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Sample records for age disease severity

  1. Sever's Disease

    MedlinePlus

    ... good flexibility while your child is growing. The stretching exercises pictured in the treatment section can lower ... your child has already recovered from Sever's disease, stretching and putting ice on the heel after activity ...

  2. Age and injury severity.

    PubMed

    Brorsson, B

    1989-01-01

    This study aims at showing if and to what extent injury severity in frontal car crashes increases with the age of front seat occupants. Data on 2658 belted drivers and front seat passengers in Volvo private car series 140, 240 and 740/760, involved in frontal crashes were extracted from the Volvo Car Crash Register. The results show that the risk of injury resulting in "medical observation" does not increase systematically with age. However, the risk of fracture with any localization is more than three times higher among those aged 65-74 than in those aged 18-24, and the risk of fracture in the rib cage is nearly eleven times higher among the older than in the younger age group. It can be concluded that the incidence of specific types of injuries - as exemplified with fractures of any localization and fractures in the rib cage - increases with advancing age.

  3. Ageing and neurodegenerative diseases.

    PubMed

    Hung, Chia-Wei; Chen, Yu-Chih; Hsieh, Wan-Ling; Chiou, Shih-Hwa; Kao, Chung-Lan

    2010-11-01

    Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.

  4. Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.

    PubMed

    Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thuy, Tran Thi; Tuan, Nguyen Minh; Hoang, Dang Minh; Dung, Nguyen Thi Phuong; Lien, Le Bich; Quy, Nguyen Thien; Hieu, Nguyen Trong; Hieu, Lu Thi Minh; Hien, Tran Tinh; Hung, Nguyen Thanh; Farrar, Jeremy; Simmons, Cameron P

    2008-08-15

    The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3(133-142)-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.

  5. Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation

    PubMed Central

    Ng, Danny S.; Yip, Yolanda W.; Bakthavatsalam, Malini; Chen, Li J.; Ng, Tse K.; Lai, Timothy Y.; Pang, Calvin P.; Brelén, Mårten E.

    2017-01-01

    Angiopoietin 2 (ANG2) is a proangiogenic cytokine which may have an implication in neovascular age related macular degeneration (nAMD). In 24 eyes of 24 subjects presenting with treatment naïve nAMD and 26 eyes of 26 control patients, aqueous humor samples were collected at the time of intervention (intravitreal injection of anti-vascular endothelial growth factor or cataract extraction). Best corrected visual acuity (BCVA) with and central macular thickness (CMT) using optical coherence tomography (OCT) were measured before each injection in the nAMD group. Aqueous cytokine levels were determined by immunoassay using a multiplex array (Quansys Biosciences, Logan, UT). Levels of ANG2 in the aqueous were significantly higher in nAMD patients than those of the control group (p < 0.0001), so were hepatocyte growth factor (HGF), interleukin-8 (IL-8) and tissue inhibitor of metalloproteinase 1 (TIMP 1), all with p < 0.001. ANG2 correlated with worse BCVA (r = 0.44, p-value = 0.027) and greater CMT (r = 0.66, p-value < 0.0001) on optical coherence tomography (OCT). ANG2 is upregulated in patients with nAMD and correlates with severity of disease at presentation. PMID:28345626

  6. Age-dependent effect of myostatin blockade on disease severity in a murine model of limb-girdle muscular dystrophy.

    PubMed

    Parsons, Stephanie A; Millay, Douglas P; Sargent, Michelle A; McNally, Elizabeth M; Molkentin, Jeffery D

    2006-06-01

    Myostatin (MSTN) is a muscle-specific secreted peptide that functions to limit muscle growth through an autocrine regulatory feedback loop. Loss of MSTN activity in cattle, mice, and humans leads to a profound phenotype of muscle overgrowth, associated with more and larger fibers and enhanced regenerative capacity. Deletion of MSTN in the mdx mouse model of Duchenne muscular dystrophy enhances muscle mass and reduces disease severity. In contrast, loss of MSTN activity in the dyW/dyW mouse model of laminin-deficient congenital muscular dystrophy, a much more severe and lethal disease model, does not improve all aspects of muscle pathology. Here we examined disease severity associated with myostatin (mstn-/-) deletion in mice nullizygous for delta-sarcoglycan (scgd-/-), a model of limb-girdle muscular dystrophy. Early loss of MSTN activity achieved either by monoclonal antibody administration or by gene deletion each improved muscle mass, regeneration, and reduced fibrosis in scgd-/- mice. However, antibody-mediated inhibition of MSTN in late-stage dystrophic scgd-/- mice did not improve disease. These findings suggest that MSTN inhibition may benefit muscular dystrophy when instituted early or if disease is relatively mild but that MSTN inhibition in severely affected or late-stage disease may be ineffective.

  7. Aging modifies the effect of GCH1 RS11158026 on DAT uptake and Parkinson's disease clinical severity.

    PubMed

    Webb, Joseph; Willette, Auriel A

    2017-02-01

    Novel single nucleotide polymorphisms within Parkinson's disease (PD) can predict disease risk, but their influence on clinical, cognitive, and neurobiological indices remains unexplored. We investigated differences between functional polymorphisms at RS11158026 coding for guanosine triphosphate cyclohydrolase-1 (GCH1), an essential enzyme for dopamine production in nigrostriatal cells. Among newly diagnosed, untreated PD subjects and age-matched controls from the Parkinson's Progression Markers Initiative, T allele carriers showed higher PD risk (odds ratio = 1.23, p = 0.048), earlier age of onset by 5 years (p = 0.003), and lower striatal dopamine reuptake transporter uptake (p = 0.003). Carriers also had increased cerebrospinal fluid α-synuclein (p = 0.016), worse motor function (p = 0.041), anxiety (p = 0.038), and executive function (p < 0.001). Strikingly, these effects were only in younger T carriers (<50 years), where aging quells the effects of these genetic factors. This suggests GCH1 variants affect early PD risk through altered dopamine uptake, and aging alters how genetic factors contribute to disease development. Future studies should investigate how aging modifies genotypes' contributions on PD risk and sequelae.

  8. Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD

    PubMed Central

    Simpson, Jodie L.; McDonald, Vanessa M.; Baines, Katherine J.; Oreo, Kevin M.; Wang, Fang; Hansbro, Philip M.; Gibson, Peter G.

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a common and serious respiratory disease, particularly in older individuals, characterised by fixed airway obstruction and persistent airway neutrophilia. The mechanisms that lead to these features are not well established. We investigated the contribution of age, prior smoking, and fixed airflow obstruction on sputum neutrophils, TLR2 expression, and markers of neutrophilic inflammation. Induced sputum from adults with COPD (n = 69) and healthy controls (n = 51) was examined. A sputum portion was dispersed, total, differential cell count and viability recorded, and supernatant assayed for CXCL8, matrix metalloproteinase- (MMP-) 9, neutrophil elastase, and soluble TLR2. Peripheral blood cells (n = 7) were stimulated and TLR2 activation examined. TLR2 levels were increased with ageing, while sputum neutrophils and total sputum MMP-9 levels increased with age, previous smoking, and COPD. In multivariate regression, TLR2 gene expression and MMP-9 levels were significant independent contributors to the proportion of sputum neutrophils after adjustment for age, prior smoking, and the presence of airflow obstruction. TLR2 stimulation led to enhanced release of MMP-9 from peripheral blood granulocytes. TLR2 stimulation activates neutrophils for MMP-9 release. Efforts to understand the mechanisms of TLR2 signalling and subsequent MMP-9 production in COPD may assist in understanding neutrophilic inflammation in COPD. PMID:23606791

  9. Disease drivers of aging

    PubMed Central

    Hodes, Richard J.; Sierra, Felipe; Austad, Steven N.; Epel, Elissa; Neigh, Gretchen N.; Erlandson, Kristine M.; Schafer, Marissa J.; LeBrasseur, Nathan K.; Wiley, Christopher; Campisi, Judith; Sehl, Mary E.; Scalia, Rosario; Eguchi, Satoru; Kasinath, Balakuntalam S.; Halter, Jeffrey B.; Cohen, Harvey Jay; Demark-Wahnefried, Wendy; Ahles, Tim A.; Barzilai, Nir; Hurria, Arti; Hunt, Peter W.

    2017-01-01

    It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship—the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. PMID:27943360

  10. 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.

  11. 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)

  12. 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.

  13. Aging as disease.

    PubMed

    De Winter, Gunnar

    2015-05-01

    In this paper, I will argue that ageing can be construed as disease. First, the concept of disease is discussed, where the distinction is made between two lines of thought, an objectivist and a subjectivist one. After determining the disease conception to be used throughout the argument, it is proposed that senescence could be seen as disease. Three common counterarguments are discussed, none of which appears strong enough to effectively counter the advocated view. In the third section, two potential implications of the view advocated here will be briefly touched upon. These are the quest for a cure or treatment for ageing and the general attitude towards the elderly. It is concluded that, utilizing an objective disease concept, ageing could be seen as a disease. None of the considered counterarguments packs enough of a punch to discard this. The implications are complex and intertwined, but need not be negative.

  14. 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.

  15. Senescence, aging, and disease.

    PubMed

    Crews, Douglas E

    2007-05-01

    All over the world people are surviving into their seventh and later decades of life more frequently today than ever before in human history. Some remain in good health, while others show chronic degenerative conditions (CDCs), frailty, and relatively rapid mortality. Thereafter, multiple factors promoting health and well-being become ever more complex as we age. After attainment of reproductive maturation, many physiological decrements occurring in concert with age reflect both senescent and disease processes, not simply the passage of time. Senescence is a process that begins with DNA, molecules and cells and ultimately terminates in cellular death, loss of organ function, and somatic frailty. These changes are different from benign changes with age that do not alter function. Both differ from the pathological processes represented by disease. Either disease or senescence may be age-related, but neither is age-determined. Disease results from pathological alterations and it affects all age groups. Diseases need not be related to senescence, which includes alterations due to inherent aspects of organismal biology. Distinctions among senescence, aging, and disease blur for the late-life CDCs because, in addition to disease processes, many CDCs are phenotypic manifestations of senescing DNA, organelles, cells, and organs. During earlier epochs of human evolution, greater environmental exposures and fewer cultural buffers likely lead to greater frailty and mortality before senescence progressed greatly, as they still do for most animals. In modern-day settings, culturally patterned behaviors have allowed human frailty to become disconnected somewhat from mortality, unlike non-human species.

  16. [Direct medical costs and influencing factors in severe hand, foot and mouth disease in children aged between six months and five years old].

    PubMed

    Zheng, Y M; Yang, J; Liao, Q H

    2017-01-06

    Objective: To estimate the direct medical cost of severe hand, foot and mouth disease (HFMD) in patients aged less than five years. Methods: A stratified sampling method was used to collect data on severe HFMD cases reported in the National HFMD surveillance database between Jan 1, 2012, and Dec 31, 2013. The sampling was referenced with the national aetiologic distribution of Enterovirus A71 (EV-A71), Coxsackievirus A16 (CV-A16) and other Enteroviruses (OEV) for severe HFMD cases and the included cases were distributed among seven geographic regions (Northeast, North China, Northwest, Central China, Southwest, East China and South China). A nationwide telephone interview using a structured questionnaire was conducted to obtain the direct medical cost and any complications that occurred in patients during the outbreak of laboratory-confirmed HFMD. After excluding the cases who could not recall their medical expenses or complications, a total of 685 cases were included in the analysis. Kruskal-Wallis H test was used to analyze the differences among patients who reported different complications. Multiple linear regression with bootstrap analysis of 500 replicates was used to explore the factors that influenced the direct medical costs. Results: Of 685 patients analyzed, 456 (66.6%) were male and 229 (33.4%) were female. The direct medical costs P50 (P25, P75) were 14 250 (10 301, 20 600) Yuan. In total, 127 (18.5%) patients were diagnosed with severe HFMD patients with respiratory disease, 38 (5.5%) patients were diagnosed with aseptic meningitis, and 378 (55.2%) with encephalitis/brainstem encephalitis/acute flaccid paralysis. Furthermore, 53 (18.5%) patients were diagnosed with myocarditis, 39 (5.7%) with pulmonary hemorrhage/pulmonary edema and 50 (7.3%) with cardiopulmonary failure. The median (interquartile range) direct medical costs were 12 360 (7 313, 16 480) Yuan for severe HFMD patients with respiratory disease, 13 803 (9 064, 19 930) Yuan for aseptic

  17. The Prevalence of Nonalcoholic Fatty Liver Disease and Related Metabolic Comorbidities Was Associated with Age at Onset of Moderate to Severe Plaque Psoriasis: A Cross-Sectional Study

    PubMed Central

    Gao, Yunlu; Ding, Yangfeng

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been found to be highly prevalent in psoriatic patients. Adult onset psoriasis could be divided into either early or late onset psoriasis. The associations between NAFLD and related metabolic comorbidities and age at onset of psoriasis have not yet been investigated. Our study was to evaluate the associations between prevalence of NAFLD and related metabolic conditions and early, late, and childhood onset psoriasis. A cross-sectional observational study was conducted on patients with moderate to severe plaque psoriasis. Data on clinical characteristics of NAFLD and related metabolic diseases (diabetes, hypertriglyceridemia, hyperuricemia, and metabolic syndrome) were collected. The prevalence of NAFLD in 439 patients (mean: 51±14 years, range: 18–85 years) was 55.8%. NAFLD was frequently identified in early onset patients (74.2%), and this diagnosis was particularly common in patients currently younger than 40 (85.3%). Diabetes was the least prevalent component of metabolic syndrome in early onset patients with metabolic syndrome but the most often found component in late onset ones. Patients with childhood onset psoriasis had the lowest frequencies of all metabolic comorbidities except hyperuricemia among the three groups. In the multivariate analyses, early onset was independently and positively associated with NAFLD, hypertriglyceridemia and hyperuricemia and independently and negatively associated with diabetes among early and late onset patients. The results suggested prevalence of NAFLD and related metabolic comorbidities was associated with age at onset of moderate to severe plaque psoriasis. Early onset of psoriasis was independently associated with greater odds of NAFLD, hypertriglyceridemia, hyperuricemia and smaller odds of diabetes compared to late onset. Early onset patients have metabolic syndrome mainly related to lipid disorders and abnormal glucose metabolism was not often involved. PMID:28099469

  18. 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.

  19. Ageing with Muscular Disease

    PubMed Central

    Martinsen, Bente; Dreyer, Pia

    2016-01-01

    Background: The demographic development with an ageing population is predicted to be the next global public health challenge. Advances in medicine and the socioeconomic development have reduced mortality and morbidity due to infectious conditions and non-communicable diseases. The increase in longevity will not be restricted to healthy people. Objective: To understand how people with muscular diseases experience ageing. Method: A literature review was conducted using the Matrix Method developed by Garrard (2007). This systematic method was used to identify, describe and interpret studies, irrespective of the methods applied. To avoid the exclusion of important sources, experiences and topics, we chose an integrative approach that accommodates the inclusion of studies with different methodologies. People with MD have gradually extended their life expectancy during the last 30 years. Thus, we reviewed the literature regarding MD and ageing without time limit. Results: We identified three themes: 1) Slowing down early 2) Accepting lifelong deterioration and 3) Striving for normality. Conclusion: People with MD live in a field of tension between a feeling of autonomy and normality and difficulties coping with reduced physical abilities. Getting older accentuates this tension since the physical strength diminishes and it is harder to maintain autonomy. The bodily challenges may coincide with the end of the rehabilitation people living with MD have received. Seemingly, no age-related rehabilitation is offered, and people living with MD are thus at risk of an unnecessarily passive life. PMID:28144383

  20. 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

  1. 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.

  2. Radiosensitive Severe Combined Immunodeficiency Disease

    PubMed Central

    Dvorak, Christopher C.; Cowan, Morton J.

    2009-01-01

    Synopsis Inherited defects in components of the non-homologous end joining DNA repair mechanism produce a T-B-NK+ severe combined immunodeficiency disease (SCID) characterized by heightened sensitivity to ionizing radiation. Patients with the radiosensitive form of SCID may also have increased short- and long-term sensitivity to the alkylator-based chemotherapy regimens traditionally utilized for conditioning prior to allogeneic hematopoietic cell transplantation (HCT). Known etiologies of radiosensitive SCID include deficiencies of Artemis, DNA Ligase IV, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and Cernunnos-XLF, all of which have been treated with HCT. Because of their sensitivity to certain forms of chemotherapy, the approach to donor selection and type of conditioning regimen utilized for a radiosensitive SCID patient requires careful consideration. Significantly more research needs to be done in order to determine the long-term outcomes of radiosensitive SCID patients following HCT, as well as to discover novel non-toxic approaches to HCT that might benefit those with intrinsic radio- and chemo-sensitivity, as well as potentially all patients undergoing an HCT. PMID:20113890

  3. 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.

  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. 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

  6. [Aging and retinal vascular diseases].

    PubMed

    Takagi, Hitoshi

    2007-03-01

    Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been

  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

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

    2016-09-01

    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.

  8. Burden of Severe Respiratory Syncytial Virus Disease Among 33–35 Weeks’ Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons

    PubMed Central

    Carbonell-Estrany, Xavier; Blanken, Maarten; Lanari, Marcello; Sheridan-Pereira, Margaret; Rodgers-Gray, Barry; Fullarton, John; Rouffiac, Elisabeth; Vo, Pamela; Notario, Gerard; Campbell, Fiona; Paes, Bosco

    2017-01-01

    Background: Moderate-late preterm infants, 33–35 weeks’ gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants. Methods: A pooled analysis was conducted on RSVH from 7 prospective, observational studies in the Northern Hemisphere from 2000 to 2014. Infants’ 330–356 wGA without comorbidity born during the respiratory syncytial virus season who did not receive respiratory syncytial virus immunoprophylaxis were enrolled. Data for the first confirmed RSVH during the season (+1 month) were analyzed. Incidence and hospitalization rate per 100 patient-seasons, intensive care unit admission and length of stay (LOS), oxygen support, mechanical ventilation and overall hospital LOS were assessed. Results: The pooled analysis comprised 7,820 infants; 267 experienced a confirmed RSVH at a median age of 8.4 weeks. The crude pooled RSVH incidence rate was 3.41% and the rate per 100 patient-seasons was 4.52. Median hospital LOS was 5.7 days. A total of 22.2% of infants required intensive care unit admission for a median LOS of 8.3 days. A total of 70.4% received supplemental oxygen support for a median of 4.9 days, and 12.7% required mechanical ventilation for a median of 4.8 days. Conclusions: The burden of RSVH in moderate-late, 33–35 weeks’ wGA preterm infants without comorbidities born during the viral season in Northern Hemisphere countries is substantial. Severe cases required prolonged and invasive supportive therapy. PMID:27755464

  9. Parthenium Dermatitis Severity Score to Assess Clinical Severity of Disease

    PubMed Central

    Verma, Kaushal K; Bansal, Arika; Bhari, Neetu; Sethuraman, Gomathy

    2017-01-01

    Background: Parthenium dermatitis is the most common type of airborne contact dermatitis in India. It is a chronic disease of a remitting and relapsing course with significant morbidity and distress, but there is no scoring system to assess its severity. Aim: To design a scoring system for the assessment of clinical severity of disease in Parthenium dermatitis and to use this scoring system in various studies to determine its sensitivity, specificity, and reproducibility. Methods and Results: In our first few studies on Parthenium dermatitis, we designed and used a basic clinical severity scoring system based on itching, morphology of the lesions, and areas involved. However, in subsequent studies, we modified it to the present scoring system as Parthenium dermatitis severity score (PDSS). Our studies showed the high sensitivity of PDSS in characterization of the disease severity at the given point of time, as well as to determine the efficacy of a prescribed treatment modality which was reliable and reproducible. Conclusion: Thus, PDSS may be used by clinicians for appropriate scoring of the clinical severity of Parthenium dermatitis and in monitoring the disease response to therapy. PMID:28216730

  10. [Measurement of disease severity in dermatology].

    PubMed

    Deckert, S; Apfelbacher, C; Schmitt, J

    2015-09-01

    In order to determine the appropriate therapy for dermatological diseases, numerous measurement instruments are available to measure disease severity. Due to the lack of laboratory parameters for some dermatological diseases to objectify the disease severity (e.g., atopic dermatitis, psoriasis), questionnaires are used. Laboratory as well as questionnaire-based measurements should be reliable, valid, and sensitive to change. In addition, measurement instruments should be feasible. Classifications of disease severity which are based on inadequate measurement properties result in incorrect clinical decisions and limit evidence-based healthcare. Therefore, systematically developed and evidence-based recommendations for the use of individual measurement instruments should be taken into consideration.

  11. Aging - RNA in Development and Disease

    PubMed Central

    Cookson, Mark R

    2011-01-01

    Given that RNA is involved in virtually all biological processes, it is perhaps not surprising that several RNA binding proteins are associated with aging and with different age related disorders. Other chapters in this volume will discuss some specific examples of diseases where RNA plays a role that are also associated with aging, such as cancer and inflammation, so here I will discuss some general aspects of how RNA changes with the aging process. I will also discuss some specific examples of RNA binding proteins that are associated with age-dependent neurological diseases as these provide an interesting framework to examine how lifetime mutations might lead to a late onset disease, although the answers to these questions are still not well understood. PMID:21898829

  12. 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

  13. Age-related eye disease.

    PubMed

    Voleti, Vinod B; Hubschman, Jean-Pierre

    2013-05-01

    As with many organs, compromised function of the eye is accompanied with age and has become increasingly prevalent with the aging population. When decreased visual loss becomes significant, patients' ability to perform activities of daily living becomes compromised. This decrease in function is met with morbidity and mortality, as well as a large socioeconomic burden throughout the world. This review summarizes the most common age-related eye diseases, including cataract, glaucoma, diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Although our understanding of the genetic and biochemical pathways of these diseases is sill at its primitive stages, we have become able to help our patients improve the quality of life as they age.

  14. [Vitamin K2 influences several diseases].

    PubMed

    Hey, Henrik; Brasen, Claus Lohman

    2015-08-03

    In this paper we discuss the evidence of vitamin K2 deficiency which is a factor in several chronic diseases like diabetes, osteoporosis, cancer, inflammatory and cardiovascular diseases. This deficiency is very common in the mentioned diseases although it is rarely treated by clinicians. Randomized clinical trials have shown that patients with osteoporosis, cardiovascular diseases and cancer can benefit from vitamin K2 supplement. Further studies are needed to ascertain the effect of vitamin K2 supplement in patients with diabetes and inflammatory bowel diseases.

  15. Mitochondrial Medicine for Aging and Neurodegenerative Diseases

    PubMed Central

    2011-01-01

    Mitochondria are key cytoplasmic organelles, responsible for generating cellular energy, regulating intracellular calcium levels, altering the reduction-oxidation potential of cells, and regulating cell death. Increasing evidence suggests that mitochondria play a central role in aging and in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Freidriech ataxia. Further, several lines of evidence suggest that mitochondrial dysfunction is an early event in most late-onset neurodegenerative diseases. Biochemical and animal model studies of inherited neurodegenerative diseases have revealed that mutant proteins of these diseases are associated with mitochondria. Mutant proteins are reported to block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins and disrupt the electron transport chain, induce free radicals, cause mitochondrial dysfunction, and, ultimately, damage neurons. This article discusses critical issues of mitochondria causing dysfunction in aging and neurodegenerative diseases, and discusses the potential of developing mitochondrial medicine, particularly mitochondrially targeted antioxidants, to treat aging and neurodegenerative diseases. PMID:18566920

  16. 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

  17. Epigenetics of Aging and Aging-related Disease

    PubMed Central

    2014-01-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging. PMID:24833581

  18. Epigenetics of aging and aging-related disease.

    PubMed

    Brunet, Anne; Berger, Shelley L

    2014-06-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging.

  19. [Neurological diseases in the aged].

    PubMed

    Kameyama, M

    1990-12-01

    In this paper, I described clinical and basic problems on neurology of the aged patients. These studies have been done in various institutions with many co-workers. 1) A PET study revealed some age differences on CBF, CMRO2, or CMRgl. But these results are not so rigid in which much of individual variations should be considered in interpretation. Calendar age is not always compatible to biological age. 2) Saccular aneurysms in the brain artery were found in 7.3% of 1200 routine autopsy series of the aged subjects. Aneurysms with external diameter exceeding 6 mm had been fatally ruptured in 14 (78%) of 18 subjects. 3) Variations of the pyramidal crossing are found responsible for bizarre clinical manifestations. Non-crossing component was more prominent in the right pyramidal tract; consequently, right pyramidal tracts including ventral and lateral one seemed to have more extensive representation in the spinal cord level. 4) I123-IMP SPECT study showed a reduced uptake in the area 4 or area 4-6 of the ALS patients. 5) I introduced a new simplified Wartenberg's maneuver, which is useful for detection of subtle pyramidal dysfunctions. 6) Cases with central pontine myelinolysis and those of paraneoplastic syndrome were presented with an emphasis on their patho-chemical mechanisms. 7) Lewis-Sumner syndrome showing multifocal persistent conduction block is not rare in the aged, in which we have already had some useful therapeutic methods. 8) Dementia complicated with neurodegenerative disease was discussed on its clinical and chemical features of mental disturbances. In ALS-dementia, CSF-homovanilic acid reduced significantly than in the control and L-dopa was effective in some patients. 9) Vascular and Alzheimer-type dementias were presented and discussed on their pathogenetic mechanism according to our recent studies with review of literature.

  20. 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

  1. [Severe interstitial lung disease from pathologic gastroesophageal reflux in children].

    PubMed

    Ahrens, P; Weimer, B; Hofmann, D

    1999-07-01

    Interstitial lung diseases comprise a heterogeneous group of pulmonary conditions that cause restrictive lung disease of poor prognosis, especially if growth failure, pulmonary hypertension and fibrosis appears. We report on the case of a girl of 11 years of age who suffered from severe nonallergic asthma in early childhood and who developed severe interstitial pulmonary disease caused by gastro-oesophageal reflux at the age of 8 years. This diagnosis was established by lung biopsy, bronchoalveolar lavage and a high amount of lipid-laden alveolar macrophages, 2-level pH measurement and oesophageal biopsy. Because therapy with oral and inhaled steroids failed and Omeprazol showed benificial effects, hemifundoplication according to THAL was performed. At present the lung function is clearly normal and there is no need of any medicaments. Following the history, we can assume the pathological gastro-oesophageal reflux to be the cause of the disease. It is important to state that there were no typical symptoms at any time pointing to gastro-oesophageal reflux disease. The development of pulmonary disease by pathological reflux is very often caused by "silent aspiration". Very typically there are no symptoms such as vomiting, heartburn and pain but only signs of chronic lung disease.

  2. Age-related risk of major adverse cardiac event risk and coronary artery disease extent and severity by coronary CT angiography: results from 15 187 patients from the International Multisite CONFIRM Study

    PubMed Central

    Nakazato, Ryo; Arsanjani, Reza; Achenbach, Stephan; Gransar, Heidi; Cheng, Victor Y.; Dunning, Allison; Lin, Fay Y.; Al-Mallah, Mouaz; Budoff, Matthew J.; Callister, Tracy Q.; Chang, Hyuk-Jae; Cademartiri, Filippo; Chinnaiyan, Kavitha; Chow, Benjamin J.W.; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp; Raff, Gilbert; Shaw, Leslee J.; Villines, Todd; Cury, Ricardo C.; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Berman, Daniel S.; Min, James K.

    2014-01-01

    Aims Prior studies evaluating the prognostic utility of cardiac CT angiography (CCTA) have been largely constrained to an all-cause mortality endpoint, with other cardiac endpoints generally not reported. To this end, we sought to determine the relationship of extent and severity of coronary artery disease (CAD) by CCTA to risk of incident major adverse cardiac events (MACEs) (defined as death, myocardial infarction, and late revascularization). Methods and results We identified subjects without prior known CAD who underwent CCTA and were followed for MACE. CAD by CCTA was defined as none (0% luminal stenosis), mild (1–49% luminal stenosis), moderate (50–69% luminal stenosis), or severe (≥70% luminal stenosis), and ≥50% luminal stenosis was considered as obstructive. CAD severity was judged on per-patient, per-vessel, and per-segment basis. Time to MACE was estimated using univariable and multivariable Cox proportional hazards models. Among 15 187 patients (57 ± 12 years, 55% male), 595 MACE events (3.9%) occurred at a 2.4 ± 1.2 year follow-up. In multivariable analyses, an increased risk of MACE was observed for both non-obstructive [hazard ratio (HR) 2.43, P < 0.001] and obstructive CAD (HR: 11.21, P < 0.001) when compared with patients with normal CCTA. Risk-adjusted MACE increased in a dose–response relationship based on the number of vessels with obstructive CAD ≥50%, with increasing hazards observed for non-obstructive (HR: 2.54, P < 0.001), obstructive one-vessel (HR: 9.15, P < 0.001), two-vessel (HR: 15.00, P < 0.001), or three-vessel or left main (HR: 24.53, P < 0.001) CAD. Among patients stratified by age <65 vs. ≥65 years, older individuals experienced higher risk-adjusted hazards for MACE for non-obstructive, one-, and two-vessel, with similar event rates for three-vessel or left main (P < 0.001 for all) compared with normal individuals age <65. Finally, there was a dose relationship of CAD findings by CCTA and MACE event rates with each

  3. Age-Associated Chronic Diseases Require Age-Old Medicine: Role of Chronic Inflammation

    PubMed Central

    Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B.

    2012-01-01

    Most chronic diseases - such as cancer, cardiovascular disease (CVD), Alzheimer disease, Parkinson disease, arthritis, diabetes and obesity - are becoming leading causes of disability and death all over the world. Some of the most common causes of these age-associated chronic diseases are lack of physical activity, poor nutrition, tobacco use, and excessive alcohol consumption. All the risk factors linked to these chronic diseases have been shown to up-regulate inflammation. Therefore, downregulation of inflammation-associated risk factors could prevent or delay these age-associated diseases. Although modern science has developed several drugs for treating chronic diseases, most of these drugs are enormously expensive and are associated with serious side effects and morbidity. In this review, we present evidence on how chronic inflammation leads to age-associated chronic disease. Furthermore, we discuss diet and lifestyle as solutions for age-associated chronic disease. PMID:22178471

  4. 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.

  5. 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

  6. 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...

  7. Disease spread in age structured populations with maternal age effects.

    PubMed

    Clark, Jessica; Garbutt, Jennie S; McNally, Luke; Little, Tom J

    2017-04-01

    Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible-infected compartmental model to investigate how age-specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission.

  8. Age, dental infections, and coronary heart disease.

    PubMed

    Mattila, K J; Asikainen, S; Wolf, J; Jousimies-Somer, H; Valtonen, V; Nieminen, M

    2000-02-01

    Epidemiological and intervention studies have suggested that infections are risk factors for coronary heart disease (CHD). Dental infections have appeared as cardiovascular risk factors in cross-sectional and in follow-up studies, and the association has been independent of the "classic" coronary risk factors. This case-control study aimed at detailed assessment of the dental pathology found in various CHD categories (including elderly patients). Altogether, 85 patients with proven coronary heart disease and 53 random controls, matched for sex, age, geographic area, and socio-economic status, were compared with regard to dental status, assessed blindly with four separate scores, and to the "classic" coronary risk factors (seven of the controls had CHD, and they were not included in the analyses). The dental indices were higher among CHD patients than in the controls, but, contrary to previous studies, the differences were not significant (between the CHD patients and their matched controls or among the different CHD categories). This result could not be explained by potential confounding factors. The participants in the present study were older and had more often undergone recent dental treatment in comparison with subjects in our earlier studies. Age correlated with the severity of dental infections only in the random controls but not in the coronary patients who, although young, already had high dental scores. We believe that the higher age of the participants in the present study is the most likely reason for the results. Other possible explanations include an age-related selection bias among older CHD patients, and the fact that those participating in studies like this may have better general health and thus also less severe dental infections. Thus, the role of dental infections as a coronary risk factor varies according to the characteristics of the population studied.

  9. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter 2007 Table ... of this page please turn Javascript on. Young Women: Lifestyle-related factors that increase heart disease risk ...

  10. Mitochondria and PGC-1α in Aging and Age-Associated Diseases

    PubMed Central

    Wenz, Tina

    2011-01-01

    Aging is the most significant risk factor for a range of degenerative disease such as cardiovascular, neurodegenerative and metabolic disorders. While the cause of aging and its associated diseases is multifactorial, mitochondrial dysfunction has been implicated in the aging process and the onset and progression of age-associated disorders. Recent studies indicate that maintenance of mitochondrial function is beneficial in the prevention or delay of age-associated diseases. A central molecule seems to be the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), which is the key regulator of mitochondrial biogenesis. Besides regulating mitochondrial function, PGC-1α targets several other cellular processes and thereby influences cell fate on multiple levels. This paper discusses how mitochondrial function and PGC-1α are affected in age-associated diseases and how modulation of PGC-1α might offer a therapeutic potential for age-related pathology. PMID:21629705

  11. Mitochondria and PGC-1α in Aging and Age-Associated Diseases.

    PubMed

    Wenz, Tina

    2011-01-01

    Aging is the most significant risk factor for a range of degenerative disease such as cardiovascular, neurodegenerative and metabolic disorders. While the cause of aging and its associated diseases is multifactorial, mitochondrial dysfunction has been implicated in the aging process and the onset and progression of age-associated disorders. Recent studies indicate that maintenance of mitochondrial function is beneficial in the prevention or delay of age-associated diseases. A central molecule seems to be the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), which is the key regulator of mitochondrial biogenesis. Besides regulating mitochondrial function, PGC-1α targets several other cellular processes and thereby influences cell fate on multiple levels. This paper discusses how mitochondrial function and PGC-1α are affected in age-associated diseases and how modulation of PGC-1α might offer a therapeutic potential for age-related pathology.

