed

    McHutchison, John G; Bacon, Bruce R

    2005-10-01

    There are at least 2.7 million individuals in the United States, most of them in their 40s and 50s, who are chronically infected with hepatitis C virus (HCV). As these infected individuals get older, about 20% will develop cirrhosis, and a significant fraction of those with cirrhosis (about 1 in 10) will then develop serious decompensated liver disease or hepatocellular carcinoma. Currently, HCV is the primary cause of death in 8000 to 12 000 people every year; the virus is also the primary reason for liver transplantation in the United States. Although the number of new cases of HCV infection has been dropping steadily since the introduction of improved blood-supply screening, the "age wave" of existing chronic HCV in baby boomers is expected to contribute to a substantial rise in morbidity, mortality, and costs over the next 2 decades. Although it is difficult to predict which HCV-infected patients will progress to serious liver disease, the availability of a combination drug regimen (peginterferon alfa plus ribavirin) that essentially "cures" the disease in more than half of treated patients now provides clinicians and pharmacists in managed care settings with the tools needed to diminish the impact of the anticipated wave of liver disease. This article reviews the epidemiology, natural history, clinical and economic burden, and screening and treatment options for HCV. PMID:16232012

  1. Prediction of Disease Severity in Patients with Early Rheumatoid Arthritis by Gene Expression Profiling

    PubMed Central

    Liu, Zheng; Sokka, Tuulikki; Maas, Kevin; Olsen, Nancy J.; Aune, Thomas M.

    2009-01-01

    In order to test the ability of peripheral blood gene expression profiles to predict future disease severity in patients with early rheumatoid arthritis (RA), a group of 17 patients (1 ± 0.2 years disease duration) was evaluated at baseline for gene expression profiles. Disease status was evaluated after a mean of 5 years using an index combining pain, global and recoded MHAQ scores. Unsupervised and supervised algorithms identified “predictor genes” whose combined expression levels correlated with follow-up disease severity scores. Unsupervised clustering algorithms separated patients into two branches. The only significant difference between these two groups was the disease severity score; demographic variables and medication usage were not different. Supervised T-Test analysis identified 19 “predictor genes” of future disease severity. Results were validated in an independent cohort of subjects of established RA with using Support Vector Machines and K-Nearest-Neighbor Classification. Our study demonstrates that peripheral blood gene expression profiles may be a useful tool to predict future disease severity in patients with early and established RA. PMID:20948566

  2. Evidence of subclinical prion disease in aged mice following exposure to bovine spongiform encephalopathy.

    PubMed

    Brown, Karen L; Mabbott, Neil A

    2014-01-01

    The occurrence of variant Creutzfeldt-Jakob (vCJD) disease in humans was almost certainly the result of consumption of food contaminated with bovine spongiform encephalopathy (BSE) prions. Despite probable widespread exposure of the UK population to BSE-contaminated food in the 1980s, vCJD has been identified predominantly in young individuals, and there have been fewer cases of clinical disease than anticipated. The reasons for this are uncertain. Following peripheral exposure, many prions replicate within the lymphoid tissues before infecting the central nervous system. We have shown that the effects of host age on the microarchitecture of the spleen significantly impair susceptibility to mouse-adapted prions after peripheral exposure. The transmission of prions between different mammalian species is considered to be limited by the 'species barrier', which is dependent on several factors, including an intact immune system. Thus, cross-species prion transmission may be much less efficient in aged individuals. To test this hypothesis, we compared prion pathogenesis in groups of young (6-8 weeks old) and aged (600 days old) mice injected with primary BSE brain homogenate. We showed that prion pathogenesis was impaired dramatically in aged mice when compared with young animals. Whereas most young mice succumbed to clinical prion disease, all aged mice failed to develop clinical disease during their lifespans. However, the demonstration that prion accumulation was detected in the lymphoid tissues of some aged mice after injection with primary BSE brain homogenate, in the absence of clinical signs of prion disease, has important implications for human health.

  3. Prevalence and Severity of Voice and Swallowing Difficulties in Mitochondrial Disease

    ERIC Educational Resources Information Center

    Read, Jennifer L.; Whittaker, Roger G.; Miller, Nick; Clark, Sue; Taylor, Robert; McFarland, Robert; Turnbull, Douglass

    2012-01-01

    Background: Mutations of mitochondrial DNA (mtDNA) cause a broad spectrum of clinical phenotypes. Anecdotal evidence suggests that voice and swallow problems are a common feature of these diseases. Aims: To characterize accurately the prevalence and severity of voice and swallow problems in a large cohort of patients with mitochondrial disease.…

  4. Selective Vulnerability of Neurons in Layer II of the Entorhinal Cortex during Aging and Alzheimer's Disease

    PubMed Central

    Stranahan, Alexis M.; Mattson, Mark P.

    2010-01-01

    All neurons are not created equal. Certain cell populations in specific brain regions are more susceptible to age-related changes that initiate regional and system-level dysfunction. In this respect, neurons in layer II of the entorhinal cortex are selectively vulnerable in aging and Alzheimer's disease (AD). This paper will cover several hypotheses that attempt to account for age-related alterations among this cell population. We consider whether specific developmental, anatomical, or biochemical features of neurons in layer II of the entorhinal cortex contribute to their particular sensitivity to aging and AD. The entorhinal cortex is a functionally heterogeneous environment, and we will also review data suggesting that, within the entorhinal cortex, there is subregional specificity for molecular alterations that may initiate cognitive decline. Taken together, the existing data point to a regional cascade in which entorhinal cortical alterations directly contribute to downstream changes in its primary afferent region, the hippocampus. PMID:21331296

  5. Influence of Deep Breathing on Heart Rate Variability in Parkinson’s Disease: Co-relation with Severity of Disease and Non-Motor Symptom Scale Score

    PubMed Central

    Jagtap, Gayatri J; Chakor, Rahul T

    2014-01-01

    Context: Dysautonomia and non-motor symptoms (NMS) in Parkinson’s disease (PD) are frequent, disabling and reduce quality of life of patient. Aims and Objective: There is a paucity of studies on autonomic dysfunction in PD in Indian population. The study aimed to evaluate autonomic dysfunction in PD patients and co-relate the findings with severity of PD and Non-Motor Symptoms Scale (NMSS) score. Materials and Methods: We evaluated autonomic function in 30 diagnosed patients of PD (age 55-70 years) and 30 healthy age-matched controls by 3 min deep breathing test (DBT). NMSS was used to identify non-motor symptoms and Hoehn and Yahr (HY) Scale to grade severity of PD. The DBT findings were co-related with severity of PD (HY staging) and NMSS score. Results: DBT was found to be abnormal in 40% while it was on borderline in 33.3% of PD patients. There was a statistically significant difference (p<0.01) between patients and control group for the DBT. NMS were reported across all the stages of PD but with variable frequency and severity for individual symptom. A negative co-relation was found between results of deep breathing test and clinical severity of disease and NMSS score. Conclusion: Abnormalities of autonomic function and NMS were integral and present across all the stages of PD patients. Early recognition and treatment of these may decrease morbidity and improve quality of life of PD patients. PMID:25177554

  6. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's disease?

    PubMed

    Kent, Brianne A

    2014-01-01

    Alzheimer's disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD. PMID:25225484

  7. Disease onset and aging in the world of circular RNAs

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    Circular ribonucleic acids (circRNAs) are non-coding RNAs of approximately 100 nucleotides in length with thousands of members in mammalian cells. The presence of circRNAs is believed to be even greater than that of messenger RNAs. Identification of circRNAs occurred approximately 37 years ago with the subsequent demonstration that covalent bonds are necessary for the unique circular structure of these ribonucleic acids. However, present understanding of the complex biological role of circRNAs remains limited and requires further elucidation. CircRNAs may impact aging, multiple disorders, function as biomarkers, and are able to regulate gene expression by acting as effective microRNA (miRNA) sponges. New work suggests that circRNAs are vital for the modulation of cellular senescence and programmed cell death pathways such as apoptosis. These non-coding RNAs can control cell cycle progression, cellular proliferation, and cellular survival impacting disorders linked to aging, cardiovascular disease, and atherosclerosis through pathways that involve cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase inhibitor 1 (p21), and mammalian forkhead transcription factors. In addition, circRNAs can oversee cellular metabolism and disorders such as diabetes mellitus through the regulation of insulin signaling as well as limit tumor progression through Wnt signaling and β-catenin pathways. Further understanding of the biology of circRNAs offers great promise for the targeting of novel strategies against a wide spectrum of disease entities. PMID:27642518

  8. Lipidomics of human brain aging and Alzheimer's disease pathology.

    PubMed

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.

  9. The hippocampus in aging and disease: From plasticity to vulnerability.

    PubMed

    Bartsch, T; Wulff, P

    2015-11-19

    The hippocampus has a pivotal role in learning and in the formation and consolidation of memory and is critically involved in the regulation of emotion, fear, anxiety, and stress. Studies of the hippocampus have been central to the study of memory in humans and in recent years, the regional specialization and organization of hippocampal functions have been elucidated in experimental models and in human neurological and psychiatric diseases. The hippocampus has long been considered a classic model for the study of neuroplasticity as many examples of synaptic plasticity such as long-term potentiation and -depression have been identified and demonstrated in hippocampal circuits. Neuroplasticity is the ability to adapt and reorganize the structure or function to internal or external stimuli and occurs at the cellular, population, network or behavioral level and is reflected in the cytological and network architecture as well as in intrinsic properties of hippocampal neurons and circuits. The high degree of hippocampal neuroplasticity might, however, be also negatively reflected in the pronounced vulnerability of the hippocampus to deleterious conditions such as ischemia, epilepsy, chronic stress, neurodegeneration and aging targeting hippocampal structure and function and leading to cognitive deficits. Considering this framework of plasticity and vulnerability, we here review basic principles of hippocampal anatomy and neuroplasticity on various levels as well as recent findings regarding the functional organization of the hippocampus in light of the regional vulnerability in Alzheimer's disease, ischemia, epilepsy, neuroinflammation and aging. PMID:26241337

  10. Chaperonomics, a new tool to study ageing and associated diseases.

    PubMed

    Brocchieri, Luciano; Conway de Macario, Everly; Macario, Alberto J L

    2007-01-01

    The participation of molecular chaperones in the process of senescence and in the mechanisms of age-related diseases is currently under investigation in many laboratories. However, accurate, complete information about the number and diversity of chaperone genes in any given genome is scarce. Consequently, the results of efforts aimed at elucidating the role of chaperones in ageing and disease are often confusing and contradictory. To remedy this situation, we have developed chaperonomics, including means to identify and characterize chaperone genes and their families applicable to humans and model organisms. The problem is difficult because in eukaryotic organisms chaperones have evolved into complex multi-gene families. For instance, the occurrence of multiple paralogs in a single genome makes it difficult to interpret results if consideration is not given to the fact that similar but distinct chaperone genes can be differentially expressed in separate cellular compartments, tissues, and developmental stages. The availability of complete genome sequences allows implementation of chaperonomics with the purpose of understanding the composition of chaperone families in all cell compartments, their evolutionary and functional relations and, ultimately, their role in pathogenesis. Here, we present a series of concatenated, complementary procedures for identifying, characterizing, and classifying chaperone genes in genomes and for elucidating evolutionary relations and structural features useful in predicting functional properties. We illustrate the procedures with applications to the complex family of hsp70 genes and show that the kind of data obtained can provide a solid basis for future research.

  11. The hippocampus in aging and disease: From plasticity to vulnerability.

    PubMed

    Bartsch, T; Wulff, P

    2015-11-19

    The hippocampus has a pivotal role in learning and in the formation and consolidation of memory and is critically involved in the regulation of emotion, fear, anxiety, and stress. Studies of the hippocampus have been central to the study of memory in humans and in recent years, the regional specialization and organization of hippocampal functions have been elucidated in experimental models and in human neurological and psychiatric diseases. The hippocampus has long been considered a classic model for the study of neuroplasticity as many examples of synaptic plasticity such as long-term potentiation and -depression have been identified and demonstrated in hippocampal circuits. Neuroplasticity is the ability to adapt and reorganize the structure or function to internal or external stimuli and occurs at the cellular, population, network or behavioral level and is reflected in the cytological and network architecture as well as in intrinsic properties of hippocampal neurons and circuits. The high degree of hippocampal neuroplasticity might, however, be also negatively reflected in the pronounced vulnerability of the hippocampus to deleterious conditions such as ischemia, epilepsy, chronic stress, neurodegeneration and aging targeting hippocampal structure and function and leading to cognitive deficits. Considering this framework of plasticity and vulnerability, we here review basic principles of hippocampal anatomy and neuroplasticity on various levels as well as recent findings regarding the functional organization of the hippocampus in light of the regional vulnerability in Alzheimer's disease, ischemia, epilepsy, neuroinflammation and aging.

  12. Preface: The aging eye: normal changes, age-related diseases, and sight-saving approaches.

    PubMed

    Chader, Gerald J; Taylor, Allen

    2013-12-13

    This volume presents articles based on a workshop held June 14 to 16, 2013 in Rancho Palos Verde, CA sponsored by the Ocular Research Symposia Foundation (ORSF). The mission of the ORSF is to focus attention on unmet needs and current research opportunities in eye research with the objective of accelerating translation of research findings to effective clinical care. In this workshop, the subject of the "The Aging Eye" was addressed, including the prevalence of eye diseases in aging and the economic burden imposed by these diseases. New research work was highlighted on the genetics, biology, biochemistry, neurochemistry, and the impact of nutrition and the environment on function in the older eye. By identifying "low-hanging fruit" (i.e., the best opportunities for successful transition of laboratory research for the prevention of and new treatments and cures for ocular diseases), we seek to spur funding at both the basic research and clinical levels, resulting in sight-saving and sight-restoration measures in the near future.

  13. Accuracy of plant specimen disease severity estimates: concepts, history, methods, ramifications and challenges for the future

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knowledge of the extent of the symptoms of a plant disease, generally referred to as severity, is key to both fundamental and applied aspects of plant pathology. Most commonly, severity is obtained visually and the accuracy of each estimate (closeness to the actual value) by individual raters is par...

  14. Severe Pediatric Adenovirus 7 Disease in Singapore Linked to Recent Outbreaks across Asia.

    PubMed

    Ng, Oon-Tek; Thoon, Koh Cheng; Chua, Hui Ying; Tan, Natalie Woon Hui; Chong, Chia Yin; Tee, Nancy Wen Sim; Lin, Raymond Tzer Pin; Cui, Lin; Venkatachalam, Indumathi; Tambyah, Paul Anantharajah; Chew, Jonathan; Fong, Raymond Kok Choon; Oh, Helen May Lin; Krishnan, Prabha Unny; Lee, Vernon Jian Ming; Tan, Boon Huan; Ng, Sock Hoon; Ting, Pei Jun; Maurer-Stroh, Sebastian; Gunalan, Vithiagaran; Khong, Wei Xin

    2015-07-01

    During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.

