Mechanisms of Quality of Life and Social Support in Inflammatory Bowel Disease.

Science.gov (United States)

Katz, Laura; Tripp, Dean A; Ropeleski, Mark; Depew, William; Curtis Nickel, J; Vanner, Stephen; Beyak, Michael J

2016-03-01

Cognitive and social factors are essential considerations in inflammatory bowel disease (IBD) patient management, but existing research is limited. This study aims to expand the IBD literature by examining the relationship between social supports and QoL, while examining mechanisms in these relationships. Consenting patients attending an IBD outpatient clinic were provided a survey package (N = 164). Regressions evaluated predictors of IBD-QoL, and catastrophizing and optimism were examined as mediators between social support and IBD-QoL. Diminished IBD-QoL was predicted by younger age, greater negative spousal responses, and less perceived spousal support. Mediation models showed helplessness catastrophizing to be the lone mediator, acting as a mechanism between both negative spousal responses and perceived spousal support with IBD-QoL. Social interaction variables are associated with IBD-QoL, but patients' experience of helplessness acts to reduce their ability to benefit from social support. Patient care should consider supportive social and cognitive factors to improve IBD-QoL.

Asbestos-related diseases in automobile mechanics.

Science.gov (United States)

Ameille, Jacques; Rosenberg, Nicole; Matrat, Mireille; Descatha, Alexis; Mompoint, Dominique; Hamzi, Lounis; Atassi, Catherine; Vasile, Manuela; Garnier, Robert; Pairon, Jean-Claude

2012-01-01

Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyse the frequency of pleural and parenchymal abnormalities on high-resolution computed tomography (HRCT) in a population of automobile mechanics. The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos-related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers; who in the case of disagreement discussed until they reached agreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. Pleural plaques were observed in five cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in one case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers.

Asbestos-related diseases in automobile mechanics

Science.gov (United States)

Ameille, Jacques; Rosenberg, Nicole; Matrat, Mireille; Descatha, Alexis; Mompoint, Dominique; Hamzi, Lounis; Atassi, Catherine; Vasile, Manuela; Garnier, Robert; Pairon, Jean-Claude

2012-01-01

Purpose Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyze the frequency of pleural and parenchymal abnormalities on HRCT in a population of automobile mechanics. Methods The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos–related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers, with further consensus in the case of disagreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. Results Pleural plaques were observed in 5 cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in 1 case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. Conclusions The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers. PMID:21965465

Relationship Between Voice and Motor Disabilities of Parkinson's Disease.

Science.gov (United States)

Majdinasab, Fatemeh; Karkheiran, Siamak; Soltani, Majid; Moradi, Negin; Shahidi, Gholamali

2016-11-01

To evaluate voice of Iranian patients with Parkinson's disease (PD) and find any relationship between motor disabilities and acoustic voice parameters as speech motor components. We evaluated 27 Farsi-speaking PD patients and 21 age- and sex-matched healthy persons as control. Motor performance was assessed by the Unified Parkinson's Disease Rating Scale part III and Hoehn and Yahr rating scale in the "on" state. Acoustic voice evaluation, including fundamental frequency (f0), standard deviation of f0, minimum of f0, maximum of f0, shimmer, jitter, and harmonic to noise ratio, was done using the Praat software via /a/ prolongation. No difference was seen between the voice of the patients and the voice of the controls. f0 and its variation had a significant correlation with the duration of the disease, but did not have any relationships with the Unified Parkinson's Disease Rating Scale part III. Only limited relationship was observed between voice and motor disabilities. Tremor is an important main feature of PD that affects motor and phonation systems. Females had an older age at onset, more prolonged disease, and more severe motor disabilities (not statistically significant), but phonation disorders were more frequent in males and showed more relationship with severity of motor disabilities. Voice is affected by PD earlier than many other motor components and is more sensitive to disease progression. Tremor is the most effective part of PD that impacts voice. PD has more effect on voice of male versus female patients. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Association of Relationship between Periodontal Disease and Cardiovascular Disease.

Science.gov (United States)

Johar, N; Dhodapkar, S V; Kumar, R; Verma, T; Jajoo, A

2017-04-01

The present study was undertaken to determine the relationship between periodontal and cardiovascular disease. Previous studies have shown some co-relation between the two conditions. We included 186 patients divided into four groups. First two Groups (A1 & A2) were the patients with cardiac disease (100 in numbers) whilst Groups (B1 & B2) (86 in numbers) were treated as controls (without cardiac disease). Following markers of periodontal disease were assessed - plaque index, calculus index, gingival and periodontal index. Markers of cardiovascular disease included were LDL, HDL, total cholesterol and CRP. Ramfjords periodontal index was used to assess the extent of periodontal disease. In the present study there was a significant increase in CRP levels in Group A1 (CVD + PD) compared to controls and overall the two cardiac groups showed a significant increase in CRP compared to controls. There was a non-significant change in lipid profile markers (LDL, HDL and total cholesterol). Periodontal Disease Index (PDI) was also increased in Group A1 compared to other groups except Group B1 and overall in cardiac groups compared to non-cardiac (PD) groups. In this study no correlation between periodontal and cardiovascular disease was found. This may be due intake of statins by few patients in Group A with a confirmed diagnosis of cardiovascular disease.

Levels of interleukin-1β in gingival crevicular fluid in patients with coronary heart disease and its relationship to periodontal status

Science.gov (United States)

Lenggogeny, Putri; Masulili, Sri Lelyati C.; Tadjoedin, Fatimah M.; Radi, Basuni

2017-02-01

Periodontitis is a risk factor for coronary heart disease (CHD). Both diseases are an inflammatory diseases and have the same potential pathogenic mechanisms. Interleukin-1β as a pro-inflammatory main cytokine, can be found in this both diseases. Gingival crevicular fluid (GCF) derived from the serum of gingival sulcus, affected by inflammatory mechanism and the amount of this fluid will increase in that situation. Objective: To analyze the relationship of interleukin-1β levels in gingival crevicular fluid (GCF) of CHD and non-CHD patients with periodontal status. Methods: Oral clinical examination (plaque index, bleeding on probing, pocket depth and clinical attachment loss) for 35 subjects with CHD and 35 non CHD were checked, laboratory test to measure the levels of Interleukin-1β was checked with enzyme-linked immunosorbent assay (ELISA). Results: There was no significant differences between interleukin-1β levels in CHD and non-CHD patients (p>0.05); there was no significant difference between the level of Interleukin-1β with periodontal status in CHD and control (non CHD) patients (p>0.05). Conclusions: levels of Interleukin-1β in CHD patients do not have a relationships with plaque index, pocket depth and clinical attachment loss, but has a relationships with bleeding on probing.

Relationship between periodontal disease and preterm low birth ...

African Journals Online (AJOL)

Introduction: Periodontal disease is a neglected bacterial infection that causes destruction of the periodontium in pregnant women. Yet its impact on the occurrence of adverse pregnancy outcomes has not systematically evaluated and there is no clear statement on the relationship between periodontal disease and preterm ...

Early Family Relationships Predict Children’s Emotion Regulation and Defense Mechanisms

Directory of Open Access Journals (Sweden)

Jallu Lindblom

2016-12-01

Full Text Available Early family relationships have been suggested to influence the development of children’s affect regulation, involving both emotion regulation and defense mechanisms. However, we lack research on the specific family predictors for these two forms of affect regulation, which have been conceptualized to differ in their functions and accessibility to consciousness. Accordingly, we examine how the (a quality and (b timing of family relationships during infancy predict child’s later emotion regulation and defense mechanisms. Parents (N = 703 reported autonomy and intimacy in marital and parenting relationships at the child’s ages of 2 and 12 months, and the child’s use of emotion regulation and immature and neurotic defenses at 7 to 8 years. As hypothesized, the results showed that functional early family relationships predicted children’s efficient emotion regulation, whereas dysfunctional relationships predicted reliance on defense mechanisms in middle childhood. Further, results showed a timing effect for neurotic defenses, partially confirming our hypothesis of early infancy being an especially important period for the development of defense mechanisms. The findings are discussed from the viewpoints of attachment and family dynamics, emotional self-awareness, and sense of security.

Analysis of relationship between blood lipid metabolism levels and hs-CRP levels in patients with chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

You Fengjian

2011-01-01

Objective: To study the relationship between blood lipid metabolism levels and hs-CRP levels in the patients with chronic obstructive pulmonary disease. Methods: The levels of plasma blood lipid (with biochemistry) and serum hs-CRP(with high-sensitive immuno turbidimetry) were determined in 96 patients with chronic obstructive pulmonary disease as well as 68 normal controls. Results: The plasma blood lipid levels in 96 patients with chronic obstructive pulmonary disease were significantly lower than those in 68 controls, plasma TC and LDL-C levels were not much difference (P>0.05), plasma HDL-C level was significantly difference (P<0.05), but TG and Lp (a) levels were very prominently difference (P<0.01). And the plasma hs-CRP level was significantly increased also (P<0.01). The close relationship was between blood lipid and hs-CRP levels. Conclusion: The study of relationship between blood lipid levels and hs-CRP levels in patients with COPD was helpful for understand the disease process as well as possible mechanisms. (authors)

Endangered species: mitochondrial DNA loss as a mechanism of human disease.

Science.gov (United States)

Herrera, Alan; Garcia, Iraselia; Gaytan, Norma; Jones, Edith; Maldonado, Alicia; Gilkerson, Robert

2015-06-01

Human mitochondrial DNA (mtDNA) is a small maternally inherited DNA, typically present in hundreds of copies in a single human cell. Thus, despite its small size, the mitochondrial genome plays a crucial role in the metabolic homeostasis of the cell. Our understanding of mtDNA genotype-phenotype relationships is derived largely from studies of the classical mitochondrial neuromuscular diseases, in which mutations of mtDNA lead to compromised mitochondrial bioenergetic function, with devastating pathological consequences. Emerging research suggests that loss, rather than mutation, of mtDNA plays a major role across a range of prevalent human diseases, including diabetes mellitus, cardiovascular disease, and aging. Here, we examine the 'rules' of mitochondrial genetics and function, the clinical settings in which loss of mtDNA is an emerging pathogenic mechanism, and explore mtDNA damage and its consequences for the organellar network and cell at large. As extranuclear genetic material arrayed throughout the cell to support metabolism, mtDNA is increasingly implicated in a host of disease conditions, opening a range of exciting questions regarding mtDNA and its role in cellular homeostasis.

Relationship between transit time and mechanical properties of a cell through a stenosed microchannel.

Science.gov (United States)

Ye, Ting; Shi, Huixin; Phan-Thien, Nhan; Lim, Chwee Teck; Li, Yu

2018-01-24

The changes in the mechanical properties of a cell are not only the cause of some diseases, but can also be a biomarker for some disease states. In recent times, microfluidic devices with built-in constrictions have been widely used to measure these changes. The transit time in such devices, defined as the time that a cell takes to pass through a constriction, has been found to be a crucial factor associated with the cell mechanical properties. Here, we use smoothed dissipative particle dynamics (SDPD), a particle-based numerical method, to explore the relationship between the transit time and mechanical properties of a cell. Three expressions of the transit time are developed from our simulation data, with respect to the stenosed size of constrictions, the shear modulus and bending modulus of cells, respectively. We show that a convergent constriction (the inlet is wider than the outlet), and a sharp-corner constriction (the constriction outlet is narrow) are better in identifying the differences in the transit time of cells. Moreover, the transit time increases and gradually approaches a constant as the shear modulus of cells increases, but increases first and then decreases as the bending modulus increases. These results suggest that the mechanical properties of cells can indeed be measured by analyzing their transit time, based on the recommended microfluidic device.

Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants

DEFF Research Database (Denmark)

Spratley, Samantha J; Hill, Chris H; Viuff, Agnete H

2016-01-01

different mutations have been identified in GALC that cause Krabbe disease but the mechanisms by which they cause disease remain unclear. We have generated monoclonal antibodies against full-length human GALC and used these to monitor the trafficking and processing of GALC variants in cell-based assays...

Close relationship processes and health: implications of attachment theory for health and disease.

Science.gov (United States)

Pietromonaco, Paula R; Uchino, Bert; Dunkel Schetter, Christine

2013-05-01

Health psychology has contributed significantly to understanding the link between psychological factors and health and well-being, but it has not often incorporated advances in relationship science into hypothesis generation and study design. We present one example of a theoretical model, following from a major relationship theory (attachment theory) that integrates relationship constructs and processes with biopsychosocial processes and health outcomes. We briefly describe attachment theory and present a general framework linking it to dyadic relationship processes (relationship behaviors, mediators, and outcomes) and health processes (physiology, affective states, health behavior, and health outcomes). We discuss the utility of the model for research in several health domains (e.g., self-regulation of health behavior, pain, chronic disease) and its implications for interventions and future research. This framework revealed important gaps in knowledge about relationships and health. Future work in this area will benefit from taking into account individual differences in attachment, adopting a more explicit dyadic approach, examining more integrated models that test for mediating processes, and incorporating a broader range of relationship constructs that have implications for health. A theoretical framework for studying health that is based in relationship science can accelerate progress by generating new research directions designed to pinpoint the mechanisms through which close relationships promote or undermine health. Furthermore, this knowledge can be applied to develop more effective interventions to help individuals and their relationship partners with health-related challenges. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Relationship between Postural Deformities and Frontal Function in Parkinson's Disease

OpenAIRE

Ninomiya, Satoko; Morita, Akihiko; Teramoto, Hiroko; Akimoto, Takayoshi; Shiota, Hiroshi; Kamei, Satoshi

2015-01-01

Postural deformities and executive dysfunction (ED) are common symptoms of Parkinson's disease (PD); however, the relationship between postural deformities and ED in patients with PD remains unclear. This study assessed the relationship between postural deformities and ED in patients with PD. Sixty-five patients with sporadic PD were assessed for the severity of postural deformities and executive function. The severity of postural deformities was scored using the United Parkinson's Disease Ra...

Relationship between Occupational Stress and Gastric Disease in Male Workers.

Science.gov (United States)

Lihm, Ho-Seob; Park, Sang-Hyun; Gong, Eun-Hee; Choi, Jong-Soon; Kim, Jung-Won

2012-09-01

Physical and mental health of workers is threatened due to various events and chronic occupational stress. This study was conducted to investigate the relationship between occupational stress and gastric disease in male workers of the shipbuilding industry. Occupational stress measured among a total of 498 workers of a shipbuilding firm who visited the hospital for health examination using the Korean Occupational Stress Scale (KOSS)-short form, and the relationship between sociodemographic factors, health-related behaviors, occupational stress, and gastric disease, and the distribution of occupational stress by sociodemographic factors in the gastric disease group was examined. There was no significant association between gastric disease and total occupational stress score and its seven sub-factors. The analysis showed that risk of gastric disease was significantly higher in the Q1 group in which the stress caused by occupational discomfort among seven sub-factors was lowest than that in the Q4 group (odds ratio, 2.819; 95% confidence interval, 1.151 to 6.908). Analysis only on the gastric disease group showed that the stress score of laborers was higher in the four sub-factors than that of office workers (P occupational stress in the low-educated and laborers. It is recommended for future studies to confirm the causal relationship between occupational stress and gastric disease by large scale studies using a KOSS which appropriately reflects workplace culture.

Review of the Relationship of Restless Legs Syndrome and Periodic Limb Movements in Sleep to Hypertension, Heart Disease, and Stroke

OpenAIRE

Walters, Arthur S.; Rye, David B.

2009-01-01

Evidence is reviewed documenting an intimate relationship among restless legs syndrome (RLS) / periodic limb movements in sleep (PLMS) and hypertension and cardiovascular and cerebrovascular disease. Sympathetic overactivity is associated with RLS/PLMS, as manifested by increased pulse rate and blood pressure coincident with PLMS. Causality is far from definitive. Mechanisms are explored as to how RLS/PLMS may lead to high blood pressure, heart disease, and stroke: (a) the sympathetic hyperac...

Relationship between Occupational Stress and Gastric Disease in Male Workers

Science.gov (United States)

Lihm, Ho-Seob; Park, Sang-Hyun; Gong, Eun-Hee; Kim, Jung-Won

2012-01-01

Background Physical and mental health of workers is threatened due to various events and chronic occupational stress. This study was conducted to investigate the relationship between occupational stress and gastric disease in male workers of the shipbuilding industry. Methods Occupational stress measured among a total of 498 workers of a shipbuilding firm who visited the hospital for health examination using the Korean Occupational Stress Scale (KOSS)-short form, and the relationship between sociodemographic factors, health-related behaviors, occupational stress, and gastric disease, and the distribution of occupational stress by sociodemographic factors in the gastric disease group was examined. Results There was no significant association between gastric disease and total occupational stress score and its seven sub-factors. The analysis showed that risk of gastric disease was significantly higher in the Q1 group in which the stress caused by occupational discomfort among seven sub-factors was lowest than that in the Q4 group (odds ratio, 2.819; 95% confidence interval, 1.151 to 6.908). Analysis only on the gastric disease group showed that the stress score of laborers was higher in the four sub-factors than that of office workers (P occupational stress in the low-educated and laborers. It is recommended for future studies to confirm the causal relationship between occupational stress and gastric disease by large scale studies using a KOSS which appropriately reflects workplace culture. PMID:23115706

Statistical Mechanics of Prion Diseases

International Nuclear Information System (INIS)

Slepoy, A.; Singh, R. R. P.; Pazmandi, F.; Kulkarni, R. V.; Cox, D. L.

2001-01-01

We present a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., mad cow disease) with concomitant prion protein misfolding and aggregation. Our studies lead us to the hypothesis that the observed broad incubation time distribution in epidemiological data reflect fluctuation dominated growth seeded by a few nanometer scale aggregates, while much narrower incubation time distributions for innoculated lab animals arise from statistical self-averaging. We model ''species barriers'' to prion infection and assess a related treatment protocol

Addictive drugs and their relationship with infectious diseases.

Science.gov (United States)

Friedman, Herman; Pross, Susan; Klein, Thomas W

2006-08-01

The use of drugs of abuse, both recreationally and medicinally, may be related to serious public health concerns. There is a relationship between addictive drugs of abuse such as alcohol and nicotine in cigarette smoke, as well as illegal drugs such as opiates, cocaine and marijuana, and increased susceptibility to infections. The nature and mechanisms of immunomodulation induced by such drugs of abuse are described in this review. The effects of opiates and marijuana, using animal models as well as in vitro studies with immune cells from experimental animals and humans, have shown that immunomodulation induced by these drugs is mainly receptor-mediated, either directly by interaction with specific receptors on immune cells or indirectly by reaction with similar receptors on cells of the nervous system. Similar studies also show that cocaine and nicotine have marked immunomodulatory effects, which are mainly receptor-mediated. Both cocaine, an illegal drug, and nicotine, a widely used legal addictive component of cigarettes, are markedly immunomodulatory and increase susceptibility to infection. The nature and mechanism of immunomodulation induced by alcohol, the most widely used addictive substance of abuse, are similar but immunomodulatory effects, although not receptor-mediated. The many research studies on the effects of these drugs on immunity and increased susceptibility to infectious diseases, including AIDS, are providing a better understanding of the complex interactions between immunity, infections and substance abuse.

Depression and Chronic Liver Diseases: Are There Shared Underlying Mechanisms?

Directory of Open Access Journals (Sweden)

Xiaoqin Huang

2017-05-01

Full Text Available The occurrence of depression is higher in patients with chronic liver disease (CLD than that in the general population. The mechanism described in previous studies mainly focused on inflammation and stress, which not only exists in CLD, but also emerges in common chronic diseases, leaving the specific mechanism unknown. This review was to summarize the prevalence and risk factors of depression in CLD including chronic hepatitis B, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, and to point out the possible underlying mechanism of this potential link. Clarifying the origins of this common comorbidity (depression and CLD may provide more information to understand both diseases.

Relationship between aortic diseases and renal cysts

International Nuclear Information System (INIS)

Hashizume, Toshikazu

2009-01-01

Based on empirical observations, patients with aortic diseases (AoD) (abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA) and aortic dissection (AD)) appeared to present with an increased incidence of renal cysts (RC) observed on computed tomography (CT). To clarify any potential relationship, I compared incidence of RC on CT scans in patients with and without AoD. A comparison was conducted on the incidence of RC on CT scans in 107 patients (74.6 years old; n=71 males, n=36 females) with AoD (57 AAA, 36 TAA, 14 AD) versus 332 control patients (73.6 years old; n=193 males, n=139 females) without AoD. Univariate analysis and multiple logistic regression were performed to evaluate the relationship between AoD and RC incidence. In patients with AoD, 65.0% presented with RC compared to only 28.6% in the control group (p<0.0001). In comparison, the AoD group presented with a higher frequency of hypertension (63.6% vs. 33.4%, p<0.0001), coronary artery disease (26.2% vs. 13.6%, p<0.0001), chronic obstructive pulmonary disease (COPD) (10.3% vs. 4.2%, p<0.0001), but no significant frequency of dyslipidemia and diabetes mellitus was observed between the 2 groups. Multivariate analysis indicated three independent predictors of AoD: hypertension (p=0.013; odds ratio=2.32), COPD (p=0.015; odds ratio=5.62) and RC (p<0.0001; odds ratio=4.88). These results indicate a significantly higher incidence of RC in patients with versus without AoD. A close relationship between AoD and RC may exist, and coincidental RC could be a potential indicator for AoD screening. (author)

Relationship between aortic diseases and renal cysts

Energy Technology Data Exchange (ETDEWEB)

Hashizume, Toshikazu [Minami Wakayama Medical Center, Tanabe, Wakayama (Japan)

2009-12-15

Based on empirical observations, patients with aortic diseases (AoD) (abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA) and aortic dissection (AD)) appeared to present with an increased incidence of renal cysts (RC) observed on computed tomography (CT). To clarify any potential relationship, I compared incidence of RC on CT scans in patients with and without AoD. A comparison was conducted on the incidence of RC on CT scans in 107 patients (74.6 years old; n=71 males, n=36 females) with AoD (57 AAA, 36 TAA, 14 AD) versus 332 control patients (73.6 years old; n=193 males, n=139 females) without AoD. Univariate analysis and multiple logistic regression were performed to evaluate the relationship between AoD and RC incidence. In patients with AoD, 65.0% presented with RC compared to only 28.6% in the control group (p<0.0001). In comparison, the AoD group presented with a higher frequency of hypertension (63.6% vs. 33.4%, p<0.0001), coronary artery disease (26.2% vs. 13.6%, p<0.0001), chronic obstructive pulmonary disease (COPD) (10.3% vs. 4.2%, p<0.0001), but no significant frequency of dyslipidemia and diabetes mellitus was observed between the 2 groups. Multivariate analysis indicated three independent predictors of AoD: hypertension (p=0.013; odds ratio=2.32), COPD (p=0.015; odds ratio=5.62) and RC (p<0.0001; odds ratio=4.88). These results indicate a significantly higher incidence of RC in patients with versus without AoD. A close relationship between AoD and RC may exist, and coincidental RC could be a potential indicator for AoD screening. (author)

Air pollution: mechanisms of neuroinflammation and CNS disease.

Science.gov (United States)

Block, Michelle L; Calderón-Garcidueñas, Lilian

2009-09-01

Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.

Effect of communication style and physician-family relationships on satisfaction with pediatric chronic disease care.

Science.gov (United States)

Swedlund, Matthew P; Schumacher, Jayna B; Young, Henry N; Cox, Elizabeth D

2012-01-01

Over 8% of children have a chronic disease and many are unable to adhere to treatment. Satisfaction with chronic disease care can impact adherence. We examine how visit satisfaction is associated with physician communication style and ongoing physician-family relationships. We collected surveys and visit videos for 75 children ages 9-16 years visiting for asthma, diabetes, or sickle cell disease management. Raters assessed physician communication style (friendliness, interest, responsiveness, and dominance) from visit videos. Quality of the ongoing relationship was measured with four survey items (parent-physician relationship, child-physician relationship, comfort asking questions, and trust in the physician), while a single item assessed satisfaction. Correlations and chi square were used to assess association of satisfaction with communication style or quality of the ongoing relationship. Satisfaction was positively associated with physician to parent (p relationships (p communication style and the quality of the ongoing relationship contribute to pediatric chronic disease visit satisfaction.

Relationship between IL1 gene polymorphisms and periodontal disease in Japanese women.

Science.gov (United States)

Tanaka, Keiko; Miyake, Yoshihiro; Hanioka, Takashi; Arakawa, Masashi

2014-04-01

Epidemiological evidence on the relationship between IL1A and/or IL1B polymorphisms and periodontal disease is inconsistent. We investigated associations between three IL1 single-nucleotide polymorphisms (SNPs) in genes encoding interleukin (IL) -1α (rs1800587) and IL-1β (rs1143634 and rs16944) and the risk of periodontal disease among young Japanese women. A case-control study was performed with a total of 1150 women, including 131 subjects who had at least one tooth with a probing pocket depth of 4 mm or deeper and 1019 periodontally healthy controls. Compared with a reference group of women with the GG genotype of SNP rs16944, those with the GA genotype had a significantly reduced risk of periodontal disease, while there was no significant relationship between the AA genotype and periodontal disease. No evident relationships were observed between SNP rs1800587 or rs1143634 and periodontal disease. Our study did not reveal any evidence of interaction between the IL1 polymorphisms and smoking. The results of this study showed that the heterozygous variant genotype of the IL1 rs16944 was significantly associated with a reduced risk of periodontal disease in young Japanese women. Smoking did not significantly modify the gene-disease associations under study.

Progress of the relationship between serum uric acid and neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Yang FU

2018-04-01

Full Text Available Serum uric acid (sUA, a natural antioxidant in human body, has been found to be related to the occurrence and development of various neurodegenerative diseases in recent years, including Parkinson's disease (PD, multiple system atrophy (MSA, Alzheimer's disease (AD and amyotrophic lateral sclerosis (ALS. Increasing of sUA level has been found to reduce the incidence of PD and ALS, but the relationship between sUA and AD, MSA remains largely unknown. The in vitro studies and animal experiments revealed that sUA can enhance the antioxidant capacity of neurons and delay neurodegeneration and apoptosis. This paper mainly reviews the progress in epidemiological and basic studies of the relationship between sUA and neurodegenerative diseases in recent years, and aims to provide a reference for future novel prevention and treatment strategies for neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2018.03.010

[Analysis of the Injury-disease Relationship between Spondylolysis and Trauma in 26 Forensic Identifications].

Science.gov (United States)

Wang, L X; Zhu, G L; Qi, L Q; Sheng, Y Y

2016-12-01

To expound the injury-disease relationship between spondylolysis and trauma for the points of forensic identification. Total 26 cases of spondylolysis were collected and the characteristics of this disease such as age, accompanied symptoms, treatment and injury manner were discussed. The causal relationship existed between trauma and injury consequence in 2 appraised individuals and both of them aged less than 50 years old. The injury manners of both were high-energy injury with combined injury and these 2 patients were treated by operation. The analysis of injury-disease relationship between spondylolysis and trauma should be paid attention in the middle-young age under 50 years old. More importantly, the injury-disease relationship should be analyzed in the patients who chose operative treatment. Copyright© by the Editorial Department of Journal of Forensic Medicine

Understanding Neurological Disease Mechanisms in the Era of Epigenetics

Science.gov (United States)

Qureshi, Irfan A.; Mehler, Mark F.

2015-01-01

The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

Relationship between manual dexterity and the unified parkinson's disease rating scale-motor exam.

Science.gov (United States)

Hwang, Sujin; Song, Chiang-Soon

2016-12-01

[Purpose] The purpose of this study was to examine the relationships between manual dexterity and the Unified Parkinson's Disease Rating Scale-Motor Exam as a clinical tool for quantifying upper extremity function in persons with Parkinson's disease. [Subjects and Methods] Thirty-two persons with idiopathic Parkinson's disease participated in this study. This study measured two clinical outcomes, the box-and-block test and the Unified Parkinson's Disease Rating Scale-Motor Exam, to investigate the relationships between manual dexterity and the Unified Parkinson's Disease Rating Scale-Motor Exam. [Results] The box-and-block test on the more affected side was positive relationship with the box-and-block test on the less affected side. The Unified Parkinson's Disease Rating Scale-motor exam score had a negative correlation with the box-and-block test results for both sides. [Conclusion] A positive association was noted between manual dexterity and motor function in patients with idiopathic Parkinson disease. The results of this study suggest that the box-and-block test and the Unified Parkinson's Disease Rating Scale-Motor Exam are good clinical measures that quantify upper extremity function and are necessary for the accurate evaluation of patients and to plan intervention strategies.

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants.

Directory of Open Access Journals (Sweden)

Steven C Bagley

2016-04-01

Full Text Available Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford, and compared to a large database of published disease-associated genetic variants (VARIMED; data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups.

Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke.

Science.gov (United States)

Walters, Arthur S; Rye, David B

2009-05-01

Evidence is reviewed documenting an intimate relationship among restless legs syndrome (RLS) / periodic limb movements in sleep (PLMS) and hypertension and cardiovascular and cerebrovascular disease. Sympathetic overactivity is associated with RLS/PLMS, as manifested by increased pulse rate and blood pressure coincident with PLMS. Causality is far from definitive. Mechanisms are explored as to how RLS/PLMS may lead to high blood pressure, heart disease, and stroke: (a) the sympathetic hyperactivity associated with RLS/PLMS may lead to daytime hypertension that in turn leads to heart disease and stroke; (b) in the absence of daytime hypertension, this sympathetic hyperactivity may predispose to heart disease and stroke either directly or indirectly via atherosclerotic plaque formation and rupture; and (c) comorbidities associated with RLS/PLMS, such as renal failure, diabetes, iron deficiency, and insomnia, may predispose to heart disease and stroke. One theoretical cause for sympathetic hyperactivity is insufficient All diencephalospinal dopaminergic neuron inhibition of sympathetic preganglionic neurons residing in the intermediolateral cell columns of the spinal cord. We cannot exclude the possibility that peripheral vascular, cardiovascular, and cerebrovascular disease may also contribute to RLS/PLMS, and mechanisms for these possibilities are also discussed.

From genome-wide association studies to disease mechanisms : celiac disease as a model for autoimmune diseases

NARCIS (Netherlands)

Kumar, Vinod; Wijmenga, Cisca; Withoff, Sebo

Celiac disease is characterized by a chronic inflammatory reaction in the intestine and is triggered by gluten, a constituent derived from grains which is present in the common daily diet in the Western world. Despite decades of research, the mechanisms behind celiac disease etiology are still not

Sublethal RNA Oxidation as a Mechanism for Neurodegenerative Disease

Directory of Open Access Journals (Sweden)

Mark A. Smith

2008-05-01

Full Text Available Although cellular RNA is subjected to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigations of the biological consequences of free radical damage. In fact, because it is largely single-stranded and its bases lack the protection of hydrogen bonding and binding by specific proteins, RNA may be more susceptible to oxidative insults than is DNA. Oxidative damage to protein-coding RNA or non-coding RNA will, in turn, potentially cause errors in proteins and/or dysregulation of gene expression. While less lethal than mutations in the genome, such sublethal insults to cells might be associated with underlying mechanisms of several chronic diseases, including neurodegenerative disease. Recently, oxidative RNA damage has been described in several neurodegenerative diseases including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and prion diseases. Of particular interest, oxidative RNA damage can be demonstrated in vulnerable neurons early in disease, suggesting that RNA oxidation may actively contribute to the onset of the disease. An increasing body of evidence suggests that, mechanistically speaking, the detrimental effects of oxidative RNA damage to protein synthesis are attenuated, at least in part, by the existence of protective mechanisms that prevent the incorporation of the damaged ribonucleotides into the translational machinery. Further investigations aimed at understanding the processing mechanisms related to oxidative RNA damage and its consequences may provide significant insights into the pathogenesis of neurodegenerative and other degenerative diseases and lead to better therapeutic strategies.

Epigenetic mechanisms in neurological disease.

Science.gov (United States)

Jakovcevski, Mira; Akbarian, Schahram

2012-08-01

The exploration of brain epigenomes, which consist of various types of DNA methylation and covalent histone modifications, is providing new and unprecedented insights into the mechanisms of neural development, neurological disease and aging. Traditionally, chromatin defects in the brain were considered static lesions of early development that occurred in the context of rare genetic syndromes, but it is now clear that mutations and maladaptations of the epigenetic machinery cover a much wider continuum that includes adult-onset neurodegenerative disease. Here, we describe how recent advances in neuroepigenetics have contributed to an improved mechanistic understanding of developmental and degenerative brain disorders, and we discuss how they could influence the development of future therapies for these conditions.

Relationship between mechanical sensitivity and postamputation pain: A prospective study

DEFF Research Database (Denmark)

Nikolajsen, Lone; IlKjær, Susanne; Jensen, Troels Staehelin

2000-01-01

of the limb and early (after 1 week) and late (after 6 months) phantom pain. Thirty-five patients scheduled for amputation of the lower limb were examined before, 1 week and 6 months after amputation. On all three examination days pressure-pain thresholds were measured and compared with the simultaneous...... recording of ongoing pain intensity assessed on a visual analogue scale (VAS). There was a weak but significant inverse relationship between preamputation thresholds and early stump and phantom pain. There was no relationship between preamputation thresholds and late stump and phantom pain. One week after...... amputation there was a significant and inverse relationship between mechanical thresholds and phantom pain but no relationship was found after 6 months. The findings suggest that although tenderness of the limb before and after amputation is related to early stump and phantom pain, the relationship is weak...

A mechanism to assess the relationship between socio-technical ...

African Journals Online (AJOL)

A mechanism to assess the relationship between socio-technical congruence and project performance in incremental model. W.A.W.M. Sobri, S.S.M. Fauzi, M.H.N.M. Nasir, R Ahmad, A.J. Suali. Abstract. No Abstract. Keywords: coordination; software development; software project; software engineering project; ...

Disease Heritability Inferred from Familial Relationships Reported in Medical Records.

Science.gov (United States)

Polubriaginof, Fernanda C G; Vanguri, Rami; Quinnies, Kayla; Belbin, Gillian M; Yahi, Alexandre; Salmasian, Hojjat; Lorberbaum, Tal; Nwankwo, Victor; Li, Li; Shervey, Mark M; Glowe, Patricia; Ionita-Laza, Iuliana; Simmerling, Mary; Hripcsak, George; Bakken, Suzanne; Goldstein, David; Kiryluk, Krzysztof; Kenny, Eimear E; Dudley, Joel; Vawdrey, David K; Tatonetti, Nicholas P

2018-05-15

Heritability is essential for understanding the biological causes of disease but requires laborious patient recruitment and phenotype ascertainment. Electronic health records (EHRs) passively capture a wide range of clinically relevant data and provide a resource for studying the heritability of traits that are not typically accessible. EHRs contain next-of-kin information collected via patient emergency contact forms, but until now, these data have gone unused in research. We mined emergency contact data at three academic medical centers and identified 7.4 million familial relationships while maintaining patient privacy. Identified relationships were consistent with genetically derived relatedness. We used EHR data to compute heritability estimates for 500 disease phenotypes. Overall, estimates were consistent with the literature and between sites. Inconsistencies were indicative of limitations and opportunities unique to EHR research. These analyses provide a validation of the use of EHRs for genetics and disease research. Copyright © 2018 Elsevier Inc. All rights reserved.

The relationship between pain and dynamic knee joint loading in knee osteoarthritis varies with radiographic disease severity. A cross sectional study.

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Henriksen, Marius; Aaboe, Jens; Bliddal, Henning

2012-08-01

In a cross sectional study, we investigated the relationships between knee pain and mechanical loading across the knee, as indicated by the external knee adduction moment (KAM) during walking in patients with symptomatic knee OA who were distinguished by different radiographic disease severities. Data from 137 symptomatic medial knee OA patients were used. Based on Kellgren/Lawrence (K/L) grading, the patients were divided into radiographically less severe (K/L ≤ 2, n=68) or severe (K/L>2, n=69) medial knee OA. Overall knee pain was rated on a 10 cm visual analog scale, and peak KAM and KAM impulses were obtained from gait analyses. Mixed linear regression analyses were performed with KAM variables as the outcome, and pain and disease severity as independent variables, adjusting for age, gender, and walking speed. In adjusted analyses, less severe patients demonstrated negative relationships between pain intensities and dynamic loading. The severe patient group showed no relationship between pain intensity and peak KAM, and a positive relationship between pain intensity and KAM impulse. In radiographically less severe knee OA, the negative relationships between pain intensity and dynamic knee joint loading indicate a natural reaction to pain, which will limit the stress on the joint. In contrast, either absent or positive relationships between pain and dynamic loading in severe OA may lead to overuse and accelerated disease progression. These findings may have a large potential interest for strategies of treatment in knee OA. Copyright © 2011 Elsevier B.V. All rights reserved.

Neuroepigenetic mechanisms in disease.

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Christopher, Michael A; Kyle, Stephanie M; Katz, David J

2017-10-16

Epigenetics allows for the inheritance of information in cellular lineages during differentiation, independent of changes to the underlying genetic sequence. This raises the question of whether epigenetic mechanisms also function in post-mitotic neurons. During the long life of the neuron, fluctuations in gene expression allow the cell to pass through stages of differentiation, modulate synaptic activity in response to environmental cues, and fortify the cell through age-related neuroprotective pathways. Emerging evidence suggests that epigenetic mechanisms such as DNA methylation and histone modification permit these dynamic changes in gene expression throughout the life of a neuron. Accordingly, recent studies have revealed the vital importance of epigenetic players in the central nervous system and during neurodegeneration. Here, we provide a review of several of these recent findings, highlighting novel functions for epigenetics in the fields of Rett syndrome, Fragile X syndrome, and Alzheimer's disease research. Together, these discoveries underscore the vital importance of epigenetics in human neurological disorders.

Relationship between health behaviors and self-reported diseases by public employees

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Janaina Maria Setto

Full Text Available Abstract Introduction: Life habits such as physical activity, leisure, eating habits, stress, smoking, and alcohol consumption can directly affect individuals' health. Objective: This study aimed to investigate the relationship between health behaviors and diseases self-reported by employees of a federal public university in southeastern Brazil. Methods: This cross-sectional study included 815 employees, of whom 347 were teachers and 468 were technical-administrative staff, aged between 20 and 65 years old. Data from this study were collected from a secondary database, from the Health Questionnaire (self-reported health conditions by teachers and technical-administrative employees, and from the institution's Vice Dean of Community Affairs. Among the variables assessed, the relationship between eating habits, physical activity, smoking, alcohol consumption, and self-reported illnesses (chronic diseases and infectious and parasitic diseases diagnosed by a doctor within the last 12 months was analyzed. Results: The mean prevalence of these diseases among teachers and technical-administrative staff was 3.1 and 2.9, respectively. This study showed a statistically significant association between unhealthy diet and cerebrovascular accidents; between irregular performance of physical activity/sedentary lifestyle and endocrine/nutritional/metabolic and digestive diseases; between overweight and cardiovascular diseases, endocrine/nutritional/metabolic diseases, diabetes mellitus, and hypertension; and between smoking and musculoskeletal diseases. Conclusion: We suggest the adoption of preventative measures and the control of risk behaviors among these employees.

Is Communication a Mechanism of Relationship Education Effects among Rural African Americans?

Science.gov (United States)

Barton, Allen W; Beach, Steven R H; Lavner, Justin A; Bryant, Chalandra M; Kogan, Steven M; Brody, Gene H

2017-10-01

Enhancing communication as a means of promoting relationship quality has been increasingly questioned, particularly for couples at elevated sociodemographic risk. In response, the current study investigated communication change as a mechanism accounting for changes in relationship satisfaction and confidence among 344 rural, predominantly low-income African American couples with an early adolescent child who participated in a randomized controlled trial of the Protecting Strong African American Families (ProSAAF) program. Approximately 9 months after baseline assessment, intent-to-treat analyses indicated ProSAAF couples demonstrated improved communication, satisfaction, and confidence compared with couples in the control condition. Improvements in communication mediated ProSAAF effects on relationship satisfaction and confidence; conversely, neither satisfaction nor confidence mediated intervention effects on changes in communication. These results underscore the short-term efficacy of a communication-focused, culturally sensitive prevention program and suggest that communication is a possible mechanism of change in relationship quality among low-income African American couples.