  12. Molecular Diagnostics of Ageing and Tackling Age-related Disease.

    PubMed

    Timmons, James A

    2017-01-01

    As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age.

  13. Darier's disease misdiagnosed as severe seborrheic dermatitis.

    PubMed

    Schwartz, Jessica L; Clinton, Tony S

    2011-12-01

    Darier's disease is a rare autosomal disorder resulting in characteristic findings of the skin, nails, and mucous membranes. Darier's disease is commonly misdiagnosed as seborrheic dermatitis or eczema. We present the case of a young adult active duty Air Force member with 5 years of skin complaints. The 23-year-old patient had been treated for seborrheic dermatitis and eczema with a variety of oral and topical treatments, which did not result in improvement of his symptoms. Upon referral to dermatology, the dermatologist noted skin, nail, and mucous membrane findings consistent with Darier's disease. A skin biopsy histologically confirmed the presence of Darier's disease and treatment was started. Although the course of the disease cannot be stopped, the patient's symptoms did reduce with the appropriate treatment. This case highlights the importance of revisiting the original diagnosis when conventional treatment fails to improve the disease course.

  14. 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

  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. Blue journal conference. Aging and susceptibility to lung disease.

    PubMed

    Thannickal, Victor J; Murthy, Mahadev; Balch, William E; Chandel, Navdeep S; Meiners, Silke; Eickelberg, Oliver; Selman, Moisés; Pardo, Annie; White, Eric S; Levy, Bruce D; Busse, Paula J; Tuder, Rubin M; Antony, Veena B; Sznajder, Jacob I; Budinger, G R Scott

    2015-02-01

    The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease.

  17. Oral Medication Adherence and Disease Severity in Pediatric Inflammatory Bowel Disease

    PubMed Central

    Hommel, Kevin A.; Denson, Lee A.; Baldassano, Robert N.

    2011-01-01

    Objective The purpose of this study was to examine the relationship of oral medication adherence and perceived adherence barriers with disease severity in a sample of adolescents with IBD. Methods Participants included 62 adolescents, aged 13–17 years, diagnosed with IBD and their parents. Measures of parent- and patient-rated oral medication adherence and related barriers, behavioral and emotional functioning per parent- and self-report, and disease severity per physician reported medical chart data were obtained. Results Fifteen percent of the sample reported clinically elevated depressive symptoms and 24% reported clinically elevated internalizing behavioral problems. Number of reported adherence barriers was 2.6 ± 1.5, and no participants reported zero barriers. Parental ratings of medication adherence (t = −2.11, p < .05) and perceived barriers to adherence (t = 2.05, p < .05) significantly predicted disease severity after statistically controlling for the contributions of behavioral and disease parameters to disease severity. Conclusions Results suggest that oral medication adherence and perceived adherence barriers are significantly related to disease severity in adolescents with IBD. These patients also may be at risk for increased behavioral and emotional problems which may impact health outcomes as well. Clinicians should make particular efforts to attend to medication adherence issues with their patients. Working with patients and families to develop solutions for eliminating adherence barriers might result in better disease outcomes. PMID:21304318

  18. Ocular signs correlate well with disease severity and genotype in Fabry disease.

    PubMed

    Pitz, Susanne; Kalkum, Gisela; Arash, Laila; Karabul, Nesrin; Sodi, Andrea; Larroque, Sylvain; Beck, Michael; Gal, Andreas

    2015-01-01

    Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination. Three ocular signs were assessed: cornea verticillata, tortuous conjunctival and/or retinal vessels, and cataract. Fabry disease severity was measured using FOS Mainz Severity Score Index and modifications thereof. Ophthalmological data were available for 1203 (699 female, 504 male) adult patients with eye findings characteristic of Fabry disease in 55.1%. Cornea verticillata had a similar distribution in women (51.1%) and men (50.8%), whereas tortuous vessels and Fabry cataract were somewhat more frequent in men than in women. Patients with cornea verticillata, selected as the principal ocular sign for this study, had more severe disease (median score, 20.0) versus those without ocular signs (11.0; P<0.001). This finding could be confirmed by applying age adjusted severity scores. Moreover, the prevalence of cornea verticillata was significantly higher in patients with null (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01). Our analyses show a correlation between the prevalence of ocular changes in Fabry disease and disease severity. Consequently, information on ocular findings and α-galactosidase A gene mutation may help assess the risk for more severe Fabry disease. These observed findings are of notable clinical importance, as Fabry disease is characterized by high clinical course variability and only weak genotype-phenotype correlation at the individual patient level. Further confirmatory studies

  19. Age-related eye disease and gender.

    PubMed

    Zetterberg, Madeleine

    2016-01-01

    Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease.

  20. 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.

  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. 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.

  3. Neuroglia in ageing and disease.

    PubMed

    Verkhratsky, Alexei; Rodríguez, José J; Parpura, Vladimir

    2014-08-01

    The proper operation of the mammalian brain requires dynamic interactions between neurones and glial cells. Various types of glial cells are susceptible to morpho-functional changes in a variety of brain pathological states, including toxicity, neurodevelopmental, neurodegenerative and psychiatric disorders. Morphological modifications include a change in the glial cell size and shape; the latter is evident by changes of the appearance and number of peripheral processes. The most blatant morphological change is associated with the alteration of the sheer number of neuroglia cells in the brain. Functionally, glial cells can undergo various metabolic and biochemical changes, the majority of which reflect upon homeostasis of neurotransmitters, in particular that of glutamate, as well as on defence mechanisms provided by neuroglia. Not only glial cells exhibit changes associated with the pathology of the brain but they also change with brain aging.

  4. NAD+ and Sirtuins in Aging and Disease

    PubMed Central

    Imai, Shin-ichiro; Guarente, Leonard

    2014-01-01

    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 anti-aging intervention, providing hope to aging societies worldwide. PMID:24786309

  5. Celiac disease presenting as severe osteopenia.

    PubMed

    Mulder, Christopher J; Cardile, Anthony P; Dickert, Judith

    2011-11-01

    The authors describe a unique presentation of celiac disease as multiple non-traumatic fractures in a young male without gastrointestinal complaints. A 29-year-old man presented with back pain and was found to have a non-traumatic compression fracture of the lumbar and thoracic spine on plain X-ray. Dual-energy x-ray absorptiometry (DXA) confirmed osteoporosis at the L3/L4 vertebral bodies. Parathyroid hormone (PTH), calcium, and vitamin D levels were normal. He had no gastrointestinal complaints, but serologic studies were positive to include an elevated gliadin IgA Ab, gliadin IgG Ab, and an elevated tissue transglutaminase IgA Ab. He was treated with a gluten-free diet, calcium, and vitamin D supplementation as well as teriparatide. Follow up bone density showed improvement and has no further fractures to date. Primary care physicians, gastroenterologists, and endocrinologists must have a high index of clinical suspicion for celiac disease in any patient who presents with low bone density regardless of the serum 25-OH vitamin D levels or presence of gastrointestinal complaints.

  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. Nutrition and AGE-ing: Focusing on Alzheimer's Disease.

    PubMed

    Abate, Giulia; Marziano, Mariagrazia; Rungratanawanich, Wiramon; Memo, Maurizio; Uberti, Daniela

    2017-01-01

    Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing ("AGE-ing") is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss food's dual role as both source of bioactive nutrients and reservoir for potential toxic compounds-paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimer's disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet.

  8. 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.

  9. 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.

  10. 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

  11. Nutrition and AGE-ing: Focusing on Alzheimer's Disease

    PubMed Central

    Marziano, Mariagrazia; Rungratanawanich, Wiramon; Memo, Maurizio

    2017-01-01

    Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing (“AGE-ing”) is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss food's dual role as both source of bioactive nutrients and reservoir for potential toxic compounds—paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimer's disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet. PMID:28168012

  12. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease.

    PubMed

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed.

  13. 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

  14. A comparison of different category scales for estimating disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant pathologists most often obtain quantitative information on disease severity using visual assessments. Category scales are widely used for assessing disease severity, including for screening germplasm. The most widely used category scale is the Horsfall-Barratt (H-B) scale, but reports show tha...

  15. Introduction to Aging, Cancer, and Age-related Diseases.

    PubMed

    Perry, Daniel P

    2010-06-01

    A rising tide of chronic age-dependent diseases, co-morbidities, and geriatric syndromes--a veritable Silver Tsunami--will soon present serious challenges for North America, Europe, Japan, and other industrialized nations. Meanwhile, a growing number of scientists, led by biogerontologists, maintain that the key to blunting the societal impact of large-scale decline and disability among older populations lies with better understanding and potential manipulation of biological mechanisms of aging itself. Well-characterized interventions that slow aging and extend health and vigor in animal models may be forerunners of technologies that preserve additional years of healthy productive life in humans. What will it take to validate these momentous insights from biogerontology and their potential applications for human populations? What are the points of resistance for key opinion leaders and policy makers? And how can biogerontologists make common cause with those outside the discipline to inform larger and more politically powerful audiences?

  16. Pathophysiology of age-related diseases

    PubMed Central

    Campisi, Giuseppina; Chiappelli, Martina; De Martinis, Massimo; Franco, Vito; Ginaldi, Lia; Guiglia, Rosario; Licastro, Federico; Lio, Domenico

    2009-01-01

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention. PMID:19737378

  17. Aging and endothelin: determinants of disease.

    PubMed

    Barton, Matthias

    2014-11-24

    Since the beginning of the 20th century human life expectancy has doubled to more than 80 years, and growth and aging of the world population now represent major challenges for healthcare providers, political decision makers, and societies. Cellular senescence is associated with a general, pro-inflammatory state, which represents the common denominator between aging and chronic diseases and their progression. Approaches to interfere with these changes and to allow healthy aging involve modulation of the cellular activity of modifiable molecular mediators (MMMs), such as signaling molecules and growth factors. ET-1 - the biologically predominant member of the endothelin peptide family - is an endothelial cell-derived peptide with a wide variety of developmental and physiological functions, which include embryogenesis, nociception, and natriuresis. In addition, ET-1 is a cytokine-like, multifunctional peptide with pro-inflammatory, mitogenic, and vasoconstrictor properties. If produced in excess amounts ET-1 promotes disease - mainly via activation of its ETA receptor. Because of its multiple disease-promoting functions ET-1 represents an ideal target MMM. Preclinical studies targeting either activity or production of ET-1 - utilizing ERAs, ARBs, or ACEIs, respectively - have demonstrated that partial regression of aging-associated changes in vasculature and kidney is possible. In this article I will review the molecular regulation of ET-1 and its role in the physiology of vascular homeostasis, aging, and cellular senescence. The clinical implications of activators of ET-1 overproduction, modalities for delaying or reversing aging-related cellular changes, as well as interventions to promote healthy aging and early disease prevention - particularly physical activity - are discussed.

  18. 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

  19. Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment

    PubMed Central

    Shapiro, Elsa G.; Nestrasil, Igor; Rudser, Kyle; Delaney, Kathleen; Kovac, Victor; Ahmed, Alia; Yund, Brianna; Orchard, Paul J.; Eisengart, Julie; Niklason, Gregory R.; Raiman, Julian; Mamak, Eva; Cowan, Morton J.; Bailey-Olson, Mara; Harmatz, Paul; Shankar, Suma P.; Cagle, Stephanie; Ali, Nadia; Steiner, Robert D.; Wozniak, Jeffrey; Lim, Kelvin O.; Whitley, Chester B.

    2015-01-01

    Objectives Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden. Methods Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes. Sixty-seven patients had volumetric MRI. Subjects were grouped by age and phenotype and MRI and compared to 96 normal controls. Results Prior to hematopoietic cell transplant, MPS IH patients were all cognitively average, but post-transplant, 59% were below average, but stable. Genotype and age at HCT were associated with cognitive ability. In attenuated MPS I, 40% were below average with genotype and somatic disease burden predicting their cognitive ability. White matter volumes were associated with IQ for controls, but not for MPS I. Gray matter volumes were positively associated with IQ in controls and attenuated MPS I patients, but negatively associated in MPS IH. Conclusions Cognitive impairment, a major difficulty for many MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association with white matter differed from controls. Many attenuated MPS patients have significant physical and/or cognitive problems and receive insufficient support services. Results provide direction for future clinical trials and better disease management. PMID:26095521

  20. Integrating gut microbiota immaturity and disease-discriminatory taxa to diagnose the initiation and severity of shrimp disease.

    PubMed

    Xiong, Jinbo; Zhu, Jinyong; Dai, Wenfang; Dong, Chunming; Qiu, Qiongfen; Li, Chenghua

    2017-04-01

    Increasing evidence has emerged a tight link among the gut microbiota, host age and health status. This osculating interplay impedes the definition of gut microbiome features associated with host health from that in developmental stages. Consequently, gut microbiota-based prediction of health status is promising yet not well established. Here we firstly tracked shrimp gut microbiota (N = 118) over an entire cycle of culture; shrimp either stayed healthy or progressively transitioned into severe disease. The results showed that the gut microbiota were significantly distinct over shrimp developmental stages and disease progression. Null model and phylogenetic-based mean nearest taxon distance (MNTD) analyses indicated that deterministic processes that governed gut community became less important as the shrimp aged and disease progressed. The predicted gut microbiota age (using the profiles of age-discriminatory bacterial species as independent variables) fitted well (r = 0.996; P < 0.001) with the age of healthy subjects, while this defined trend was disrupted by disease. Microbiota-for-age Z-scores (MAZ, here defined as immaturity) were relative stable among healthy shrimp, but sharply decreased when disease emerged. By distinguishing between age- and disease- discriminatory taxa, we developed a model, bacterial indicators of shrimp health status, to diagnose disease from healthy subjects with 91.5% accuracy. Notably, the relative abundances of the bacterial indicators were indicative for shrimp disease severity. These findings, in aggregate, add our understanding on the gut community assembly patterns over shrimp developmental stages and disease progression. In addition, shrimp disease initiation and severity can be accurately diagnosed using gut microbiota immaturity and bacterial indicators.

  1. Orthodontic approach for patients with severe periodontal disease.

    PubMed

    Arun, Tülin; Sayinsu, Korkmaz; Nalbantgil, Didem

    2005-01-01

    Although comprehensive orthodontic treatment cannot preclude the possibility of periodontal disease developing later, it can be a useful part of the overall treatment plan for a patient who already has periodontal involvement. A careful clinical examination must determine the patient's dental health status, including any existing destruction or deficiencies of the teeth and their support, as well as the patient's ability to achieve and maintain good overall oral hygiene. Two major criteria should be considered in the treatment of these patients: (1) the patient should be seen frequently for periodontal maintenance and (2) minimal orthodontic forces should be applied. Segmented archwires could be used for the treatment mechanics. After treatment, splinting of the teeth is necessary both short- and long-term. With this orthodontic approach, both dental esthetics and function improve and can be maintained. A male patient, 50 years of age, with severe periodontal involvement was referred to the authors' clinic, from the periodontal department, for treatment. The mandibular incisors were intruded by using segmental archwires. At the end of treatment, permanent retention was required due to the severe bone loss.

  2. 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.

  3. Management of severe rheumatological disease in the burn center.

    PubMed

    Reddy, Preetham; Ahrenholz, David H; Mohr, William J; Gertner, Elie

    2012-01-01

    In recent years, Burn Center has evolved to become a "wound intensive care unit" treating disease processes other than those due to thermal injury. Recent data have shown that more than 16% of admissions to Burn Centers are for nonburn injuries, particularly severe dermatologic diseases. The role of the Burn Center has been expanded to include treatment of patients with severe cutaneous manifestations of rheumatologic diseases. This approach has not been described before. All collagen vascular disease admissions to the Burn Center from 2005 to 2010 have been reviewed. There were 16 admissions where intensive wound management was a major component of the disease management. Disease processes included systemic lupus erythematosus, progressive systemic sclerosis, Raynaud's phenomenon, antiphospholipid syndrome, and dermatomyositis, among others. The authors describe five of these cases in detail. Comanagement of these patients by the Rheumatology and Burn services led to outstanding, successful outcomes. Collagen vascular diseases represent another area where the Burn Center may be the appropriate site for therapy.

  4. Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

    PubMed

    Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

    2017-03-01

    Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research.

  5. Chronic kidney Disease and the Aging Population.

    PubMed

    Tonelli, Marcello; Riellae, Miguel

    2014-01-01

    Youth, which is forgiven everything, forgives itself nothing: age, which forgives itself everything, is forgiven nothing. George Bernard Shaw The proportion of older people in the general population is steadily increasing worldwide, with the most rapid growth in low-and middle-income countries [1]. This demographic change is to be celebrated, because it is the consequence of socioeconomic development and better life expectancy. However, population aging also has important implications for society - in diverse areas including health systems, labor markets, public policy, social programs, and family dynamics [2]. A successful response to the aging population will require capitalizing on the opportunities that this transition offers, as well as effectively addressing its challenges. Chronic kidney disease (CKD) is an important public health problem that is characterized by poor health outcomes and very high health care costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke - all of which are key causes of death and disability in older people [3]. Since the prevalence of CKD is higher in older people, the health impact of population aging will depend in part on how the kidney community responds. March 13, 2014 will mark the celebration of the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of kidney disease. The topic for WKD 2014 is "CKD in older people". This article reviews the key links between kidney function, age, health and illness - and discusses the implications of the aging population for the care of people with CKD.

  6. When neurogenesis encounters aging and disease.

    PubMed

    Lazarov, Orly; Mattson, Mark P; Peterson, Daniel A; Pimplikar, Sanjay W; van Praag, Henriette

    2010-12-01

    In this review, we consider the evidence that a reduction in neurogenesis underlies aging-related cognitive deficits and impairments in disorders such as Alzheimer's disease (AD). The molecular and cellular alterations associated with impaired neurogenesis in the aging brain are discussed. Dysfunction of presenilin-1, misprocessing of amyloid precursor protein and toxic effects of hyperphosphorylated tau and β-amyloid probably contribute to impaired neurogenesis in AD. Because factors such as exercise, environmental enrichment and dietary energy restriction enhance neurogenesis, and protect against age-related cognitive decline and AD, knowledge of the underlying neurogenic signaling pathways could lead to novel therapeutic strategies for preserving brain function. In addition, manipulation of endogenous neural stem cells and stem cell transplantation, as stand-alone or adjunct treatments, seems promising.

  7. When Neurogenesis Encounters Aging and Disease

    PubMed Central

    Lazarov, Orly; Mattson, Mark P.; Peterson, Daniel A.; Pimplikar, Sanjay W.; van Praag, Henriette

    2010-01-01

    In this review, we consider the evidence that a reduction in neurogenesis underlies aging-related cognitive deficits, and impairments in disorders such as Alzheimer's disease (AD). The molecular and cellular alterations associated with impaired neurogenesis in the aging brain are discussed. Dysfunction of presenilin-1, misprocessing of amyloid precursor protein and toxic effects of hyperphosphorylated tau and β-amyloid likely contribute to impaired neurogenesis in AD. Since factors such as exercise, enrichment and dietary energy restriction enhance neurogenesis, and protect against age-related cognitive decline and AD, knowledge of the underlying neurogenic signaling pathways could lead to novel therapeutic strategies for preserving brain function. In addition, manipulation of endogenous neural stem cells and stem cell transplantation, as stand-alone or adjunct treatments, seem promising. PMID:20961627

  8. 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

  9. 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

  10. Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection

    PubMed Central

    Virlogeux, Victor; Fang, Vicky J.; Wu, Joseph T.; Ho, Lai-Ming; Malik Peiris, J. S.; Leung, Gabriel M.; Cowling, Benjamin J.

    2016-01-01

    Background Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. Methods We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome (SARS) coronavirus, using data from the epidemic in 2003 in Hong Kong. Results We estimated the incubation period of SARS based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found significant associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. Conclusions Our findings suggest that patients with a shorter incubation period proceeded to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association. PMID:26133021

  11. Cellular Regulation of Amyloid Formation in Aging and Disease

    PubMed Central

    Stroo, Esther; Koopman, Mandy; Nollen, Ellen A. A.; Mata-Cabana, Alejandro

    2017-01-01

    As the population is aging, the incidence of age-related neurodegenerative diseases, such as Alzheimer and Parkinson disease, is growing. The pathology of neurodegenerative diseases is characterized by the presence of protein aggregates of disease specific proteins in the brain of patients. Under certain conditions these disease proteins can undergo structural rearrangements resulting in misfolded proteins that can lead to the formation of aggregates with a fibrillar amyloid-like structure. Cells have different mechanisms to deal with this protein aggregation, where the molecular chaperone machinery constitutes the first line of defense against misfolded proteins. Proteins that cannot be refolded are subjected to degradation and compartmentalization processes. Amyloid formation has traditionally been described as responsible for the proteotoxicity associated with different neurodegenerative disorders. Several mechanisms have been suggested to explain such toxicity, including the sequestration of key proteins and the overload of the protein quality control system. Here, we review different aspects of the involvement of amyloid-forming proteins in disease, mechanisms of toxicity, structural features, and biological functions of amyloids, as well as the cellular mechanisms that modulate and regulate protein aggregation, including the presence of enhancers and suppressors of aggregation, and how aging impacts the functioning of these mechanisms, with special attention to the molecular chaperones. PMID:28261044

  12. Systemic DNA damage responses in aging and diseases

    PubMed Central

    Ribezzo, Flavia; Shiloh, Yosef; Schumacher, Björn

    2016-01-01

    The genome is constantly attacked by a variety of genotoxic insults. The causal role for DNA damage in aging and cancer is exemplified by genetic defects in DNA repair that underlie a broad spectrum of acute and chronic human disorders that are characterized by developmental abnormalities, premature aging, and cancer predisposition. The disease symptoms are typically tissue-specific with uncertain genotype-phenotype correlation. The cellular DNA damage response (DDR) has been extensively investigated ever since yeast geneticists discovered DNA damage checkpoint mechanisms, several decades ago. In recent years, it has become apparent that not only cell-autonomous but also systemic DNA damage responses determine the outcome of genome instability in organisms. Understanding the mechanisms of non-cell-autonomous DNA damage responses will provide important new insights into the role of genome instability in human aging and a host of diseases including cancer and might better explain the complex phenotypes caused by genome instability. PMID:26773346

  13. Reflexive and Volitional Saccades: Biomarkers of Huntington Disease Severity and Progression

    PubMed Central

    Patel, Saumil S.; Jankovic, Joseph; Hood, Ashley J.; Jeter, Cameron B.; Sereno, Anne B.

    2011-01-01

    Background Huntington disease (HD) is a genetic, neurodegenerative disorder characterized by chorea, behavioral co-morbidities, cognitive deficits, and eye movement abnormalities. We sought to evaluate whether reflexive and voluntary orienting prove useful as biomarkers of disease severity in HD. Methods Eleven HD subjects were evaluated with the motor subscale of the Unified Huntington Disease Rating Scale (UHDRS) and the Montreal Cognitive Assessment. Using an infrared eye tracker, we also measured latency and error rates of horizontal and vertical saccades using prosaccade and antisaccade eye movement tasks. We calculated simple and age-controlled correlations between eye movement and clinical parameters. Results Prosaccade latency correlated with total chorea score. HD patients with greater clinical severity were significantly slower in the prosaccade task. Antisaccade error rate also correlated with UHDRS motor score and total chorea score. HD patients with greater clinical severity as measured by either measure made significantly more errors in the antisaccade task. All these correlations remained significant even when age was taken into account. Conclusions The results of the present age-controlled study show for the first time that both reflexive and voluntary eye motor control in HD patients decrease with increase in disease severity suggesting declines in both motor and cognitive function. Thus, relatively simple eye movement parameters (latency and error rate) obtained from simple tasks (prosaccade and antisaccade) may serve as quantitative biomarkers of sub-cortical and cortical disease severity in HD and could aid in predicting onset, distinguishing subtypes, or evaluating disease progression and novel therapies. PMID:22018763

  14. 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.

  15. 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

  16. Severe exacerbation of Crohn's disease during sunitinib treatment.

    PubMed

    Boers-Sonderen, Marye J; Mulder, Sasja F; Nagtegaal, Iris D; Jacobs, Joannes F M; Wanten, Geert J; Hoentjen, Frank; van Herpen, Carla M

    2014-02-01

    Sunitinib is a multiple tyrosine kinase inhibitor of the vascular endothelial growth factor and platelet-derived growth factor pathway and inhibits angiogenesis, cell proliferation, and tumor cell invasion, and stimulates apoptosis. Treatment with sunitinib in first-line metastatic renal cell carcinoma improves progression-free survival and overall survival compared with interferon-α. Crohn's disease is characterized by chronic immune-mediated intestinal inflammation. Although the exact pathogenesis of Crohn's disease remains unknown, the involvement of angiogenesis is acknowledged. It is unknown whether sunitinib interferes with the natural course of Crohn's disease. We describe a patient with metastatic renal cell carcinoma and a history of Crohn's disease who was treated with sunitinib and developed a severe exacerbation of Crohn's disease. After rechallenge with sunitinib, a second exacerbation occurred. We therefore conclude that angiogenesis inhibitors should be administered with care in patients with a history of Crohn's disease.

  17. The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis.

    PubMed

    Harshman, Stephanie G; Shea, M Kyla

    2016-06-01

    Vitamin K is an enzyme cofactor required for the carboxylation of vitamin K dependent proteins, several of which have been implicated in diseases of aging. Inflammation is recognized as a crucial component of many chronic aging diseases and evidence suggests vitamin K has an anti-inflammatory action that is independent of its role as an enzyme co-factor. Vitamin K-dependent proteins and inflammation have been implicated in cardiovascular disease and osteoarthritis, which are leading causes of disability and mortality in older adults. The purpose of this review is to summarize observational studies and randomized trials focused on vitamin K status and inflammation, cardiovascular disease, and osteoarthritis. Although mechanistic evidence suggests a protective role for vitamin K in these age-related conditions, the benefit of vitamin K supplementation is controversial because observational data are equivocal and the number of randomized trials is few.

  18. Median and Ulnar Neuropathy Assessment in Parkinson's Disease regarding Symptom Severity and Asymmetry.

    PubMed

    Yardimci, Nilgul; Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla

    2016-01-01

    Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD.

  19. Median and Ulnar Neuropathy Assessment in Parkinson's Disease regarding Symptom Severity and Asymmetry

    PubMed Central

    Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla

    2016-01-01

    Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD. PMID:27843673

  20. Curative treatment for severe sickle cell disease: allogeneic transplantation.

    PubMed

    Oshrine, Benjamin; Talano, Julie-An

    2015-04-01

    Sickle cell disease is an inherited hematologic disorder that in its severe form can result in substantial morbidity and early mortality. Patients with this disorder can suffer from severe pain, lung disease, and strokes, resulting in chronic debilitating conditions, end organ dysfunction, and organ failure. The health care costs of caring for these chronically ill patients are substantial. Allogeneic transplantation is a modality that has the potential to cure these patients. To date, matched sibling donor transplantation is widely accepted as a standard of care for pediatric patients. Utilizing alternative donors for transplant is still under investigation, as is transplant for adult patients with sickle cell disease. This review focuses on the most recent data for hematopoietic cell transplantation for patients with sickle cell disease.

  1. 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

  2. Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

    PubMed Central

    Di Germanio, Clara; Bernier, Michel; de Cabo, Rafael; Barboni, Barbara

    2016-01-01

    The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat “inflammaging,” anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis. Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases. PMID:27921031

  3. 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

  4. Manifestation of severe coronary heart disease after anabolic drug abuse.

    PubMed

    Mewis, C; Spyridopoulos, I; Kühlkamp, V; Seipel, L

    1996-02-01

    Anabolic steroids are frequently abused, thus increasing the risk of cardiovascular disease, despite the known unfavorable influence on lipid profiles. We report on a young bodybuilder who presented with ventricular tachycardia as the first manifestation of severe underlying coronary heart disease. Coronary angiogram revealed severe stenotic lesions in the right coronary artery and the left descending coronary artery, and hypokinetic regions corresponded to posterolateral and anterior myocardial infarctions. This young patient had a history without any coronary risk factors, but with a 2-year abuse of the anabolic steroid stanazolol. No report published so far has shown possible atherogenic consequences of long-term abuse of stanazolol.

  5. Compartmentalized immune response reflects clinical severity of beryllium disease.

    PubMed

    Newman, L S; Bobka, C; Schumacher, B; Daniloff, E; Zhen, B; Mroz, M M; King, T E

    1994-07-01

    Although beryllium disease has been associated with a bronchoalveolar lavage (BAL) lymphocytosis and T cell-mediated immune response, we do not know if either the BAL cellular profile or the compartmentalized pulmonary response to the antigen reflect the severity of the disease. We studied 110 subjects divided into three groups of subjects: beryllium disease patients (n = 55), beryllium-sensitized patients without disease (n = 8), and control subjects (n = 47). Evaluation included completion of a respiratory symptom questionnaire, clinical examination, chest radiograph, spirometry, body plethysmographic lung volumes, and diffusing capacity (DLCO). In the patient groups, we performed maximal exercise testing with an indwelling arterial line. In addition, we examined BAL and performed blood and BAL beryllium lymphocyte transformation tests (BeLT) as measures of the beryllium-specific T cell-mediated response in these two compartments. In beryllium disease patients we correlated the BAL cellular constituents with clinical parameters indicative of disease severity. Beryllium disease patients exhibited elevated numbers of white cells and lymphocytes in BAL compared with both other groups; however, this lymphocytic alveolitis was significantly obscured in smokers. The BAL cellular constituents correlated with BAL BeLT but not with the blood BeLT. BAL cellular constituents also correlated with the radiographic profusion of small opacities, FEV1/FVC, DLCO, maximal achievable work load, VO2max, and measures of gas exchange at rest and at maximum exercise. We conclude that the lymphocyte-predominant pulmonary inflammatory response in beryllium disease is related to the magnitude of the localized response to antigen and that BAL cellularity, differential cell count, and BeLT reflect beryllium disease clinical severity.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. [A case of complex Crohn's disease with severe complication].

    PubMed

    Tian, Li; Tang, Anliu; Liu, Fen; Guo, Qin; Wang, Xiaoyan; Shen, Shourong

    2016-04-01

    Crohn's disease (CD) is a nonspecific chronic intestinal inflammatory disease with unknown etiology. The course of CD is persistent and recurrent. In the progress, CD can come with many complications such as obstruction, fistula formation, perforation, and hemorrhage. The early diagnosis, treatment, and the time of the surgery for CD pose a big controversy and challenge. There was a female patient diagnosed as Crohn's disease with severe complication in department of Gastroenterology of the Third Xiangya Hospital, Central South University.  We reported the diagnosis and treatment on this patient. The choice for the medicine and surgury was discussed.

  7. 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.

  8. 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.

  9. 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

  10. Metabolomic signatures associated with disease severity in multiple sclerosis

    PubMed Central

    Alonso, Cristina; Agirrezabal, Ion; Kotelnikova, Ekaterina; Zubizarreta, Irati; Pulido-Valdeolivas, Irene; Saiz, Albert; Comabella, Manuel; Montalban, Xavier; Villar, Luisa; Alvarez-Cermeño, Jose Carlos; Fernández, Oscar; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Castro, Azucena

    2017-01-01

    Objective: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. Methods: We studied 2 cohorts of patients with MS: a retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS). Metabolomic profiling (lipids and amino acids) was performed by ultra-high-performance liquid chromatography coupled to mass spectrometry in serum samples. Data analysis was performed using parametric methods, principal component analysis, and partial least square discriminant analysis for assessing the differences between cases and controls and for subgroups based on disease severity. Results: We identified metabolomics signatures with high accuracy for classifying patients vs controls as well as for classifying patients with medium to high disability (EDSS >3.0). Among them, sphingomyelin and lysophosphatidylethanolamine were the metabolites that showed a more robust pattern in the time series analysis for discriminating between patients and controls. Moreover, levels of hydrocortisone, glutamic acid, tryptophan, eicosapentaenoic acid, 13S-hydroxyoctadecadienoic acid, lysophosphatidylcholines, and lysophosphatidylethanolamines were associated with more severe disease (non-relapse-free or increase in EDSS). Conclusions: We identified metabolomic signatures composed of hormones, lipids, and amino acids associated with MS and with a more severe course. PMID:28180139

  11. 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

  12. 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…

  13. The aged gut in inflammatory bowel diseases.

    PubMed

    Ardesia, M; Villanacci, V; Fries, W

    2015-12-01

    Senescence is accompanied by various anatomical and functional alterations starting from mastication and deglutition and consequent modifications of nutrition. In addition, the widespread use of proton pump inhibitors and non-steroidal anti-inflammatory drugs in aged subjects weakens the gastric barrier, thus contributing to easier entry of microbes into the gastrointestinal tract. The microbiota of the elderly is less stable than that of younger adults, therefore, gut dysbiosis is more frequent. Dysbiosis represents a key factor for infections, e.g. Clostridium difficile, especially after antibiotic treatment, but also represents an important step for the development of inflammatory bowel diseases (IBD). IBD onset in the elderly needs careful evaluation in order to distinguish this entity from other pathologies that may affect the gut in senescence. Colitis associated with diverticula, drug-induced, ischemic, and microscopic colitides are among the possible diseases and, therefore, a careful macroscopic and histologic evaluation is mandatory. Finally, late onset IBD represents an important challenge for physicians since it occurs in subjects with frequent comorbidities and relative concomitant treatments. Although there is some evidence that disease course of elderly-onset IBD follows a milder course, overall morbidity, hospitalization rates and even mortality, the latter mostly due to comorbidities, are increased, especially in emergency settings.