  15. Pedestrian and Pedalcyclist Injury Costs in the United States by Age and Injury Severity

    PubMed Central

    Miller, Ted R.; Zaloshnja, Eduard; Lawrence, Bruce A.; Crandall, Jeff; Ivarsson, Johan; Finkelstein, A. Eric

    2004-01-01

    This paper estimates the incidence, unit costs, and annual costs of pedestrian and pedalcycle crash injuries in the United States. It includes medical care costs, household and wage work losses, and the value of pain, suffering, and lost quality of life. The estimates are broken down by body region and severity. They rely heavily on data from the health care system. Costs of pedestrian and pedalcycle injuries in 2000 will total $40 billion over the lifetimes of the injured. Most pedalcyclist injury costs and half of pedestrian injury costs do not involve motor vehicles. Youth ages 5–14 face greater annual risks when walking or driving their own pedaled vehicles than when being driven. Children under age 5 experience higher costs than their elders when injured as pedestrians. Our results suggest European and Japanese component tests used to design pedestrian injury countermeasures for motor vehicles are too narrow. Separate lower limb testing is needed for younger children. Testing for torso/vertebral column injury of adults also seems desirable. PMID:15319130

  16. Dermatological disease in the older age group: a cross-sectional study in aged care facilities

    PubMed Central

    Deo, Maneka S; Vandal, Alain C; Jarrett, Paul

    2015-01-01

    Objectives To estimate the prevalence of dermatological disease in aged care facilities, and the relationship between cognitive or physical disability and significant disease. Setting 2 large aged care facilities in Auckland, New Zealand, each providing low and high level care. Participants All 161 residents of the facilities were invited to participate. The only exclusion criterion was inability to obtain consent from the individual or designated guardian. 88 participants were recruited—66 females (75%), 22 males (25%) with average age 87.1 years (SD 5.5 years). Primary and secondary outcome measures Primary—presence of significant skin disease (defined as that which in the opinion of the investigators needed treatment or was identified as a patient concern) diagnosed clinically on full dermatological examination by a dermatologist or dermatology trainee. Secondary—functional and cognitive status (Rehabilitation Complexity Scale and Abbreviated Mental Test Score). Results 81.8% were found to have at least one significant condition. The most common disorders were onychomycosis 42 (47.7%), basal cell carcinoma 13 (14.8%), asteototic eczema 11 (12.5%) and squamous cell carcinoma in situ 9 (10.2%). Other findings were invasive squamous cell carcinoma 7 (8%), bullous pemphigoid 2 (2.3%), melanoma 2 (2.3%), lichen sclerosus 2 (2.3%) and carcinoma of the breast 1 (1.1%). Inflammatory disease was more common in those with little physical disability compared with those with serious physical disability (OR 3.69; 95% CI 1.1 to 12.6, p=0.04). No significant association was found between skin disease and cognitive impairment. Conclusions A high rate of dermatological disease was found. Findings ranged from frequent but not life-threatening conditions (eg, onychomycosis), to those associated with a significant morbidity (eg, eczema, lichen sclerosus and bullous pemphigoid), to potentially life-threatening (eg, squamous cell carcinoma, melanoma and breast cancer

  17. Associations between peripheral blood eosinophil counts in patients with systemic sclerosis and disease severity.

    PubMed

    Ando, Katsutoshi; Nakashita, Tamao; Kaneko, Norihiro; Takahashi, Kazuhisa; Motojima, Shinji

    2016-01-01

    Increased levels of serum pro-fibrotic cytokines have been reported in patients with systemic sclerosis (SSc). Some of these cytokines also play an important role in the differentiation and migration of eosinophils. The aim of this study was to determine whether eosinophilic inflammation is caused in SSc. We retrospectively reviewed the peripheral blood eosinophil counts in 70 untreated patients with SSc and compared them with those in patients with other major collagen diseases. We additionally evaluated a possible association with disease severity. Eosinophil counts were significantly higher levels in patients with SSc than in those with other collagen diseases, whereas total leukocyte counts were not. Eosinophil counts correlated positively with both severe interstitial lung disease (ILD; r = 0.255, p = 0.033) and modified Rodnan total skin thickness score (m-Rodnan TSS) in SSc (r = 0.347, p = 0.003), but did not correlate with ILD severity in other collagen diseases. In conclusion, peripheral eosinophil counts were higher in patients with SSc than in those with other collagen diseases and were correlated with increased disease severity. Our data suggest that eosinophilic inflammation is involved in the pathogenesis and progression of SSc. PMID:27610320

  18. Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity.

    PubMed

    Huijbers, Maartje G; Vink, Anna-Fleur D; Niks, Erik H; Westhuis, Ruben H; van Zwet, Erik W; de Meel, Robert H; Rojas-García, Ricardo; Díaz-Manera, Jordi; Kuks, Jan B; Klooster, Rinse; Straasheijm, Kirsten; Evoli, Amelia; Illa, Isabel; van der Maarel, Silvère M; Verschuuren, Jan J

    2016-02-15

    Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect disease severity or treatment responsiveness. We mapped the MuSK epitopes of 255 longitudinal serum samples of 53 unique MuSK MG patients from three independent cohorts with ELISA. Antibodies against the MuSK Iglike-1 domain determine disease severity. Epitope spreading outside this domain did not contribute to disease severity nor to pyridostigmine responsiveness. This provides a rationale for epitope specific treatment strategies.

  19. Aging syndrome genes and premature coronary artery disease

    PubMed Central

    Low, Adrian F; O'Donnell, Christopher J; Kathiresan, Sekar; Everett, Brendan; Chae, Claudia U; Shaw, Stanley Y; Ellinor, Patrick T; MacRae, Calum A

    2005-01-01

    Background Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD. Methods We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire LMNA gene, including the promoter and untranslated regions, was performed using a combination of TaqMan® probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the KLOTHO gene was typed using restriction digest of a PCR amplicon. Results Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the LMNA or KLOTHO loci between the two groups. In addition, there was no evidence of excess homozygosity at the LMNA locus. Conclusion Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO. PMID:16262891

  20. Aging, Transition, and Estimating the Global Burden of Disease

    PubMed Central

    Seligman, Benjamin J.; Cullen, Mark R.; Horwitz, Ralph I.

    2011-01-01

    Background The World Health Organization's Global Burden of Disease (GBD) reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries. Methods and Results Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd) probability of 0.22 (0.06) to 0.46 (0.1). For females, the increase was from 0.26 (0.06) to 0.65 (0.08). By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2) to 0.09 (0.06). Among females, the decline was from 0.36 (0.12) to 0.15 (0.08). Conclusions These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered. PMID:21629652

  1. The school age child with congenital heart disease.

    PubMed

    Boyle, Lynn; Kelly, Michelle M; Reynolds, Kathryn; Conlan, Misty; Taylor, Felisha

    2015-01-01

    Currently, in the United States, there are approximately 1 in 150 adults living with congenital heart disease (CHD) (). Infant and childhood mortality related to CHD decreased by 31% between 1987 and 2005 (). This survival trend is predicted to increase each year due to advancements in treatment and management of CHD. This significant shift in the epidemiology of CHD requires nurses to take action in preparing children with CHD and their families for their teenage years and young adulthood. The school-age child is the ideal age to begin teaching the child about their healthcare needs and how to care for themselves in preparation for the future. The school-age child with CHD has specific physical, intellectual, emotional, and developmental needs that must be considered and managed using a multidisciplinary approach. Pediatric nurses must be aware of these needs as they help the child and their family seamlessly and successfully transition into young adulthood as a happy and healthy CHD survivor. PMID:25330332

  2. Macroalgae Has No Effect on the Severity and Dynamics of Caribbean Yellow Band Disease

    PubMed Central

    Vu, Ivana; Smelick, Gillian; Harris, Sam; Lee, Sarah C.; Weil, Ernesto; Whitehead, Robert F.; Bruno, John F.

    2009-01-01

    By removing herbivores and promoting increases in macroalgae, overfishing is thought to indirectly cause coral disease and mortality. We performed three field manipulations to test the general hypothesis that overfishing and the subsequent alteration of coral reef trophic dynamics are a cause of coral epizootics. Specifically, we asked whether the presence of macroalgae can influence within- and among-colony spread rates of Caribbean Yellow Band Disease in Montastraea faveolata. Macroalgae were placed next to infected and healthy, adult and small coral colonies to measure effects on disease spread rate, coral growth and coral survival. Surprisingly, the addition of macroalgae did not affect disease severity or coral fitness. Our results indicate that macroalgae have no effect on the severity and dynamics of Caribbean Yellow Band Disease and that fisheries management alone will not mitigate the effects of this important epizootic. PMID:19223986

  3. Macroalgae has no effect on the severity and dynamics of Caribbean yellow band disease.

    PubMed

    Vu, Ivana; Smelick, Gillian; Harris, Sam; Lee, Sarah C; Weil, Ernesto; Whitehead, Robert F; Bruno, John F

    2009-01-01

    By removing herbivores and promoting increases in macroalgae, overfishing is thought to indirectly cause coral disease and mortality. We performed three field manipulations to test the general hypothesis that overfishing and the subsequent alteration of coral reef trophic dynamics are a cause of coral epizootics. Specifically, we asked whether the presence of macroalgae can influence within- and among-colony spread rates of Caribbean Yellow Band Disease in Montastraea faveolata. Macroalgae were placed next to infected and healthy, adult and small coral colonies to measure effects on disease spread rate, coral growth and coral survival. Surprisingly, the addition of macroalgae did not affect disease severity or coral fitness. Our results indicate that macroalgae have no effect on the severity and dynamics of Caribbean Yellow Band Disease and that fisheries management alone will not mitigate the effects of this important epizootic.

  4. Short-term effect of severe exposure to methylmercury on atherosclerotic heart disease and hypertension mortality in Minamata.

    PubMed

    Inoue, Sachiko; Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

    2012-02-15

    Recent studies suggest potential adverse effects of methylmercury exposure on myocardial infarction and hypertension, although the evidence is still limited. We thus evaluated this association using age-standardized mortality ratios (ASMRs) in Minamata, where severe methylmercury poisoning had occurred. We obtained mortality data from annual vital statistics and demographic statistics from census. We then compared mortality of atherosclerotic heart disease including degenerative heart disease and hypertension in Minamata-city with those in Kumamoto Prefecture, which includes Minamata city, as a control. We estimated ASMRs and 95% confidence intervals (CIs) during the period from 1953 to 1970. ASMRs of atherosclerotic heart disease were continuously decreased during the period from 1953 to 1967. In contrast, the ASMR of hypertension was significantly elevated during the period from 1963 to 1967 (SMR=1.38, CI; 1.06-1.80); but they decreased later. Although dilution is present in this ecological study, our study supports the notion that methylmercury exposure induces hypertension. PMID:22277149

  5. Short-term effect of severe exposure to methylmercury on atherosclerotic heart disease and hypertension mortality in Minamata.

    PubMed

    Inoue, Sachiko; Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

    2012-02-15

    Recent studies suggest potential adverse effects of methylmercury exposure on myocardial infarction and hypertension, although the evidence is still limited. We thus evaluated this association using age-standardized mortality ratios (ASMRs) in Minamata, where severe methylmercury poisoning had occurred. We obtained mortality data from annual vital statistics and demographic statistics from census. We then compared mortality of atherosclerotic heart disease including degenerative heart disease and hypertension in Minamata-city with those in Kumamoto Prefecture, which includes Minamata city, as a control. We estimated ASMRs and 95% confidence intervals (CIs) during the period from 1953 to 1970. ASMRs of atherosclerotic heart disease were continuously decreased during the period from 1953 to 1967. In contrast, the ASMR of hypertension was significantly elevated during the period from 1963 to 1967 (SMR=1.38, CI; 1.06-1.80); but they decreased later. Although dilution is present in this ecological study, our study supports the notion that methylmercury exposure induces hypertension.

  6. Long-term result of autologous cultivated oral mucosal epithelial transplantation for severe ocular surface disease.

    PubMed

    Prabhasawat, Pinnita; Ekpo, Pattama; Uiprasertkul, Mongkol; Chotikavanich, Suksri; Tesavibul, Nattaporn; Pornpanich, Kanograt; Luemsamran, Panitee

    2016-09-01

    The present study aimed to investigate the clinical outcomes of autologous cultivated oral mucosal epithelial transplantation (COMET) on human amniotic membrane (AM) for corneal limbal stem cell deficiency (LSCD). In this prospective, noncomparative case series, 20 eyes (18 patients) with bilateral severe ocular surface disease were chosen to undergo COMET on human AM. The primary outcome was clinical success, and the secondary outcomes were the best-corrected visual acuity difference, corneal opacification, symblepharon formation, and complications. The mean patient age was 48.2 ± 15.5 years. The mean follow-up time was 31.9 ± 12.1 months (range 8-50 months). All except one eye exhibited complete epithelialization within the first postoperative week. A successful clinical outcome, defined as a stable ocular surface without epithelial defects, a clear cornea without fibrovascular tissue invasion at the pupillary area, and no or mild ocular surface inflammation, was obtained in 15 of 20 eyes (75 %). The clinical success rate at 1 year was 79.3 %, and that at 4 years (end of follow-up) was 70.5 %. Fourteen of 20 (70 %) eyes exhibited improvement in visual acuity after COMET, and some required subsequent cataract surgery (2 eyes), penetrating keratoplasty (3 eyes), or keratoprosthesis implantation (1 eye). Preoperative symblepharon was eliminated in most eyes (8 of 13, 61.5 %) after COMET combined with eyelid reconstruction when needed. The only complication was corneal perforation (1 eye) induced by a severe eyelid abnormality; treatment with a tectonic corneal graft was successful. COMET can successfully restore ocular surface damage in most eyes with corneal LSCD. PMID:27507558

  7. Daytime Physical Activity and Sleep in Hospitalized Older Adults: Association with Demographic Characteristics and Disease Severity

    PubMed Central

    Beveridge, Claire; Knutson, Kristen; Spampinato, Lisa; Flores, Andrea; Meltzer, David O.; Van Cauter, Eve; Arora, Vineet M.

    2016-01-01

    OBJECTIVES To assess objectively measured daytime physical activity and sleep duration and efficiency in hospitalized older adults and explore associations with demographic characteristics and disease severity. DESIGN Prospective cohort study. SETTING University of Chicago Medical Center general medicine wards. PARTICIPANTS Community-dwelling inpatients aged 50 and older (N = 120) MEASUREMENTS Physical activity and sleep were measured using wrist accelerometers. Information on Charlson Comorbidity Index and length of stay was collected from charts. Random-effects linear regression analysis was used to examine the association between in-hospital sleep and physical activity. RESULTS From March 2010 to May 2013, 120 participants wore wrist actigraphy monitors for at least 2 nights and 1 intervening day. Median activity level over the waking period was 77 counts/min (interquartile range 51–121 counts/min), an activity level that approximately corresponds to sitting while watching television (65 counts/min). Mean sleep duration the night before the activity interval was 289 ± 157 minutes, and mean sleep efficiency the night before the activity interval was 65.2 ± 26.9%. Mean activity counts/min were lowest for the oldest participants (oldest quartile 62, 95% confidence interval (CI) = 50–75; youngest quartile 121, 95% CI = 98–145, trend test P < .001) and those with highest Charlson Comorbidity Index (highest tertile 71, 95% CI = 60–83; lowest tertile 125, 95% CI = 104–147, trend test P = .01). Controlling for severity of illness and demographic characteristics, activity declined by 3 counts/min (95% CI = −5.65 to −0.43, P = .02) for each additional hour of inpatient sleep. CONCLUSION Older, sicker adults are less physically active during hospitalization. In contrast to studies in the community, inpatients who slept more were not more active. This may highlight that need for sleep is greater in the hospital than in the community. PMID:26131982

  8. Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria.

    PubMed

    Barber, Bridget E; William, Timothy; Grigg, Matthew J; Parameswaran, Uma; Piera, Kim A; Price, Ric N; Yeo, Tsin W; Anstey, Nicholas M

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

  9. Wheat - Its growth and disease severity as deduced from ERTS-1

    NASA Technical Reports Server (NTRS)

    Kanemasu, E. T.; Niblett, C. L.; Manges, H.; Lenhert, D.; Newman, M. A.