Relationship Between Ischemic Heart Disease and Sexual Satisfaction.

Science.gov (United States)

Ghanbari Afra, Leila; Taghadosi, Mohsen; Gilasi, Hamid Reza

2015-06-10

Ischemic heart disease is a life-threatening condition. Considerable doubts exist over the effects of this disease on patients' sexual activity and satisfaction. The aim of this study was to evaluate the relationship between ischemic heart disease and sexual satisfaction. In a retrospective cohort study, the convenience sample of 150 patients exposure with ischemic heart disease and 150 people without exposure it was drawn from Shahid Beheshti hospital, Kashan, Iran. Sampling was performed from March to September 2014. We employed the Larson's Sexual Satisfaction Questionnaire for gathering the data. Data were analyzed using descriptive statistics and Chi-square, t-test and linear regression analysis. The means of sexual satisfaction in patients exposure with ischemic heart disease and among the subjects without exposure it were 101.47±13.42 and 100.91±16.52, respectively. There was no significant difference between the two groups regarding sexual satisfaction. However, sexual satisfaction was significantly correlated with gender and the use of cardiac medications (P valuepay closer attention to patient education about sexual issues.

Chemical Relationship On Detection Of Ganoderma Disease On Oil Palm Tree System

Science.gov (United States)

Imran, S. N. M.; Baharudin, F.; Ali, M. F.; Rahiman, M. H. F.

2018-04-01

Detection of fungal disease is the major issues in agricultural management and production. This disease would attack the plantation area and damaging the based root or the stem tissue of the trees. In oil palm industry, Basal Stem Rot (BSR) is the major disease in Malaysia that caused by a fungal named Ganoderma Boninense species. Since agricultural areas in Malaysia are the great factors that contribute in the economic sector, therefore the prevention and controlling this disease situation are needed to reduce the extent of the infection. These plant diseases are mostly being caused by the inflectional disease form such as viruses, viroids, bacteria, protozoa and even parasitic plants. It also could included mites and vertebrate or small insects that consume the plant tissues. Studies focused more on the breeding and relationship of the disease in the stumps, roots and soil system if oil palm trees by identifying the heavy metal; Phosphorus, copper, Iron, Manganese, Potassium and Zinc characteristic. Samples were taken from various types of physical appearance of the trees. It shows the relationship of the fungal disease breeding between oil palm trees and the heavy metals does affect the tree’s system.

Bidirectional relationship between diabetes and periodontal disease: Review of Evidence

International Nuclear Information System (INIS)

Mirza, B.A.Q.; Syed, A.; Izhar, F.; Ali Khan, A.A.

2010-01-01

Presently there are 170 million diabetic patients worldwide. Pakistan ranks sixth in the world with approximately 6.2 million in the 20-79 year age affected by the diabetes. 6-10% of the 35-44 year old diabetic patients have been reported to be affected by moderate form of periodontal disease in Pakistan. Periodontal disease is referred to as sixth complication of diabetes. The association between diabetes and periodontal disease has been reported for more than 40 years but reverse has not been the focus of researchers until recently. Studies have suggested a bidirectional relationship between periodontal disease and glycemic control with each disease having a potential impact on the other. (author)

Multiple mechanisms of transmission of the Caribbean coral disease white plague

Science.gov (United States)

Clemens, E.; Brandt, M. E.

2015-12-01

White plague is one of the most devastating coral diseases in the Caribbean, and yet important aspects of its epidemiology, including how the disease transmits, remain unknown. This study tested potential mechanisms and rates of transmission of white plague in a laboratory setting. Transmission mechanisms including the transport of water, contact with macroalgae, and predation via corallivorous worms and snails were tested on the host species Orbicella annularis. Two of the tested mechanisms were shown to transmit disease: water transport and the corallivorous snail Coralliophila abbreviata. Between these transmission mechanisms, transport of water between a diseased coral and a healthy coral resulted in disease incidence significantly more frequently in exposed healthy corals. Transmission via water transport also occurred more quickly and was associated with higher rates of tissue loss (up to 3.5 cm d-1) than with the corallivorous snail treatment. In addition, water that was in contact with diseased corals but was filtered with a 0.22-μm filter prior to being introduced to apparently healthy corals also resulted in the transmission of disease signs, but at a much lower rate than when water was not filtered. This study has provided important information on the transmission potential of Caribbean white plague disease and highlights the need for a greater understanding of how these processes operate in the natural environment.

The potential mechanisms for motor complications of Parkinson's disease

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SUN Sheng-gang

2013-08-01

Full Text Available Parkinson's disease (PD is a common neurodegenerative disease. Dopaminergic replacement therapy is still considered as a major treatment for PD. However, long-term dopaminergic replacement therapy for PD patients is frequently associated with the development of motor complications. To date, the mechanisms underlying motor complications have not been completely understood yet. Moreover, parts of motor complications are lack of therapeutic alternatives. All these characters make this disorder difficult and challenging to manage. Increasing number of researches have been proposed in recent years for elucidating the underlying mechanisms of levodopa-related motor complications, resulting in much progression. For better understanding the management of motor complications, here we provide an overview of the current knowledge of the potential mechanisms, including the pharmacodynamic and pharmacokinetic mechanisms of levodopa and levodopa-associated neurotransmitter systems.

The overdiagnosis of what? On the relationship between the concepts of overdiagnosis, disease, and diagnosis.

Science.gov (United States)

Hofmann, Bjørn

2017-12-01

Overdiagnosis and disease are related concepts. Widened conceptions of disease increase overdiagnosis and vice versa. This is partly because there is a close and complex relationship between disease and overdiagnosis. In order to address the problems with overdiagnosis, we may benefit from a closer understanding this relationship. Accordingly, the objective of this article is to elucidate the relationship between disease and overdiagnosis. To do so, the article starts with scrutinizing how overdiagnosis can explain the expansion of the concept of disease. Then it investigates how definitions of disease address various challenges of overdiagnosis. The article specifically investigates recent attempts to clarify the relationship between the concepts of disease and overdiagnosis. Several shortcomings are identified and lead to a closer analysis of overdiagnosis in the diagnostic process. Contrary to recent contributions to the field, it is argued that cases of overdiagnosis are not cases of disease. They are non-verified labelling of disease. It is revealed how overdiagnosis establishes an unwarranted link between indicative phenomena, such as polyps or cell changes, and harm, and thereby generates a link to disease. One implication of this study is that we should stop attributing disease language to indicative phenomena. That is, we should stop calling it "cancer screening" when we are actually searching for polyps. Another implications is that we should strive for scientific progress in differentiating phenomena that are of negative value to us from those that are not. In overdiagnosis we diagnose something that is not disease: it is over-diagnosis.

Corino de Andrade disease: mechanisms and impact on reproduction

Science.gov (United States)

Lopes, Rita A; Coelho, Teresa; Barros, Alberto; Sousa, Mário

2017-01-01

Familial amyloid polyneuropathy was first described by Corino de Andrade in 1952 in Northern Portugal. It is a fatal autosomal dominant neurodegenerative disorder characterized by a progression of neurologic symptoms, beginning early in the reproductive life. The Transthyretin gene mutation originates a mutated protein that precipitates in the connective tissue as amyloid deposits. This disease is presently named Transthyretin-related hereditary amyloidosis. We performed an extensive review on this disease based on searches in Medical databases and in paper references. In this review, we briefly summarize the epidemiology and the mechanisms involved on amyloid deposition; we detailed how to evaluate the mechanisms implicated on the development of the major signs and symptoms associated with reproductive dysfunction; and we discuss the mechanisms involved in secondary sexual dysfunction after psychological treatments. Treatment of the disease is directed towards relieving specific symptoms in association with liver transplant, and molecular and genetic therapeutics. Although the current clinical trials indicate symptoms relief, no data on the reproductive function was reported. Thus, preimplantation genetic diagnosis is presently the only available technique that eradicates the disease as it avoids the birth of new patients. PMID:28609277

Relationship between Occupational Stress and Gastric Disease in Male Workers

OpenAIRE

Lihm, Ho-Seob; Park, Sang-Hyun; Gong, Eun-Hee; Choi, Jong-Soon; Kim, Jung-Won

2012-01-01

Background Physical and mental health of workers is threatened due to various events and chronic occupational stress. This study was conducted to investigate the relationship between occupational stress and gastric disease in male workers of the shipbuilding industry. Methods Occupational stress measured among a total of 498 workers of a shipbuilding firm who visited the hospital for health examination using the Korean Occupational Stress Scale (KOSS)-short form, and the relationship between ...

The Relationship between Ischemic Heart Disease and Diabete

DEFF Research Database (Denmark)

Norgaard, Mette Lykke

2012-01-01

THE FOLLOWING OBJECTIVES ON THE SUBJECT: The relationship between ischemic heart disease and diabetes: 1. To examine the short- and long-term risk of death and cardiovascular outcomes in patients with incident diabetes and in patients with first-time MI during a 10 year period in Denmark, using the general...... diabetes increases with increasing severity of heart failure. Focus on the development of diabetes in patients with ischemic heart disease with or without the presence of heart failure still compose a public health matter, because early and aggressive evidence-based therapy is thought to reduce......Diabetes is a well-established risk factor for cardiovascular disease and is common among patients with acute myocardial infarction (MI), where the prevalence is as high as 20%. Patients with diabetes requiring glucose-lowering medication (GLM) have been reported as having the same long-term risk...

Can mechanical ventilation strategies reduce chronic lung disease?

Science.gov (United States)

Donn, Steven M; Sinha, Sunil K

2003-12-01

Chronic lung disease (CLD) continues to be a significant complication in newborn infants undergoing mechanical ventilation for respiratory failure. Although the aetiology of CLD is multifactorial, specific factors related to mechanical ventilation, including barotrauma, volutrauma and atelectrauma, have been implicated as important aetiologic mechanisms. This article discusses the ways in which these factors might be manipulated by various mechanical ventilatory strategies to reduce ventilator-induced lung injury. These include continuous positive airway pressure, permissive hypercapnia, patient-triggered ventilation, volume-targeted ventilation, proportional assist ventilation, high-frequency ventilation and real-time monitoring.

The relationship between helicobacter pylori infection and gastro-esophageal reflux disease

OpenAIRE

Batool M Mahdi

2011-01-01

Background : Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. Aim: The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. Patients and Methods: The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 ...

Chronic Wasting Disease: Transmission Mechanisms and the Possibility of Harvest Management

Science.gov (United States)

Potapov, Alex; Merrill, Evelyn; Pybus, Margo; Lewis, Mark A.

2016-01-01

We develop a model of CWD management by nonselective deer harvest, currently the most feasible approach available for managing CWD in wild populations. We use the model to explore the effects of 6 common harvest strategies on disease prevalence and to identify potential optimal harvest policies for reducing disease prevalence without population collapse. The model includes 4 deer categories (juveniles, adult females, younger adult males, older adult males) that may be harvested at different rates, a food-based carrying capacity, which influences juvenile survival but not adult reproduction or survival, and seasonal force of infection terms for each deer category under differing frequency-dependent transmission dynamics resulting from environmental and direct contact mechanisms. Numerical experiments show that the interval of transmission coefficients β where the disease can be controlled is generally narrow and efficiency of a harvest policy to reduce disease prevalence depends crucially on the details of the disease transmission mechanism, in particular on the intensity of disease transmission to juveniles and the potential differences in the behavior of older and younger males that influence contact rates. Optimal harvest policy to minimize disease prevalence for each of the assumed transmission mechanisms is shown to depend on harvest intensity. Across mechanisms, a harvest that focuses on antlered deer, without distinguishing between age classes reduces disease prevalence most consistently, whereas distinguishing between young and older antlered deer produces higher uncertainty in the harvest effects on disease prevalence. Our results show that, despite uncertainties, a modelling approach can determine classes of harvest strategy that are most likely to be effective in combatting CWD. PMID:26963921

Substitution Relationship Between The Agency Problem Control Mechanisms in Malaysia: Simultaneous Equation Analysis

Directory of Open Access Journals (Sweden)

D. Agus Harjito

2009-05-01

Full Text Available This study investigates the substitution relationship (substitutability between debt policy, insider ownership, and dividend policy as the agency problem control mechanism in Malaysia. If the substitution relationship exists between the agency control mechanisms, the agency problem can be reduced through this relationship. Reducing the agency problem as a result can increase the firm value proxied by Tobin’s Q. This study employs 396 firms sample listed on Malaysian Bourse from 2001 to 2004. To achieves the objectives, this study uses two-stage least square method. The results of this study indicate that the substitutability between debt policy, insider ownership, and dividend policy as agency problem control mechanism does not fully exist in Malaysia. Apparently the substitutability only exists for debt policy and dividend. There is no substitution between debt policy and insider ownership as well as between dividend policy and insider ownership. Key words: debt policy, insider ownership, dividend policy, agency problem, firm value

Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

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Ole A Andreassen

Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

Bidirectional relationship between renal function and periodontal disease in older Japanese women.

Science.gov (United States)

Yoshihara, Akihiro; Iwasaki, Masanori; Miyazaki, Hideo; Nakamura, Kazutoshi

2016-09-01

The purpose of this study was to evaluate the reciprocal effects of chronic kidney disease (CKD) and periodontal disease. A total of 332 postmenopausal never smoking women were enrolled, and their serum high-sensitivity C-reactive protein, serum osteocalcin and serum cystatin C levels were measured. Poor renal function was defined as serum cystatin C > 0.91 mg/l. Periodontal disease markers, including clinical attachment level and the periodontal inflamed surface area (PISA), were also evaluated. Logistic regression analysis was conducted to evaluate the relationships between renal function and periodontal disease markers, serum osteocalcin level and hsCRP level. The prevalence-rate ratios (PRRs) on multiple Poisson regression analyses were determined to evaluate the relationships between periodontal disease markers and serum osteocalcin, serum cystatin C and serum hsCRP levels. On logistic regression analysis, PISA was significantly associated with serum cystatin C level. The odds ratio for serum cystatin C level was 2.44 (p = 0.011). The PRR between serum cystatin C level and periodontal disease markers such as number of sites with clinical attachment level ≥6 mm was significantly positive (3.12, p periodontal disease can have reciprocal effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[A study of relationship between occupational stress and diseases in secondary school teachers].

Science.gov (United States)

Zhang, Yang; Zhu, Tao; Tang, Liu; Li, Jian; Lan, Yajia

2015-10-01

To analyze the relationship between occupational stress and diseases in secondary school teachers in a city of Sichuan Province, and to provide a basis for the evaluation of the long-term effects of occupational stress in teachers. With secondary school teachers as the target population, the stratified cluster sampling was adopted to conduct three studies among 780, 119, and 689 secondary school teachers in a city of Sichuan Province in 1999, 2005, and 2009, respectively. The Occupational Stress Inventory-Revised Edition (OSI-R) and working ability index (WAI) were used to investigate occupational stress and diseases in secondary school teachers. The variation of occupational stress in secondary school teachers was compared between different periods and the relationship between the intensity of stress and diseases was evaluated, on the basis of which the variation of the relationship over time was analyzed. There were significant differences in occupational stress in secondary school teachers between different periods (Pstress and psychological stress were significantly higher in 2009 than in 1999 (Poccupational stress in 2009 changed with cardiovascular, respiratory, and mental diseases. The incidence of abnormal psychological stress was a risk factor for all chronic, respiratory, and mental diseases (OR: 1.88, 2.25, and 5.91). The time dependence of odds ratio was only found in the risk of respiratory diseases: occupational stress resulted in a significant increase in the risk of respiratory diseases over time (Pstress was a risk factor for mental diseases (OR=2.31). The intensity of occupational stress in secondary school teachers changes over time. Occupational stress elevates the risks of certain diseases and has a time-dependent effect on the risk of respiratory diseases. Occupational stress in secondary school teachers needs more attention and effective prevention.

Relationship between chronic obstructive pulmonary disease and subclinical coronary artery disease in long-term smokers

DEFF Research Database (Denmark)

Rasmussen, Thomas; Køber, Lars; Pedersen, Jesper Holst

2013-01-01

Cardiovascular conditions are reported to be the most frequent cause of death in patients with chronic obstructive pulmonary disease (COPD). However, it remains unsettled whether severity of COPD per se is associated with coronary artery disease (CAD) independent of traditional cardiovascular risk...... factors. The aim of this study was to examine the relationship between the presence and severity of COPD and the amount of coronary artery calcium deposit, an indicator of CAD and cardiac risk, in a large population of current and former long-term smokers....

Efficient chemical-disease identification and relationship extraction using Wikipedia to improve recall.

Science.gov (United States)

Lowe, Daniel M; O'Boyle, Noel M; Sayle, Roger A

2016-01-01

Awareness of the adverse effects of chemicals is important in biomedical research and healthcare. Text mining can allow timely and low-cost extraction of this knowledge from the biomedical literature. We extended our text mining solution, LeadMine, to identify diseases and chemical-induced disease relationships (CIDs). LeadMine is a dictionary/grammar-based entity recognizer and was used to recognize and normalize both chemicals and diseases to Medical Subject Headings (MeSH) IDs. The disease lexicon was obtained from three sources: MeSH, the Disease Ontology and Wikipedia. The Wikipedia dictionary was derived from pages with a disease/symptom box, or those where the page title appeared in the lexicon. Composite entities (e.g. heart and lung disease) were detected and mapped to their composite MeSH IDs. For CIDs, we developed a simple pattern-based system to find relationships within the same sentence. Our system was evaluated in the BioCreative V Chemical-Disease Relation task and achieved very good results for both disease concept ID recognition (F1-score: 86.12%) and CIDs (F1-score: 52.20%) on the test set. As our system was over an order of magnitude faster than other solutions evaluated on the task, we were able to apply the same system to the entirety of MEDLINE allowing us to extract a collection of over 250 000 distinct CIDs. © The Author(s) 2016. Published by Oxford University Press.

BLAT2DOLite: An Online System for Identifying Significant Relationships between Genetic Sequences and Diseases.

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Liang Cheng

Full Text Available The significantly related diseases of sequences could play an important role in understanding the functions of these sequences. In this paper, we introduced BLAT2DOLite, an online system for annotating human genes and diseases and identifying the significant relationships between sequences and diseases. Currently, BLAT2DOLite integrates Entrez Gene database and Disease Ontology Lite (DOLite, which contain loci of gene and relationships between genes and diseases. It utilizes hypergeometric test to calculate P-values between genes and diseases of DOLite. The system can be accessed from: http://123.59.132.21:8080/BLAT2DOLite. The corresponding web service is described in: http://123.59.132.21:8080/BLAT2DOLite/BLAT2DOLiteIDMappingPort?wsdl.

Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools

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Adrian Kee Keong Teo

2015-09-01

Major conclusions: hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

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Kubben, Nard; Misteli, Tom

2017-10-01

Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

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Claudio Franceschi

2018-03-01

Full Text Available Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs and geriatric syndromes (GSs, is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are

THE CLINICAL AND PATHOGENETIC RELATIONSHIP BETWEEN BEHCET'S DISEASE AND MENTAL DISORDERS

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Daria Anatolyevna Ishchenko

2013-01-01

Full Text Available The paper analyzes the results of an investigation into the relationship between Behcet's disease (BB and mental disorders. It establishes the importance of an emotional stress factor for developing the clinical symptoms and disease. In its turn, the systemic immune inflammatory disease and its complications become a source of mental disorders. The literature describes different variants of BB, but anxiety-depressive spectrum disorders and moderate cognitive impairments are most common. The presence of depression contributes significantly to lower quality of life in patients with BB.

An Investigation into the Relationship between Cigarette Smoking and Diverticular Disease of the Colon

OpenAIRE

Christopher G Jamieson; Michael J Weinberg; Joanne Lorraine

1990-01-01

A retrospective study was conducted to determine the relationship between cigarette smoking and diverticular disease of the colon. One hundred and two patients undergoing barium enema were assessed for diverticular disease and smoking history. No significant positive association between smoking and diverticular disease was found.

Relationship between occupational stress and cardiovascular diseases risk factors in drivers.

Science.gov (United States)

Biglari, Hamed; Ebrahimi, Mohammad Hossein; Salehi, Maryam; Poursadeghiyan, Mohsen; Ahmadnezhad, Iman; Abbasi, Milad

2016-11-18

Of all work stressors, occupational stress is the leading cause of many disorders among workers. Drivers are classified as a high risk group for work related stress. This study set out to determine the relationship between risk factors of cardiovascular diseases and occupational stress among drivers. Two hundred and twenty two Ilam's intercity drivers were selected for the study. For measuring work stress, the Osipow work stress questionnaire was used. After a 10-h fasting period, systolic and diastolic blood pressure was recorded. Intravenous blood samples were taken to determine cholesterol, triglyceride and blood glucose levels. The independent samples t-test and Pearson's correlation test were used to assess the relationship between variables and occupational stress. Seventy-one percent of the intercity drivers suffered from average to acute stress, and 3.1% of them suffered from acute stress. There was no significant relationship between occupational stress and diastolic blood pressure (p = 0.254) among the drivers. Nevertheless, the Pearson's correlation test demonstrated a strong relationship between work stress and blood glucose (p stress were observed in the Ilam's intercity drivers. Occupational stress may have effect on blood glucose levels but the results did not suggest a considerable relationship between risk factors of cardiovascular diseases and occupational stress among intercity drivers. Int J Occup Med Environ Health 2016;29(6):895-901. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Temporal relationship between onset of Graves' ophthalmopathy and onset of thyroidal Graves' disease

NARCIS (Netherlands)

Wiersinga, W. M.; Smit, T.; van der Gaag, R.; Koornneef, L.

1988-01-01

The temporal relationship between the onset of Graves' ophthalmopathy and the onset of thyroidal Graves' disease was evaluated in 125 consecutive patients with Graves' ophthalmopathy. Thyroidal Graves' disease--past or present--was clinically evident in 99 patients (79%): hyperthyroidism in 3 cases.

Oxidative stress as a mechanism of added sugar-induced cardiovascular disease.

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Prasad, Kailash; Dhar, Indu

2014-12-01

Added sugars comprising of table sugar, brown sugar, corn syrup, maple syrup, honey, molasses, and other sweeteners in the prepared processed foods and beverages have been implicated in the pathophysiology of cardiovascular diseases. This article deals with the reactive oxygen species (ROS) as a mechanism of sugar-induced cardiovascular diseases. There is an association between the consumption of high levels of serum glucose with cardiovascular diseases. Various sources of sugar-induced generation of ROS, including mitochondria, nicotinamide adenine dinucleotide phosphate-oxidase, advanced glycation end products, insulin, and uric acid have been discussed. The mechanism by which ROS induce the development of atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias have been discussed in detail. In conclusion, the data suggest that added sugars induce atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias and that these effects of added sugars are mediated through ROS.

Infectivity versus Seeding in Neurodegenerative Diseases Sharing a Prion-Like Mechanism

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Natalia Fernández-Borges

2013-01-01

Full Text Available Prions are considered the best example to prove that the biological information can be transferred protein to protein through a conformational change. The term “prion-like” is used to describe molecular mechanisms that share similarities with the mammalian prion protein self-perpetuating aggregation and spreading characteristics. Since prions are presumably composed only of protein and are infectious, the more similar the mechanisms that occur in the different neurodegenerative diseases, the more these processes will resemble an infection. In vitro and in vivo experiments carried out during the last decade in different neurodegenerative disorders such as Alzheimer's disease (AD, Parkinson's diseases (PD, and amyotrophic lateral sclerosis (ALS have shown a convergence toward a unique mechanism of misfolded protein propagation. In spite of the term “infection” that could be used to explain the mechanism governing the diversity of the pathological processes, other concepts as “seeding” or “de novo induction” are being used to describe the in vivo propagation and transmissibility of misfolded proteins. The current studies are demanding an extended definition of “disease-causing agents” to include those already accepted as well as other misfolded proteins. In this new scenario, “seeding” would be a type of mechanism by which an infectious agent can be transmitted but should not be used to define a whole “infection” process.

Molecular mechanisms underlying the potential antiobesity-related diseases effect of cocoa polyphenols

NARCIS (Netherlands)

Ali, F.; Ismail, A.; Kersten, A.H.

2014-01-01

Obesity and related metabolic diseases (e.g., type 2 diabetes, cardiovascular diseases, and hypertension) are the most prevailing nutrition-related issues in the world. An emerging feature of obesity is their relationship with chronic inflammation that begins in white adipose tissue and eventually

Relationship satisfaction reduces the risk of maternal infectious diseases in pregnancy: the Norwegian Mother and Child Cohort Study.

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Roger Ekeberg Henriksen

Full Text Available The aims of this study were to explore the degree to which relationship satisfaction predicts the risk of infectious diseases during pregnancy and to examine whether relationship satisfaction moderates the association between stressful life events and the risk of infections.This was a prospective study based on data from the Norwegian Mother and Child Cohort Study (MoBa conducted by the Norwegian Institute of Public Health. Pregnant women (n = 67,244 completed questionnaires concerning relationship satisfaction and nine different categories of infectious diseases as well as socioeconomic characteristics and stressful life events. Associations between the predictor variables and the infectious diseases were assessed by logistic regression analyses. A multiple regression analysis was performed to assess a possible interaction of relationship satisfaction with stressful life events on the risk for infectious diseases.After controlling for marital status, age, education, income, and stressful life events, high levels of relationship satisfaction at week 15 of gestation were found to predict a significantly lower risk for eight categories of infectious diseases at gestational weeks 17-30. No significant interaction effect was found between relationship satisfaction and stressful life events on the risk for infections.

Relationship satisfaction reduces the risk of maternal infectious diseases in pregnancy: the Norwegian Mother and Child Cohort Study.

Science.gov (United States)

Henriksen, Roger Ekeberg; Torsheim, Torbjørn; Thuen, Frode

2015-01-01

The aims of this study were to explore the degree to which relationship satisfaction predicts the risk of infectious diseases during pregnancy and to examine whether relationship satisfaction moderates the association between stressful life events and the risk of infections. This was a prospective study based on data from the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Pregnant women (n = 67,244) completed questionnaires concerning relationship satisfaction and nine different categories of infectious diseases as well as socioeconomic characteristics and stressful life events. Associations between the predictor variables and the infectious diseases were assessed by logistic regression analyses. A multiple regression analysis was performed to assess a possible interaction of relationship satisfaction with stressful life events on the risk for infectious diseases. After controlling for marital status, age, education, income, and stressful life events, high levels of relationship satisfaction at week 15 of gestation were found to predict a significantly lower risk for eight categories of infectious diseases at gestational weeks 17-30. No significant interaction effect was found between relationship satisfaction and stressful life events on the risk for infections.

Chinese Herbal Medicine on Cardiovascular Diseases and the Mechanisms of Action.

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Liu, Cuiqing; Huang, Yu

2016-01-01

Cardiovascular diseases are the principal cause of death worldwide. The potentially serious adverse effects of therapeutic drugs lead to growing awareness of the role of Chinese herbal medicine in the treatment of cardiovascular diseases. Chinese herbal medicine has been widely used in many countries especially in China from antiquity; however, the mechanisms by which herbal medicine acts in the prevention and treatment of cardiovascular diseases are far from clear. In this review, we briefly describe the characteristics of Chinese herbal medicine by comparing with western medicine. Then we summarize the formulae and herbs/natural products applied in the clinic and animal studies being sorted according to the specific cardiovascular diseases. Most importantly, we elaborate the existing investigations into mechanisms by which herbal compounds act at the cellular levels, including vascular smooth muscle cells, endothelial cells, cardiomyocytes and immune cells. Future research should focus on well-designed clinic trial, in-depth mechanic study, investigations on side effects of herbs and drug interactions. Studies on developing new agents with effectiveness and safety from traditional Chinese medicine is a promising way for prevention and treatment of patients with cardiovascular diseases.

Transcending the biomarker mindset: deciphering disease mechanisms at the single cell level.

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Danna, Erika A; Nolan, Garry P

2006-02-01

The application of proteomics to disease research promises to enhance the understanding and treatment of many human maladies through the identification of molecular profiles associated with each disease. However, although much is made of the utility of molecular signatures as markers of disease state, insufficient emphasis is often placed on the simultaneous need for biological mechanism inquiry. Focused and detailed analyses of disease-associated signaling networks have the potential to be more mechanistically informative than large-scale proteomic profiling approaches, providing insight into the cellular processes involved in pathogenesis, disease progression and therapeutic resistance; while still providing diagnostic or clinical management direction. Phospho-specific flow cytometry provides a method for the analysis of pathological signaling networks, enabling the investigation of disease mechanisms at the single-cell level.

Kidney disease and obesity: epidemiology, mechanisms and treatment.

Science.gov (United States)

Câmara, Niels Olsen Saraiva; Iseki, Kunitoshi; Kramer, Holly; Liu, Zhi-Hong; Sharma, Kumar

2017-03-01

The theme of World Kidney Day 2017 is 'kidney disease and obesity: healthy lifestyle for healthy kidneys'. To mark this event, Nature Reviews Nephrology invited five leading researchers to describe changes in the epidemiology of obesity-related kidney disease, advances in current understanding of the mechanisms and current approaches to the management of affected patients. The researchers also highlight new advances that could lead to the development of novel treatments and identify areas in which further basic and clinical studies are needed.

[Relationship between disease burden and research funding through the Health Research Foundation in Spain].

Science.gov (United States)

Gómez-García, Teresa; Moreno-Casbas, Teresa; González-María, Esther; Fuentelsaz-Gallego, Carmen

2014-01-01

To analyze the relationship between burden of disease during 2007-2009 and public funding of research in health in Spain during 2008-2010. Descriptive cross-sectional study of burden of disease and funding allocated for research in diseases in the Spanish National Health System. A review was made of a total of 6,573 project titles funded for the years 2008, 2009 and 2010. During this period, a total of 472.7 million Euros were assigned as grants for research projects. Malignant tumors and neuropsychiatric diseases were the illnesses with greatest funding support. During the study period, it was estimated that there was a total of 15,253,331.3 disability-adjusted life years (DALYs) in Spain, with neuropsychiatric diseases being the category representing most DALYs with 4,396,900 (28.8%). The relationship between funding and DALYs was obtained with a Pearson r equal to 0.759 (p<0.001). The study of congenital diseases had higher funding per DALY than any other disease with an investment of 290.4€/DALY. Among these, the study of cleft palate and esophageal atresia, with ratios of 3,432.7€/DALY and 3,387.6€/DALY respectively, obtained the greatest funding. The study shows that the relative distribution of economic resources in the study period is consistent with the burden suffered by the Spanish population. This relationship is altered by the funding of the study of congenital anomalies, because of the low number of projects in this area. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity.

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Haliloglu, Sema; Carlioglu, Ayse; Akdeniz, Derya; Karaaslan, Yasar; Kosar, Ali

2014-09-01

Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain and the presence of specific tender points. The prevalence of FM has been estimated at 2-7 % of the general global population. The presence of FM in several rheumatic diseases with a structural pathology has been reported as 11-30 %. The objectives of this study were to determine the prevalence of FM and to evaluate the possible relationship between FM existence and disease activity among rheumatic diseases. The study group included 835 patients--197 rheumatoid arthritis (RA), 67 systemic lupus erythematosus (SLE), 119 ankylosing spondylitis (AS), 238 osteoarthritis (OA), 14 familial Mediterranean fever (FMF), 53 Behçet's disease (BD), 71 gout, 25 Sjögren's syndrome (SS), 20 vasculitis, 29 polymyalgia rheumatica (PMR), and two polymyositis (PM)--with or without FM. Recorded information included age, gender, laboratory parameters, presence of fatigue, and disease activity indexes. The prevalence of FM in patients with rheumatologic diseases was found to be 6.6 % for RA, 13.4 % for SLE, 12.6 % for AS, 10.1 % for OA, 5.7 % for BD, 7.1 % for FMF, 12 % for SS, 25 % for vasculitis, 1.4 % for gout, and 6.9 % for PMR. One out of two patients with PM was diagnosed with FM. Some rheumatologic cases (AS, OA) with FM were observed mostly in female patients (p = 0.000). Also, there were significant correlations between disease activity indexes and Fibromyalgia Impact Questionnaire scores for most rheumatologic patients (RA, AS, OA, and BD) (p diseases, and its recognition is important for the optimal management of these diseases. Increased pain, physical limitations, and fatigue may be interpreted as increased activity of these diseases, and a common treatment option is the prescription of higher doses of biologic agents or corticosteroids. Considerations of the FM component in the management of rheumatologic diseases increase the likelihood of the success of the treatment.

Making partner relationship management systems work: The role of partnership governance mechanisms

OpenAIRE

Storey, C.; Kocabasoglu-Hillmer, C.

2013-01-01

While the adoption of Partner Relationship Management (PRM) systems by suppliers to manage and monitor its network of partners (i.e. resellers) has been on the rise, the performance improvements have not been consistently realized. Governance theory suggests this may be due to how the PRM system builds on the mechanisms employed by the supplier to oversee their partners. This study investigates how the two capabilities of PRM systems (relationship and fulfillment capabilities) and two partner...

Gender differences in the relationship between built environment and non-communicable diseases: A systematic review.

Science.gov (United States)

Valson, Joanna Sara; Kutty, V Raman

2018-02-05

Non-communicable diseases are on the rise globally. Risk factors of non-communicable diseases continue to be a growing concern in both developed and developing countries. With significant rise in population and establishment of buildings, rapid changes have taken place in the built environment. Relationship between health and place, particularly with non-communicable diseases has been established in previous literature. This systematic review assesses the current evidence on influence of gender in the relationship between built environment and non-communicable diseases. A systematic literature search using PubMed was done to identify all studies that reported relationship between gender and built environment. All titles and abstracts were scrutinised to include only articles based on risk factors, prevention, treatment and outcome of non-communicable diseases. The Gender Analysis Matrix developed by the World Health Organization was used to describe the findings of gender differences. Sex differences, biological susceptibility, gender norms/ values, roles and activities related to gender and access to/control over resources were themes for the differences in the relationship. A total of 15 out of 214 articles met the inclusion criteria. Majority of the studies were on risk factors of non-communicable diseases, particularly cardiovascular diseases. Gender differences in physical access to recreational facilities, neighbourhood perceptions of safety and walkability have been documented. Men and women showed differential preferences to walking, engaging in physical activity and in perceiving safety of the neighbourhood. Girls and boys showed differences in play activities at school and in their own neighbourhood environment. Safety from crime and safety from traffic were also perceived important to engage in physical activity. Gender norms and gender roles and activities have shown basis for the differences in the prevalence of non-communicable diseases. Sparse

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

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Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

2012-04-01

Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena

Research progress of rehabilitation therapy in Parkinson's disease and its mechanism

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Jin LIU

2017-07-01

Full Text Available Parkinson's disease (PD is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rehabilitation therapy can delay the development of disease, improve motor symptoms and non - motor symptoms (NMS, and consequently improve the activities of daily living (ADL in patients with PD. The mechanism of rehabilitation improving the symptoms of PD is very complex, involving a variety of molecular mechanisms. Thus, this review will focus on the effect of rehabilitation therapy on PD and the underlying molecular mechanism including neurotransmitters, trophic factors, synaptic plasticity and immune system. DOI: 10.3969/j.issn.1672-6731.2017.06.003

Immune Evasion Mechanisms of Entamoeba histolytica: Progression to Disease.

Science.gov (United States)

Begum, Sharmin; Quach, Jeanie; Chadee, Kris

2015-01-01

Entamoeba histolytica (Eh) is a protozoan parasite that infects 10% of the world's population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO) production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells) that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states

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Cunningham TJ

2014-09-01

Full Text Available Timothy J Cunningham,1 Earl S Ford,1 Janet B Croft,1 Melissa T Merrick,2 Italia V Rolle,3 Wayne H Giles1 1Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA; 2Division of Violence Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA; 3Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA Purpose: Adverse childhood experiences (ACEs before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD in the general population. Materials and methods: Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs and their corresponding 95% confidence intervals (CIs for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Results: Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61, sexual abuse (PR =1.69, 95% CI: 1.36, 2.10, living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81, witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72, and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80 during childhood compared to those with no individual ACEs

Structural and functional measures of social relationships and quality of life among older adults: does chronic disease status matter?

Science.gov (United States)

Liao, Jing; Brunner, Eric J

2016-01-01

To evaluate the relative importance of structural and functional social relationships for quality of life (QoL) and the extent to which diagnosed chronic disease modifies these associations. Multivariate linear regression was used to investigate time-lagged associations between structural and functional measures of social relationships and QoL assessed 5 years apart by CASP-19, in 5925 Whitehall II participants (mean age 61, SD 6.0). Chronic disease was clinically verified coronary heart disease, stroke, diabetes or cancer. Social relationships-QoL associations were consistent across disease status (P-values for interaction: 0.15-0.99). Larger friend network (β = 1.9, 95% CI 1.5-2.3), having a partner (β = 1.2, 95% CI 0.5-1.7), higher confiding support (β = 2.2, 95% CI 1.8-2.7) and lower negative aspects of close relationships (β = 3.3, 95% CI 2.8-3.8) were independently related to improved QoL in old age. The estimated difference in QoL due to social relationships was equivalent to up to 0.5 SD of the CASP-19 score and was stronger than the effect of chronic disease (coronary heart disease β = 2.0, 95% CI 1.4-2.6). We found that beneficial aspects of social relationships in relation to QoL were, in order of importance: avoiding negative aspects of close relationships, having confiding support, having a wide network of friends and having a partner. These associations were not modified by chronic disease. Thus, despite inevitable physical deterioration, we may be able to enhance a satisfying late life by optimizing our social relationships.

Biomarkers and mechanisms of natural disease resistance in dairy cows

NARCIS (Netherlands)

Altena, van S.E.C.

2016-01-01

The aim of this thesis was to define and test biomarkers for disease resistance in dairy cows and to determine the underlying mechanism in natural disease resistance. The health status of the cows is an important issue in dairy farming. Due to the mandatory reduction in the use of antibiotics,

Issues in the use of costume and its relationship to skin diseases in ...

African Journals Online (AJOL)

This article focuses on the fundamental issues in the use of costumes and its relationship to skin diseases in the Nigerian theatre. It examines skin diseases that can be contracted through the use of contaminated costumes which can bring infections to the human skin. In the Nigerian theatre, like other theatre traditions ...

The Relationship Between Child Mortality Rates and Prevalence of Celiac Disease.

Science.gov (United States)

Biagi, Federico; Raiteri, Alberto; Schiepatti, Annalisa; Klersy, Catherine; Corazza, Gino R

2018-02-01

Some evidence suggests that prevalence of celiac disease in the general population is increasing over time. Because the prognosis of celiac disease was a dismal one before discovering the role of gluten, our aim was to investigate a possible relationship between children under-5 mortality rates and prevalence rates of celiac disease. Thanks to a literature review, we found 27 studies performed in 17 different countries describing the prevalence of celiac disease in schoolchildren; between 1995 and 2011, 4 studies were performed in Italy. A meta-analysis of prevalence rates was performed. Prevalence was compared between specific country under-5 mortality groups, publication year, and age. In the last decades, under-5 mortality rates have been decreasing all over the world. This reduction is paralleled by an increase of the prevalence of celiac disease. The Spearman correlation coefficient was -63%, 95% confidence interval -82% to -33% (P celiac disease in the general population. In the near future, the number of patients with celiac disease will increase, thanks to the better environmental conditions that nowadays allow a better survival of children with celiac disease.

Detection of mechanical and disease stresses in citrus plants by fluorescence spectroscopy

Science.gov (United States)

Belasque, J., Jr.; Gasparoto, M. C. G.; Marcassa, L. G.

2008-04-01

We have investigated the detection of mechanical and disease stresses in citrus plants (Citrus limonia [L.] Osbeck) using laser-induced fluorescence spectroscopy. Due to its economic importance we have chosen to investigate the citrus canker disease, which is caused by the Xanthomonas axonopodis pv. citri bacteria. Mechanical stress was also studied because it plays an important role in the plant's infection by such bacteria. A laser-induced fluorescence spectroscopy system, composed of a spectrometer and a 532 nm10 mW excitation laser was used to perform fluorescence spectroscopy. The ratio of two chlorophyll fluorescence bands allows us to detect and discriminate between mechanical and disease stresses. This ability to discriminate may have an important application in the field to detect citrus canker infected trees.