  14. 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

  15. Growth Differentiation Factor 15 Predicts Chronic Liver Disease Severity

    PubMed Central

    Lee, Eaum Seok; Kim, Seok Hyun; Kim, Hyun Jin; Kim, Kyung Hee; Lee, Byung Seok; Ku, Bon Jeong

    2017-01-01

    Background/Aims Growth differentiation factor 15 (GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is emerging as a biomarker for several diseases. The aim of this study was to determine the clinical performances of GDF-15 for the prediction of liver fibrosis and severity in chronic liver disease. Methods The serum GDF-15 levels were examined via enzyme immunoassay in 145 patients with chronic liver disease and 101 healthy individuals. The patients with chronic liver disease consisted of 54 patients with chronic hepatitis, 44 patients with compensated liver cirrhosis, and 47 patients with decompensated liver cirrhosis. Results Of the patients with chronic liver diseases, the decompensated liver cirrhosis patients had an increased serum GDF-15 (3,483 ng/L) level compared with the patients with compensated liver cirrhosis (1,861 ng/L) and chronic hepatitis (1,232 ng/L). The overall diagnostic accuracies of GDF-15, as determined by the area under the receiver operating characteristic curves, were as follows: chronic hepatitis=0.656 (>574 ng/L, sensitivity, 53.7%; specificity, 79.2%), compensated liver cirrhosis=0.886 (>760 ng/L, sensitivity, 75.6%; specificity, 92.1%), and decompensated liver cirrhosis=0.984 (>869 ng/L, sensitivity, 97.9%; specificity, 94.1%). Conclusions This investigation represents the first study to demonstrate the availability of GDF-15 in chronic liver disease. GDF-15 comprised a useful biomarker for the prediction of liver fibrosis and severity in chronic liver disease. PMID:27728964

  16. 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.

  17. Of sound mind and body: depression, disease, and accelerated aging

    PubMed Central

    M. Wolkowitz, Owen; I. Reus, Victor; H. Mellon, Synthia

    2011-01-01

    Major depressive disorder (MDD) is associated with a high rate of developing serious medical comorbidities such as cardiovascular disease, stroke, dementia, osteoporosis, diabetes, and the metabolic syndrome. These are conditions that typically occur late in life, and it has been suggested that MDD may be associated with “accelerated aging.” We review several moderators and mediators that may accompany MDD and that may give rise to these comorbid medical conditions. We first review the moderating effects of psychological styles of coping, genetic predisposition, and epigenetic modifications (eg, secondary to childhood adversity). We then focus on several interlinked mediators occurring in MDD (or at least in subtypes of MDD) that may contribute to the medical comorbidity burden and to accelerated aging: limbic-hypothalamic-pituitary-adrenal axis alterations, diminution in glucocorticoid receptor function, altered glucose tolerance and insulin sensitivity, excitotoxicity, increases in intracellular calcium, oxidative stress, a proinflammatory milieu, lowered levels of “counter-regulatory” neurosteroids (such as allopregnanolone and dehydroepiandrosterone), diminished neurotrophic activity, and accelerated cell aging, manifest as alterations in telomerase activity and as shortening of telomeres, which can lead to apoptosis and cell death. In this model, MDD is characterized by a surfeit of potentially destructive mediators and an insufficiency of protective or restorative ones. These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators. PMID:21485744

  18. Control of mitochondrial integrity in ageing and disease.

    PubMed

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

    2014-07-05

    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.

  19. The 'golden age' of DNA methylation in neurodegenerative diseases.

    PubMed

    Fuso, Andrea

    2013-03-01

    DNA methylation reactions are regulated, in the first instance, by enzymes and the intermediates that constitute the 'so called' one-carbon metabolism. This is a complex biochemical pathway, also known as the homocysteine cycle, regulated by the presence of B vitamins (folate, B6, B12) and choline, among other metabolites. One of the intermediates of this metabolism is S-adenosylmethionine, which represent the methyl donor in all the DNA methyltransferase reactions in eukaryotes. The one-carbon metabolism therefore produces the substrate necessary for the transferring of a methyl group on the cytosine residues of DNA; S-adenosylmethionine also regulates the activity of the enzymes that catalyze this reaction, namely the DNA methyltransferases (DNMTs). Alterations of this metabolic cycle can therefore be responsible for aberrant DNA methylation processes possibly leading to several human diseases. As a matter of fact, increasing evidences indicate that a number of human diseases with multifactorial origin may have an epigenetic basis. This is also due to the great technical advances in the field of epigenetic research. Among the human diseases associated with epigenetic factors, aging-related and neurodegenerative diseases are probably the object of most intense research. This review will present the main evidences linking several human diseases to DNA methylation, with particular focus on neurodegenerative diseases, together with a short description of the state-of-the-art of methylation assays.

  20. 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.

  1. Detection of Severe Respiratory Disease Epidemic Outbreaks by CUSUM-Based Overcrowd-Severe-Respiratory-Disease-Index Model

    PubMed Central

    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. PMID:24069063

  2. 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.

  3. Heritability of Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

    2007-01-01

    Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

  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. 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

  6. The Effect of Age on the Susceptibility and Severity of Demyelination

    DTIC Science & Technology

    2015-10-01

    EAE, aging, neurofascin, transgenics, demyelinating disease, multiple sclerosis . Accomplishments- The accomplishments on this project will be...results will impact our understanding of the consequences of multiple sclerosis in an aging population. In particular we have determined that in the

  7. Correlation between ankle brachial index and coronary artery disease severity in elderly Egyptians.

    PubMed

    Amer, Moatasem S; Tawfik, Heba Mohamed; Elmoteleb, Ayman M Abd; Maamoun, Manar M A

    2014-11-01

    We investigated the association between ankle brachial index (ABI) and coronary heart disease (CHD) severity in elderly Egyptians using different measures. We conducted a case-control study from November 2010 to June 2012 including 200 male and female patients with ischemia≥60 years who were divided into 100 cases and 100 controls according to ABI and redivided according to age. They underwent coronary angiography followed by ABI measurement using a hand-held Doppler. The CHD severity was estimated using the SYNTAX and Jeopardy scores and number of diseased vessels, which increased significantly in patients with peripheral artery disease (P<.001) for all. All 3 measures had strong negative correlation with ABI (P≤.001 for Jeopardy, <.001 for SYNTAX scores, and .004 for number of diseased vessels) and were correlated with each other. We concluded that ABI can reflect CHD severity in elderly Egyptians.

  8. 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

  9. Lycopene Deficiency in Ageing and Cardiovascular Disease.

    PubMed

    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.

  10. Genetic mouse models of brain ageing and Alzheimer's disease.

    PubMed

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed.

  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.

  13. Validation of anti-aging drugs by treating age-related diseases.

    PubMed

    Blagosklonny, Mikhail V

    2009-03-28

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.

  14. 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.

  15. 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

  16. 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

  17. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy

    PubMed Central

    Trollet, Capucine; Stojkovic, Tanya; de Becdelievre, Alix; Perie, Sophie; Pouget, Jean; Eymard, Bruno

    2017-01-01

    Objective: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. The genetic cause is an expanded (GCN)n mutation in the PABPN1 gene encoding for the polyadenylate-binding protein nuclear 1. We hypothesized a potential correlation between the size of the (GCN)n expansion and the severity of the phenotype. To do this, we characterized the distribution of the genotypes as well as their correlation with age at diagnosis and phenotypical features in a large cohort of heterozygous and homozygous patients with OPMD in France with a confirmed molecular diagnosis of PABPN1. Methods: We explored 354 unrelated index cases recruited between 1999 and 2014 in several neuromuscular centers in France. Results: This cohort allowed us to characterize the frequency of mutated alleles in the French population and to demonstrate a statistical correlation between the size of the expansion and the mean age at diagnosis. We also confirmed that homozygous patients present with a more severe disease. Conclusions: It has been difficult to establish phenotype–genotype correlations because of the rare nature of this disease. Our work demonstrates that patients with OPMD with longer PABPN1 expansion are on average diagnosed at an earlier age than patients with a shorter expansion, confirming that polyalanine expansion size plays a role in OPMD, with an effect on disease severity and progression. PMID:28011929

  18. Predictors of disease severity in patients admitted to a cholera treatment center in urban Haiti.

    PubMed

    Valcin, Claude-Lyne; Severe, Karine; Riche, Claudia T; Anglade, Benedict S; Moise, Colette Guiteau; Woodworth, Michael; Charles, Macarthur; Li, Zhongze; Joseph, Patrice; Pape, Jean W; Wright, Peter F

    2013-10-01

    Cholera, previously unrecognized in Haiti, spread through the country in the fall of 2010. An analysis was performed to understand the epidemiological characteristics, clinical management, and risk factors for disease severity in a population seen at the GHESKIO Cholera Treatment Center in Port-au-Prince. A comprehensive review of the medical records of patients admitted during the period of October 28, 2010-July 10, 2011 was conducted. Disease severity on admission was directly correlated with older age, more prolonged length of stay, and presentation during the two epidemic waves seen in the observation period. Although there was a high seroprevalence of human immunodeficiency virus (HIV), severity of cholera was not greater with HIV infection. This study documents the correlation of cholera waves with rainfall and its reduction in settings with improved sanitary conditions and potable water when newly introduced cholera affects all ages equally so that interventions must be directed throughout the population.

  19. 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...

  20. 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.

  1. 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

  2. Screening-detected rheumatic heart disease can progress to severe disease

    PubMed Central

    Wheaton, Gavin R; Mataika, Reapi L; Kado, Joseph H; Colquhoun, Samantha M; Remenyi, Bo; Steer, Andrew C

    2016-01-01

    Objectives Echocardiography is a sensitive test for rheumatic heart disease (RHD) screening; however the natural history of RHD detected on screening has not been established. We aimed to evaluate the progression of screening-detected RHD in Fiji. Methods All young people previously diagnosed with RHD through screening, with echocardiograms available for review, were eligible. All baseline echocardiograms were reported again. Participants underwent follow-up echocardiography. A paediatric cardiologist determined the diagnosis using the World Heart Federation criteria and assessed the severity of regurgitation and stenosis. Results Ninety-eight participants were recruited (mean age, 17 years; median duration of follow-up, 7.5 years). Two other children had died from severe RHD. Fourteen of 20 (70%) definite RHD cases persisted or progressed, including four (20%) requiring valve surgery. Four (20%) definite RHD cases improved to borderline RHD and two (10%) to normal. Four of 17 (24%) borderline cases progressed to definite RHD (moderate: 2; severe: 2) and two (12%) improved to normal. Four of the 55 cases reclassified as normal at baseline progressed to borderline RHD. Cases with a follow-up interval >5 years were more likely to improve (37% vs 6%, p=0.03). Conclusions The natural history of screening-detected RHD is not benign. Most definite RHD cases persist and others may require surgery or succumb. Progression of borderline cases to severe RHD demonstrates the need for monitoring and individualised consideration of prophylaxis. Robust health system structures are needed for follow-up and delivery of secondary prophylaxis if RHD screening is to be scaled up. PMID:27933106

  3. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants

    PubMed Central

    Jong, Victor L.; Ahout, Inge M. L.; van den Ham, Henk-Jan; Jans, Jop; Zaaraoui-Boutahar, Fatiha; Zomer, Aldert; Simonetti, Elles; Bijl, Maarten A.; Brand, H. Kim; van IJcken, Wilfred F. J.; de Jonge, Marien I.; Fraaij, Pieter L.; de Groot, Ronald; Osterhaus, Albert D. M. E.; Eijkemans, Marinus J.; Ferwerda, Gerben; Andeweg, Arno C.

    2016-01-01

    Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challenging at the first visit to the pediatric wards and RSV infections may rapidly progress to severe disease. In this study we investigate whether there exists a genomic signature that can accurately predict the course of RSV. We used early blood microarray transcriptome profiles from 39 hospitalized infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease. This signature yielded an area under the receiver operating characteristic curve (AUC) of 0.966 using leave-one-out cross-validation on the experimental data and an AUC of 0.858 on an independent validation cohort consisting of 53 infants. A combination of the gene signature with age and sex yielded an AUC of 0.971. Thus, the presented signature may serve as the basis to develop a prognostic test to support clinical management of RSV patients. PMID:27833115

  4. The effects of adapted tango on spatial cognition and disease severity in Parkinson's disease.

    PubMed

    McKee, Kathleen E; Hackney, Madeleine E

    2013-01-01

    The authors determined effects of community-based adapted tango on spatial cognition and disease severity in Parkinson's disease (PD) while controlling for the effects of social interaction. Thirty-three individuals with mild-to-moderate PD (stage I-III) were assigned to twenty 90-min tango (n = 24) or education (n = 9) lessons over 12 weeks. Disease severity, spatial cognition, balance, and fall incidence were evaluated pre-, post-, and 10-12 weeks postintervention. The authors evaluated differences using t tests and analyses of variance. Twenty-three tango and 8 education participants finished. Tango participants improved on disease severity (p = .008), and spatial cognition (p = .021) compared with education participants. Tango participants also improved in balance (p = .038), and executive function (p = .012). Gains were maintained 10-12 weeks postintervention. Multimodal exercise with structured syllabi may improve disease severity and spatial cognition in PD.

  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. 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

  7. [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.

  8. 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.

  9. Hematopoietic stem cell transplantation for severe combined immunodeficiency diseases.

    PubMed

    Cowan, Morton J; Neven, Benedicte; Cavazanna-Calvo, M; Fischer, A; Puck, Jennifer

    2008-01-01

    Hematopoietic stem cell transplantation (HSCT) is the only curative option for most children with severe combined immunodeficiency disease (SCID). Survival for SCID following HSCT has significantly improved over the past several decades, and ranges from 70% to 95% depending on the clinical condition of the child at the time of transplant, the availability of an HLA-matched sibling donor, and the SCID genotype/phenotype. In this article we will review the types of SCID and discuss the critical HSCT issues that confront us today, including the optimal source of donor cells when an HLA-matched sibling is not available, as well as the pros and cons of using conditioning therapy pretransplant. As SCID children have been followed for several decades, it is becoming apparent that long-term outcome and durable T and B cell immune reconstitution are quite variable depending on the initial treatment and source of donor cells. Finally, the development of methods to improve the early diagnosis of SCID along with designing prospective trials to evaluate the best approaches to curing these diseases with minimal toxicity are critical to improving outcomes for children with SCID.

  10. 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

  11. Plasma testosterone in male patients with Huntington's disease: relations to severity of illness and dementia.

    PubMed

    Markianos, Manolis; Panas, Marios; Kalfakis, Nikos; Vassilopoulos, Dimitrios

    2005-04-01

    Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive loss among other, of dopaminergic receptors in striatum, cortex, and hypothalamus. Central dopaminergic activity has been implicated in the regulation of sex hormones. Several features of testosterone deficiency, such as reduced muscle mass, depressive mood, and cognitive impairment, are often present in HD patients, but data on their testosterone levels are lacking. We assessed plasma levels of testosterone, LH, and FSH in 42 male patients with HD, confirmed by molecular genetic analysis, and searched for differences from age-matched healthy male subjects and for relations to CAG repeat number, age, age range, 26 to 76 (mean, 50.7 +/- 12.3) years; duration of illness range, 1 to 23 (mean, 6.7 +/- 6.3) years; and CAG repeat numbers from 40 to 65 (45.1 +/- 3.8). Disease symptomatology was assessed using the Unified Huntington's Disease Rating Scale. Testosterone and LH levels of the patients were significantly lower compared to the levels of 44 age-matched (mean age, 48.9 +/- 13.0, range, 26-76 years) healthy men. Severity of illness was negatively related to plasma testosterone levels. Further, low testosterone levels were associated with dementia but not with depression or psychotic features. Clinical studies with selected HD patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well-being, and, eventually, neuroprotective effects.

  12. 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

  13. Abnormalities of proximal femoral growth after severe Perthes' disease.

    PubMed

    Sponseller, P D; Desai, S S; Millis, M B

    1989-08-01

    We studied the pattern of proximal femoral growth after severe Perthes' disease (Catterall grade III or IV) by retrospective analysis of serial radiographs in 52 hips (46 patients). Our aim was to determine the relationship between proximal femoral growth abnormalities and metaphyseal cysts, epiphyseal extrusion, physeal narrowing, and extensive epiphyseal necrosis. The average follow-up after treatment was 9.8 years (range 4 to 16 years), and 37 of the hips were followed to skeletal maturity. Slowing of proximal femoral growth was common: symmetrical abnormality was seen in 26 hips and asymmetrical abnormality in nine. However, definite premature closure of the proximal femoral physis was seen in only three hips. Abnormality seemed to be due to altered growth velocity rather than to bar formation in most cases. Metaphyseal cysts, epiphyseal extrusion and physeal narrowing during the active stage of the disease, alone or in combination, were found to be neither sensitive nor specific predictors of the subsequent growth pattern.

  14. 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

    2015-07-02

    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.

  15. A proposed strategy for international collaborative research in brain aging and Alzheimer's disease.

    PubMed

    Khachaturian, Z S; Radebaugh, T S

    1990-01-01

    A description and discussion are given of several of the programmes initiated by the United States' National Institute on Aging that could be expanded to facilitate multicentre collaboration studies. It includes: the Alzheimer's Disease Research Centers; the Alzheimer's Disease Patient Registry Program; the World Health Organization Special Programme for Research on Aging; and how collaborative links with scientists working on this disease in other countries may be established.

  16. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity.

    PubMed

    Hopp, Katharina; Ward, Christopher J; Hommerding, Cynthia J; Nasr, Samih H; Tuan, Han-Fang; Gainullin, Vladimir G; Rossetti, Sandro; Torres, Vicente E; Harris, Peter C

    2012-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations to PKD1 or PKD2, triggering progressive cystogenesis and typically leading to end-stage renal disease in midlife. The phenotypic spectrum, however, ranges from in utero onset to adequate renal function at old age. Recent patient data suggest that the disease is dosage dependent, where incompletely penetrant alleles influence disease severity. Here, we have developed a knockin mouse model matching a likely disease variant, PKD1 p.R3277C (RC), and have proved that its functionally hypomorphic nature modifies the ADPKD phenotype. While Pkd1+/null mice are normal, Pkd1RC/null mice have rapidly progressive disease, and Pkd1RC/RC animals develop gradual cystogenesis. These models effectively mimic the pathophysiological features of in utero-onset and typical ADPKD, respectively, correlating the level of functional Pkd1 product with disease severity, highlighting the dosage dependence of cystogenesis. Additionally, molecular analyses identified p.R3277C as a temperature-sensitive folding/trafficking mutant, and length defects in collecting duct primary cilia, the organelle central to PKD pathogenesis, were clearly detected for the first time to our knowledge in PKD1. Altogether, this study highlights the role that in trans variants at the disease locus can play in phenotypic modification of dominant diseases and provides a truly orthologous PKD1 model, optimal for therapeutic testing.

  17. 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

  18. Severe hyponatraemia secondary to desmopressin therapy in von Willebrand's disease.

    PubMed

    Bertholini, D M; Butler, C S

    2000-04-01

    A 42-year-old female with von Willebrand's disease was managed with desmopressin and tranexamic acid to aid haemostasis following a vaginal hysterectomy. Severe acute hyponatraemia (134 to 108 mmol/l) developed over two days, culminating in a generalized tonic-clonic seizure and cerebral oedema. Fluid restriction, cessation of desmopressin and hypertonic saline administration led to a full recovery. Desmopressin is known to reduce free water elimination and produce hyponatraemia, but its extent and rate of development in this patient was surprising. Close monitoring of serum sodium and fluid balance is recommended in these patients.

  19. 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

  20. 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

  1. 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

  2. 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

  3. Environmental determinants of severity in sickle cell disease.

    PubMed

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

    2015-09-01

    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.

  4. 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)

  5. 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.

  6. Low serum albumin concentrations are associated with disease severity in patients with myasthenia gravis

    PubMed Central

    Weng, Yi-Yun; Yang, De-Hao; Qian, Mei-Zi; Wei, Mao-Mao; Yin, Fang; Li, Jia; Li, Xiang; Chen, Ying; Ding, Zhang-Na; He, Yi-Bo; Zhang, Xu

    2016-01-01

    Abstract Serum albumin (S-Alb) is a widely used biomarker of nutritional status and disease severity in patients with autoimmune diseases. We investigated the correlation between S-Alb and the severity of myasthenia gravis (MG). A total number of 166 subjects were recruited in the study. Subjects were divided into 3 groups (T1 to T3) by S-Alb levels: T1: 21.1 to 38.4 g/L, T2: 38.5 to 41.5 g/L, T3: 41.6 to 48.9 g/L. Regression analysis was performed to determine the correlation of initial albumin concentrations and the severity of disease of MG. Lower levels of S-Alb were observed in subjects with increased disease severity than those with slight disease severity, meanwhile, incidence of myasthenia crisis increased in the lower albumin tertiles (P < 0.001). The disease severity assessment was performed according to the criteria established by the Myasthenia Gravis Foundation of America. After adjusting for age, sex, body mass index (BMI), and duration of disease, it showed that higher S-Alb concentrations were associated with lower disease severity. Odds ratios (ORs) of T2 to T3 were 0.241 (95% CI: 0.103–0.566, P < 0.001), 0.140 (95% CI: 0.054–0.367, P < 0.001) when compared with subjects in the T1, respectively. When subjects were stratified into hypoalbuminemia and normal albumin groups, we found that the association between S-Alb and MG remained significant in the hypoalbuminemia group only (OR: 0.693, 95% CI: 0.550–0.874, P = 0.002) after further adjustment for age, sex, BMI, and duration of disease. This is the first study to demonstrate that S-Alb was independently associated with MG severity. In patients with low S-Alb, S-Alb concentration could be a potential biomarker for MG disability. PMID:27684858

  7. 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

  8. Severe preeclampsia: anesthetic implications of the disease and its management.

    PubMed

    Turner, Judi A

    2009-01-01

    Preeclampsia is a significant, multifactorial, multiorgan disease affecting 6%-8% of all pregnancies in the United States and is the third leading cause of maternal mortality. As such, it is incumbent upon any anesthesia provider involved in obstetric cases to be familiar with the varied manifestations of the disease, management goals from an obstetric standpoint, and the implications for provision of anesthesia in this patient group. Despite improvements in the diagnosis and management of preeclampsia, severe complications can occur in both the mother and the fetus. A systematic approach to the anesthetic evaluation is therefore necessary to reduce morbidity and mortality and to improve outcomes. The potential pitfalls of general anesthesia, including failed intubation, in these complicated patients make regional anesthesia the preferred choice in many cases. Recent studies have shown that spinal anesthesia is often appropriate for preeclamptic patients, even in severe cases. Nevertheless, it is important to be aware of the potential contraindications to neuraxial anesthesia and to prepare for the possibility of encountering a difficult airway.

  9. 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…

  10. 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

  11. 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

  12. Hyponatraemia: more than just a marker of disease severity?

    PubMed

    Schrier, Robert W; Sharma, Shailendra; Shchekochikhin, Dmitry

    2013-01-01

    Hyponatraemia--the most common serum electrolyte disorder--has also emerged as an important marker of the severity and prognosis of important diseases such as heart failure and cirrhosis. Acute hyponatraemia can cause severe encephalopathy, but the rapid correction of chronic hyponatraemia can also profoundly impair brain function and even cause death. With the expanding elderly population and the increased prevalence of hyponatraemia in this segment of society, prospective studies are needed to examine whether correcting hyponatraemia in the elderly will diminish cognitive impairment, improve balance and reduce the incidence of falls and fractures. Given that polypharmacy is also common in the elderly population, the various medications that may stimulate arginine vasopressin release and/or enhance the hormone's action to increase water absorption must also be taken into consideration. Whether hyponatraemia in a patient with cancer is merely a marker of poor prognosis or whether its presence may alter the patient's quality of life remains to be examined. In any case, hyponatraemia can no longer be considered as just a biochemical bystander in the ill patient. A systematic diagnostic approach is necessary to determine the specific aetiology of a patient's hyponatraemia. Therapy must then be dictated not only by recognized reversible causes such as advanced hypothyroidism, adrenal insufficiency, diuretics or other medicines, but also by whether the hyponatraemia occurred acutely or chronically. Information is emerging that the vast majority of cases of hyponatraemia are caused by the nonosmotic release of arginine vasopressin. Now that vasopressin V2-receptor blockers are available, a new era of clinical investigation is necessary to examine whether hyponatraemia is just a marker of severe disease or whether correction of hyponatraemia could improve a patient's quality of life. Such an approach must involve prospective randomized studies in different groups of

  13. Redefining meaningful age groups in the context of disease.

    PubMed

    Geifman, Nophar; Cohen, Raphael; Rubin, Eitan

    2013-12-01

    Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.

  14. 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.

  15. The important role of lipid peroxidation processes in aging and age dependent diseases.

    PubMed

    Spiteller, Gerhard

    2007-09-01

    Any change in the cell membrane structure activates lipoxygenases (LOX). LOX transform polyunsaturated fatty acids (PUFAs) to lipidhydroperoxide molecules (LOOHs). When cells are severely wounded, this physiological process switches to a non-enzymatic lipid peroxidation (LPO) process producing LOO* radicals. These oxidize nearly all-biological molecules such as lipids, sugars, and proteins. The LOO* induced degradations proceed by transfer of the radicals from cell to cell like an infection. The chemical reactions induced by LO* and LOO* radicals seem to be responsible for aging and induction of age dependent diseases.Alternatively, LO* and LOO* radicals are generated by frying of fats and involve cholesterol-PUFA esters and thus induce atherogenesis. Plants and algae are exposed to LOO* radicals generating radiation. In order to remove LOO* radicals, plants and algae transform PUFAs to furan fatty acids, which are incorporated after consumption of vegetables into mammalian tissues where they act as excellent scavengers of LOO* and LO* radicals.

  16. Local variability in respiratory syncytial virus disease severity

    PubMed Central

    Brandenburg, A.; Jeannet, P.; Steensel-Moll, H.; Ott, A.; Rothbarth, P.; Wunderli, W.; Suter, S.; Neijens, H.; Osterhaus, A.; Siegrist, C.

    1997-01-01

    

 Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children's Hospital (Rotterdam, the Netherlands), but as more benign infections in others such as the Geneva Children's Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994-5) and retrospectively (1993-4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v 23.9%), the rate of admission to the intensive care unit (3.6 v 28.1%), mechanical ventilation (0 v 7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8 v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1 v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.

 PMID:9487963

  17. Severe Kawasaki disease in a 3-month-old patient: a case report

    PubMed Central

    2013-01-01

    Background Kawasaki disease is a multi-system vasculitis which usually occurs in children under 5 years of age. In infants under three months of age, it is very rare and usually associated with a high incidence of incomplete or atypical forms, often unresponsive to treatment. This condition increases the risk of cardiovascular complications such as coronary artery aneurysms. Case presentation We describe a 3-month-old infant who developed early and severe aneurysms in three coronary arteries despite a timely administration of intravenous immunoglobulins, followed by three days of intravenous methylprednisolone. Conclusion This case report underlines that the development of coronary artery aneurysm correlates with a delayed diagnosis and treatment, incomplete or atypical forms of the disease, and additionally the severity of clinical presentation, especially in cases of very young infants below 3 months of age. Our case is notable because of the very young age of the patient, the severity of clinical presentation with an early development of coronary artery aneurysms and the unresponsiveness to the therapy. PMID:24294914

  18. 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…

  19. [Dementia and lifestyle-related diseases in Japanese aging society].

    PubMed

    Iwamoto, Toshihiko

    2011-05-01

    Recently, the number of elderly patients with dementia has been increasing in Japan because of both the extension of average life expectancy and a considerable rise in the incidence of dementia with age. For these reasons, dementia in Japan has become common, and more than half of all cases are Alzheimer disease. This disease has typically been considered to be a degenerative disorder due to genetic abnormalities, but recent epidemiological studies have indicated that lifestyle-related diseases such as hypertension, diabetes, dyslipidemia, and obesity in midlife could accelerate the dementing process, via either vascular changes in cerebral infarction or Alzheimer-related pathological changes with plaque and tangle formations which result in dementia in later life. Furthermore, several studies have suggested that a high intake of vegetables and fish, an active daily life, and lifelong education might positively influence cognitive function as neuroprotective factors. Therefore, we should try to prevent dementia based on the clinical and hygienic management of the lifestyles and lifestyle-related diseases, even in the youth.

  20. 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…

  1. Aging and Alzheimer's Disease: Lessons from the Nun Study.

    ERIC Educational Resources Information Center

    Snowdon, David A.

    1997-01-01

    Describes a woman who maintained high cognitive test scores until her death at 101 years of age despite anatomical evidence of Alzheimer's disease. The woman was part of a larger "Nun Study" in which 678 sisters donated their brains to teach others about the etiology of aging and Alzheimer's disease. Findings are discussed. (RJM)

  2. Age Is a Critical Risk Factor for Severe Fever with Thrombocytopenia Syndrome

    PubMed Central

    Ding, Shujun; Niu, Guoyu; Xu, Xuehua; Li, Jinping; Zhang, Xiaomei; Yin, Haiying; Zhang, Naijie; Jiang, Xiaolin; Wang, Shiwen; Liang, Mifang; Wang, Xianjun; Yu, Xue-jie

    2014-01-01

    Background Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease in East Asia. SFTS is a tick borne hemorrhagic fever caused by SFTSV, a new bunyavirus named after the syndrome. We investigated the epidemiology of SFTS in Laizhou County, Shandong Province, China. Methods We collected serum specimens of all patients who were clinically diagnosed as suspected SFTS cases in 2010 and 2011 in Laizhou County. The patients' serum specimens were tested for SFTSV by real time fluorescence quantitative PCR (RT-qPCR). We collected 1,060 serum specimens from healthy human volunteers by random sampling in Laizhou County in 2011. Healthy persons' serum specimens were tested for specific SFTSV IgG antibody by ELISA. Results 71 SFTS cases were diagnosed in Laizhou County in 2010 and 2011, which resulted in the incidence rate of 4.1/100,000 annually. The patients ranged from 15 years old to 87 years old and the median age of the patients were 59 years old. The incidence rate of SFTS was significantly higher in patients over 40 years old and fatal cases only occurred in patients over 50 years old. 3.3% (35/1,060) of healthy people were positive to SFTSV IgG antibody. The SFTSV antibody positive rate was not significantly different among people at different age groups. Conclusion Our results revealed that seroprevalence of SFTSV in healthy people in Laizhou County was not significantly different among age groups, but SFTS patients were mainly elderly people, suggesting that age is the critical risk factor or determinant for SFTS morbidity and mortality. PMID:25369237

  3. Dietary Approaches that Delay Age-Related Diseases

    PubMed Central

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood

  4. 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…

  5. 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

  6. Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 1: locomotor and exploratory behaviour.

    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

    Age-related cognitive dysfunction syndrome (CDS) has been reported in dogs and it is considered a natural model for Alzheimer's disease in humans. Changes in spontaneous activity (including locomotor and exploratory behaviour) and social responsiveness have been related to the age and cognitive status of kennel-reared Beagle dogs. The aim of this study was to assess the influence of age and severity of CDS on locomotor and exploratory behaviour of privately owned dogs. This is the first part of a two-part report on spontaneous activity in pet dogs. An open-field (OF) test and a curiosity test were administered at baseline and 6 months later to young (1-4 years, n=9), middle-aged (5-8 years, n=9), cognitively unimpaired aged (≥ 9 years, n=31), and cognitively impaired aged ( ≥ 9 years, n=36) animals. Classification of cognitive status was carried out using an owner-based observational questionnaire, and in the cognitively impaired group, the dogs were categorised as having either mild or severe cognitive impairment. Dogs were recorded during sessions in the testing room and the video-recordings were subsequently analysed. The severity of CDS (but not age) influenced locomotion and exploratory behaviour so that the more severe the impairment, the higher the locomotor activity and frequency of corner-directed (aimless) behaviours, and the lower the frequency of door-aimed activities. Curiosity directed toward novel stimuli exhibited an age-dependent decline although severely affected animals displayed more sniffing episodes directed towards the objects. OF activity did not change after 6 months. Testing aged pet dogs for spontaneous behaviour might help to better characterise cognitively affected individuals.

  7. Genetic Influences on Cystic Fibrosis Lung Disease Severity

    PubMed Central

    Weiler, Colleen A.; Drumm, Mitchell L.