    1974-01-01

    The spectral reflectance of a cropped surface changes as the plant develops. An indicator of crop growth is leaf area index (ratio of green leaf area to soil area). The leaf area index, disease severity, and yield were determined for several winter wheat fields in Kansas during the 1973 growing season. Multispectral scanner (MSS) data from Earth Resources Technology Satellite-1 (ERTS-1) showed a high correlation (r greater than or equal to 0.90) between crop growth and MSS4/MSS5, and crop growth and MSS5/MSS6. Wheat disease severity and yields were significantly correlated at the 5% level with MSS4/MSS6 and with MSS4/MSS7. Further investigation is required before ERTS imagery can be routinely used detecting and estimating disease severity and yield reduction.

  10. Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label

    PubMed Central

    2011-01-01

    Introduction The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice. Methods The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents. Results A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection

  11. Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases

    PubMed Central

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-01-01

    Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia. Hypoxia is linked to prominent epigenetic changes in chromatin landscape. Screening studies have indicated that the stabilization of HIF-1α increases the expression of distinct histone lysine demethylases (KDM). HIF-1α stimulates the expression of KDM3A, KDM4B, KDM4C, and KDM6B, which enhance gene transcription by demethylating H3K9 and H3K27 sites (repressive epigenetic marks). In addition, HIF-1α induces the expression of KDM2B and KDM5B, which repress transcription by demethylating H3K4me2,3 sites (activating marks). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites. These epigenetic marks have important role in the control of heterochromatin segments and 3D folding of chromosomes, as well as the genetic loci regulating cell type commitment, proliferation, and cellular senescence, e.g. the INK4 box. A chronic stimulation of HIF-1α can provoke tissue fibrosis and cellular senescence, which both are increasingly present with aging and age-related diseases. We will review the regulation of HIF-1α-dependent induction of KDMs and clarify their role in

  12. Assessment of the relationship between asymmetric dimethylarginine and severity of erectile dysfunction and coronary artery disease.

    PubMed

    Aktoz, Tevfik; Aktoz, Meryem; Tatlı, Ersan; Kaplan, Mustafa; Turan, Fatma N; Barutcu, Ahmet; Atakan, Irfan H; Demir, Muzaffer; Altun, Armagan

    2010-12-01

    The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between plasma ADMA concentration and severity of erectile dysfunction (ED) and coronary artery disease (CAD). We measured plasma levels of ADMA in 92 male patients. Patients were divided into three groups: group 1 (n = 41), patients with ED and without CAD; group 2 (n = 29), patients with stable CAD; group 3 (n = 22), control group (patients without CAD or ED). Erectile function was evaluated by the erectile function domain of the international index of erectile function (IIEF-EFD) a validated 15-item self-administered questionnaire. Erectile function is specifically addressed by six questions that form the so-called erectile function domain of the questionnaire. Each question is scored 0-5. ED is defined as any value < 26. Patients with CAD who have stable angina pectoris were selected after coronary angiography. ADMA was analyzed by ELISA method. Group 1 had significantly higher concentrations of plasma ADMA than groups 2 and 3 (respectively, 0.75 ± 0.40 vs. 0.50 ± 0.30, P = 0.013; 0.75 ± 0.40 vs. 0.50 ± 0.25, P = 0.021). There was negative correlation between ADMA and IIEF-EFD score in all groups (n = 92) (r = -0.322, P = 0.002). In a multiple logistic regression analysis adjusting for age, hyperlipidemia, ADMA remained independent predictor for severe ED. Odds ratio for plasma ADMA was 14.151 (1.101-181.940; P = 0.042). First of all, this study provides that ADMA concentrations are significantly higher in patients who have ED when compared to patients with CAD and controls. Second, there was a negative correlation between ADMA and severity of ED. Elevating levels of circulating ADMA is an independent risk factor for severe of ED, and ADMA may be a link between CAD and ED. PMID:20091222

  13. Hormonal determinants of the severity of andropausal and depressive symptoms in middle-aged and elderly men with prediabetes.

    PubMed

    Rabijewski, Michał; Papierska, Lucyna; Kuczerowski, Roman; Piątkiewicz, Paweł

    2015-01-01

    Andropausal and depressive symptoms are common in aging males and may be associated with hormone deficiency. We investigated the severity of andropausal and depressive symptoms, as well as their hormonal determinants, in 196 middle-aged and elderly men (age range: 40-80 years) with prediabetes (PD) and in 184 healthy peers. PD was diagnosed according to the definition of the American Diabetes Association. The severity of andropausal and depressive symptoms was assessed using the Aging Males' Symptoms Rating Scale and the Self-Rating Depression Scale. Total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) were measured. The prevalence of andropausal syndrome in men with PD was significantly higher than that in healthy men (35% vs 11%, respectively). In men with PD aged 40-59 years, the severity of sexual, psychological, and all andropausal symptoms was greater than in healthy peers, while in elderly men (60-80 years), only the severity of psychological symptoms was greater than in healthy peers. The severity of depressive symptoms in the middle-aged men with PD was greater than in healthy peers, while the severity of depressive symptoms in elderly men with PD and healthy peers was similar. The higher prevalence of andropausal symptoms was independently associated with cFT and IGF-1 in middle-aged men and with TT and DHEAS in elderly men with PD. The more severe depression symptoms were associated with low TT and DHEAS in middle-aged men and with low cFT and DHEAS in elderly men with PD. In conclusion, the prevalence of andropausal symptoms, especially psychological, was higher in prediabetic patients as compared to healthy men, while the severity of depressive symptoms was higher only in middle-aged men with PD. Hormonal determinants of andropausal and depressive symptoms are different in middle-aged and elderly patients, but endocrine tests are necessary in all men with PD.

  14. Evaluation of anticardiolipin antibodies in tobacco users and non-tobacco users with severe chronic periodontal disease

    PubMed Central

    Yadalam, Pradeep K.; Rajapandian, K.; Ravishankar, P. L.; Vartharajan, Kalaivani; Subramaniam, Srinath; Dinakar, Mithra

    2016-01-01

    Aims: Many studies have proven that b2-glycoprotein-I-dependent anticardiolipin is elevated in periodontal diseases. Systemic lupus erythematosus and antiphospholipid syndrome, which are usually associated with high antiphospholipid antibodies, are more prone to adverse pregnancy outcomes and cardiovascular sequelae. Therefore, the aim of the present study is to evaluate IgG, IgM anticardiolipin antibodies in tobacco users and non-tobacco users with severe chronic periodontal disease. Materials and Methods: Based on the Armitage classification, 2000, 40 severe periodontitis (group D) (mean clinical attachment loss greater than 2.5 mm) male patients were selected for the study with the age range of 35–65 years and good general health from the Department of periodontics, SRM Kattankulathur Dental College, Chennai. They were classified as smokers (20 subjects) and non-smokers (20 subjects). Blood samples were collected and IgG, IgM antibodies were semi-quantitatively analyzed by enzyme-linked immunosorbent assay. The data thus collected were statistically analyzed by independent student's t-test. Results: Results showed that smokers with severe periodontitis exhibited marked increase in anticardiolipin IgG, IgM compared to non-smokers. They showed a positive correlation and statistical significance (P < 0.0001) between mean clinical attachment loss and IgG and IgM values. Conclusions: Results showed a rise in anticardiolipin antibodies in smokers with severe periodontitis, which indicates that these patients are more prone to coronary heart disease. PMID:27382544

  15. Influence of sex and disease severity on gene expression profiles in individuals with idiopathic pulmonary fibrosis

    PubMed Central

    McGee, Sean P; Zhang, Hongmei; Karmaus, Wilfried; Sabo-Attwood, Tara

    2014-01-01

    Epidemiological studies suggest sex-specific trends in the prevalence and mortality of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) that are distinct for each disease. While the expression of numerous immune and extracellular matrix (ECM) genes in the lung have been well characterized in these diseases, associations elucidating their sex-specific expression patterns by disease type and severity, and the evaluation of hormone-related genes, have not been well studied. Here we performed targeted transcriptional profiling of 48 genes was performed on lung tissue samples from males and females with mild or medium severity IPF or COPD. The genes assessed included those involved in inflammation, ECM remodeling and hormonal processes. Data for 36 lung tissue samples were obtained that were stratified by disease and sex. Expression levels revealed a subset of genes which show differential expression among sexes, disease type, and disease severity. The most significant observations were the increased expression primarily of ECM genes in medium severity IPF (CATHK, COL1A1, COL3, MMP1, MMP7, IL-1RN) compared to mild IPF and COPD. Two genes, CH3L1 and MMP7 showed a tendency of interaction between sex and disease in IPF severity. Surprisingly, there were no significant differences in any of the sex genes measured between the IPF groups; however, ESR1 and AR expression levels were higher and lower, respectively, compared to COPD samples. Overall, this work highlights two genes, CH3L1 and MMP7, that may contribute to gender trends observed for IPF and COPD and are potential targets for future research. PMID:24959312

  16. Several herbal compounds in Okinawa plants directly inhibit the oncogenic/aging kinase PAK1.

    PubMed

    Nguyen, Binh Cao Quan; Taira, Nozomi; Tawata, Shinkichi

    2014-12-01

    The p21-activated kinase 1 (PAK1) is emerging as a promising therapeutic target, and the search for blockers of this oncogenic/aging kinase would be potentially useful for the treatment of various diseases/disorders in the future. Here, we report for the first time the anti-PAK1 activity of compounds derived from three distinct Okinawa plants. 5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) from alpinia inhibited directly PAK1 more strongly than mimosine and mimosinol from leucaena. Cucurbitacin I isolated from bitter gourd/melon also exhibited a moderate anti-PAK1 activity. Hispidin, a metabolite of DK, strongly inhibited PAK1 with the IC50 = 5.7 μM. The IC50 of three hispidin derivatives (H1-3) for PAK1 inhibition ranges from 1.2 to 2.0 μM, while mimosine tetrapeptides [mimosine-Phe-Phe-Tyr (MFFY) and mimosine-Phe-Trp-Tyr (MFWY)] inhibit PAK1 at nanomolar level (IC50 of 0.13 and 0.60 μM, respectively). Thus, we hope these derivatives of hispidin and mimosine could be used as potential leading compounds for developing far more potent anti-PAK1 drugs which would be useful for clinical application in the future. PMID:25639302

  17. 13C-methacetin breath test correlates with clinical indices of liver disease severity in patients with primary biliary cirrhosis.

    PubMed

    Kochel-Jankowska, A; Hartleb, M; Jonderko, K; Kaminska, M; Kasicka-Jonderko, A

    2013-02-01

    This prospective study intended to ascertain if cytochrome P450 dependent liver function is affected in early and late histological stages of primary biliary cirrhosis (PBC). The study included 32 female PBC patients (mean age 55.4 years, range 33-70) and 16 aged-matched healthy women (mean age 52.6 years, range 38-65). In every subject a 13(C)-methacetin breath test (13(C)-MBT) was applied, and the results were related to histological Ludwig's staging system and several indices of liver disease severity comprising the MAYO-1, MAYO-2, MELD, and Child-Pugh score. The 13(C)-MBT differentiated healthy controls from the patients with Ludwig IV and Ludwig III histopathological stages of PBC. The most significant relationships (i.e. explaining >50% of the variance) were found between measurements of the momentary breath 13(C) elimination from 6 to 18 minutes as well as the 15-min or 30-min cumulative elimination and the MAYO-1 or MAYO-2 scores. The breath test poorly correlated with histopathological features of PBC, however, it accurately discriminated cirrhotic from non-cirrhotic patients (momentary breath 13(C) elimination at 40 min, AUROC 0,958). In conclusion, 13(C)-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.

  18. Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment.

    PubMed

    Lindeboom, Jaap; Weinstein, Henry

    2004-04-19

    In this review, the neuropsychological symptoms of different diseases in the elderly are described. After a brief explanation of relevant principles in the neuropsychological assessment of older individuals, a summary of the complex relation between ageing and cognition is presented. It may be concluded that cognitive decline is not an inevitable outcome of ageing, and may well be the result of unrecognised pathology. The term mild cognitive impairment is reserved for patients whose impairment is objectively demonstrable but is not pronounced in more than one domain of cognition and does not seriously affect activities of daily living. The initial phase of Alzheimer's disease is marked by a progressive deterioration of episodic memory. When the process advances, the impairment spreads to other functions, such as semantic memory, language and visuo-spatial ability. Vascular dementia is the second most common type of dementia; however, it is increasingly being recognised that vascular dementia is actually a heterogeneous syndrome and that several vascular pathologies can lead to cognitive deterioration. In contrast to the striking deficits produced by cortical infarcts, lesions of the subcortical white matter are mainly associated with a non-specific slowing of behaviour. Cerebrovascular disease also plays an important role in forms of cognitive decline other than dementia, and as such, it appears to be no less prevalent in old age than Alzheimer's disease. Neuropsychology is an important asset to the study and treatment of cognitive decline, but must be embedded in a multi-disciplinary context.

  19. Impact of Hospital Variables on Case Mix Index as a Marker of Disease Severity

    PubMed Central

    Mendez, Carmen M.; Harrington, Darrell W.; Christenson, Peter

    2014-01-01

    Abstract Case mix index (CMI) has become a standard indicator of hospital disease severity in the United States and internationally. However, CMI was designed to calculate hospital payments, not to track disease severity, and is highly dependent on documentation and coding accuracy. The authors evaluated whether CMI varied by characteristics affecting hospitals' disease severity (eg, trauma center or not). The authors also evaluated whether CMI was lower at public hospitals than private hospitals, given the diminished financial resources to support documentation enhancement at public hospitals. CMI data for a 14-year period from a large public database were analyzed longitudinally and cross-sectionally to define the impact of hospital variables on average CMI within and across hospital groups. Between 1996 and 2007, average CMI declined by 0.4% for public hospitals, while rising significantly for private for-profit (14%) and nonprofit (6%) hospitals. After the introduction of the Medicare Severity Diagnosis Related Group (MS-DRG) system in 2007, average CMI increased for all 3 hospital types but remained lowest in public vs. private for-profit or nonprofit hospitals (1.05 vs. 1.25 vs. 1.20; P<0.0001). By multivariate analysis, teaching hospitals, level 1 trauma centers, and larger hospitals had higher average CMI, consistent with a marker of disease severity, but only for private hospitals. Public hospitals had lower CMI across all subgroups. Although CMI had some characteristics of a disease severity marker, it was lower across all strata for public hospitals. Hence, caution is warranted when using CMI to adjust for disease severity across public vs. private hospitals. (Population Health Management 2014;17:28–34) PMID:23965045

  20. Vitamin D level among Egyptian patients with chronic spontaneous urticaria and its relation to severity of the disease.

    PubMed

    Abdel-Rehim, Asmaa S M; Sheha, Dina S; Mohamed, Nesrine A

    2014-01-01

    Vitamin D has an important role in the immune system. Decreased serum vitamin D level is known to be associated with autoimmune and atopic diseases. This study aimed to assess vitamin D status in patients with chronic spontaneous urticaria (CSU) and its relation with severity of the disease. This case-control study was conducted on 22 patients and 20 age and sex matched controls. Patients were subjected to clinical assessment, routine laboratory examination: complete blood picture (CBC), erythrocyte sedimentation rate (ESR), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), anti-thyroid antibody, anti-nuclear antibody (ANA), total immunoglobulin E (IgE), vitamin D assay and stool analysis, and special investigations including: skin prick test (SPT), autologous serum skin test (ASST) and urticaria activity score (UAS). Patients' mean age was 32.8 ± 13.17 years. The median and interquartile range of duration of illness was 2.5 (1-4) years and of Ig E was 79 (62-312) IU/ml. According to UAS; 14 (63.6%) had severe and 8 (36.4%) had moderate degree illness. The mean vitamin D level among the patients was 28.4 ± 9.09 nmol/L. Vitamin D level was significantly lower among patients in comparison to controls (28.4 ± 9.09 vs. 104.5 ± 76.8, t = 4.4 P < 0.01). Vitamin D correlated negatively with IgE level (r = -0.45, P < 0.05), meanwhile it was insignificantly correlated with age and duration of illness (r = -0.117 and 0.34 respectively, P > 0.05). In conclusion; Low vitamin D level (r = 0.45) is associated with chronic spontaneous urticaria but has no relation with the severity of the disease.