Parkinson Disease: The Relationship Between Non-motor Symptoms and Motor Phenotype.

Science.gov (United States)

Ba, Fang; Obaid, Mona; Wieler, Marguerite; Camicioli, Richard; Martin, W R Wayne

2016-03-01

Parkinson disease (PD) presents with motor and non-motor symptoms (NMS). The NMS often precede the onset of motor symptoms, but may progress throughout the disease course. Tremor dominant, postural instability gait difficulty (PIGD), and indeterminate phenotypes can be distinguished using Unified PD Rating scales (UPDRS-III). We hypothesized that the PIGD phenotype would be more likely to develop NMS, and that the non-dopamine-responsive axial signs would correlate with NMS severity. We conducted a retrospective cross-sectional chart review to assess the relationship between NMS and PD motor phenotypes. PD patients were administered the NMS Questionnaire, the UPDRS-III, and the Mini-Mental State Examination score. The relationship between NMS burden and PD subtypes was examined using linear regression models. The prevalence of each NMS among difference PD motor subtypes was analyzed using chi-square test. PD patients with more advanced disease based on their UPDRS-III had higher NMS Questionnaire scores. The axial component of UPDRS-III correlated with higher NMS. There was no correlation between NMS and tremor scores. There was a significant correlation between PIGD score and higher NMS burden. PIGD group had higher prevalence in most NMS domains when compared with tremor dominant and indeterminate groups independent of disease duration and severity. NMS profile and severity vary according to motor phenotype. We conclude that in the PD population, patients with a PIGD phenotype who have more axial involvement, associated with advanced disease and poor motor response, have a higher risk for a higher NMS burden.

Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study.

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Kudo, Chieko; Shin, Wee Soo; Minabe, Masato; Harai, Kazuo; Kato, Kai; Seino, Hiroaki; Goke, Eiji; Sasaki, Nobuhiro; Fujino, Takemasa; Kuribayashi, Nobuichi; Pearce, Youko Onuki; Taira, Masato; Maeda, Hiroshi; Takashiba, Shogo

2015-09-01

It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of "chronic inflammation". Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care. A pilot multicenter cross-sectional study was conducted on 37 medical patients with lifestyle-related diseases under consultation in participating medical clinics, and 79 periodontal patients not undergoing medical treatment but who were seen by participating dental clinics. Systemic examination and periodontal examination were performed at baseline, and the relationships between periodontal and atherosclerosis-related clinical markers were analyzed. There was a positive correlation between LDL-C level and plasma IgG antibody titer to Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut-off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer was significantly correlated with the level of low-density lipoprotein cholesterol (LDL-C). This study suggested that infection with periodontal bacteria (Porphyromonas gingivalis) is associated with the progression of atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as the clinical risk marker for atherosclerosis related to periodontal disease. Moreover, the application of the blood examination as a medical check may lead to the development of collaborative medical and dental care within the local medical clinical system for the purpose of preventing the lifestyle-related disease.

A model of cardiovascular disease giving a plausible mechanism for the effect of fractionated low-dose ionizing radiation exposure.

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Mark P Little

2009-10-01

Full Text Available Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally exposed groups receiving small daily radiation doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1 concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and cancer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapolation would be appropriate for this endpoint.

Relationship between Postural Deformities and Frontal Function in Parkinson’s Disease

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Satoko Ninomiya

2015-01-01

Full Text Available Postural deformities and executive dysfunction (ED are common symptoms of Parkinson’s disease (PD; however, the relationship between postural deformities and ED in patients with PD remains unclear. This study assessed the relationship between postural deformities and ED in patients with PD. Sixty-five patients with sporadic PD were assessed for the severity of postural deformities and executive function. The severity of postural deformities was scored using the United Parkinson’s Disease Rating Scale item 28 score: no postural deformity (0, mild postural deformities (1, or severe postural deformities (2–4. Executive function was assessed using the Behavioral Assessment of the Dysexecutive Syndrome (BADS and an age-controlled standardized BADS score <70 was defined as ED. Age-controlled standardized BADS scores were compared across the three groups using the Kruskal-Wallis test. Relationship between ED and the severity of postural deformities was assessed using the Mann-Whitney U test. Age-controlled standardized BADS score significantly differed among the three groups P=0.005. ED was significantly related to the severity of postural deformities P=0.0005. The severity of postural deformities was associated with a lower age-controlled standardized BADS score and ED, and these findings suggest that postural deformities were associated with frontal dysfunction in patients with PD.

Advances in mechanism research of pain in Parkinson's disease

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Hui LIU

2017-09-01

Full Text Available Parkinson's disease (PD, a neurodegenerative disease, is very common in middle aged and older people. There are two kinds of symptoms: motor symptoms and non - motor symptoms (NMS. Pain, a commonly reported NMS of PD, can significantly affect the quality of life, thus causing more attention. However, mechanisms of pain in PD is not clear, and need to be further researched. DOI: 10.3969/j.issn.1672-6731.2017.08.006

Immune evasion mechanisms of Entamoeba histolytica: progression to disease

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Sharmin eBegum

2015-12-01

Full Text Available Entamoeba histolytica (Eh is a protozoan parasite that infects 10% of the world’s population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

Relationship between biochemical factors and skin symptoms in chronic venous disease.

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Takai, Yasushi; Hiramoto, Keiichi; Nishimura, Yoshiyuki; Ooi, Kazuya

2017-05-01

Chronic venous disease (CVD) is a common venous disease of the lower extremities and patients often develop symptoms of itching and skin roughness. An easy to use and objective skin examination was recently developed that allows measurement of the level of stratum corneum content and transepidermal water loss (TEWL), which can indicate the status of the barrier function of the stratum corneum. Previous studies demonstrated that histamine production from mast cells, and tryptase and matrix metalloprotease-9 levels were associated with skin inflammation. This study aimed to clarify the relationship between dry skin and inflammatory mediators that mediate the skin symptoms of CVD subjects. The study enrolled 27 subjects with CVD and a control group consisting of 9 volunteers. The itching onset frequency was higher in women (70.4%) compared with men (50.0%). To analyze the mechanisms involved in itching we measured blood inflammatory mediators pre- and post-sclerotherapy. There was a significant decrease in Substance P, histamine, IgE, and tryptase levels post-sclerotherapy compared with those at pre-sclerotherapy. These levels were associated with the severity of itching. In addition, compared with the control subjects, there was a significant increase in the stratum corneum water content and a decrease in the TEWL in the 27 patients with CVD. This was associated with a decrease in the itching symptoms. Our findings indicate that sclerotherapy decreased levels of inflammatory mediators, increased stratum corneum water content and decreased TEWL, which coincided with reduced itching in CVD patients, indicating they might be therapeutic targets.

Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases.

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Han, Eugene; Lee, Yong Ho

2017-12-01

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.

Nuclear Mechanics in Disease

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Zwerger, Monika; Ho, Chin Yee; Lammerding, Jan

2015-01-01

Over the past two decades, the biomechanical properties of cells have emerged as key players in a broad range of cellular functions, including migration, proliferation, and differentiation. Although much of the attention has focused on the cytoskeletal networks and the cell’s microenvironment, relatively little is known about the contribution of the cell nucleus. Here, we present an overview of the structural elements that determine the physical properties of the nucleus and discuss how changes in the expression of nuclear components or mutations in nuclear proteins can affect not only nuclear mechanics but also modulate cytoskeletal organization and diverse cellular functions. These findings illustrate that the nucleus is tightly integrated into the surrounding cellular structure. Consequently, changes in nuclear structure and composition are highly relevant to normal development and physiology and can contribute to many human diseases, such as muscular dystrophy, dilated cardiomyopathy, (premature) aging, and cancer. PMID:21756143

Molecular mechanisms of disorders of lipid metabolism in chronic kidney disease.

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Moradi, Hamid; Vaziri, Nosratola D

2018-01-01

Chronic kidney disease (CKD) is a progressive condition marked by protracted kidney damage which over time can lead to end stage renal disease (ESRD). CKD can be categorized into different stages based on the extent of renal damage and degree of renal dysfunction with ESRD requiring renal replacement therapy considered the final stage. It is important to note that CKD in all of its forms is associated with accelerated atherosclerosis, cardiovascular (CV) disease and poor CV outcomes. While a number of factors contribute to the high risk of CV mortality in this patient population, dyslipidemia is considered to be a key player in the pathogenesis of CV disease in CKD. Molecular mechanisms responsible for CKD-associated lipid disorders are unique and greatly influenced by the stage of renal disease, presence and degree of proteinuria and in patients with ESRD, modality of renal replacement therapy. This article provides a detailed overview of the molecular mechanisms which cause dyslipidemia and the nature of lipid disorders associated with CKD and ESRD.

Governance mechanisms in transnational business relationships

OpenAIRE

Homburg, Christian; Kiedaisch, Ingo; Cannon, Joseph P.

1999-01-01

Empirical research on buyer-supplier relationships has almost exclusively examined domestic (both firms from the same country) exchange. The growing importance of international marketing and global sourcing suggest a need to understand relationships across national boundaries -- transnational business relationships. Drawing on theories of governance, the authors hypothesize differences in governance between domestic and transnational business relationships. They examine the use...

Additional mechanisms conferring genetic susceptibility to Alzheimer's disease

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Miguel eCalero

2015-04-01

Full Text Available Familial Alzheimer's disease (AD, mostly associated with early onset, is caused by mutations in three genes (APP, PSEN1 and PSEN2 involved in the production of the amyloid  peptide. In contrast, the molecular mechanisms that trigger the most common late onset sporadic AD remain largely unknown. With the implementation of an increasing number of case-control studies and the upcoming of large-scale genome-wide association studies (GWAS there is a mounting list of genetic risk factors associated to common genetic variants that have been associated to sporadic AD. Besides APOE, that presents a strong association with the disease (OR~4, the rest of these genes have moderate or low degrees of association, with OR ranging from 0.88 to 1.23. Taking together, these genes may account only for a fraction of the attributable AD risk and therefore, rare variants and epistastic gene interactions should be taken into account in order to get the full picture of the genetic risks associated to AD. Here, we review recent whole-exome studies looking for rare variants, somatic brain mutations with a strong association to the disease, and several studies dealing with epistasis as additional mechanisms conferring genetic susceptibility to AD. Altogether, recent evidence underlines the importance of defining molecular and genetic pathways and networks rather than the contribution of specific genes.

The relationship between helicobacter pylori infection and gastro-esophageal reflux disease.

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Mahdi, Batool M

2011-03-01

Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 as compared with 30 healthy patients from a control group that was age and sex matched. Helicobacter pylori CagA+ was identified by an immunological test (Immunochromatography test) (ACON, USA). Helicobacter pyloriCagA+ was present in 42/60 (70%) of the patients with gastro-esophageal reflux disease and in 11/30 (36.6%) patients in the control group (p=0.002). The Odds ratio = 0.8004 with 95% Confidence Interval = from 0.3188 to 2.0094. The relative risk=1.35 that indicates an association between Helicobacter pylori and disease. The presence of Helicobacter pylori is significantly increased in patients with gastro-esophageal reflux disease as compared with the control group.

Mechanisms of Disease: Host-Pathogen Interactions between Burkholderia Species and Lung Epithelial Cells

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David, Jonathan; Bell, Rachel E.; Clark, Graeme C.

2015-01-01

Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widely recognized as an important player in innate immunity and the early response to infections. Here we review the complex relationship between Burkholderia species and epithelial cells with an emphasis on the most pathogenic species, Burkholderia pseudomallei and Burkholderia mallei. The current gaps in knowledge in our understanding are highlighted along with the epithelial host-pathogen interactions that offer potential opportunities for therapeutic intervention. PMID:26636042

Trends in gluten research and its relationship to autoimmune and allergic diseases

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Edward J. Ciaccio

Full Text Available Introduction: Gluten is a protein found in certain grains, and causes an autoimmune response in celiac disease patients. Although the subject of considerable research, gluten research foci and future directions are largely unknown. Methods: The MEDLINE search tool was used to evaluate research trends. For perspective, yearly publications on gluten and other celiac disease reactive proteins were compared to food allergy proteins research. Then the relationship of gluten publications to affiliated keywords was determined. The affiliated keywords belonged to one of several groups: grains, vitamins and minerals, interaction, autoimmunity, genetics, or enzymes. The yearly number of publications in the peer-reviewed medical literature was determined for each relationship from years 1960–2013. The relationships were graphed, and linear regression analysis was used to determine the rate of change in publications per year, and the coefficient of determination. Results: Among celiac disease reactive proteins (gluten, gliadin, and glutenin and selected food allergy proteins (ovalbumin, lysozyme, ovomucoid, and Ara h, gluten showed the greatest rate of increase in published medical research (+20.01 studies/year since 1996, r2=0.97. Additionally, there were sharp increases in the rate of gluten research publications per year in association with keywords ‘autoimmunity’ (+7.69 studies/year since 1997, ‘wheat’ (+6.08 studies/year since 1999, and ‘transglutaminase’ enzyme (+5.05 studies/year since 1995. The longest running moderate trend was research on ‘gluten’ and ‘antibodies’ (+2.50 studies/year, r2=0.92 since 1971. Conclusions: Research on gluten as a reactive protein is of rapidly growing interest in the medical literature. MEDLINE is helpful to determine foci and future directions. Keywords: Celiac disease, Gluten, Gliadin, Medline, Transglutaminase

[Disease concept, etiology and mechanisms of multiple sclerosis].

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Kira, Jun-Ichi

2014-11-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system(CNS). MS is assumed to be caused by a complex interplay between genes and environments. Autoimmune mechanisms targeting CNS myelin has long been proposed, yet it has not been proved. Th17 cells producing interleukin-17 and Th1 cells producing interferon-gamma are postulated to play major roles in initiating inflammation while regulatory T cell functions are dampened. The forth nationwide survey of MS in Japan revealed that MS prevalence showed four-folds increase over 30 years and the increase was especially prominent in female. Thus, westernized life style and improved sanitation are suspected to increase MS susceptibility. Genome-wide association studies in Western MS patients disclosed more than 100 disease-susceptibility genes, most of which are immune-related genes. It therefore supports immune-mediated mechanisms to be operative. Detailed magnetic resonance imaging studies revealed an early atrophy of the cerebral gray matter where T cell infiltration is pathologically scarce. Therefore, neurodegenerative process also takes place in the early course beside neuroinflammation.

Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

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Silvia Sookoian

Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

Dose-response relationships for environmentally mediated infectious disease transmission models.

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Andrew F Brouwer

2017-04-01

Full Text Available Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose-response relationship. Much of the work characterizing the functional forms of dose-response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose-response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i middle- and high-dose data do not constrain the low-dose response, and different dose-response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain.

Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases (also published in Journal of Periodontology 2013 Apr 84 (4 Suppl): S51-69)

NARCIS (Netherlands)

Schenkein, H.A.; Loos, B.G.

2013-01-01

Aims In this article, inflammatory mechanisms that link periodontal diseases to cardiovascular diseases are reviewed. Methods This article is a literature review. Results Studies in the literature implicate a number of possible mechanisms that could be responsible for increased inflammatory

Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

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Nicola Gaetano Gatta

2016-11-01

Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or –OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review describes the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

Understanding The Relationships Between Noncommunicable Diseases, Unhealthy Lifestyles, And Country Wealth.

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Bollyky, Thomas J; Templin, Tara; Andridge, Caroline; Dieleman, Joseph L

2015-09-01

The amount of international aid given to address noncommunicable diseases is minimal. Most of it is directed to wealthier countries and focuses on the prevention of unhealthy lifestyles. Explanations for the current direction of noncommunicable disease aid include that these are diseases of affluence that benefit from substantial research and development into their treatment in high-income countries and are better addressed through domestic tax and policy measures to reduce risk-factor prevalence than through aid programs. This study assessed these justifications. First, we examined the relationships among premature adult mortality, defined as the probability that a person who has lived to the age of fifteen will die before the age of sixty from noncommunicable diseases; the major risk factors for these diseases; and country wealth. Second, we compared noncommunicable and communicable diseases prevalent in poor and wealthy countries alike, and their respective links to economic development. Last, we examined the respective roles that wealth and risk prevention have played in countries that achieved substantial reductions in premature mortality from noncommunicable diseases. Our results support greater investment in cost-effective noncommunicable disease preventive care and treatment in poorer countries and a higher priority for reducing key risk factors, particularly tobacco use. Project HOPE—The People-to-People Health Foundation, Inc.

Thermostability in rubredoxin and its relationship to mechanical rigidity

Science.gov (United States)

Rader, A. J.

2010-03-01

The source of increased stability in proteins from organisms that thrive in extreme thermal environments is not well understood. Previous experimental and theoretical studies have suggested many different features possibly responsible for such thermostability. Many of these thermostabilizing mechanisms can be accounted for in terms of structural rigidity. Thus a plausible hypothesis accounting for this remarkable stability in thermophilic enzymes states that these enzymes have enhanced conformational rigidity at temperatures below their native, functioning temperature. Experimental evidence exists to both support and contradict this supposition. We computationally investigate the relationship between thermostability and rigidity using rubredoxin as a case study. The mechanical rigidity is calculated using atomic models of homologous rubredoxin structures from the hyperthermophile Pyrococcus furiosus and mesophile Clostridium pasteurianum using the FIRST software. A global increase in structural rigidity (equivalently a decrease in flexibility) corresponds to an increase in thermostability. Locally, rigidity differences (between mesophilic and thermophilic structures) agree with differences in protection factors.

Thermostability in rubredoxin and its relationship to mechanical rigidity

International Nuclear Information System (INIS)

Rader, A J

2010-01-01

The source of increased stability in proteins from organisms that thrive in extreme thermal environments is not well understood. Previous experimental and theoretical studies have suggested many different features possibly responsible for such thermostability. Many of these thermostabilizing mechanisms can be accounted for in terms of structural rigidity. Thus a plausible hypothesis accounting for this remarkable stability in thermophilic enzymes states that these enzymes have enhanced conformational rigidity at temperatures below their native, functioning temperature. Experimental evidence exists to both support and contradict this supposition. We computationally investigate the relationship between thermostability and rigidity using rubredoxin as a case study. The mechanical rigidity is calculated using atomic models of homologous rubredoxin structures from the hyperthermophile Pyrococcus furiosus and mesophile Clostridium pasteurianum using the FIRST software. A global increase in structural rigidity (equivalently a decrease in flexibility) corresponds to an increase in thermostability. Locally, rigidity differences (between mesophilic and thermophilic structures) agree with differences in protection factors

The Relationship between Speech Production and Speech Perception Deficits in Parkinson's Disease

Science.gov (United States)

De Keyser, Kim; Santens, Patrick; Bockstael, Annelies; Botteldooren, Dick; Talsma, Durk; De Vos, Stefanie; Van Cauwenberghe, Mieke; Verheugen, Femke; Corthals, Paul; De Letter, Miet

2016-01-01

Purpose: This study investigated the possible relationship between hypokinetic speech production and speech intensity perception in patients with Parkinson's disease (PD). Method: Participants included 14 patients with idiopathic PD and 14 matched healthy controls (HCs) with normal hearing and cognition. First, speech production was objectified…

Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states.

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Cunningham, Timothy J; Ford, Earl S; Croft, Janet B; Merrick, Melissa T; Rolle, Italia V; Giles, Wayne H

2014-01-01

Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population. Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only. ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1

NARCIS (Netherlands)

Grabowski, Gregory A.; Kacena, Katherine; Cole, J. Alexander; Hollak, Carla E. M.; Zhang, Lin; Yee, John; Mistry, Pramod K.; Zimran, Ari; Charrow, Joel; vom Dahl, Stephan

2009-01-01

Purpose: To determine whether enzyme therapy with imiglucerase/ alglucerase demonstrates dose-response relationships with doses and disease parameters used in routine clinical practice for Gaucher disease type 1 patients. Methods: Analyses included all patients with Gaucher disease type 1 on enzyme

Relationship Between IL1 Gene Polymorphisms and Periodontal Disease in Japanese Women

OpenAIRE

Tanaka, Keiko; Miyake, Yoshihiro; Hanioka, Takashi; Arakawa, Masashi

2014-01-01

Epidemiological evidence on the relationship between IL1A and/or IL1B polymorphisms and periodontal disease is inconsistent. We investigated associations between three IL1 single-nucleotide polymorphisms (SNPs) in genes encoding interleukin (IL) -1α (rs1800587) and IL-1β (rs1143634 and rs16944) and the risk of periodontal disease among young Japanese women. A case–control study was performed with a total of 1150 women, including 131 subjects who had at least one tooth with a probing pocket de...

Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

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Jay S. Coggan

2015-09-01

Full Text Available Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases.

Examination of Mechanisms Responsible for Organic Dust-related Diseases: Mediator Release induced by Microorgansims. A review

DEFF Research Database (Denmark)

Norn, Svend; Clementsen, Paul; Kristensen, K.S.

1994-01-01

Farmakologi, org. dust-related diseases, bacteria, pathogenic mechanisms, mediator release, entoxins - fungal spores......Farmakologi, org. dust-related diseases, bacteria, pathogenic mechanisms, mediator release, entoxins - fungal spores...

Effect of transoral tracheal wash on respiratory mechanics in dogs with respiratory disease.

Science.gov (United States)

Vaught, Meghan E; Rozanski, Elizabeth A; deLaforcade, Armelle M

2018-01-01

The purpose of this study was to determine the impact of a transoral tracheal wash (TOTW) on respiratory mechanics in dogs and to describe the use of a critical care ventilator (CCV) to determine respiratory mechanics. Fourteen client-owned dogs with respiratory diseases were enrolled. Respiratory mechanics, including static compliance (C stat ) and static resistance (R stat ), were determined before and after TOTW. Pre- and post-wash results were compared, with a P -value of mechanics, as observed by a reduction in C stat , presumably due to airway flooding and collapse. While no long-lasting effects were noted in these clinical patients, this effect should be considered when performing TOTW on dogs with respiratory diseases. Respiratory mechanics testing using a CCV was feasible and may be a useful clinical testing approach.

Gut microbiota, immunity and disease: a complex relationship

Directory of Open Access Journals (Sweden)

Michele M Kosiewicz

2011-09-01

Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gut microbiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

ALLERGIC PATHOLOGY AND CELIAC DISEASE — MECHANISM OF COMMUNITY AND DIFFERENCES

Directory of Open Access Journals (Sweden)

M.O. Revnova

2010-01-01

Full Text Available The article is devoted to the differentiation of allergic diseases and celiac in children. It covers in detail the mechanisms of the pathogenesis of immune inflammation in celiac disease, clinical picture with the main and additional symptoms and markers of this pathology. In the article the author shares data of her own experience and provides the own diagnostic algorithm.Key words: allergic pathology, celiac disease, children. (Pediatric Pharmacology. – 2010; 7(1:76-80

The relationship between urban sprawl and coronary heart disease in women.

Science.gov (United States)

Griffin, Beth Ann; Eibner, Christine; Bird, Chloe E; Jewell, Adria; Margolis, Karen; Shih, Regina; Ellen Slaughter, Mary; Whitsel, Eric A; Allison, Matthew; Escarce, Jose J

2013-03-01

Studies have reported relationships between urban sprawl, physical activity, and obesity, but - to date - no studies have considered the relationship between sprawl and coronary heart disease (CHD) endpoints. In this analysis, we use longitudinal data on post-menopausal women from the Women's Health Initiative (WHI) Clinical Trial to analyze the relationship between metropolitan statistical area (MSA)-level urban compactness (the opposite of sprawl) and CHD endpoints including death, any CHD event, and myocardial infarction. Models control for individual and neighborhood socio-demographic characteristics. Women who lived in more compact communities at baseline had a lower probability of experiencing a CHD event and CHD death or MI during the study follow-up period. One component of compactness, high residential density, had a particularly noteworthy effect on outcomes. Finally, exploratory analyses showed evidence that the effects of compactness were moderated by race and region. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lnc2Meth: a manually curated database of regulatory relationships between long non-coding RNAs and DNA methylation associated with human disease.

Science.gov (United States)

Zhi, Hui; Li, Xin; Wang, Peng; Gao, Yue; Gao, Baoqing; Zhou, Dianshuang; Zhang, Yan; Guo, Maoni; Yue, Ming; Shen, Weitao; Ning, Shangwei; Jin, Lianhong; Li, Xia

2018-01-04

Lnc2Meth (http://www.bio-bigdata.com/Lnc2Meth/), an interactive resource to identify regulatory relationships between human long non-coding RNAs (lncRNAs) and DNA methylation, is not only a manually curated collection and annotation of experimentally supported lncRNAs-DNA methylation associations but also a platform that effectively integrates tools for calculating and identifying the differentially methylated lncRNAs and protein-coding genes (PCGs) in diverse human diseases. The resource provides: (i) advanced search possibilities, e.g. retrieval of the database by searching the lncRNA symbol of interest, DNA methylation patterns, regulatory mechanisms and disease types; (ii) abundant computationally calculated DNA methylation array profiles for the lncRNAs and PCGs; (iii) the prognostic values for each hit transcript calculated from the patients clinical data; (iv) a genome browser to display the DNA methylation landscape of the lncRNA transcripts for a specific type of disease; (v) tools to re-annotate probes to lncRNA loci and identify the differential methylation patterns for lncRNAs and PCGs with user-supplied external datasets; (vi) an R package (LncDM) to complete the differentially methylated lncRNAs identification and visualization with local computers. Lnc2Meth provides a timely and valuable resource that can be applied to significantly expand our understanding of the regulatory relationships between lncRNAs and DNA methylation in various human diseases. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Effect and Mechanism of Chinese Herbal Medicine on Parkinson's Disease.

Science.gov (United States)

Zeng, Bai-Yun

2017-01-01

Parkinson's disease is a progressive neurodegenerative disorder. Although both genetic and environmental factors are implicated in the development of Parkinson's disease, the cause of the disease is still unclear. So far conventional treatments to Parkinson's are symptomatic relief and focused mainly on motor symptoms. Chinese herbal medicine has been used to treat many conditions in China, Korea, Japan, and many Southeast Asian countries for 1000 years. During past a few decades, Chinese herbal medicine has gained wider and increasing acceptance within both public and medical profession due to its effectiveness on many conditions in western countries. In this chapter, mechanisms of action of many Chinese herbal compounds/extracts and Chinese herb formulas on the models of Parkinson's were reviewed. Further, reports of effectiveness of Chinese herb formulas on patients with Parkinson's were summarized. It was shown that both Chinese herbal compounds/extracts and herb formulas have either specific target mechanisms of action or multitargets mechanisms of action, as antioxidant, antiinflammatory, and antiapoptosis agents. Clinical studies showed that Chinese herb formulas as an adjunct improved both motor and nonmotor symptoms, and reduced dose of dopaminergic drugs and occurrence of dyskinesia. The evidence from the studies suggests that Chinese herb medicine has potential, acting as neuroprotective to slow down the progression of Parkinson's, and it is able to simultaneously treat both motor and nonmotor symptoms of Parkinson's. More studies are needed to explore the new compounds/extracts derived from Chinese herbs, in particular, their mechanisms of action. It is hopeful that new drugs developed from Chinese herb compounds/extracts and Chinese herb formulas will lead to better and complimentary therapy to PD. © 2017 Elsevier Inc. All rights reserved.

Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

Science.gov (United States)

Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

2016-11-01

In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially misfolded intermediates aggregate via the interaction with the complementary intermediates and consequently enhance oligomers formation that grows into fibrils and proto-fibrils. The amyloid fibrils for example, accumulate in the brain and central nervous system (CNS) as amyloid deposits in the Parkinson's disease (PD), Alzheimer's disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other neurodegenerative diseases. Treatment of such misfolding maladies is considered as one of the most important challenges of the 21st century. Currently, several treatments strategies have been and are being discovered. These therapeutic interventions partly reversed or prevented the pathological state. More recently, a new approach was discovered, which employs nanobodies that targets multisteps in fibril formation pathway that may possibly completely cure these misfolding diseases. Keeping the above views in mind in the current review, we have comprehensively discussed the different mechanisms underlying protein misfolding thereby leading to diseases conditions and their therapeutic interventions.

Recent advances in delivery mechanisms for aerosol therapy during pediatric respiratory diseases.

Science.gov (United States)

Wu, Yue'E; Zhang, Chonglin; Zhen, Qing

2018-04-01

The treatment of pediatric surgery diseases via utilization of aerosol delivery mechanisms is in progress for the betterment of pediatric care. Over the years, aerosol therapy has come to play an integral role in the treatment of pediatric respiratory diseases. Inhaled aerosol agents such as bronchodilators, corticosteroids, antibiotics, and mucolytics are commonly delivered to spontaneously breathing pediatric patients with a tracheostomy. Administering therapeutic inhaled aerosols to pediatric patients is challenging. The pediatric population ranges in age, which means patients with different airway sizes, breathing patterns, and cooperation levels. These patient-related factors impact the deposition of aerosol drugs in the lungs. The present review article will discuss the recent advancements in the delivery mechanisms for aerosol therapy in pediatric patients with respiratory diseases.

The Relationship Between the Gensini Score and Complete Blood Count Parameters in Coronary Artery Disease

Directory of Open Access Journals (Sweden)

Muhammet Raşit Sayın

2012-08-01

Full Text Available Introduction: The aim of this study was to evaluate the relationship between the extend andseverity of coronary artery disease (CAD determined by the Gensini score and complete bloodcount parameters (white blood cell, hemoglobin, platelet, mean platelet volume, lymphocyte,neutrophil.Patients and Methods: Ninety patients with CAD underwent coronary angiography (40 females,mean age 61 ± 1.2 years were included in this study. Patients with acute coronary syndrome andprior cardiovascular disease excluded from the study. The association between the extent andseverity of CAD, which were assessed by the Gensini score, and complete blood count parameterswas analyzed by a correlation analysis.Results: Coronary angiography revealed, 6 (6.7% patients had three, 16 (17.8% patients hadtwo, and 24 (26.7% patients had single-vessel disease; 44 (48.9% patients had non-criticalstenosis. The mean Gensini score was 19.1 ± 2.1. We found a relationship between white bloodcell and neutrophil counts and the Gensini score. There was no relationship between Gensiniscore and the mean platelet volume and other parameters.Conclusion: The present study supports the hypothesis that inflammation is one of the maincomponent in the pathogenesis of CAD.

Social Relationships and Health: The Toxic Effects of Perceived Social Isolation

OpenAIRE

Cacioppo, John T.; Cacioppo, Stephanie

2014-01-01

Research in social epidemiology suggests that the absence of positive social relationships is a significant risk factor for broad-based morbidity and mortality. The nature of these social relationships and the mechanisms underlying this association are of increasing interest as the population gets older and the health care costs associated with chronic disease escalate in industrialized countries. We review selected evidence on the nature of social relationships and focus on one particular fa...

Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes.

Science.gov (United States)

Han, Kyu-Ho; Hashimoto, Naoto; Fukushima, Michihiro

2016-01-07

Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide. The metabolism of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, regulate the expression of ALD-associated proteins and peptides, namely, catalase, superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase. These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway and antioxidant responsive elements. Furthermore, these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines. These phenomena are likely induced via the regulation of mitogen-activating protein kinase (MAPK) pathways by plant antioxidants, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.

Molecular mechanisms of acrolein toxicity: relevance to human disease.

Science.gov (United States)

Moghe, Akshata; Ghare, Smita; Lamoreau, Bryan; Mohammad, Mohammad; Barve, Shirish; McClain, Craig; Joshi-Barve, Swati

2015-02-01

Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Elucidation of Molecular Pathogenic Mechanisms of Norrie Disease

OpenAIRE

Luhmann, Ulrich F.O.

2010-01-01

Summary Norrie disease (ND) is a rare X-linked recessive congenital blindness, sometimes associated with deafness and mental retardation. In this thesis the molecular pathogenic mechanisms of this syndrome should be elucidated using the Ndph knockout mouse model. Gene expression studies but also histology and protein biochemistry were used to characterize the affected organs, eye and brain. Gene expression analyses of eyes at p21 using cDNA subtrac...

Relationships between chemical structure, mechanical properties and materials processing in nanopatterned organosilicate fins

Directory of Open Access Journals (Sweden)

Gheorghe Stan

2017-04-01

Full Text Available The exploitation of nanoscale size effects to create new nanostructured materials necessitates the development of an understanding of relationships between molecular structure, physical properties and material processing at the nanoscale. Numerous metrologies capable of thermal, mechanical, and electrical characterization at the nanoscale have been demonstrated over the past two decades. However, the ability to perform nanoscale molecular/chemical structure characterization has only been recently demonstrated with the advent of atomic-force-microscopy-based infrared spectroscopy (AFM-IR and related techniques. Therefore, we have combined measurements of chemical structures with AFM-IR and of mechanical properties with contact resonance AFM (CR-AFM to investigate the fabrication of 20–500 nm wide fin structures in a nanoporous organosilicate material. We show that by combining these two techniques, one can clearly observe variations of chemical structure and mechanical properties that correlate with the fabrication process and the feature size of the organosilicate fins. Specifically, we have observed an inverse correlation between the concentration of terminal organic groups and the stiffness of nanopatterned organosilicate fins. The selective removal of the organic component during etching results in a stiffness increase and reinsertion via chemical silylation results in a stiffness decrease. Examination of this effect as a function of fin width indicates that the loss of terminal organic groups and stiffness increase occur primarily at the exposed surfaces of the fins over a length scale of 10–20 nm. While the observed structure–property relationships are specific to organosilicates, we believe the combined demonstration of AFM-IR with CR-AFM should pave the way for a similar nanoscale characterization of other materials where the understanding of such relationships is essential.

Possible mechanisms for arsenic-induced proliferative diseases

Energy Technology Data Exchange (ETDEWEB)

Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

1996-12-31

Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

BioM2MetDisease: a manually curated database for associations between microRNAs, metabolites, small molecules and metabolic diseases.

Science.gov (United States)

Xu, Yanjun; Yang, Haixiu; Wu, Tan; Dong, Qun; Sun, Zeguo; Shang, Desi; Li, Feng; Xu, Yingqi; Su, Fei; Liu, Siyao; Zhang, Yunpeng; Li, Xia

2017-01-01

BioM2MetDisease is a manually curated database that aims to provide a comprehensive and experimentally supported resource of associations between metabolic diseases and various biomolecules. Recently, metabolic diseases such as diabetes have become one of the leading threats to people’s health. Metabolic disease associated with alterations of multiple types of biomolecules such as miRNAs and metabolites. An integrated and high-quality data source that collection of metabolic disease associated biomolecules is essential for exploring the underlying molecular mechanisms and discovering novel therapeutics. Here, we developed the BioM2MetDisease database, which currently documents 2681 entries of relationships between 1147 biomolecules (miRNAs, metabolites and small molecules/drugs) and 78 metabolic diseases across 14 species. Each entry includes biomolecule category, species, biomolecule name, disease name, dysregulation pattern, experimental technique, a brief description of metabolic disease-biomolecule relationships, the reference, additional annotation information etc. BioM2MetDisease provides a user-friendly interface to explore and retrieve all data conveniently. A submission page was also offered for researchers to submit new associations between biomolecules and metabolic diseases. BioM2MetDisease provides a comprehensive resource for studying biology molecules act in metabolic diseases, and it is helpful for understanding the molecular mechanisms and developing novel therapeutics for metabolic diseases. http://www.bio-bigdata.com/BioM2MetDisease/. © The Author(s) 2017. Published by Oxford University Press.

Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

Science.gov (United States)

Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

2017-11-01

Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Relationship between Marketing Strategies and Governance Mechanisms: A Study in Exploration Chain Beef Cattle

Directory of Open Access Journals (Sweden)

Filipe Quevedo-Silva

2015-09-01

Full Text Available The relationship between actors has been unspoilt by marketing through the bias of Transaction Costs Economics. Some authors suggest that a marketing strategy can directly impact the transactional characteristics and hence the governance mechanisms chosen to coordinate transactions. Studies suggest that future work in the field of marketing include, among other factors, aspects related to the relationship between the actors. In this context, this article aims to analyze how marketing strategies can affect the choice of governance mechanisms. The study object is the chain of beef, view their representation to the national economy. To this end, we conducted a qualitative study using semi-structured interviews with various actors in the chain. It was possible to verify the existence of the relationship between marketing strategy and governance structure. In one of the cases, product differentiation, translated into more specific assets, led the producer to perform a relational contract with the fridge and to distribute your product, make an integration with retailers, through the opening of a boutique of meat. Factor that was not observed in transactions involving producers on products without distinction, for which the transactions via spot market are prevalent.  

Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

DEFF Research Database (Denmark)

Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah

2016-01-01

’s disease (PD), Alzheimer’s disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other......In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post......-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially...

Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

Science.gov (United States)

Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

2015-01-01

A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

Directory of Open Access Journals (Sweden)

Yidan Ma

Full Text Available A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women

Science.gov (United States)

Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

2015-01-01

A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed. PMID:26309232

Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms

Directory of Open Access Journals (Sweden)

Fengyuan Li

2016-01-01

Full Text Available Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.

Cardiovascular diseases and periodontology.

Science.gov (United States)

Seymour, R A; Preshaw, P M; Thomason, J M; Ellis, J S; Steele, J G

2003-04-01

Cardiovascular diseases represent a widespread heterogeneous group of conditions that have significant morbidity and mortality. The various diseases and their treatments can have an impact upon the periodontium and the delivery of periodontal care. In this paper we consider three main topics and explore their relationship to the periodontist and the provision of periodontal treatment. The areas reviewed include the effect of cardiovascular drugs on the periodontium and management of patients with periodontal diseases; the risk of infective endocarditis arising from periodontal procedures; the inter-relationship between periodontal disease and coronary artery disease. Calcium-channel blockers and beta-adrenoceptor blockers cause gingival overgrowth and tooth demineralisation, respectively. Evidence suggests that stopping anticoagulant therapy prior to periodontal procedures is putting patients at a greater risk of thromboembolic disorders compared to the risk of prolonged bleeding. The relationship between dentistry and infective endocarditis remains a controversial issue. It would appear that spontaneous bacteraemia arising from a patient's oral hygiene practices is more likely to be the cause of endocarditis than one-off periodontal procedures. The efficacy of antibiotic prophylaxis is uncertain (and unlikely to be proven), and the risk of death from penicillin appears to be greater than the risk of death arising from infective endocarditis. Finally, the association between periodontal disease and coronary artery disease has been explored and there seem to be many issues with respect to data handling interpretation. Many putative mechanisms have been suggested; however, these only further highlight the need for intervention studies.

STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF DITERPENES FOR TREATMENT OF ALZHEIMER'S DISEASE

Directory of Open Access Journals (Sweden)

Gabriel F. dos Santos

Full Text Available Alzheimer's disease is an irreversible, degenerative and age-related disease which is growing more and more with the increase in life expectancy. Kaurane diterpenes are a class of natural products available in large amounts in nature and isolated from plants grown worldwide. In the present work¸ twenty-seven kaurane diterpenes of natural origin and some readily available derivatives were assayed for acetylcholinesterase inhibition and the structure-activity relationship was analyzed. The kaurenoic acid derivatives screened showed to be promising inhibitors of AChE, which could provide new leads for drugs to fight Alzheimer's disease symptoms. Among them, eleven compounds showed activities comparable or higher than the positive control galantamine. Existence of an allylic hydroxyl group showed to be an important structural feature for AChE inhibition. In addition, presence of free hydroxyl groups at C-17 and C-19, furnished a diol especially active, able to completely inhibit AChE.

Relationship between stress factor and periodontal disease in a rural area population in Japan

OpenAIRE

Akhter, Rahena; Hannan, MA; Okhubo, R; Morita, M

2005-01-01

Objectives: Several studies conducted in Western countries have shown significant associations between stress factors and periodontal disease. However, there have been only a few studies conducted in Asian countries. The present study was designed to identify possible relationship between stress and periodontal disease in residents of a rural area in Japan. Material and Methods: Data were collected from 1,089 adults with at least six natural teeth in a typical farming district of Japan. S...