    2013-01-01

    Understanding the causes of variation in clinical manifestations of disease should allow for design of new or improved therapeutic strategies to treat the disease. If variation is caused by genetic differences between individuals, identifying the genes involved should present therapeutic targets, either in the proteins encoded by those genes or the pathways in which they function. The technology to identify and genotype the millions of variants present in the human genome has evolved rapidly over the past two decades. Originally only a small number of polymorphisms in a small number of subjects could be studied realistically, but speed and scope have increased nearly as dramatically as cost has decreased, making it feasible to determine genotypes of hundreds of thousands of polymorphisms in thousands of subjects. The use of such genetic technology has been applied to cystic fibrosis (CF) to identify genetic variation that alters the outcome of this single gene disorder. Candidate gene strategies to identify these variants, referred to as “modifier genes,” has yielded several genes that act in pathways known to be important in CF and for these the clinical implications are relatively clear. More recently, whole-genome surveys that probe hundreds of thousands of variants have been carried out and have identified genes and chromosomal regions for which a role in CF is not at all clear. Identification of these genes is exciting, as it provides the possibility for new areas of therapeutic development. PMID:23630497

  8. 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

  9. Ageing and the border between health and disease.

    PubMed

    MacNee, William; Rabinovich, Roberto A; Choudhury, Gourab

    2014-11-01

    Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Since the proportion of the world's population aged >60 years will double in the next four decades, this will be accompanied by an increased incidence of chronic age-related diseases that will place a huge burden on healthcare resources. There is increasing evidence that many chronic inflammatory diseases represent an acceleration of the ageing process. Chronic pulmonary diseases represents an important component of the increasingly prevalent multiple chronic debilitating diseases, which are a major cause of morbidity and mortality, particularly in the elderly. The lungs age and it has been suggested that chronic obstructive pulmonary disease (COPD) is a condition of accelerated lung ageing and that ageing may provide a mechanistic link between COPD and many of its extrapulmonary effects and comorbidities. In this article we will describe the physiological changes and mechanisms of ageing, with particular focus on the pulmonary effects of ageing and how these may be relevant to the development of COPD and its major extrapulmonary manifestations.

  10. 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.

  11. Taste Bud Homeostasis in Health, Disease, and Aging

    PubMed Central

    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

  12. Autonomic nervous system dysfunction and their relationship with disease severity in children with atopic asthma.

    PubMed

    Emin, Ozkaya; Esra, Gursoy; Aysegül, Demir; Ufuk, Erenberk; Ayhan, Sogut; Rusen, Dundaroz M

    2012-09-30

    The involvement of autonomic imbalance has been reported in the pathogenesis of allergic diseases. The aim of this study was to investigate the association between the clinical severity of childhood asthma with autonomic nervous system (ANS) dysfunction and to define whether the severity of asthma correlates with ANS activity. In this case-control study, we evaluated the ANS activity by testing heart rate variability (HRV) and sympathetic skin response (SRR) in 77 asthmatic children, age 7-12 yrs, who had no co-morbidity and compared them with 40 gender- and age-matched control subjects. According to the severity of their asthma, study subjects were further divided into three groups: I (mild asthmatics), II (moderate asthmatics), and III (severe asthmatics). Inter-group ANS scale scores differed significantly (p<0.01) between Groups I and III and between Groups II and III. Combined use of HRV and SSR provides a higher degree of sensitivity for assessing disease severity in cases of pediatric asthma.

  13. The Relationship Between Nonsuicidal Self-Injury Age of Onset and Severity of Self-Harm.

    PubMed

    Ammerman, Brooke A; Jacobucci, Ross; Kleiman, Evan M; Uyeji, Lauren L; McCloskey, Michael S

    2017-02-03

    This study examined how age of nonsuicidal self-injury (NSSI) onset relates to NSSI severity and suicidality using decision tree analyses (nonparametric regression models that recursively partition predictor variables to create groupings). Those with an earlier age of NSSI onset reported greater NSSI frequency, NSSI methods, and NSSI-related hospital visits. No significant splits were found for suicide ideation or attempts, although those with an earlier onset were more likely to have a suicide plan. Overall, findings suggest that onset of NSSI before age 12 is associated with more severe NSSI and may be a crucial age for prevention efforts.

  14. Association between thyroid autoimmunity and fibromyalgic disease severity.

    PubMed

    Bazzichi, Laura; Rossi, Alessandra; Giuliano, Tiziana; De Feo, Francesca; Giacomelli, Camillo; Consensi, Arianna; Ciapparelli, Antonio; Consoli, Giorgio; Dell'osso, Liliana; Bombardieri, Stefano

    2007-12-01

    Our objectives were to investigate thyroid abnormalities and autoimmunity in 120 patients affected by fibromyalgia (FM) and to study their relationships with clinical data and symptoms. Thyroid assessment by means of antithyroglobulin antibodies, antithyroid peroxidase antibodies, free triiodo-thyronine, free thyroxine, and thyroid stimulating hormone analyses was carried out. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, fatigue, and other symptoms, and the presence of depression or anxiety disorders were evaluated. The basal thyroid hormone levels of FM patients were in the normal range, while 41% of the patients had at least one thyroid antibody. Patients with thyroid autoimmunity showed a higher percentage of dry eyes, burning, or pain with urination, allodynia, blurred vision, and sore throat. Correlations found between thyroid autoimmunity and age or with the presence of depression or anxiety disorders were not significant. However, in the cohort of post-menopausal patients, the frequency of thyroid autoimmunity was higher with respect to pre-menopausal patients. In conclusion, autoimmune thyroiditis is present in an elevated percentage of FM patients, and it has been associated with the presence of typical symptoms of the disease.

  15. The application of information theory for the research of aging and aging-related diseases.

    PubMed

    Blokh, David; Stambler, Ilia

    2016-03-19

    This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information-theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease.

  16. Astroglia dynamics in ageing and Alzheimer's disease.

    PubMed

    Verkhratsky, Alexei; Zorec, Robert; Rodríguez, Jose J; Parpura, Vladimir

    2016-02-01

    Ageing of the brain is the major risk factor for neurodegenerative disorders that result in cognitive decline and senile dementia. Ageing astrocytes undergo complex and region specific remodelling which can reflect life-long adaptive plasticity. In neurodegeneration, astroglial cells are similarly a subject for morpho-functional changes hampering the homoeostasis, defence and regeneration of the central nervous system. Region-specific astroglial atrophy with the loss of function and astroglial reactivity have been reported in virtually all forms of neurodegenerative pathologies. Modulating these astroglia changes may represent a fertile ground for novel therapeutic intervention strategies to prevent, delay progression and/or ameliorate pathology. While at present this bodacious goal represents a wishful thinking, further understanding of astroglial role in ageing and neurodegeneration could bring us closer to laying the foundations for such cell-specific therapeutic approaches.

  17. White matter microstructure among youth with perinatally acquired HIV is associated with disease severity

    PubMed Central

    Uban, Kristina A.; Herting, Megan M.; Williams, Paige L.; Ajmera, Tanvi; Gautam, Prapti; Yanling, Huo; Malee, Kathleen M.; Yogev, Ram; Csernansky, John G.; Wang, Lei; Nichols, Sharon L.; Sowell, Elizabeth R.

    2015-01-01

    Objectives We investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally-acquired HIV (PHIV). Design PHIV youth (n=40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16±2 yrs) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter (WM) microstructure within PHIV youth. PHIV youth were compared to 314 controls from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Methods Diffusion tensor imaging and tractography were utilized to assess WM microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth. Results Whole brain fractional anisotropy (FA) was reduced, but radial (RD) and mean (MD) diffusivity were increased, in PHIV compared to control youth. Within PHIV youth, more severe past HIV disease was associated with reduced FA of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated MD of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO FA levels. Conclusion Our findings suggest that PHIV youth have higher risk of alterations in WM microstructure compared to typically developing youth, and certain alterations are related to past disease severity. Further, WM alterations potentially mediate associations between HIV disease and working memory. PMID:26125138

  18. 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

  19. SLC44A2 single nucleotide polymorphisms, isoforms, and expression: Association with severity of Meniere's disease?

    PubMed

    Nair, Thankam S; Kommareddi, Pavan K; Galano, Maria M; Miller, Danielle M; Kakaraparthi, Bala Naveen; Telian, Steven A; Arts, H Alex; El-Kashlan, Hussam; Kilijanczyk, Alyse; Lassig, Amy Anne D; Graham, Martin P; Fisher, Susan G; Stoll, Stefan W; Nair, Rajan P; Elder, James T; Carey, Thomas E

    2016-12-01

    SLC44A2 was discovered as the target of an antibody that causes hearing loss. Knockout mice develop age related hearing loss, loss of sensory cells and spiral ganglion neurons. SLC44A2 has polymorphic sites implicated in human disease. Transfusion related acute lung injury (TRALI) is linked to rs2288904 and genome wide association studies link rs2288904 and rs9797861 to venous thromboembolism (VTE), coronary artery disease and stroke. Here we report linkage disequilibrium of rs2288904 with rs3087969 and the association of these SLC44A2 SNPs with Meniere's disease severity. Tissue-specific isoform expression differences suggest that the N-terminal domain is linked to different functions in different cell types. Heterozygosity at rs2288904 CGA/CAA and rs3087969 GAT/GAC showed a trend for association with intractable Meniere's disease compared to less severe disease and to controls. The association of SLC44A2 SNPs with VTE suggests that thrombi affecting cochlear vessels could be a factor in Meniere's disease.

  20. Respiratory rehabilitation in severe restrictive lung disease secondary to tuberculosis.

    PubMed

    Yang, G F; Alba, A; Lee, M

    1984-09-01

    There is a need for portable and less expensive devices for patients with chronic respiratory insufficiency. The case of a 44-year-old Hispanic woman is illustrative. The patient had severe restrictive lung disease secondary to right phrenic nerve crush/pneumoperitoneum and left pneumonectomy/decortication for bilateral lower lobe tuberculosis. In 1969, 12 years after her last operation, she developed dyspnea, coryza, and somnolence. She was hospitalized with a PaO2 of 30mmHg; PaCO2 of 77mmHg and a pH of 7.28. Pulmonary function tests showed alveolar hypoventilation and her resting ventilation was between 2.26 to 3.74L/min. Her vital capacity was 1130cc (37% of predicted value) and maximum breathing capacity was 36L/min (44% of predicted value). From 1969, she used a poncho (wraparound) ventilator for her long-term respiratory care and modified the poncho suit to meet her personal needs. In 1971, she discovered that a mouth intermittent positive pressure ventilation (MIPPV) method, often used by patients with neuromuscular disorders, was easier to apply. Since then, she has continued to use a Bantam Respirator with MIPPV and a lipguard/mouthpiece during the night, and the respirator with a mouthpiece for a few hours during the days. However, when she has an upper respiratory infection or feels tired, she finds that she needs the greater rest and comfort that the poncho provides. With the assistance of these two respiratory devices, she has been able to complete her education, marry, and lead a fulfilling life in the community. This patient is considered the first person with severe lung pathology to utilize MIPPV for sleep.

  1. Human Immunodeficiency Virus Disease Severity, Psychiatric Symptoms, and Functional Outcomes in Perinatally Infected Youth

    PubMed Central

    Nachman, Sharon; Chernoff, Miriam; Williams, Paige; Hodge, Janice; Heston, Jerry; Gadow, Kenneth D.

    2012-01-01

    Objective To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. Design Cross-sectional analysis of entry data from an observational, prospective 2-year study. Logistic and linear regression models adjusted for potential confounders were used. Setting Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. Participants Youth aged 6 to 17 years who had HIV infection (N=319). Main Exposures Antiretroviral treatment and perinatal HIV infection. Main Outcome Measures Youth and primary care-givers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social, and academic functioning; and quality of life. Results Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms, older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms, higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage at study entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms. A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. Conclusion Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic, and social

  2. 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

  3. 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.

  4. 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.

  5. Revisiting Unplanned Endotracheal Extubation and Disease Severity in Intensive Care Units.

    PubMed

    Chuang, Ming-Lung; Lee, Chai-Yuan; Chen, Yi-Fang; Huang, Shih-Feng; Lin, I-Feng

    2015-01-01

    Most reports regarding unplanned extubation (UE) are case-control studies with matching age and disease severity. To avoid diminishing differences in matched factors, this study with only matching duration of mechanical ventilation aimed to re-examine the risk factors and the factors governing outcomes of UE in intensive care units (ICUs). This case-control study was conducted on 1,775 subjects intubated for mechanical ventilation. Thirty-seven (2.1%) subjects with UE were identified, and 156 non-UE subjects were randomly selected as the control group. Demographic data, acute Physiological and Chronic Health Evaluation II (APACHE II) scores, and outcomes of UE were compared between the two groups. Logistic regression analysis was used to identify the risk factors of UE. Milder disease, younger age, and higher Glasgow Coma Scale (GCS) scores with more frequently being physically restrained (all p<0.05) were related to UE. Logistic regression revealed that APACHE II score (odds ratio (OR) 0.91, p<0.01), respiratory infection (OR 0.24, p<0.01), physical restraint (OR 5.36, p<0.001), and certain specific diseases (OR 3.79-5.62, p<0.05) were related to UE. The UE patients had a lower ICU mortality rate (p<0.01) and a trend of lower in-hospital mortality rate (p = 0.08). Cox regression analysis revealed that in-hospital mortality was associated with APACHE II score, age, shock, and oxygen used, all of which were co-linear, but not UE. The results showed that milder disease with higher GCS scores thereby requiring a higher use of physical restraints were related to UE. Disease severity but not UE was associated with in-hospital mortality.

  6. Geriatric surgery is about disease, not age

    PubMed Central

    Preston, Stephen D; Southall, Ashley RD; Nel, Mark; Das, Saroj K

    2008-01-01

    Summary Maintaining life span and quality of life remains a valid aim of surgery in elderly people. Surgery can be an effective way of restoring both length and quality of life to older people. Minimally invasive techniques and surgery under local anaesthesia make fewer demands on geriatric physiology; given that co-morbidity is a stronger predictor of outcome from surgery than age, this is a significant consideration. PMID:18687864

  7. Comorbidity Cohort (2C) study: Cardiovascular disease severity and comorbid osteoarthritis in primary care

    PubMed Central

    2012-01-01

    Background Two of the commonest chronic diseases experienced by older people in the general population are cardiovascular diseases and osteoarthritis. These conditions also commonly co-occur, which is only partly explained by age. Yet, there have been few studies investigating specific a priori hypotheses in testing the comorbid interaction between two chronic diseases and related health and healthcare outcomes. It is also unknown whether the stage or severity of the chronic disease influences the comorbidity impact. The overall plan is to investigate the interaction between cardiovascular severity groups (hypertension, ischaemic heart disease and heart failure) and osteoarthritis comorbidity, and their longitudinal impact on health and healthcare outcomes relative to either condition alone. Methods From ten general practices participating in a research network, adults aged 40 years and over were sampled to construct eight exclusive cohort groups (n = 9,676). Baseline groups were defined on the basis of computer clinical diagnostic data in a 3-year time-period (between 2006 and 2009) as: (i) without cardiovascular disease or osteoarthritis (reference group), (ii) index cardiovascular disease groups (hypertension, ischaemic heart disease and heart failure) without osteoarthritis, (iii) index osteoarthritis group without cardiovascular disease, and (vi) index cardiovascular disease groups comorbid with osteoarthritis. There were three main phases to longitudinal follow-up. The first (survey population) was to invite cohorts to complete a baseline postal health questionnaire, with 10 monthly brief interval health questionnaires, and a final 12-month follow-up questionnaire. The second phase (linkage population) was to link the collected survey data to patient clinical records with consent for the 3-year time-period before baseline, during the 12-month survey period and the 12 months after final questionnaire (total 5 years). The third phase (denominator

  8. Hispanic Americans and African Americans with multiple sclerosis have more severe disease course than Caucasian Americans.

    PubMed

    Ventura, Rachel E; Antezana, Ariel O; Bacon, Tamar; Kister, Ilya

    2016-11-01

    Whether disease course in Hispanic Americans (HA) with multiple sclerosis (MS) is different from Caucasian Americans (CA) or African Americans (AA) is unknown. We compared MS severity in the three main ethnic populations in our tertiary MS clinics using disease duration-adjusted rank score of disability: Patient-Derived Multiple Sclerosis Severity Score (P-MSSS). The age- and gender-adjusted P-MSSS was significantly higher in HA (3.9 ± 2.6) and AA (4.5 ± 3.0) compared to CA (3.4 ± 2.6; p < 0.0001 for both). Adjusting for insurance did not change these results. These findings suggest that HA, as AA, have more rapid disability accumulation than CA.

  9. 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.…

  10. Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease.

    PubMed

    Brewer, George J

    2007-02-01

    In this review, we point out that natural selection does not act to lessen human diseases after the reproductive and caregiving period and that normal levels of iron and copper that may be healthy during the reproductive years appear to be contributing to diseases of aging and possibly the aging process itself. It is clear that oxidant damage contributes to many of the diseases of aging, such as atherosclerosis, Alzheimer's disease, Parkinson's diseases, diabetes, diseases of inflammation, diseases of fibrosis, diseases of autoimmunity, and so on. It is equally clear that both iron and copper can contribute to excess production of damaging reactive oxygen species through Fenton chemistry. Here, we examine the evidence that "normal" levels of iron and copper contribute to various diseases of aging.

  11. 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

  12. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

    PubMed Central

    Amin, Kawa; Rasool, Aram H; Hattem, Ali; Al-Karboly, Taha AM; Taher, Taher E; Bystrom, Jonas

    2017-01-01

    AIM To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease. METHODS Levels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other. PMID:28293081

  13. The impact of dementia severity on caregiver burden in frontotemporal dementia and Alzheimer disease.

    PubMed

    Mioshi, Eneida; Foxe, David; Leslie, Felicity; Savage, Sharon; Hsieh, Sharpley; Miller, Laurie; Hodges, John R; Piguet, Olivier

    2013-01-01

    Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD- behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA)-or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD.

  14. Brain amyloid-β oligomers in ageing and Alzheimer's disease.

    PubMed

    Lesné, Sylvain E; Sherman, Mathew A; Grant, Marianne; Kuskowski, Michael; Schneider, Julie A; Bennett, David A; Ashe, Karen H

    2013-05-01

    Alzheimer's disease begins about two decades before the onset of symptoms or neuron death, and is believed to be caused by pathogenic amyloid-β aggregates that initiate a cascade of molecular events culminating in widespread neurodegeneration. The microtubule binding protein tau may mediate the effects of amyloid-β in this cascade. Amyloid plaques comprised of insoluble, fibrillar amyloid-β aggregates are the most characteristic feature of Alzheimer's disease. However, the correspondence between the distribution of plaques and the pattern of neurodegeneration is tenuous. This discrepancy has stimulated the investigation of other amyloid-β aggregates, including soluble amyloid-β oligomers. Different soluble amyloid-β oligomers have been studied in several mouse models, but not systematically in humans. Here, we measured three amyloid-β oligomers previously described in mouse models-amyloid-β trimers, Aβ*56 and amyloid-β dimers-in brain tissue from 75 cognitively intact individuals, ranging from young children to the elderly, and 58 impaired subjects with mild cognitive impairment or probable Alzheimer's disease. As in mouse models, where amyloid-β trimers appear to be the fundamental amyloid-β assembly unit of Aβ*56 and are present in young mice prior to memory decline, amyloid-β trimers in humans were present in children and adolescents; their levels rose gradually with age and were significantly above baseline in subjects in their 70s. Aβ*56 levels were negligible in children and young adults, rose significantly above baseline in subjects in their 40s and increased steadily thereafter. Amyloid-β dimers were undetectable until subjects were in their 60s; their levels then increased sharply and correlated with plaque load. Remarkably, in cognitively intact individuals we found strong positive correlations between Aβ*56 and two pathological forms of soluble tau (tau-CP13 and tau-Alz50), and negative correlations between Aβ*56 and two postsynaptic

  15. The impact of illness in patients with moderate to severe gastro-esophageal reflux disease

    PubMed Central

    El-Dika, Samer; Guyatt, Gordon H; Armstrong, David; Degl'innocenti, Alessio; Wiklund, Ingela; Fallone, Carlo A; Tanser, Lisa; van Zanten, Sander Veldhuyzen; Heels-Ansdell, Diane; Wahlqvist, Peter; Chiba, Naoki; Barkun, Alan N; Austin, Peggy; Schünemann, Holger J

    2005-01-01

    Background Gastro-esophageal reflux disease (GERD) is a common disease. It impairs health related quality of life (HRQL). However, the impact on utility scores and work productivity in patients with moderate to severe GERD is not well known. Methods We analyzed data from 217 patients with moderate to severe GERD (mean age 50, SD 13.7) across 17 Canadian centers. Patients completed three utility instruments – the standard gamble (SG), the feeling thermometer (FT), and the Health Utilities Index 3 (HUI 3) – and several HRQL instruments, including Quality of Life in Reflux and Dyspepsia (QOLRAD) and the Medical Outcomes Short Form-36 (SF-36). All patients received a proton pump inhibitor, esomeprazole 40 mg daily, for four to six weeks. Results The mean scores on a scale from 0 (dead) to 1 (full health) obtained for the FT, SG, and HUI 3 were 0.67 (95% CI, 0.64 to 0.70), 0.76 (95% CI, 0.75 to 0.80), and 0.80 (95% CI, 0.77 to 0.82) respectively. The mean scores on the SF-36 were lower than the previously reported Canadian and US general population mean scores and work productivity was impaired. Conclusion GERD has significant impact on utility scores, HRQL, and work productivity in patients with moderate to severe disease. Furthermore, the FT and HUI 3 provide more valid measurements of HRQL in GERD than the SG. After treatment with esomeprazole, patients showed improved HRQL. PMID:16004616

  16. Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

    PubMed Central

    Perez, Geovanny F.; Jain, Amisha; Kurdi, Bassem; Megalaa, Rosemary; Pancham, Krishna; Huseni, Shehlanoor; Isaza, Natalia; Rodriguez-Martinez, Carlos E.; Rose, Mary C.; Pillai, Dinesh; Nino, Gustavo

    2016-01-01

    Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32–37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life. PMID:27775602

  17. Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity.

    PubMed

    Perez, Geovanny F; Jain, Amisha; Kurdi, Bassem; Megalaa, Rosemary; Pancham, Krishna; Huseni, Shehlanoor; Isaza, Natalia; Rodriguez-Martinez, Carlos E; Rose, Mary C; Pillai, Dinesh; Nino, Gustavo

    2016-10-20

    Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32-37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

  18. Aging and age-related diseases--from endocrine therapy to target therapy.

    PubMed

    Bao, Qi; Pan, Jie; Qi, Hangfei; Wang, Lu; Qian, Huan; Jiang, Fangzhen; Shao, Zheren; Xu, Fengzhi; Tao, Zhiping; Ma, Qi; Nelson, Peter; Hu, Xueqing

    2014-08-25

    Aging represents an important health issue not only for the individual, but also for society in general. Burdens associated with aging are expanding as longevity increases. This has led to an enhanced focus on issues related to aging and age-related diseases. Until recently, anti-aging endocrine-therapy has been largely limited to hormone-replacement therapy (HRT) that is associated with multiple side effects, including an increased risk of cancer. This has greatly limited the application of HRT in anti-aging therapy. Recently, the focus of anti-aging research has expanded from endocrine signaling pathways to effects on regulatory gene networks. In this regard, the GHRH-GH-IGF-1/Insulin, TOR-S6K1,NAD(+)-Sirtuin, P53, Klotho and APOE pathways have been linked to processes associated with age-related diseases, including cancer, cardiovascular disease, diabetes, osteoporosis, and neurodegenerative diseases, all of which directly influence health in aging, and represent key targets in anti-aging therapy.

  19. Predictors of progression to severe Alzheimer’s disease in an incidence sample

    PubMed Central

    Rabins, Peter V.; Schwartz, Sarah; Black, Betty S.; Corcoran, Christopher; Fauth, Elizabeth; Mielke, Michele; Christensen, Jessica; Lyketsos, Constantine; Tschanz, JoAnn

    2013-01-01

    Background Little is known about factors influencing time to severe Alzheimer’s disease (AD). Methods Incident cases of AD in the Cache County Memory Study were identified. Severe AD was defined as Mini-Mental State Examination score of ≤10 or Clinical Dementia Rating Scale score of 3; cases with either Mini-Mental State Examination score of ≥16 or Clinical Dementia Rating <2 were not categorized as severe AD. Kaplan–Meier, log-rank tests, and Cox analyses were used to identify demographic, clinical, and genetic correlates of time to progression to severe AD. Results Sixty-eight of 335 cases of incident AD developed severe dementia. In bivariate analyses, female gender, less than high school education, at least one clinically significant Neuropsychiatric Inventory domain at baseline, and the youngest and oldest ages exhibited shorter time to severe AD. In competing risk analysis, subjects with mild or at least one clinically significant Neuropsychiatric Inventory domain score, and subjects with worse health were more likely to progress to severe dementia or death. Conclusions Demographic and clinical variables predict progression to severe AD. Further study should examine whether these relationships are causal or correlational. PMID:23123228

  20. Complex two-gene modulation of lung disease severity in children with cystic fibrosis

    PubMed Central

    Dorfman, Ruslan; Sandford, Andrew; Taylor, Chelsea; Huang, Baisong; Frangolias, Daisy; Wang, Yongqian; Sang, Richard; Pereira, Lilian; Sun, Lei; Berthiaume, Yves; Tsui, Lap-Chee; Paré, Peter D.; Durie, Peter; Corey, Mary; Zielenski, Julian

    2008-01-01

    Although cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-β1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function. PMID:18292811

  1. Saccadic Eye Movement Characteristics in Adult Niemann-Pick Type C Disease: Relationships with Disease Severity and Brain Structural Measures

    PubMed Central

    Abel, Larry A.; Bowman, Elizabeth A.; Velakoulis, Dennis; Fahey, Michael C.; Desmond, Patricia; Macfarlane, Matthew D.; Looi, Jeffrey Chee Leong; Adamson, Christopher L.; Walterfang, Mark

    2012-01-01

    Niemann-Pick Type C disease (NPC) is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters. We compared horizontal saccadic velocity, latency, gain, antisaccade error percentage and self-paced saccade generation in 9 adult NPC patients to data from 10 age-matched controls. These saccadic measures were correlated with appropriate MRI-derived brain structural measures (e.g., dorsolateral prefrontal cortex, frontal eye fields, supplemental eye fields, parietal eye fields, pons, midbrain and cerebellar vermis) and with measures of disease severity and duration. The best discriminators between groups were reflexive saccade gain and the two volitional saccade measures. Gain was also the strongest correlate with disease severity and duration. Most of the saccadic measures showed strongly significant correlations with neurophysiologically appropriate brain regions. While our patient sample is small, the apparent specificity of these relationships suggests that as new diagnostic methods and treatments become available for NPC, a broader range of saccadic measures may be useful tools for the assessment of disease progression and treatment efficacy. PMID:23226429

  2. Health- and Disease-Related Biomarkers in Aging Research

    PubMed Central

    Thompson, Hilaire J.; Voss, Joachim G.

    2011-01-01

    This article focuses on a synthesis of knowledge about healthy aging research in human beings and then synthesized nurse-led research in gerontology and geriatrics that use biomarkers. Healthy aging research has attracted considerable attention in the biomedical and basic sciences within the context of four major areas: (a) genetic variations as an expression of successful or unsuccessful aging; (b) caloric restriction as an intervention to slow the progression of aging; (c) immunological aging; (d) neurobiology of the aging brain. A systematic review of the literature was performed to identify nurse-led geriatric-related biomarker research. Nurse researchers who have chosen to integrate biomarkers as part of their research studies have been working in six focal areas, which are reviewed: health promotion within risk populations, cancer, vascular disease, Alzheimer’s disease, caregiving, and complementary therapies. The article provides a discussion of contributions to date, identifying existing gaps and future research opportunities. PMID:20077975

  3. 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.

  4. Aging Is Not a Disease: Implications for Intervention

    PubMed Central

    Rattan, Suresh I. S.

    2014-01-01

    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. PMID:24900942

  5. 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...

  6. Sympathetic regulation during thermal stress in human aging and disease

    PubMed Central

    Greaney, Jody L.; Kenney, W. Larry; Alexander, Lacy M.

    2015-01-01

    Humans control their core temperature within a narrow range via precise adjustments of the autonomic nervous system. In response to changing core and/or skin temperature, several critical thermoregulatory reflex effector responses are initiated and include shivering, sweating, and changes in cutaneous blood flow. Cutaneous vasomotor adjustments, mediated by modulations in sympathetic nerve activity (SNA), aid in the maintenance of thermal homeostasis during cold and heat stress since (1) they serve as the first line of defense of body temperature and are initiated before other thermoregulatory effectors, and (2) they are on the efferent arm of non-thermoregulatory reflex systems, aiding in the maintenance of blood pressure and organ perfusion. This review article highlights the sympathetic responses of humans to thermal stress, with a specific focus on primary aging as well as impairments that occur in both heart disease and type 2 diabetes mellitus. Age- and pathology-related changes in efferent muscle and skin SNA during cold and heat stress, measured directly in humans using microneurography, are discussed. PMID:26627337

  7. Age as a Moderator of Change Following Compensatory Cognitive Training in Individuals With Severe Mental Illnesses.

    PubMed

    Thomas, Kelsey R; Puig, Olga; Twamley, Elizabeth W

    2016-08-22

    Objective: This study explored whether age moderated cognitive, symptom, and functional changes over a 12-week compensatory cognitive training (CCT) intervention for participants with severe mental illnesses. CCT focused on the cognitive domains of attention, learning, prospective memory, and executive functioning, often impaired in this population. Method: Seventy-seven unemployed individuals (46 participants with severe mood disorders and 31 participants with schizophrenia/schizoaffective disorder; mean age = 44 years) received CCT for 12 weeks in the context of a supported employment program. Participants were administered cognitive, symptom severity, and functional measures at baseline and 3-, 6-, and 12-month follow-ups, as well as at 18 and 24 months for symptom/functional measures. Mixed effects models, controlling for diagnosis, examined whether age impacted the trajectories of change following CCT. Results: Analyses showed several significant time by age interactions; younger participants improved more over time on category fluency, β = -.280, t(42.10) = -2.76, p = .008, and financial capacity (UCSD Performance-Based Skills Assessment), β = -.194, t(54.02) = -2.21, p = .031, whereas older participants showed greater reduction in positive symptom severity (Positive and Negative Syndrome Scale), β = -.109, t(78.35) = -2.34, p = .022, and less functional decline on the Independent Living Skills Survey, β = .118, t(109.77) = 2.05, p = .043. Conclusions and Implications for Practice: Age moderated the effects of CCT over time on measures of cognition, symptom severity, and functioning. Younger participants improved on objective measures of verbal processing speed and financial capacity, whereas older participants showed reduced positive symptom severity and less decline in self-reported daily functioning. These findings suggest that CCT may differentially benefit persons with severe mental illnesses depending on age. (PsycINFO Database Record

  8. Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

    PubMed Central

    Moe, Nina; Krokstad, Sidsel; Stenseng, Inger Heimdal; Christensen, Andreas; Skanke, Lars Høsøien; Risnes, Kari Ravndal; Nordbø, Svein Arne; Døllner, Henrik

    2017-01-01

    Background It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). Methods We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. Results A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. Conclusions Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children. PMID:28095451

  9. Increased brain-predicted aging in treated HIV disease

    PubMed Central

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  10. Production of Complex Syntax in Normal Aging and Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Bates, Elizabeth; And Others

    1995-01-01

    This study compared the production of complex syntax by 16 older adults diagnosed with probable Alzheimer's disease and 25 age-matched control subjects. It found that although individuals diagnosed with Alzheimer's disease did not produce frank lexical or grammatical errors, they did find it difficult to access the "best fit" between meaning and…

  11. 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

  12. 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.

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

    DOE PAGES

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; ...

    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

  14. 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

  15. Exacerbation-related impairment of quality of life and work productivity in severe and very severe chronic obstructive pulmonary disease

    PubMed Central

    Solem, Caitlyn T; Sun, Shawn X; Sudharshan, Lavanya; Macahilig, Cynthia; Katyal, Monica; Gao, Xin

    2013-01-01

    Purpose Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined. This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype. Patients and methods A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited. Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire – Specific Health Problem [WPAI-SHP]). The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions. Results A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included. In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations. Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%). Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006). The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001). Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001). One additional

  16. 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.

  17. Disseminated Bacillus Calmette Guerin Disease in a Twin Infant with Severe Combined Immunodeficiency Disease

    PubMed Central

    Mittal, Hema; Faridi, MMA; Kumar, Pankaj; Aggarwal, Anju

    2014-01-01

    Fatal-disseminated Bacillus Calmette Guerin (BCG) disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR) and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature. PMID:25191057

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Review: quantifying mitochondrial dysfunction in complex diseases of aging.

    PubMed

    Horan, Martin P; Pichaud, Nicolas; Ballard, J William O

    2012-10-01

    There is accumulating evidence that mitochondrial respiratory malfunction is associated with aging-associated complex diseases. However, progress in our understanding of these diseases has been hampered by the sensitivity and throughput of systems employed to quantify dysfunction and inherent limitations of the biological systems studied. In this review, we describe and contrast two methodologies that have been developed for measuring mitochondrial function to address the need for improved sensitivity and increased throughput. We then consider the utility of each methodology in studying three biological systems: isolated mitochondria, cultured cells, and cell fibers and tissues. Finally, we discuss the application of each methodology in the study of mitochondrial dysfunction in Alzheimer's disease, type 2 diabetes mellitus, and aging-associated autophagy impairment and mitochondrial malfunction. We conclude that the methodologies are complementary, and researchers may need to examine multiple biological systems to unravel complex diseases of aging.