  1. [Ulcerative colitis in a 6-year-old boy with severe coeliac disease - a case report].

    PubMed

    Pawłowska-Kamieniak, Agnieszka; Krawiec, Paulina; Pac-Kożuchowska, Elżbieta; Mroczkowska-Juchkiewcz, Agnieszka; Kominek, Katarzyna

    2016-01-01

    Coeliac disease is a chronic immune-mediated inflammation of the small intestine elicited by the gluten ingestion in genetically susceptible people. In coeliac patients there is higher incidence of other autoimmune disorders like type 1 diabetes or Hashimoto's thyroiditis. The coexistence of coeliac disease and inflammatory bowel disease is rare. The spectrum of presentation of coeliac disease and inflammatory bowel disease may be similar. However, those disorders require various therapeutic approaches. Thus, early recognition of the overlap between coeliac disease and inflammatory bowel disease is crucial to apply appropriate treatment and to prevent possible complications. We report a case of a 6-year-old boy with a delay in physical and psychomotor development, rickets, severe anaemia and bloody diarrhoea. He was diagnosed with coeliac disease and ulcerative disease. The coexistence of both disorders is extremely rare in childhood. However, ulcerative colitis should be considered in coeliac children on restrictive gluten-free diet with persistent diarrhoea or bleeding from lower gastrointestinal tract. Screening for coeliac disease should be considered in children with ulcerative colitis with impaired physical development and lack of remission despite of proper treatment.

  2. Mechanisms of yogic practices in health, aging, and disease.

    PubMed

    Kuntsevich, Viktoriya; Bushell, William C; Theise, Neil D

    2010-01-01

    Mechanisms underlying the modulating effects of yogic cognitive-behavioral practices (eg, meditation, yoga asanas, pranayama breathing, caloric restriction) on human physiology can be classified into 4 transduction pathways: humoral factors, nervous system activity, cell trafficking, and bioelectromagnetism. Here we give examples of these transduction pathways and how, through them, yogic practices might optimize health, delay aging, and ameliorate chronic illness and stress from disability. We also recognize that most studies of these mechanisms remain embedded in a reductionist paradigm, investigating small numbers of elements of only 1 or 2 pathways. Moreover, often, subjects are not long-term practitioners, but recently trained. The models generated from such data are, in turn, often limited, top-down, without the explanatory power to describe beneficial effects of long-term practice or to provide foundations for comparing one practice to another. More flexible and useful models require a systems-biology approach to gathering and analysis of data. Such a paradigm is needed to fully appreciate the deeper mechanisms underlying the ability of yogic practice to optimize health, delay aging, and speed efficient recovery from injury or disease. In this regard, 3 different, not necessarily competing, hypotheses are presented to guide design of future investigations, namely, that yogic practices may: (1) promote restoration of physiologic setpoints to normal after derangements secondary to disease or injury, (2) promote homeostatic negative feedback loops over nonhomeostatic positive feedback loops in molecular and cellular interactions, and (3) quench abnormal "noise" in cellular and molecular signaling networks arising from environmental or internal stresses.

  3. Aberrant subcellular neuronal calcium regulation in aging and Alzheimer's disease.

    PubMed

    Camandola, Simonetta; Mattson, Mark P

    2011-05-01

    In this mini-review/opinion article we describe evidence that multiple cellular and molecular alterations in Alzheimer's disease (AD) pathogenesis involve perturbed cellular calcium regulation, and that alterations in synaptic calcium handling may be early and pivotal events in the disease process. With advancing age neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular calcium dynamics. Altered proteolytic cleavage of the β-amyloid precursor protein (APP) in response to the aging process in combination with genetic and environmental factors results in the production and accumulation of neurotoxic forms of amyloid β-peptide (Aβ). Aβ undergoes a self-aggregation process and concomitantly generates reactive oxygen species that can trigger membrane-associated oxidative stress which, in turn, impairs the functions of ion-motive ATPases and glutamate and glucose transporters thereby rendering neurons vulnerable to excitotoxicity and apoptosis. Mutations in presenilin-1 that cause early-onset AD increase Aβ production, but also result in an abnormal increase in the size of endoplasmic reticulum calcium stores. Some of the events in the neurodegenerative cascade can be counteracted in animal models by manipulations that stabilize neuronal calcium homeostasis including dietary energy restriction, agonists of glucagon-like peptide 1 receptors and drugs that activate mitochondrial potassium channels. Emerging knowledge of the actions of calcium upstream and downstream of Aβ provides opportunities to develop novel preventative and therapeutic interventions for AD. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. PMID:20950656

  4. Single nucleotide polymorphisms in the dystroglycan gene do not correlate with disease severity in hereditary inclusion body myopathy.

    PubMed

    Gottlieb, Emily; Ciccone, Carla; Darvish, Daniel; Naiem-Cohen, Shahrouz; Dalakas, Marinos C; Savelkoul, Paul J; Krasnewich, Donna M; Gahl, William A; Huizing, Marjan

    2005-01-01

    Aberrant glycosylation of dystroglycan occurs in certain muscular dystrophies, including hereditary inclusion body myopathy (HIBM). HIBM harbors a widely varying clinical severity and age of onset, which raised the suspicion of the presence of disease modifier genes. We considered the highly polymorphic dystroglycan gene (DAG1) as a feasible candidate modifier gene. DAG1 genomic DNA was sequenced for 32 HIBM patients, mainly of Persian-Jewish descent. Five novel DAG1 single nucleotide polymorphisms (SNPs) were identified, bringing the total number of SNPs to 19. However, no direct correlation between DAG1 SNPs and clinical severity of HIBM could be detected. Several identified SNPs substitute an amino acid and might modulate dystroglycan function or glycosylation status, and deserve further research. These data are valuable for future studies on the role of DAG1 in HIBM and other muscular dystrophies, especially those dystrophies that involve abnormal glycosylation of dystroglycan.

  5. The Effect of Continuity of Care on Emergency Room Use for Diabetic Patients Varies by Disease Severity

    PubMed Central

    Hsu, Chia-Hsiang; Chou, Yiing-Jenq; Pu, Christy

    2016-01-01

    Background Although many studies have reported that high-quality continuity of care (COC) is associated with improved patient outcomes for patients with diabetes, few studies have investigated whether this positive effect of COC depends on the level of diabetes severity. Methods A total of 3781 newly diagnosed diabetic patients selected from the 2005 National Health Insurance database were evaluated for the period 2005–2011. Generalized estimating equations combined with negative binomial estimation were used to determine the influence of COC on the overall emergency room (ER) use and diabetes mellitus (DM)-specific ER use. Analyses were stratified according to diabetes severity (measured using the Diabetes Complications Severity Index [DCSI]), comorbidities (measured using the Charlson comorbidity score), and age. Results COC effects varied according to diabetes severity. Stratified analysis showed that the positive effect of COC on DM-specific ER use was the highest for a DCSI of 0 (least severe), with an incidence rate ratio (IRR) of 0.49 (95% CI, 0.41–0.59) in the high-COC group (reference group: low-COC group). Compared with the low-COC group, high-quality COC had a significant beneficial effect on overall ER use in younger patients (IRR 0.51; 95% CI, 0.39–0.66 for the youngest [18–40 years] group, and IRR 0.67; 95% CI, 0.59–0.76 for the oldest [>65 years] group) and those with a high number of comorbidities. Conclusions The positive effects of high-quality COC on the treatment outcomes of patient with diabetes, based on the overall and DM-specific ER use, depends on the level of disease severity. Therefore, providing health education to enhance high-quality COC when the disease severity is low may be critical for ensuring optimal positive effects during diabetes disease progression. PMID:26902167

  6. [Moderate or severe aquired valvular heart disease in pregnancy--what does determine the management? Experence, intuition or guidelines?].

    PubMed

    Greszata, Lidia; Stępińska, Janina

    2015-01-01

    Epidemiology of acquired valvular heart diseases has changed significantly over last decades. Degenerative aortic valve stenosis is the most common acquired valvular disease with high prevalence in elderly population. Another common disorder is ischemic mitral regurgitation secondary to myocardial infarction. Both above-mentioned heart disorders are not typical for women in reproductive age. Rheumatic heart valve disease has become infrequent in Polish population. Mitral stenosis, the most prevalent of rheumatic valvular disorders, affects 5% of pregnant women with heart disease and rheumatic aortic stenosis is responsible for 0.5-3% of heart diseases in this population. Despite the fact that acquired valvular disorders are becoming less common among pregnant women, they still remain an important issue and their management should be well known. Discussion about pregnancy should be a part of management of young women with valvular heart disease. Severe valve disorders should be corrected when planning pregnancy. The final management should always be based on collaborative decision made by the patient and health professionals.

  7. The relationship between aminopyrine breath test and severity of liver disease in cirrhosis

    SciTech Connect

    Morelli, A.; Narducci, F.; Pelli, M.A.; Farroni, F.; Vedovelli, A.

    1981-08-01

    Twenty-two patients with cirrhosis were evaluated by the 2 hr.-(C14)-aminopyrine breath test, the conventional liver tests and two systems for grading the severity of liver disease. Twenty-three patients with noncirrhotic liver disease and 15 controls were also studied. Reduced 14CO2 values were found in 21 of the 22 cirrhotic patients and seven of those had noncirrhotic liver disease associated with severe functional reserve impairment. The values in patients with minor liver diseases or cholestasis were normal. In the cirrhotic patients 2 hr.-(C14)-aminopyrine breath test scores correlated with prothrombin time, retention of bromosulfalein, fasting serum bile acid, albumin, bilirubin, serum aspartate aminotransferase and, above all, with the scores of the two clinical rating systems. The 2 hr.-(C14)-aminopyrine breath test was superior to conventional tests in quantifying the degree of hepatic functional reserve and forecasting the prognosis.

  8. [Wilson's disease with severe neurological manifestations: response to trientine plus zinc therapy].

    PubMed

    Serra, B; Primo, J; García, M; Amorós, I; Aragó, M; Merino, C

    2004-05-01

    In patients with Wilson's disease and neurological manifestations, treatment with D-penicillamine can cause worsening of neurological symptoms, usually in the first few weeks of treatment. Because the neurological damage can be severe and irreversible, the use of D-penicillamine is controversial, and several authors believe that it should be avoided. Studies of the use of ammonium tetrathiomolybdate as an alternative chelating agent for the initial treatment of neurologic Wilson's disease are still in the experimental phase. Published experience on the simultaneous use of trientine, another chelating agent, and zinc, which blocks intestinal absorption of copper, is promising but limited. We present the case of a 17 year-old boy with severe neurologic Wilson's disease that had first presented six years previously. The patient showed a complete recovery after six months of treatment with a combination of trientine and zinc acetate.

  9. Polyparasitism Is Associated with Increased Disease Severity in Toxoplasma gondii-Infected Marine Sentinel Species

    PubMed Central

    Gibson, Amanda K.; Raverty, Stephen; Lambourn, Dyanna M.; Huggins, Jessica; Magargal, Spencer L.; Grigg, Michael E.

    2011-01-01

    In 1995, one of the largest outbreaks of human toxoplasmosis occurred in the Pacific Northwest region of North America. Genetic typing identified a novel Toxoplasma gondii strain linked to the outbreak, in which a wide spectrum of human disease was observed. For this globally-distributed, water-borne zoonosis, strain type is one variable influencing disease, but the inability of strain type to consistently explain variations in disease severity suggests that parasite genotype alone does not determine the outcome of infection. We investigated polyparasitism (infection with multiple parasite species) as a modulator of disease severity by examining the association of concomitant infection of T. gondii and the related parasite Sarcocystis neurona with protozoal disease in wild marine mammals from the Pacific Northwest. These hosts ostensibly serve as sentinels for the detection of terrestrial parasites implicated in water-borne epidemics of humans and wildlife in this endemic region. Marine mammals (151 stranded and 10 healthy individuals) sampled over 6 years were assessed for protozoal infection using multi-locus PCR-DNA sequencing directly from host tissues. Genetic analyses uncovered a high prevalence and diversity of protozoa, with 147/161 (91%) of our sampled population infected. From 2004 to 2009, the relative frequency of S. neurona infections increased dramatically, surpassing that of T. gondii. The majority of T. gondii infections were by genotypes bearing Type I lineage alleles, though strain genotype was not associated with disease severity. Significantly, polyparasitism with S. neurona and T. gondii was common (42%) and was associated with higher mortality and more severe protozoal encephalitis. Our finding of widespread polyparasitism among marine mammals indicates pervasive contamination of waterways by zoonotic agents. Furthermore, the significant association of concomitant infection with mortality and protozoal encephalitis identifies polyparasitism as

  10. Nonalcoholic fatty liver disease and aging: epidemiology to management.

    PubMed

    Bertolotti, Marco; Lonardo, Amedeo; Mussi, Chiara; Baldelli, Enrica; Pellegrini, Elisa; Ballestri, Stefano; Romagnoli, Dante; Loria, Paola

    2014-10-21

    Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients. PMID:25339806

  11. Nonalcoholic fatty liver disease and aging: Epidemiology to management

    PubMed Central

    Bertolotti, Marco; Lonardo, Amedeo; Mussi, Chiara; Baldelli, Enrica; Pellegrini, Elisa; Ballestri, Stefano; Romagnoli, Dante; Loria, Paola

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients. PMID:25339806

  12. Compound heterozygous deletions of PMP22 causing severe Charcot-Marie-Tooth disease of the Dejerine-Sottas disease phenotype.

    PubMed

    Al-Thihli, Khalid; Rudkin, Teresa; Carson, Nancy; Poulin, Chantal; Melançon, Serge; Der Kaloustian, Vazken M

    2008-09-15

    Dejerine-Sottas disease (DSD) is a particular phenotype of the Charcot-Marie-Tooth (CMT) disease spectrum that is genetically heterogeneous. It represents a severe form of hypertrophic axonal and demyelinating neuropathy. Although it is predominantly inherited as an autosomal recessive condition, autosomal dominant inheritance has also been described. To date, the autosomal recessive forms of DSD are classified into several CMT type 4 (CMT4) subclasses based on allelic heterogeneity. We present a 7-year-old boy with a severe form of CMT disease consistent with the autosomal recessive phenotype of DSD. He was found to be a compound heterozygote for mutations in the PMP22 gene resulting in homozygous deletion of exons 2 and 3. The maternally inherited allele was the typical 1.5 Mb deletion involving PMP22 seen with hereditary neuropathy with liability to pressure palsy (HNPP). The paternally inherited allele was a deletion of exons 2 and 3. Both parents presented with a typical clinical picture of HNPP. To our knowledge, this is the first patient reported with large deletions involving both PMP22 alleles. Our patient has also developed severe gastroesophageal reflux disease (GERD), a clinical feature not previously reported with CMT or DSD. The correlation of the phenotype and the molecular defects observed in this patient may set a new subcategory in the classification of DSD. PMID:18698610

  13. Autophagy: a druggable process that is deregulated in aging and human disease

    PubMed Central

    Kroemer, Guido

    2015-01-01

    Autophagy (“self-eating”) constitutes one of the most spectacular yet subtly regulated phenomena in cell biology. Similarly to cell division, differentiation, and death, autophagy is perturbed in multiple diseases, in that excessive or deficient autophagy may contribute to pathogenesis. Numerous attempts have been launched to identify specific inducers or inhibitors of autophagy and to use them for the therapeutic correction of its deregulation. At present, several major disease categories (including but not limited to age-related, cardiovascular, infectious, neoplastic, neurodegenerative, and metabolic pathologies) are being investigated for pathogenic aberrations in autophagy and their pharmacologic rectification. Driven by promising preclinical results, several clinical trials are exploring autophagy as a therapeutic target. PMID:25654544

  14. [Treatment with vitamin D and slowing of progression to severe stage of Alzheimer's disease].