The diversity–disease relationship

NARCIS (Netherlands)

Huang, Z.Y.X.; Langevelde, van F.; Estrada-Peña, A.; Suzán, G.; Boer, de W.F.

2016-01-01

The dilution effect, that high host species diversity can reduce disease risk, has attracted much attention in the context of global biodiversity decline and increasing disease emergence. Recent studies have criticized the generality of the dilution effect and argued that it only occurs under

Shared genetic variants suggest common pathways in allergy and autoimmune diseases

DEFF Research Database (Denmark)

Kreiner-Møller, Eskil; Waage, Johannes; Standl, Marie

2017-01-01

Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed two GWAS on self-r...

Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

Science.gov (United States)

Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases

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Lee J. Martin

2010-03-01

Full Text Available Alzheimer’s disease (AD, Parkinson’s disease (PD and amyotrophic lateral sclerosis (ALS are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations, triggering neurodegeneration according to a cell death matrix theory. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. In PD, mutations in putative mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This review summarizes how mitochondrial pathobiology might contribute to neuronal death in AD, PD, and ALS and could serve as a target for drug therapy.

[Relationship between periodontitis and levels of high-sensitivity C-reactive protein].

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Pan, Heng-biao; Chen, Hui; Zhou, Na; Jin, Dan; Zhang, Jing; Peng, Chun-mei

2010-08-01

To evaluate the relationship between periodontitis and the traditional risk factors of coronary heart disease (CHD), as well as the role in the mechanisms responsible for high-sensitivity C-reactive protein (hsCRP) in the relationship of peridontitis and CHD. A periodontal examination was conducted on a total of 356 subjects, and community periodontal index of treatment needs (CPITN) was obtained from each subject. Periodontal status was categorized into TN periodontal, hsCRP concentration and routinely CHD serological indexes. In the groups of TN periodontal pockets were found in the Group hsCRP > or = 3.0 mg x L(-1) (P periodontal disease.

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases.

Science.gov (United States)

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-07-28

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.

Molecular mechanisms in lithium-associated renal disease: a systematic review.

Science.gov (United States)

Rej, Soham; Pira, Shamira; Marshe, Victoria; Do, André; Elie, Dominique; Looper, Karl J; Herrmann, Nathan; Müller, Daniel J

2016-11-01

Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease. We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium's effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers. From a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD. Future studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium's biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events.

Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice.

Science.gov (United States)

Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Susumu, Nobuyuki; Aoki, Daisuke

2012-04-01

Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.

Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

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Marcel eLevy Nogueira

2015-09-01

Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases.

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Fridkis-Hareli, Masha

2008-02-15

Organ-specific autoimmune diseases affect particular targets in the body, whereas systemic diseases engage multiple organs. Both types of autoimmune diseases may coexist in the same patient, either sequentially or concurrently, sustained by the presence of autoantibodies directed against the corresponding autoantigens. Multiple factors, including those of immunological, genetic, endocrine and environmental origin, contribute to the above condition. Due to association of certain autoimmune disorders with HLA alleles, it has been intriguing to examine the immunogenetic basis for autoantigen presentation leading to the production of two or more autoantibodies, each distinctive of an organ-specific or systemic disease. This communication offers the explanation for shared autoimmunity as illustrated by organ-specific blistering diseases and the connective tissue disorders of systemic nature. Several hypothetical mechanisms implicating HLA determinants, autoantigenic peptides, T cells, and B cells have been proposed to elucidate the process by which two autoimmune diseases are induced in the same individual. One of these scenarios, based on the assumption that the patient carries two disease-susceptible HLA genes, arises when a single T cell epitope of each autoantigen recognizes its HLA protein, leading to the generation of two types of autoreactive B cells, which produce autoantibodies. Another mechanism functioning whilst an epitope derived from either autoantigen binds each of the HLA determinants, resulting in the induction of both diseases by cross-presentation. Finally, two discrete epitopes originating from the same autoantigen may interact with each of the HLA specificities, eliciting the production of both types of autoantibodies. Despite the lack of immediate or unequivocal experimental evidence supporting the present hypothesis, several approaches may secure a better understanding of shared autoimmunity. Among these are animal models expressing the transgenes

Relationships between surface coverage ratio and powder mechanics of binary adhesive mixtures for dry powder inhalers.

Science.gov (United States)

Rudén, Jonas; Frenning, Göran; Bramer, Tobias; Thalberg, Kyrre; Alderborn, Göran

2018-04-25

The aim of this paper was to study relationships between the content of fine particles and the powder mechanics of binary adhesive mixtures and link these relationships to the blend state. Mixtures with increasing amounts of fine particles (increasing surface coverage ratios (SCR)) were prepared using Lactopress SD as carrier and micro particles of lactose as fines (2.7 µm). Indicators of unsettled bulk density, compressibility and flowability were derived and the blend state was visually examined by imaging. The powder properties studied showed relationships to the SCR characterised by stages. At low SCR, the fine particles predominantly gathered in cavities of the carriers, giving increased bulk density and unchanged or improved flow. Thereafter, increased SCR gave a deposition of particles at the enveloped carrier surface with a gradually more irregular adhesion layer leading to a reduced bulk density and a step-wise reduced flowability. The mechanics of the mixtures at a certain stage were dependent on the structure and the dynamics of the adhesion layer and transitions between the stages were controlled by the evolution of the adhesion layer. It is advisable to use techniques based on different types of flow in order to comprehensively study the mechanics of adhesive mixtures. Copyright © 2018 Elsevier B.V. All rights reserved.

Up-Beat UK: A programme of research into the relationship between coronary heart disease and depression in primary care patients

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Pariante Carmine M

2011-05-01

Full Text Available Abstract Background Coronary heart disease and depression are both common health problems and by 2020 will be the two leading causes of disability worldwide. Depression has been found to be more common in patients with coronary heart disease but the nature of this relationship is uncertain. In the United Kingdom general practitioners are now being remunerated for case-finding for depression in patients with coronary heart disease, however it is unclear how general practitioners should manage these patients. We aim to explore the relationship between coronary heart disease and depression in a primary care population and to develop an intervention for patients with coronary heart disease and depression. Methods/design This programme of research will consist of 4 inter-related studies. A 4 year prospective cohort study of primary care patients with coronary heart disease will be conducted to explore the relationship between coronary heart disease and depression. Within this, a nested case-control biological study will investigate genetic and blood-biomarkers as predictors of depression in this sample. Two qualitative studies, one of patients' perspectives of treatments for coronary heart disease and co-morbid depression and one of primary care professionals' views on the management of patients with coronary heart disease and depression will inform the development of an intervention for this patient group. A feasibility study for a randomised controlled trial will then be conducted. Discussion This study will provide information on the relationship between coronary heart disease and depression that will allow health services to determine the efficiency of case-finding for depression in this patient group. The results of the cohort study will also provide information on risk factors for depression. The study will provide evidence on the efficacy and feasibility of a joint patient and professional led intervention and data necessary to plan a

Developmental Origins of Chronic Renal Disease: An Integrative Hypothesis

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F. Boubred

2013-01-01

Full Text Available Cardiovascular diseases are one of the leading causes of mortality. Hypertension (HT is one of the principal risk factors associated with death. Chronic kidney disease (CKD, which is probably underestimated, increases the risk and the severity of adverse cardiovascular events. It is now recognized that low birth weight is a risk factor for these diseases, and this relationship is amplified by a rapid catch-up growth or overfeeding during infancy or childhood. The pathophysiological and molecular mechanisms involved in the “early programming” of CKD are multiple and partially understood. It has been proposed that the developmental programming of arterial hypertension and chronic kidney disease is related to a reduced nephron endowment. However, this mechanism is still discussed. This review discusses the complex relationship between birth weight and nephron endowment and how early growth and nutrition influence long term HT and CKD. We hypothesize that fetal environment reduces moderately the nephron number which appears insufficient by itself to induce long term diseases. Reduced nephron number constitutes a “factor of vulnerability” when additional factors, in particular a rapid postnatal growth or overfeeding, promote the early onset of diseases through a complex combination of various pathophysiological pathways.

Deciphering deterioration mechanisms of complex diseases based on the construction of dynamic networks and systems analysis

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Li, Yuanyuan; Jin, Suoqin; Lei, Lei; Pan, Zishu; Zou, Xiufen

2015-03-01

The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.

RELATIONSHIP BETWEEN PERIODONTAL DISEASE INDEX AND LOW BIRTH WEIGHT BABIES IN PREGNANT WOMEN WITH PERIODONTITIS

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Ira Komara

2016-03-01

Full Text Available Objective: To identify the relationship between periodontitis in pregnant women through the periodontal disease index (PDI and low birth weight babies. Methods: A case-control study was conducted to determine the relationship between periodontitis in pregnant women through the periodontal disease index (PDI and the low birth weight babies (LBW. The participants were mothers with periodontitis and non-periodontitis mothers aged 20–35 years who gave birth in the Department of Obstetrics and Gynecology-Dr. Hasan Sadikin General Hospital, Bandung in the period of December to January 2005. Results: Based on the chisquare test results a highly significant relationship between periodontitis and low birth weight (p=0.002 was found. The Odd’s ratio showed that the risk of low birth weight in pregnant women with periodontitis was 15.58 times higher compared to those who did not suffer from periodontitis. The periodontal disease index has an accuracy of 88.6% in predicting the incidence of LBW. It strongly influenced the incidence of LBW with a high Odd’s ratio of 28.0. Pregnant women who suffer from periodontitis with a PDI > 3.25, have 19.2 times higher risk for delivering babies with LBW compared to the non-periodontitis mothers. Conclusions: The loss of attachment affects the possibility of delivering LBW babies.

Relationships between Mechanical Variables in the Traditional and Close-Grip Bench Press

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Lockie Robert G.

2017-12-01

Full Text Available The study aim was to determine relationships between mechanical variables in the one-repetition maximum (1RM traditional bench press (TBP and close-grip bench press (CGBP. Twenty resistance-trained men completed a TBP and CGBP 1RM. The TBP was performed with the preferred grip; the CGBP with a grip width of 95% biacromial distance. A linear position transducer measured: lift distance and duration; work; and peak and mean power, velocity, and force. Paired samples t-tests (p < 0.05 compared the 1RM and mechanical variables for the TBP and CGBP; effect sizes (d were also calculated. Pearson’s correlations (r; p < 0.05 computed relationships between the TBP and CGBP. 1RM, lift duration, and mean force were greater in the TBP (d = 0.30-3.20. Peak power and velocity was greater for the CGBP (d = 0.50-1.29. The 1RM TBP correlated with CGBP 1RM, power, and force (r = 0.685-0.982. TBP work correlated with CGBP 1RM, lift distance, power, force, and work (r = 0.542-0.931. TBP power correlated with CGBP 1RM, power, force, velocity, and work (r = 0.484-0.704. TBP peak and mean force related to CGBP 1RM, power, and force (r = 0.596-0.980. Due to relationships between the load, work, power, and force for the TBP and CGBP, the CGBP could provide similar strength adaptations to the TBP with long-term use. The velocity profile for the CGBP was different to that of the TBP. The CGBP could be used specifically to improve high-velocity, upper-body pushing movements.

Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology

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Jose A. Santiago

2017-05-01

Full Text Available Neurodegenerative diseases are rarely caused by a mutation in a single gene but rather influenced by a combination of genetic, epigenetic and environmental factors. Emerging high-throughput technologies such as RNA sequencing have been instrumental in deciphering the molecular landscape of neurodegenerative diseases, however, the interpretation of such large amounts of data remains a challenge. Network biology has become a powerful platform to integrate multiple omics data to comprehensively explore the molecular networks in the context of health and disease. In this review article, we highlight recent advances in network biology approaches with an emphasis in brain-networks that have provided insights into the molecular mechanisms leading to the most prevalent neurodegenerative diseases including Alzheimer’s (AD, Parkinson’s (PD and Huntington’s diseases (HD. We discuss how integrative approaches using multi-omics data from different tissues have been valuable for identifying biomarkers and therapeutic targets. In addition, we discuss the challenges the field of network medicine faces toward the translation of network-based findings into clinically actionable tools for personalized medicine applications.

Relationship between Motor Symptoms, Cognition, and Demographic Characteristics in Treated Mild/Moderate Parkinson's Disease.

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Jay S Schneider

Full Text Available Although Parkinson's disease (PD is a progressive neurodegenerative disorder characterized primarily by motor symptoms, PD patients, at all stages of the disease, can experience cognitive dysfunction. However, the relationships between cognitive and motor symptoms and specific demographic characteristics are not well defined, particularly for patients who have progressed to requiring dopaminergic medication.To examine relationships between motor and cognitive symptoms and various demographic factors in mild to moderate, PD patients requiring anti-PD medication.Cognitive function was assessed in 94 subjects with a variety of neuropsychological tests during baseline evaluations as part of an experimental treatment study. Data were analyzed in relation to Unified Parkinson's Disease Rating Scale motor scores and demographic variables.Of the UPDRS subscores analyzed, posture/balance/gait was associated with the highest number of adverse cognitive outcomes followed by speech/facial expression, bradykinesia, and rigidity. No associations were detected between any of the cognitive performance measures and tremor. Motor functioning assessed in the "off" condition correlated primarily with disease duration; neuropsychological performance in general was primarily related to age.In PD patients who have advanced to requiring anti-PD therapies, there are salient associations between axial signs and cognitive performance and in particular, with different aspects of visuospatial function suggesting involvement of similar circuits in these functions. Associations between executive functions and bradykinesia also suggest involvement similar circuits in these functions.

The Progress of Mitophagy and Related Pathogenic Mechanisms of the Neurodegenerative Diseases and Tumor

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Ying Song

2015-01-01

Full Text Available Mitochondrion, an organelle with two layers of membrane, is extremely vital to eukaryotic cell. Its major functions are energy center and apoptosis censor inside cell. The intactness of mitochondrial membrane is important to maintain its structure and function. Mitophagy is one kind of autophagy. In recent years, studies of mitochondria have shown that mitophagy is regulated by various factors and is an important regulation mechanism for organisms to maintain their normal state. In addition, abnormal mitophagy is closely related to several neurodegenerative diseases and tumor. However, the related signal pathway and its regulation mechanism still remain unclear. As a result, summarizing the progress of mitophagy and its related pathogenic mechanism not only helps to reveal the complicated molecular mechanism, but also helps to find a new target to treat the related diseases.

Comorbidity of periodontal disease

DEFF Research Database (Denmark)

Holmstrup, Palle; Damgaard, Christian; Olsen, Ingar

2017-01-01

Increasing evidence has suggested an independent association between periodontitis and a range of comorbidities, for example cardiovascular disease, type 2 diabetes, rheumatoid arthritis, osteoporosis, Parkinson's disease, Alzheimer's disease, psoriasis, and respiratory infections. Shared....... The present article presents an overview of the evidence linking periodontitis with selected systemic diseases and calls for increased cooperation between dentists and medical doctors to provide optimal screening, treatment, and prevention of both periodontitis and its comorbidities....... inflammatory pathways are likely to contribute to this association, but distinct causal mechanisms remain to be defined. Some of these comorbid conditions may improve by periodontal treatment, and a bidirectional relationship may exist, where, for example, treatment of diabetes can improve periodontal status...

Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathways

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Kelly N Holohan

2013-01-01

Full Text Available Two of the main research priorities in the United States are cancer and neurodegenerative diseases, which are attributed to abnormal patterns of cellular behavior. MicroRNAs (miRNA have been implicated as regulators of cellular metabolism, and thus are an active topic of investigation in both disease areas. There is presently a more extensive body of work on the role of miRNAs in cancer compared to neurodegenerative diseases, and therefore it may be useful to examine whether there is any concordance between the functional roles of miRNAs in these diseases. As a case study, the roles of miRNAs in Alzheimer’s disease (AD and their functions in various cancers will be compared. A number of miRNA expression patterns are altered in individuals with AD compared with healthy older adults. Among these, some have also been shown to correlate with neuropathological changes including plaque and tangle accumulation, as well as expression levels of other molecules known to be involved in disease pathology. Importantly, these miRNAs have also been shown to have differential expression and or functional roles in various types of cancer. To examine possible intersections between miRNA functions in cancer and AD, we review the current literature on eight of these miRNAs in cancer and AD, focusing on their roles in known biological pathways. We propose a pathway-driven model in which some molecular processes show an inverse relationship between cancer and neurodegenerative disease (e.g., proliferation and apoptosis whereas others are more parallel in their activity (e.g., immune activation and inflammation. A critical review of these and other molecular mechanisms in cancer may shed light on the pathophysiology of AD, and highlight key areas for future research. Conclusions from this work may be extended to other neurodegenerative diseases for which some molecular pathways have been identified but which have not yet been extensively researched for mi

Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders

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Martin Hofmann-Apitius

2015-12-01

Full Text Available Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies—data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI; which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations

Knowledge of medical doctors in Turkey about the relationship between periodontal disease and systemic health.

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Taşdemir, Zekeriya; Alkan, Banu Arzu

2015-01-01

Understanding the relationship between periodontal disease (PD) and systemic health (SH) is necessary for the accurate diagnosis and treatment of both. The aim of this study was to evaluate the knowledge of medical doctors in Turkey with regard to the association between PD and SH. This study was carried out using self-reported questionnaires that were sent to medical doctors who work at various universities and public and private hospitals in different cities in Turkey. The questionnaires consisted of questions about the demographic information of the medical doctors, as well as the knowledge of those doctors about the relationship between PD and SH. In total, 1,766 responses were received and 90.8% of the participants agreed that there was a relationship between PD and SH. Diabetes mellitus was the most frequent systemic disease (66.8%) known to be related to PD. Of the participants, 56.5% of the medical doctors referred their patients to periodontists for different reasons. Gingival bleeding was the most frequent reason for patient referrals, with 44% of doctors giving such referrals. Doctors who worked in basic medical sciences were significantly less aware of the relationship between PD and SH than the doctors in other specialties. Although the vast majority of the medical doctors reported that they knew the relationship between PD and SH, the findings of this study showed that this awareness was not supported by precise knowledge, and often failed to translate into appropriate clinical practice.

Relationship between dysphagia and depressive states in patients with Parkinson's disease.

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Han, Meng; Ohnishi, Hirofumi; Nonaka, Michio; Yamauchi, Rika; Hozuki, Takayoshi; Hayashi, Takashi; Saitoh, Masaki; Hisahara, Shin; Imai, Tomihiro; Shimohama, Shun; Mori, Mitsuru

2011-07-01

Aspiration pneumonia related to dysphagia is known to be the leading cause of death in patients with Parkinson's disease (PD). We investigated the relationship between depressive states and dysphagia in patients with PD. A hundred and twenty-seven PD patients gave their informed consent and were enrolled in this study. We used the Beck Depression Inventory (BDI) questionnaire to determine the participants' depressive states, and also used a questionnaire to assess participants' state of dysphagia. Participants were divided into four groups according to their BDI score. We compared the PD patients with Swallowing Disturbances Questionnaire (SDQ) scores of more than or equal to 11 with the SDQ scores of less than 11 regarding depressive categories. A logistic regression analysis was conducted to calculate odds ratios (ORs) and their 95% confidence intervals (95%CI) adjusting for age, sex, disease duration, wearing-off phenomenon and severity of movement disorder. OR (95%CI) of depressive categories, in which the trivial class was set as a reference group, were 3.28 (0.93-11.55), 13.44 (3.10-58.16), 30.35 (5.65-162.97) in the mild class, the moderate class and the severe class, respectively. This study suggests that there may be a strong relationship between depressive states and dysphagia in patients with PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

RELATIONSHIP OF SOME MARKERS OF PSYCHO-EMOTIONAL STATE AND DEVELOPMENT OF SOMATIC PATHOLOGY IN THE PATIENTS WITH OCCUPATIONAL DISEASES

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Игорь Петрович Данилов

2017-10-01

Conclusions. The relationship between the emotional and personal attitude to health and a healthy lifestyle and the development of somatic diseases in the patients with occupational diseases has been revealed.

Relationships between the curing conditions and some mechanical properties of hybrid thermosetting materials

International Nuclear Information System (INIS)

Dias Filho, Newton L.; Aquino, Hermes A. de; Cardoso, Celso X.

2006-01-01

The relationship between the heat of polymerization (ΑH) and activation energy (E a ) parameters, obtained by differential scanning calorimetry (DSC) and the ratio of epoxy resin to hardener of the thermosetting materials based on an organic-inorganic hybrid epoxy resin (OG) was investigated. Activation energy (E a ) and heat of polymerization (ΑH) increased with an increasing OG content, up to 70 wt %. Further increase in OG content to 80 wt % reduced E a and ΑH. Dynamic mechanical analysis indicates that the maximum cross-link density is obtained at 83 wt % OG, whereas fracture toughness and tensile modulus mechanical properties are maximized at 70 wt % OG. (author)

Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

NARCIS (Netherlands)

Feng, Yen Chen Anne; Cho, Kelly; Lindstrom, Sara; Kraft, Peter; Cormack, Jean; Blalock, Kendra; Campbell, Peter T.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Figueiredo, Jane; James Gauderman, W.; Gong, Jian; Green, Roger C.; Gruber, Stephen B.; Harju, John F.; Harrison, Tabitha A.; Jacobs, Eric J; Jenkins, Mark A.; Jiao, Shuo; Li, Li; Lin, Yi; Manion, Frank J.; Moreno, Victor; Mukherjee, Bhramar; Peters, Ulrike; Raskin, Leon; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Stenzel, Stephanie L.; Thomas, Duncan C.; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos-Santos-Silva, Isabel; Hunter, David J.; Lindström, Sara; Kraft, Peter; Ahsan, Habib; Whittemore, Alice S.; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Uitterlinden, Andre G; Hofman, Albert; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Crisponi, Laura; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Easton, Douglas F.; Turnbull, Clare A.; Rahman, Nazneen; Kote-Jarai, Zsofia; Muir, Kenneth; Giles, Graham G.; Severi, Gianluca; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schumacher, Fred; Travis, Ruth C.; Riboli, Elio; Kraft, Peter; Hunter, David J.; Gapstur, Susan M.; Berndt, Sonja I.; Chanock, Stephen J.; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; McKay, James D.; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil E; Landi, Maria Teresa; Heinrich, Joachim; Risch, Angela; Wu, Xifeng; Ye, Yuanqing; Christiani, David C.; Amos, Christopher I; Liang, Liming; Driver, Jane A.; IGAP Consortium, Colorectal Transdisciplinary Study (CORECT); Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE)

2017-01-01

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer’s disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from

Study on the relationship between serum leptin level and ischemic cerebrovascular disease (ICVD)

International Nuclear Information System (INIS)

Luo Nanping; Hu Chengjing; Wang Ruishan; Yin Qiuxia; Niu Aijun; Xue Lian; Xue Shenwu; Chen Qing

2004-01-01

Objective: To investigate the inter-relationship among serum leptin insulin resistance and blood lipids, and to explore the role of leptin in the pathogenesis of ischemic cerebrovascular diseases (ICVD). Methods: Levels of serum leptin, insulin and blood lipids were determined with RIA in 131 patients with different types of ICVD and 36 controls. Results: The levels of serum leptin in ICVD patients were significantly higher than those in the controls (P<0.01). Changes of blood lipids and insulin paralleled those of leptin (cxcept with HDL-C). The serum leptin were positively correlated to cholesterol, TG and insulin levels (r=0.45, P<0.05; r=0.31, P<0.05, r=0.55, P<0.01), but negatively correlated to HDL-C (r=-0.88, P<0.05). Conclusion: The high expression of leptin in ICVD patients is associated with high lipid and insulin levels. The close relationship among them indicates that high leptin levels play an important role in the pathogenesis of metabolic syndrome as well as atheromatous cerebrovascular diseases. (authors)

[Relationships between psychosomatics and somatopsychiatry in modern medicine].

Science.gov (United States)

Paleev, N R; Krasnov, V N

2009-01-01

Progress in many clinical disciplines and neurobiology for the last decades give reason to reconsider some fundamental provisions of psychosomatic medicine and its relationships with somatopsychiatry. The universally accepted biopsychosocial model of the disease as proposed by V.N.Bekhterev implies involvement of psychological and psychosocial factors at early stages of many forms of somatic pathology. Intricate interplay between somatic and psychic components is exemplified by correlation of cardiovascular disorders and depression. Depression is diagnosed in 17-27% of the patients with coronary heart disease undergoing coronary angiography and in 16-45% of the post-infarction cases. Frequency of depression/hypertensive disease comorbidity is estimated at 30%. Similarity of pathogenetic mechanisms of cardiovascular diseases and depressive states is due to stress as their common provoking factor. Another important aspect of the relationship between medicine and psychiatry (disregarded until recently) is high frequency of somatic disorders in psychiatric patients. Cooperation of psychiatrists and representatives of different medical disciplines in such areas as research and practical health care is needed to address this problem.

Relationships Between Essential Manganese Biology and Manganese Toxicity in Neurological Disease.

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Pfalzer, Anna C; Bowman, Aaron B

2017-06-01

Manganese (Mn) is critical for neurodevelopment but also has been implicated in the pathophysiology of several neurological diseases. We discuss how Mn requirements intersect with Mn biology and toxicity, and how these requirements may be altered in neurological disease. Furthermore, we discuss the emerging evidence that the level of Mn associated with optimal overall efficiency for Mn biology does not necessarily coincide with optimal cognitive outcomes. Studies have linked Mn exposures with urea cycle metabolism and autophagy, with evidence that exposures typically neurotoxic may be able to correct deficiencies in these processes at least short term. The line between Mn-dependent biology and toxicity is thus blurred. Further, new work suggests that Mn exposures correlating to optimal cognitive scores in children are associated with cognitive decline in adults. This review explores relationships between Mn-dependent neurobiology and Mn-dependent neurotoxicity. We propose the hypothesis that Mn levels/exposures that are toxic to some biological processes are beneficial for other biological processes and influenced by developmental stage and disease state.

A systematic review of the application and utility of geographical information systems for exploring disease-disease relationships in paediatric global health research: the case of anaemia and malaria.

Science.gov (United States)

Aimone, Ashley Mariko; Perumal, Nandita; Cole, Donald C

2013-01-10

Malaria and anaemia are important health problems among children globally. Iron deficiency anaemia may offer protection against malaria infection and iron supplementation may increase the risk of malaria-related hospitalization and mortality. The nature and mechanism of these relationships, however, remain largely unresolved, resulting in concern and uncertainty around policies for non-selective iron supplementation in malaria endemic areas. Use of geographical information systems (GIS) to investigate this disease-disease interaction could contribute important new information for developing safe and effective anaemia and malaria interventions. To assess the current state of knowledge we conducted a systematic review of peer-reviewed and grey literature. Our primary objective was to qualitatively assess the application and utility of geographical concepts or spatial analyses in paediatric global health research. The secondary objective was to identify geographical factors that may be associated with anaemia and malaria prevalence or incidence among children 0-5 years of age living in low- and middle-income countries. Evaluation tools for assessing the quality of geographical data could not be found in the peer-reviewed or grey literature, and thus adapted versions of the STROBE (Strengthening The Reporting of Observational Studies in Epidemiology) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods were used to create reporting, and overall evidence quality scoring systems. Among the 20 included studies, we found that both malaria and anaemia were more prevalent in rural communities compared to urban areas. Geographical factors associated with malaria prevalence included regional transmission stability, and proximity to a mosquito breeding area. The prevalence of anaemia tended to vary inversely with greater or poorer access to community services such as piped water. Techniques for investigating geographic relationships ranged from

A systematic review of the application and utility of geographical information systems for exploring disease-disease relationships in paediatric global health research: the case of anaemia and malaria

Directory of Open Access Journals (Sweden)

Aimone Ashley Mariko

2013-01-01

Full Text Available Abstract Malaria and anaemia are important health problems among children globally. Iron deficiency anaemia may offer protection against malaria infection and iron supplementation may increase the risk of malaria-related hospitalization and mortality. The nature and mechanism of these relationships, however, remain largely unresolved, resulting in concern and uncertainty around policies for non-selective iron supplementation in malaria endemic areas. Use of geographical information systems (GIS to investigate this disease-disease interaction could contribute important new information for developing safe and effective anaemia and malaria interventions. To assess the current state of knowledge we conducted a systematic review of peer-reviewed and grey literature. Our primary objective was to qualitatively assess the application and utility of geographical concepts or spatial analyses in paediatric global health research. The secondary objective was to identify geographical factors that may be associated with anaemia and malaria prevalence or incidence among children 0–5 years of age living in low- and middle-income countries. Evaluation tools for assessing the quality of geographical data could not be found in the peer-reviewed or grey literature, and thus adapted versions of the STROBE (Strengthening The Reporting of Observational Studies in Epidemiology and GRADE (Grades of Recommendation, Assessment, Development and Evaluation methods were used to create reporting, and overall evidence quality scoring systems. Among the 20 included studies, we found that both malaria and anaemia were more prevalent in rural communities compared to urban areas. Geographical factors associated with malaria prevalence included regional transmission stability, and proximity to a mosquito breeding area. The prevalence of anaemia tended to vary inversely with greater or poorer access to community services such as piped water. Techniques for investigating geographic

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

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Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

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

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Pierpaola Davalli

2016-01-01

Full Text Available 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.

Mechanisms in endocrinology: the crosstalk between thyroid gland and adipose tissue: signal integration in health and disease.

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Santini, Ferruccio; Marzullo, Paolo; Rotondi, Mario; Ceccarini, Giovanni; Pagano, Loredana; Ippolito, Serena; Chiovato, Luca; Biondi, Bernadette

2014-10-01

Obesity and thyroid diseases are common disorders in the general population and they frequently occur in single individuals. Alongside a chance association, a direct relationship between 'thyroid and obesity' has been hypothesized. Thyroid hormone is an important determinant of energy expenditure and contributes to appetite regulation, while hormones and cytokines from the adipose tissue act on the CNS to inform on the quantity of energy stores. A continuous interaction between the thyroid hormone and regulatory mechanisms localized in adipose tissue and brain is important for human body weight control and maintenance of optimal energy balance. Whether obesity has a pathogenic role in thyroid disease remains largely a matter of investigation. This review highlights the complexity in the identification of thyroid hormone deficiency in obese patients. Regardless of the importance of treating subclinical and overt hypothyroidism, at present there is no evidence to recommend pharmacological correction of the isolated hyperthyrotropinemia often encountered in obese patients. While thyroid hormones are not indicated as anti-obesity drugs, preclinical studies suggest that thyromimetic drugs, by targeting selected receptors, might be useful in the treatment of obesity and dyslipidemia. © 2014 European Society of Endocrinology.

Pathways and mechanisms linking dietary components to cardiometabolic disease: thinking beyond calories.

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Stanhope, K L; Goran, M I; Bosy-Westphal, A; King, J C; Schmidt, L A; Schwarz, J-M; Stice, E; Sylvetsky, A C; Turnbaugh, P J; Bray, G A; Gardner, C D; Havel, P J; Malik, V; Mason, A E; Ravussin, E; Rosenbaum, M; Welsh, J A; Allister-Price, C; Sigala, D M; Greenwood, M R C; Astrup, A; Krauss, R M

2018-05-14

Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis. © 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches.

Science.gov (United States)

Siasos, Gerasimos; Tsigkou, Vasiliki; Kokkou, Eleni; Oikonomou, Evangelos; Vavuranakis, Manolis; Vlachopoulos, Charalambos; Verveniotis, Alexis; Limperi, Maria; Genimata, Vasiliki; Papavassiliou, Athanasios G; Stefanadis, Christodoulos; Tousoulis, Dimitris

2014-01-01

It has been clear that at least 1 billion adults worldwide are smokers and at least 700 million children are passive smokers at home. Smoking exerts a detrimental effect to many organ systems and is responsible for illnesses such as lung cancer, pneumonia, chronic obstructive pulmonary disease, cancer of head and neck, cancer of the urinary and gastrointestinal tract, periodontal disease, cataract and arthritis. Additionally, smoking is an important modifiable risk factor for the development of cardiovascular disease such as coronary artery disease, stable angina, acute coronary syndromes, sudden death, stroke, peripheral vascular disease, congestive heart failure, erectile dysfunction and aortic aneurysms via initiation and progression of atherosclerosis. A variety of studies has proved that cigarette smoking induces oxidative stress, vascular inflammation, platelet coagulation, vascular dysfunction and impairs serum lipid pro-file in both current and chronic smokers, active and passive smokers and results in detrimental effects on the cardiovascular system. The aim of this review is to depict the physical and biochemical properties of cigarette smoke and, furthermore, elucidate the main pathophysiological mechanisms of cigarette-induced atherosclerosis and overview the new therapeutic approaches for smoking cessation and augmentation of cardiovascular health.

A review of the relationship between leg power and selected chronic disease in older adults

DEFF Research Database (Denmark)

Strollo, S. E.; Caserotti, Paolo; Ward, R. E.

2015-01-01

characterized. Importantly, individuals with these conditions have shown improved leg power with training. METHODS: A search was performed using PubMed to identify original studies published in English from January 1998 to August 2013. Leg power studies, among older adults ≥ 50 years of age, which assessed......OBJECTIVE: This review investigates the relationship between leg muscle power and the chronic conditions of osteoarthritis, diabetes mellitus, and cardiovascular disease among older adults. Current literature assessing the impact of chronic disease on leg power has not yet been comprehensively......), diabetes mellitus (n=5), and cardiovascular disease (n=6). Studies generally supported associations of lower leg power among older adults with chronic disease, although small sample sizes, cross-sectional data, homogenous populations, varied disease definitions, and inconsistent leg power methods limited...

Survey of Network-Based Approaches to Research of Cardiovascular Diseases

Directory of Open Access Journals (Sweden)

Anida Sarajlić

2014-01-01

Full Text Available Cardiovascular diseases (CVDs are the leading health problem worldwide. Investigating causes and mechanisms of CVDs calls for an integrative approach that would take into account its complex etiology. Biological networks generated from available data on biomolecular interactions are an excellent platform for understanding interconnectedness of all processes within a living cell, including processes that underlie diseases. Consequently, topology of biological networks has successfully been used for identifying genes, pathways, and modules that govern molecular actions underlying various complex diseases. Here, we review approaches that explore and use relationships between topological properties of biological networks and mechanisms underlying CVDs.

Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease

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Shi, Riyi; Page, Jessica; Tully, Melissa

2016-01-01

Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and organ systems they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and instigator of oxidative stress, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models by conserving myelin structural integrity and alleviating functional deficits. This evidence is indicative that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease. PMID:25879847

DNA replication stress: from molecular mechanisms to human disease.

Science.gov (United States)

Muñoz, Sergio; Méndez, Juan

2017-02-01

The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of "replicative stress" (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.

The Potential Mechanisms of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease

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Xiaopeng Zhu

2016-10-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR, a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. Increase of insulin sensitivity, regulation of adenosine monophosphate-activated protein kinase (AMPK pathway, improvement of mitochondrial function, alleviation of oxidative stress, LDLR mRNA stabilization, and regulation of gut microenvironment are the major targets of BBR in the treatment of NAFLD. Additionally, reduction of proprotein convertase subtilisin/kexin 9 (PCSK9 expression and DNA methylation are also involved in pharmacological mechanisms of berberine in the treatment of NAFLD. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, delivery routes, and drug dose can be considered in the future research.

Relationship Between Helicobacter Pylori Infection and Chronic Obstructive Pulmonary Disease

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Mohammad-Ali Seif-Rabiei

2011-11-01

Full Text Available There is some evidence indicating the role of Helicobacter pylori infection in pathogenesis of extragastrointestinal diseases including skin, vascular, and autoimmune disorders, as well as some respiratory diseases. The aim of this study was to investigate the association between H. pylori and chronic obstructive pulmonary disease (COPD. In a case-control study, 90 patients with COPD and 90 age- and sex- matched control subjects were included. Serum samples were tested for anti-H. pylori and anti-CagA IgG by ELISA. A physician completed a questionnaire including demographic characteristics, habitual history, and spirometric findings for each patient. Of 90 patients with COPD 66 (51% had mild, 31 (34.4% moderate, and 13 (14.4% sever disease. There was no significant association between H. pylori IgG seropositivity and COPD. Serum levels of anti-CagA IgG were significantly higher in patients with COPD than in the control subjects (P < 0.001. No association was observed between H. pylori infection and severity of COPD. The results suggest that there is an association between CagA-positive H. pylori infections and COPD. Further studies should be planned to investigate the potential pathogenic mechanisms that might underlie these associations.

Relationships between the curing conditions and some mechanical properties of hybrid thermosetting materials

Energy Technology Data Exchange (ETDEWEB)

Dias Filho, Newton L.; Aquino, Hermes A. de [UNESP, Ilha Solteira, SP (Brazil). Dept. de Fisica e Quimica]. E-mail: nldias@dfq.feis.unesp.br; Cardoso, Celso X. [UNESP, Presidente Prudente, SP (Brazil). Dept. de Fisica, Quimica e Biologia

2006-09-15

The relationship between the heat of polymerization ({alpha}H) and activation energy (E{sub a}) parameters, obtained by differential scanning calorimetry (DSC) and the ratio of epoxy resin to hardener of the thermosetting materials based on an organic-inorganic hybrid epoxy resin (OG) was investigated. Activation energy (E{sub a}) and heat of polymerization ({alpha}H) increased with an increasing OG content, up to 70 wt %. Further increase in OG content to 80 wt % reduced E{sub a} and {alpha}H. Dynamic mechanical analysis indicates that the maximum cross-link density is obtained at 83 wt % OG, whereas fracture toughness and tensile modulus mechanical properties are maximized at 70 wt % OG. (author)

Mechanisms of physical activity limitation in chronic lung diseases.

Science.gov (United States)

Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

2012-01-01

In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients' quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.

Mechanisms of Physical Activity Limitation in Chronic Lung Diseases

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Ioannis Vogiatzis

2012-01-01

Full Text Available In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i the imbalance between ventilatory capacity and demand, (ii the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients’ quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.

Osteoarthritis of the temporomandibular joint organ and its relationship to disc displacement

NARCIS (Netherlands)

Stegenga, B

2001-01-01

To overcome disagreements with regard to the relationship between disc displacement and osteoarthritis of the temporomandibular joint (TMJ), the evidence for suggested disease mechanisms and clinical course of these disorders is reviewed. The TMJ behaves as a complex organ in which biochemical and

Mechanisms linking brain insulin resistance to Alzheimer's disease

Science.gov (United States)

Matioli, Maria Niures P.S.; Nitrini, Ricardo

2015-01-01

Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

Mechanisms linking brain insulin resistance to Alzheimer's disease

Directory of Open Access Journals (Sweden)

Maria Niures P.S. Matioli

Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.

Science.gov (United States)

Raththagala, Madushi; Brewer, M Kathryn; Parker, Matthew W; Sherwood, Amanda R; Wong, Brian K; Hsu, Simon; Bridges, Travis M; Paasch, Bradley C; Hellman, Lance M; Husodo, Satrio; Meekins, David A; Taylor, Adam O; Turner, Benjamin D; Auger, Kyle D; Dukhande, Vikas V; Chakravarthy, Srinivas; Sanz, Pascual; Woods, Virgil L; Li, Sheng; Vander Kooi, Craig W; Gentry, Matthew S

2015-01-22

Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated tertiary and quaternary structure. Structure-guided mutagenesis combined with biophysical and biochemical analyses reveal the basis for normal function of laforin in glycogen metabolism. Analyses of LD patient mutations define the mechanism by which subsets of mutations disrupt laforin function. These data provide fundamental insights connecting glycogen metabolism to neurodegenerative disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

Science.gov (United States)

Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

2017-08-01

Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of a feedback loop involving β-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease.