  3. AGER -429T/C Is Associated with an Increased Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet; Abely, M.; Belleguic, C.; Bellon, G.; Bessaci, K.; Bonnel, A.S.; Brémont, F.; Brouard, J.; Bui, S.; Chiron, R.; Chumbi-Flores, R.; Clement, A.; Corvol, H.; Dalphin, J.C.; Dalphin, M.L.; David, V.; de Miranda, S.; Derelle, J.; Domblides, P.; Dominique, S.; Dubus, J.C.; Durieu, I.; Dury, S.; Ellaffi, M.; Epaud, R.; Fanton, A.; Fayon, M.; Fleurence, E.; Foucaud, P.; Ginies, J.L.; Godbert, B.; Grenet, D.; Guillot, M.; Héraud, M. C.; Housset, B.; Hubert, D.; Huet, F.; Kessler, R.; Labbé, A.; Laurans, M.; le Bourgeois, M.; le Roux, P.; Llerena, C.; Loeuille, G.A.; Marguet, C.; Mely, L.; Moisan-Petit, V.; Munck, A.; Murris-Espin, M.; Nove Josserand, R.; Pautard, J.C.; Pin, I.; Pramil, S.; Prevotat, A.; Rault, G.; Reix, P.; Remus, N.; Renouil, M.; Reynaud-Gaubert, M.; Richaud Thiriez, B.; Roussey, M.; Sermet-Gaudelus, I.; Stremler, N.; Uffredi, M.L.; Urban, T.; Vigneron, P.; Wallaert, B.; Weiss, L.

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease. PMID:22860029

  4. AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.

    PubMed

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.

  5. [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.

  6. Memantine effects on behaviour in moderately severe to severe Alzheimer's disease: a post-marketing surveillance study.

    PubMed

    Clerici, Francesca; Vanacore, Nicola; Elia, Antonietta; Spila-Alegiani, Stefania; Pomati, Simone; Da Cas, Roberto; Raschetti, Roberto; Mariani, Claudio

    2012-02-01

    The aim of this study is to evaluate memantine effectiveness on behavioural and psychological symptoms of dementia (BPSD) in clinical practice and to identify variables that may predict the therapy effects. The effects of memantine on behaviour were analysed in the database of a post-marketing surveillance study promoted by the Lombardy Region Health Office and involving 43 Alzheimer's disease (AD) Units. From July to December 2005, 399 moderately severe-to-severe AD patients free of cholinergic medications were enrolled, treated with memantine and followed-up for 6 months. BPSD were assessed in a subgroup of 297 patients [mean age 77 ± 8 years; 73% females; mean neuropsychiatric inventory (NPI) score 28 ± 24] for whom the 12-item NPI subscores at baseline, and at 3 and 6 months were available. The 12 BPSD were clustered as follows: affect, physical behaviour, psychosis and hypomania. The main outcome measure was the proportion of individual cluster responders at 6 months of therapy. The proportion of individual cluster responders was 30% affect, 24% physical behaviour, 29% psychosis, 27% hypomania. Patients taking 20 mg memantine daily during the study period had a statistically significant higher probability to experience behavioural improvement than those who discontinued treatment or did not complete memantine titration (affect OR 9.0; 95% CI 3.8-21.6; physical behaviour OR 17.8; 95% CI 5.9-53.6; psychosis OR 23.6; 95% CI 5.1-110.8). The logistic regression analysis was not applicable to the hypomania subsyndrome because of the low cluster prevalence. The standard 20 mg daily memantine treatment regimen was found to be associated with a modest 6-month behavioural improvement in the affect, physical behaviour and psychosis domains in 24-30% of patients.

  7. 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

  8. The effects of road-surface conditions, age, and gender on driver-injury severities.

    PubMed

    Morgan, Abigail; Mannering, Fred L

    2011-09-01

    Drivers' adaptation to weather-induced changes in roadway-surface conditions is a complex process that can potentially be influenced by many factors including age and gender. Using a mixed logit analysis, this research assesses the effects that age, gender, and other factors have on crash severities by considering single-vehicle crashes that occurred on dry, wet, and snow/ice-covered roadway surfaces. With an extensive database of single-vehicle crashes from Indiana in 2007 and 2008, estimation results showed that there were substantial differences across age/gender groups under different roadway-surface conditions. For example, for all females and older males, the likelihood of severe injuries increased when crashes occurred on wet or snow/ice surfaces-but for male drivers under 45 years of age, the probability of severe injuries decreased on wet and snow/ice surfaces - relative to dry-surface crashes. This and many other significant differences among age and gender groups suggest that drivers perceive and react to pavement-surface conditions in very different ways, and this has important safety implications. Furthermore, the empirical findings of this study highlight the value of considering subsets of data to unravel the complex relationships within crash-injury severity analysis.

  9. Unpicking the Semantic Impairment in Alzheimer’s Disease: Qualitative Changes with Disease Severity

    PubMed Central

    Corbett, Faye; Jefferies, Elizabeth; Burns, Alistair; Ralph, Matthew A. Lambon

    2012-01-01

    Despite a vast literature examining semantic impairment in Alzheimer's disease (AD), consensus regarding the nature of the deficit remains elusive. We re-considered this issue in the context of a framework that assumes semantic cognition can break down in two ways: (1) core semantic representations can degrade or (2) cognitive control mechanisms can become impaired [1]. We hypothesised and confirmed that the nature of semantic impairment in AD changes with disease severity. Patients at mild or severe stages of the disorder exhibited impairment across various semantic tasks but the nature of those deficits differed qualitatively for the two groups. Commensurate with early dysfunction of the cognitive control, temporoparietal-frontal-cingulate network, characteristics of deregulated semantic cognition were exhibited by the mild AD cases. In contrast, the severe AD group reproduced features of additional degradation of core semantic representations. These results suggest that spread of pathology into lateral anterior temporal lobes in later stage AD produces degradation of semantic representations, exacerbating the already deregulated system. Moreover, the dual nature of severe patients’ impairment was highlighted by disproportionately poor performance on tasks placing high demand on both conceptual knowledge and control processes–e.g., category fluency. PMID:22207420

  10. Unpicking the semantic impairment in Alzheimer's disease: qualitative changes with disease severity.

    PubMed

    Corbett, Faye; Jefferies, Elizabeth; Burns, Alistair; Ralph, Matthew A Lambon

    2012-01-01

    Despite a vast literature examining semantic impairment in Alzheimer's disease (AD), consensus regarding the nature of the deficit remains elusive. We re-considered this issue in the context of a framework that assumes semantic cognition can break down in two ways: (1) core semantic representations can degrade or (2) cognitive control mechanisms can become impaired. We hypothesised and confirmed that the nature of semantic impairment in AD changes with disease severity. Patients at mild or severe stages of the disorder exhibited impairment across various semantic tasks but the nature of those deficits differed qualitatively for the two groups. Commensurate with early dysfunction of the cognitive control, temporoparietal-frontal-cingulate network, characteristics of deregulated semantic cognition were exhibited by the mild AD cases. In contrast, the severe AD group reproduced features of additional degradation of core semantic representations. These results suggest that spread of pathology into lateral anterior temporal lobes in later stage AD produces degradation of semantic representations, exacerbating the already deregulated system. Moreover, the dual nature of severe patients' impairment was highlighted by disproportionately poor performance on tasks placing high demand on both conceptual knowledge and control processes--e.g., category fluency.

  11. Trends in age-adjusted coronary heart disease mortality rates in Slovakia between 1993 and 2009.

    PubMed

    Psota, Marek; Pekarciková, Jarmila; O'Mullane, Monica; Rusnák, Martin

    2013-06-01

    Cardiovascular diseases (CVD) and especially coronary heart disease (CHD) are the main causes of death in the Slovak Republic (SR). The aim of this study is to explore trends in age-adjusted coronary heart disease mortality rates in the whole Slovak population and in the population of working age between the years 1993 and 2009. A related indicator - potential years of life lost (PYLL) due to CHD--was calculated in the same period for males and females. Crude CHD mortality rates were age-adjusted using European standard population. The joinpoint Poisson regression was performed in order to find out the annual percentage change in trends. The age-adjusted CHD mortality rates decreased in the Slovak population and also in the population of working age. The change was significant only within the working-age sub-group. We found that partial diagnoses (myocardial infarction and chronic ischaemic heart disease) developed in the mirror-like manner. PYLL per 100,000 decreased during the observed period and the decline was more prominent in males. For further research we recommend to focus on several other issues, namely, to examine the validity of cause of death codes, to examine the development of mortality rates in selected age groups, to find out the cause of differential development of mortality rates in the Slovak Republic in comparison with the Czech Republic and Poland, and to explain the causes of decrease of the age-adjusted CHD mortality rates in younger age groups in Slovakia.

  12. Impact of the severity of chronic periodontal disease on quality of life.

    PubMed

    Meusel, Dayse R D Z; Ramacciato, Juliana C; Motta, Rogério H L; Brito Júnior, Rui B; Flório, Flávia M

    2015-06-01

    We examined the impact of the severity of periodontal disease on quality of life in adults with chronic periodontitis. One hundred patients (age, 30-58 years) who were assisted at the Basic Health Care Unit in the city of Passo Fundo, RS, Brazil underwent clinical examination of all standing teeth, including gingival bleeding on probing, probing depth, and clinical attachment level, and were divided into those with mild/moderate (n = 49; group G1) and severe (n = 51; group G2) chronic periodontitis. The participants were then interviewed, using a structured questionnaire. The Brazilian Oral Health Impact Profile (OHIP-14Br) questionnaire was used to assess oral health-related quality of life. Associations were investigated, and those with a P value of less than 0.2 were tested using multiple logistic regression models. Those with a P value of 0.05 or less were considered significant. There was a significant association between G2 and education level (P = 0.00051). OHIP-14Br score was higher for G2 (24.1) than for G1 (18.2) (P = 0.0455). Severe chronic periodontitis was associated with low education level (≤8 years) (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.2-7.3) and pronunciation difficulties (OR, 3.1; 95% CI, 1.0-9.3). In conclusion, periodontal disease severity was inversely associated with quality of life among Brazilian adults.

  13. Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease.

    PubMed

    Nicholls, David G

    2002-11-01

    Mitochondria plays a complex multi-factorial role in the cell. In addition to their primary role in ATP generation, the organelles sequester calcium and both generate and detoxify reactive oxygen species. All these functions are intimately inter-linked through the central bioenergetic parameter of the proton electrochemical gradient across the inner mitochondrial membrane. Subtle changes in respiratory chain capacity, substrate supply, glutathione levels, cytoplasmic calcium and membrane potential occur in aging and in conditions predisposing towards neurodegenerative disease. These interactions are incompletely understood and in this review I present an overview of some of the current research in this area, and its possible relevance to aging and aging-related disease.

  14. Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

    PubMed Central

    Potts, James A.; Gibbons, Robert V.; Rothman, Alan L.; Srikiatkhachorn, Anon; Thomas, Stephen J.; Supradish, Pra-on; Lemon, Stephenie C.; Libraty, Daniel H.; Green, Sharone; Kalayanarooj, Siripen

    2010-01-01

    Background Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. Methods and Findings We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different categories of dengue disease severity to distinguish between patients at elevated risk of developing a severe dengue illness and those at low risk. A diagnostic algorithm using WBC count, percent monocytes, platelet count, and hematocrit achieved 97% sensitivity to identify patients who went on to develop DSS while correctly excluding 48% of non-severe cases. Addition of an indicator of severe plasma leakage to the WHO definition led to 99% sensitivity using WBC count, percent neutrophils, AST, platelet count, and age. Conclusions This study identified two easily applicable diagnostic algorithms using early clinical indicators obtained within the first 72 hours of illness onset. The algorithms have high sensitivity to distinguish patients at elevated risk of developing severe dengue illness from patients at low risk, which included patients with mild dengue and other non-dengue febrile illnesses. Although these algorithms need to be validated in other populations, this study highlights the potential usefulness of specific clinical indicators early in illness. PMID:20689812

  15. Neuroimaging of Cerebrovascular Disease in the Aging Brain

    PubMed Central

    Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

    2012-01-01

    Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

  16. 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.

  17. 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.

  18. Severe sickle cell disease--pathophysiology and therapy.

    PubMed

    Buchanan, George; Vichinsky, Elliott; Krishnamurti, Lakshmanan; Shenoy, Shalini

    2010-01-01

    Over 70,000 people live with sickle cell disease (SCD) in the United States and multitudes worldwide. About 2000 afflicted babies are born in this country each year. In African countries such as Nigeria, over 100,000 babies are born with the disease each year. Great strides have been made in the conservative management of SCD. However, the medical and psychosocial cost of supporting patients with this chronic illness is enormous and spans a lifetime. Hematopoietic stem cell transplantation (HSCT) can abrogate SCD manifestations, and is the best option for cure today. Yet, this treatment modality is underutilized as less than 500 transplants are reported in the Center for International Blood and Marrow Transplant Research (CIBMTR) database because of its significant risk of morbidity and mortality. There is growing understanding of the pathophysiology of the disease, and this, coupled with advances in transplantation and new approaches to therapy, continue to improve care of patients with SCD both in children and during adulthood. Continuing investigation seeks to predict the course of the disease and to determine timing and modality of therapy in order to optimize outcomes.

  19. Atypical pestivirus and severe respiratory disease in calves, Europe.

    PubMed

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

    2011-08-01

    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.

  20. 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.

  1. 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

  2. Oxidative stress and epigenetic regulation in ageing and age-related diseases.

    PubMed

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

    2013-08-28

    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.

  3. Hydrogen Sulfide, the Next Potent Preventive and Therapeutic Agent in Aging and Age-Associated Diseases

    PubMed Central

    Zhang, Yuan; Tang, Zhi-Han; Ren, Zhong; Qu, Shun-Lin; Liu, Mi-Hua; Liu, Lu-Shan

    2013-01-01

    Hydrogen sulfide (H2S) is the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide. It is physiologically generated by cystathionine-γ-lyase, cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase. H2S has been gaining increasing attention as an important endogenous signaling molecule because of its significant effects on the cardiovascular and nervous systems. Substantial evidence shows that H2S is involved in aging by inhibiting free-radical reactions, activating SIRT1, and probably interacting with the age-related gene Klotho. Moreover, H2S has been shown to have therapeutic potential in age-associated diseases. This article provides an overview of the physiological functions and effects of H2S in aging and age-associated diseases, and proposes the potential health and therapeutic benefits of H2S. PMID:23297346

  4. Continuity and Change in Cognition and Autism Severity from Toddlerhood to School Age

    ERIC Educational Resources Information Center

    Clark, Megan L. E.; Barbaro, Josephine; Dissanayake, Cheryl

    2017-01-01

    This paper charted the cognitive and behavioural profiles from toddlerhood to middle childhood in 48 children diagnosed with ASD at 24 months. The Mullen Scales of Early Learning (MSEL) was administered at 24- and 48-months and the Wechsler Abbreviated Scale of Intelligence (WASI) at school age. Autism severity was derived using The Autism…

  5. 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

  6. Maternal behavioural risk factors for severe childhood diarrhoeal disease in Kinshasa, Zaire.

    PubMed

    Dikassa, L; Mock, N; Magnani, R; Rice, J; Abdoh, A; Mercer, D; Bertrand, W

    1993-04-01

    This study examines the relationship between severe diarrhoeal disease and maternal knowledge and behaviours related to hygiene and sanitation. Some 107 paediatric cases admitted to two hospitals in Kinshasa, Zaire in 1988 were matched on age and nearest-neighbour status to 107 controls. Personal interviews and observational methods were used to assess knowledge and behaviours related to hygiene and sanitation. Cases and controls had equivalent socioeconomic status, demographic profiles and access to water and sanitation facilities. However, cases generally exhibited lower levels of knowledge and less sanguine sanitary practices than did controls. Of particular interest was the finding that very specific behavioural items distinguished cases from controls. The disposal of the child faeces and household garbage and mother's knowledge that poor caretaker cleanliness was a cause of diarrhoea in children showed the strongest associations with risk of diarrhoea. There was an exponential relationship between the number of these items a mother answered incorrectly and the odds of diarrhoeal disease. The risk attributable to these three variables was as high as 70%. These findings provide further support for the view that focused educational interventions may have a substantial impact on the occurrence of severe diarrhoeal disease in low-income countries.

  7. The ABC’s of Trait Anger, Psychological Distress, and Disease Severity in HIV

    PubMed Central

    McIntosh, Roger C.; Hurwitz, Barry E.; Antoni, Michael; Gonzalez, Alex; Seay, Julia; Schneiderman, Neil

    2015-01-01

    Background Trait anger consists of affective, behavioral, and cognitive (ABC) dimensions and may increase vulnerability for interpersonal conflict, diminished social support, and greater psychological distress. The concurrent influence anger and psychosocial dysfunction on HIV disease severity is unknown. Purpose Examine plausible psychosocial avenues (e.g. coping, social support, psychological distress) whereby trait anger may indirectly influence HIV disease status. Methods 377 HIV seropositive adults, aged 18–55 years (58% AIDS-defined) completed a battery of psychosocial surveys and provided a fasting blood sample for HIV-1 viral load and T-lymphocyte count assay. Results A second-order factor model confirmed higher levels of the multidimensional anger trait was directly associated with elevated psychological distress and avoidant coping (p<.001) and indirectly associated with greater HIV disease severity (p<.01) (CFI=.90, RMSEA=.06, SRMR=.06). Conclusion The model supports ABC components of anger may negatively influence immune function through various psychosocial mechanisms; however longitudinal study is needed to elucidate these effects. PMID:25385204

  8. Nitroxide pharmaceutical development for age-related degeneration and disease

    PubMed Central

    Zarling, Jacob A.; Brunt, Vienna E.; Vallerga, Anne K.; Li, Weixing; Tao, Albert; Zarling, David A.; Minson, Christopher T.

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed. PMID:26594225

  9. Nitroxide pharmaceutical development for age-related degeneration and disease.

    PubMed

    Zarling, Jacob A; Brunt, Vienna E; Vallerga, Anne K; Li, Weixing; Tao, Albert; Zarling, David A; Minson, Christopher T

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed.

  10. 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.

  11. Free triiodothyronine in relation to coronary severity at different ages: Gensini score assessment in 4206 euthyroid patients

    PubMed Central

    Zhou, Bing-Yang; Guo, Yuan-Lin; Wu, Na-Qiong; Zhu, Cheng-Gang; Gao, Ying; Qing, Ping; Li, Xiao-Lin; Wang, Yao; Liu, Geng; Dong, Qian; Li, Jian-Jun

    2016-01-01

    Objective To study whether free triiodothyronine (FT3) within normal range has effects on the presence and severity of coronary artery disease (CAD) in different gender and age groups. Methods A total of 4206 euthyroid patients were consecutively enrolled and divided into CAD group (n = 3306) and non-CAD group (n = 900). All patients underwent coronary angiography (CAG). Gensini score (GS) was used to determine the severity of coronary artery stenosis. Severe CAD was defined as GS > 32 and mild CAD was defined as GS ≤ 32. Logistic regression analysis and linear regression analysis were conducted to determine the association of FT3 with CAD in patients with different gender and ages. Results Concentration of FT3 was lower in patients with CAD than that in angiography-normal control group (P < 0.05). In addition, concentration of FT3 was lower in severe CAD than that in mild CAD. After adjusting for traditional cardiovascular risk factors and potential confounders, FT3 was negatively correlated with the presence of CAD, but not in the old patients (> 65 years old). Multivariable linear regression analysis showed that FT3 was negatively associated with GS in male and young patients with stable CAD, but not in the old patients. Conclusions Low FT3 within normal range was negatively associated with the presence and severity of CAD in young patients, but not in the old ones. Further studies are needed to confirm our findings. PMID:28321241

  12. Surgical treatment of patients with kidney and bladder cancer in case of severe concomitant cardiovascular diseases.

    PubMed

    Davydov, M I; Akchurin, R S; Gerasimov, S S; Belov, Yu V; Matveev, V B; Brand, Ya B; Cheban, O I

    2014-01-01

    It was operated 17 patients with kidney and bladder cancer against the background of severe concomitant coronary artery disease (52.9%), aortic aneurysm (35.3%) or combination of coronary artery disease with Leriche syndrome (5.9%) or hemodynamically significant stenosis of internal carotid artery (5.9%). Patients were operated for the period from 1998 to 2012. All patients were male at the age from 39 to 80 years (mean 62.1 years). The first stage of kidney cancer was diagnosed in 8 (53.3%) patients, the second stage - in 1 (6.7%) patient, the third stage - in 2 (13.3%) patients and the fourth stage was observed in 4 (26.7%) patients. Bladder cancer had 1 and 2 stages. Simultaneous operations were performed in 3 (17.6%) patients. 12 (70.6%) patients were operated consequentially. Surgery for kidney cancer was not done in 2 (11.8%) of 17 patients because of patient death after coronary bypass surgery or patient refusal of surgery after carotid arteries stenting. Intraoperative and postoperative complications have been developed in 9 (52.9%) of 17 patients. 2 (11.8%) patients died. The complications frequency and mortality after simultaneous operations were 25% (1 of 4) and 0. These parameters were 57.1% (8 of 14) and 14.3% respectively in case of consequent tactics. It was not observed myocardial infarction and aortic aneurysm rupture after surgeries for kidney and bladder cancer. Overall 1, 3, 5 - year survival of patients with kidney cancer and severe concomitant cardiovascular diseases was 100%, 73.3% and 52.4% respectively. It was concluded that surgical treatment of severe concomitant coronary artery disease and aortic aneurysm in patients with kidney and bladder cancer decreases risk of myocardial infarction and aortic aneurysm rupture in intraoperative and postoperative periods.

  13. 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.

  14. Arterial–Ventricular Coupling with Aging and Disease

    PubMed Central

    Chantler, Paul D.; Lakatta, Edward G.

    2012-01-01

    Age is the dominant risk factor for cardiovascular diseases. Understanding the coupling between the left ventricle (LV) and arterial system, termed arterial–ventricular coupling (EA/ELV), provides important mechanistic insights into the complex cardiovascular system and its changes with aging in the absence and presence of disease. EA/ELV can be indexed by the ratio of effective arterial elastance (EA; a measure of the net arterial load exerted on the LV) to left ventricular end-systolic elastance (ELV; a load-independent measure of left ventricular chamber performance). Age-associated alterations in arterial structure and function, including diameter, wall thickness, wall stiffness, and endothelial dysfunction, contribute to a gradual increase in resting EA with age. Remarkably there is a corresponding increase in resting ELV with age, due to alterations to LV remodeling (loss in myocyte number, increased collagen) and function. These age-adaptations at rest likely occur, at least, in response to the age-associated increase in EA and ensure that EA/ELV is closely maintained within a narrow range, allowing for optimal energetic efficiency at the expense of mechanical efficacy. This optimal coupling at rest is also maintained when aging is accompanied by the presence of hypertension, and obesity, despite further increases in EA and ELV in these conditions. In contrast, in heart failure patients with either reduced or preserved ejection fraction, EA/ELV at rest is impaired. During dynamic exercise, EA/ELV decreases, due to an acute mismatch between the arterial and ventricular systems as ELV increases disproportionate compared to EA (≈200 vs. 40%), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. However, with advancing age the reduction in EA/ELV during acute maximal exercise is blunted, due to a blunted increase ELV. This impaired EA/ELV is further amplified in the presence of disease, and may

  15. Relationship between age of recognition of first disturbances and severity in young children with autism.

    PubMed

    Baghdadli, Amaria; Picot, Marie C; Pascal, Céline; Pry, René; Aussilloux, Charles

    2003-06-01

    Autism is now thought to be present right from birth. Although usually not officially diagnosed until after the child's second birthday, parents often report disturbances before then. The age of detection of disturbances varies and may be linked to differences in the severity of the autism and its associated retardation. This study evaluates the developmental characteristics of 193 children with pervasive developmental disorder, using the same standard procedures for all subjects. Our goal was to determine the relationship between age of parental recognition of disturbances and disorder severity. The results indicated mainly a link between early abnormalities, associated medical condition and severity measured on cognitive tests. They suggest systematic screening for signs of autism in very young children.

  16. Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease

    PubMed Central

    Kikah, Ngum; Ekokobe, Fonkem; Atem, Folefac D.

    2016-01-01

    Objective The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. Methods We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn’t experience onset of CVD) and Cox proportional regression analysis, with offspring’s age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. Results Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. Conclusions Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of

  17. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed

    Baird, J K; Basri, H; Weina, P; MaGuire, J D; Barcus, M J; Picarema, H; Elyazar, I R F; Ayomi, E; Sekartuti

    2003-08-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection.

  18. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed Central

    Baird, J. K.; Basri, H.; Weina, P.; MaGuire, J. D.; Barcus, M. J.; Picarema, H.; Elyazar, I. R. F.; Ayomi, E.; Sekartuti

    2003-01-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection. PMID:12948380

  19. Mortality, morbidity, and disease severity of patients with aspiration pneumonia

    PubMed Central

    Lanspa, Michael J.; Jones, Barbara E.; Brown, Samuel M.; Dean, Nathan C.

    2013-01-01

    Background Aspiration pneumonia is a common syndrome, although less well characterized than other pneumonia syndromes. We describe a large population of patients with aspiration pneumonia. Methods In this retrospective population study, we queried the electronic medical record at a tertiary-care, university-affiliated hospital from 1996–2006. Patients were initially identified by ICD-9 code 507.x; subsequent physician chart review excluded patients with aspiration pneumonitis and those without a confirmatory radiograph. Patients with community-acquired aspiration pneumonia were compared to a contemporaneous population of community-acquired pneumonia (CAP) patients. We compared CURB-65 predicted mortality with actual 30-day mortality. Results We identified 628 patients with aspiration pneumonia, of which 510 were community-acquired. Median age was 77, with 30-day mortality of 21%. Compared to CAP patients, patients with community-acquired aspiration pneumonia had more frequent inpatient admission (99% vs. 58%) and ICU admission (38% vs. 14%), higher Charlson comorbidity index (3 vs. 1), and higher prevalence of “do not resuscitate/intubate” orders (24% vs. 11%). CURB-65 predicted mortality poorly in aspiration pneumonia patients (AUC 0.66). Conclusions Patients with community-acquired aspiration pneumonia are older, have more comorbidities, and demonstrate higher mortality than CAP patients, even after adjustment for age and comorbidities. CURB-65 poorly predicts mortality in this population. PMID:23184866

  20. Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide

    PubMed Central

    Fitzpatrick, Anne M.; Gaston, Benjamin M.; Erzurum, Serpil C.; Teague, W. Gerald

    2010-01-01

    Background Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined. Objective To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation. Methods A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (FENO). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria. Results Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of FENO and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEV1 and increase in FENO persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%). Conclusion Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and FENO. Clinical implications Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high FENO. PMID:17157650

  1. 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

  2. Epigenetic Determinants of Healthy and Diseased Brain Aging and Cognition

    PubMed Central

    S., Akbarian; S., Beeri M.; V., Haroutunian

    2014-01-01

    A better understanding of normal and diseased brain aging and cognition will have a significant public health impact, given that the oldest-old persons over 85 years of age represent the fastest growing segment in the population in developed countries, with over 30 million new cases of dementia predicted to occur world-wide each year by 2040. Dysregulation of gene expression, and more generally, genome organization and function, is thought to contribute to age-related declines in cognition. Remarkably, nearly all neuronal nuclei that reside in an aged brain had permanently exited from the cell cycle during prenatal development, and DNA methylation and histone modifications and other molecular constituents of the epigenome are likely to play a critical role in the maintenance of neuronal health and function throughout the entire lifespan. Here, we provide an overview on age-related changes in the brain’s chromatin structures, highlight potential epigenetic drug targets for cognitive decline and age-related neurodegenerative disease and discuss opportunities and challenges when studying ‘epigenetic biomarkers’ in aging research. PMID:23571692

  3. 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

  4. 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.

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

    PubMed Central

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

    2016-01-01

    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 have profound social and economic costs. Population aging also reveals an opportunity; that is, 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 healthy lifespan, or healthspan. 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 the 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

  6. 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.

  7. 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

  8. The Relationship Between Age of Gambling Onset and Adolescent Problematic Gambling Severity

    PubMed Central

    Rahman, Ardeshir S.; Pilver, Corey E.; Desai, Rani A.; Steinberg, Marvin A.; Rugle, Loreen; Krishnan-Sarin, Suchitra; Potenza, Marc N.

    2012-01-01

    The aim of this study was to characterize the association between problem gambling severity and multiple health, functioning and gambling variables in adolescents aged 13–18 stratified by age of gambling onset. Survey data in 1624 Connecticut high school students stratified by age of gambling onset (≤11 years vs. ≥ 12 years) were analyzed in descriptive analyses and in logistic regression models. Earlier age of onset was associated with problem gambling severity as indexed by a higher frequency of at-risk/problem gambling (ARPG). Most health, functioning and gambling measures were similarly associated with problem gambling severity in the earlier- and later-age-of-gambling-onset groups with the exception of participation in non-strategic forms of gambling, which was more strongly associated with ARPG in the earlier-onset (OR=1.74, 95%CI=[1.26, 2.39]) as compared to later-onset (OR=0.94, 95%CI=[0.60, 1.48]) group (Interaction OR=1.91, 95%CI=[1.18, 3.26]). Post-hoc analysis revealed that earlier-onset ARPG was more strongly associated with multiple forms of non-strategic gambling including lottery (instant, traditional) and slot-machine gambling. The finding that problem gambling severity is more closely associated with multiple non-strategic forms of gambling amongst youth with earlier onset of gambling highlights the relevance of these types of youth gambling. The extent to which non-strategic forms of gambling may serve as a gateway to other forms of gambling or risk behaviors warrants additional study, and efforts targeting youth gambling should consider how best to address non-strategic gambling through education, prevention, treatment and policy efforts. PMID:22410208

  9. Small molecule SIRT1 activators for the treatment of aging and age-related diseases

    PubMed Central

    Hubbard, Basil P.; Sinclair, David A.

    2014-01-01

    Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, significantly extending healthy years of life. In this review we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD+-dependent deacylases that are central to the body’s response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that the two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs. PMID:24439680

  10. Dependence as a unifying construct in defining Alzheimer's disease severity.

    PubMed

    McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J Michael; Sullivan, Sean D; Spackman, D Eldon; Neumann, Peter J; Cohen, Joshua; Stern, Yaakov

    2010-11-01

    This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression.

  11. 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

  12. 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…

  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.

  14. Radiographic evaluation of destructive periodontal disease in blue mink in relation to age and blood morphology

    PubMed Central

    2005-01-01

    Abstract In this study, blood samples and jaws were collected from 2 genotypes of blue mink (n = 289) in order to examine phenotypic expression of specific characteristics of Chediak-Higashi Syndrome (C-HS). Blood samples were subjected to differential counts to assess the proportion of abnormal polymorphonuclear leukocytes characteristic for CH-S (C-HS-leukocytes). Abnormal leukocytes with characteristic signs of C-HS were found in blood smears from all mink included in this study. Four teeth in one half of the mandible (P3, P4, M1, M2) were subjected to quantitative radiographic evaluation of alveolar bone loss and tooth loss. There was a high prevalence of destructive periodontal disease among blue mink included in this study. Mild to moderate periodontal disease (defined by less than 50% alveolar bone loss related to 1 or more teeth) affected 73.7% of young mink (age = 7 mo) and 67.9% of older animals (age ≥ 19 mo). Severe periodontal disease (defined by more than 50% bone loss related to one or more teeth) was not detected in mink aged 7 mo, but affected 15.3% of mink aged 19 mo and 39.6% of mink aged 31 mo. The positive relationship between age and periodontal disease was statistically significant (P < 0.01). The prevalence of tooth loss was found to be high among blue mink aged >19 mo (21.6%) and was also significantly related to age (P < 0.01). A significant positive interaction between alveolar bone loss and tooth loss (P < 0.01), implies that the highly prevalent tooth loss in the mink was related to and possibly caused by destructive periodontal disease. There was no significant difference in the prevalence of periodontal disease between the 2 genotypes and age was found to be the only statistical predictor of poor production results (P < 0.01) in blue mink. PMID:15971677

  15. The role of macroautophagy in the ageing process, anti-ageing intervention and age-associated diseases.

    PubMed

    Bergamini, E; Cavallini, G; Donati, A; Gori, Z

    2004-12-01

    Macroautophagy is a degradation/recycling system ubiquitous in eukariotic cells, which generates nutrients during fasting under the control of amino acids and hormones, and contributes to the turnover and rejuvenation of cellular components (long-lived proteins, cytomembranes and organelles). Tight coupling between these two functions may be the weak point in cell housekeeping. Ageing denotes a post-maturational deterioration of tissues and organs with the passage of time, due to the progressive accumulation of the misfunctioning cell components because of oxidative damage and an age-dependent decline of turnover rate and housekeeping. Caloric restriction (CR) and lower insulin levels may slow down many age-dependent processes and extend lifespan. Recent evidence is reviewed showing that autophagy is involved in ageing and in the anti-ageing action of anti-ageing calorie restriction: function of autophagy declines during adulthood and is almost negligible at older age; CR prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation; protection of autophagic proteolysis from the age-related decline co-varies with the duration and level of anti-ageing food restriction like the effects of CR extending lifespan; the pharmacological stimulation of macroautophagy has anti-ageing effects. Besides the involvement in ageing, macroautophagy may have an essential role in the pathogenesis of many age-associated diseases. Higher protein turnover may not fully account for the anti-ageing effects of macroautophagy, and effects of macroautophagy on housekeeping of the cell organelles, antioxidant machinery of cell membranes and transmembrane cell signaling should also be considered.

  16. [Antidepressive pharmacotherapy. In slight and severe disease, young and old].