    PubMed

    Chaves, Marcelo; Toral, Ana; Bisonni, Ana; Rojas, Juan I; Fernández, Cecilia; García Basalo, María José; Basallo, María J; Matusevich, Daniel; Cristiano, Edgardo; Golimstok, Angel

    2014-01-01

    The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimer's disease. We performed a retrospective study including patients with mild stage of Alzheimer's disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimer's disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11% of the patients (n = 23) remained in the mild stage of the disease, 54% (n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35% (n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimer's disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimer's disease.

  15. Fasting can protect young and middle-aged Drosophila melanogaster flies against a severe cold stress.

    PubMed

    Le Bourg, Éric

    2013-10-01

    Flies were starved with water before being subjected to various severe stresses (heat, cold, fungal infection, hydrogen peroxide) immediately after starvation or after a delay. Starvation of young and middle-aged flies increased resistance to a long cold stress (0 °C for up to 48 h), mainly if there was a 2-6 h delay between starvation and the cold stress, but positive effects in old flies were hardly observed. No positive effect was observed on resistance to the other stresses and starvation rather decreased resistance to them. It thus seems that fasting increases frailty but also puts at play mechanisms increasing resistance to cold. Starvation also increased learning scores but this could be linked to decreased positive phototaxis tendencies, and not to a better learning ability. Starvation appears to be a mild stress with limited hormetic effects, but studying the mechanisms of these effects is of interest because fasting is maybe of therapeutic value in human beings.

  16. Pathology supported genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer's disease.

    PubMed

    Kotze, Maritha J; van Rensburg, Susan J

    2012-09-01

    Chronic, multi-factorial conditions caused by a complex interaction between genetic and environmental risk factors frequently share common disease mechanisms, as evidenced by an overlap between genetic risk factors for cardiovascular disease (CVD) and Alzheimer's disease (AD). Single nucleotide polymorphisms (SNPs) in several genes including ApoE, MTHFR, HFE and FTO are known to increase the risk of both conditions. The E4 allele of the ApoE polymorphism is the most extensively studied risk factor for AD and increases the risk of coronary heart disease by approximately 40%. It furthermore displays differential therapeutic responses with use of cholesterol-lowering statins and acetylcholinesterase inhibitors, which may also be due to variation in the CYP2D6 gene in some patients. Disease expression may be triggered by gene-environment interaction causing conversion of minor metabolic abnormalities into major brain disease due to cumulative risk. A growing body of evidence supports the assessment and treatment of CVD risk factors in midlife as a preventable cause of cognitive decline, morbidity and mortality in old age. In this review, the concept of pathology supported genetic testing (PSGT) for CVD is described in this context. PSGT combines DNA testing with biochemical measurements to determine gene expression and to monitor response to treatment. The aim is to diagnose treatable disease subtypes of complex disorders, facilitate prevention of cumulative risk and formulate intervention strategies guided from the genetic background. CVD provides a model to address the lifestyle link in most chronic diseases with a genetic component. Similar preventative measures would apply for optimisation of heart and brain health.

  17. Ageing, lifestyle modifications, and cardiovascular disease in developing countries.

    PubMed

    Dominguez, L J; Galioto, A; Ferlisi, A; Pineo, A; Putignano, E; Belvedere, M; Costanza, G; Barbagallo, M

    2006-01-01

    Developing countries face the double menace of still prevalent infectious diseases and increasing cardiovascular disease (CVD) with epidemic proportions in the near future, linked to demographic changes (expansion and ageing), and to urbanisation and lifestyle modifications. It is estimated that the elderly population will increase globally (over 80% during the next 25 years), with a large share of this rise in the developing world because of expanding populations. Increasing longevity prolongs the time exposure to risk factors, resulting in a greater probability of CVD. As a paradox, increased longevity due to improved social and economical conditions associated with lifestyle changes in the direction of a rich diet and sedentary habits in the last century, is one of the main contributors to the incremental trend in CVD. The variable increase rate of CVD in different nations may reflect different stages of "epidemiological transition" and it is probable that the relatively slow changes seen in developing populations through the epidemiological transition may occur at an accelerated pace in individuals migrating from nations in need to affluent societies (i.e. Hispanics to the USA, Africans to Europe). Because of restrained economic conditions in the developing world, the greatest gains in controlling the CVD epidemic lies in its prevention. Healthy foods should be widely available and affordable, and healthy dietary practices such as increased consumption of fresh fruits and vegetables, reduced consumption of saturated fat, salt, and simple sugars, may be promoted in all populations. Specific strategies for smoking and overweight control may be regulation of marketed tobacco and unhealthy fast food and promotion of an active lifestyle. Greater longevity and economic progress are accompanied by an increasing burden of CVD and other chronic diseases with an important decrease in quality of life, which should question the benefit of these additional years without

  18. Adrenocorticotropic hormone and cortisol levels in relation to inflammatory response and disease severity in children with meningococcal disease.

    PubMed

    van Woensel, J B; Biezeveld, M H; Alders, A M; Eerenberg, A J; Endert, E; Hack, E C; von Rosenstiel, I A; Kuijpers, T W

    2001-12-15

    This prospective observational study investigated the relationship of the hypothalamic-pituitary-adrenal axis to inflammatory markers and to disease severity in children with meningococcal disease. In total, 32 children were studied: 10 with distinct meningococcal meningitis (MM), 10 with MM and septic shock, and 12 with fulminant meningococcal septicemia (FMS). Levels of adrenocorticotropic hormone (ACTH) and interleukin (IL)-6, IL-8, and IL-10 were lowest in the MM group and dramatically elevated in the FMS group. Cortisol and C-reactive protein levels were highest in the MM group and relatively low in the FMS group. Levels of ACTH and inflammatory markers decreased within the first 24 h of admission, but cortisol levels did not fluctuate. Cortisol was significantly inversely correlated with IL-6, IL-8, and IL-10 (P < or =.04). These results suggest that the adrenal reserve in children is insufficient to handle the extreme conditions and stress associated with severe meningococcal disease.

  19. Polygenic risk of Parkinson disease is correlated with disease age at onset

    PubMed Central

    Escott‐Price, Valentina; Nalls, Mike A.; Morris, Huw R.; Lubbe, Steven; Brice, Alexis; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Hardy, John; Singleton, Andrew B.

    2015-01-01

    Objective We have investigated the polygenic architecture of Parkinson disease (PD) and have also explored the potential relationship between an individual's polygenic risk score and their disease age at onset. Methods This study used genotypic data from 4,294 cases and 10,340 controls obtained from the meta‐analysis of PD genome‐wide association studies. Polygenic score analysis was performed as previously described by the International Schizophrenia Consortium, testing whether the polygenic score alleles identified in 1 association study were significantly enriched in the cases relative to the controls of 3 independent studies. Linear regression was used to investigate the relationship between an individual's polygenic score for PD risk alleles and disease age at onset. Results Our polygenic score analysis has identified significant evidence for a polygenic component enriched in the cases of each of 3 independent PD genome‐wide association cohorts (minimum p = 3.76 × 10−6). Further analysis identified compelling evidence that the average polygenic score in patients with an early disease age at onset was significantly higher than in those with a late age at onset (p = 0.00014). Interpretation This provides strong support for a large polygenic contribution to the overall heritable risk of PD and also suggests that early onset forms of the illness are not exclusively caused by highly penetrant Mendelian mutations, but can also be contributed to by an accumulation of common polygenic alleles with relatively low effect sizes. Ann Neurol 2015;77:582–591 PMID:25773351

  20. Compound heterozygous PMP22 deletion mutations causing severe Charcot-Marie-Tooth disease type 1.

    PubMed

    Abe, Akiko; Nakamura, Kazuyuki; Kato, Mitsuhiro; Numakura, Chikahiko; Honma, Tomomi; Seiwa, Chizuru; Shirahata, Emi; Itoh, Aiko; Kishikawa, Yumiko; Hayasaka, Kiyoshi

    2010-11-01

    We present a 3⅓-year-old girl with severe Charcot-Marie-Tooth disease type 1 (Dejerine-Sottas disease), who was a compound heterozygote carrying a deletion of the whole peripheral myelin protein 22 (PMP22) and a deletion of exon 5 in the other PMP22 allele. Haplotype analyses and sequence determination revealed a 11.2 kb deletion spanning from intron 4 to 3'-region of PMP22, which was likely generated by nonhomologous end joining. Severely affected patients carrying a PMP22 deletion must be analyzed for the mutations of the other copy of PMP22. PMID:20739940

  1. Effect of age on left ventricular function during exercise in patients with coronary artery disease

    SciTech Connect

    Hakki, A.H.; DePace, N.L.; Iskandrian, A.S.

    1983-10-01

    The purpose of this study was to assess the effect of age on left ventricular performance during exercise in 79 patients with coronary artery disease (greater than or equal to 50% narrowing of one or more major coronary arteries). Fifty patients under the age of 60 years (group I) and 29 patients 60 years or older (group II) were studied. Radionuclide angiograms were obtained at rest and during symptom-limited upright bicycle exercise. The history of hypertension, angina or Q wave myocardial infarction was similar in both groups. Multivessel coronary artery disease was present in 30 patients (60%) in group I and in 19 patients (66%) in group II (p . not significant). There were no significant differences between the two groups in the hemodynamic variables (at rest or during exercise) of left ventricular ejection fraction, end-diastolic volume, end-systolic volume and cardiac index. Exercise tolerance was higher in group I than in group II (7.8 +/- 0.4 versus 5.7 +/- 0.4 minutes, p . 0.009), although the exercise heart rate and rate-pressure product were not significantly different between the groups. There was poor correlation between age and ejection fraction, end-diastolic volume and end-systolic volume at rest and during exercise. Abnormal left ventricular function at rest or an abnormal response to exercise was noted in 42 patients (84%) in group I and in 25 patients (86%) in group II (p . not significant). Thus, in patients with coronary artery disease, age does not influence left ventricular function at rest or response to exercise. Older patients with coronary artery disease show changes in left ventricular function similar to those in younger patients with corresponding severity of coronary artery disease.

  2. The influence of age at disease onset on disease activity and disability: results from the Ontario Best Practices Research Initiative.

    PubMed

    Ruban, T N; Jacob, B; Pope, J E; Keystone, E C; Bombardier, C; Kuriya, B

    2016-03-01

    This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA <60 years. Group differences were compared, and multivariate linear regression models were used to test the influence of age at onset on Disease Activity Score in 28 Joints with erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire (HAQ) scores. The swollen joint count (6.2 vs. 5.3), acute phase reactants (C-reactive protein (CRP) 17.4 vs. 11.8 mg/L, ESR 30.6 vs. 21.5 mm/h), and comorbidity burden were higher in late-onset RA compared to young-onset RA (p < 0.01). Mean DAS28-ESR (4.6 vs. 4.3) and HAQ (1.2 vs. 1.1) scores were higher in late-onset RA patients (p < 0.05). Late-onset RA patients received more initial disease-modifying antirheumatic drug (DMARD) monotherapy and corticosteroids in comparison to greater DMARD/biologic combination therapy in young-onset RA patients (p < 0.05). Adjusted multivariate analyses showed that late-onset RA was independently associated with higher mean DAS28-ESR and HAQ scores, but not CDAI. Late-onset RA patients have greater disease activity that may contribute to disability early in the disease course. Despite this, initial treatment consists of less combination DMARD and biologic use in late-onset RA patients. This may have implications for future response to therapy and development of joint damage, disability, and comorbidities in this group.

  3. Ethical and legal challenges posed by severe acute respiratory syndrome: implications for the control of severe infectious disease threats.

    PubMed

    Gostin, Lawrence O; Bayer, Ronald; Fairchild, Amy L

    2003-12-24

    The appearance and spread of severe acute respiratory syndrome (SARS) on a global level raised vital legal and ethical issues. National and international responses to SARS have profound implications for 3 important ethical values: privacy, liberty, and the duty to protect the public's health. This article examines, through legal and ethical lenses, various methods that countries used in reaction to the SARS outbreak: surveillance and contact tracing, isolation and quarantine, and travel restrictions. These responses, at least in some combination, succeeded in bringing the outbreak to an end. The article articulates a set of legal and ethical recommendations for responding to infectious disease threats, seeking to reconcile the tension between the public's health and individual rights to privacy, liberty, and freedom of movement. The ethical values that inform the recommendations include the precautionary principle, the least restrictive/intrusive alternative, justice, and transparency. Development of a set of legal and ethical recommendations becomes even more essential when, as was true with SARS and will undoubtedly be the case with future epidemics, scientific uncertainty is pervasive and urgent public health action is required.

  4. Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store

    PubMed Central

    Thibault, Olivier; Gant, John C; Landfield, Philip W

    2007-01-01

    Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+ transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. In addition, other studies have reported aging- or AD model-related alterations in Ca2+ release from ryanodine receptors (RyR) on intracellular stores. The Ca2+-sensitive RyR channels amplify plasmalemmal Ca2+ influx by the mechanism of Ca2+-induced Ca2+ release (CICR). Considerable evidence indicates that a preferred functional link is present between L-VGCCs and RyRs which operate in series in heart and some brain cells. Here, we review studies implicating RyRs in altered Ca2+ regulation in cell toxicity, aging, and AD. A recent study from our laboratory showed that increased CICR plays a necessary role in the emergence of Ca2+-related biomarkers of aging. Consequently, we propose an expanded L-VGCC/Ca2+ hypothesis, in which aging/pathological changes occur in both L-type Ca2+ channels and RyRs, and interact to abnormally amplify Ca2+ transients. In turn, the increased transients result in dysregulation of multiple Ca2+-dependent processes and, through somewhat different pathways, in accelerated functional decline during aging and AD. PMID:17465978

  5. A severe case of Legionnaire's disease connected to the BBC outbreak in 1988.

    PubMed

    Richards, N C; McKinley, K P

    1989-01-01

    On 1 May 1988 a senior Naval Officer, serving at HMS Warrior, was admitted to RAF Halton where a diagnosis of Legionnaire's disease was made. He suffered severe pneumonia and neurological symptoms, and although he eventually responded to treatment, he still suffers sequelae. On 19 April, he was in the vicinity of the BBC at the time of the outbreak of Legionnaire's disease. His clinical findings are reported in this article along with a brief history and discussion of the diagnosis and prevention of Legionnaire's disease.