Science.gov (United States)

Schonauer, Sophie; Körschen, Heinz G; Penno, Anke; Rennhack, Andreas; Breiden, Bernadette; Sandhoff, Konrad; Gutbrod, Katharina; Dörmann, Peter; Raju, Diana N; Haberkant, Per; Gerl, Mathias J; Brügger, Britta; Zigdon, Hila; Vardi, Ayelet; Futerman, Anthony H; Thiele, Christoph; Wachten, Dagmar

2017-04-14

The lysosomal acid β-glucosidase GBA1 and the non-lysosomal β-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease. However, the role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. Here, we report a GBA1-dependent down-regulation of GBA2 activity in patients with Gaucher disease. Using an experimental approach combining cell biology, biochemistry, and mass spectrometry, we show that sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity. We propose a negative feedback loop, in which sphingosine inhibits GBA2 activity in Gaucher cells, preventing further sphingosine accumulation and, thereby, cytotoxicity. Our findings add a new chapter to the understanding of the complex molecular mechanism underlying Gaucher disease and the regulation of β-glucosidase activity in general. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Determining the structure-mechanics relationships of dense microtubule networks with confocal microscopy and magnetic tweezers-based microrheology.

Science.gov (United States)

Yang, Yali; Valentine, Megan T

2013-01-01

The microtubule (MT) cytoskeleton is essential in maintaining the shape, strength, and organization of cells. Its spatiotemporal organization is fundamental for numerous dynamic biological processes, and mechanical stress within the MT cytoskeleton provides an important signaling mechanism in mitosis and neural development. This raises important questions about the relationships between structure and mechanics in complex MT structures. In vitro, reconstituted cytoskeletal networks provide a minimal model of cell mechanics while also providing a testing ground for the fundamental polymer physics of stiff polymer gels. Here, we describe our development and implementation of a broad tool kit to study structure-mechanics relationships in reconstituted MT networks, including protocols for the assembly of entangled and cross-linked MT networks, fluorescence imaging, microstructure characterization, construction and calibration of magnetic tweezers devices, and mechanical data collection and analysis. In particular, we present the design and assembly of three neodymium iron boron (NdFeB)-based magnetic tweezers devices optimized for use with MT networks: (1) high-force magnetic tweezers devices that enable the application of nano-Newton forces and possible meso- to macroscale materials characterization; (2) ring-shaped NdFeB-based magnetic tweezers devices that enable oscillatory microrheology measurements; and (3) portable magnetic tweezers devices that enable direct visualization of microscale deformation in soft materials under applied force. Copyright © 2013 Elsevier Inc. All rights reserved.

Insights into mechanisms of transmission and pathogenesis from transgenic mouse models of prion diseases

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Moreno, Julie A.; Telling, Glenn C.

2018-01-01

Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, sometimes referred to as transmissible spongiform encephalopathies (TSE’s), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrPC) by the pathogenic isoform (PrPSc) that is the basis of prion formation in TSE’s, is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer’s and Parkinson’s diseases. The peerless infectious properties of TSE prions, and the unparalleled tools for their study, therefore enable elucidation of mechanisms of template-mediated conformational propagation that are generally applicable to these related disease states. Many unresolved issues remain including the exact molecular nature of the prion, the detailed cellular and molecular mechanisms of prion propagation, and the means by which prion diseases can be both genetic and infectious. In addition, we know little about the mechanism by which neurons degenerate during prion diseases. Tied to this, the physiological role of the normal form of the prion protein remains unclear and it is uncertain whether or not loss of this function contributes to prion pathogenesis. The factors governing the transmission of prions between species remain unclear, in particular the means by which prion strains and PrP primary structure interact to affect inter-species prion transmission. Despite all these unknowns, advances in our understanding of prions have occurred because of their transmissibility to experimental animals and the development of transgenic (Tg) mouse models has done much to further our understanding about various aspects of prion biology. In this review we will focus on advances in our understanding of prion biology that

The relationship between different dimensions of alcohol use and the burden of disease-an update.

Science.gov (United States)

Rehm, Jürgen; Gmel, Gerhard E; Gmel, Gerrit; Hasan, Omer S M; Imtiaz, Sameer; Popova, Svetlana; Probst, Charlotte; Roerecke, Michael; Room, Robin; Samokhvalov, Andriy V; Shield, Kevin D; Shuper, Paul A

2017-06-01

Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health outcomes to be used in global and national Comparative Risk Assessments (CRAs). Systematic review of reviews and meta-analyses on alcohol consumption and health outcomes attributable to alcohol use. For dimensions of exposure: volume of alcohol use, blood alcohol concentration and patterns of drinking, in particular heavy drinking occasions were studied. For liver cirrhosis, quality of alcohol was additionally considered. For all outcomes (mortality and/or morbidity): cause of death and disease/injury categories based on International Classification of Diseases (ICD) codes used in global CRAs; harm to others. In total, 255 reviews and meta-analyses were identified. Alcohol use was found to be linked causally to many disease and injury categories, with more than 40 ICD-10 three-digit categories being fully attributable to alcohol. Most partially attributable disease categories showed monotonic relationships with volume of alcohol use: the more alcohol consumed, the higher the risk of disease or death. Exceptions were ischaemic diseases and diabetes, with curvilinear relationships, and with beneficial effects of light to moderate drinking in people without heavy irregular drinking occasions. Biological pathways suggest an impact of heavy drinking occasions on additional diseases; however, the lack of medical epidemiological studies measuring this dimension of alcohol use precluded an in-depth analysis. For injuries, except suicide, blood alcohol concentration was the most important dimension of alcohol use. Alcohol use caused marked harm to others, which has not yet been researched sufficiently. Research since 2010 confirms the importance of alcohol use as a risk factor for disease and injuries; for some health outcomes, more than one dimension of use needs to be considered. Epidemiological

The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD.

Directory of Open Access Journals (Sweden)

Jee Lee

Full Text Available Some have suggested that chronic obstructive pulmonary disease (COPD is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR, we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS. The subjects were followed for approximately 7.5 years during which time their vital status, FEV(1 and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy "mid-life" volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy "mid-life" volunteers (p<.001. Compared to individuals in the 4(th quartile of relative telomere length (i.e. longest telomere group, the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324 and total mortality (HR, 1.29; p = 0.0425. Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD.

Does sleep disturbance affect the amyloid clearance mechanisms in Alzheimer's disease?

Science.gov (United States)

Yulug, Burak; Hanoglu, Lutfu; Kilic, Ertugrul

2017-10-01

Sleep is an important factor that plays a key role in Alzheimer's disease pathogenesis. However, it is still unclear whether poor-quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in Aβ clearance metabolism. To that end, we discuss possible mechanisms underlying the bidirectional interaction between the sleep deprivation and Aβ clearance pathways. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Relationship Between Prehypertension/Hypertension and Periodontal Disease: A Prospective Cohort Study.

Science.gov (United States)

Kawabata, Yuya; Ekuni, Daisuke; Miyai, Hisataka; Kataoka, Kota; Yamane, Mayu; Mizutani, Shinsuke; Irie, Koichiro; Azuma, Tetsuji; Tomofuji, Takaaki; Iwasaki, Yoshiaki; Morita, Manabu

2016-03-01

Most cross-sectional studies have found a significant positive relationship between periodontal disease and prehypertension/hypertension. However, these studies had limitations and there are few prospective cohort studies in young adults. The purpose of this prospective cohort study was to investigate whether periodontal disease was related to prehypertension/hypertension in Japanese university students. Students (n = 2,588), who underwent health examinations before entering university and before graduation, were included in the analysis. The association between periodontal disease such as the percentage of bleeding on probing (BOP) and community periodontal index (CPI) scores, and change in blood pressure status was determined. At the reexamination, the numbers of participants with prehypertension (systolic blood pressure 120-139mm Hg or diastolic blood pressure 80-89mm Hg) and hypertension (≥140/90mm Hg) were 882 (34.1%) and 109 (4.2%), respectively. In a logistic regression model, the risk of hypertension was significantly associated with male (odds ratio (OR): 6.31; 95% confidence interval (CI): 2.63-15.13; P periodontal disease defined as the presence of both probing pocket depth (PPD) ≥ 4mm and BOP ≥ 30% at baseline (OR: 2.74; 95% CI: 1.19-6.29; P = 0.02) in participants with prehypertension at baseline. On the other hand, the risk of prehypertension was not associated with presence of periodontal disease (OR: 0.93; 95% CI: 0.51-1.70; P = 0.82). In the short-term prospective cohort study, a significant association between presence of periodontal disease and hypertension was observed in Japanese university students. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect and mechanism of acupuncture on Alzheimer's disease.

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Zeng, Bai-Yun; Salvage, Sarah; Jenner, Peter

2013-01-01

Alzheimer's disease is the most common form of dementia diagnosed in the aging population worldwide. The cause of Alzheimer's is still not clear. There is no cure for the disease and current treatments are only symptomatic relieve. The search for new treatment is made ever more urgent due to increasing population aging. Acupuncture has been in practice in China for more than 3000 years and used to treat a wide variety of conditions including cardiovascular and psychiatric diseases, acute, and chronic pain. In this chapter, we review recent development on the effects and mechanisms of acupuncture on Alzheimer's disease. In Alzheimer's animal models, acupuncture stimulation at acupoints enhances cholinergic neurotransmission, trophic factor releasing, reduces apoptotic and oxidative damages, improves synaptic plasticity and decreases the levels of Aβ proteins in the hippocampus and relevant brain regions. The biochemical modulations by acupuncture in the brains of Alzheimer's models are correlated with the cognitive improvement. In Alzheimer's patients, functional brain images demonstrated that acupuncture increased in the activity in the temporal lobe and prefrontal lobe which are related to the memory and cognitive function. Although only a few acupuncture clinical studies with a small number of participants are reported, they represent an important step forward in the research of both acupuncture and Alzheimer's. Translation of acupuncture research in animal model studies into the human subjects will undoubtedly enhance acupuncture efficacy in clinical study and treatment which could eventually lead to a safer, well-tolerated and inexpensive form of care for Alzheimer's patients. © 2013 Elsevier Inc. All rights reserved.

Microchimerism in Graves' Disease

Science.gov (United States)

Galofré, Juan C.

2012-01-01

Microchimerism is the presence of cells from one individual in another genetically distinct individual. Pregnancy is the main cause of natural microchimerism through transplacental bidirectional cell trafficking between mother and fetus. The consequences of pregnancy-related microchimerism are under active investigation. However, many authors have suggested a close relationship linking fetal microchimerism and the development of autoimmune diseases. It has been more than ten years now since the demonstration of the presence of a significant high number of fetal microchimeric cells residing in thyroid glands from operated patients with Graves' disease. This intrathyroidal fetal microchimerism is an attractive candidate mechanism for the modulation of Graves' disease in pregnancy and the postpartum period. PMID:22577597

The relationship between different information sources and disease-related patient knowledge and anxiety in patients with inflammatory bowel disease.

Science.gov (United States)

Selinger, C P; Carbery, I; Warren, V; Rehman, A F; Williams, C J; Mumtaz, S; Bholah, H; Sood, R; Gracie, D J; Hamlin, P J; Ford, A C

2017-01-01

Patient education forms a cornerstone of management of inflammatory bowel disease (IBD). The Internet has opened new avenues for information gathering. To determine the relationship between different information sources and patient knowledge and anxiety in patients with IBD. The use of information sources in patients with IBD was examined via questionnaire. Anxiety was assessed with the hospital anxiety and depression scale and disease-related patient knowledge with the Crohn's and colitis knowledge score questionnaires. Associations between these outcomes and demographics, disease-related factors, and use of different information sources were analysed using linear regression analysis. Of 307 patients (165 Crohn's disease, 142 ulcerative colitis) 60.6% were female. Participants used the hospital IBD team (82.3%), official leaflets (59.5%), and official websites (53.5%) most frequently in contrast to alternative health websites (9%). University education (P sex (P = 0.004), clinically active disease (P sources are associated with better knowledge or worse anxiety levels. Face-to-face education and written information materials remain the first line of patient education. Patients should be guided towards official information websites and warned about the association between the use of alternative health websites or random links and anxiety. © 2016 John Wiley & Sons Ltd.

Relationship between vacA Types and Development of Gastroduodenal Diseases

OpenAIRE

Thi Huyen Trang, Tran; Thanh Binh, Tran; Yamaoka, Yoshio

2016-01-01

The Helicobacter pylori vacuolating cytotoxin (VacA) is a secreted pore-forming toxin and a major virulence factor in the pathogenesis of H. pylori infection. While VacA is present in almost all strains, only some forms are toxigenic and pathogenic. While vacA and its genotypes are considered as markers of H. pylori-related diseases or disorders, the pathophysiological mechanisms of VacA and its genotypes remain controversial. This review outlines key findings of publications regarding vacA w...

Pathogenic mechanisms in chronic obstructive pulmonary disease due to biomass smoke exposure.

Science.gov (United States)

Silva, Rafael; Oyarzún, Manuel; Olloquequi, Jordi

2015-06-01

Chronic obstructive pulmonary disease (COPD) mortality and morbidity have increased significantly worldwide in recent decades. Although cigarette smoke is still considered the main risk factor for the development of the disease, estimates suggest that between 25% and 33% of COPD patients are non-smokers. Among the factors that may increase the risk of developing COPD, biomass smoke has been proposed as one of the most important, affecting especially women and children in developing countries. Despite the epidemiological evidence linking exposure to biomass smoke with adverse health effects, the specific cellular and molecular mechanisms by which this pollutant can be harmful for the respiratory and cardiovascular systems remain unclear. In this article we review the main pathogenic mechanisms proposed to date that make biomass smoke one of the major risk factors for COPD. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

[Ginseng prescription rules and molecular mechanism in treating coronary heart disease based on data mining and integrative pharmacology].

Science.gov (United States)

Li, Sen; Tang, Shi-Huan; Liu, Jin-Ling; Su, Jin; He, Fu-Yuan

2018-04-01

The ancient dragon Materia Medica, Compendium of Materia Medica and other works recorded that the main effect of ginseng is tonifying qi. It is reported that the main active ingredient of ginseng is ginsenoside. Modern studies have found that ginseng mono saponins are effective for cardiovascular related diseases. This paper preliminary clarified the efficacy of traditional ginseng-nourishing qi and cardiovascular disease through the traditional Chinese medicine (TCM) inheritance auxiliary platform and integration platform of association of pharmacology. With the help of TCM inheritance auxiliary platform-analysis of "Chinese medicine database", Chinese medicine treatment of modern diseases that ginseng rules, so the traditional effect associated with modern medicine and pharmacology; application integration platform enrichment analysis on the target of drug and gene function, metabolic pathway, to further explore the molecular mechanism of ginseng in the treatment of coronary heart disease, aimed at mining the molecular mechanism of ginseng in the treatment of coronary heart disease. Chinese medicine containing ginseng 307 prescriptions, 87 kinds of disease indications, western medicine disease Chinese medicine therapy for ginseng main coronary heart disease; analysis of molecular mechanism of ginseng pharmacology integration platform for the treatment of coronary heart disease. Ginsenosides（Ra₁, Ra₂, Rb₁, Rb₂, Rg₁, Ro) bind these targets, PRKAA1, PRKAA2, NDUFA4, COX5B, UQCRC1, affect chemokines, non-alcoholic fatty liver, gonadotropin, carbon metabolism, glucose metabolism and other pathways to treat coronary heart disease indirectly. The molecular mechanism of Panax ginseng's multi-component, multi-target and synergistic action is preliminarily elucidated in this paper. Copyright© by the Chinese Pharmaceutical Association.

Relationship between free volume and mechanical properties of polyurethane irradiated by gamma rays

International Nuclear Information System (INIS)

Heliang Sui; Xin Ju; Xueyong Liu; Fachun Zhong; Xiaoyan Li; Baoyi Wang

2014-01-01

Polyurethane was irradiated at various gamma radiation doses up to 1,000 kGy at room temperature in nitrogen. Positron annihilation lifetime spectroscopy, tensile test and dynamic mechanical analysis were used to find the relationship between free volume and mechanical properties. An increase of the free volume fraction in soft segments (SS) and a decrease of the free volume fraction in hard segments (HS) during gamma radiation was observed and analyzed. The results showed that HS in polyurethane had the excellent resistance to gamma radiation, whereas SS had a tendency to degrade. The reason for the decrease of the strain at break and the ultimate tensile strength was analyzed, which showed the changes in the mechanical properties of polyurethane irradiated by gamma rays were mainly determined by the changes of free volume in SS. If the resistance properties of polyurethanes exposed to radiations need to be improved, SS should be paid more attention to. (author)

The relationship between cerebrovascular disease and homocysteine, folate and vitamin B12 in serum

International Nuclear Information System (INIS)

Wang Wei; Yang Chen; Shi Yizhen; Liu Zengli

2005-01-01

To investigate the relationship between cerebrovascular disease and the serum levels of homocysteine(Hcy), folate and vitamin B 12 , the serum levels of Hcy, folate and vitamin B 12 in 148 patients with cerebrovascular disease were measured by fluorescence polarization immuno- assay and chemiluminescence and were compared with those in healthy controls. The result showed that the serum Hcy levels in patients with cerebral infarction, cerebral hemorrhage and vertebrobasilar ischemiay were significantly higher than those in healthy controls (P 12 levels were signifieantly lower (P 0.05). No significantly higher ratio of increased Hcy levels was observed in patient with complications (P> 0.05). Our conclusion is that hyperhomocysteinemia may be a new and an independent risk factor for cerebrovascular disease. The serum Hcy level is correlated with decreased levels of folate and vitamin B 12 but not obviously correlated with hypertension, diabetes and coronary heart disease. (authors)

Mechanisms of Change in the Relationship between Self-Compassion, Emotion Regulation, and Mental Health: A Systematic Review.

Science.gov (United States)

Inwood, Elisa; Ferrari, Madeleine

2018-04-19

Research suggests that self-compassion may improve mental health by promoting emotion regulation (Berking & Whitley, ). This review aimed to identify studies which investigated the relationship between self-compassion, emotion regulation, and mental health in order to examine the role of emotional regulation as a mechanism of change. Searches were conducted in PsycINFO, CINAHL, Medline complete, Web of Science and Scopus databases. Inclusion criteria required publications to be: peer reviewed, published in English, contain validated measures of self-compassion and emotion regulation, and report a direct analysis on the relationship between these constructs. The search yielded five studies which met inclusion criteria. Emotion regulation significantly mediated the relationship between self-compassion and mental health. This pattern was consistent across community and clinical samples, for a range of mental health symptoms including stress, depression, and post-traumatic stress disorder. A critical limitation of the review was that all included studies used cross-sectional data, limiting interpretations regarding causation. Results provide preliminary evidence that emotion regulation may be a mechanism of change in the relationship between self-compassion and mental health. Self-compassion may be a pertinent preliminary treatment target for individuals who avoid experiences of emotions. © 2018 The International Association of Applied Psychology.

The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease

Directory of Open Access Journals (Sweden)

Dan-dan Cheng

2017-05-01

Full Text Available Helicobacter pylori (H. pylori which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD. Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.

Benefits and complications of noninvasive mechanical ventilation for acute exacerbation of chronic obstructive pulmonary disease.

Science.gov (United States)

Rocha, Eduardo; Carneiro, Elida Mara

2008-06-01

Chronic obstructive pulmonary disease (COPD) is defined as a syndrome characterized by usually progressive chronic airflow limitation which is associated to a bronchial hyperresponsiveness and is partially reversible. Noninvasive mechanical ventilation is an alternative treatment for patients with COPD exacerbations. The objective of the literature reviews was to verify noninvasive mechanical ventilation benefits and complications in acute exacerbations of chronic obstructive pulmonary disease in patients. This national and international's scientific literature review was developed according to criteria established for documentary research in the MedLine, LILACS, SciElo, PubMed and Cochrane, databases using the key words: chronic obstructive pulmonary disease and noninvasive mechanical ventilation. Inclusion criteria were articles published from 1995 to 2007; in English, Spanish and Portuguese; studies in the human model and with no gender restriction. Noninvasive mechanical ventilation can reduce partial pressure of carbon dioxide, improve gas exchange, alleviate symptoms as dyspnea caused by fatigue of the respiratory muscles, reduce duration of hospitalization, decrease need for invasive mechanical ventilation, reduce number of complications and also lessen hospital mortality. The main complications found were: facial skin erythema, claustrophobia, nasal congestion, face pain, eye irritation, aspiration pneumonia, hypotension, pneumothorax, aerophagia, hypercapnia, gastric insufflation, vomit, bronchoaspiration, morning headaches, face injuries, air embolism and, last but not least, discomfort of the patient. Noninvasive mechanical ventilation can be more effective in patients with moderate-severe exacerbations of COPD and these complications can be minimized by an adequate interface also by the contribution of the physiotherapist experience.

Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

Science.gov (United States)

Low, Felicia M; Gluckman, Peter D; Hanson, Mark A

2011-06-01

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

Science.gov (United States)

Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T; Texier, Yves; van Beersum, Sylvia E C; Horn, Nicola; Willer, Jason R; Mans, Dorus A; Dougherty, Gerard; Lamers, Ideke J C; Coene, Karlien L M; Arts, Heleen H; Betts, Matthew J; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J F; Marcelis, Carlo L; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A; Toedt, Grischa; van Dam, Teunis J P; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L; Blacque, Oliver E; Gibson, Toby J; Huynen, Martijn A; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E; Franco, Brunella; Giles, Rachel H; Ueffing, Marius; Russell, Robert B; Roepman, Ronald

2016-05-13

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database.

Directory of Open Access Journals (Sweden)

Allan Peter Davis

pharmaceutical drug makers in finding commonalities in disease mechanisms, which in turn could help identify new therapeutics, new indications for existing pharmaceuticals, potential disease comorbidities, and alerts for side effects.

Unraveling the mechanisms underlying postural instability in Parkinson's disease using dynamic posturography

NARCIS (Netherlands)

Nonnekes, J.H.; Kam, D. de; Geurts, A.C.; Weerdesteijn, V.G.M.; Bloem, B.R.

2013-01-01

Postural instability, one of the cardinal symptoms of Parkinson's disease (PD), has devastating consequences for affected patients. Better strategies to prevent falls are needed, but this calls for an improved understanding of the complex mechanisms underlying postural instability. We must also

The fundamental role of mechanical properties in the progression of cancer disease and inflammation

International Nuclear Information System (INIS)

Mierke, Claudia Tanja

2014-01-01

The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in

The fundamental role of mechanical properties in the progression of cancer disease and inflammation

Science.gov (United States)

Mierke, Claudia Tanja

2014-07-01

The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in

Relationship Between Spiritual Well-Being and Hope in Patients with Cardiovascular Disease.

Science.gov (United States)

Yaghoobzadeh, Ameneh; Soleimani, Mohammad Ali; Allen, Kelly A; Chan, Yiong Huak; Herth, Kaye A

2018-06-01

Spirituality and hope have been identified as important constructs in health research, since both are thought to enhance a person's ability to cope with the consequences of serious illness. The aim of this study was to examine the relationship between spiritual well-being and hope in patients with cardiovascular disease. Using descriptive, correlational methodology, the investigator gathered data on a convenience sample of 500 patients with cardiovascular disease who were hospitalized in a medical institution in Iran. The study was conducted over a four-month period. Participants completed a demographic questionnaire, the Spiritual Well-Being Scale (SWBS) and the Herth Hope Index (HHI). The mean score on the SWBS and HHI was 86.21 (SD 12.46) and 34.80 (SD 5.05), respectively. Multivariate predictors for spiritual well-being were female gender (p = 0.047), religiosity (p = 0.018), and hope (p spiritual well-being (p spiritual well-being and hope. Therefore, this study has implications for those providing care to patients with cardiovascular disease.

The application of phase analysis of gated myocardial perfusion imaging to assess left ventricular mechanical dyssynchrony in cardiovascular disease

International Nuclear Information System (INIS)

Wang Jianfeng; Wang Yuetao

2013-01-01

Left ventricular mechanical dyssynchrony is closely related to the severity of cardiovascular disease, it is essential to assess left ventricular mechanical dyssynchrony accurately for early prediction of adverse cardiac events and prognosis assessment of the cardiac resynchronization therapy. As a new technology to assess left ventricular mechanical dyssynchrony, the phase analysis of gated myocardial perfusion imaging (GMPI) can get both quantitative indicators of regional myocardial perfusion, evaluation of regional myocardial viability and scar tissue, as well as quantitative analysis of left ventricular function and left ventricular mechanical synchrony, it has broad application prospects in cardiovascular disease to assess left ventricular mechanical dyssynchrony and prognosis assessment. This review mainly described the applications of GMPI phase analysis in the cardiovascular disease. (authors)

Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity.

Science.gov (United States)

Monnery, Bryn D; Wright, Michael; Cavill, Rachel; Hoogenboom, Richard; Shaunak, Sunil; Steinke, Joachim H G; Thanou, Maya

2017-04-15

The mechanism of polycation cytotoxicity and the relationship to polymer molecular weight is poorly understood. To gain an insight into this important phenomenon a range of newly synthesised uniform (near monodisperse) linear polyethylenimines, commercially available poly(l-lysine)s and two commonly used PEI-based transfectants (broad 22kDa linear and 25kDa branched) were tested for their cytotoxicity against the A549 human lung carcinoma cell line. Cell membrane damage assays (LDH release) and cell viability assays (MTT) showed a strong relationship to dose and polymer molecular weight, and increasing incubation times revealed that even supposedly "non-toxic" low molecular weight polymers still damage cell membranes. The newly proposed mechanism of cell membrane damage is acid catalysed hydrolysis of lipidic phosphoester bonds, which was supported by observations of the hydrolysis of DOPC liposomes. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Chemotext: A Publicly Available Web Server for Mining Drug-Target-Disease Relationships in PubMed.

Science.gov (United States)

Capuzzi, Stephen J; Thornton, Thomas E; Liu, Kammy; Baker, Nancy; Lam, Wai In; O'Banion, Colin P; Muratov, Eugene N; Pozefsky, Diane; Tropsha, Alexander

2018-02-26

Elucidation of the mechanistic relationships between drugs, their targets, and diseases is at the core of modern drug discovery research. Thousands of studies relevant to the drug-target-disease (DTD) triangle have been published and annotated in the Medline/PubMed database. Mining this database affords rapid identification of all published studies that confirm connections between vertices of this triangle or enable new inferences of such connections. To this end, we describe the development of Chemotext, a publicly available Web server that mines the entire compendium of published literature in PubMed annotated by Medline Subject Heading (MeSH) terms. The goal of Chemotext is to identify all known DTD relationships and infer missing links between vertices of the DTD triangle. As a proof-of-concept, we show that Chemotext could be instrumental in generating new drug repurposing hypotheses or annotating clinical outcomes pathways for known drugs. The Chemotext Web server is freely available at http://chemotext.mml.unc.edu .

Exercise training on cardiovascular diseases: Role of animal models in the elucidation of the mechanisms

Directory of Open Access Journals (Sweden)

Bruno Rodrigues

2017-05-01

Full Text Available Abstract Cardiovascular diseases, which include hypertension, coronary artery disease/myocardial infarction and heart failure, are one of the major causes of disability and death worldwide. On the other hand, physical exercise acts in the preventionand treatment of these conditions. In fact, several experiments performed in human beings have demonstrated the efficiency of physical exercise to alter clinical signals observed in these diseases, such as high blood pressure and exercise intolerance. However, even if human studies demonstrated the clinical efficiency of physical exercise, most extensive mechanisms responsible for this phenomenon still have to be elucidated. In this sense, studies using animal models seem to be a good option to demonstrate such mechanisms. Therefore, the aims of the present study are describing the main pathophysiological characteristics of the animal models used in the study of cardiovascular diseases, as well as the main mechanismsassociated with the benefits of physical exercise.

Mechanical problem-solving strategies in Alzheimer's disease and semantic dementia.

Science.gov (United States)

Lesourd, Mathieu; Baumard, Josselin; Jarry, Christophe; Etcharry-Bouyx, Frédérique; Belliard, Serge; Moreaud, Olivier; Croisile, Bernard; Chauviré, Valérie; Granjon, Marine; Le Gall, Didier; Osiurak, François

2016-07-01

The goal of this study was to explore whether the tool-use disorders observed in Alzheimer's disease (AD) and semantic dementia (SD) are of the same nature as those observed in left brain-damaged (LBD) patients. Recent evidence indicates that LBD patients with apraxia of tool use encounter difficulties in solving mechanical problems, characterized by the absence of specific strategies. This pattern may show the presence of impaired mechanical knowledge, critical for both familiar and novel tool use. So, we explored the strategies followed by AD and SD patients in mechanical problem-solving tasks in order to determine whether mechanical knowledge is also impaired in these patients. We used a mechanical problem-solving task in both choice (i.e., several tools were proposed) and no-choice (i.e., only 1 tool was proposed) conditions. We analyzed quantitative data and strategy profiles. AD patients but not SD patients met difficulties in solving mechanical problem-solving tasks. However, the key finding is that AD patients, despite their difficulties, showed strategy profiles that are similar to that of SD patients or controls. Moreover, AD patients exhibited a strategy profile distinct from the one previously observed in LBD patients. Those observations lead us to consider that difficulties met by AD patients to solve mechanical problems or even to use familiar tools may not be caused by mechanical knowledge impairment per se. In broad terms, what we call apraxia of tool use in AD is certainly not the same as apraxia of tool use observed in LBD patients. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Mechanical cough augmentation techniques in amyotrophic lateral sclerosis/motor neuron disease

OpenAIRE

Rafiq, M.K.; Bradburn, M.; Mustfa, N.; Mcdermott, C.J.; Annane, D.

2016-01-01

© 2016 The Cochrane Collaboration.This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of mechanical insufflator/exsufflator (MI-E) and the breath-stacking technique for reducing morbidity and mortality and enhancing quality of life in people with amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).

CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Directory of Open Access Journals (Sweden)

Deepak A. Deshpande

2018-01-01

Full Text Available Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+ signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3 and CD38-cyclic ADP-ribose (CD38/cADPR are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.

CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Science.gov (United States)

Deshpande, Deepak A.; Guedes, Alonso G. P.; Graeff, Richard; Dogan, Soner; Subramanian, Subbaya; Walseth, Timothy F.

2018-01-01

Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed. PMID:29576747

Social Relationships and Health: Is Feeling Positive, Negative, or Both (Ambivalent) about your Social Ties Related to Telomeres?

Science.gov (United States)

Uchino, Bert N.; Cawthon, Richard M.; Smith, Timothy W.; Light, Kathleen C.; McKenzie, Justin; Carlisle, McKenzie; Gunn, Heather; Birmingham, Wendy; Bowen, Kimberly

2012-01-01

Objective The quality of one’s personal relationships has been linked to morbidity and mortality across different diseases. As a result, it is important to examine more integrative mechanisms that might link relationships across diverse physical health outcomes. In this study, we examine associations between relationships and telomeres which predict general disease risk. These questions are pursued in the context of a more comprehensive model of relationships that highlights the importance of jointly considering positive and negative aspects of social ties. Method 136 individuals from a community sample (ages 48 to 77) completed the social relationships index which allows a determination of relationships that differ in their positive and negative substrates (i.e., ambivalent, supportive, aversive, indifferent). Telomere length was determined from peripheral blood mononuclear cells via quantitative PCR. Results Participants who had a higher number of ambivalent ties in their social networks evidenced shorter telomeres. These results were independent of other relationships types (e.g., supportive), as well as standard control variables (e.g., age, health behaviors, medication use). Gender moderated the links between ambivalent ties and telomere length with these associations seen primarily in women. Follow-up analyses revealed that the links between ambivalent ties and telomeres were primarily due to friendships, parents, and social acquaintances. Conclusions Consistent with epidemiological findings, these data highlight a novel and integrative biological mechanism by which social ties may impact health across diseases, and further suggests the importance of incorporating both positivity and negativity in the study of specific relationships and physical health. PMID:22229928

Pemphigus—A Disease of Desmosome Dysfunction Caused by Multiple Mechanisms

Directory of Open Access Journals (Sweden)

Volker Spindler

2018-02-01

Full Text Available Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins (Dsgs 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the role of other antibodies is unclear. Dsg3 interactions can be directly reduced by specific autoantibodies. Autoantibodies also alter the activity of signaling pathways, some of which regulate cell cohesion under baseline conditions and alter the turnover of desmosomal components. These pathways include Ca2+, p38MAPK, PKC, Src, EGFR/Erk, and several others. In this review, we delineate the mechanisms relevant for pemphigus pathogenesis based on the histology and the ultrastructure of patients’ lesions. We then dissect the mechanisms which can explain the ultrastructural hallmarks detectable in pemphigus patient skin. Finally, we reevaluate the concept that the spectrum of mechanisms, which induce desmosome dysfunction upon binding of pemphigus autoantibodies, finally defines the clinical phenotype.

Action mechanisms of transcranial direct current stimulation in Alzheimer's disease and memory loss.

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Hansen, Niels

2012-01-01

The pharmacological treatment of Alzheimer's disease (AD) is often limited and accompanied by drug side effects. Thus alternative therapeutic strategies such as non-invasive brain stimulation are needed. Few studies have demonstrated that transcranial direct current stimulation (tDCS), a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilitation in depressive patients, Parkinson's disease, and stroke. tDCS improves working and visual recognition memory in humans and object-recognition learning in the elderly. AD's neurobiological mechanisms comprise changes in neuronal activity and the cerebral blood flow (CBF) caused by altered microvasculature, synaptic dysregulation from ß-amyloid peptide accumulation, altered neuromodulation via degenerated modulatory amine transmitter systems, altered brain oscillations, and changes in network connectivity. tDCS alters (i) neuronal activity and (ii) human CBF, (iii) has synaptic and non-synaptic after-effects (iv), can modify neurotransmitters polarity-dependently, (v) and alter oscillatory brain activity and (vi) functional connectivity patterns in the brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it improves cognitive function in manner based on a disease mechanism. Moreover, it could prove valuable in other types of dementia. Future large-scale clinical and mechanism-oriented studies may enable us to identify its therapeutic validity in other types of demential disorders.

Research progress in role of iron overload in non-alcoholic fatty liver disease

OpenAIRE

LI Guangming

2013-01-01

Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD). The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iro...

Human Environmental Disease Network: A computational model to assess toxicology of contaminants.

Science.gov (United States)

Taboureau, Olivier; Audouze, Karine

2017-01-01

During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants associated with diverse human disorders. However, the relationships between diseases based on chemical exposure rarely have been studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration of systems biology and chemical toxicology using information on chemical contaminants and their disease relationships reported in the TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships, allowing inclusion of some degrees of significance in the disease-disease associations. Such a network can be used to identify uncharacterized connections between diseases. Examples are discussed for type 2 diabetes (T2D). Additionally, this computational model allows confirmation of already known links between chemicals and diseases (e.g., between bisphenol A and behavioral disorders) and also reveals unexpected associations between chemicals and diseases (e.g., between chlordane and olfactory alteration), thus predicting which chemicals may be risk factors to human health. The proposed human EDN model allows exploration of common biological mechanisms of diseases associated with chemical exposure, helping us to gain insight into disease etiology and comorbidity. This computational approach is an alternative to animal testing supporting the 3R concept.

Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease

NARCIS (Netherlands)

Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W.; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P.

2015-01-01

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship

Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

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Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

2014-01-01

Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

A study on a relationship between prevalence of respiratory disease and air pollution in two areas

OpenAIRE

五島,正規

2000-01-01

There have been many studies on the relationship between prevalence and incidence of respiratory disease and air pollution. This study was conducted by organized efforts of a regional medical association. Every member of the association reported the numbers of patients with respiratory diseases such as asthmatic bronchitis, chronic bronchitis, and bronchial asthma, and the total number of patients who consulted him/her. The former report was conducted in K city, and this study was of the Y ar...

Unraveling Alzheimer's: Making Sense of the Relationship between Diabetes and Alzheimer's Disease1.

Science.gov (United States)

Schilling, Melissa A

2016-01-01

Numerous studies have documented a strong association between diabetes and Alzheimer's disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intranasal insulin or the inhibition of IDE would exacerbate the disease. Such antithetical conclusions pose a serious obstacle to making progress on treatments. However, careful integration of multiple strands of research, with attention to the methods used in different studies, makes it possible to disentangle the research on AD. This integration suggests that there is an important relationship between insulin, IDE, and AD that yields multiple pathways to AD depending on the where deficiency or excess in the cycle occurs. I review evidence for each of these pathways here. The results suggest that avoiding excess insulin, and supporting robust IDE levels, could be important ways of preventing and lessening the impact of AD. I also describe what further tests need to be conducted to verify the arguments made in the paper, and their implications for treating AD.

Mortality from cardiovascular diseases in the Semipalatinsk historical cohort, 1960-1999, and its relationship to radiation exposure.

Science.gov (United States)

Grosche, Bernd; Lackland, Daniel T; Land, Charles E; Simon, Steven L; Apsalikov, Kazbek N; Pivina, Ludmilla M; Bauer, Susanne; Gusev, Boris I

2011-11-01

The data on risk of mortality from cardiovascular disease due to radiation exposure at low or medium doses are inconsistent. This paper reports an analysis of the Semipalatinsk historical cohort exposed to radioactive fallout from nuclear testing in the vicinity of the Semipalatinsk Nuclear Test Site, Kazakhstan. The cohort study, which includes 19,545 persons of exposed and comparison villages in the Semipalatinsk region, had been set up in the 1960s and comprises 582,656 person-years of follow-up between 1960 and 1999. A dosimetric approach developed by the U.S. National Cancer Institute (NCI) has been used. Radiation dose estimates in this cohort range from 0 to 630 mGy (whole-body external). Overall, the exposed population showed a high mortality from cardiovascular disease. Rates of mortality from cardiovascular disease in the exposed group substantially exceeded those of the comparison group. Dose-response analyses were conducted for both the entire cohort and the exposed group only. A dose-response relationship that was found when analyzing the entire cohort could be explained completely by differences between the baseline rates in exposed and unexposed groups. When taking this difference into account, no statistically significant dose-response relationship for all cardiovascular disease, for heart disease, or for stroke was found. Our results suggest that within this population and at the level of doses estimated, there is no detectable risk of radiation-related mortality from cardiovascular disease.

The relationship between disease and function and perceived health in very frail elders.

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Mulrow, C D; Gerety, M B; Cornell, J E; Lawrence, V A; Kanten, D N

1994-04-01

To study associations between disease and observed function and self-perceived health in very frail elders. Cross-sectional survey of nine nursing homes in San Antonio, TX. 194 elderly long-stay nursing home residents dependent in at least two ADLs and without severe cognitive impairment. Burden of disease (BOD) was chart abstracted using a standardized protocol that assessed types and severities of 59 categorizations of chronic and acute medical conditions. Observed function and self-perceived health status were assessed independently by the Katz Activities of Daily Living scale (ADL) and the Sickness Impact Profile (SIP), respectively. Summary BOD scores had a low, but statistically significant, univariate correlation with ADL scores (r = 0.21, P = 0.003) and no significant correlation with SIP scores (R = -0.008). Multiple linear regression analyses, including the 24 most frequent disease categories, showed that disease explained significant amounts of ADL (r2 = 0.25, P = 0.001) and borderline significant amounts of SIP (r2 = 0.16, P = 0.11). Models including both disease and sociodemographic, cognitive, and affective variables showed disease added significant incremental explantation beyond the other factors to ADL (incremental r2 = 0.14, P = 0.04), but not to SIP (incremental r2 = 0.08, P > 0.10). Disease, observed function, and self-perceived health status are separate, but interrelated entities, with disease having a stronger relationship to observed function than self-perceived health. Comprehensive assessment of frail elders may need to include all three areas, and studies that focus on one area should take into account the other two as potential important covariates.

[Relationship between daily mean temperature and emergency department visits for respiratory diseases: a time-series analysis].