    PubMed

    Baghai, T C; Volz, H P; Möller, H J

    2009-02-01

    During the past decade a variety of promising new compounds launched onto the market not only enhancing serotonergic and noradrenergic neurotransmission, but also influencing the dopamine and the melatonergic receptor system. In spite of misleading discussions both in the specialized and in the lay press the clinical effectiveness of antidepressants still is indisputable. The main advantages of the newer drugs are the broadening of the spectrum treatments and a far better tolerability profile in comparison to older compounds. Predominantly depression of medium to high severity should be treated pharmacologically. Especially severe depression seems to respond better to dually acting antidepressants. In children effectiveness of Omega3-fatty acids has been shown, in adolescents SSRI treatment was efficacious. Older patients respond to all antidepressant mechanisms, but more selective substances should be preferred due to a better tolerability. The study of new treatment options is of major importance to provide better strategies for the clinical management of depression in the future, and is thus also of great socio-economic importance.

  17. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.

    PubMed

    Kitada, Munehiro; Kume, Shinji; Takeda-Watanabe, Ai; Kanasaki, Keizo; Koya, Daisuke

    2013-02-01

    Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.

  18. Optic nerve head biomechanics in aging and disease.

    PubMed

    Downs, J Crawford

    2015-04-01

    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.

  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. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson's Disease.

    PubMed

    Claassen, Daniel O; Dobolyi, David G; Isaacs, David A; Roman, Olivia C; Herb, Joshua; Wylie, Scott A; Neimat, Joseph S; Donahue, Manus J; Hedera, Peter; Zald, David H; Landman, Bennett A; Bowman, Aaron B; Dawant, Benoit M; Rane, Swati

    2016-05-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson's disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson's Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2(nd), or 3(rd) order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning.

  1. Brain dopamine-serotonin vesicular transport disease presenting as a severe infantile hypotonic parkinsonian disorder.

    PubMed

    Jacobsen, Jessie C; Wilson, Callum; Cunningham, Vicki; Glamuzina, Emma; Prosser, Debra O; Love, Donald R; Burgess, Trent; Taylor, Juliet; Swan, Brendan; Hill, Rosamund; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

    2016-03-01

    Two male siblings from a consanguineous union presented in early infancy with marked truncal hypotonia, a general paucity of movement, extrapyramidal signs and cognitive delay. By mid-childhood they had made little developmental progress and remained severely hypotonic and bradykinetic. They developed epilepsy and had problems with autonomic dysfunction and oculogyric crises. They had a number of orthopaedic problems secondary to their hypotonia. Cerebrospinal fluid (CSF) neurotransmitters were initially normal, apart from mildly elevated 5-hydroxyindolacetic acid, and the children did not respond favourably to a trial of levodopa-carbidopa. The youngest died from respiratory complications at 10 years of age. Repeat CSF neurotransmitters in the older sibling at eight years of age showed slightly low homovanillic acid and 5-hydroxyindoleacetic acid levels. Whole-exome sequencing revealed a novel mutation homozygous in both children in the monoamine transporter gene SLC18A2 (p.Pro237His), resulting in brain dopamine-serotonin vesicular transport disease. This is the second family to be described with a mutation in this gene. Treatment with the dopamine agonist pramipexole in the surviving child resulted in mild improvements in alertness, communication, and eye movements. This case supports the identification of the causal mutation in the original case, expands the clinical phenotype of brain dopamine-serotonin vesicular transport disease and confirms that pramipexole treatment may lead to symptomatic improvement in affected individuals.

  2. 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...

  3. Compromised respiratory adaptation and thermoregulation in aging and age-related diseases.

    PubMed

    Chan, Sic L; Wei, Zelan; Chigurupati, Srinivasulu; Tu, Weihong

    2010-01-01

    Mitochondrial dysfunction and reactive oxygen species (ROS) production are at the heart of the aging process and are thought to underpin age-related diseases. Mitochondria are not only the primary energy-generating system but also the dominant cellular source of metabolically derived ROS. Recent studies unravel the existence of mechanisms that serve to modulate the balance between energy metabolism and ROS production. Among these is the regulation of proton conductance across the inner mitochondrial membrane that affects the efficiency of respiration and heat production. The field of mitochondrial respiration research has provided important insight into the role of altered energy balance in obesity and diabetes. The notion that respiration and oxidative capacity are mechanistically linked is making significant headway into the field of aging and age-related diseases. Here we review the regulation of cellular energy and ROS balance in biological systems and survey some of the recent relevant studies that suggest that respiratory adaptation and thermodynamics are important in aging and age-related diseases.

  4. Visual Function and Its Relationship with Severity of Early, and Activity of Neovascular, Age-Related Macular Degeneration

    PubMed Central

    Loughman, James; Sabour-Pickett, Sarah; Nolan, John M.; Klein, Barbara; Klein, Ronald; Beatty, Stephen

    2017-01-01

    Purpose To investigate the relationship between visual function and severity of early age-related macular degeneration (AMD) and activity of neovascular (nv-) AMD. Methods The following data was collected from 66 eyes of 66 subjects with early AMD and 47 eyes of 47 subjects with active nv-AMD: corrected distance visual acuity (CDVA); contrast sensitivity (CS); glare disability (GD); and retinotopic ocular sensitivity (ROS) of the central 5° of the retina, by microperimetry. Fundus photographic grading of early AMD was performed in a masked fashion. Mean foveal thickness (MFT) was measured by spectral domain optical coherence tomography in patients with nv-AMD. Results In subjects with early AMD, there was an inverse and statistically significant relationship between measures of ROS within the central 5° of retina (including fixation) and severity of early AMD (p=0.01). In eyes with active nv-AMD, an inverse and statistically significant relationship was observed between measures of MFT and measures of ROS at the central 5° of retina (r=-0.34; p=0.02). No other measures, including CDVA, were significantly related to severity of early AMD, or to MFT in nv-AMD. Conclusion Although ROS was cross-sectionally associated with disease severity, and inversely related to MFT, an important determinant of need-to-treat in cases of nv-AMD, further research is required to determine the appropriateness of ROS for monitoring early and active neovascular forms of this disease.

  5. 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

  6. Age estimation from dental cementum incremental lines and periodontal disease.

    PubMed

    Dias, P E M; Beaini, T L; Melani, R F H

    2010-12-01

    Age estimation by counting incremental lines in cementum added to the average age of tooth eruption is considered an accurate method by some authors, while others reject it stating weak correlation between estimated and actual age. The aim of this study was to evaluate this technique and check the influence of periodontal disease on age estimates by analyzing both the number of cementum lines and the correlation between cementum thickness and actual age on freshly extracted teeth. Thirty one undecalcified ground cross sections of approximately 30 µm, from 25 teeth were prepared, observed, photographed and measured. Images were enhanced by software and counts were made by one observer, and the results compared with two control-observers. There was moderate correlation ((r)=0.58) for the entire sample, with mean error of 9.7 years. For teeth with periodontal pathologies, correlation was 0.03 with a mean error of 22.6 years. For teeth without periodontal pathologies, correlation was 0.74 with mean error of 1.6 years. There was correlation of 0.69 between cementum thickness and known age for the entire sample, 0.25 for teeth with periodontal problems and 0.75 for teeth without periodontal pathologies. The technique was reliable for periodontally sound teeth, but not for periodontally diseased teeth.

  7. Levodopa changes the severity of freezing in Parkinson's disease.

    PubMed

    Fietzek, Urban M; Zwosta, Jens; Schroeteler, Frauke E; Ziegler, Kerstin; Ceballos-Baumann, Andres O

    2013-10-01

    Oral levodopa has been proposed to be one of the more effective medications to alleviate freezing of gait, but there is limited data on its efficacy. We evaluated the gait phenomenology of 20 Parkinson's disease patients with freezing of gait before and 60 min after a standardized levodopa dose using a rating scale based on the assumption that festination and akinetic freezing share a common pathophysiology. Levodopa abolished festination and freezing in 20% of patients (p < 0.0001), and reduced the freezing sum score from a median of 15 (IQR 6.75-27.5) to 3.5 (1-11.25), p < 0.001) in all but one of the remainder. Pre-dose ratings correlated with post-dose ratings, in that those patients with lower pre-dose item-scores also showed lower post-dose outcome scores. Levodopa's effect on both festination and akinetic freezing was linear, thereby supporting the concept that festination and freezing are variants on a continuity of episodic gait disorders in PD.

  8. EFFECT OF AGE ON KAINATE-INDUCED SEIZURE SEVERITY AND CELL DEATH

    PubMed Central

    McCord, Meghan C.; Lorenzana, Ariana; Bloom, Christopher S.; Chancer, Zackary O.; Schauwecker, P. Elyse

    2008-01-01

    While the onset and extent of epilepsy increases in the aged population, the reasons for this increased incidence remain unexplored. The present study used two inbred strains of mice (C57BL/6J and FVB/NJ) to address the genetic control of age-dependent neurodegeneration by building upon previous experiments that have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death. We determined if seizure induction and seizure-induced cell death are affected differentially in young adult, mature, and aged male C57BL/6J and FVB/NJ mice administered the excitotoxin, kainic acid. Dose response testing was performed in three-four groups of male mice from each strain. Following kainate injections, mice were scored for seizure activity and brains from mice in each age group were processed for light microscopic histopathologic evaluation seven days following kainate administration to evaluate the severity of seizure-induced brain damage. Irrespective of the dose of kainate administered or the age group examined, resistant strains of mice (C57BL/6J) continued to be resistant to seizure-induced cell death. In contrast, aged animals of the FVB/NJ strain were more vulnerable to the induction of behavioral seizures and associated neuropathology after systemic injection of kainic acid than young or middle-aged mice. Results from these studies suggest that the age-related increased susceptibility to the neurotoxic effects of seizure induction and seizure-induced injury is regulated in a strain-dependent manner, similar to previous observations in young adult mice. PMID:18479826

  9. Blood dendritic cell frequency declines in idiopathic Parkinson's disease and is associated with motor symptom severity.

    PubMed

    Ciaramella, Antonio; Salani, Francesca; Bizzoni, Federica; Pontieri, Francesco E; Stefani, Alessandro; Pierantozzi, Mariangela; Assogna, Francesca; Caltagirone, Carlo; Spalletta, Gianfranco; Bossù, Paola

    2013-01-01

    The role of inflammation in Parkinson's Disease (PD) is well appreciated, but its underlying mechanisms are still unclear. Our objective was to determine whether dendritic cells (DC), a unique type of migratory immune cells that regulate immunological response and inflammation have an impact on PD. In a case-control study including 80 PD patients and 80 age- and gender-matched healthy control subjects, the two main blood subsets of plasmacytoid and myeloid DC were defined by flow cytometry analysis. Clinical evaluation of subjects consisting of cognition and depression assessment was performed using the Mini Mental State Examination and the Beck Depression Inventory. The severity of motor symptoms was measured using the Unified Parkinson's Disease Rating Scale-Part III. Comparison between patient and control DC measures and their relationships with clinical assessments were evaluated.The following main results were obtained: 1) the level of circulating DC (mainly the myeloid subset) was significantly reduced in PD patients in comparison with healthy controls; 2) after controlling for depressive and cognitive characteristics, the frequency of myeloid DC was confirmed as one of the independent determinants of PD; 3) the number of both myeloid and plasmacytoid DC was negatively associated with motor symptom severity. Overall, the decline of blood DC, perhaps due to the recruitment of immune cells to the site of disease-specific lesions, can be considered a clue of the immune alteration that characterizes PD, suggesting innovative exploitations of DC monitoring as a clinically significant tool for PD treatment. Indeed, this study suggests that reduced peripheral blood DC are a pathologically-relevant factor of PD and also displays the urgency to better understand DC role in PD for unraveling the immune system contribution to disease progression and thus favoring the development of innovative therapies ideally based on immunomodulation.

  10. Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication

    PubMed Central

    2016-01-01

    Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. This manuscript provides an overview of many of the known determinants, modifiers, and correlates of disease severity in SCD. Despite this wealth of data, modeling the variable and multisystem pathology of SCD continues to be difficult. The current status of prediction of specific adverse outcomes and global disease severity in SCD is also reviewed, highlighting recent successes and ongoing challenges. PMID:27013545

  11. A common brain network links development, aging, and vulnerability to disease.

    PubMed

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  12. 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

  13. Screening for Future Cardiovascular Disease Using Age Alone Compared with Multiple Risk Factors and Age

    PubMed Central

    Wald, Nicholas J.; Simmonds, Mark; Morris, Joan K.

    2011-01-01

    Background Risk factors such as blood pressure and serum cholesterol are used, with age, in screening for future cardiovascular disease (CVD) events. The value of using these risk factors with age compared with using age alone is not known. We compared screening for future CVD events using age alone with screening using age and multiple risk factors based on regular Framingham risk assessments. Methods Ten-year CVD risk was estimated using Framingham risk equations in a hypothetical sample population of 500,000 people aged 0–89 years. Risk estimates were used to identify individuals who did and did not have a CVD event over a ten-year period. For screening using age alone (age screening) and screening using multiple risk factors and age (Framingham screening) we estimated the (i) detection rate (sensitivity); (ii) false–positive rate; (iii) proportion of CVD-free years of life lost in affected individuals with positive results (person-years detection rate); and (iv) cost per CVD-free life year gained from preventive treatment. Results Age screening using a cut-off of 55 years detected 86% of all first CVD events arising in the population every year and 72% of CVD-free years of life lost for a 24% false-positive rate; for five yearly Framingham screening the false-positive rate was 21% for the same 86% detection rate. The estimated cost per CVD-free year of life gained was £2,000 for age screening and £2,200 for Framingham screening if a Framingham screen costs £150 and the annual cost of preventive treatment is £200. Conclusion Age screening for future CVD events is simpler than Framingham screening with a similar screening performance and cost-effectiveness. It avoids blood tests and medical examinations. The advantages of age screening in the prevention of heart attack and stroke warrant considering its use in preference to multiple risk factor screening. PMID:21573224

  14. Can a normal peak expiratory flow exclude severe chronic obstructive pulmonary disease?

    PubMed Central

    Perez-Padilla, R.; Vollmer, W. M.; Vázquez-García, J. C.; Enright, P. L.; Menezes, A. M. B.; Buist, A. S.

    2011-01-01

    SUMMARY BACKGROUND Chronic obstructive pulmonary disease (COPD) is underdiagnosed. One barrier to diagnosis is the limited availability of spirometry testing, but in adults at risk for COPD, a normal pre-bronchodilator (pre-BD) peak expiratory flow (PEF) may rule out clinically significant COPD. OBJECTIVE To identify post-BD airway obstruction using data from 13 708 individuals aged ≥40 years from the PLATINO and BOLD studies. METHODS We evaluated different cut-off points of pre-BD. The PEF was obtained from a diagnostic-quality spirometer (not a mechanical PEF meter). At least one of the following COPD risk factors was present in 77% of the subjects: chronic respiratory symptoms; exposure to tobacco smoke, biomass smoke or dust in the workplace; or a previous diagnosis of asthma, COPD, emphysema or chronic bronchitis. RESULTS Although the positive predictive value was low as expected, a pre-BD PEF of ≥70% predicted effectively ruled out Stages III and IV COPD of the Global Initiative for Chronic Obstructive Lung Disease. Among those with at least one risk factor, only 12% would require confirmatory spirometry using this criterion. CONCLUSIONS Adding PEF measurement to a screening questionnaire may rule out severe to very severe COPD without the need for pre- and post-BD spirometry testing. Confirmation is needed from a study using inexpensive PEF meters or pocket spirometers with a staged screening protocol. PMID:19275802

  15. A-type lamins and cardiovascular disease in premature aging syndromes.

    PubMed

    Dorado, Beatriz; Andrés, Vicente

    2017-01-10

    Lamin A is a nuclear intermediate filament protein with important structural and regulatory roles in most differentiated mammalian cells. Excessive accumulation of its precursor prelamin A or the mutant form called 'progerin' causes premature aging syndromes. Progeroid 'laminopathies' are characterized by severe cardiovascular problems (cardiac electrical defects, vascular calcification and stiffening, atherosclerosis, myocardial infarction, and stroke) and premature death. Here, we review studies in cell and mouse models and patients that are unraveling how abnormal prelamin A and progerin accumulation accelerates cardiovascular disease and aging. This knowledge is essential for developing effective therapies to treat progeria and may help identify new mechanisms underlying normal aging.

  16. The effect of chair yoga in older adults with moderate and severe Alzheimer's disease.

    PubMed

    McCaffrey, Ruth; Park, Juyoung; Newman, David; Hagen, Dyana

    2014-01-01

    Using a quasi-experimental single-group design, this study examined the feasibility of older adults with Alzheimer's disease (AD)-type dementia to complete the Sit 'N' Fit Chair Yoga Program. Physical function of participants who completed the program was measured. The nine older adults with AD (mean age = 83) participated in the 8-week Sit 'N' Fit Chair Yoga Program. To measure physical function, the Six-Minute Walk Test, the Gait Speed Test, and the Berg Balance Scale were administered at pre-intervention, 4 weeks, 8 weeks, and 1 month after program completion. All participants completed the program. Positive changes were seen across all physical measures. Further study, using a larger sample and including a control group, is needed to fully determine the effect of the Sit 'N' Fit Chair Yoga Program on older adults with moderate to severe AD.

  17. [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

  18. Severe multivessel coronary artery disease and high-sensitive troponin T

    PubMed Central

    Huziuk, Inga Magdalena

    2015-01-01

    Introduction A key problem in stable coronary artery disease (CAD) is non-invasive identification of patients with severe multivessel CAD. Determination of biomarkers that have pro-inflammatory properties (C-reactive protein – hsCRP) and indicate heart muscle ischemia (high-sensitive troponin T – hsTnT) can contribute to the improvement of stratification in this regard. The aim of the study The aim of the study was to identify factors associated with the presence of multivessel CAD in clinically stable men. Material and methods The study included 92 symptomatic men (mean age 64.05 ± 9.42 years) with preserved left ventricular function, scheduled for elective coronary angiography. Patients were divided and analyzed in two groups: with multivessel coronary artery disease (2-3-vessel disease, n = 46) vs. without multivessel coronary artery disease (n = 46). Results Patients with multivessel CAD had significantly higher levels of hsTnT (0.01 vs. 0.007, p = 0.0021) and fasting glucose (6.0 vs. 5.45, p = 0.0112). Based on the drawn ROC curves, the cut-off points were determined for hsTnT ≥ 0.0085 ng/ml and fasting plasma glucose ≥ 5.85 mmol/l. From multivariate analysis only hsTnT in concentration higher than the cut-off point enhanced the risk of multivessel CAD (OR 4.286, 95% CI: 1.79-10.263, p = 0.001). Conclusions In men with stable CAD, preserved systolic left ventricular function and non-high cardiovascular risk determined from the initial concentration of hsCRP, elevated level of hsTnT was independently associated with the risk of multivessel coronary artery disease. PMID:26336496

  19. Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community.

    PubMed

    Houben, M L; Coenjaerts, F E J; Rossen, J W A; Belderbos, M E; Hofland, R W; Kimpen, J L L; Bont, L

    2010-07-01

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, with remarkable variability in disease severity. Factors determining severity of disease in previously healthy infants are still unclear. It was hypothesized that disease severity is correlated with viral load in primary RSV infection. Infants of a healthy birth cohort were included at signs of their first respiratory tract infection. Nasopharyngeal aspirate was obtained within 48-96 hr and disease severity was assessed with a previously published severity scoring model. PCR was applied to test the aspirates in a semi-quantitative way for the presence of 10 respiratory pathogens. In case of multiple infection, the pathogen with the highest load was defined as the primary pathogen. The correlation between disease severity and viral load was analyzed. A total of 82 infants were included over a period of 2 years. Median age at first respiratory tract infection was 3 months. Pathogens were detected in 77 (94%) infants; more than one pathogen was detected in 35 (43%) infants. RSV was present in aspirates of 30 infants; in 16 aspirates RSV was the primary pathogen. A negative correlation between RSV CT-value and disease severity was found in all RSV cases (rho = -0.52, P = 0.003) and in cases with RSV as the primary pathogen (rho = -0.54, P = 0.03). In conclusion, this is the first report on viral loads in previously healthy infants with RSV infection in the community. Disease severity correlated positively with viral load during primary RSV infection.

  20. 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

  1. Age and diagnostic performance of Alzheimer disease CSF biomarkers

    PubMed Central

    Rosén, E.; Hansson, O.; Andreasen, N.; Parnetti, L.; Jonsson, M.; Herukka, S.-K.; van der Flier, W.M.; Blankenstein, M.A.; Ewers, M.; Rich, K.; Kaiser, E.; Verbeek, M.M.; Olde Rikkert, M.; Tsolaki, M.; Mulugeta, E.; Aarsland, D.; Visser, P.J.; Schröder, J.; Marcusson, J.; de Leon, M.; Hampel, H.; Scheltens, P.; Wallin, A.; Eriksdotter-Jönhagen, M.; Minthon, L.; Winblad, B.; Blennow, K.; Zetterberg, H.

    2012-01-01

    Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid β1–42, increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. Methods: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43–89 years) and 304 controls (67, 44–91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43–89 years) followed for at least 2 years, or until dementia diagnosis. Results: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. Conclusion: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations. PMID:22302554

  2. Factors related to onset age of Huntington disease.

    PubMed Central

    Myers, R H; Madden, J J; Teague, J L; Falek, A

    1982-01-01

    One prominent feature of Huntington disease (HD) is the variable age at which the characteristic neurological or psychiatric symptoms appear. Ages of manifestation varying from 4 to 65 years are found in a sample of 95 HD pedigrees compiled since 1968 from the Southeastern United States. Significant parent-child correlations of age of onset indicate consistency of onset age within nuclear families. However, an average intrafamily range of 9 years and an average intrapedigree range of 12 years reveal substantial variability of onset age within these groups. Of the nine cases of juvenile-onset HD identified in this sample, seven were of paternal descent. The preponderance of juvenile patients inheriting the HD gene from a father confirms similar findings from other studies. In addition, a trend toward earlier onset in all offspring of paternal transmission suggests that the juvenile-onset phenomenon is only the tail of a shift in the curve of onset ages for this group. A trend toward earlier onset in successive generations was noted. This "anticipation" may reflect the finding that persons of early onset in prior generations are selectively nonreproductive as a result of manifestation of the disorder. By identifying familial factors influencing onset age of HD, it may be possible to more effectively evaluate environmental factors that influence the onset of the disorder. PMID:6211092

  3. 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

  4. 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.

  5. 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

  6. Flavonoids and Age Related Disease: Risk, benefits and critical windows

    PubMed Central

    Prasain, JK; Carlson, SH; Wyss, JM

    2010-01-01

    Plant derived products are consumed by a large percentage of the population to prevent, delay and ameliorate disease burden; however, relatively little is known about the efficacy, safety and underlying mechanisms of these traditional health products, especially when taken in concert with pharmaceutical agents. The flavonoids are a group of plant metabolites that are common in the diet and appear to provide some health benefits. While flavonoids are primarily derived from soy, many are found in fruits, nuts and more exotic sources, e.g., kudzu. Perhaps the strongest evidence for the benefits of flavonoids in diseases of aging relates to their effect on components of the metabolic syndrome. Flavonoids from soy, grape seed, kudzu and other sources all lower arterial pressure in hypertensive animal models and in a limited number of tests in humans. They also decrease the plasma concentration of lipids and buffer plasma glucose. The underlying mechanisms appear to include antioxidant actions, central nervous system effects, gut transport alterations, fatty acid sequestration and processing, PPAR activation and increases in insulin sensitivity. In animal models of disease, dietary flavonoids also demonstrate a protective effect against cognitive decline, cancer and metabolic disease. However, research also indicates that the flavonoids can be detrimental in some settings and, therefore, are not universally safe. Thus, as the population ages, it is important to determine the impact of these agents on prevention/attenuation of disease, including optimal exposure (intake, timing/duration) and potential contraindications. PMID:20181448

  7. Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases.

    PubMed

    Grillo, M A; Colombatto, S

    2008-06-01

    Advanced glycation end-products (AGEs) are formed from the so-called Amadori products by rearrangement followed by other reactions giving rise to compounds bound irreversibly. The structure of some of them is shown and the mechanism of formation is described. Several AGE binding molecules (Receptors for AGE, RAGE) are known and it is thought that many of the effects caused by AGEs are mediated by RAGE. Some of these were shown to be toxic, and called TAGE. The mechanism of detoxification of glyoxal and methylglyoxal by the glyoxalase system is described and also the possibility to eliminate glycated proteins by deglycation enzymes. Compounds able to inhibit AGEs formation are also taken into consideration.

  8. Severe to profound deafness may be associated with MYH9-related disease: report of 4 patients.

    PubMed

    Canzi, P; Pecci, A; Manfrin, M; Rebecchi, E; Zaninetti, C; Bozzi, V; Benazzo, M

    2016-10-01

    MYH9-related disease (MYH9-RD) is a rare genetic syndromic disorder characterised by congenital thrombocytopenia and is associated with the risk of developing progressive sensorineural hearing loss, nephropathy and presenile cataracts during childhood or adult life. All consecutive patients enrolled in the Italian Registry for MYH9-RD with severe to profound deafness were included in a retrospective study. The study population involved 147 Italian patients with MYH9-RD: hearing loss was identified in 52% of cases and only 4 patients (6%) presented severe to profound deafness at a mean age of 33 years. Deafness was associated with mild spontaneous bleeding in all patients and with kidney involvement in 3 cases. Cochlear implantation was carried out in 3 cases with benefit, and no major complications were observed. Diagnosis was performed about 28 years after the first clinical manifestation of MYH9-RD, which was never suspected by an otolaryngologist. The clinical and diagnostic aspects of 4 patients with severe to profound deafness are discussed with a focus on therapeutic implications.

  9. Accelerated Aging Influences Cardiovascular Disease Risk in Rheumatoid Arthritis

    PubMed Central

    Crowson, Cynthia S.; Therneau, Terry M.; Davis, John M.; Roger, Véronique L.; Matteson, Eric L.; Gabriel, Sherine E.

    2014-01-01

    OBJECTIVE To determine whether the impact of aging on cardiovascular disease (CVD) risk in the general population (as estimated by the Framingham risk score [FRS]) differs in patients with rheumatoid arthritis (RA). METHODS A population-based inception cohort of Olmsted County, Minnesota residents aged ≥30 years who fulfilled 1987 ACR criteria for RA in 1988–2008 was assembled and followed until death, migration, or 7-1-2012. Data on CVD events were collected by medical record review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk. RESULTS The study included 563 patients with RA without prior CVD (mean age: 55 years, 72% women; 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean follow-up of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the age effect on CVD risk in seropositive RA was nearly double its effect in the general population with additional log(age) coefficients of 2.91 for women (p=0.002) and 2.06 for men (p=0.027). CONCLUSION Age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation. PMID:23818136

  10. 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).

  11. Pain in thalassaemia: the effects of age on pain frequency and severity.

    PubMed

    Haines, Dru; Martin, Marie; Carson, Susan; Oliveros, Olivia; Green, Sage; Coates, Thomas; Eile, Jennifer; Schilling, Leann; Dinu, Bogan; Mendoza, Tito; Gerstenberger, Eric; Trachtenberg, Felicia; Vichinsky, Elliott

    2013-03-01

    Pain is not a symptom generally associated with thalassaemia. However, providers have noted increasing patient reports of pain, creating an impetus for this prospective, observational assessment of pain in thalassaemia patients. The primary study goals were to assess pain prevalence, severity, location, and potential risk factors. This was a multicentre, prospective study of thalassaemia patients receiving care at 12 Thalassaemia Clinical Research Network sites. Pain was assessed using the Brief Pain Inventory. Two hundred and fifty-two thalassaemia patients ranging in age from 12 to 71 years (mean 28.8) were enrolled. Sixty-four per cent reported experiencing pain during the last 4 weeks, 22% of whom reported pain on a daily basis. Ordinal regression analysis of pain ratings demonstrated significant (P < 0.001) correlation of increased age with increased pain, irrespective of diagnosis, transfusion status, gender, bone density, chelator type or iron overload. Eighty-one per cent reported having pain for 1 year or longer and 31% reported pain for five or more years. Pain is a major cause of morbidity and an unrecognized problem for patients with thalassaemia. Age is the strongest predictor of frequency and severity. Little else is known about the aetiology and predictors of this pain syndrome.

  12. 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.

  13. Sirtuin 1 and Aging Theory for Chronic Obstructive Pulmonary Disease

    PubMed Central

    Conti, V.; Corbi, G.; Manzo, V.; Pelaia, G.; Filippelli, A.; Vatrella, A.

    2015-01-01

    Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the “aging theory for COPD” was also discussed. PMID:26236580

  14. 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.

  15. 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.

  16. How many standard area diagram sets are needed for accurate disease severity assessment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Standard area diagram sets (SADs) are widely used in plant pathology: a rater estimates disease severity by comparing an unknown sample to actual severities in the SADs and interpolates an estimate as accurately as possible (although some SADs have been developed for categorizing disease too). Most ...

  17. 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…

  18. Versatile Functions of Caveolin-1 in Aging-related Diseases

    PubMed Central

    Nguyen, Kim Cuc Thi

    2017-01-01

    Caveolin-1 (Cav-1) is a trans-membrane protein that is a major component of the caveolae structure on the plasma membrane. Cav-1 is involved in the regulation of various cellular processes, including cell growth, differentiation, endocytosis, and in particular it has been implied in cellular senescence. Here we review current knowledge about Cav-1 in cellular signaling and discuss the role of Cav-1 in aging-related diseases. PMID:28184336

  19. NF-κB in Aging and Disease

    PubMed Central

    Tilstra, Jeremy S.; Clauson, Cheryl L.; Niedernhofer, Laura J.; Robbins, Paul D.

    2011-01-01

    Stochastic damage to cellular macromolecules and organelles is thought to be a driving force behind aging and associated degenerative changes. However, stress response pathways activated by this damage may also contribute to aging. The IKK/NF-κB signaling pathway has been proposed to be one of the key mediators of aging. It is activated by genotoxic, oxidative, and inflammatory stresses and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell cycle progression, cell senescence, and inflammation. Transcriptional activity of NF-κB is increased in a variety of tissues with aging and is associated with numerous age-related degenerative diseases including Alzheimer’s, diabetes and osteoporosis. In mouse models, inhibition of NF-κB leads to delayed onset of age-related symptoms and pathologies. In addition, NF-κB activation is linked with many of the known lifespan regulators including insulin/IGF-1, FOXO, SIRT, mTOR, and DNA damage. Thus NF-κB represents a possible therapeutic target for extending mammalian healthspan. PMID:22396894

  20. Can we define maternal age as a genetic disease?

    PubMed

    Wilding, M

    2014-01-01

    >Maternal age is strongly associated with a decrease in the probability of achieving pregnancy and the birth of a healthy child. Among current theories of the mechanism of this decrease is the hypothesis that a progressive degeneration of the respiratory capacity of mitochondria in eggs of women of advanced age leads to an energy deficit and consequent secondary effects on the oocyte and developing embryo. Mitochondria are uniquely inherited through the female germ line and these organelles contain DNA sequences that are independent from the genome. It is therefore possible that offspring born to females of advanced age inherit suboptimal mitochondria and that these persist throughout the life of the new being. This could in turn lead to long-term consequences for the offspring of females of advanced age such as a reduced potential lifespan in relation to the age of the mother at conception. In this review and hypothesis, we discuss the evidence relating to this theory and suggest that on this basis the maternal age effect could be classified as an inheritable genetic disease.

  1. [Age distribution of urinary tract infections (UTIs) and their severity grade in children (author's transl)].

    PubMed

    Elo, J; Tallgren, L G; Sarna, S

    1982-03-01

    Urinary tract infections in 339 children (77 boys and 262 girls) have been followed up. An excretory urography and a urethrocystography were done for all the children. The frequency of functional and anatomical abnormalities is given. The severity grade of UTI was determined according to the classification of Elo and Stenström. Almost all episodes of UTI among boys occurred during the first three years of life and were mostly severe. After the 3rd year of life the occurrence of UTI among the boys was sporadic. Among the girls the severe episodes dominates during the first three years of life, but after that the episodes tended to become milder in character becoming mostly asymptomatic. The peak of asymptomatic episodes among girls was at 10 years of age. After that age the number of episodes dropped abruptly. The classification used, based on the erythrocyte sedimentation rate (ESR) and on white blood cell count (WBC), has shown to be useful and makes it possible to differentiate between renal (pyelonephritic) episodes and the lower tract episodes.

  2. Hutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations.

    PubMed

    Gonzalo, Susana; Kreienkamp, Ray; Askjaer, Peter

    2017-01-01

    Products of the LMNA gene, primarily lamin A and C, are key components of the nuclear lamina, a proteinaceous meshwork that underlies the inner nuclear membrane and is essential for proper nuclear architecture. Alterations in lamin A and C that disrupt the integrity of the nuclear lamina affect a whole repertoire of nuclear functions, causing cellular decline. In humans, hundreds of mutations in the LMNA gene have been identified and correlated with over a dozen degenerative disorders, referred to as laminopathies. These diseases include neuropathies, muscular dystrophies, lipodystrophies, and premature aging diseases. This review focuses on one of the most severe laminopathies, Hutchinson-Gilford Progeria Syndrome (HGPS), which is caused by aberrant splicing of the LMNA gene and expression of a mutant product called progerin. Here, we discuss current views about the molecular mechanisms that contribute to the pathophysiology of this devastating disease, as well as the strategies being tested in vitro and in vivo to counteract progerin toxicity. In particular, progerin accumulation elicits nuclear morphological abnormalities, misregulated gene expression, defects in DNA repair, telomere shortening, and genomic instability, all of which limit cellular proliferative capacity. In patients harboring this mutation, a severe premature aging disease develops during childhood. Interestingly, progerin is also produced in senescent cells and cells from old individuals, suggesting that progerin accumulation might be a factor in physiological aging. Deciphering the molecular mechanisms whereby progerin expression leads to HGPS is an emergent area of research, which could bring us closer to understanding the pathology of aging.