  6. Interacting disturbances: wildfire severity affected by stage of forest disease invasion.

    PubMed

    Metz, Margaret R; Frangioso, Kerri M; Meentemeyer, Ross K; Rizzo, David M

    2011-03-01

    Sudden oak death (SOD) is an emerging forest disease causing extensive tree mortality in coastal California forests. Recent California wildfires provided an opportunity to test a major assumption underlying discussions of SOD and land management: SOD mortality will increase fire severity. We examined prefire fuels from host species in a forest monitoring plot network in Big Sur, California (USA), to understand the interactions between disease-caused mortality and wildfire severity during the 2008 Basin Complex wildfire. Detailed measurements of standing dead woody stems and downed woody debris 1-2 years prior to the Basin fire provided a rare picture of the increased fuels attributable to SOD mortality. Despite great differences in host fuel abundance, we found no significant difference in burn severity between infested and uninfested plots. Instead, the relationship between SOD and fire reflected the changing nature of the disease impacts over time. Increased SOD mortality contributed to overstory burn severity only in areas where the pathogen had recently invaded. Where longer-term disease establishment allowed dead material to fall and accumulate, increasing log volumes led to increased substrate burn severity. These patterns help inform forest management decisions regarding fire, both in Big Sur and in other areas of California as the pathogen continues to expand throughout coastal forests.

  7. Age differences in emotional responses to daily stress: the role of timing, severity, and global perceived stress.

    PubMed

    Scott, Stacey B; Sliwinski, Martin J; Blanchard-Fields, Fredda

    2013-12-01

    Research on age differences in emotional responses to daily stress has produced inconsistent findings. Guided by recent theoretical advances in aging theory (S. T. Charles, 2010, Strength and vulnerability integration: A model of emotional well-being across adulthood, Psychological Bulletin, Vol. 136, pp. 1068-1091) that emphasize the importance of context for predicting when and how age is related to affective well-being, the current study examined age differences in emotional responses to everyday stressors. The present study examined how three contextual features (e.g., timing of exposure, stressor severity, global perceived stress [GPS]) moderate age differences in emotional experience in an ecological momentary assessment study of adults (N = 190) aged 18-81 years. Results indicated that older adults' negative affect (NA) was less affected by exposure to recent stressors than younger adults, but that there were no age differences in the effects of stressor exposure 3-6 hr afterward. Higher levels of GPS predicted amplified NA responses to daily stress, and controlling for GPS eliminated age differences in NA responses to stressors. No age differences in NA responses as a function of stressor severity were observed. In contrast, older age was associated with less of a decrease in PA when exposed to recent stressors or with more severe recent stressors. There were no age differences in the effect of previous stressor exposure or severity on PA, or any interactions between momentary or previous stress and GPS on PA. Together, these results support the notion that chronic stress plays a central role in emotional experience in daily life. We discuss the implications of these results for emotion theories of aging.

  8. Celiac disease causing severe osteomalacia: an association still present in Morocco!

    PubMed

    Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

    2014-01-01

    Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities.

  9. Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases.

    PubMed

    Chen, Rong; Shi, Lisong; Hakenberg, Jörg; Naughton, Brian; Sklar, Pamela; Zhang, Jianguo; Zhou, Hanlin; Tian, Lifeng; Prakash, Om; Lemire, Mathieu; Sleiman, Patrick; Cheng, Wei-Yi; Chen, Wanting; Shah, Hardik; Shen, Yulan; Fromer, Menachem; Omberg, Larsson; Deardorff, Matthew A; Zackai, Elaine; Bobe, Jason R; Levin, Elissa; Hudson, Thomas J; Groop, Leif; Wang, Jun; Hakonarson, Hakon; Wojcicki, Anne; Diaz, George A; Edelmann, Lisa; Schadt, Eric E; Friend, Stephen H

    2016-05-01

    Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 genes in 589,306 genomes led to the identification of 13 adults harboring mutations for 8 severe Mendelian conditions, with no reported clinical manifestation of the indicated disease. Our findings demonstrate the promise of broadening genetic studies to systematically search for well individuals who are buffering the effects of rare, highly penetrant, deleterious mutations. They also indicate that incomplete penetrance for Mendelian diseases is likely more common than previously believed. The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies. PMID:27065010

  10. Prevalence, Type, Distribution, and Severity of Cerebral Palsy in Relation to Gestational Age: A Meta-Analytic Review

    ERIC Educational Resources Information Center

    Himpens, E.; Van den Broeck, C.; Oostra, A.; Calders, P.; Vanhaesebrouck, P.

    2008-01-01

    The aim of this review is to determine the relationship between gestational age (GA) and prevalence, type, distribution, and severity of cerebral palsy (CP). Epidemiological studies with cohorts expressed by GA were assessed. A comprehensive meta-analysis and meta-regression was performed on four fetal age categories. Studies of children with CP…

  11. Hyperuricemia Inversely Correlates with Disease Severity in Taiwanese Nonalcoholic Steatohepatitis Patients

    PubMed Central

    Huang, Jee-Fu; Yeh, Ming-Lun; Yu, Ming-Lung; Huang, Chung-Feng; Dai, Chia-Yen; Hsieh, Ming-Yen; Hsieh, Meng-Hsuan; Huang, Ching-I; Lin, Zu-Yau; Chen, Shinn-Chern; Hsiao, Pi-Jung; Shin, Shyi-Jang; Chuang, Wan-Long

    2015-01-01

    Background & Aims Asians are more susceptible to non-alcoholic steatohepatitis (NASH) as well as metabolic disorder than other ethnicities. We aimed to assess the interaction between metabolic factors and fibrosis in Taiwanese NASH patients. Methods A total of 130 biopsy-proven Taiwanese NASH patients (94 males, age = 43.0 ± 13.0 years) were consecutively enrolled. Their demographic, metabolic profiles and histopathological manifestations were analyzed. Results Twenty-four (18.5%) NASH patients were non-obese. Thirty-three (25.4%) patients had significant fibrosis (F2) or more: 22 (16.9%) patients were of F2, whilst 11 (8.5%) patients were of advanced fibrosis (F3-4). The prevalence of metabolic syndrome, diabetes and hypertension were 60.8%, 39.4%, and 61.5%, respectively. There was a significant inverse correlation between hyperuricemia and fibrosis stages, ranging from 48.4% of F0-1, 33.3% of F2, and 9.1% of F3-4, respectively (P = 0.01, linear trend). Multivariate logistic regression analysis showed that a decreased serum albumin level (OR = 40.0, 95% CI = 4.5–300, P = 0.001) and normal uric acid level (OR = 5.6, 95% CI = 1.5–21.7, P = 0.01) were the significant factors associated with significant fibrosis. Conclusions Hyperuricemia inversely predicts fibrosis stages. Females might carry a more disease severity than males in Taiwanese NASH patients. PMID:26441244

  12. An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli

    PubMed Central

    Porter, Chad K.; Riddle, Mark S.; Alcala, Ashley N.; Sack, David A.; Chakraborty, Subhra; Gutierrez, Ramiro L.; Savarino, Stephen J.; Darsley, Michael; McKenzie, Robin; DeNearing, Barbara; Steinsland, Hans; Tribble, David R.; Bourgeois, A. Louis

    2016-01-01

    Background Experimental human challenge models have played a major role in enhancing our understanding of infectious diseases. Primary outcomes have typically utilized overly simplistic outcomes that fail to entirely account for complex illness syndromes. We sought to characterize clinical outcomes associated with experimental infection with enterotoxigenic Escherichia coli (ETEC) and to develop a disease score. Methods Data were obtained from prior controlled human ETEC infection studies. Correlation and univariate regression across sign and symptom severity was performed. A multiple correspondence analysis was conducted. A 3-parameter disease score with construct validity was developed in an iterative fashion, compared to standard outcome definitions and applied to prior vaccine challenge trials. Results Data on 264 subjects receiving seven ETEC strains at doses from 1x105 to 1x1010 cfu were used to construct a standardized dataset. The strongest observed correlation was between vomiting and nausea (r = 0.65); however, stool output was poorly correlated with subjective activity-impacting outcomes. Multiple correspondence analyses showed covariability in multiple signs and symptoms, with severity being the strongest factor corresponding across outcomes. The developed disease score performed well compared to standard outcome definitions and differentiated disease in vaccinated and unvaccinated subjects. Conclusion Frequency and volumetric definitions of diarrhea severity poorly characterize ETEC disease. These data support a disease severity score accounting for stool output and other clinical signs and symptoms. Such a score could serve as the basis for better field trial outcomes and gives an additional outcome measure to help select future vaccines that warrant expanded testing in pivotal pre-licensure trials. PMID:26938983

  13. Prospective cohort studies of dengue viral transmission and severity of disease.

    PubMed

    Endy, Timothy P; Yoon, In-Kyu; Mammen, Mammen P

    2010-01-01

    As the four serotypes of dengue virus (DENV) systematically spread throughout the tropical and subtropical regions globally, dengue is increasingly contributing to the overall morbidity and mortality sustained by populations and thereby challenging the health infrastructures of most endemic countries. DENV-human host-mosquito vector interactions are complex and cause in humans either asymptomatic or subclinical DENV infection, mild to severe dengue fever (DF), severe dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Over the past decade, we have seen an increase in research funding and public health efforts to offset the effects of this pandemic. Though multiple vaccine development efforts are underway, the need remains to further characterize the determinants of varying severities of clinical outcomes. Several long-term prospective studies on DENV transmission and dengue severity have sought to define the epidemiology and pathogenesis of this disease. Yet, more studies are required to quantify the disease burden on different populations, explore the impact of DENV serotype-specific transmission on host-responses and dengue severity and measure the economic impact of dengue on a population. In this section, we will review the critical past and recent findings of dengue prospective studies on our understanding of the disease and the potential role of future prospective cohort studies in advancing issues required for vaccine field evaluations.

  14. Genetic evidence for common pathways in human age-related diseases.

    PubMed

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms.

  15. Carrier testing for severe childhood recessive diseases by next-generation sequencing.

    PubMed

    Bell, Callum J; Dinwiddie, Darrell L; Miller, Neil A; Hateley, Shannon L; Ganusova, Elena E; Mudge, Joann; Langley, Ray J; Zhang, Lu; Lee, Clarence C; Schilkey, Faye D; Sheth, Vrunda; Woodward, Jimmy E; Peckham, Heather E; Schroth, Gary P; Kim, Ryan W; Kingsmore, Stephen F

    2011-01-12

    Of 7028 disorders with suspected Mendelian inheritance, 1139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~10% of pediatric hospitalizations. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening to most severe disease genes has hitherto been impractical. Here, we report a preconception carrier screen for 448 severe recessive childhood diseases. Rather than costly, complete sequencing of the human genome, 7717 regions from 437 target genes were enriched by hybrid capture or microdroplet polymerase chain reaction, sequenced by next-generation sequencing (NGS) to a depth of up to 2.7 gigabases, and assessed with stringent bioinformatic filters. At a resultant 160x average target coverage, 93% of nucleotides had at least 20x coverage, and mutation detection/genotyping had ~95% sensitivity and ~100% specificity for substitution, insertion/deletion, splicing, and gross deletion mutations and single-nucleotide polymorphisms. In 104 unrelated DNA samples, the average genomic carrier burden for severe pediatric recessive mutations was 2.8 and ranged from 0 to 7. The distribution of mutations among sequenced samples appeared random. Twenty-seven percent of mutations cited in the literature were found to be common polymorphisms or misannotated, underscoring the need for better mutation databases as part of a comprehensive carrier testing strategy. Given the magnitude of carrier burden and the lower cost of testing compared to treating these conditions, carrier screening by NGS made available to the general population may be an economical way to reduce the incidence of and ameliorate suffering associated with severe recessive childhood disorders. PMID:21228398

  16. Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing

    PubMed Central

    Bell, Callum J.; Dinwiddie, Darrell L.; Miller, Neil A.; Hateley, Shannon L.; Ganusova, Elena E.; Mudge, Joann; Langley, Ray J.; Zhang, Lu; Lee, Clarence C.; Schilkey, Faye D.; Sheth, Vrunda; Woodward, Jimmy E.; Peckham, Heather E.; Schroth, Gary P.; Kim, Ryan W.; Kingsmore, Stephen F.

    2011-01-01

    Of 7028 disorders with suspected Mendelian inheritance, 1139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~10% of pediatric hospitalizations. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening to most severe disease genes has hitherto been impractical. Here, we report a preconception carrier screen for 448 severe recessive childhood diseases. Rather than costly, complete sequencing of the human genome, 7717 regions from 437 target genes were enriched by hybrid capture or microdroplet polymerase chain reaction, sequenced by next-generation sequencing (NGS) to a depth of up to 2.7 gigabases, and assessed with stringent bioinformatic filters. At a resultant 160× average target coverage, 93% of nucleotides had at least 20× coverage, and mutation detection/genotyping had ~95% sensitivity and ~100% specificity for substitution, insertion/deletion, splicing, and gross deletion mutations and single-nucleotide polymorphisms. In 104 unrelated DNA samples, the average genomic carrier burden for severe pediatric recessive mutations was 2.8 and ranged from 0 to 7. The distribution of mutations among sequenced samples appeared random. Twenty-seven percent of mutations cited in the literature were found to be common polymorphisms or misannotated, underscoring the need for better mutation databases as part of a comprehensive carrier testing strategy. Given the magnitude of carrier burden and the lower cost of testing compared to treating these conditions, carrier screening by NGS made available to the general population may be an economical way to reduce the incidence of and ameliorate suffering associated with severe recessive childhood disorders. PMID:21228398

  17. Concordance between severity of disease, prevalence of nonmotor symptoms, patient-reported quality of life and disability and use of medication in Parkinson's disease.

    PubMed

    Raggi, Alberto; Leonardi, Matilde; Covelli, Venusia; Albanese, Alberto; Soliveri, Paola; Carella, Francesco; Romito, Luigi

    2012-08-01

    The aim of this study was to test the concordance between disease severity, prevalence of nonmotor symptoms, age, health-related quality of life (HRQoL), disability and medication use in patients with Parkinson's disease (PD). Severity was classified with the Hoehn and Yahr (HY) scale and Levodopa Equivalent Daily Dose (LEDD) calculated. HRQoL was evaluated with the SF-36, disability with the WHO-DAS II and nonmotor symptoms with the NMSQuest. Patients were clustered using SF-36 and WHO-DAS II into three groups covering the continuum from low disability and HRQoL, to severe disability and HRQoL decrement. Contingency Coefficient were used to verify the relationships between clusters and HY stage; ANOVA to evaluate differences in NMS, age and LEDD between clusters; odds ratio to test the likelihood of taking levodopa or dopamine agonist and being member of the three clusters; t test to evaluate differences in LEDD between patients with HY ≥3 or ≤2. Eighty-six patients were clustered: 48 had low disability and HRQoL decrement, 18 intermediate disability and HRQoL decrement and 20 high disability and HRQoL decrement. A significant relationship was found between PD severity groups, HRQoL and disability profiles. No differences for age and LEDD were observed in the three groups, and those with more disability and lower HRQoL reported a higher number of nonmotor symptoms; patients in HY ≥3 were prescribed higher doses of drugs. In conclusion, we found a substantial concordance between PD staging, prevalence of nonmotor symptoms and patient-reported HRQoL and disability measures. In our opinion, the SF-36 and the WHO-DAS II can be used for profiling patients.