Science.gov (United States)

Mo, Yun-zheng; Zheng, Ya-an; Tao, Hui; Xu, Mei-mei; Li, Guo-xing; Dong, Feng-ming; Liu, Jun-han; Pan, Xiao-chuan

2012-06-18

To quantitatively evaluate the influences of daily mean air temperature (DMT) on Emergency Department Visits (EDVs) for the respiratory diseases. The EDV data from medical records for respiratory diseases in Peking University Third Hospital between January 2004 and June 2009 were collected. The data of the air pollutants (SO(2), NO(2) and PM(10)) and meteorological factors at the same time periods were also collected from the local authorities of Beijing. Time-series analysis and generalized additive models (GAM) were used to explore the exposurrre-response relationship between DMT and EDVs for respiratory diseases. A total of 35 073 patients [males 14 707(41.93%,14 707/35 073), females 19 122(54.52%,19 122/35 073) and gender missing 1 244(3.55%, 1 244/35 073)] EDVs for respiratory diseases were included. The relationship between DMT and EDVs for the respiratory diseases was mainly of "V" shape, the optimum temperature(OT) was about 4 °C and the effect of DMT was significant with a 0-3 day lag structure for most of the models. When DMT≤OT, each 1°C decrease in DMT corresponded to 3.75% (95% CI of RR: 0.938 3-0.965 3), 3.10% (95% CI of RR:0.949 2-0.989 1), 4.09% (95% CI of RR:0.940 7-0.977 8) increase of EDVs for the overall, male, and female, respectively. When DMT>OT, the value caused by each increase in 1°C in DMT was 1.54% (95% CI of RR:1.006 6-1.024 3), 1.80% (95% CI of RR:1.005 3-1.030 9), and 1.51 (95% CI of RR:1.003 2- 1.027 2), respectively. The effect was statistically significant within the 0-3 day lag. When DMT≤OT, the effect was stronger for the older people, while the effect was strongest for the 45-59 years old people. The relationship between DMT and EDVs for respiratory diseases is mainly of "V" type, with an optimum temperature of 4 °C.Both DMT decrease when DMT≤OT and increase when DMT>OT correspond to different increase of EDVs for respiratory diseases. Low DMT has stronger effect than high DMT. Different age group and gender have

Mechanisms of renal NaCl retention in proteinuric disease

DEFF Research Database (Denmark)

Svenningsen, Per; Friis, Ulla G; Versland, Jostein B

2013-01-01

In diseases with proteinuria, for example nephrotic syndrome and pre-eclampsia, there often are suppression of plasma renin-angiotensin-aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed...... of proteolytic activation of ENaC has been explored. Proteolysis leads to putative release of an inhibitory peptide from the extracellular domain of the gamma ENaC subunit. This leads to full activation of the channel. Plasminogen has been demonstrated in urine from patients with nephrotic syndrome and pre-eclampsia...

Aberrant and alternative splicing in skeletal system disease.

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Fan, Xin; Tang, Liling

2013-10-01

The main function of skeletal system is to support the body and help movement. A variety of factors can lead to skeletal system disease, including age, exercise, and of course genetic makeup and expression. Pre-mRNA splicing plays a crucial role in gene expression, by creating multiple protein variants with different biological functions. The recent studies show that several skeletal system diseases are related to pre-mRNA splicing. This review focuses on the relationship between pre-mRNA splicing and skeletal system disease. On the one hand, splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP5. On the other hand, alternative splicing without genomic mutation may generate some marker protein isoforms, for example, FN, VEGF and CD44. Therefore, understanding the relationship between pre-mRNA splicing and skeletal system disease will aid in uncovering the mechanism of disease and contribute to the future development of gene therapy. © 2013 Elsevier B.V. All rights reserved.

Relationship between Metabolic Syndrome Components and Periodontal Disease in a Japanese General Population: the Suita Study.

Science.gov (United States)

Kikui, Miki; Kokubo, Yoshihiro; Ono, Takahiro; Kida, Momoyo; Kosaka, Takayuki; Yamamoto, Masaaki; Watanabe, Makoto; Maeda, Yoshinobu; Miyamoto, Yoshihiro

2017-05-01

A positive association between metabolic syndrome (MetS) and periodontal status has recently been noted. However, no study has evaluated the relationship by sex and in a general urban population using the uniform definition proposed in the 2009 Joint Interim Statement. The aim of this study was to clarify the relationship between MetS and periodontal status using the uniform definition in a general urban Japanese population. A total of 1,856 Japanese men and women (mean age: 66.4 years) were studied using data from the Suita study. Periodontal status was evaluated by the Community Periodontal Index (CPI). MetS was defined using the 2009 Joint Interim Statement. The associations of the MetS and its components with periodontal disease were investigated using multiple logistic regression analysis adjusting for age, drinking, and smoking. Among the components of the MetS, low HDL cholesterol level was significantly associated with periodontal disease in men and women [odds ratios (OR)=2.39 and 1.53; 95% confidence intervals=1.36-4.19 and 1.06-2.19]. Furthermore, the risk of periodontal disease showed 1.43-, 1.42-, and 1.89-fold increases in those with 2, 3, and ≥4 components, respectively, compared with those having no components (P trend ＜0.001). For the analysis by sex, the risk of periodontal disease was increased 2.27- and 1.76-fold in those with ≥4 components in men and women, respectively (both P trend =0.001). These findings suggest that MetS and lower HDL cholesterol are associated with periodontal disease. Subjects with two or more MetS components had a significantly higher prevalence of periodontal disease.

Protective influence of healthful nutrition on mechanisms of environmental pollutant toxicity and disease risks.

Science.gov (United States)

Hoffman, Jessie B; Hennig, Bernhard

2017-06-01

Human exposures to environmental contaminants around the world contribute to the global burden of disease and thus require urgent attention. Exploring preventive measures against environmental exposure and disease risk is essential. While a sedentary lifestyle and/or poor dietary habits can exacerbate the deleterious effects resulting from exposure to toxic chemicals, much emerging evidence suggests that positive lifestyle changes (e.g., healthful nutrition) can modulate and/or reduce the toxicity of environmental pollutants. Our work has shown that diets high in anti-inflammatory bioactive food components (e.g., phytochemicals or polyphenols) are possible strategies for modulating and reducing the disease risks associated with exposure to toxic pollutants in the environment. Thus, consuming healthy diets rich in plant-derived bioactive nutrients may reduce the vulnerability to diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationships between nutrition and other lifestyle modifications and toxicant-induced diseases. © 2017 New York Academy of Sciences.

Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.

Science.gov (United States)

Marei, Hadir; Malliri, Angeliki

2017-07-03

Abnormal Rac1 signaling is linked to a number of debilitating human diseases, including cancer, cardiovascular diseases and neurodegenerative disorders. As such, Rac1 represents an attractive therapeutic target, yet the search for effective Rac1 inhibitors is still underway. Given the adverse effects associated with Rac1 signaling perturbation, cells have evolved several mechanisms to ensure the tight regulation of Rac1 signaling. Thus, characterizing these mechanisms can provide invaluable information regarding major cellular events that lead to aberrant Rac1 signaling. Importantly, this information can be utilized to further facilitate the development of effective pharmacological modulators that can restore normal Rac1 signaling. In this review, we focus on the pathological role of Rac1 signaling, highlighting the benefits and potential drawbacks of targeting Rac1 in a clinical setting. Additionally, we provide an overview of available compounds that target key Rac1 regulatory mechanisms and discuss future therapeutic avenues arising from our understanding of these mechanisms.

Assessment of waist/hip ratio and its relationship with coronary heart disease in community hospital of district swat

International Nuclear Information System (INIS)

Ahmad, R.; Ahmad, A.; Jan, S.; Rehman, I.U.

2007-01-01

To evaluate the relationship between central obesity (Abdominal adiposity), measured by Waist/Hip ratio and the development of Coronary Heart Disease in adult population of district Swat. The study comprised of 100 subjects, 34 Control, 33 Hypertensive subjects and 33 subjects with Coronary Heart Disease. Weight, Height, Waist/Hip ratio and Blood Pressure of subjects with Coronary Heart Disease (CHD) were compared with Hypertensive subjects and Control subjects. Patients with Coronary Heart Disease had higher Waist/Hip ratio and Blood Pressure than Hypertensive subjects, which in turn had higher values than control subjects. Waist/hip ratio is the dominant risk factor predicting Coronary Heart Disease. (author)

The Relationship Between Air Particulate Levels and Upper Respiratory Disease in Soldiers Deployed to Bosnia (1997-1998)

National Research Council Canada - National Science Library

Hastings, Deborah

2001-01-01

This study had three objectives: to determine if there is a relationship between air particulate levels and upper respiratory disease in soldiers deployed to Bosnia between 1997-98, to establish a method for linking environmental...

Evaluation of the knowledge of pregnant women about the relationship between oral diseases and pregnancy complications

Directory of Open Access Journals (Sweden)

Carmem Dolores de Sá Catão

Full Text Available INTRODUCTION: Chronic persistent low-level infection in pregnant women, such as periodontal disease (PD may impair maternal-fetal unit, since the infectious process induces the release of chemical mediators involved in the process of prematurity. OBJECTIVE: To assess the knowledge of mothers as regards the relationship between oral diseases and pregnancy complications. METHOD: A cross-sectional epidemiological study was conducted with 104 pregnant women indexed in the Primary Care Information System (SIAB, in the Family Health Strategies (FHS, using a structured questionnaire. Data were recorded in SPSS and analyzed using descriptive and inferential statistics, considering a significance level of 5%. RESULT: Most patients (64.4% were domestic workers, (48.1% aged 24 to 34 years, (55.8% showed complete the 2nd grade and incomplete high school education, and (49% were primiparous. Among the participants, 76% were unaware of the relationship between oral disease, prematurity and giving birth to low birth weight babies. Statistically significant association was found between: educational level and knowledge about prenatal dental care (p = 0.012; since it was shown that 90.4% ignored the existence of this activity and 65.4% had never received information about the care of baby's oral hygiene (p = 0.003. CONCLUSION: Most women were unaware of the relationship of PD with prematurity, and showed lack of information about the care of mother and baby oral hygiene, highlighting the need for greater integration between the dental surgeon and other primary care professionals to promote oral health care of pregnant women and reduce the ratio of PD with pregnancy complications.

Conflicting relationship between age-dependent disorders, valvular heart disease and coronary artery disease by covariance structure analysis: Possible contribution of natriuretic peptide

Science.gov (United States)

Yoshida, Jun; Inoue, Yasunori; Morimoto, Satoshi; Tanaka, Toshikazu; Ogawa, Takayuki

2017-01-01

Background It is conceivable that contemporary valvular heart disease (VHD) is affected largely by an age-dependent atherosclerotic process, which is similar to that observed in coronary artery disease (CAD). However, a comorbid condition of VHD and CAD has not been precisely examined. The first objective of this study was to examine a possible comorbid condition. Provided that there is no comorbidity, the second objective was to search for the possible reasons by using conventional risk factors and plasma B-type natriuretic peptide (BNP) because BNP has a potentiality to suppress atherosclerotic development. Methods The study population consisted of 3,457 patients consecutively admitted to our institution. The possible comorbid condition of VHD and CAD and the factors that influence the comorbidity were examined by covariance structure analysis and multivariate analysis. Results The distribution of the patients with VHD and those with CAD in the histograms showed that the incidence of VHD and the severity of CAD rose with seniority in appearance. The real statistical analysis was planned by covariance structure analysis. The current path model revealed that aging was associated with VHD and CAD severity (P < 0.001 for each); however, as a notable result, there was an inverse association regarding the comorbid condition between VHD and CAD (Correlation coefficient [β]: -0.121, P < 0.001). As the second objective, to clarify the factors leading to this inverse association, the contribution of conventional risk factors, such as age, gender, hypertension, smoking, diabetes, obesity and dyslipidemia, to VHD and CAD were examined by multivariate analysis. However, these factors did not exert an opposing effect on VHD and CAD, and the inverse association defied explanation. Since different pathological mechanisms may contribute to the formation of VHD and CAD, a differentially proposed path model using plasma BNP revealed that an increase in plasma BNP being drawn by

Conflicting relationship between age-dependent disorders, valvular heart disease and coronary artery disease by covariance structure analysis: Possible contribution of natriuretic peptide.

Science.gov (United States)

Fukumoto, Risa; Kawai, Makoto; Minai, Kosuke; Ogawa, Kazuo; Yoshida, Jun; Inoue, Yasunori; Morimoto, Satoshi; Tanaka, Toshikazu; Nagoshi, Tomohisa; Ogawa, Takayuki; Yoshimura, Michihiro

2017-01-01

It is conceivable that contemporary valvular heart disease (VHD) is affected largely by an age-dependent atherosclerotic process, which is similar to that observed in coronary artery disease (CAD). However, a comorbid condition of VHD and CAD has not been precisely examined. The first objective of this study was to examine a possible comorbid condition. Provided that there is no comorbidity, the second objective was to search for the possible reasons by using conventional risk factors and plasma B-type natriuretic peptide (BNP) because BNP has a potentiality to suppress atherosclerotic development. The study population consisted of 3,457 patients consecutively admitted to our institution. The possible comorbid condition of VHD and CAD and the factors that influence the comorbidity were examined by covariance structure analysis and multivariate analysis. The distribution of the patients with VHD and those with CAD in the histograms showed that the incidence of VHD and the severity of CAD rose with seniority in appearance. The real statistical analysis was planned by covariance structure analysis. The current path model revealed that aging was associated with VHD and CAD severity (P < 0.001 for each); however, as a notable result, there was an inverse association regarding the comorbid condition between VHD and CAD (Correlation coefficient [β]: -0.121, P < 0.001). As the second objective, to clarify the factors leading to this inverse association, the contribution of conventional risk factors, such as age, gender, hypertension, smoking, diabetes, obesity and dyslipidemia, to VHD and CAD were examined by multivariate analysis. However, these factors did not exert an opposing effect on VHD and CAD, and the inverse association defied explanation. Since different pathological mechanisms may contribute to the formation of VHD and CAD, a differentially proposed path model using plasma BNP revealed that an increase in plasma BNP being drawn by VHD suppressed the

[The Relationships among Perceived Parental Bonding, Illness Perception, and Anxiety in Adult Patients with Congenital Heart Diseases].

Science.gov (United States)

Shin, Nayeon; Jang, Youha; Kang, Younhee

2017-04-01

The purposes of this study were to identify the relationships among perceived parental bonding, illness perception, and anxiety and to determine the influences of perceived parental bonding and illness perception on anxiety in adult patients with congenital heart diseases. In this study a descriptive correlational design with survey method was utilized. The participants were 143 adult patients with congenital heart disease being cared for in the cardiology out-patient clinic of A medical center. Data were collected using the Parental Bonding Instrument, Illness Perception Questionnaire Revised Scale, and Cardiac Anxiety Questionnaire Scale. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation analysis, and hierarchial regression analyses. There showed significant positive relationships of anxiety with maternal overprotection, consequences, and personal control respectively. Among predictors, maternal overprotection (β=.45), consequence (β=.26), and personal control (β=-.03) had statistically significant influence on anxiety. Nursing interventions to decrease maternal overprotection and negative consequence, and to enhance personal control are essential to decrease the anxiety of adult patients with congenital heart diseases. © 2017 Korean Society of Nursing Science

[Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease].

Science.gov (United States)

Lee, Kwang Jae

2015-08-01

The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.

Relationships Between Components of Blood Pressure and Cardiovascular Events in Patients with Stable Coronary Artery Disease and Hypertension.

Science.gov (United States)

Vidal-Petiot, Emmanuelle; Greenlaw, Nicola; Ford, Ian; Ferrari, Roberto; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Parkhomenko, Alexander; Bhatt, Deepak L; Steg, P Gabriel

2018-01-01

Observational studies have shown a J-shaped relationship between diastolic blood pressure (BP) and cardiovascular events in hypertensive patients with coronary artery disease. We investigated whether the increased risk associated with low diastolic BP reflects elevated pulse pressure (PP). In 22 672 hypertensive patients with coronary artery disease from the CLARIFY registry (Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease), followed for a median of 5.0 years, BP was measured annually and averaged. The relationships between PP and diastolic BP, alone or combined, and the primary composite outcome (cardiovascular death or myocardial infarction) were analyzed using multivariable Cox proportional hazards models. Adjusted hazard ratios for the primary outcome were 1.62 (95% confidence interval [CI], 1.40-1.87), 1.00 (ref), 1.07 (95% CI, 0.94-1.21), 1.54 (95% CI, 1.32-1.79), and 2.34 (95% CI, 1.95-2.81) for PPhypertensive patients with coronary artery disease persists in patients within the lowest-risk PP range and is therefore unlikely to be solely the consequence of an increased PP reflecting advanced vascular disease. URL: http://www.clarify-registry.com. Unique identifier: ISRCTN43070564. © 2017 American Heart Association, Inc.

Lipidomics: Novel insight into the biochemical mechanism of lipid metabolism and dysregulation-associated disease.

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Zhao, Ying-Yong; Miao, Hua; Cheng, Xian-Long; Wei, Feng

2015-10-05

The application of lipidomics, after genomics, proteomics and metabolomics, offered largely opportunities to illuminate the entire spectrum of lipidome based on a quantitative or semi-quantitative level in a biological system. When combined with advances in proteomics and metabolomics high-throughput platforms, lipidomics provided the opportunity for analyzing the unique roles of specific lipids in complex cellular processes. Abnormal lipid metabolism was demonstrated to be greatly implicated in many human lifestyle-related diseases. In this review, we focused on lipidomic applications in brain injury disease, cancer, metabolic disease, cardiovascular disease, respiratory disease and infectious disease to discover disease biomarkers and illustrate biochemical metabolic pathways. We also discussed the analytical techniques, future perspectives and potential problems of lipidomic applications. The application of lipidomics in disease biomarker discovery provides the opportunity for gaining novel insights into biochemical mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Relationship between halitosis and periodontal disease - associated oral bacteria in tongue coatings.

Science.gov (United States)

Amou, T; Hinode, D; Yoshioka, M; Grenier, D

2014-05-01

The objective of our study was to investigate the relationship between halitosis and oral bacteria in tongue coating (TC) and saliva samples from patients with halitosis, and to evaluate the effect of tongue cleaning on halitosis. Ninety-four participants complaining of oral malodour were included in the study. Organoleptic (OR) values, volatile sulphur compound (VSC) concentrations determined by gas chromatography and TC scores were used as clinical parameters of halitosis. Quantitative real-time polymerase chain reactions were used to determine the numbers of periodontal disease-associated oral bacteria. There was a significant correlation between TC scores and OR values, methylmercaptan (CH3 SH) concentrations and VSC concentrations (Spearman's rank-correlation coefficient test, P periodontal disease-associated oral bacteria in TCs are closely related to halitosis and that tongue cleaning may be an effective method for improving halitosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

Science.gov (United States)

Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

2015-01-01

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

Alzheimer's disease: relationship between cognitive aspects and power and coherence EEG measures

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Lineu C. Fonseca

2011-12-01

Full Text Available OBJECTIVE: To evaluate the relationship between specific cognitive aspects and quantitative EEG measures, in patients with mild or moderate Alzheimer's disease (AD. METHOD: Thirty-eight AD patients and 31 controls were assessed by CERAD neuropsychological battery (Consortium to Establish a Registry for AD and the electroencephalogram (EEG. The absolute power and coherences EEG measures were calculated at rest. The correlations between the cognitive variables and the EEG were evaluated. RESULTS: In the AD group there were significant correlations between different coherence EEG measures and Mini-Mental State Examination, verbal fluency, modified Boston naming, word list memory with repetition, word list recall and recognition, and constructional praxis (p<0.01. These correlations were all negative for the delta and theta bands and positive for alpha and beta. There were no correlations between cognitive aspects and absolute EEG power. CONCLUSION: The coherence EEG measures reflect different forms in the relationship between regions related to various cognitive dysfunctions.

Relationship between leptin concentrations and disease activity in patients with rheumatoid arthritis.

Science.gov (United States)

Batún-Garrido, José Antonio de Jesús; Salas-Magaña, Marisol; Juárez-Rojop, Isela Esther; Hernández-Núñez, Eúfrates; Olán, Francisco

2018-05-11

Multiple studies have found a direct relationship between leptin concentrations and disease activity in rheumatoid arthritis. We studied 77 patients with the diagnosis of rheumatoid arthritis; the leptin determination was through an enzyme immunoassay. Disease activity was assessed by the DAS-28 CRP. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations. 40.3% of the patients were in remission, 41.6% were mildly active, 11.7% were moderately active and 6.5% were severely active. The results show an independent association between higher concentrations of leptin and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4; 95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC 1.2-1,9; p .045). The data suggest that serum leptin is elevated in patients with active RA. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Relationships among the structural topology, bond strength, and mechanical properties of single-walled aluminosilicate nanotubes.

Science.gov (United States)

Liou, Kai-Hsin; Tsou, Nien-Ti; Kang, Dun-Yen

2015-10-21

Carbon nanotubes (CNTs) are regarded as small but strong due to their nanoscale microstructure and high mechanical strength (Young's modulus exceeds 1000 GPa). A longstanding question has been whether there exist other nanotube materials with mechanical properties as good as those of CNTs. In this study, we investigated the mechanical properties of single-walled aluminosilicate nanotubes (AlSiNTs) using a multiscale computational method and then conducted a comparison with single-walled carbon nanotubes (SWCNTs). By comparing the potential energy estimated from molecular and macroscopic material mechanics, we were able to model the chemical bonds as beam elements for the nanoscale continuum modeling. This method allowed for simulated mechanical tests (tensile, bending, and torsion) with minimum computational resources for deducing their Young's modulus and shear modulus. The proposed approach also enabled the creation of hypothetical nanotubes to elucidate the relative contributions of bond strength and nanotube structural topology to overall nanotube mechanical strength. Our results indicated that it is the structural topology rather than bond strength that dominates the mechanical properties of the nanotubes. Finally, we investigated the relationship between the structural topology and the mechanical properties by analyzing the von Mises stress distribution in the nanotubes. The proposed methodology proved effective in rationalizing differences in the mechanical properties of AlSiNTs and SWCNTs. Furthermore, this approach could be applied to the exploration of new high-strength nanotube materials.

Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases.

Science.gov (United States)

Tarín, Juan J; García-Pérez, Miguel A; Hamatani, Toshio; Cano, Antonio

2015-04-15

The present review aims to ascertain whether different infertility etiologies share particular genes and/or molecular pathways with other pathologies and are associated with distinct and particular risks of later-life morbidity and mortality. In order to reach this aim, we use two different sources of information: (1) a public web server named DiseaseConnect ( http://disease-connect.org ) focused on the analysis of common genes and molecular mechanisms shared by diseases by integrating comprehensive omics and literature data; and (2) a literature search directed to find clinical comorbid relationships of infertility etiologies with only those diseases appearing after infertility is manifested. This literature search is performed because DiseaseConnect web server does not discriminate between pathologies emerging before, concomitantly or after infertility is manifested. Data show that different infertility etiologies not only share particular genes and/or molecular pathways with other pathologies but they have distinct clinical relationships with other diseases appearing after infertility is manifested. In particular, (1) testicular and high-grade prostate cancer in male infertility; (2) non-fatal stroke and endometrial cancer, and likely non-fatal coronary heart disease and ovarian cancer in polycystic ovary syndrome; (3) osteoporosis, psychosexual dysfunction, mood disorders and dementia in premature ovarian failure; (4) breast and ovarian cancer in carriers of BRCA1/2 mutations in diminished ovarian reserve; (5) clear cell and endometrioid histologic subtypes of invasive ovarian cancer, and likely low-grade serous invasive ovarian cancer, melanoma and non-Hodgkin lymphoma in endometriosis; and (6) endometrial and ovarian cancer in idiopathic infertility. The present data endorse the principle that the occurrence of a disease (in our case infertility) is non-random in the population and suggest that different infertility etiologies are genetically and clinically

The relationship of microstructure and temperature to fracture mechanics parameters in reaction bonded silicon nitride

International Nuclear Information System (INIS)

Jennings, H.M.; Dalgleish, B.J.; Pratt, P.L.

1978-01-01

The development of physical properties in reaction bonded silicon nitride has been investigated over a range of temperatures and correlated with microstructure. Fracture mechanics parameters, elastic moduli, strength and critical defect size have been determined. The nitrided microstructure is shown to be directly related to these observed properties and these basic relationships can be used to produce material with improved properties. (orig.) [de

Relationship between periodontal disease and preterm low birth weight: systematic review.

Science.gov (United States)

Teshome, Amare; Yitayeh, Asmare

2016-01-01

Periodontal disease is a neglected bacterial infection that causes destruction of the periodontium in pregnant women. Yet its impact on the occurrence of adverse pregnancy outcomes has not systematically evaluated and there is no clear statement on the relationship between periodontal disease and preterm low birth weight. The objective of this study was to summarize the evidence on the impact of periodontal disease on preterm low birth weight. We searched the following data bases from January 2005 to December 2015: CINAHL (cumulative index to nursing and allied health literature), MEDLINE, AMED, EMBASE (excerpta medica database), Cochrane library and Google scholar. Only case-control studies with full text in English were eligible. Critical appraisal of the identified articles was done by two authors independently to provide the possible relevance of the papers for inclusion in the review process. The selected Case control studies were critically appraised with 12 items structured checklist adapted from national institute of health (NIH). Odds ratio (OR) or risk ratios (RR) were extracted from the selected studies. The two reviewers who selected the appropriate studies also extracted the data and evaluated the risk of bias. Of 229 articles, ten studies with a total of 2423 participants with a mean age ranged from 13 to 49 years were met the inclusion criteria. The studies focused on preterm birth, low birth weight and /or preterm low birth weight and periodontitis. Of the selected studies, 9 implied an association between periodontal disease and increased risk of preterm birth, low birth weight and /or preterm low birth weight outcome (ORs ranging from 2.04 to 4.19) and only one study found no evidence of association. Periodontal disease may be one of the possible risk factor for preterm low birth weight infant. However, more precise studies with randomized clinical trial with sufficient follow-up period must be done to confirm the association.

Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data.

Directory of Open Access Journals (Sweden)

Jonathan D Mosley

Full Text Available A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1 non-synonymous SNPs (nsSNPs associated with "mechanistic phenotypes", comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1 thrombosis, evaluated in a population of 1,655 African Americans; and (2 four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs, and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03, driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10-5, FDR p = 0.03 (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L while the additive model showed enrichment related to chromatid segregation (p = 4×10-6, FDR p = 0.005 (KIF25, PINX1. We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.

The relationship between performance on the Infectious Diseases In-Training and Certification Examinations.

Science.gov (United States)

Grabovsky, Irina; Hess, Brian J; Haist, Steven A; Lipner, Rebecca S; Hawley, Janine L; Woodward, Stephanie; Engleberg, N Cary

2015-03-01

The Infectious Diseases Society of America In-Training Examination (IDSA ITE) is a feedback tool used to help fellows track their knowledge acquisition during fellowship training. We determined whether the scores on the IDSA ITE and from other major medical knowledge assessments predict performance on the American Board of Internal Medicine (ABIM) Infectious Disease Certification Examination. The sample was 1021 second-year fellows who took the IDSA ITE and ABIM Infectious Disease Certification Examination from 2008 to 2012. Multiple regression analysis was used to determine if ABIM Infectious Disease Certification Examination scores were predicted by IDSA ITE scores, prior United States Medical Licensing Examination (USMLE) scores, ABIM Internal Medicine Certification Examination scores, fellowship director ratings of medical knowledge, and demographic variables. Logistic regression was used to evaluate if these same assessments predicted a passing outcome on the certification examination. IDSA ITE scores were the strongest predictor of ABIM Infectious Disease Certification Examination scores (β = .319), followed by prior ABIM Internal Medicine Certification Examination scores (β = .258), USMLE Step 1 scores (β = .202), USMLE Step 3 scores (β = .130), and fellowship directors' medical knowledge ratings (β = .063). IDSA ITE scores were also a significant predictor of passing the Infectious Disease Certification Examination (odds ratio, 1.017 [95% confidence interval, 1.013-1.021]). The significant relationship between the IDSA ITE score and performance on the ABIM Infectious Disease Certification Examination supports the use of the ITE as a valid feedback tool in fellowship training. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Quality of life and life satisfaction in patients with Behçet's disease: relationship with disease activity.

Science.gov (United States)

Bodur, Hatice; Borman, Pinar; Ozdemir, Yildiz; Atan, Ciğdem; Kural, Gülcan

2006-05-01

Quality of life (QoL) and life satisfaction (LS) are important outcome factors in chronic inflammatory conditions such as Behçet's disease (BD). The aim of this study was to investigate QoL and LS in patients with BD and determine the relationship with disease activity. Forty-one patients with BD and 40 control subjects were involved in the study. Demographic properties were obtained. Disease activity was assessed by Turkish version of BD Current Activity Form (BDCAF) in BD patients. QoL and psychological well-being were assessed by Nottingham Health Profile (NHP) and Life Satisfaction Index (LSI), respectively, in both patients and control groups. The related disease activity measures of QoL and LS were determined. Twenty-two male and 19 female BD patients with a mean age of 33.3+/-9.3 years and 20 male and 20 female control subjects with a mean age of 33.3+/-4.1 years were involved. According to BDCAF, no patient had central nervous system involvement. Thirty-four patients had headache, 33 patients had fatigue, 30 patients had articular involvement, 29 had mucocutaneous lesions, 27 had gastrointestinal involvement, 21 patients had ocular involvement, and 7 patients had vascular involvement. The scores of all dimensions of NHP were significantly higher and the mean score of LSI was significantly lower in BD patients than in control subjects (pimpression of disease activity and joint involvement. In conclusion, patients with BD have impaired QoL and disturbed psychological well-being. Current management strategies focusing on fatigue, arthralgia, mucocutaneous lesions, and efforts to measure psychosocial aspects and symptoms of the patients by their point of view will help to improve QoL and raise the LS in patients suffering from BD.

Relationship between neural rhythm generation disorders and physical disabilities in Parkinson's disease patients' walking.

Science.gov (United States)

Ota, Leo; Uchitomi, Hirotaka; Ogawa, Ken-ichiro; Orimo, Satoshi; Miyake, Yoshihiro

2014-01-01

Walking is generated by the interaction between neural rhythmic and physical activities. In fact, Parkinson's disease (PD), which is an example of disease, causes not only neural rhythm generation disorders but also physical disabilities. However, the relationship between neural rhythm generation disorders and physical disabilities has not been determined. The aim of this study was to identify the mechanism of gait rhythm generation. In former research, neural rhythm generation disorders in PD patients' walking were characterized by stride intervals, which are more variable and fluctuate randomly. The variability and fluctuation property were quantified using the coefficient of variation (CV) and scaling exponent α. Conversely, because walking is a dynamic process, postural reflex disorder (PRD) is considered the best way to estimate physical disabilities in walking. Therefore, we classified the severity of PRD using CV and α. Specifically, PD patients and healthy elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We compared the contributions of CV and α to the accuracy of this classification. In this study, 45 PD patients and 17 healthy elderly people walked 200 m. The severity of PRD was determined using the modified Hoehn-Yahr scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD, respectively. As a result, CV differentiated no-PRD from PRD, indicating the correlation between CV and PRD. Considering that PRD is independent of neural rhythm generation, this result suggests the existence of feedback process from physical activities to neural rhythmic activities. Moreover, α differentiated obvious-PRD from mild-PRD. Considering α reflects the intensity of interaction between factors, this result suggests the change of the interaction. Therefore, the interaction between neural rhythmic and physical activities is thought to plays an important role for gait rhythm generation. These characteristics have

Mechanisms of protein misfolding in conformational lung diseases.

LENUS (Irish Health Repository)

McElvaney, N G

2012-08-01

Genetic or environmentally-induced alterations in protein structure interfere with the correct folding, assembly and trafficking of proteins. In the lung the expression of misfolded proteins can induce a variety of pathogenetic effects. Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two major clinically relevant pulmonary disorders associated with protein misfolding. Both are genetic diseases the primary causes of which are expression of mutant alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) and SERPINA1, respectively. The most common and best studied mutant forms of CFTR and AAT are ΔF508 CFTR and the Glu342Lys mutant of AAT called ZAAT, respectively. Non-genetic mechanisms can also damage protein structure and induce protein misfolding in the lung. Cigarette-smoke contains oxidants and other factors that can modify a protein\\'s structure, and is one of the most significant environmental causes of protein damage within the lung. Herein we describe the mechanisms controlling the folding of wild type and mutant versions of CFTR and AAT proteins, and explore the consequences of cigarette-smoke-induced effects on the protein folding machinery in the lung.

Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited

NARCIS (Netherlands)

Paumgartner, Gustav; Beuers, Ulrich

2002-01-01

Ursodeoxycholic acid (UCDA) is increasingly used for the treatment of cholestatic liver diseases. Experimental evidence suggests three major mechanisms of action: (1) protection of cholangiocytes against cytotoxicity of hydrophobic bile acids, resulting from modulation of the composition of mixed

The relationship between Helicobacter pylori-associated gastritis or ulcer disease and gastric emptying

International Nuclear Information System (INIS)

Kao Chiahung; Wang Shyhjen; Chen Granhum; Yeh Shinhwa

1994-01-01

Forty-five patients with Helicobacter pylori (HP)-associated gastritis or ulcer disease were included in this study. Radionuclide-labelled solid meals were used to calculate gastric emptying times (GETs) and carbon-14 urea breath tests ( 14 C UBTs) were used to measure the HP colonies quantitatively. The patients were assessed according to the following two criteria: (a) the HP colony number (i.e. high or low) and (b) the recorded duration of the GET (i.e. long or short). There was no statistically significant difference in the incidence of abnormal GET between high and low 14 C UBT patients or in the incidence of abnormal 14 C UBT between long and short GET cases. In conclusion, no significant relationship between HP-associated gastritis or ulcer disease and GET was found in this study. (orig.)

Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

Directory of Open Access Journals (Sweden)

Agathi-Vasiliki Goula

2013-07-01

Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

Examination of the relationship between preservice science teachers' scientific reasoning and problem solving skills on basic mechanics

Science.gov (United States)

Yuksel, Ibrahim; Ates, Salih

2018-02-01

The purpose of this study is to determine relationship between scientific reasoning and mechanics problem solving skills of students in science education program. Scientific Reasoning Skills Test (SRST) and Basic Mechanics Knowledge Test (BMKT) were applied to 90 second, third and fourth grade students who took Scientific Reasoning Skills course at science teaching program of Gazi Faculty of Education for three successive fall semesters of 2014, 2015 and 2016 academic years. It was found a statistically significant positive (p = 0.038 <0.05) but a low correlation (r = 0.219) between SRST and BMKT. There were no significant relationship among Conservation Laws, Proportional Thinking, Combinational Thinking, Correlational Thinking, Probabilistic Thinking subskills of reasoning and BMKT. There were significant and positive correlation among Hypothetical Thinking and Identifying and Controlling Variables subskills of reasoning and BMKT. The findings of the study were compared with other studies in the field and discussed.

Host-Parasite Relationship in Cystic Echinococcosis: An Evolving Story

Science.gov (United States)

Siracusano, Alessandra; Delunardo, Federica; Teggi, Antonella; Ortona, Elena

2012-01-01

The larval stage of Echinococcus granulosus causes cystic echinococcosis, a neglected infectious disease that constitutes a major public health problem in developing countries. Despite being under constant barrage by the immune system, E. granulosus modulates antiparasite immune responses and persists in the human hosts with detectable humoral and cellular responses against the parasite. In vitro and in vivo immunological approaches, together with molecular biology and immunoproteomic technologies, provided us exciting insights into the mechanisms involved in the initiation of E. granulosus infection and the consequent induction and regulation of the immune response. Although the last decade has clarified many aspects of host-parasite relationship in human cystic echinococcosis, establishing the full mechanisms that cause the disease requires more studies. Here, we review some of the recent developments and discuss new avenues in this evolving story of E. granulosus infection in man. PMID:22110535

Exploring the relationship between periodontal disease and pregnancy complications.

Science.gov (United States)

Bobetsis, Yiorgos A; Barros, Silvana P; Offenbacher, Steven

2006-10-01

Increasing evidence suggests that maternal gingivitis and periodontitis may be a risk factor for preterm birth and other adverse pregnancy outcomes. To clarify the possible mechanisms behind the association between periodontal disease and preterm delivery, the authors reviewed studies of the effect of infection with periodontal pathogens in animal models on pregnancy outcomes including fetal growth, placental structural abnormalities and neonatal health. After the first report, in 1996, of a potential association between maternal periodontal disease and delivery of a preterm/low-birth-weight infant in humans, many case control and prospective studies were published. This review summarizes these, as well as early studies involving periodontal intervention to reduce risk. Although there are some conflicting findings and potential problems regarding uncontrolled underlying risk factors, most of the clinical studies indicate a positive correlation between periodontal disease and preterm birth. Recent studies also have shown that there are microbiologic and immunological findings that strongly support the association. The studies indicate that periodontal infection can lead to placental-fetal exposure and, when coupled with a fetal inflammatory response, can lead to preterm delivery. Data from animal studies raise the possibility that maternal periodontal infections also may have adverse long-term effects on the infant's development. Education for patients and health care providers regarding the biological plausibility of the association and the potential risks is indicated, but there is insufficient evidence at this time for health care policy recommendations to provide maternal periodontal treatments for the purpose of reducing the risk of adverse pregnancy outcomes.

Cardiometabolic factors and disease duration in patients with Parkinson's disease.

Science.gov (United States)

Cassani, Erica; Cereda, Emanuele; Barichella, Michela; Madio, Carmen; Cancello, Raffaella; Caccialanza, Riccardo; Zini, Michela; Cilia, Roberto; Pezzoli, Gianni

2013-01-01

Previous studies have reported that patients with Parkinson's disease (PD) have a favorable cardiometabolic risk profile. The aim of this study was to investigate the relationship between cardiometabolic risk factors and the duration of disease. One hundred and fifty patients with PD (56.7% men) were studied, measuring body mass index (BMI), waist circumference (WC), body fat percentage (BF%) by impedance, fasting glucose, serum lipids, and transaminases. In sex- and age-adjusted correlation models, duration of PD was inversely related to BMI (r = -0.20; P HDL) levels were positively correlated with disease duration (P HDL-cholesterol ratio was also inversely associated with duration of PD (P HDL levels and total HDL-cholesterol ratio were favorably associated with duration of PD. This factor may contribute to cardiometabolic protection in PD. The mechanisms underlying this association deserve further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

Physical activity as a possible mechanism behind the relationship between green space and health: a multilevel analysis.

NARCIS (Netherlands)

Maas, J.; Verheij, R.A.; Spreeuwenberg, P.; Groenewegen, P.P.

2008-01-01

Background: The aim of this study was to investigate whether physical activity (in general, and more specifically, walking and cycling during leisure time and for commuting purposes, sports and gardening) is an underlying mechanism in the relationship between the amount of green space in people's

Relationship between maternal periodontal disease and low birth weight babies

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Ahmad Haerian-Ardakani

2013-01-01

Full Text Available Background: Periodontal infections, which serve as a reservoir of inflammatory mediators, may pose a threat to the fetal-placental unit and cause adverse pregnancy outcomes. Objective: The aim of this study was assessing the periodontal status of women during puerperium and determining the possible relationship between their periodontal disease and low birth weight delivery. Materials and Methods: This was a case-control study. The sample included 88 ex-pregnant women were seen at maternity hospitals of Yazd, Iran. Half of the mothers had low birth babies (LBW (birth weight below 2500g- case group and the others had normal weight babies (>2500g- control group. The mothers’ data were obtained from medical files, interview and periodontal clinical examination carried out up to 3 days after delivery. Bleeding on probing, presence of supra-gingival calculus and CPITN (Community Periodontal Index for Treatment Needs were used for periodontal assessment Results: Among the known risk factors of LBW babies, history of previous LBW infant among case mothers reached statistical significance (p=0.0081, Student t-test. Mothers of LBW infants had less healthy areas of gingiva (p=0.042, and more deep pockets (p=0.0006, Mann-Whitney test. Conclusion: The maternal periodontal disease can be a potential independent risk factor for LBW.

Relationship of Inflammatory Biomarkers with Severity of Peripheral Arterial Disease

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Kimihiro Igari

2016-01-01

Full Text Available 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.

Evaluation of the relationship between Chlamydia pecorum sequence types and disease using a species-specific multi-locus sequence typing scheme (MLST)

NARCIS (Netherlands)

Jelocnik, Martina; Walker, Evelyn; Pannekoek, Yvonne; Ellem, Judy; Timms, Peter; Polkinghorne, Adam

2014-01-01

Chlamydia pecorum is globally associated with several ovine diseases including keratoconjunctivitis and polyarthritis. The exact relationship between the variety of C. pecorum strains reported and the diseases described in sheep remains unclear, challenging efforts to accurately diagnose and manage

Mechanical properties of the normal human cartilage-bone complex in relation to age

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Ding, Ming; Dalstra, M; Linde, F

1998-01-01

OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by mea...... that are of importance for the understanding of the etiology and pathogenesis of degenerative joint diseases, such as arthrosis....