  3. Molecular Epidemiology and Disease Severity of Human Respiratory Syncytial Virus in Vietnam

    PubMed Central

    Tran, Dinh Nguyen; Pham, Thi Minh Hong; Ha, Manh Tuan; Tran, Thi Thu Loan; Dang, Thi Kim Huyen; Yoshida, Lay-Myint; Okitsu, Shoko; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2013-01-01

    Respiratory syncytial virus (RSV) is a major cause of acute respiratory infections (ARIs) in children worldwide and can cause high mortality, especially in developing countries. However, information on the clinical and molecular characteristics of RSV infection in developing countries is limited. From April 2010 to May 2011, 1,082 nasopharyngeal swabs were collected from children with ARI admitted to the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for RSV and genotyped by reverse transcription-PCR and sequencing. Demographic and clinical data was also recorded. RSV was found in 23.8% (257/1,082) of samples. RSV A was the dominant subgroup, accounting for 91.4% (235/257), followed by RSV B, 5.1% (13/257), and 9 cases (3.5%) were mixed infection of these subgroups. The phylogenetic analysis revealed that all group A strains belonged to the GA2 genotype. All group B strains belonged to the recently identified BA genotype, and further clustered into 2 recently described subgenotypes BA9 and BA10. One GA2 genotype strain had a premature stop codon which shortened the G protein length. RSV infection was significantly associated with younger age and higher severity score than those without. Co-infection with other viruses did not affect disease severity. RSV A caused more severe disease than RSV B. The results from this study will not only contribute to the growing database on the molecular diversity of RSV circulating worldwide but may be also useful in clinical management and vaccine development. PMID:23349659

  4. Molecular insights into the premature aging disease progeria.

    PubMed

    Vidak, Sandra; Foisner, Roland

    2016-04-01

    Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disease presenting many features resembling the normal aging process. HGPS patients die before the age of 20 years due to cardiovascular problems and heart failure. HGPS is linked to mutations in the LMNA gene encoding the intermediate filament protein lamin A. Lamin A is a major component of the nuclear lamina, a scaffold structure at the nuclear envelope that defines mechanochemical properties of the nucleus and is involved in chromatin organization and epigenetic regulation. Lamin A is also present in the nuclear interior where it fulfills lamina-independent functions in cell signaling and gene regulation. The most common LMNA mutation linked to HGPS leads to mis-splicing of the LMNA mRNA and produces a mutant lamin A protein called progerin that tightly associates with the inner nuclear membrane and affects the dynamic properties of lamins. Progerin expression impairs many important cellular processes providing insight into potential disease mechanisms. These include changes in mechanosignaling, altered chromatin organization and impaired genome stability, and changes in signaling pathways, leading to impaired regulation of adult stem cells, defective extracellular matrix production and premature cell senescence. In this review, we discuss these pathways and their potential contribution to the disease pathologies as well as therapeutic approaches used in preclinical and clinical tests.

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

    PubMed

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

    2016-05-01

    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.

  6. Experimental investigation of fiberglass sandwich composite bending behaviour after severe aging condition

    NASA Astrophysics Data System (ADS)

    Gambaro, Carla; Lertora, Enrico; Mandolfino, Chiara

    2016-10-01

    Fiber Reinforced Polymer (FRP) sandwich panels are increasing their application as structural and non-structural components in all kinds of construction. By varying the material and thickness of core and face sheets, it is possible to obtain sandwich structures with different properties and performance. In particular, their advantages as lightweight and high mechanical properties make them extremely suitable for the transport industry. One of the most critical aspects regarding composite materials for engineering application is their performance after hygrothermal aging. The panels used in this study are composed of low density core, made by thermosetting resin foam with microspheres and glass fibers rolled until obtaining the required thickness, and two face sheets of the same material but realized in high density. In this study, the authors focused on the bending behaviour of this kind of sandwich panel, as received and after severe aging cycles.

  7. 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...

  8. Should we screen children with severe acute malnutrition for celiac disease?

    PubMed

    Kumar, Praveen; Mishra, Kirtisudha; Singh, Preeti; Rai, Kiran

    2012-04-01

    The clinical features of severe acute malnutrition (SAM) often overlap with the common manifestations of celiac disease. In this observational pilot study, 76 children fulfilling the case definition of SAM were investigated for celiac disease, tuberculosis and HIV. Celiac disease was diagnosed in 13.1% of SAM children while tuberculosis and HIV were diagnosed in 9.3% and 4%, respectively.

  9. 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.

  10. 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

  11. Sever's Disease

    MedlinePlus

    ... puts constant pressure on the heel. Poor-fitting shoes can contribute to the condition by not providing ... is to make sure that kids wear proper shoes. Good quality, well-fitting shoes with shock-absorbent ( ...

  12. Sever's Disease

    MedlinePlus

    ... results from physical activities and sports that involve running and jumping, especially those that take place on ... cause pain until all symptoms are gone, especially running barefoot or on hard surfaces because hard impact ...

  13. 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

  14. Spatial prediction of wheat Septoria leaf blotch (Septoria tritici) disease severity in central Ethiopia

    USGS Publications Warehouse

    Wakie, Tewodros; Kumar, Sunil; Senay, Gabriel; Takele, Abera; Lencho, Alemu

    2016-01-01

    A number of studies have reported the presence of wheat septoria leaf blotch (Septoria tritici; SLB) disease in Ethiopia. However, the environmental factors associated with SLB disease, and areas under risk of SLB disease, have not been studied. Here, we tested the hypothesis that environmental variables can adequately explain observed SLB disease severity levels in West Shewa, Central Ethiopia. Specifically, we identified 50 environmental variables and assessed their relationships with SLB disease severity. Geographically referenced disease severity data were obtained from the field, and linear regression and Boosted Regression Trees (BRT) modeling approaches were used for developing spatial models. Moderate-resolution imaging spectroradiometer (MODIS) derived vegetation indices and land surface temperature (LST) variables highly influenced SLB model predictions. Soil and topographic variables did not sufficiently explain observed SLB disease severity variation in this study. Our results show that wheat growing areas in Central Ethiopia, including highly productive districts, are at risk of SLB disease. The study demonstrates the integration of field data with modeling approaches such as BRT for predicting the spatial patterns of severity of a pathogenic wheat disease in Central Ethiopia. Our results can aid Ethiopia's wheat disease monitoring efforts, while our methods can be replicated for testing related hypotheses elsewhere.

  15. Natural Antibodies as Rheostats for Susceptibility to Chronic Diseases in the Aged

    PubMed Central

    Rothstein, Thomas L.

    2016-01-01

    Natural antibodies are spontaneously produced in the absence of infection or immunization, and are both anti-microbial and autoreactive. Autoreactive natural antibodies can bind noxious molecules, such as those involved in clinical situations of atherosclerosis (oxLDL), malignancy (NGcGM3), and neurodegeneration (amyloid, tau) and can affect the fate of their targets or the cells bearing them to maintain homeostasis. Clinically relevant natural antibodies have been shown to decline with advancing age in those few situations where measurements have been made. Consistent with this, human B-1 cells that are thought to be responsible for generating natural antibodies also decline with advancing age. These findings together suggest that an age-related decline in amount or efficacy of homeostatic natural antibodies is associated with relative loss of protection against molecules involved in several diseases whose incidence rises in the older age population, and that those individuals experiencing greatest loss are at greatest risk. In this view, natural antibodies act as rheostats for susceptibility to several age-related diseases. These considerations suggest that administration of natural antibodies, or of factors that maintain B-1 cells and/or enhance production of natural antibodies by B-1 cells, may serve to counteract the onset or progression of age-related chronic illness. PMID:27092140

  16. Cortical cathepsin D activity and immunolocalization in Alzheimer disease, critical coronary artery disease, and aging.

    PubMed

    Haas, U; Sparks, D L

    1996-09-01

    The activity and immunocytochemical localization of cathepsin D in the frontal cortex were investigated in patients with Alzheimer disease (AD) and two groups of nondemented subjects; individuals with critical coronary artery disease (cCAD; > 75% stenosis) and non-heart disease controls (non-HD). The cathepsin D activity significantly increased with age in the non-HD population. No such age-related increase was observed in either AD or cCAD. Enzymatic activity was significantly increased in only the midaged, but not the older AD and cCAD subjects compared to controls. Immunocytochemical reactivity paralleled cathepsin D enzymatic activity. Frontal cortex neurons displayed an increased accumulation of cathepsin D immunoreactivity in aging (non-HD controls) with a further increase in cCAD, especially in the midaged group. Such immunoreactivity was markedly increased in AD. There was also an apparent age-related increase in the number of cathepsin D immunoreactive neurons in the non-HD population and a disease-related increase in only the mid-aged AD and cCAD subjects compared to controls. Senile plaques (SP) occurred in all AD patients, many cCAD, and a few of the oldest non-HD subjects, and they were immunoreactive to cathepsin D in each group. The data suggest a possible relationship between activation of cathepsin D and SP formation in AD, cCAD, and aging.

  17. Regulation of muscle atrophy in aging and disease.

    PubMed

    Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia

    2010-01-01

    Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.

  18. 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

  19. Circulating Heat Shock Protein 70 in Health, Aging and Disease

    PubMed Central

    2011-01-01

    Background Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters. Results Serum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients. Conclusions The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients. PMID:21443787

  20. Annual direct medical costs of bronchiectasis treatment: Impact of severity, exacerbations, chronic bronchial colonization and chronic obstructive pulmonary disease coexistence.

    PubMed

    de la Rosa, David; Martínez-Garcia, Miguel-Angel; Olveira, Casilda; Girón, Rosa; Máiz, Luis; Prados, Concepción

    2016-04-12

    Patients with bronchiectasis (BE) present exacerbations that increase with severity of the disease. We aimed to determine the annual cost of BE treatment according to its severity, determined by FACED score, as well as the parameters associated with higher costs. Multicentre historical cohorts study with patients from six hospitals in Spain. The costs arising during the course of a year from maintenance treatment, exacerbations, emergency visits and hospital admissions were analysed. In total, 456 patients were included (56.4% mild BE, 26.8% moderate BE and 16.9% severe BE). The mean cost was €4671.9 per patient, which increased significantly with severity. In mild BE, most of the costs were due to bronchodilators and inhaled steroids; in severe BE, most were due to exacerbations and inhaled antibiotics. Forced expiratory volume in 1 second (FEV1%), age, colonization byPseudomonas aeruginosaand the number of admissions were independently related to higher costs. The highest costs were found in patients with BE associated with chronic obstructive pulmonary disease, with the most exacerbations and with chronic bronchial colonization byPseudomonas aeruginosa(PA). In conclusion, BE patients gave rise to high annual costs, and these were doubled on each advance in severity on the FACED score. FEV1%, age, colonization by PA and the number of admissions were independently related to higher costs.

  1. 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

  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. 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

  4. Severe respiratory syncytial virus (RSV) infection in infants with neuromuscular diseases and immune deficiency syndromes.

    PubMed

    Resch, Bernhard; Manzoni, Paolo; Lanari, Marcello

    2009-09-01

    Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection (LRTI) in infants and children. There is growing evidence of severe RSV disease in infants with neuromuscular diseases and immune deficiency syndromes. Factors predisposing to a more severe course of RSV disease in neuromuscular diseases include the impaired ability to clear secretions from the airways due to ineffective cough, respiratory muscle weakness, high prevalence of gastro-oesophageal reflux and swallowing dysfunction which leads to aspiration. Similarly, pulmonary disease is a common presenting feature and complication of T-cell immunodeficiency. Infants with severe congenital and acquired immune deficiency syndromes may demonstrate prolonged viral shedding in RSV LRTI and are reported to have increased morbidity and mortality associated with RSV infection. Although not indicated in most guideline statements, palivizumab prophylaxis for these uncommon underlying conditions is under consideration by clinicians. Prospective studies are needed to determine the burden of RSV disease in these children.

  5. Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

    PubMed

    Esopenko, Carrie; Levine, Brian

    2015-02-15

    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.

  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. Prophylaxis in von Willebrand Disease: Coming of Age?

    PubMed

    Saccullo, Giorgia; Makris, Mike

    2016-07-01

    Although in most cases von Willebrand disease (VWD) is a mild disorder, a subgroup of patients experience frequent bleeding. In contrast to severe hemophilia in which prophylaxis is the accepted standard of care, this is less frequently used in VWD. Most type 1 VWD patients can be adequately managed with episodic desmopressin and tranexamic acid. In patients with more severe disease, especially those with type 3 VWD, joint bleeds, epistaxis, menorrhagia, and gastrointestinal bleeding are problematic and usually require treatment with von Willebrand factor/factor VIII (VWF/FVIII) concentrate. While in the past these patients were managed with on-demand VWF/FVIII concentrate, several recent reports have demonstrated the value of prophylactic treatment. Despite some uncertainties about the economic impact of treatment of severe VWD, prophylaxis with VWF concentrate should now be considered as the standard of care for the more severe end of the spectrum of affected individuals. The recent introduction of recombinant VWF concentrate is likely to improve the acceptability of prophylaxis in VWD.

  8. Ages of celiac disease: from changing environment to improved diagnostics.

    PubMed

    Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro

    2011-08-28

    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.

  9. 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

  10. Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

    PubMed Central

    Hmida-Ben Brahim, Dorra; Chourabi, Marwa; Ben Amor, Sana; Harrabi, Imed; Trabelsi, Saoussen; Haddaji-Mastouri, Marwa; Gribaa, Moez; Sassi, Sihem; Gahbiche, Fatma Ezzahra; Lamouchi, Turkia; Mougou-Zereli, Soumaya; Ben Ammou, Sofiane; Saad, Ali

    2014-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population. PMID:25254119

  11. Management of women with Gaucher disease in the reproductive age.

    PubMed

    Rosenbaum, Hanna

    2015-02-01

    Gaucher disease (GD) is a lysosomal disorder caused by inherited deficiency of glucocerebrosidase, resulting in the accumulation of glucocerebroside in macrophages, termed "Gaucher cells" (GCs), leading to multiorgan involvement, with hepatosplenomegaly, cytopenias, pulmonary hypertension and osseous complications. The characteristic feature of GD is the organ GCs infiltration compromising their function by inducing local inflammation, infarcts and fibrosis. Enzyme replacement therapy (ERT) available for over two decades improves hematological abnormalities, reverses the visceromegaly, ameliorates bone symptoms and prevents further skeletal complications. GD affects most female events during the reproductive age, particularly, fertility, pregnancy, delivery and puerperium. While pregnancy in GD may exacerbate disease manifestations, the disease may have deleterious effect on female reproductive health milestones. ERT has a beneficial effect on the pregnancy outcome in terms of the risk of spontaneous abortion and GD-related complications, particularly bleeding during delivery and postpartum. Treatment approaches and management aspects of reproductive age events are reviewed hereby, with a focus on the outcome improvement of pregnancies, deliveries and postpartum period in GD patients.

  12. Aging and infectious diseases in the developing world.

    PubMed

    Gavazzi, Gaëtan; Herrmann, Francois; Krause, Karl-Heinz

    2004-07-01

    Although demographic aging does not remain restricted to industrialized countries, the medical challenge arising from the aging population will be distinct in the developing world. This is particularly true with respect to infectious diseases, which have a distinct spectrum in the elderly population, as well as a greater overall relevance in the developing world. Tropical diseases have a specific presentation and epidemiology in elderly patients. Infectious diseases with a worldwide distribution impact elderly patients in the developing world in a specific manner, which is most obvious with respect to human immunodeficiency virus and tuberculosis but is also true with respect to "trivial" manifestations of infection, such as diarrhea and pneumonia. Malnutrition contributes in a major way to the immunodeficiency of elderly patients in the developing world. Poorly controlled use of antimicrobial drugs leads to multidrug-resistant microorganisms, which, together with the limited resources available for drug treatment, makes appropriate treatment of infections in elderly patients in developing countries very difficult. Infections in elderly patients will have an increasing impact on the public health and economy of developing countries.

  13. 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.

  14. Developmental origin of age-related coronary artery disease

    PubMed Central

    Wei, Ke; Díaz-Trelles, Ramon; Liu, Qiaozhen; Diez-Cuñado, Marta; Scimia, Maria-Cecilia; Cai, Wenqing; Sawada, Junko; Komatsu, Masanobu; Boyle, Joseph J.; Zhou, Bin; Ruiz-Lozano, Pilar; Mercola, Mark

    2015-01-01

    Aim Age and injury cause structural and functional changes in coronary artery smooth muscle cells (caSMCs) that influence the pathogenesis of coronary artery disease. Although paracrine signalling is widely believed to drive phenotypic changes in caSMCs, here we show that developmental origin within the fetal epicardium can have a profound effect as well. Methods and results Fluorescent dye and transgene pulse-labelling techniques in mice revealed that the majority of caSMCs are derived from Wt1+, Gata5-Cre+ cells that migrate before E12.5, whereas a minority of cells are derived from a later-emigrating, Wt1+, Gata5-Cre− population. We functionally evaluated the influence of early emigrating cells on coronary artery development and disease by Gata5-Cre excision of Rbpj, which prevents their contribution to coronary artery smooth muscle cells. Ablation of the Gata5-Cre+ population resulted in coronary arteries consisting solely of Gata5-Cre− caSMCs. These coronary arteries appeared normal into early adulthood; however, by 5–8 months of age, they became progressively fibrotic, lost the adventitial outer elastin layer, were dysfunctional and leaky, and animals showed early mortality. Conclusion Taken together, these data reveal heterogeneity in the fetal epicardium that is linked to coronary artery integrity, and that distortion of the coronaries epicardial origin predisposes to adult onset disease. PMID:26054850

  15. 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.

  16. 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.

  17. The impact of inflammatory rheumatic diseases on the presentation, severity, and outcome of acute coronary syndrome.

    PubMed

    Ben-Zvi, Ilan; Goldenberg, Ilan; Matetzky, Shlomi; Grossman, Chagai; Elis, Avishay; Gavrielov-Yusim, Natalie; Livneh, Avi

    2016-01-01

    Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case-control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to 120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7% in the study and control group, respectively, p > 0.05), re-hospitalization (20 vs. 21.1%, respectively, p > 0.05), and severe congestive heart failure (7.7 vs. 6.9%, respectively, p > 0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality.

  18. 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.

  19. 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

  20. Lack of Evidence of Increased West Nile Virus Disease Severity in the United States in 2012

    PubMed Central

    Lindsey, Nicole P.; Staples, J. Erin; Delorey, Mark J.; Fischer, Marc

    2014-01-01

    In the United States, West Nile virus (WNV) causes annual seasonal outbreaks that fluctuate in size and scope. There was a large multistate outbreak of WNV in 2012, with more human disease cases reported nationally than any year since 2003. We evaluated national surveillance data to determine if the higher number of WNV cases reported in 2012 was associated with changes in the epidemiology or severity of disease compared with 2004–2011. Despite an increased incidence of neuroinvasive disease in 2012, national surveillance data showed no evidence of changes in epidemiology or increased disease severity compared with the previous 8 years. PMID:24218412

  1. 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…

  2. 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.

  3. 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

  4. 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

  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.

  6. National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

    PubMed

    Baird, Kristin; Steinberg, Seth M; Grkovic, Lana; Pulanic, Drazen; Cowen, Edward W; Mitchell, Sandra A; Williams, Kirsten M; Datiles, Manuel B; Bishop, Rachel; Bassim, Carol W; Mays, Jacqueline W; Edwards, Dean; Cole, Kristen; Avila, Daniele N; Taylor, Tiffany; Urban, Amanda; Joe, Galen O; Comis, Leora E; Berger, Ann; Stratton, Pamela; Zhang, Dan; Shelhamer, James H; Gea-Banacloche, Juan C; Sportes, Claude; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2013-04-01

    Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/μL, HR = 3.95; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this

  7. Genomewide association study for onset age in Parkinson disease

    PubMed Central

    Latourelle, Jeanne C; Pankratz, Nathan; Dumitriu, Alexandra; Wilk, Jemma B; Goldwurm, Stefano; Pezzoli, Gianni; Mariani, Claudio B; DeStefano, Anita L; Halter, Cheryl; Gusella, James F; Nichols, William C; Myers, Richard H; Foroud, Tatiana

    2009-01-01

    Background Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age. Methods Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy. Results Meta-analysis across the three studies detected consistent association (p < 1 × 10-5) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 × 10-7) lies between the genes QSER1 and PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 × 10-6) which lies in an intron of the AAK1 gene. This gene is closely related to GAK, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases. Conclusion Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis. PMID:19772629

  8. Complex and differential glial responses in Alzheimer's disease and ageing.

    PubMed

    Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

    2016-01-01

    Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

  9. Dynamics of DNA methylation in aging and Alzheimer's disease.

    PubMed

    Irier, Hasan A; Jin, Peng

    2012-10-01

    Gene expression is modulated by epigenetic factors that come in varying forms, such as DNA methylation, histone modifications, microRNAs, and long noncoding RNAs. Recent studies reveal that these epigenetic marks are important regulatory factors in brain function. In particular, DNA methylation dynamics are found to be essential components of epigenetic regulation in the mammalian central nervous system. In this review, we provide an overview of the literature on DNA methylation in neurodegenerative diseases, with a special focus on methylation of 5-position of cytosine base (5mC) and hydroxymethylation of 5-position of cytosine base (5hmC) in the context of neurodegeneration associated with aging and Alzheimer's disease.

  10. 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.

  11. Severe pulmonary hypertension in lung disease: phenotypes and response to treatment.

    PubMed

    Brewis, Melanie J; Church, Alistair C; Johnson, Martin K; Peacock, Andrew J

    2015-11-01

    Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO) group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery pressure ≥35 mmHg is reported in only a small proportion. Whether these should be treated as patients in WHO group 1 (i.e. pulmonary arterial hypertension) with PH-targeted therapies is unknown. We compared the phenotypic characteristics and outcomes of 118 incident patients with severe PH and lung disease with 74 idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with pulmonary vasodilators. Lung disease patients were older, more hypoxaemic, and had lower gas transfer, worse New York Heart Association functional class and lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those with lung disease was driven by the interstitial lung disease (ILD) cohort. In contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease did not lead to improvement in 6MWD or functional class, but neither was deterioration seen. NT-proBNP decreased from 2200 to 1596 pg·mL(-1) (p=0.015). Response varied by lung disease phenotype, with poorer outcomes in patients with ILD and emphysema with preserved forced expiratory volume in 1 s. Further study is required to investigate whether vasodilator therapy may delay disease progression in severe PH with lung disease.

  12. 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.

  13. Dupuytren disease: an evolving understanding of an age-old disease.

    PubMed

    Black, Eric M; Blazar, Philip E

    2011-12-01

    Dupuytren disease, a clinical entity originally described more than 400 years ago, is a progressive disease of genetic origin. Excessive myofibroblast proliferation and altered collagen matrix composition lead to thickened and contracted palmar fascia; the resultant digital flexion contractures may severely limit function. The pathophysiology is multifactorial and remains a topic of research and debate. Genetic predisposition, trauma, inflammatory response, ischemia, and environment, as well as variable expression of proteins and growth factors within the local tissue, all play a role in the disease process. Common treatments of severe disease include open fasciectomy or fasciotomy. These procedures may be complicated by the complex anatomic relationships between cords (pathologic contracted fascia) and adjacent neurovascular structures. Recent advances in the management of Dupuytren disease involve less invasive treatments, such as percutaneous needle fasciotomy and injectable collagenase Clostridium histolyticum. Postoperative management focuses on minimizing the cellular response of cord disruption and maximizing range of motion through static or dynamic extension splinting.

  14. 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

  15. The type of dietary fat affects the severity of autoimmune disease in NZB/NZW mice.

    PubMed Central

    Alexander, N. J.; Smythe, N. L.; Jokinen, M. P.

    1987-01-01

    The type of dietary fat dramatically affects the onset of autoimmune disease in lupus-prone female New Zealand Black/New Zealand White F1 (B/W) mice. Disease development was strikingly slowed in mice fed a diet containing quantities of omega-3 fatty acids (fish oil, FO). By 10 months of age, 94% of the FO mice were still living, whereas all the mice fed a saturated fat diet (lard,L) were dead. Those mice fed a corn oil (CO) diet were intermediate with 35% alive at the 10-month time evaluation. Long after the L and CO groups had succumbed to glomerulonephritis, the FO group had negligible proteinuria. Both B and T cell function, particularly antibody production and resultant circulating immune complex (CIC) levels, were modified by the type of dietary fat. FO mice exhibited lower levels of anti-ds-DNA and lower levels of CICs than L or CO mice. B/W antibody response to a T-independent antigen (DNP-dextran) was enhanced at 8 months of age in FO mice, whereas it was suppressed in L mice. T-dependent (sheep red blood cell) responses at that time period were reduced in all the diet groups, a reflection of the reduced numbers of accessory T cells as determined by FACS analysis. The natural killer (NK) response to YAC-1 cells decreased in the L group from 5 to 9 months of age but remained unchanged in the CO and FO groups. Severe glomerulonephritis was the most common histopathologic finding in the L and CO groups. Arteritis was found in the spleens of nearly all the L and CO mice. Arteritis of the heart, colon and intestine, stomach, kidney, and liver were also seen principally in the L mice. In contrast, most FO mice had minimal to mild glomerulonephritis and no or minimal arteritis in the spleen. It is likely omega-3 fatty acids of fish oil reduce immune-complex-induced glomerulonephritis through production of prostaglandin metabolites with attenuated activity and/or through altering cell membrane structure and fluidity, which may, in turn, affect the responsiveness of

  16. 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

  17. Ancillary testing, diagnostic/classification criteria and severity grading in Behçet disease.

    PubMed

    Okada, Annabelle A; Stanford, Miles; Tabbara, Khalid

    2012-12-01

    Since there is no pathognomonic clinical sign or laboratory test to distinguish Behçet disease from other uveitic entities, the diagnosis must be made based on characteristic ocular and systemic findings in the absence of evidence of other disease that can explain the findings. Ancillary tests, including ocular and brain imaging studies, are used to assess the severity of intraocular inflammation and systemic manifestations of Behçet disease, to identify latent infections and other medical conditions that might worsen with systemic treatment, and to monitor for adverse effects of drugs used. There are two diagnostic or classification criteria in general use by the uveitis community, one from Japan and one from an international group; both rely on a minimum number and/or combination of clinical findings to identify Behçet disease. Finally, several grading schemes have been proposed to assess severity of ocular disease and response to treatment.

  18. [Severe chronic pain with allodynia in Parkinson's disease: a case report].

    PubMed

    Ito, S; Asahina, M; Asahina, M; Oki, T; Hattori, T

    2001-01-01

    We report a 61-year-old man with Parkinson's disease, who had a 3-year history of severe chronic pain with allodynia in the lower extremities prior to motor symptoms. He always had tingling pain around the ankles, and tactile sensation induced severe burning pain expanding to the toes and thighs, so his pain was considered to be allodynia. Pain and motor symptoms were ameliorated by L-dopa therapy and exacerbated by withdrawal of L-dopa. Pain is known to occur in Parkinson's disease, but severe pain rarely occurs. To our knowledge, allodynia, which is usually recognized in causalgia or reflex sympathetic dystrophy, has never been reported in Parkinson's disease. Patients with Parkinson's disease may complain severe causalgia-like pain as an initial symptom.

  19. 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

  20. Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1.

    PubMed

    Grosse, Scott D; Lam, Wendy K K; Wiggins, Lisa D; Kemper, Alex R

    2017-01-26

    The US Secretary of Health and Human Services recommended in February 2016 that mucopolysaccharidosis type 1 (MPS I) be added to the recommended uniform screening panel for state newborn screening programs. One of the key factors in this decision was the evidence suggesting that earlier treatment with hematopoietic cell transplantation (HCT) for the most severe form, Hurler syndrome (MPS IH), would lead to improved cognitive outcomes. Consistent evidence from peer-reviewed studies suggests that transplantation in the first year of life is associated with improved developmental quotient or intelligence quotient and continued cognitive growth, with earlier age of treatment associated with improved outcomes. However, available evidence suggests that cognitive functioning and attention can still lag behind unaffected age-matched children, leading to the need for special education services. Verbal and nonverbal cognitive abilities outcomes may be affected differently by HCT. With the recent addition of MPS I to the recommended uniform screening panel, future work is needed to evaluate the impact of earlier, presymptomatic detection and treatment initiation and other supportive therapies on cognitive outcomes.Genet Med advance online publication 26 January 2017Genetics in Medicine (2017); doi:10.1038/gim.2016.223.

  1. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    PubMed Central

    Bacalhau, Sílvia; Freitas, Cristina; Valente, Rosalina; Barata, Deolinda; Neves, Conceição; Schäfer, Katrin; Lubatschofski, Annelie; Schulz, Ansgar; Neves, João Farela

    2011-01-01

    In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highlighting the specific strategies adopted. PMID:22110512

  2. Antibody Avidity Following Secondary Dengue Virus Type 2 Infection Across a Range of Disease Severity

    PubMed Central

    Lau, Louis; Green, Angela M.; Balmaseda, Angel; Harris, Eva

    2015-01-01

    Background The four dengue virus serotypes (DENV1-4) are responsible for the most prevalent mosquito-borne viral illness in humans. DENV causes a spectrum of disease from self-limiting dengue fever (DF) to severe, life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Antibodies from one infection can contribute to either protection or increased disease severity in a subsequent infection with a distinct DENV serotype. The effectiveness of the antibody response is modulated by both the affinity and avidity of the antibody/antigen interaction. Objectives We investigated how antibody avidity developed over time following secondary DENV2 infection across different disease severities. Study design We analyzed sera from 42 secondary DENV2-infected subjects (DF, n=15; DHF, n=16; DSS, n=11) from a pediatric hospital-based dengue study in Nicaragua. IgG avidity against DENV2 virions was measured in samples collected during acute and convalescent phases as well as 3, 6, and 18 months post-illness using a urea enzyme-linked immunosorbent assay. Results The data show a significant increase in avidity from acute to convalescent phase followed by a decrease from convalescent phase to 3 months post-symptom onset, then a plateau. Linear regression analysis comparing antibody avidity between disease severity groups over time indicate that individuals with more severe disease (DHF/DSS) experienced greater decay in antibody avidity over time compared to less severe disease (DF), and ROC curve analysis showed that at 18 months post-illness, lower avidity was associated with previously having experienced more severe disease. Conclusions These data suggest that increased dengue disease severity is associated with lower antibody avidity at later time-points post-illness. PMID:26209381

  3. Decompensation of chronic stable alcoholic liver disease by severe exfoliative dermatitis.

    PubMed

    Shawcross, Debbie L; Mookerjee, Rajeshwar P; Jalan, Rajiv

    2003-04-01

    Of the numerous precipitants of hepatic decompensation in chronic liver disease, there are no reports in the literature documenting an acute decompensation following an acute episode of severe dermatitis. This case highlights the haemodynamic consequences of a severe flare up of exfoliative dermatitis in a patient with stable chronic alcoholic liver disease, speculates on the mechanism by which this may provoke clinical decompensation and the impact this may have upon liver failure.

  4. 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

  5. Effects of Host Resistance and Shading Density on the Disease Severity of Hydrangea Leaf Spot

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leaf spot, caused by Cercospora hydrangeae Ellis & Everh., is a common disease of bigleaf hydrangea (Hydrangea macrophylla) in ornamental nurseries and gardens. Experiments were conducted to determine the effects of cultivars and shading density on the disease severity. Two year-old plants of six bi...

  6. 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.…

  7. Severe Acute Respiratory Distress Syndrome during Infliximab Therapy in a Patient with Crohn Disease

    PubMed Central

    Schoehl, Johanna; Mechie, Nicolae-Catalin; Schwoerer, Harald; Moerer, Onnen; Quintel, Michael; Buck, Cordula; Ellenrieder, Volker; Neesse, Albrecht; Amanzada, Ahmad

    2016-01-01

    The occurrence of a noninfectious interstitial lung disease is a rare but life-threatening side effect of infliximab, an antitumor necrosis factor alpha antibody. The following case report of a patient with Crohn disease shows an extremely dramatic progression to a severe acute respiratory distress syndrome. PMID:27920644

  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. Disease onset and aging in the world of circular RNAs.

    PubMed

    Maiese, Kenneth

    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.

  10. Effects of age, gender, and gonadectomy on neurochemistry and behavior in animal models of Parkinson's disease.

    PubMed

    Tamás, Andrea; Lubics, Andrea; Lengvári, István; Reglodi, Dóra

    2006-04-01

    The effects of aging and gender on the neurochemistry of the dopaminergic system have been studied extensively; however, data on comparative behavioral consequences of lesions of the dopaminergic system in aging and in female animals are limited. This study presents experimental results on the behavioral and morphological outcome in young, aging, and gonadectomized male and female rats in the 6-OHDA model of Parkinson's disease. Both young and aging male animals were more susceptible to 6-OHDA than females: female rats had significantly less dopaminergic cell loss and showed a higher degree of behavioral recovery. Although the dopaminergic cell loss was only slightly more in the aging rats of the same sex, they showed more severe behavioral deficits in both gender groups. Ovariectomy did not significantly influence the dopaminergic cell loss, but behavioral recovery was worse when compared to non-ovariectomized females. In contrast, castrated males had significantly less dopaminergic cell loss than non-castrated males, but the behavioral recovery was not significantly better. The obtained results are discussed in light of the available literature on the age and gender differences in animals models of Parkinson's disease.