  18. Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis

    PubMed Central

    Kalafateli, Maria; Triantos, Christos; Tsochatzis, Emmanuel; Michalaki, Marina; Koutroumpakis, Efstratios; Thomopoulos, Konstantinos; Kyriazopoulou, Venetsanea; Jelastopulu, Eleni; Burroughs, Andrew; Lambropoulou-Karatza, Chryssoula; Nikolopoulou, Vasiliki

    2015-01-01

    AIM: To investigate the adipokine levels of leptin, adiponectin, resistin, visfatin, retinol-binding protein 4 (RBP4), apelin in alcoholic liver cirrhosis (ALC). METHODS: Forty non-diabetic ALC patients [median age: 59 years, males: 35 (87.5%), Child-Pugh (CP) score: median 7 (5-12), CP A/B/C: 18/10/12, Model for End-stage Liver Disease (MELD): median 10 (6-25), follow-up: median 32.5 mo (10-43)] were prospectively included. The serum adipokine levels were estimated in duplicate by ELISA. Somatometric characteristics were assessed with tetrapolar bioelectrical impedance analysis. Pearson’s rank correlation coefficient was used to assess possible associations with adipokine levels. Univariate and multivariate Cox regression analysis was used to determine independent predictors for overall survival. RESULTS: Body mass index: median 25.9 (range: 20.1-39.3), fat: 23.4% (7.6-42.1), fat mass: 17.8 (5.49-45.4), free fat mass: 56.1 (39.6-74.4), total body water (TBW): 40.6 (29.8-58.8). Leptin and visfatin levels were positively associated with fat mass (P < 0.001/P = 0.027, respectively) and RBP4 with TBW (P = 0.025). Median adiponectin levels were significantly higher in CPC compared to CPA (CPA: 7.99 ± 14.07, CPB: 7.66 ± 3.48, CPC: 25.73 ± 26.8, P = 0.04), whereas median RBP4 and apelin levels decreased across the spectrum of disease severity (P = 0.006/P = 0.034, respectively). Following adjustment for fat mass, visfatin and adiponectin levels were significantly increased from CPA to CPC (both P < 0.001), whereas an inverse correlation was observed for both RBP4 and apelin (both P < 0.001). In the multivariate Cox regression analysis, only MELD had an independent association with overall survival (HR = 1.53, 95%CI: 1.05-2.32; P = 0.029). CONCLUSION: Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis. PMID:25780301

  19. Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis

    PubMed Central

    Asner, Sandra A.; Science, Michelle E.; Tran, Dat; Smieja, Marek; Merglen, Arnaud; Mertz, Dominik

    2014-01-01

    Background Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. Methods We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. Results Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04). Conclusions No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation. PMID:24932493

  20. The relationship between dapsone dose, serum concentration and disease severity in dermatitis herpetiformis.

    PubMed

    Sanders, S W; Zone, J J

    1986-01-01

    20 patients with dermatitis herpetiformis maintained on once daily dosing of dapsone were studied to investigate the pharmacodynamics of dapsone in suppressing clinical disease. Multiple correlation analysis was performed on variables including dosage requirements, serum concentration of dapsone and monoacetyl dapsone, acetylation ratio, IgA-containing circulating immune complexes, adherence to a gluten-free diet, and clinical disease severity. It was found that: 1. dapsone exhibits good bioavailability in dermatitis herpetiformis with absorption being unaffected by presumed gluten-sensitive enteropathy; 2. there is wide variation in serum concentrations of dapsone and monoacetyl dapsone with no specific "therapeutic level"; 3. acetylator phenotype was unrelated to dapsone dose requirement; 4. serum dapsone concentration had only a weak correlation with disease severity; and 5. there was poor correlation between IgA circulating immune complexes and dapsone serum concentration. The use of daily dapsone dose requirements or dapsone serum concentration necessary for disease suppression as an indicator of disease severity in the research setting is inappropriate. Measurements of serum concentration of the parent drug (dapsone) or principal metabolite (monoacetyl dapsone) do not serve as a useful guide to therapeutic management.

  1. Severe, persistent visual impairment associated with occipital calcification and coeliac disease.

    PubMed

    Millington, Rebecca S; James-Galton, Merle; Barbur, John L; Plant, Gordon T; Bridge, Holly

    2015-09-01

    While coeliac disease is primarily a disease of the digestive system, there have been several reports of neurological effects, both motor and cognitive. Here, we present the case of a woman with coeliac disease, under dietary control, in whom there is profound long-standing visual disturbance including reduction of visual fields, loss of rapid flicker and colour sensitivity and severe deficits in acuity. Structural magnetic resonance imaging (MRI) indicates large regions of calcification and abnormal tissue that is restricted to the occipital cortex, particularly the posterior region. Functional MRI indicates an absence of normal visual activation in the primary visual cortex, but at least in one hemisphere, there is neural activity to moving stimuli in visual motion area hMT+. White matter microstructure in the pathway between the lateral geniculate nucleus and hMT+ is normal compared to healthy control subjects, but is severely abnormal between the lateral geniculate nucleus and primary visual cortex. This case study illustrates the very specific nature of cortical deficit that can arise in association with coeliac disease, and highlights the importance of early dietary control for the disease.

  2. The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil

    PubMed Central

    Campanharo, Felipe F.; Cecatti, Jose G.; Haddad, Samira M.; Parpinelli, Mary A.; Born, Daniel; Costa, Maria L.; Mattar, Rosiane

    2015-01-01

    Background To evaluate maternal heart disease as a cause or complicating factor for severe morbidity in the setting of the Brazilian Network for Surveillance of Severe Maternal Morbidity. Methods and Findings Secondary data analysis of this multicenter cross-sectional study was implemented in 27 referral obstetric units in Brazil. From July 2009 to June 2010, a prospective surveillance was conducted among all delivery hospitalizations to identify cases of severe maternal morbidity (SMM), including Potentially Life-Threatening Conditions (PLTC) and Maternal Near Miss (MNM), using the new criteria established by the WHO. The variables studied included: sociodemographic characteristics, clinical and obstetric history of the women; perinatal outcome and the occurrence of maternal outcomes (PLTC, MNM, MD) between groups of cardiac and non-cardiac patients. Only heart conditions with hemodynamic impact characterizing severity of maternal morbidity were considered. 9555 women were included in the Network with severe pregnancy-related complications: 770 maternal near miss cases and 140 maternal death cases. A total of 293 (3.6%) cases were related to heart disease and the condition was known before pregnancy in 82.6% of cases. Maternal near miss occurred in 15% of cardiac disease patients (most due to clinical-surgical causes, p<0.001) and 7.7% of non-cardiac patients (hemorrhagic and hypertensive causes, p<0.001). Maternal death occurred in 4.8% of cardiac patients and in 1.2% of non-cardiac patients, respectively. Conclusions In this study, heart disease was significantly associated with a higher occurrence of severe maternal outcomes, including maternal death and maternal near miss, among women presenting with any severe maternal morbidity. PMID:26650684

  3. Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease.

    PubMed

    Guarner, Verónica; Rubio-Ruiz, Maria Esther

    2015-01-01

    Aging is associated with immunosenescence and accompanied by a chronic inflammatory state which contributes to metabolic syndrome, diabetes and their cardiovascular consequences. Risk factors for cardiovascular diseases (CVDs) and diabetes overlap, leading to the hypothesis that both share an inflammatory basis. Obesity is increased in the elderly population, and adipose tissue induces a state of systemic inflammation partially induced by adipokines. The liver plays a pivotal role in the metabolism of nutrients and exhibits alterations in the expression of genes associated with inflammation, cellular stress and fibrosis. Hepatic steatosis and its related inflammatory state (steatohepatitis) are the main hepatic complications of obesity and metabolic diseases. Aging-linked declines in expression and activity of endoplasmic reticulum molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the unfolded protein response. These changes predispose aged individuals to CVDs. CVDs and endothelial dysfunction are characterized by a chronic alteration of inflammatory function and markers of inflammation and the innate immune response, including C-reactive protein, interleukin-6, TNF-α, and several cell adhesion molecules are linked to the occurrence of myocardial infarction and stroke in healthy elderly populations and patients with metabolic diseases.

  4. Relation between Severity of Chronic Illness and Adjustment in Children and Adolescents with Sickle Cell Disease.

    ERIC Educational Resources Information Center

    Hurtig, Anita Landau; And Others

    1989-01-01

    The study with 70 children and adolescents with sickle cell disease did not support the hypothesis that illness severity (measured by frequency of hospitalization) would affect adjustment (measured by IQ, self-esteem, social and personal adjustment, behavioral problems, school performance, and peer relations). (Author/DB)

  5. Variants in 9p21 Predicts Severity of Coronary Artery Disease in a Chinese Han Population.

    PubMed

    Jing, Jinjin; Su, Li; Zeng, Ying; Tang, Xiaojun; Wei, Jie; Wang, Long; Zhou, Li

    2016-09-01

    Recent genome-wide association studies identified the common genetic variants in 9p21 were associated with the coronary artery disease (CAD). However, whether this locus could predict the severity of CAD in Chinese Han population is unclear. 499 CAD patients who underwent coronary angiography (CAG) have been enrolled for this study. The single-nucleotide polymorphisms rs2383207 and rs2383206 in 9p21 were genotyped in 499 CAG cases and 1519 controls in Chinese Han population. The gene dosage of 9p21 was stratified by the degree of vascular lesions and tested for association with the severity of CAD. Rs2383207 and rs2383206 demonstrated significant associations with 2-vessel and 3-vessel disease (P = 2.0×10(-3) and 1.9×10(-4) , respectively). GG genotypes of rs2383206 occurred higher proportion of left main trunk (LM) disease (P = 6.0×10(-3) ). GG genotypes of rs2383207 occurred higher proportion of left anterior descending artery disease (LAD) and right CAD (RCA) (P = 2.7×10(-6) and 1.6×10(-4) , respectively). The risk allele G of rs2383207 was associated with severity of CAD estimated by the Gensini score (P = 3.6×10(-5) ). Rs2383207 may strongly influence the development of CAD in Chinese Han population. The gene dosage in 9p21 could predict the severity of CAD. PMID:27461153

  6. Disease severity of organic rice as affected by host resistance, fertility and tillage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies were conducted to determine the effect of fertilizer inputs and tillage methods on disease incidence in an organic rice production system. The results of these studies suggest that organically produced rice is more vulnerable to infection of narrow brown leaf spot and brown spot. Thi...

  7. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity.

    PubMed

    Vaughn, D W; Green, S; Kalayanarooj, S; Innis, B L; Nimmannitya, S; Suntayakorn, S; Endy, T P; Raengsakulrach, B; Rothman, A L; Ennis, F A; Nisalak, A

    2000-01-01

    Viremia titers in serial plasma samples from 168 children with acute dengue virus infection who were enrolled in a prospective study at 2 hospitals in Thailand were examined to determine the role of virus load in the pathogenesis of dengue hemorrhagic fever (DHF). The infecting virus serotype was identified for 165 patients (DEN-1, 46 patients; DEN-2, 47 patients; DEN-3, 47 patients, DEN-4, 25 patients). Patients with DEN-2 infections experienced more severe disease than those infected with other serotypes. Eighty-one percent of patients experienced a secondary dengue virus infection that was associated with more severe disease. Viremia titers were determined for 41 DEN-1 and 46 DEN-2 patients. Higher peak titers were associated with increased disease severity for the 31 patients with a peak titer identified (mean titer of 107.6 for those with dengue fever vs. 108.5 for patients with DHF, P=.01). Increased dengue disease severity correlated with high viremia titer, secondary dengue virus infection, and DEN-2 virus type.

  8. Disease severity estimates - effects of rater accuracy and assessments methods for comparing treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of disease is fundamental to the discipline of plant pathology, and estimates of severity are often made visually. However, it is established that visual estimates can be inaccurate and unreliable. In this study estimates of Septoria leaf blotch on leaves of winter wheat from non-treated ...

  9. Association of the Functional MICA-129 Polymorphism With the Severity of Chronic Chagas Heart Disease.

    PubMed

    Ayo, Christiane Maria; Oliveira, Amanda Priscila de; Camargo, Ana Vitória da Silveira; Mattos, Cinara Cássia Brandão de; Bestetti, Reinaldo Bulgarelli; Mattos, Luiz Carlos de

    2015-10-15

    MICA-129 polymorphism affects the binding affinity of MICA molecules with the NKG2D receptor and influences effector cell function. The genotype met/met was associated with the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease, while the val/val genotype was associated with the absence of LVSD.

  10. All Is Not Lost: Positive Behaviors in Alzheimer’s Disease and Behavioral-Variant Frontotemporal Dementia with Disease Severity

    PubMed Central

    Midorikawa, Akira; Leyton, Cristian E.; Foxe, David; Landin-Romero, Ramon; Hodges, John R.; Piguet, Olivier

    2016-01-01

    Background: Anecdotal evidence indicates that some patients with dementia exhibit novel or increased positive behaviors, such as painting or singing, after the disease onset. Due to the lack of objective measures, however, the frequency and nature of these changes has not been formally investigated. Objective: This study aimed to systematically identify changes in these behaviors in the two most common younger-onset dementia syndromes: Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD). Methods: Sixty-three caregivers of patients with dementia (32 caregivers of AD patients and 31 caregivers of bvFTD patients) participated in the study. Caregivers rated the presence and frequency of positive and negative behavior changes after the onset of dementia using the Hypersensory and Social/Emotional Scale (HSS) questionnaire, focusing on three domains: sensory processing, cognitive skills, and social/emotional processing. Six composites scores were obtained reflecting these three domains (two composite scores for each domain). Differences across scores and ratios of increased and decreased behaviors were analyzed between AD and bvFTD, at different disease severity levels. Results: After disease onset, significant changes in the sensory processing domain were observed across disease severity levels, particularly in AD. Composite scores of the other domains did not change significantly. Importantly, however, some novel or increased positive behaviors were present in between 10% (Music activities) and 70% (Hypersensitivity) of AD and bvFTD patients, regardless of disease severity. Conclusions: We provide the first systematic investigation of positive behaviors in AD and bvFTD. The newly developed HSS questionnaire is a valid measure to characterize changes and progression of positive behaviors in patients with dementia. PMID:27472884

  11. Hippocampal sclerosis and TDP-43 pathology in aging and Alzheimer’s Disease

    PubMed Central

    Nag, Sukriti; Yu, Lei; Capuano, Ana W.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.; Schneider, Julie A.