RELATIONSHIP OF SPIRITUAL-WELLBEING WITH ANXIETY AND DEPRESSION IN PATIENTS WITH CARDIAC HEART DISEASE

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Aan Nuraeni

2018-02-01

Full Text Available Background: Anxiety and depression are problems faced by patients with chronic diseases such as patients with Coronary Heart Disease (CHD. Both of these can also worsen the condition of CHD patients, thus needs to be prevented and handled. It is stated that spirituality can enhance constructive coping skills in patients with chronic diseases. But how it relates to anxiety and depression in patients with CHD in Indonesia was still unknown. Objective: The study purpose was to identify the relationship of spiritual wellbeing with the incidence of anxiety and depression in CHD patients. Methods: The research used descriptive correlative quantitative with cross sectional approach. The instruments used to measure the variabels were Zung Self-rating Anxiety Scale, Beck Depression Inventory II, and Spirituality Index of Well-Being scale. Data were taken on 100 respondents within 3 months in outpatient cardiac unit with the consecutive sampling technique and analyzed by spearman correlation test. Results: The results showed mean of the anxiety; depression; and spiritual well-being respectively were 47.66; 43; and 60. Based on spearman test, spiritual wellbeing correlated with anxiety significantly p= 0.000(r=-0.371 and so was depression p= 0.000 (r=-0.571. Conclusions: There was a significant relationship between spiritual well-being with anxiety and depression with a negative correlation direction. The higher the spiritual well-being will be the lower the level of anxiety and depression. Thus nurses need to strengthen the spiritual aspects of CHD patients to prevent psychosocial problems.

Mortality from Cardiovascular Diseases in the Semipalatinsk Historical Cohort, 1960–1999, and its Relationship to Radiation Exposure

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Grosche, Bernd; Lackland, Daniel T.; Land, Charles E.; Simon, Steven L.; Apsalikov, Kazbek N.; Pivina, Ludmilla M.; Bauere, Susanne; Gusev, Boris I.

2013-01-01

The data on risk of mortality from cardiovascular disease due to radiation exposure at low or medium doses are inconsistent. This paper reports an analysis of the Semipalatinsk historical cohort exposed to radioactive fallout from nuclear testing in the vicinity of the Semipalatinsk Nuclear Test Site, Kazakhstan. The cohort study, which includes 19,545 persons of exposed and comparison villages in the Semipalatinsk region, had been set up in the 1960s and comprises 582,656 person-years of follow-up between 1960 and 1999. A dosimetric approach developed by the U.S. National Cancer Institute (NCI) has been used. Radiation dose estimates in this cohort range from 0 to 630 mGy (wholebody external). Overall, the exposed population showed a high mortality from cardiovascular disease. Rates of mortality from cardiovascular disease in the exposed group substantially exceeded those of the comparison group. Dose–response analyses were conducted for both the entire cohort and the exposed group only. A dose–response relationship that was found when analyzing the entire cohort could be explained completely by differences between the baseline rates in exposed and unexposed groups. When taking this difference into account, no statistically significant dose–response relationship for all cardiovascular disease, for heart disease, or for stroke was found. Our results suggest that within this population and at the level of doses estimated, there is no detectable risk of radiation related mortality from cardiovascular disease. PMID:21787182

The Relationship between Parental Rearing Behavior, Resilience, and Depressive Symptoms in Adolescents with Congenital Heart Disease

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Ju Ryoung Moon

2017-09-01

Full Text Available ObjectivesParental rearing behavior is one factor that influences the strength of resilience. In turn, resilience influences depression. However, it is unclear whether resilience has a mediating effect on the relationship between parental rearing and depression in adolescents with congenital heart disease (CHD. Therefore, the associations between parental rearing behavior and resilience and between rearing behavior and symptoms of depression were investigated with respect to age, gender and disease severity.Subjects and methodsPatients completed a parental rearing behavior questionnaire, a resilience scale and the Children’s Depression Inventory during a routine clinic visit. Structural equation modeling with maximum likelihood estimation was used to analyze the data.ResultsThe median age of the 180 patients included in the study was 17.8 years, and 64% were male. Lower resilience was found to be associated with overprotection, punishment, rejection, and control. There was a strong relationship between resilience and symptoms of depression. Resilience varied according to gender, age group, and disease severity.ConclusionParental rearing behaviors such as emotional warmth, rejection, punishment, control, and overprotection have a significant influence on adolescent’s resilience. When developing intervention programs to increase resilience and reduce depression in adolescents with CHD, parenting attitudes, gender, age, and CHD severity should be considered.

Human Environmental Disease Network

DEFF Research Database (Denmark)

Taboureau, Olivier; Audouze, Karine

2017-01-01

During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...

Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases

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Irina V. Kholodenko

2017-01-01

Full Text Available The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable.

A novel mechanical lung model of pulmonary diseases to assist with teaching and training

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Shaw Geoffrey M

2006-08-01

Full Text Available Abstract Background A design concept of low-cost, simple, fully mechanical model of a mechanically ventilated, passively breathing lung is developed. An example model is built to simulate a patient under mechanical ventilation with accurate volumes and compliances, while connected directly to a ventilator. Methods The lung is modelled with multiple units, represented by rubber bellows, with adjustable weights placed on bellows to simulate compartments of different superimposed pressure and compliance, as well as different levels of lung disease, such as Acute Respiratory Distress Syndrome (ARDS. The model was directly connected to a ventilator and the resulting pressure volume curves recorded. Results The model effectively captures the fundamental lung dynamics for a variety of conditions, and showed the effects of different ventilator settings. It was particularly effective at showing the impact of Positive End Expiratory Pressure (PEEP therapy on lung recruitment to improve oxygenation, a particulary difficult dynamic to capture. Conclusion Application of PEEP therapy is difficult to teach and demonstrate clearly. Therefore, the model provide opportunity to train, teach, and aid further understanding of lung mechanics and the treatment of lung diseases in critical care, such as ARDS and asthma. Finally, the model's pure mechanical nature and accurate lung volumes mean that all results are both clearly visible and thus intuitively simple to grasp.

Oxidative Stress: A Pathogenic Mechanism for Niemann-Pick Type C Disease

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Mary Carmen Vázquez

2012-01-01

Full Text Available Niemann-Pick type C (NPC disease is a neurovisceral atypical lipid storage disorder involving the accumulation of cholesterol and other lipids in the late endocytic pathway. The pathogenic mechanism that links the accumulation of intracellular cholesterol with cell death in NPC disease in both the CNS and the liver is currently unknown. Oxidative stress has been observed in the livers and brains of NPC mice and in different NPC cellular models. Moreover, there is evidence of an elevation of oxidative stress markers in the serumof NPC patients. Recent evidence strongly suggests that mitochondrial dysfunction plays an important role in NPC pathogenesis and that mitochondria could be a significant source of oxidative stress in this disease. In this context, the accumulation of vitamin E in the late endosomal/lysosomal compartments in NPC could lead to a potential decrease of its bioavailability and could be another possible cause of oxidative damage. Another possible source of reactive species in NPC is the diminished activity of different antioxidant enzymes. Moreover, because NPC is mainly caused by the accumulation of free cholesterol, oxidized cholesterol derivatives produced by oxidative stress may contribute to the pathogenesis of the disease.

[Relationship between quality of life and disability level in patients with occupational disease].

Science.gov (United States)

Li, Hongmei; Lin, Mingjing; Zhang, Wenwen; Li, Jing; Zou, Jianfang

2015-10-01

To investigate the relationship between the quality of life (QOL) and disability level in patients with occupational disease and to investigate the influencing factors for QOL. A total of 255 patients with occupational disease were selected from three specialized hospitals dedicated to occupational disease and the department of occupational medicine of one comprehensive hospital using cluster sampling from December 2013 to May 2014. A survey was carried out using WHOQOL-BREF and general questionnaire (including disability level), and statistical analysis was also performed using t test, F test, analysis of variance, and multivariate stepwise regression analysis. The QOL scores of patients with occupational diseases, from high to low, were social domain (11.48 ± 2.86), psychological domain (10.60 ± 2.28), physiological domain (10.54 ± 1.65), and environmental domain (10.50 ± 2.55), scores of which were significantly lower than the normal levels (Poccupational diseases of different disability levels (P>0.05). Also, QOL showed no significant differences between stage I, II and III patients with pneumoconiosis (P>0.05). The patients with pneumoconiosis were divided into mild, moderate, and severe groups, and the QOL scores of patients with mild pneumoconiosis in psychological and environmental domains were significantly higher than those of the patients with moderate or severe pneumoconiosis (Poccupational poisoning was divided into mild, moderate and severe groups, and the three groups showed no significant differences in QOL score (P>0.05). Multivariate regression analysis showed that the QOL score of each domain was mainly influenced by the degree of lung injury, complications, course of disease, age of onset, income, and employment status. The QOL of patients with occupational disease is significantly reduced, and disability level cannot accurately reflect their QOL. The treatment of patients with occupational disease should focus on their complications, and at

An Investigation into the Relationship between Owner Knowledge, Diet, and Dental Disease in Guinea Pigs (Cavia porcellus

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Rosemary Norman

2016-11-01

Full Text Available Recent studies have highlighted a high prevalence of dental disease in domestic guinea pigs, yet the aetiology of this multi-factorial disease is still unclear. Factors that have been associated with dental disease include feeding a diet that is high in energy but low in fibre, feeding an insufficiently abrasive diet, a lack of dietary calcium, and genetics. As many of these factors relate to the husbandry requirements of guinea pigs, owner awareness of dietary requirements is of the utmost importance. An online questionnaire was created based on previous research into the husbandry and feeding of rabbits. Guinea pig owners were asked to answer questions on the clinical history of their animals and their diet and management. In total, 150 surveys were completed for 344 guinea pigs, where owners of multiple animals could complete the survey for individuals. According to the owners, 6.7% of guinea pigs had been clinically diagnosed with dental disease, but 16.6% had signs consistent with dental disease. The specific clinical signs of having difficulty eating (Exp(B = 33.927, Nagelkerke R 2 = 0.301, p < 0.05 and producing fewer or smaller faecal droppings (Exp(B = 13.733, Nagelkerke R 2 = 0.149, p < 0.05 were predictive for the presence of dental disease. Having access to an outside environment, including the use of runs on both concrete and grass, was significantly related to not displaying clinical signs of dental disease (Exp(B = 1.894, Nagelkerke R 2 = 0.021, p < 0.05. There was no significant relationship between owner knowledge, guinea pig diet, and dental disease in the study population. This study highlights the importance of access to the outdoors for the health and welfare of guinea pigs in addition to the need for owners to be alert to key clinical signs. A relationship between diet and dental disease was not identified in this study; however, the underlying aetiological causes of this condition require further investigation.

Relationship of adiponectin level with lipid profile in type-2 diabetic men with coronary heart disease

International Nuclear Information System (INIS)

Durrani, S.; Jan, M.R.; Shah, J.; Khan, M.A.

2015-01-01

Cerebro-vascular disease is a commonest long term complication of type-2 diabetes mellitus. The study was done to determine concentration of serum adiponectin and lipid profile in type-2 diabetic men with coronary heart disease (CHD) in the region of Khyber Pakhtunkhwa (KPK), and to find possible relationship between them. Methods: This was a cross-sectional study comprising of randomly selected thirty six healthy adult males and thirty six type-2 diabetic males with coronary heart disease. Their fasting blood samples were analysed for serum adiponectin, fasting blood glucose, glycosylated haemoglobin and lipid profile which included total cholesterol (T-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The relationship of adiponectin with other variables in type-2 diabetic men with coronary heart disease was determined with Pearson correlations coefficient (r). Results: Type-2 diabetic males with coronary heart disease when compared to healthy males showed significantly low levels of serum adiponectin (p=<0.001) and HDL-C (p=<0.001) and significantly high level of FBG (p=<0.001), HbA1c (p=<0.001), TC (p=<0.05), TG (p=<0.05) and LDL-C (p=<0.05). Serum adiponectin level showed a significant negative correlation with FBG (r = -0.332; p= 0.04), HbA1c (r = -0.818; p=<0.01) and TG (r = -0.640; p=<0.01) in type-2 diabetic men with coronary heart disease. Adiponectin showed a significant positive association with HDL-C in controls (r = 0.948; p=<0.01) and patients of type-2 diabetes with CHD (r = 0.650; p=<0.01). Conclusion: Serum adiponectin concentration is markedly decreased in patients of type-2 diabetes with coronary heart disease. Hypoadiponectinemia is related with deranged lipid profile, i.e., high TG and low HDL-C levels in type-2 diabetic men with CHD. Moreover, adiponectin is associated positively with HDL-C and negatively with HbA1c and TG levels in the studied population. (author)

Aberrant regulation of DNA methylation in amyotrophic lateral sclerosis: a new target of disease mechanisms.

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Martin, Lee J; Wong, Margaret

2013-10-01

Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. A diagnosis is fatal owing to degeneration of motor neurons in brain and spinal cord that control swallowing, breathing, and movement. ALS can be inherited, but most cases are not associated with a family history of the disease. The mechanisms causing motor neuron death in ALS are still unknown. Given the suspected complex interplay between multiple genes, the environment, metabolism, and lifestyle in the pathogenesis of ALS, we have hypothesized that the mechanisms of disease in ALS involve epigenetic contributions that can drive motor neuron degeneration. DNA methylation is an epigenetic mechanism for gene regulation engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to carbon-5 in cytosine residues in gene regulatory promoter and nonpromoter regions. Recent genome-wide analyses have found differential gene methylation in human ALS. Neuropathologic assessments have revealed that motor neurons in human ALS show significant abnormalities in Dnmt1, Dnmt3a, and 5-methylcytosine. Similar changes are seen in mice with motor neuron degeneration, and Dnmt3a was found abundantly at synapses and in mitochondria. During apoptosis of cultured motor neuron-like cells, Dnmt1 and Dnmt3a protein levels increase, and 5-methylcytosine accumulates. Enforced expression of Dnmt3a, but not Dnmt1, induces degeneration of cultured neurons. Truncation mutation of the Dnmt3a catalytic domain and Dnmt3a RNAi blocks apoptosis of cultured neurons. Inhibition of Dnmt catalytic activity with small molecules RG108 and procainamide protects motor neurons from excessive DNA methylation and apoptosis in cell culture and in a mouse model of ALS. Thus, motor neurons can engage epigenetic mechanisms to cause their degeneration, involving Dnmts and increased DNA methylation. Aberrant DNA methylation in vulnerable cells is a new direction for discovering mechanisms of ALS

Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine.

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Lambers Heerspink, Hiddo J; Oberbauer, Rainer; Perco, Paul; Heinzel, Andreas; Heinze, Georg; Mayer, Gert; Mayer, Bernd

2015-08-01

Diabetic kidney disease (DKD) is a complex, multifactorial disease and is associated with a high risk of renal and cardiovascular morbidity and mortality. Clinical practice guidelines for diabetes recommend essentially identical treatments for all patients without taking into account how the individual responds to the instituted therapy. Yet, individuals vary widely in how they respond to medications and therefore optimal therapy differs between individuals. Understanding the underlying molecular mechanisms of variability in drug response will help tailor optimal therapy. Polymorphisms in genes related to drug pharmacokinetics have been used to explore mechanisms of response variability in DKD, but with limited success. The complex interaction between genetic make-up and environmental factors on the abundance of proteins and metabolites renders pharmacogenomics alone insufficient to fully capture response variability. A complementary approach is to attribute drug response variability to individual variability in underlying molecular mechanisms involved in the progression of disease. The interplay of different processes (e.g. inflammation, fibrosis, angiogenesis, oxidative stress) appears to drive disease progression, but the individual contribution of each process varies. Drugs at the other hand address specific targets and thereby interfere in certain disease-associated processes. At this level, biomarkers may help to gain insight into which specific pathophysiological processes are involved in an individual followed by a rational assessment whether a specific drug's mode of action indeed targets the relevant process at hand. This article describes the conceptual background and data-driven workflow developed by the SysKid consortium aimed at improving characterization of the molecular mechanisms underlying DKD at the interference of the molecular impact of individual drugs in order to tailor optimal therapy to individual patients. © The Author 2015. Published by

Impact of Typical Aging and Parkinson's Disease on the Relationship among Breath Pausing, Syntax, and Punctuation

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Huber, Jessica E.; Darling, Meghan; Francis, Elaine J.; Zhang, Dabao

2012-01-01

Purpose: The present study examines the impact of typical aging and Parkinson's disease (PD) on the relationship among breath pausing, syntax, and punctuation. Method: Thirty young adults, 25 typically aging older adults, and 15 individuals with PD participated. Fifteen participants were age- and sex-matched to the individuals with PD.…

Alcohol consumption patterns in Thailand and their relationship with non-communicable disease.

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Wakabayashi, Mami; McKetin, Rebecca; Banwell, Cathy; Yiengprugsawan, Vasoontara; Kelly, Matthew; Seubsman, Sam-ang; Iso, Hiroyasu; Sleigh, Adrian

2015-12-24

Heavy alcohol consumption is an established risk factor for non-communicable diseases (NCDs) but few studies have investigated drinking and disease risk in middle income, non-western countries. We report on the relationship between alcohol consumption and NCDs in Thailand. A nationwide cross sectional survey was conducted of 87,151 Thai adult open university students aged 15 to 87 years (mean age 30.5 years) who were recruited into the Thai Cohort Study. Participants were categorized as never having drunk alcohol (n = 22,527), as being occasional drinkers who drank infrequently but heavily (4+ glasses/occasion - occasional heavy drinkers, n = 24,152) or drank infrequently and less heavily (migration and other recognized risks for NCDs (sedentary lifestyle and poor diet). After adjustment for these factors the odds ratios (ORs) for several NCDs outcomes - high cholesterol, hypertension, and liver disease - were significantly elevated among both occasional heavy drinkers (1.2 to 1.5) and regular heavy drinkers (1.5 to 2.0) relative to never drinkers. Heavy alcohol consumption of 4 or more glasses per occasion, even if the occasions were infrequent, was associated with elevated risk of NCDs in Thailand. These results highlight the need for strategies in Thailand to reduce the quantity of alcohol consumed to prevent alcohol-related disease. Thailand is fortunate that most of the female population is culturally protected from drinking and this national public good should be endorsed and supported.

The relationship between Helicobacter pylori-associated gastritis or ulcer disease and gastric emptying

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Kao Chiahung (Dept. of Nuclear Medicine, Taichung Veterans General Hospital (Taiwan, Province of China)); Wang Shyhjen (Dept. of Nuclear Medicine, Taichung Veterans General Hospital (Taiwan, Province of China)); Chen Granhum (Div. of Gastroenterology, Taichung Veterans General Hospital (Taiwan, Province of China)); Yeh Shinhwa (Dept. of Nuclear Medicine, Taichung Veterans General Hospital (Taiwan, Province of China))

1994-03-01

Forty-five patients with Helicobacter pylori (HP)-associated gastritis or ulcer disease were included in this study. Radionuclide-labelled solid meals were used to calculate gastric emptying times (GETs) and carbon-14 urea breath tests ([sup 14]C UBTs) were used to measure the HP colonies quantitatively. The patients were assessed according to the following two criteria: (a) the HP colony number (i.e. high or low) and (b) the recorded duration of the GET (i.e. long or short). There was no statistically significant difference in the incidence of abnormal GET between high and low [sup 14]C UBT patients or in the incidence of abnormal [sup 14]C UBT between long and short GET cases. In conclusion, no significant relationship between HP-associated gastritis or ulcer disease and GET was found in this study. (orig.)

Environmental pollution and kidney diseases.

Science.gov (United States)

Xu, Xin; Nie, Sheng; Ding, Hanying; Hou, Fan Fan

2018-05-01

The burden of disease and death attributable to environmental pollution is becoming a public health challenge worldwide, especially in developing countries. The kidney is vulnerable to environmental pollutants because most environmental toxins are concentrated by the kidney during filtration. Given the high mortality and morbidity of kidney disease, environmental risk factors and their effect on kidney disease need to be identified. In this Review, we highlight epidemiological evidence for the association between kidney disease and environmental pollutants, including air pollution, heavy metal pollution and other environmental risk factors. We discuss the potential biological mechanisms that link exposure to environmental pollutants to kidney damage and emphasize the contribution of environmental pollution to kidney disease. Regulatory efforts should be made to control environmental pollution and limit individual exposure to preventable or avoidable environmental risk. Population studies with accurate quantification of environmental exposure in polluted regions, particularly in developing countries, might aid our understanding of the dose-response relationship between pollutants and kidney diseases.

Relationship between Audiometric slope and tinnitus pitch in tinnitus patients: insights into the mechanisms of tinnitus generation.

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Martin Schecklmann

Full Text Available BACKGROUND: Different mechanisms have been proposed to be involved in tinnitus generation, among them reduced lateral inhibition and homeostatic plasticity. On a perceptual level these different mechanisms should be reflected by the relationship between the individual audiometric slope and the perceived tinnitus pitch. Whereas some studies found the tinnitus pitch corresponding to the maximum hearing loss, others stressed the relevance of the edge frequency. This study investigates the relationship between tinnitus pitch and audiometric slope in a large sample. METHODOLOGY: This retrospective observational study analyzed 286 patients. The matched tinnitus pitch was compared to the frequency of maximum hearing loss and the edge of the audiogram (steepest hearing loss by t-tests and correlation coefficients. These analyses were performed for the whole group and for sub-groups (uni- vs. bilateral (117 vs. 338 ears, pure-tone vs. narrow-band (340 vs. 115 ears, and low and high audiometric slope (114 vs. 113 ears. FINDINGS: For the right ear, tinnitus pitch was in the same range and correlated significantly with the frequency of maximum hearing loss, but differed from and did not correlate with the edge frequency. For the left ear, similar results were found but the correlation between tinnitus pitch and maximum hearing loss did not reach significance. Sub-group analyses (bi- and unilateral, tinnitus character, slope steepness revealed identical results except for the sub-group with high audiometric slope which revealed a higher frequency of maximum hearing loss as compared to the tinnitus pitch. CONCLUSION: The study-results confirm a relationship between tinnitus pitch and maximum hearing loss but not to the edge frequency, suggesting that tinnitus is rather a fill-in-phenomenon resulting from homeostatic mechanisms, than the result of deficient lateral inhibition. Sub-group analyses suggest that audiometric steepness and the side of affected ear

Relationship between Audiometric Slope and Tinnitus Pitch in Tinnitus Patients: Insights into the Mechanisms of Tinnitus Generation

Science.gov (United States)

Schecklmann, Martin; Vielsmeier, Veronika; Steffens, Thomas; Landgrebe, Michael; Langguth, Berthold; Kleinjung, Tobias

2012-01-01

Background Different mechanisms have been proposed to be involved in tinnitus generation, among them reduced lateral inhibition and homeostatic plasticity. On a perceptual level these different mechanisms should be reflected by the relationship between the individual audiometric slope and the perceived tinnitus pitch. Whereas some studies found the tinnitus pitch corresponding to the maximum hearing loss, others stressed the relevance of the edge frequency. This study investigates the relationship between tinnitus pitch and audiometric slope in a large sample. Methodology This retrospective observational study analyzed 286 patients. The matched tinnitus pitch was compared to the frequency of maximum hearing loss and the edge of the audiogram (steepest hearing loss) by t-tests and correlation coefficients. These analyses were performed for the whole group and for sub-groups (uni- vs. bilateral (117 vs. 338 ears), pure-tone vs. narrow-band (340 vs. 115 ears), and low and high audiometric slope (114 vs. 113 ears)). Findings For the right ear, tinnitus pitch was in the same range and correlated significantly with the frequency of maximum hearing loss, but differed from and did not correlate with the edge frequency. For the left ear, similar results were found but the correlation between tinnitus pitch and maximum hearing loss did not reach significance. Sub-group analyses (bi- and unilateral, tinnitus character, slope steepness) revealed identical results except for the sub-group with high audiometric slope which revealed a higher frequency of maximum hearing loss as compared to the tinnitus pitch. Conclusion The study-results confirm a relationship between tinnitus pitch and maximum hearing loss but not to the edge frequency, suggesting that tinnitus is rather a fill-in-phenomenon resulting from homeostatic mechanisms, than the result of deficient lateral inhibition. Sub-group analyses suggest that audiometric steepness and the side of affected ear affect this

Wildlife disease prevalence in human-modified landscapes.

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Brearley, Grant; Rhodes, Jonathan; Bradley, Adrian; Baxter, Greg; Seabrook, Leonie; Lunney, Daniel; Liu, Yan; McAlpine, Clive

2013-05-01

Human-induced landscape change associated with habitat loss and fragmentation places wildlife populations at risk. One issue in these landscapes is a change in the prevalence of disease which may result in increased mortality and reduced fecundity. Our understanding of the influence of habitat loss and fragmentation on the prevalence of wildlife diseases is still in its infancy. What is evident is that changes in disease prevalence as a result of human-induced landscape modification are highly variable. The importance of infectious diseases for the conservation of wildlife will increase as the amount and quality of suitable habitat decreases due to human land-use pressures. We review the experimental and observational literature of the influence of human-induced landscape change on wildlife disease prevalence, and discuss disease transmission types and host responses as mechanisms that are likely to determine the extent of change in disease prevalence. It is likely that transmission dynamics will be the key process in determining a pathogen's impact on a host population, while the host response may ultimately determine the extent of disease prevalence. Finally, we conceptualize mechanisms and identify future research directions to increase our understanding of the relationship between human-modified landscapes and wildlife disease prevalence. This review highlights that there are rarely consistent relationships between wildlife diseases and human-modified landscapes. In addition, variation is evident between transmission types and landscape types, with the greatest positive influence on disease prevalence being in urban landscapes and directly transmitted disease systems. While we have a limited understanding of the potential influence of habitat loss and fragmentation on wildlife disease, there are a number of important areas to address in future research, particularly to account for the variability in increased and decreased disease prevalence. Previous studies

Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships.

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Geevarghese, Ruben; Lumsden, Daniel E; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

2016-01-01

Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.

Relationship Between Changes in Fat and Lean Depots Following Weight Loss and Changes in Cardiovascular Disease Risk Markers.

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Clifton, Peter M

2018-04-04

Gluteofemoral fat mass has been associated with improved cardiovascular disease risk factors. It is not clear if loss of this protective fat during weight loss partially negates the effect of loss of visceral fat. The aim of this study was to examine regional fat loss in a large weight-loss cohort from one center and to determine if fat loss in the leg and total lean tissue loss is harmful. We combined the data from 7 of our previously published 3-month weight-loss studies and examined the relationship between regional fat and lean tissue loss and changes in cardiovascular disease risk factors in 399 participants. At baseline, leg fat was positively associated with high-density lipoprotein cholesterol in women and inversely with fasting triglyceride level in both sexes. Abdominal lean tissue was also related to systolic blood pressure in men. Changes in regional fat and lean tissue were positively associated with changes in glucose, insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol and systolic and diastolic blood pressure ( r =0.11-0.22, P lean tissue dominating in multivariate regression. After adjustment for total weight or total fat change, these relationships disappeared except for a positive relationship between arm and lean leg mass loss and changes in triglycerides and systolic blood pressure. Loss of leg fat and leg lean tissue was directly associated with beneficial changes in cardiovascular disease risk markers. Loss of lean tissue may not have an adverse effect on cardiovascular disease risk, and measures to retain lean tissue during weight loss may not be necessary. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations

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Low Wang, Cecilia C.; Hess, Connie N.; Hiatt, William R.; Goldfine, Allison B.

2016-01-01

Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multi-factorial risk reduction with statins and other lipid lowering agents, anti-hypertensive therapies, and anti-hyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes than for those without. This review considers the mechanisms, history, controversies, new pharmacologic agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes and heart disease outside of the acute care setting. PMID:27297342

Glaucoma and Alzheimer Disease: A Single Age-Related Neurodegenerative Disease of the Brain.

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Mancino, Raffaele; Martucci, Alessio; Cesareo, Massimo; Giannini, Clarissa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

2017-12-06

Open Angle Glaucoma is one of the leading causes of irreversible blindness worldwide. Elevated intraocular pressure is considered an important risk factor for glaucoma, however a subset of patients experience disease progression even in presence of normal intraocular pressure values. This implies that risk factors other than intraocular pressure are involved in the pathogenesis of glaucoma. A possible relationship between glaucoma and neurodegenerative diseases such as Alzheimer Disease has been suggested. In this regard, we have recently described a high prevalence of alterations typical of glaucoma, using Heidelberg Retinal Tomograph-3 (HRT-3), in a group of patients with Alzheimer Disease. Interestingly, these alterations were not associated with elevated intraocular pressure or abnormal Central Corneal Thickness values. Alzheimer Disease is the most common form of dementia associated with progressive deterioration of memory and cognition. Complaints related to vision are common among Alzheimer Disease patients. Features common to both diseases, including risk factors and pathophysiological mechanisms, gleaned from the recent literature do suggest that Alzheimer Disease and glaucoma can be considered age-related neurodegenerative diseases that may co-exist in the elderly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Association between periodontal diseases and systemic diseases

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Patrícia Weidlich

2008-08-01

Full Text Available Current evidence suggests that periodontal disease may be associated with systemic diseases. This paper reviewed the published data about the relationship between periodontal disease and cardiovascular diseases, adverse pregnancy outcomes, diabetes and respiratory diseases, focusing on studies conducted in the Brazilian population. Only a few studies were found in the literature focusing on Brazilians (3 concerning cardiovascular disease, 7 about pregnancy outcomes, 9 about diabetes and one regarding pneumonia. Although the majority of them observed an association between periodontitis and systemic conditions, a causal relationship still needs to be demonstrated. Further studies, particularly interventional well-designed investigations, with larger sample sizes, need to be conducted in Brazilian populations.

Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions

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Bingham, Clifton O.; Moni, Malini

2015-01-01

Purpose of review This review was conducted to focus on the recent clinical and translational research related to the associations between periodontal disease and rheumatoid arthritis. Recent findings There is a growing interest in the associations between oral health and autoimmune and inflammatory diseases. A number of epidemiologic studies have described associations between rheumatoid arthritis and periodontal disease. Recent clinical studies continue to support these reports, and are increasingly linked with biological assessments to better understand the nature of these relationships. A number of recent studies have evaluated the periopathogenic roles of Porphyromonas gingivalis, the oral microbiome, and mechanisms of site-specific and substrate-specific citrullination. These are helping to further elucidate the interactions between these two inflammatory disease processes. Summary Studies of clinical oral health parameters, the gingival microenvironment, autoantibodies and biomarkers, and rheumatoid arthritis disease activity measures are providing a better understanding of the potential mechanisms responsible for rheumatoid arthritis and periodontal disease associations. The cumulative results and ongoing studies have the promise to identify novel mechanisms and interventional strategies to improve patient outcomes for both conditions. PMID:23455329

Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease.

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Muscogiuri, Giovanna; Mitri, Joanna; Mathieu, Chantal; Badenhoop, Klaus; Tamer, Gonca; Orio, Francesco; Mezza, Teresa; Vieth, Reinhold; Colao, Annamaria; Pittas, Anastassios

2014-09-01

It has been suggested that vitamin D may play a role in the pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1 diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's disease and polycystic ovary syndrome (PCOS). In this review, we debate the role of vitamin D in the pathogenesis of endocrine diseases. Narrative overview of the literature synthesizing the current evidence retrieved from searches of computerized databases, hand searches and authoritative texts. Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships have been reported not only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of T2DM, but the available evidence is not consistent. Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Ongoing randomized controlled trials are expected to provide insights into the efficacy and safety of vitamin D in the management of endocrine disease. © 2014 European Society of Endocrinology.

Relationships between the circadian system and Alzheimer's disease-like symptoms in Drosophila.

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Dani M Long

Full Text Available Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer's disease (AD, are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per01. No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism.

Host-Parasite Relationship in Cystic Echinococcosis: An Evolving Story

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Alessandra Siracusano

2012-01-01

Full Text Available The larval stage of Echinococcus granulosus causes cystic echinococcosis, a neglected infectious disease that constitutes a major public health problem in developing countries. Despite being under constant barrage by the immune system, E. granulosus modulates antiparasite immune responses and persists in the human hosts with detectable humoral and cellular responses against the parasite. In vitro and in vivo immunological approaches, together with molecular biology and immunoproteomic technologies, provided us exciting insights into the mechanisms involved in the initiation of E. granulosus infection and the consequent induction and regulation of the immune response. Although the last decade has clarified many aspects of host-parasite relationship in human cystic echinococcosis, establishing the full mechanisms that cause the disease requires more studies. Here, we review some of the recent developments and discuss new avenues in this evolving story of E. granulosus infection in man.

Natural products as promising drug candidates for the treatment of Alzheimer's disease: molecular mechanism aspect.

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Ansari, Niloufar; Khodagholi, Fariba

2013-07-01

Alzheimer's disease (AD) is the most common neurodegenerative disorder to date, with no curative or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles. Extent studies on pathology of the disease have made important discoveries regarding mechanism of disease and potential therapeutic targets. Many cellular changes including oxidative stress, disruption of Ca2+ homeostasis, inflammation, metabolic disturbances, and accumulation of unfolded/misfolded proteins can lead to programmed cell death in AD. Despite intensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look at alternative therapies. Use of natural products and culinary herbs in medicine has gained popularity in recent years. Several natural substances with neuroprotective effects have been widely studied. Most of these compounds have remarkable antioxidant properties and act mainly by scavenging free radical species. Some of them increase cell survival and improve cognition by directly affecting amyloidogenesis and programmed cell death pathways. Further studies on these natural products and their mechanism of action, parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine. This review discussed some natural products with potential neuroprotective properties against Aβ with respect to their mechanism of action.

Relationship Between Disease Characteristics and Oral Radiologic Findings in Systemic Sclerosis: Results From a Canadian Oral Health Study.

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Baron, Murray; Hudson, Marie; Dagenais, Marie; Macdonald, David; Gyger, Geneviève; El Sayegh, Tarek; Pope, Janet; Fontaine, Audrey; Masetto, Ariel; Matthews, Debora; Sutton, Evelyn; Thie, Norman; Jones, Niall; Copete, Maria; Kolbinson, Dean; Markland, Janet; Nogueira-Filho, Getulio; Robinson, David; Fritzler, Marvin; Wang, Mianbo; Gornitsky, Mervyn

2016-05-01

Systemic sclerosis (SSc; scleroderma) is associated with a wide periodontal ligament (PDL) and mandibular erosions. We investigated the clinical correlates of SSc with these radiologic abnormalities. Subjects from the Canadian Scleroderma Research Group cohort underwent detailed radiologic examinations. Associations between radiologic abnormalities and clinical manifestations of SSc were examined with univariate and multivariate analyses. The study included 159 subjects; 90.6% were women, the mean ± SD age was 56 ± 10 years, diffuse disease was present in 28.3%, and mean ± SD disease duration was 13.7 ± 8.4 years. Widening of the PDL involving at least 1 tooth was present in 38% of subjects, and 14.5% had at least 1 site in the mandible with an erosion. In analyses adjusting for age, disease duration, sex, smoking, and education, we found significant associations between the number of teeth with widening of the PDL and disease severity assessed by the physician global assessment (PGA) (relative risk [RR] 1.19, 95% confidence interval [95% CI] 1.02-1.39, P = 0.028). Analyses replacing the PGA with the skin score, disease subset, or anti-topoisomerase I antibodies confirmed the relationship with indices of disease severity. There was no relationship between either the number of teeth with periodontal disease or the number of missing teeth, and the number of teeth with wide PDL. A smaller interdental distance (RR 0.89, 95% CI 0.82-0.97, P = 0.006), but not disease severity, facial skin score, or ischemia was associated with a larger number of erosions. In SSc, a wide PDL may reflect generalized overproduction of collagen, and mandibular erosions are related to local factors in the oral cavity. © 2016, American College of Rheumatology.

Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation

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Snow Robert W

2009-08-01

Full Text Available Abstract Background Clinical malaria has proven an elusive burden to enumerate. Many cases go undetected by routine disease recording systems. Epidemiologists have, therefore, frequently defaulted to actively measuring malaria in population cohorts through time. Measuring the clinical incidence of malaria longitudinally is labour-intensive and impossible to undertake universally. There is a need, therefore, to define a relationship between clinical incidence and the easier and more commonly measured index of infection prevalence: the "parasite rate". This relationship can help provide an informed basis to define malaria burdens in areas where health statistics are inadequate. Methods Formal literature searches were conducted for Plasmodium falciparum malaria incidence surveys undertaken prospectively through active case detection at least every 14 days. The data were abstracted, standardized and geo-referenced. Incidence surveys were time-space matched with modelled estimates of infection prevalence derived from a larger database of parasite prevalence surveys and modelling procedures developed for a global malaria endemicity map. Several potential relationships between clinical incidence and infection prevalence were then specified in a non-parametric Gaussian process model with minimal, biologically informed, prior constraints. Bayesian inference was then used to choose between the candidate models. Results The suggested relationships with credible intervals are shown for the Africa and a combined America and Central and South East Asia regions. In both regions clinical incidence increased slowly and smoothly as a function of infection prevalence. In Africa, when infection prevalence exceeded 40%, clinical incidence reached a plateau of 500 cases per thousand of the population per annum. In the combined America and Central and South East Asia regions, this plateau was reached at 250 cases per thousand of the population per annum. A temporal

Periodontal Disease and Systemic Diseases: An Update for the Clinician.

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John, Vanchit; Alqallaf, Hawra; De Bedout, Tatiana

2016-01-01

A link between periodontal disease and various systemic diseases has been investigated for several years. Interest in unearthing such a link has grown as the health care profession is looking for a better understanding of disease processes and their relationships to periodontal and other oral diseases. The article aims to provide recent information on the relationship between periodontal disease and systemic diseases such as; cardiovascular, respiratory, endocrine, musculoskeletal, and reproductive system related abnormalities.

The Relationship Between Periodontal Disease and Neoplasms of the Oral Cavity: A Review Article

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Nourelahi

2016-08-01

Full Text Available Context Oral cavity is one of the most common sites for neoplasms with a multifactorial etiology. Tobacco and alcohol are the main risk factors. Periodontal disease is an inflammatory disease affecting periodontal tissues such as gingiva, periodontal ligament and alveolar bone. Periodontal disease is linked to many systemic diseases. Recently a link between periodontal disease and cancer is suggested. The current review article aimed to evaluate the association between periodontal disease and risk of cancer in the oral cavity and some related factors. Evidence Acquisition Evidence suggests that oral cavity cancer is significantly more prevalent in patients with periodontal disease, poor oral hygiene or more missing teeth. Clinically, gingival squamous cell carcinoma (GSCC usually appears as an exophytic mass with a granular, papillary or verrucous surface or presents as an ulcerative lesion. Some reported cases of GSCC mimicking periodontal disease include gingival enlargement with no bone invasion, dentoalveolar abscess, erosive erythematosus lesion with keratotic papules, root exposure and tooth mobility, verrucous leukoplakia, verruciform xanthoma and development of hyperplastic granulation tissue after tooth extraction. Greater burden of oral flora that produce carcinogenic metabolites, human papilloma virus (HPV and other viruses that are residents of periodontal pocket, increased amount of inflammatory mediators and markers and some periodontal pathogens affecting cell cycle leading to mutation and dysplasia are considered as the rational for the relationship between malignant lesions of oral cavity and periodontal disease. Results Cancer of the oral cavity and periodontal disease are related from different aspects. Periodontal disease and tooth loss are considered as independent risk factors for cancer. Gingival squamous cell carcinoma can also mimic periodontal disease leading to misdiagnosis and delayed commencement of appropriate

The relationship between coping, health competence and patient participation among patients with inactive inflammatory bowel disease.