  11. 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

  12. Differences in initial stroke severity between Mexican Americans and non-Hispanic whites vary by age: the Brain Attack Surveillance in Corpus Christi (BASIC) project

    PubMed Central

    Wing, Jeffrey J.; Baek, Jonggyu; Sánchez, Brisa N.; Lisabeth, Lynda D.; Smith, Melinda A.; Morgenstern, Lewis B.; Zahuranec, Darin B.

    2014-01-01

    Background A wide variety of racial and ethnic disparities in stroke epidemiology and treatment have been reported. Race-ethnic differences in initial stroke severity may be one important determinant of differences in outcome after stroke. The overall goal of this study was to move beyond ethnic comparisons in the mean or median severity, and instead investigate ethnic differences in the entire distribution of initial stroke severity. Additionally, we investigated whether age modifies the relationship between ethnicity and initial stroke severity as this may be an important determinant of racial differences in outcome after stroke. Methods Ischemic stroke cases were identified from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project. National Institutes of Health Stroke Scale (NIHSS) was determined from the medical record or abstracted from the chart. Ethnicity was reported as Mexican American (MA) or non-Hispanic white (NHW). Quantile regression was used to model the distribution of NIHSS score by age category (45–59, 60–74, 75+) to test whether ethnic differences exist over different quantiles of NIHSS (5 percentile increments). Crude models examined the interaction between age category and ethnicity; models were then adjusted for history of stroke/transient ischemic attack, hypertension, atrial fibrillation, coronary artery disease, and diabetes. Results were adjusted for multiple comparisons. Results There were 4,366 ischemic strokes, with median age 72 years (IQR: 61–81), 55% MA and median NIHSS of 4 (IQR: 2–8). MAs were younger, more likely to have a history of hypertension and diabetes, but less likely to have atrial fibrillation compared to NHWs. In the crude model, the ethnicity-age interaction was not statistically significant. After adjustment, the ethnicity-age interaction became significant at the 85th and 95th percentiles of NIHSS distribution. MAs in the younger age category (45–59) were significantly less

  13. 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

  14. Kawasaki disease shock syndrome: a rare and severe complication of Kawasaki disease.

    PubMed

    Çakan, Mustafa; Gemici, Hakan; Aktay-Ayaz, Nuray; Keskindemirci, Gonca; Bornaun, Helen; İkizoğlu, Tarkan; Çeliker, Alpay

    2016-01-01

    Kawasaki disease is an acute systemic vasculitis that occurs most commonly in young children. It affects medium-sized muscular arteries and the coronary arteries are the predominant site of involvement. Morbidity and mortality is generally due to coronary artery aneurysms that develop during the chronic phase. Although it is well known that Kawasaki disease can cause myocarditis, tachycardia and heart failure during acute stage, Kawasaki disease shock syndrome has been recently described. It is characterized by hypotension, signs and symptoms of poor perfusion and a shock-like state. Herein we describe two cases of Kawasaki disease shock syndrome that were treated in the pediatric intensive care unit and followed a course without morbidity or mortality.

  15. 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.

  16. Is Mitral Annular Calcification Associated With Atherosclerotic Risk Factors and Severity and Complexity of Coronary Artery Disease?

    PubMed

    Bhatt, Hemal; Sanghani, Dharmesh; Julliard, Kell; Fernaine, George

    2015-08-01

    We assessed the association of mitral annular calcification (MAC) with atherosclerotic risk factors and severity and complexity of coronary artery disease (CAD). Cardiac catheterization reports and electronic medical records from 2010 to 2011 were retrospectively reviewed. A total of 481 patients were divided into 2 groups: MAC present (209) and MAC absent (272). All major cardiovascular risk factors, comorbidities, and coronary lesion characteristics were included. On linear regression analysis, age (P = .001, β 1.12) and female gender (P = .031, β 0.50) were the independent predictors of MAC. Mitral annular calcification was not independently associated with the presence of lesions with >70% stenosis (P = .283), number of obstructive vessels (P = .469), lesions with 50% to 70% stenosis (P = .458), and Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score (P = .479). Mitral annular calcification is probably a benign marker of age-related degenerative changes in the heart independent of the severity and complexity of CAD.

  17. Systemic oxidative stress associated with the neurological diseases of aging.

    PubMed

    Serra, Jorge A; Domínguez, Raúl O; Marschoff, Enrique R; Guareschi, Eduardo M; Famulari, Arturo L; Boveris, Alberto

    2009-12-01

    Markers of oxidative stress were measured in blood samples of 338 subjects (965 observations): Alzheimer's, vascular dementia, diabetes (type II) superimposed to dementias, Parkinson's disease and controls. Patients showed increased thiobarbituric acid reactive substances (+21%; P < 0.05), copper-zinc superoxide dismutase (+64%; P < 0.001) and decreased antioxidant capacity (-28%; P < 0.001); pairs of variables resulted linearly related across groups (P < 0.001). Catalase and glutathione peroxidase, involved in discrimination between diseases, resulted non-significant. When diabetes is superimposed with dementias, changes resulted less marked but significant. Also, superoxide dismutase resulted not linearly correlated with any other variable or age-related (pure Alzheimer's peaks at 70 years, P < 0.001). Systemic oxidative stress was significantly associated (P < 0.001) with all diseases indicating a disbalance in peripheral/adaptive responses to oxidative disorders through different free radical metabolic pathways. While other changes - methionine cycle, insulin correlation - are also associated with dementias, the responses presented here show a simple linear relation between prooxidants and antioxidant defenses.

  18. 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

  19. 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...

  20. Severe hemolytic disease of the premature newborn due to RH1 incompatibility: a case report

    PubMed Central

    UWINGABIYE, JEAN; ZAHID, HAFID; LABRINI, FAYÇAL; EL KHAZRAJI, ABDELHAK; YAHYAOUI, ANASS; HADEF, RACHID; MESSAOUDI, NEZHA

    2016-01-01

    We report a case of dramatic outcome of severe hemolytic disease in a newborn due to RH1 incompatibility. A newborn with A RH1 blood group was admitted in the Mohammed V Military Teaching Hospital for the problem of hydrops fetalis associated with RH1 incompatibility. The blood group of his mother, aged 31, was AB RH1-negative and that of his 37 year old father was A RH1. The mother had a history of 4 term deliveries, 3 abortions, and 1 living child. There was no prevention by anti-D immunoglobulin postpartum. The mother’s irregular agglutinin test was positive and the pregnancy was poorly monitored. The laboratory tests of the newborn showed a high total serum bilirubin level (30 mg/L) and macrocytic regenerative anemia (Hemoglobin=4 g/dL, mean corpuscular volume = 183 fL, reticulocytes count =176600/m3). The blood smear showed 1256 erythroblasts per 100 leukocytes, Howell–Jolly bodies and many macrocytes. The direct antiglobulin test was positive. He was transfused with red blood cell concentrates and treated with conventional phototherapy. The evolution was unfavourable; he died three days after the death of his mother. The monitoring of these high-risk pregnancies requires specialized centers and a close collaboration between the gynaecologist and the blood transfusion specialist to strengthen the prevention, as well as clinico-biological monitoring in patients with a history of RH1 fetomaternal alloimunization. PMID:27857529

  1. Predicting Ebola Severity: A Clinical Prioritization Score for Ebola Virus Disease

    PubMed Central

    Okoni-Williams, Harry Henry; Suma, Mohamed; Mancuso, Brooke; Al-Dikhari, Ahmed; Faouzi, Mohamed

    2017-01-01

    Background Despite the notoriety of Ebola virus disease (EVD) as one of the world’s most deadly infections, EVD has a wide range of outcomes, where asymptomatic infection may be almost as common as fatality. With increasingly sensitive EVD diagnosis, there is a need for more accurate prognostic tools that objectively stratify clinical severity to better allocate limited resources and identify those most in need of intensive treatment. Methods/Principal Findings This retrospective cohort study analyses the clinical characteristics of 158 EVD(+) patients at the GOAL-Mathaska Ebola Treatment Centre, Sierra Leone. The prognostic potential of each characteristic was assessed and incorporated into a statistically weighted disease score. The mortality rate among EVD(+) patients was 60.8% and highest in those aged <5 or >25 years (p<0.05). Death was significantly associated with malaria co-infection (OR = 2.5, p = 0.01). However, this observation was abrogated after adjustment to Ebola viral load (p = 0.1), potentially indicating a pathologic synergy between the infections. Similarly, referral-time interacted with viral load, and adjustment revealed referral-time as a significant determinant of mortality, thus quantifying the benefits of early reporting as a 12% mortality risk reduction per day (p = 0.012). Disorientation was the strongest unadjusted predictor of death (OR = 13.1, p = 0.014) followed by hiccups, diarrhoea, conjunctivitis, dyspnoea and myalgia. Including these characteristics in multivariate prognostic scores, we obtained a 91% and 97% ability to discriminate death at or after triage respectively (area under ROC curve). Conclusions/Significance This study proposes highly predictive and easy-to-use prognostic tools, which stratify the risk of EVD mortality at or after EVD triage. PMID:28151955

  2. Histology and immunohistochemistry of severe inflammatory bowel disease versus lymphoma in the ferret (Mustela putorius furo).

    PubMed

    Watson, Megan K; Cazzini, Paola; Mayer, Joerg; Gottdenker, Nicole; Reavill, Drury; Parry, Nicola; Fox, James G; Sakamoto, Kaori

    2016-05-01

    Inflammatory bowel disease (IBD) is a common disorder of ferrets (Mustela putorius furo) that may progress to lymphoma. Although routine histology is used to distinguish between these diseases, misclassifications may occur. Immunohistochemistry (IHC) is commonly used to distinguish between IBD and lymphoma in small animals. The objective of our study was to determine the agreement in the diagnosis reached solely using hematoxylin and eosin (HE)-stained, full-thickness sections versus using a combination of HE and IHC. Enteric sections from 44 ferrets previously diagnosed with IBD or intestinal lymphoma and 3 control ferrets were analyzed by pathologists with expertise in ferrets. A pathologist blinded to the original diagnosis assessed the same HE-stained sections. Analysis was then repeated using HE sections in parallel with sections stained using antibodies against CD3 and CD79a. No significant difference was found between the original HE diagnosis and the HE diagnosis reached by the blinded pathologist (p = 0.91) or between the blinded pathologist's HE versus HE with IHC diagnosis (p = 0.16). In the 2 cases where disagreement was present, IHC was pivotal in reaching a final diagnosis. There was no significant age (p = 0.29) difference between diagnoses; however, significantly more male ferrets were affected with IBD than females (p = 0.004). Immunophenotype of the lymphoma was not correlated with predilection for location in the intestinal wall (p = 0.44). Results suggest that although IHC is not necessary to distinguish IBD from intestinal lymphoma in ferrets, it can be useful a definitive diagnosis in cases of severe IBD.

  3. Virulence characteristics accounting for fire blight disease severity in apple trees and seedlings.

    PubMed

    Lee, Steven A; Ngugi, Henry K; Halbrendt, Noemi O; O'Keefe, Grace; Lehman, Brian; Travis, James W; Sinn, Judith P; McNellis, Timothy W

    2010-06-01

    The gram-negative bacterium Erwinia amylovora is the causal agent of fire blight, the most destructive bacterial disease of rosaceous plants, including apple and pear. Here, we compared the virulence levels of six E. amylovora strains (Ea273, CFBP1367, Ea581a, E2002a, E4001a, and HKN06P1) on apple trees and seedlings. The strains produced a range of disease severity, with HKN06P1 producing the greatest disease severity in every assay. We then compared virulence characteristic expression among the six strains, including growth rates in immature apple fruit, amylovoran production, levansucrase activity, biofilm formation, carbohydrate utilization, hypersensitive cell death elicitation in tobacco leaves, and protein secretion profiles. Multiple regression analysis indicated that three of the virulence characteristics (amylovoran production, biofilm formation, and growth in immature apple fruit) accounted for >70% of the variation in disease severity on apple seedlings. Furthermore, in greenhouse-grown 'Gala' trees, >75% of the variation in disease severity was accounted for by five of the virulence characteristics: amylovoran production, biofilm formation, growth in immature apple fruit, hypersensitive cell death elicitation, and sorbitol utilization. This study demonstrates that virulence factor expression levels account for differences in disease severity caused by wild isolates of E. amylovora on apple trees.

  4. 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.

  5. Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein.

    PubMed

    Rhee, Eun-Jung; Lee, Won-Young; Kim, Se-Yeon; Kim, Byung-Jin; Sung, Ki-Chul; Kim, Bum-Su; Kang, Jin-Ho; Oh, Ki-Won; Oh, Eun-Sook; Baek, Ki-Hyun; Kang, Moo-Ii; Woo, Hee-Yeon; Park, Hyo-Soon; Kim, Sun-Woo; Lee, Man-Ho; Park, Jung-Roe

    2005-03-01

    OPG (osteoprotegerin) is an inhibitor of osteoclastogenesis and recent work suggests it has a role in atherosclerosis. Therefore we measured serum OPG levels in patients with coronary artery disease, compared the serum OPG levels among the different groups according to the number of stenotic vessels and determined whether there was any correlation with aortic calcification, LV (left ventricular) mass index and serum CRP (C-reactive protein) levels. Subjects (n=100; mean age, 57 years) who underwent coronary angiograms were enrolled. Blood pressure, body mass index, fasting blood glucose, lipid profiles and CRP levels were measured and the LV mass indices were calculated using ECGs. Serum OPG levels were measured by ELISA. The presence of calcification in the aortic notch was checked by a chest X-ray. The subjects were divided into four groups according to the number of stenotic vessels. The mean serum OPG levels increased significantly as the number of stenotic vessels increased, and the mean serum OPG levels were higher in the group with three-vessel disease compared with the groups with no- or one-vessel disease. The mean serum CRP level was significantly higher in the group with three-vessel disease compared with the groups with no-, one- and two-vessel disease. Age and LV mass index showed significant positive correlations with serum OPG levels, although significance was lost after an adjustment for age. Serum CRP levels were positively correlated with serum OPG levels even after an adjustment for age. There were no differences in serum OPG levels according to the presence of fasting hyperglycaemia or aortic calcification. In conclusion, serum OPG level was related to the severity of stenotic coronary arteries and serum CRP levels. LV mass indices showed no significant correlation with OPG levels. The precise mechanism for the role of OPG in atherosclerosis needs to be investigated further.

  6. 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.

  7. 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

  8. Parasite Biomass-Related Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Vivax Malaria

    PubMed Central

    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. 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

  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. Efficacy and Safety of Dupilumab in Patients ≥12 to <18 Years of Age, With Moderate-to-Severe Atopic Dermatitis

    ClinicalTrials.gov

    2017-02-13

    Moderate-to-Severe Atopic Dermatiti; Dermatitis, Dermatitis Atopic; Eczema, Skin Diseases, Skin; Diseases Genetic, Genetic; Diseases Inborn, Skin; Disease, Eczematous Skin; Hypersensitivity, Immediate; Hypersensitivity, Immune System Diseases; Dermatitis, Atopic

  12. Effects of polyphenols on brain ageing and Alzheimer's disease: focus on mitochondria.

    PubMed

    Schaffer, Sebastian; Asseburg, Heike; Kuntz, Sabine; Muller, Walter E; Eckert, Gunter P

    2012-08-01

    The global trend of the phenomenon of population ageing has dramatic consequences on public health and the incidence of neurodegenerative diseases. Physiological changes that occur during normal ageing of the brain may exacerbate and initiate pathological processes that may lead to neurodegenerative disorders, especially Alzheimer's disease (AD). Hence, the risk of AD rises exponentially with age. While there is no cure currently available, sufficient intake of certain micronutrients and secondary plant metabolites may prevent disease onset. Polyphenols are highly abundant in the human diet, and several experimental and epidemiological evidences indicate that these secondary plant products have beneficial effects on AD risks. This study reviews current knowledge on the potential of polyphenols and selected polyphenol-rich diets on memory and cognition in human subjects, focusing on recent data showing in vivo efficacy of polyphenols in preventing neurodegenerative events during brain ageing and in dementia. Concentrations of polyphenols in animal brains following oral administration have been consistently reported to be very low, thus eliciting controversial discussion on their neuroprotective effects and potential mechanisms. Whether polyphenols exert any direct antioxidant effects in the brain or rather act by evoking alterations in regulatory systems of the brain or even the body periphery is still unclear. To understand the mechanisms behind the protective abilities of polyphenol-rich foods, an overall understanding of the biotransformation of polyphenols and identification of the various metabolites arising in the human body is also urgently needed.

  13. A 'Disease Severity Index' to identify individuals with Subjective Memory Decline who will progress to mild cognitive impairment or dementia.

    PubMed

    Ferreira, Daniel; Falahati, Farshad; Linden, Cecilia; Buckley, Rachel F; Ellis, Kathryn A; Savage, Greg; Villemagne, Victor L; Rowe, Christopher C; Ames, David; Simmons, Andrew; Westman, Eric

    2017-03-13

    Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer's disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials.

  14. Resveratrol: a multitargeted agent for age-associated chronic diseases.

    PubMed

    Harikumar, Kuzhuvelil B; Aggarwal, Bharat B

    2008-04-15

    Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g; NFkappaB, STAT3, HIF-1alpha, beta-catenin and PPAR-gamma), suppress the expression of antiapoptotic gene products (e.g; Bcl-2, Bcl-X(L), XIAP and survivin), inhibit protein kinases (e.g; src, PI3K, JNK, and AKT), induce antioxidant enzymes (e,g; catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS, and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D, and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating

  15. Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity

    PubMed Central

    Fortney, Kristen; Dobriban, Edgar; Garagnani, Paolo; Pirazzini, Chiara; Monti, Daniela; Mari, Daniela; Atzmon, Gil; Barzilai, Nir; Franceschi, Claudio; Owen, Art B.; Kim, Stuart K.

    2015-01-01

    We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population. Next, we used iGWAS to harness information from 14 meta-analyses of disease and trait GWAS to identify longevity loci in two studies of long-lived humans. In a standard GWAS analysis, only one locus in these studies is significant (APOE/TOMM40) when controlling the false discovery rate (FDR) at 10%. With iGWAS, we identify eight genetic loci to associate significantly with exceptional human longevity at FDR < 10%. We followed up the eight lead SNPs in independent cohorts, and found replication evidence of four loci and suggestive evidence for one more with exceptional longevity. The loci that replicated (FDR < 5%) included APOE/TOMM40 (associated with Alzheimer’s disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease). Our results implicate new loci in longevity and reveal a genetic overlap between longevity and age-related diseases and traits, including coronary artery disease and Alzheimer’s disease. iGWAS provides a new analytical strategy for uncovering SNPs that influence extreme longevity, and can be applied more broadly to boost power in other studies of complex phenotypes. PMID:26677855

  16. Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity.

    PubMed

    Fortney, Kristen; Dobriban, Edgar; Garagnani, Paolo; Pirazzini, Chiara; Monti, Daniela; Mari, Daniela; Atzmon, Gil; Barzilai, Nir; Franceschi, Claudio; Owen, Art B; Kim, Stuart K

    2015-12-01

    We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population. Next, we used iGWAS to harness information from 14 meta-analyses of disease and trait GWAS to identify longevity loci in two studies of long-lived humans. In a standard GWAS analysis, only one locus in these studies is significant (APOE/TOMM40) when controlling the false discovery rate (FDR) at 10%. With iGWAS, we identify eight genetic loci to associate significantly with exceptional human longevity at FDR < 10%. We followed up the eight lead SNPs in independent cohorts, and found replication evidence of four loci and suggestive evidence for one more with exceptional longevity. The loci that replicated (FDR < 5%) included APOE/TOMM40 (associated with Alzheimer's disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease). Our results implicate new loci in longevity and reveal a genetic overlap between longevity and age-related diseases and traits, including coronary artery disease and Alzheimer's disease. iGWAS provides a new analytical strategy for uncovering SNPs that influence extreme longevity, and can be applied more broadly to boost power in other studies of complex phenotypes.

  17. Cervical flexion myelopathy in a patient showing apparent long tract signs: a severe form of Hirayama disease.

    PubMed

    Sakai, Kenji; Ono, Kenjiro; Okamoto, Yoshiyuki; Murakami, Hideki; Yamada, Masahito

    2011-05-01

    We describe an 18-year-old male with cervical flexion myelopathy with Hirayama disease-like features who showed apparent long tract signs. He first experienced insidious-onset hand muscle weakness and atrophy at the age of 15. Subsequently, he developed sensory disturbance in his lower limb. Neurological examination revealed atrophy and weakness in the right hand and forearm, pyramidal signs in the right lower extremity, and disturbance of superficial sensation in the lower left half of the body. Cervical magnetic resonance images and computed tomographic myelography revealed anterior displacement with compression of the cervical cord in flexion that was more apparent in the right side. The right side of the cervical cord showed severe atrophy. The mechanisms of myelopathy in our patient appeared to be same as that of "tight dural canal in flexion," which has been reported to be the mechanism of juvenile muscular atrophy of the unilateral upper extremity (Hirayama disease). Patients with Hirayama disease generally show minimal sensory signs and no pyramidal signs. An autopsy case of Hirayama disease revealed confined necrosis of the cervical anterior horn without obvious changes in the white matter. Our patient's disease progression suggests that cervical flexion myelopathy patients with severe cervical cord compression in flexion may develop extensive cervical cord injury beyond the anterior horn.

  18. 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

  19. Interleukin-6 in Aging and Chronic Disease: A Magnificent Pathway

    PubMed Central

    Maggio, Marcello; Guralnik, Jack M.; Longo, Dan L.; Ferrucci, Luigi

    2009-01-01

    The human interleukin IL-6 was originally cloned in 1986. In 1993, William Ershler, in his article “IL-6: A Cytokine for Gerontologists,” indicated IL-6 as one of the main signaling pathways modulating the complex relationship between aging and chronic morbidity. Over the last 12 years, our understanding of the role of IL-6 in human physiology and pathology has substantially grown, although some of the questions originally posed by Ershler are still debated. In this review, we will focus on IL-6 structure, IL-6 signaling, and trans signaling pathways, and the role of IL-6 in geriatric syndromes and chronic disease. In the final section of this review, we dissect the critical elements of the IL-6 signaling pathway and point out targets for intervention that are targeted by emerging drugs, some still on the horizon and others already being tested in clinical trials. PMID:16799139

  20. The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Dichtel, Laura E; Corey, Kathleen E; Misdraji, Joseph; Bredella, Miriam A; Schorr, Melanie; Osganian, Stephanie A; Young, Brian J; Sung, Joshua C; Miller, Karen K

    2017-01-01

    Objectives: The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies. Methods: A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1. Results: Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2–4 vs. 0–1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels. Conclusions: Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets. PMID

  1. Depressive Symptoms, Cardiac Disease Severity, and Functional Status in Patients With Coronary Artery Disease (from the Heart and Soul Study).

    PubMed

    Schopfer, David W; Regan, Mathilda; Heidenreich, Paul A; Whooley, Mary A

    2016-11-01

    Patient-reported health status is highly valued as a key measure of health care quality, yet little is known about the extent to which it is determined by subjective perception compared with objective measures of disease severity. We sought to compare the associations of depressive symptoms and objective measures of cardiac disease severity with perceived functional status in patients with stable coronary artery disease. We assessed depressive symptoms, severity of cardiovascular disease, and perceived functional status in a cross-sectional study of 1,023 patients with stable coronary artery disease. We compared the extent to which patient-reported functional status was influenced by depressive symptoms versus objective measures of disease severity. We then evaluated perceived functional status as a predictor of subsequent cardiovascular hospitalizations during 8.8 years of follow-up. Patients with depressive symptoms were more likely to report poor functional status than those without depressive symptoms (44% vs 17%; p <0.001). After adjustment for traditional risk factors and co-morbid conditions, independent predictors of poor functional status were depressive symptoms (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.89 to 3.79), poor exercise capacity (OR 2.30, 95% CI 1.65 to 3.19), and history of heart failure (OR 1.61, 95% CI 1.12 to 2.29). Compared with patients who had class I functional status, those with class II functional status had a 96% greater rate (hazard ratio 1.96, 95% CI 1.15 to 3.34) and those with class III or IV functional status had a 104% greater rate (hazard ratio 2.04, 95% CI 1.12 to 3.73) of hospitalization for HF, adjusted for baseline demographic characteristics, co-morbidities, cardiac disease severity, and depressive symptoms. In conclusion, depressive symptoms and cardiac disease severity were independently associated with patient-reported functional status. This suggests that perceived functional status may be as strongly

  2. [Dental caries of the developmental age as a civilization disease].

    PubMed

    Wójcicka, Anna; Zalewska, Magdalena; Czerech, Ewa; Jabłoński, Robert; Grabowska, Stanisława Zyta; Maciorkowska, Elzbieta

    2012-01-01

    According to the definition of the World Health Organization (WHO), dental caries is a local pathological process of the extrasomatic background, leading to enamel decalcification, decomposition of dental hard tissue, and in consequence to formation of a dental cavity. Morbidity of dental caries increases with age, reaching 100% of children, aged from 6 to 7. Poland is one of few European countries where the incidence of dental caries in children did not decrease, despite recommendations of WHO for 2000 year, aimed at the decrease in the incidence of dental caries among 6-year-old children to the level of 50%. The recommendation of WHO for 2015 year is to reduce the incidence of dental caries to 30% among 6-year-olds, i.e., 70% of 6 year-old children should be free of dental caries. Apart from genetic conditioning, inappropriate health behaviors, nutritional habits and gastroesophageal reflux disease influence the development of dental caries. Consumption of 'fast food' and drinking sweetened beverages of low pH contribute markedly to the development of dental caries, decreasing simultaneously consumption of pro healthy foods, including milk and cereals. Taking into consideration perspective clinical examinations of children and adolescents, evaluating the relationship between dental caries and nutritional habits as well as environmental conditioning, the study shows current data about factors, contributing to the incidence of dental caries in children, collected from the literature. The attention was paid to the relationship between dental caries and gastroesophageal reflux disease and the necessity of its early diagnostics and proper treatment.

  3. B10 Cell Frequencies and Suppressive Capacity in Myasthenia Gravis Are Associated with Disease Severity

    PubMed Central

    Yi, John S.; Russo, Melissa A.; Massey, Janice M.; Juel, Vern; Hobson-Webb, Lisa D.; Gable, Karissa; Raja, Shruti M.; Balderson, Kristina; Weinhold, Kent J.; Guptill, Jeffrey T.

    2017-01-01

    Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated disease. The mechanisms for loss of self-tolerance in this disease are not well understood, and recently described regulatory B cell (Breg) subsets have not been thoroughly investigated. B10 cells are a subset of Bregs identified by the production of the immunosuppressive cytokine, interleukin-10 (IL-10). B10 cells are known to strongly inhibit B- and T-cell inflammatory responses in animal models and are implicated in human autoimmunity. In this study, we examined quantitative and qualitative aspects of B10 cells in acetylcholine receptor autoantibody positive MG (AChR-MG) patients and healthy controls. We observed reduced B10 cell frequencies in AChR-MG patients, which inversely correlated with disease severity. Disease severity also affected the function of B10 cells, as B10 cells in the moderate/severe group of MG patients were less effective in suppressing CD4 T-cell proliferation. These results suggest that B10 cell frequencies may be a useful biomarker of disease severity, and therapeutics designed to restore B10 cell frequencies could hold promise as a treatment for this disease through restoration of self-tolerance. PMID:28239367

  4. Non-Dimensional Formulation of Ventricular Work-Load Severity Under Concomitant Heart Valve Disease

    NASA Astrophysics Data System (ADS)

    Dong, Melody; Simon-Walker, Rachael; Dasi, Lakshmi

    2012-11-01

    Current guidelines on assessing the severity of heart valve disease rely on dimensional disease specific measures and are thus unable to capture severity under a concomitant heart valve disease scenario. Experiments were conducted to measure ventricular work-load in an in-house in-vitro left heart simulator. In-house tri-leaflet heart valves were built and parameterized to model concomitant heart valve disease. Measured ventricular power varied non-linearly with cardiac output and mean aortic pressure. Significant data collapse could be achieved by the non-dimensionalization of ventricular power with cardiac output, fluid density, and a length scale. The dimensionless power, Circulation Energy Dissipation Index (CEDI), indicates that concomitant conditions require a significant increase in the amount of work needed to sustain cardiac function. It predicts severity without the need to quantify individual disease severities. This indicates the need for new fluid-dynamics similitude based clinical guidelines to assist patients with multiple heart valve diseases. Funded by the American Heart Association.

  5. 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.

  6. Multiple morbidities in companion dogs: a novel model for investigating age-related disease

    PubMed Central

    Jin, Kelly; Hoffman, Jessica M.; Creevy, Kate E.; O’Neill, Dan G.; Promislow, Daniel E.L.

    2016-01-01

    The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons. Mean lifespan shows twofold variation across dog breeds. In addition, dogs closely share the environments of their owners, and substantial veterinary resources are dedicated to comprehensive diagnosis of conditions in dogs. However, while dogs are therefore useful for studying multimorbidity, little is known about how aging influences the accumulation of multiple concurrent disease conditions across dog breeds. The current study examines how age, body weight, and breed contribute to variation in multimorbidity in over 2,000 companion dogs visiting private veterinary clinics in England. In common with humans, we find that the number of diagnoses increases significantly with age in dogs. However, we find no significant weight or breed effects on morbidity number. This surprising result reveals that while breeds may vary in their average longevity and causes of death, their age-related trajectories of morbidities differ little, suggesting that age of onset of disease may be the source of variation in lifespan across breeds. Future studies with increased sample sizes and longitudinal monitoring may help us discern more breed-specific patterns in morbidity. Overall, the large increase in multimorbidity seen with age in dogs mirrors that seen in humans and lends even more credence to the value of companion dogs as models for human morbidity and mortality. PMID:27876455

  7. FoxP3+ Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies

    PubMed Central

    Meyer zu Hörste, Gerd; Cordes, Steffen; Mausberg, Anne K.; Zozulya, Alla L.; Wessig, Carsten; Sparwasser, Tim; Mathys, Christian; Wiendl, Heinz; Hartung, Hans-Peter; Kieseier, Bernd C.

    2014-01-01

    Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies. PMID:25286182

  8. Efficacy and safety of memantine in moderate-to-severe Alzheimer disease: the evidence to date.

    PubMed

    Bullock, Roger

    2006-01-01

    Memantine, a moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist, is currently the only agent approved for moderately severe to severe Alzheimer disease (AD) in Europe and for moderate-to-severe Alzheimer disease in the United States. In clinical trials, memantine has consistently demonstrated a reduced rate of deterioration on global, cognitive, functional, and behavioral measures, across a range of outcome measures compared with usual care. Notably, improvements versus placebo were seen in individual activities of daily living and behavior, particularly agitation. Efficacy was demonstrated in patients with newly diagnosed Alzheimer disease, patients previously or currently receiving acetylcholinesterase inhibitors, and both institutionalized and community-dwelling Alzheimer disease patients. Memantine has a tolerability profile similar to placebo. This review presents the results of key clinical trials, and includes clinically relevant analyses, such as numbers-needed-to-treat and effect sizes. Increased dependency and institutionalization are significant cost drivers in Alzheimer disease. Memantine is able to reduce dependency, caregiver time required, and mean monthly caregiver and societal costs. Recent studies of the relationship between Alzheimer disease progression, caregiver burden, and healthcare costs emphasize the need for treatments such as memantine that can slow the rate of decline in Alzheimer disease.

  9. BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

    PubMed Central

    Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

    2012-01-01

    Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

  10. The Role of Celiac Disease in Severity of Liver Disorders and Effect of a Gluten Free Diet on Diseases Improvement

    PubMed Central

    Rostami-Nejad, Mohammad; Haldane, Thea; AlDulaimi, David; Alavian, Seyed Moayed; Zali, Mohammad Reza; Rostami, Kamran

    2013-01-01

    Context Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. Evidence Acquisition PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. Results Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. Conclusions Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia. PMID:24348636

  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. The alpha-globin genotype does not influence sickle cell disease severity in a retrospective cross-validation study of the pediatric severity score.

    PubMed

    Joly, Philippe; Pondarré, Corinne; Bardel, Claire; Francina, Alain; Martin, Cyril

    2012-01-01

    To validate the recently proposed pediatric severity score (PSS) for sickle cell disease (SCD), we retrospectively assembled clinical data from a cohort of 122 patients with SCD (105 S/S or S/β(0) -thal. and 17 S/C) followed up for at least 2 years. Besides age and α- and β-globin genotypes, four new parameters were also tested against the PSS: duration of data assembly, neonatal screening, use of transcranial Doppler ultrasound to prevent vasculopathies and β-globin gene cluster haplotype. Once again, the PSS clearly differentiated patients by their β-globin genotype (P=0.004) but not by their age during data assembly (P=0.159). But, surprisingly, alpha-gene deletions were not associated with a lower PSS (P=0.604), possibly reflecting the opposite effects of α-thalassemia on global SCD severity. As for the newly tested parameters, the PSS appeared not to be influenced by the duration of data assembly (P=0.071) and neonatal screening (P=0.678) but rather by the introduction of transcranial Doppler ultrasound (P=0.006). Moreover, the Senegal haplotype at the homozygous state may be associated with a lower PSS. Methodologically, our data globally confirm the usefulness of the PSS to identify major etiological factors of SCD gravity. Nevertheless, the score is surely underestimated for patients who have been switched to a chronic therapy before the main SCD complications. Biologically, our study questions about the exact influence of α-thalassemia on global SCD severity.

  13. 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

  14. 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 signi