    2015-01-01

    Objective To investigate the association of hippocampal sclerosis (HS) with TAR-DNA binding protein of 43 kDa (TDP-43) and other common age-related pathologies, dementia, probable Alzheimer’s disease (AD), mild cognitive impairment (MCI) and cognitive domains in community-dwelling older subjects. Methods Diagnoses of dementia, probable AD and MCI in 636 autopsied subjects from the Religious Order Study and the Rush Memory and Aging Project were based on clinical evaluation and cognitive performance tests. HS was defined as severe neuronal loss and gliosis in the hippocampal CA1and/or subiculum. The severity and distribution of TDP-43 was assessed and other age-related pathologies were also documented. Results HS was more common in those aged > 90 years (18.0%) compared to younger subjects (9.2%). HS cases commonly coexisted with TDP-43 pathology (86%), which was more severe (p < 0.001) in HS cases. Although, HS also commonly coexisted with AD and Lewy body (LB) pathology; only TDP-43 pathology increased the odds of HS (OR=2.63; 95% CI 2.07-3.34). In logistic regression models accounting for age, TDP-43 and other common age-related pathologies; HS cases had higher odds of dementia (OR=3.71; 95% CI=1.93-7.16), MCI and probable AD (OR=3.75; 95% CI=2.01-7.02). In linear regression models, including an interaction term for HS and TDP-43 pathology; HS with coexisting TDP-43 was associated with lower function in multiple cognitive domains while HS without TDP-43 did not have statistically significant associations. TDP-43 without HS was separately related to lower episodic memory. Interpretation The combined role of hippocampal sclerosis and TDP-43 pathology are significant factors underlying global cognitive impairment and probable AD in older subjects. PMID:25707479

  12. The prognostic value of injury severity, location of event, and age at injury in pediatric traumatic head injuries

    PubMed Central

    Halldorsson, Jonas G; Flekkoy, Kjell M; Arnkelsson, Gudmundur B; Tomasson, Kristinn; Gudmundsson, Kristinn R; Arnarson, Eirikur Orn

    2008-01-01

    Aims To estimate the prognostic value of injury severity, location of event, and demographic parameters, for symptoms of pediatric traumatic head injury (THI) 4 years later. Methods Data were collected prospectively from Reykjavik City Hospital on all patients age 0–19 years, diagnosed with THI (n = 408) during one year. Information was collected on patient demographics, location of traumatic event, cause of injury, injury severity, and ICD-9 diagnosis. Injury severity was estimated according to the Head Injury Severity Scale (HISS). Four years post-injury, a questionnaire on late symptoms attributed to the THI was sent. Results Symptoms reported were more common among patients with moderate/severe THI than among others (p < 0.001). The event location had prognostic value (p < 0.05). Overall, 72% of patients with moderate/severe motor vehicle-related THI reported symptoms. There was a curvilinear age effect (p < 0.05). Symptoms were least frequent in the youngest age group, 0–4 years, and most frequent in the age group 5–14 years. Gender and urban/rural residence were not significantly related to symptoms. Conclusions Motor vehicle related moderate/severe THI resulted in a high rate of late symptoms. Location had a prognostic value. Patients with motor vehicle-related THI need special consideration regardless of injury severity. PMID:18728737

  13. Worse Prognosis for Stage IA Lung Cancer Patients with Smoking History and More Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    Kage, Hidenori; Murakawa, Tomohiro; Sato, Yasunori; Ota, Satoshi; Fukayama, Masashi; Nakajima, Jun

    2015-01-01

    Purpose: This retrospective study examined whether the severity of chronic obstructive lung disease (COPD) affects surgical outcomes. Methods: The subjects were 243 consecutive patients who underwent lobectomy for clinical stage IA lung cancer from 1999 to 2008 in our hospital. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system was used to classify the severity of COPD in smokers. Results: Among the 149 smokers, 62 were diagnosed with COPD (25 as GOLD 1, 33 as GOLD 2, and 4 as GOLD 3). In univariate analysis, postoperative pulmonary complications were associated with male sex and more severe COPD. The frequencies were 17.1% in non-COPD, 24.0% in GOLD 1-COPD, and 46.0% in GOLD 2/3-COPD smokers (p = 0.0006). In univariate analysis, older age, smoking history, higher smoking pack-years and more severe COPD were associated with poor relapse-free survival. Relapse-free survival at five years was 80.7%, 66.9%, and 61.3% in non-COPD, GOLD 1-COPD, and GOLD 2/3-COPD smokers, respectively (p = 0.0005). Multivariate analyses showed that only GOLD 2/3-COPD was associated with postoperative pulmonary complications and relapse-free survival. Inhaled bronchodilators were prescribed preoperatively to 24.3% of the GOLD 2/3-COPD group. Conclusion: Smokers with GOLD 2/3-COPD are at high risk for pulmonary complications and have an unfavorable long-term prognosis. PMID:25641032

  14. Measuring the effects of Meniere's disease: results of the Patient-Oriented Severity Index (MD POSI) version 1.

    PubMed

    Murphy, M P; Gates, G A

    1999-04-01

    We describe the development and initial psychometric testing of a new self-report instrument for quantifying the impact of Meniere's disease (MD) on patients' lives: the Meniere's Disease Patient-Oriented Severity Index (MD POSI). Eighty-five volunteers with chronic MD took a self-administered MD POSI. The internal consistency form of reliability was determined by calculating Cronbach's alpha. The relationship between total MD POSI problem severity scores and responses to a global question concerning the degree to which his or her MD had changed the patient's life assessed construct-related validity. The total problem severity score yielded excellent reliability (Cronbach's alpha = .928). No significant age or gender effects were seen. A highly statistically significant association was noted between total problem severity scores and the degree to which the patient's life had been changed by his or her MD (Spearman rank correlation = .526, p < .0001), indicating excellent construct-related validity. The material included in the initial questionnaire provides important information that can be used clinically to quantify the impact of MD on patients' health status. A beta version of the instrument is in the process of validation and determination of its sensitivity to change in health status.

  15. Surgical treatment of nonalcoholic fatty liver disease in severely obese patients

    PubMed Central

    Vander Naalt, Steven J; Gurria, Juan P; Holterman, AiXuan L

    2014-01-01

    Obesity is a multi-organ system disease with underlying metabolic abnormalities and chronic systemic inflammation. Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of obesity metabolic dysfunction and its associated cardiovascular- and liver-related morbidities and mortality. Our current understanding of NAFLD pathogenesis, disease characteristics, the role of insulin resistance, chronic inflammation, gut–liver and gut–brain crosstalk and the effectiveness of pharmacotherapy is still evolving. Bariatric surgery significantly improves metabolic and NAFLD histology in severely obese patients, although its positive effects on fibrosis are not universal. Bariatric surgery benefits NAFLD through its metabolic effect on insulin resistance, inflammation, and insulinotropic and anorexinogenic gastrointestinal hormones. Further studies are needed to understand the natural course of NAFLD in severely obese patients and the role of weight loss surgery as a primary treatment for NAFLD. PMID:25378958

  16. Severe viral oesophagitis, pharyngitis, and stomatitis as antecedents of ileocecal Crohn's disease

    PubMed Central

    Waluga, Marek; Budzyńska, Agnieszka; Kajor, Maciej; Hartleb, Marek

    2015-01-01

    We present a 22-year-old male who developed a severe erosive oesophagitis extending to the pharynx and oral cavity without obvious risk factors. Endoscopic image suggested viral aetiology that could not be confirmed by routine serological diagnostics of infections with cytomegalovirus, Epstein-Barr virus, and Herpes simplex virus. The histopathological evaluation also gave no definite clues to the aetiology of the inflammation. Treatment with acyclovir was ineffective, but gancyclovir therapy caused spectacular clinical improvement and healing of erosions. Two months later the patient presented febrile diarrhoea that was a symptom of ileocecal Crohn's disease proven by endoscopy, enterography, and histopathology. It is the first report of severe viral oesophagitis preceding clinical manifestation of Crohn's disease. This observation warrants further study towards the viral aetiology of oral, pharyngeal, and oesophageal erosions, frequently associated with Crohn's disease. PMID:25960815

  17. Genetic variation in Chlamydia trachomatis and their hosts: impact on disease severity and tissue tropism

    PubMed Central

    Byrne, Gerald I

    2014-01-01

    Chlamydia trachomatis infections are a global health problem. This obligate intracellular bacterial pathogen comprises lymphogranuloma venereum (L1–L3), ocular (A–C) and genital (D–K) serovars. Although genetically similar, each serovar group differs in disease severity and tissue tropism through mechanisms that are not well understood. It is clear that host genetic differences also play a role in chlamydial disease outcome and key host polymorphisms are beginning to emerge from both human and experimental animal studies. In this review, we will highlight pathogen and host genes that link genetic diversity, disease severity and tissue tropism. We will also use this information to provide new insights that may be helpful in developing improved management strategies for these important pathogens. PMID:24020741

  18. Correlation of carotid artery disease severity and vasomotor response of cerebral blood vessels.

    PubMed

    Krdžić, Ivana; Čovičković-Šternić, Nadežda; Katsiki, Niki; Isenović, Esma R; Radak, Đorđe

    2015-05-01

    We assessed reactivity of cerebral vessels on hypercapnia in patients with carotid occlusive disease. The effects of vascular risk factors on carotid atherosclerosis and vasomotor reactivity (VMR) of cerebral arterioles were also examined. Patients (n = 50) with carotid stenosis (≥30% in 1 or both sides) were included; 30 patients acted as controls. Hypertension, hyperlipidemia, diabetes, cardiac diseases, inflammation, and smoking were recorded. Vasomotor reactivity was assessed with the apnea test by transcranial Doppler ultrasonography and estimated by flow velocity changes in the middle cerebral artery before and after hypercapnia induction. Vasomotor reactivity was defined by the breath holding index, and values under 0.69 were considered critical for VMR impairment. Vasomotor reactivity reduction was significant (P = .004) in patients with severe carotid stenosis (>70%) and with symptomatic carotid disease (P < .05). The risk factors did not significantly influence VMR reduction. Severe carotid stenosis impairs VMR and may increase the risk of stroke, especially in symptomatic patients.

  19. First report of Oryctes rhinoceros nudivirus (Coleoptera: Scarabaeidae) causing severe disease in Allomyrina dichotoma in Korea.

    PubMed

    Lee, Seokhyun; Park, Kwan-Ho; Nam, Sung-Hee; Kwak, Kyu-Won; Choi, Ji-Young

    2015-01-01

    Oryctes rhinoceros nudivirus (OrNV) has been known to cause severe disease in coconut palm rhinoceros beetle, Oryctes rhinoceros, in Southeastern Asia and is used as a biological control to reduce the pest population. Here, we report for the first time that the OrNV may have landed on Korea and may be the major pathogen for diseased larvae of Korean horn beetle, Allomyrina dichotoma. After peroral inoculation, over 60% of infected larvae perished in 6 wk. This viral disease spreads very fast in several locations throughout Korea. This threat not only makes economic loss of local farms rearing A. dichotoma larvae but also may disturb the ecosystem by transmitting to wild A. dichotoma. PMID:25765317

  20. Homozygotes for oculopharyngeal muscular dystrophy have a severe form of the disease.

    PubMed

    Blumen, S C; Brais, B; Korczyn, A D; Medinsky, S; Chapman, J; Asherov, A; Nisipeanu, P; Codère, F; Bouchard, J P; Fardeau, M; Tomé, F M; Rouleau, G A

    1999-07-01

    Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) usually begins with ptosis or dysphagia during the fifth or sixth decade of life. We studied 7 patients with OPMD symptoms starting before the age of 36 years. All were found to be homozygotes for the dominant (GCG)9 OPMD mutation. On average, disease onset was 18 years earlier than in heterozygotes, and patients had a significantly larger number of muscle nuclei containing intranuclear inclusions (INIs) (9.4 vs 4.9%).

  1. Age and Adaptive Functioning in Children and Adolescents with ASD: The Effects of Intellectual Functioning and ASD Symptom Severity.

    PubMed

    Hill, Trenesha L; Gray, Sarah A O; Kamps, Jodi L; Enrique Varela, R

    2015-12-01

    The present study examined the moderating effects of intellectual functioning and ASD symptom severity on the relation between age and adaptive functioning in 220 youth with autism spectrum disorder (ASD). Regression analysis indicated that intellectual functioning and ASD symptom severity moderated the relation between age and adaptive functioning. For younger children with lower intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Similarly, for older children with higher intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Analyses by subscales suggest that this pattern is driven by the Conceptual subscale. Clinical and research implications are discussed.

  2. Age and Adaptive Functioning in Children and Adolescents with ASD: The Effects of Intellectual Functioning and ASD Symptom Severity.

    PubMed

    Hill, Trenesha L; Gray, Sarah A O; Kamps, Jodi L; Enrique Varela, R

    2015-12-01

    The present study examined the moderating effects of intellectual functioning and ASD symptom severity on the relation between age and adaptive functioning in 220 youth with autism spectrum disorder (ASD). Regression analysis indicated that intellectual functioning and ASD symptom severity moderated the relation between age and adaptive functioning. For younger children with lower intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Similarly, for older children with higher intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Analyses by subscales suggest that this pattern is driven by the Conceptual subscale. Clinical and research implications are discussed. PMID:26174048

  3. College Students' Ageist Behavior: The Role of Aging Knowledge and Perceived Vulnerability to Disease

    ERIC Educational Resources Information Center

    Stahl, Sarah T.; Metzger, Aaron

    2013-01-01

    This cross-sectional study examined the associations among perceived vulnerability to disease, aging knowledge, and ageism (positive and negative) in a sample of undergraduate students enrolled in a human development course (N = 649; M age = 19.94 years, SD = 2.84 years). Perceived vulnerability to disease and aging knowledge were associated with…

  4. Knowledge about Aging and Alzheimer Disease: A Comparison of Professional Caregivers and Noncaregivers

    ERIC Educational Resources Information Center

    Rust, Tiana B.; See, Sheree Kwong

    2007-01-01

    This study assessed professional caregivers of persons with Alzheimer disease (AD) and non-caregivers' knowledge about aging and AD. Participants completed modified versions of the Alzheimer Disease Knowledge Test and the multiple-choice version of the Facts on Aging Quiz #1. Overall, knowledge levels about AD and aging were low. Caregivers were…

  5. IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease.

    PubMed

    Nemetz, A; Nosti-Escanilla, M P; Molnár, T; Köpe, A; Kovács, A; Fehér, J; Tulassay, Z; Nagy, F; García-González, M A; Peña, A S

    1999-06-01

    There is evidence of a disbalance in the inflammatory regulation of patients with inflammatory bowel diseases (IBD). Interleukin-1 beta plays an important role in the pro-inflammatory response. Our aim was to study the influence which IL1B gene polymorphisms may have on the severity and course of these diseases. Ninety-six patients with ulcerative colitis (UC), 98 patients with Crohn's disease (CD), and 132 ethnically matched healty individuals (HC) were typed for the polymorphic sites in the promoter region (position -511) and in exon 5 (position +3953) of the IL1B gene, using polymerase chain reaction (PCR)-based methods. In the CD group a significant association (P = 0.009) was found in this pair of genes. Homozygotes for allele 1 at position +3953 were more often present (69% vs 31%) in the subgroup of patients carrying at least one copy of allele 2 at position -511. This association was significant in patients with non-perforating disease (P = 0.002), but was not present in patients with perforating-fistulizing disease. The distribution of both allelic pairs in the non-fistulizing group proved to be significantly different from HC (P < 0.05), UC (P < 0.03), and the fistulizing group (P < 0.05). There was a similar association in non-operated patients (P = 0.024), whereas no such association was found in surgically treated patients. Among carriers of allele 2 at position -511, UC patients with more severe bleeding symptoms (P = 0.006) were less frequently found. These results suggest that IL1B gene polymorphisms participate in determining the course and severity of inflammatory bowel disease and contribute to explain the heterogeneity of these diseases.

  6. Apathy in Parkinson's disease is related to executive function, gender and age but not to depression

    PubMed Central

    Meyer, Antonia; Zimmermann, Ronan; Gschwandtner, Ute; Hatz, Florian; Bousleiman, Habib; Schwarz, Nadine; Fuhr, Peter

    2015-01-01

    Deficits in executive functions occur in up to 93% of patients with Parkinson's disease (PD). Apathy, a reduction of motivation and goal-directed behavior is an important part of the syndrome; affecting both the patients as well as their social environment. Executive functions can be subdivided into three different processes: initiation, shifting and inhibition. We examined the hypotheses, (1) that apathy in patients with Parkinson's disease is only related to initiation and not to shifting and inhibition, and (2) that depression and severity of motor signs correlate with apathy. Fifty-one non-demented patients (19 = female) with PD were evaluated for apathy, depression and executive functions. Executive function variables were summarized with an index variable according to the defined executive processes. Linear regression with stepwise elimination procedure was used to select significant predictors. The significant model (R2 = 0.41; p < 0.01) revealed influences of initiation (b = −0.79; p < 0.01), gender (b = −7.75; p < 0.01), age (b = −0.07; p < 0.05) and an age by gender interaction (b = 0.12; p < 0.01) on apathy in Parkinson's disease. Motor signs, depression and level of education did not influence the relation. These results support an association of apathy and deficits of executive function in PD. Initiation strongly correlates with apathy, whereas depression does not. We conclude, that initiation dysfunction in a patient with Parkinson's disease heralds apathy. Apathy and depression can be dissociated. Additionally, apathy is influenced by age and gender: older