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Gandhi, Seema; Jedel, S; Hood, M M; Mutlu, E; Swanson, G; Keshavarzian, A

2014-05-01

Coping is an integral part of adjustment for patients with Inflammatory Bowel Disease but has not been well described in the literature. This study explored the relationship between coping, perceived health competence, patient preference for involvement in their treatment, depression and quality of life, particularly among patients with inactive disease (in remission). Subjects (n=70) with active and inactive IBD completed questionnaires, including the Inflammatory Bowel Disease Quality of Life Questionnaire, Beck Depression Inventory, Perceived Health Competence Scale and the Coping Inventory for Stressful Situations. The Harvey Bradshaw Index measured disease activity. Patients with inactive IBD demonstrated significantly more interest in participating in their treatment (pperceived health competence (p=.001), less depressive symptoms (pperceived control of their health, and exhibit less depression symptoms. Our findings may increase awareness of the importance of identifying coping strategies for IBD patients, including those in remission. © 2013.

A 17 year-old girl with a demyelinating disease requiring mechanical ventilation: a case report

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Katsenos Chrysostomos

2013-01-01

Full Text Available Abstract Background Demyelinating diseases cause destruction of the myelin sheath, while axons are relatively spared. Pathologically, demyelination can be the result of an inflammatory process, viral infection, acquired metabolic derangement and ischemic insult. Three diseases that can cause inflammatory demyelination of the CNS are: Multiple sclerosis (MS, Acute disseminated encephalomyelitis (ADEM and Acute hemorrhagic leucoencephalitis. Differentiation is not always easy and there is considerable overlaping. Data about adults with acute demyelination requiring ICU admission is limited. Case presentation A 17 year old Greek female was hospitalised in the ICU because of acute respiratory failure requiring mechanical ventilation. She had a history of febrile disease one month before, acute onset of paraplegia, diplopia, progressive arm weakness and dyspnea. Her consciousness was not impaired. A demyelinating central nervous system (CNS disease, possibly post infectious encephalomyelitis (ADEM was the underlying condition. The MRI of the brain disclosed diffused expanded cerebral lesions involving the optic nerve, basal ganglia cerebellum, pons and medulla oblongata. There was also extended involvement of the cervical and thoracic part of the spinal cord. CSF leukocyte count was elevated with lymphocyte predominance. The patient required mechanical ventilation for two months. Then she was transferred to a rehabilitation centre. Three years later she remains paraplegic. Since then she has not suffered any other demyelination attack. Conclusions Demyelinating diseases can cause acute respiratory failure when the spinal cord is affected. Severe forms of these diseases, making necessary ICU admission, is less frequently reported. Intensivists should be aware of the features of these rare diseases.

Lifelong bilingualism and neural reserve against Alzheimer's disease: a review of findings and potential mechanisms.

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Gold, Brian T

2015-03-15

Alzheimer's disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

Mesenchymal Stromal Cells: What Is the Mechanism in Acute Graft-Versus-Host Disease?

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Neil Dunavin

2017-07-01

Full Text Available After more than a decade of preclinical and clinical development, therapeutic infusion of mesenchymal stromal cells is now a leading investigational strategy for the treatment of acute graft-versus-host disease (GVHD. While their clinical use continues to expand, it is still unknown which of their immunomodulatory properties contributes most to their therapeutic activity. Herein we describe the proposed mechanisms, focusing on the inhibitory activity of mesenchymal stromal cells (MSCs at immunologic checkpoints. A deeper understanding of the mechanism of action will allow us to design more effective treatment strategies.

Selenium in Graves' disease

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Jadwiga Kryczyk

2013-05-01

Full Text Available The aim of this study was to present the current state of knowledge of the role of selenium in Graves’ disease. Recently, in the pathogenesis and course of this autoimmune disease, more attention has been paid to the relationship between oxidative stress and the antioxidant system, where selenium compounds play an important role. The thyroid is the organ with the highest selenium concentration in the human body. Selenium compounds, having antioxidant properties, protect thyrocytes against the destructive effects of reactive oxygen species (ROS, which are generated during the synthesis of thyroid hormones. Therefore, strengthening the body’s defense mechanisms, which protect against the formation and activity of ROS during medical treatment of Graves’ disease patients, may be an effective adjuvant in commonly used methods of therapy.

Questionnaire-based Study on the Relationship between Pet-keeping and Allergic Diseases in Young Children in Japan

OpenAIRE

Toshiyuki Fukao; Osamu Fukutomi; Kouichiro Hirayama; Takahide Teramoto; Hideo Kaneko; Masashi Kondo; Eiko Matsui; Naomi Kondo

2005-01-01

Background: It is still unclear how early exposure to pets is related to the risk of developing atopy-related diseases in children. There are few reports on this pet-allergy relationship in Japan although much controversial data have been reported in Europe and the USA. Methods: A questionnaire on pet-keeping and allergic diseases was distributed to parents of children 3-6 years of age who belonged to 4 kindergarten and 2 nursery schools in Gifu city and surrounding areas. A total of 1185 ...

A Fuzzy Collusive Attack Detection Mechanism for Reputation Aggregation in Mobile Social Networks: A Trust Relationship Based Perspective

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Bo Zhang

2016-01-01

Full Text Available While the mechanism of reputation aggregation proves to be an effective scheme for indicating an individual’s trustworthiness and further identifying malicious ones in mobile social networks, it is vulnerable to collusive attacks from malicious nodes of collaborative frauds. To conquer the challenge of detecting collusive attacks and then identifying colluders for the reputation system in mobile social networks, a fuzzy collusive attack detection mechanism (FCADM is proposed based on nodes’ social relationships, which comprises three parts: trust schedule, malicious node selection, and detection traversing strategy. In the first part, the trust schedule provides the calculation method of interval valued fuzzy social relationships and reputation aggregation for nodes in mobile social networks; further, a set of fuzzy valued factors, that is, item judgment factor, node malicious factor, and node similar factor, is given for evaluating the probability of collusive fraud happening and identifying single malicious nodes in the second part; and moreover, a detection traversing strategy is given based on random walk algorithm under the perspectives of fuzzy valued nodes’ trust schedules and proposed malicious factors. Finally, our empirical results and analysis show that the proposed mechanism in this paper is feasible and effective.

Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

LENUS (Irish Health Repository)

Hampel, Harald

2010-06-01

Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer\\'s disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40\\/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.

Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.

LENUS (Irish Health Repository)

Hampel, Harald

2012-02-01

Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer\\'s disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40\\/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.

The relationship of periodontal disease to diseases and disorders at distant sites: communication to health care professionals and patients.

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Lamster, Ira B; DePaola, Dominick P; Oppermann, Rui V; Papapanou, Panos N; Wilder, Rebecca S

2008-10-01

The body of research defining relationships among periodontal disease and certain systemic diseases and disorders has been expanding, and questions have been raised regarding what information should be conveyed to health care professionals and patients. Representatives from dentistry, medicine, the academic community and the insurance industry convened a two-day workshop July 23 and 24, 2007. The workshop participants achieved general consensus on a number of issues, including the need for greater cooperation between the health care professions. This cooperation should translate into improved clinical care as physicians refer patients for dental care, and dentists are proactive in regard to the general health of their patients. Communication to health care professionals requires a multifaceted approach that includes publication of research findings in medical and dental journals, cooperation among professional organizations and initiatives at the local level such as presentations at medical grand rounds. Dental schools should play a role in their health science centers. Communication with patients may improve through the use of targeted informational brochures in the offices of medical specialists, appropriate media campaigns and efforts led by local dental organizations. It is too early to provide specific recommendations regarding the treatment of periodontal disease to improve specific health outcomes, but dentists can become advocates for a general health promotion and disease prevention message. The lifestyles approach includes an improved diet, smoking cessation, appropriate hygiene practices and stress reduction. These strategies can improve oral and general health outcomes.

Ocular surface immunity: homeostatic mechanisms and their disruption in dry eye disease.

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Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

2012-05-01

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mathematical Modeling of Protein Misfolding Mechanisms in Neurological Diseases: A Historical Overview.

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Carbonell, Felix; Iturria-Medina, Yasser; Evans, Alan C

2018-01-01

Protein misfolding refers to a process where proteins become structurally abnormal and lose their specific 3-dimensional spatial configuration. The histopathological presence of misfolded protein (MP) aggregates has been associated as the primary evidence of multiple neurological diseases, including Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob disease. However, the exact mechanisms of MP aggregation and propagation, as well as their impact in the long-term patient's clinical condition are still not well understood. With this aim, a variety of mathematical models has been proposed for a better insight into the kinetic rate laws that govern the microscopic processes of protein aggregation. Complementary, another class of large-scale models rely on modern molecular imaging techniques for describing the phenomenological effects of MP propagation over the whole brain. Unfortunately, those neuroimaging-based studies do not take full advantage of the tremendous capabilities offered by the chemical kinetics modeling approach. Actually, it has been barely acknowledged that the vast majority of large-scale models have foundations on previous mathematical approaches that describe the chemical kinetics of protein replication and propagation. The purpose of the current manuscript is to present a historical review about the development of mathematical models for describing both microscopic processes that occur during the MP aggregation and large-scale events that characterize the progression of neurodegenerative MP-mediated diseases.

Mechanical power, thrust power and propelling efficiency: relationships with elite sprint swimming performance.

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Gatta, Giorgio; Cortesi, Matteo; Swaine, Ian; Zamparo, Paola

2018-03-01

The purpose of this study was to explore the relationships between mechanical power, thrust power, propelling efficiency and sprint performance in elite swimmers. Mechanical power was measured in 12 elite sprint male swimmers: (1) in the laboratory, by using a whole-body swimming ergometer (W' TOT ) and (2) in the pool, by measuring full tethered swimming force (F T ) and maximal swimming velocity (V max ): W' T  = F T  · V max . Propelling efficiency (η P ) was estimated based on the "paddle wheel model" at V max . V max was 2.17 ± 0.06 m · s -1 , η P was 0.39 ± 0.02, W' T was 374 ± 62 W and W' TOT was 941 ± 92 W. V max was better related to W' T (useful power output: R = 0.943, P swimming performance. The ratio W' T /W' TOT (0.40 ± 0.04) represents the fraction of total mechanical power that can be utilised in water (e.g., η P ) and was indeed the same as that estimated based on the "paddle wheel model"; this supports the use of this model to estimate η P in swimming.

Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease

NARCIS (Netherlands)

Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.

2007-01-01

Objective: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,

Perceived genetic knowledge, attitudes toward genetic testing, and the relationship between these among patients with a chronic disease.

NARCIS (Netherlands)

Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.

2007-01-01

OBJECTIVE: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,

Anxiety in close relationships is higher and self-esteem lower in patients with irritable bowel syndrome compared to patients with inflammatory bowel disease.

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Bengtsson, Mariette; Sjöberg, Klas; Candamio, Martina; Lerman, Annie; Ohlsson, Bodil

2013-04-01

Previous research has suggested an interaction between personality factors and inflammatory bowel disease (IBD) as well as irritable bowel syndrome (IBS). We therefore aimed to elucidate differences in psychological and coping functioning between patients with IBD and IBS, and to assess the relationship of disease activity with these functions. Seventy-four patients with IBD (mean age 43±17 years, range 18-82 years) and 81 patients with IBS (mean age 37±12 years, range 21-66 years) completed the questionnaires; Rosenberg Self-Esteem Scale, Toronto Alexithymia, Experiences in Close Relationships, and Sense of Coherence. Disease activity was evaluated either by the Harvey-Bradshaw index, the Simple Clinical Colitis Activity Index, or the Visual Analogue Scale for Irritable Bowel Syndrome. The study revealed that patients with IBS had higher degree of anxiety in close relationships than patients with IBD (p=0.003), and lower self-esteem (p=0.001). No other statistical differences between the whole groups IBS and IBD or between subgroups were seen. The fact that patients with IBS seem to have higher levels of anxiety in relationships and lower self-esteem could influence the way the patient deal with the disease and how the communication with health care professionals works out. A higher awareness of the importance of past negative life events should be taken into consideration. Whether the disease or the personal traits are the primary event should be addressed in future research. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

the Multitargets Pharmacological Mechanism of Qishenkeli Acting on the Coronary Heart Disease

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Yong Wang

2012-01-01

Full Text Available In this paper, we present a case study of Qishenkeli (QSKL to research TCM’s underlying molecular mechanism, based on drug target prediction and analyses of TCM chemical components and following experimental validation. First, after determining the compositive compounds of QSKL, we use drugCIPHER-CS to predict their potential drug targets. These potential targets are significantly enriched with known cardiovascular disease-related drug targets. Then we find these potential drug targets are significantly enriched in the biological processes of neuroactive ligand-receptor interaction, aminoacyl-tRNA biosynthesis, calcium signaling pathway, glycine, serine and threonine metabolism, and renin-angiotensin system (RAAS, and so on. Then, animal model of coronary heart disease (CHD induced by left anterior descending coronary artery ligation is applied to validate predicted pathway. RAAS pathway is selected as an example, and the results show that QSKL has effect on both rennin and angiotensin II receptor (AT1R, which eventually down regulates the angiotensin II (AngII. Bioinformatics combing with experiment verification can provide a credible and objective method to understand the complicated multitargets mechanism for Chinese herbal formula.

Emerging role of chemokine CC motif ligand 4 related mechanisms in diabetes mellitus and cardiovascular disease: friends or foes?

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Chang, Ting-Ting; Chen, Jaw-Wen

2016-08-24

Chemokines are critical components in pathology. The roles of chemokine CC motif ligand 4 (CCL4) and its receptor are associated with diabetes mellitus (DM) and atherosclerosis cardiovascular diseases. However, due to the complexity of these diseases, the specific effects of CCL4 remain unclear, although recent reports have suggested that multiple pathways are related to CCL4. In this review, we provide an overview of the role and potential mechanisms of CCL4 and one of its major receptors, fifth CC chemokine receptor (CCR5), in DM and cardiovascular diseases. CCL4-related mechanisms, including CCL4 and CCR5, might provide potential therapeutic targets in DM and/or atherosclerosis cardiovascular diseases.

Case Report of the Use of Mechanical Ventilation Protective Modes in Werdnig-Hoffmann Disease Domiciliary

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I.V. Gutsul

2014-08-01

Full Text Available The article describes our own clinical observation of using mechanical ventilation protective modes in a child with Werdnig-Hoffmann disease and contracture of the upper and lower extremities.

IGF-I and IGFBP2 in peripheral artery disease

DEFF Research Database (Denmark)

Urbonaviciene, Grazina; Frystyk, Jan; Urbonavicius, Sigitas

2014-01-01

BACKGROUND AND OBJECTIVES: The search for novel risk factors of cardiovascular disease (CVD) has provided valuable clinical data concerning underlying mechanism of disease. Increasing evidence indicates a possible involvement of insulin-like growth factor-I (IGF-I) and its binding protein 2 (IGFBP......-2) in the pathogenesis of CVD disorders. The aim of this study was to examine the relationship between levels of IGF-I and IGFBP-2 with all-cause and CVD mortality in a prospective study of patients with lower-extremity peripheral artery disease (PAD). METHODS AND MATERIAL: Serum IGF-I and IGFBP-2...... levels were obtained in 440 patients (257 males) with symptomatic PAD. Patients were followed for a median of 6.1 (IQ 5.1-7.2) years. The relationship between times to lethal outcome and baseline serum IGF-I and IFGBP-2 levels were examined by Cox proportional hazard analysis. The role of IFGBP-2...

The relationship between stress and Alzheimer's disease

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Nicholas J. Justice

2018-02-01

Full Text Available Stress is critically involved in the development and progression of disease. From the stress of undergoing treatments to facing your own mortality, the physiological processes that stress drives have a serious detrimental effect on the ability to heal, cope and maintain a positive quality of life. This is becoming increasingly clear in the case of neurodegenerative diseases. Neurodegenerative diseases involve the devastating loss of cognitive and motor function which is stressful in itself, but can also disrupt neural circuits that mediate stress responses. Disrupting these circuits produces aberrant emotional and aggressive behavior that causes long-term care to be especially difficult. In addition, added stress drives progression of the disease and can exacerbate symptoms. In this review, I describe how neural and endocrine pathways activated by stress interact with ongoing neurodegenerative disease from both a clinical and experimental perspective. Keywords: Alzheimer's disease, Stress, Cortisol, Corticosteroids, CRF, CRH

Relationship between microstructure and mechanical properties in ODS materials for nuclear application

International Nuclear Information System (INIS)

De Carlan, Y.

2013-01-01

Oxide Dispersion Strengthened ferritic/martensitic alloys are developed as prospective cladding materials for future Sodium-Cooled-Fast-Reactors (GEN IV) [1]. These advanced alloys present a good resistance to irradiation and a high creep rupture strength due to a reinforcement by the homogeneous dispersion of hard nano-sized particles (such as Y 2 O 3 or YTiO). ODS alloys are elaborated by powder metallurgy, consolidated by hot extrusion and manufactured into cladding tube using the Pilger cold-rolling process [2, 3]. ODS alloys present usually low ductility and high hardness. The aim of this talk is to present the specificity of the metallurgy of ODS materials in relationship with the main mechanical properties (tensile and creep properties, toughness, transition temperature). Two types of alloys will be presented: Fe-9Cr martensitic ODS and Fe-14Cr ferritic ODS alloys. Mechanical properties of the materials depend on the metallurgical state (fine grains, recrystallized, martensitic) and very different behaviors are observed as a function of final microstructure. For example, for a Fe-9Cr ODS alloy, tempered martensite lets obtaining material with high strength whereas softened ferrite see figure 1 [4] tolerates high deformation levels. (authors)

Recent Developments in the Study of Social Relationships, Stress Responses, and Physical Health

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Hostinar, Camelia E.

2015-01-01

This selective review aims to highlight some of the most recent empirical or theoretical advancements in the study of social relationships as buffers against stress and as protective factors against risk for disease, focusing on articles published between 2013 and 2015. The review summarizes novel findings showing that social relationships can protect individuals against negative health outcomes associated with chronic adversity and can be associated with reduced cumulative physiological damage (allostatic load). There is also evidence that some relationships can be a source of stress. Additionally, recent findings concerning the psychological and neurobiological mechanisms of action for social support, the developmental patterning of social stress-buffering and recent experimental studies attempting to change relationships to affect health are also reviewed. PMID:26366429

Unraveling Alzheimer?s: Making Sense of the Relationship between Diabetes and Alzheimer?s Disease 1

OpenAIRE

Schilling, Melissa A.

2016-01-01

Numerous studies have documented a strong association between diabetes and Alzheimer?s disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intra...

In silico studies in drug research against neurodegenerative diseases.

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Makhouri, Farahnaz Rezaei; Ghasemi, Jahan B

2017-08-22

Neurodegenerative diseases such as Alzheimer's disease (AD), progressive neurodegenerative forms of Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis, spinal cerebellar ataxias, and spinal and bulbar muscular atrophy are described by slow and selective dysfunction and degeneration of neurons and axons in the central nervous system (CNS). Computer-aided or in silico design methods have matured into powerful tools for reducing the number of ligands that should be screened in experimental assays. In the present review, the authors provide a basic background about neurodegenerative diseases and in silico techniques in the drug research. Furthermore, they review the various in silico studies reported against various targets in neurodegenerative diseases, including homology modeling, molecular docking, virtual high-throughput screening, quantitative structure activity relationship (QSAR), hologram quantitative structure activity relationship (HQSAR), 3D pharmacophore mapping, proteochemometrics modeling (PCM), fingerprints, fragment-based drug discovery, Monte Carlo simulation, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design, support vector machines, and machine learning approaches. Neurodegenerative diseases have a multifactorial pathoetiological origin, so scientists have become persuaded that a multi-target therapeutic strategy aimed at the simultaneous targeting of multiple proteins (and therefore etiologies) involved in the development of a disease is recommended in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The effect of menopause on the relationship between hyperlipidemia and periodontal disease via salivary 8-hydroxy-2'-deoxyguanosine and myeloperoxidase levels.

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Kemer Doğan, Esra Sinem; Kırzıoğlu, Fatma Yeşim; Doğan, Burak; Fentoğlu, Özlem; Kale, Banu

2018-03-01

Impairment of the lipid metabolism could affect the periodontal disease; increased oxidative stress may have a role in this relationship. The aim of the present study was to evaluate the role of menopause in the relationship between hyperlipidemia and periodontal disease via oxidative stress markers in saliva. Sixty-seven women were enrolled in the study and divided into four groups as systemically healthy and premenopause (C) (n = 18), hyperlipidemia and premenopause (H) (n = 16), systemically healthy and postmenopause (M) (n = 17), and hyperlipidemia and postmenopause (MH) (n = 16). Sociodemographics, periodontal and metabolic parameters, and saliva oxidative markers (myeloperoxidase [MPO] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) were evaluated. Menopause and/or hyperlipidemia were associated with an increase in all evaluated periodontal parameters. Saliva 8-OHdG and MPO levels were higher in menopausal groups (M and MH). Multivariate linear regression analyses revealed that hyperlipidemia was related to an increase in periodontal parameters. Salivary oxidative stress markers and periodontal parameters were also positively associated with menopause and hyperlipidemia. Saliva 8-OHdG and MPO levels may indicate that the relationship between periodontal disease and hyperlipidemia is aggravated by menopause.

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.

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Hongwei Chu

Full Text Available Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE. Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor". Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

RELATIONSHIP OF AIRWAY HYPERRESPONSIVENESS TO RESPIRATORY SYMPTOMS AND DIURNAL PEAK FLOW VARIATION IN PATIENTS WITH OBSTRUCTIVE LUNG-DISEASE

NARCIS (Netherlands)

BRAND, PLP; POSTMA, DS; KERSTJENS, HAM; KOETER, GH

This study reports on the relationship of airway hyperresponsiveness (AH) with respiratory symptoms and diurnal peak flow expiratory (PEF) variation in 221 hyperresponsive patients with moderately severe airways obstruction. The disease was in a stable phase in all patients. Closely adhering to the

Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

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Mougabure-Cueto, Gastón; Picollo, María Inés

2015-09-01

Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

Sympathetic Overactivity in Chronic Kidney Disease: Consequences and Mechanisms

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Jasdeep Kaur

2017-08-01

Full Text Available The incidence of chronic kidney disease (CKD is increasing worldwide, with more than 26 million people suffering from CKD in the United States alone. More patients with CKD die of cardiovascular complications than progress to dialysis. Over 80% of CKD patients have hypertension, which is associated with increased risk of cardiovascular morbidity and mortality. Another common, perhaps underappreciated, feature of CKD is an overactive sympathetic nervous system. This elevation in sympathetic nerve activity (SNA not only contributes to hypertension but also plays a detrimental role in the progression of CKD independent of any increase in blood pressure. Indeed, high SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure. This brief review will discuss some of the consequences of sympathetic overactivity and highlight some of the potential pathways contributing to chronically elevated SNA in CKD. Mechanisms leading to chronic sympathoexcitation in CKD are complex, multifactorial and to date, not completely understood. Identification of the mechanisms and/or signals leading to sympathetic overactivity in CKD are crucial for development of effective therapeutic targets to reduce the increased cardiovascular risk in this patient group.

The importance of balanced pro-inflammatory and anti-inflammatory mechanisms in diffuse lung disease

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Strieter Robert

2002-01-01

Full Text Available Abstract The lung responds to a variety of insults in a remarkably consistent fashion but with inconsistent outcomes that vary from complete resolution and return to normal to the destruction of normal architecture and progressive fibrosis. Increasing evidence indicates that diffuse lung disease results from an imbalance between the pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favors pro-inflammatory mediators dictating the development of chronic diffuse lung disease. This review focuses on the mediators that influence this imbalance.

Myocardial Architecture, Mechanics, and Fibrosis in Congenital Heart Disease

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Sarah Ghonim

2017-05-01

Full Text Available Congenital heart disease (CHD is the most common category of birth defect, affecting 1% of the population and requiring cardiovascular surgery in the first months of life in many patients. Due to advances in congenital cardiovascular surgery and patient management, most children with CHD now survive into adulthood. However, residual and postoperative defects are common resulting in abnormal hemodynamics, which may interact further with scar formation related to surgical procedures. Cardiovascular magnetic resonance (CMR has become an important diagnostic imaging modality in the long-term management of CHD patients. It is the gold standard technique to assess ventricular volumes and systolic function. Besides this, advanced CMR techniques allow the acquisition of more detailed information about myocardial architecture, ventricular mechanics, and fibrosis. The left ventricle (LV and right ventricle have unique myocardial architecture that underpins their mechanics; however, this becomes disorganized under conditions of volume and pressure overload. CMR diffusion tensor imaging is able to interrogate non-invasively the principal alignments of microstructures in the left ventricular wall. Myocardial tissue tagging (displacement encoding using stimulated echoes and feature tracking are CMR techniques that can be used to examine the deformation and strain of the myocardium in CHD, whereas 3D feature tracking can assess the twisting motion of the LV chamber. Late gadolinium enhancement imaging and more recently T1 mapping can help in detecting fibrotic myocardial changes and evolve our understanding of the pathophysiology of CHD patients. This review not only gives an overview about available or emerging CMR techniques for assessing myocardial mechanics and fibrosis but it also describes their clinical value and how they can be used to detect abnormalities in myocardial architecture and mechanics in CHD patients.

Relationship between nonalcoholic fatty liver disease and adipocyte fatty acid-binding protein

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ZHOU Xiaoli

2013-12-01

Full Text Available ObjectiveTo investigate the relationship between nonalcoholic fatty liver disease (NAFLD and serum level of adipocyte fatty acid-binding protein (AFABP. MethodsA total of 160 patients who underwent physical examination in the Affiliated Hospital of Ningxia Medical University from July to November 2010 were included in our study. These subjects were divided into two groups according to the diagnostic criteria for NAFLD formulated by the Chinese Medical Association: control group (n=71 and NAFLD group (n=89. The two groups were compared with respect to general condition, body mass index (BMI, blood pressure, AFABP, serum insulin, and other serological indices. The relationship of serum AFABP with NAFLD and other metabolic parameters was analyzed using the Spearman linear correlation coefficient. Comparison of measurement data was made by t test and rank sum test; comparison of enumeration data was made by chi-square test. ResultsThere were more males than females in the NAFLD group. Compared with the control group, the NAFLD group had higher BMI and levels of blood glucose, triglyceride (TG, aspartate aminotransferase (AST, alanine aminotransferase (ALT, and uric acid and lower high-density lipoprotein (HDL level; in addition, the NAFLD group had significantly higher serum AFABP and insulin levels and homeostasis model assessment-estimated insulin resistance (HOMA-IR. The Spearman correlation analysis showed that serum AFABP was positively correlated with NAFLD, BMI, HOMA-IR, serum insulin, blood glucose, TG, ALT, AST, and uric acid but negatively correlated with HDL. After adjustment for sex, age, and BMI, serum AFABP was positively correlated with NAFLD, HOMA-IR, serum insulin, blood glucose, TG, ALT, and uric acid, but had no significant correlation with HDL and AST. ConclusionSerum AFABP is closely associated with NAFLD and may be an independent plasma marker of this disease. AFABP plays a causative role in the pathogenesis of NAFLD.

Health-related behavior as a mechanism behind the relationship between neighborhood social capital and individual health: a multilevel analysis.

NARCIS (Netherlands)

Mohnen, S.M.; Völker, B.; Flap, H.; Groenewegen, P.P.

2012-01-01

BACKGROUND: Although various studies have found a positive association between neighborhood social capital and individual health, the mechanism explaining this direct effect is still unclear. Neighborhood social capital is the access to resources that are generated by relationships between people in

Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

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Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

2016-01-01

With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

A nonalcoholic fatty liver disease cirrhosis model in gerbil : the dynamic relationship between hepatic lipid metabolism and cirrhosis

NARCIS (Netherlands)

Li, Wei; Guan, Zheng; Brisset, Jean C.; Shi, Qiaojuan; Lou, Qi; Ma, Yue; Suriguga, Su; Ying, Huazhong; Sa, Xiaoying; Chen, Zhenwen; Quax, Wim J.; Chu, Xiaofeng

2018-01-01

Nonalcoholic fatty liver disease (NAFLD) usually takes decades to develop into cirrhosis, which limits the longitudinal study of NAFLD. This work aims at developing a NAFLD-caused cirrhosis model in gerbil and examining the dynamic relationship between hepatic lipid metabolism and cirrhosis. We fed

From SARS to H7N9: the mechanism of responding to emerging communicable diseases has made great progress in China.

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Yao, Linong; Chen, Enfu; Chen, Zhiping; Gong, Zhenyu

2013-12-01

The outbreak of severe acute respiratory syndrome (SARS) in 2003 indicated that China's existing former mechanism for emergency management was very vulnerable. The Chinese Government has since established a new mechanism for responding to emerging communicable diseases. This paper examined the current status of and developments in China's response to emerging communicable diseases from the outbreak of SARS in 2003 to the outbreak of H7N9 virus infection in 2013. Results indicated that the current mechanism for emergency responses to emerging communicable diseases in China has made great achievements in terms of command and decision-making, organization and collaboration, monitoring and early warning systems, protection, and international communication and cooperation. This mechanism for responding to emerging communicable diseases allowed China to successfully deal with outbreaks of the H5N1 bird flu, H1N1 flu, and H7N9 bird flu. However, a better coordination system, a more complete Office of Responses to Public Health Emergencies, administrative responsibility and error correction, better personnel training, and government responsibility may help to improve the response to emerging communicable diseases. Such improvements are eagerly anticipated.

The relationship between depression and periodontal diseases.

Science.gov (United States)

Hwang, S H; Park, S G

2018-03-01

A cross-sectional study was conducted to investigate whether depression is associated with periodontal diseases in a representative sample of South Korean adults Methods: We used data from the sixth Korea National Health and Nutrition Examination Survey (KNHANES VI), conducted in 2014. We included in this study 4328 participants aged over 20 years (1768 males and 2560 females). Depression was assessed with the Patient Health Questionnaire (PHQ-9) and history of physician-diagnosed depression. Periodontal diseases were assessed a gingival bleeding, calculus and periodontal pockets. The data were analyzed using the chi-square test and multiple logistic regression. People with any periodontal diseases tended to be old, male, married, low income, poor education, blue-collar occupation, diabetes mellitus, hypertension, overweight, smoking, not using dental floss or interdental brush in univariate analysis. Neither self-reported nor diagnosed depression was associated with the presence of any or severe periodontal disease in the total sample. In participants aged 20-29 years only, the presence of any periodontal disease was associated with self-reported depression (OR, 2.031; 95% CI, 1.011-4.078). In the same age group, the presence of severe periodontal disease was associated with both self-reported depression (OR, 6.532; 95% CI, 2.190-19.483) and diagnosed depression (OR, 7.729; 95% CI, 1.966-30.389). Self-reported depression was significantly associated with the presence of any or severe periodontal disease, and diagnosed depression was significantly associated with severe periodontal diseases only in participants aged 20-29 years. Copyright© 2018 Dennis Barber Ltd.

Study of General health, resiliency, and defense mechanisms in patients with migraine headache

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Alireza Aghayusefi

2013-06-01

Full Text Available Background: Migraine is a neurological disease that the etiology, several factors affect its onset or its exacerbation. One of the factors affecting disease is psychological factors such as defense mechanisms, resiliency, and general health. This study assessed the relationship between general health, resiliency, and general defense mechanisms, and also predicts the general health of people with migraine headaches that have a high resiliency and use mature defense mechanisms. Material and Methods: 50 women with migraine headache in the city of Bushehr using defense mechanisms, resiliency, and general health questionnaires were studied. For statistical analysis, Pearson correlation and multiple regression tests were used by SPSS 17 software. Results: The results showed that most of the defense mechanisms of migraine sufferers are Immature and Neuroticism. There is significant negative correlation between the deterioration of general health and resiliency as well as the mature defense mechanism (p=0/003, and also there is a significant positive correlation between this deterioration with neuroticism (p=0/040 and immature defense mechanisms (p=0/041. On the other hand there is significant negative correlation between resiliencies with immature (p=0/009 and neuroticism defense mechanisms (p=0/04, and also with mature defense mechanism has a significant positive correlation (p=0/003. Also, as more people use the mature defense mechanism, their deterioration of general health will be reduced, but this relationship will be stronger with the presence of resiliency. So migraine people use the mature defense mechanisms with high resiliency will have more favorable general health (less deterioration of general health. Conclusion: This study showed that migraine patients use the mature defense mechanisms with high resiliency will have more favorable general health (less deterioration of general health.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

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Wei-Ming Xu

2018-01-01

Full Text Available Background: Ischemic heart disease (IHD has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated.Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures.Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules. These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620 and Renin-angiotensin system (hsa04614, with the molecular functions of angiotensin maturation (GO:0002003 and response to bacterium (GO:0009617, which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO and published biomedical literatures.Conclusion: A network medicine

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

Science.gov (United States)

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

Science.gov (United States)

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

Relationship between quantum walks and relativistic quantum mechanics

International Nuclear Information System (INIS)

Chandrashekar, C. M.; Banerjee, Subhashish; Srikanth, R.

2010-01-01

Quantum walk models have been used as an algorithmic tool for quantum computation and to describe various physical processes. This article revisits the relationship between relativistic quantum mechanics and the quantum walks. We show the similarities of the mathematical structure of the decoupled and coupled forms of the discrete-time quantum walk to that of the Klein-Gordon and Dirac equations, respectively. In the latter case, the coin emerges as an analog of the spinor degree of freedom. Discrete-time quantum walk as a coupled form of the continuous-time quantum walk is also shown by transforming the decoupled form of the discrete-time quantum walk to the Schroedinger form. By showing the coin to be a means to make the walk reversible and that the Dirac-like structure is a consequence of the coin use, our work suggests that the relativistic causal structure is a consequence of conservation of information. However, decoherence (modeled by projective measurements on position space) generates entropy that increases with time, making the walk irreversible and thereby producing an arrow of time. The Lieb-Robinson bound is used to highlight the causal structure of the quantum walk to put in perspective the relativistic structure of the quantum walk, the maximum speed of walk propagation, and earlier findings related to the finite spread of the walk probability distribution. We also present a two-dimensional quantum walk model on a two-state system to which the study can be extended.

Regulation mechanisms of pituitary-thyroid axis in normal subjects and patients with Graves' disease

International Nuclear Information System (INIS)

Takagi, Shinko; Yamauchi, Kazuyuki; Mori, Yuichi

1986-01-01

The regulatory mechanism of the pituitary-thyroid axis in normal subjects and patients with Graves' disease was investigated using a highly sensitive TSH assay based on the immunoradiometric assay. All of the normal subjects had detectable TSH values within the range 0.35 to 6.0 μU/ml. No negative correlations between TSH and free thyroid hormones existed in normal subjects. Patients with thyroid carcinoma who seemed to have normal pituitary-thyroid function showed a rapid increase of TSH after total thyroidectomy. On the other hand, while untreated patients with Graves' disease all had undetectable TSH values, these patients took 1 to 3.5 months longer to normalize their TSH values than to normalize free thyroid hormones on antithyroid drug therapy. During the recovery phase by the treatment with decrease of antithyroid drug or supplement of T 4 from iatrogenic hypothyroid state after treatment for Graves' disease and thyroid carcinoma, normalization of TSH levels was delayed than that of free thyroid hormones. Patients with Graves' disease in remission showed an extremely positive correlation between basal and peak TSH levels in TRH test, and a negative correlation between basal TSH and FT 4 . In conclusion, an individual patient may have a different set point concerning the regulatory mechanism of the pituitary-thyroid axis, and the persistence of the hyperthyroid state would seem to have caused some reversible dysfunction of the pituitary gland. (author)

Contentious host-microbiota relationship in inflammatory bowel disease--can foes become friends again?

Science.gov (United States)

Satokari, Reetta

2015-01-01

Inflammatory bowel diseases (IBDs) are chronic debilitating disorders of unknown etiology, consisting of two main conditions, ulcerative colitis and Crohn's disease. Major advances have recently taken place in human genetic studies of IBD and over 160 risk loci for these two diseases have been uncovered. These genetic data highlight a key role for genes that code for immunological and epithelial barrier functions. Environmental factors also make substantial contributions to the pathogenesis of IBD and account for the growing incidence of the diseases around the world. Intestinal microbiota creates resistance to infection, provides nutrients, and educates the immune system and in many ways has a significant impact on human health. Aberrant microbiota composition and decreased diversity (dysbiotic microbiota) are key etiopathological events in IBD. Dysbiotic microbiota can lead to loss of normal, regulatory immune effects in the gut mucosa. This may play a central role in the development and perpetuation of chronic inflammation. Further, the expression of specific innate immune receptors that recognize microbes is altered in the IBD epithelium. Therefore, the combination of host side epithelial barrier functions and the presence of dysbiotic microbiota in the gut together promote inflammation. New therapeutic options targeting microbiota are currently considered for IBD and they may, in the future, provide means to reverse the pathogenic host-microbiota relationship into a symbiotic one. In this review, the focus is on the intestinal microbiota and host-microbe interactions in IBD.

Exposure to Agrochemicals and Cardiovascular Disease: A Review.

Science.gov (United States)

Sekhotha, Matome M; Monyeki, Kotsedi D; Sibuyi, Masezi E

2016-02-18

In the agricultural world there is a continuous loss of food, fiber and other commodities due to pests, disease and weeds before harvesting time. These losses had create lots of financial burden to the farm owners that might lead to shutting down of their daily business. Worldwide, there is an overall very high loss of agricultural products due to weeds growth alone. To counteract this problem most farmers resort to the use of agrochemicals to increase their production but compromising the health of their farmworkers. The purpose of the study will be to assess the relationship between the agrochemical particles and cardiovascular diseases among farmworkers. Non-systematic review was used to collect data. The following database were use: Medline, EBSCO, and Science Direct to search for the existing journal articles. This study addresses the relationship between agrochemicals particles and cardiovascular diseases in the farming industries using literature review. Other researchers had already done an extensive research on the pathway of potential mechanisms linking the ultrafine particulate matter to cardiovascular diseases. The outcomes of those investigations were the clinical results of events that might lead to the development of myocardial infarction, congestive heart failure (CHF), stroke, arrhythmia and sudden death. Xenobiotic compounds that maybe implicated in the pathophysiology of human cardiovascular diseases, will be examined and included in this study. There is compelling evidence suggesting that toxic free radicals of pesticides play an important role in human health. There is a close relationship between agrochemicals particle and cardiovascular diseases.

The relationship between stress and Alzheimer's disease.

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Justice, Nicholas J

2018-02-01

Stress is critically involved in the development and progression of disease. From the stress of undergoing treatments to facing your own mortality, the physiological processes that stress drives have a serious detrimental effect on the ability to heal, cope and maintain a positive quality of life. This is becoming increasingly clear in the case of neurodegenerative diseases. Neurodegenerative diseases involve the devastating loss of cognitive and motor function which is stressful in itself, but can also disrupt neural circuits that mediate stress responses. Disrupting these circuits produces aberrant emotional and aggressive behavior that causes long-term care to be especially difficult. In addition, added stress drives progression of the disease and can exacerbate symptoms. In this review, I describe how neural and endocrine pathways activated by stress interact with ongoing neurodegenerative disease from both a clinical and experimental perspective.

Smoking in inflammatory bowel diseases: good, bad or ugly?

Science.gov (United States)

Lakatos, Peter Laszlo; Szamosi, Tamas; Lakatos, Laszlo

2007-12-14

Smoking is an important environmental factor in inflammatory bowel disease (IBD), having different effects in ulcerative colitis (UC) and Crohn's disease (CD). A recent meta-analysis partially confirmed previous findings that smoking was found to be protective against ulcerative colitis and, after onset of the disease, might improve its course, decreasing the need for colectomy. However, smoking increases the risk of developing CD and worsens its course, increasing the need for steroids, immunosuppressants and re-operations. Smoking cessation aggravates ulcerative colitis and improves CD. Data are however, largely conflictive as well as the potential mechanisms involved in this dual relationship are still unknown. In this review article, the authors review the role of smoking in inflammatory bowel diseases.

[Relationship between socioeconomic status and the prevalence of cardiovascular disease among retired residents living in a community, Shanghai].

Science.gov (United States)

Xie, Chunyan; Qin, Chenxi; Wang, Geng; Yu, Canqing; Wang, Jin; Dai, Liqiang; Lyu, Jun; Gao, Wenjing; Wang, Shengfeng; Zhan, Siyan; Hu, Yonghua; Cao, Weihua; Li, Liming

2014-05-01

To explore the relationship between socioeconomic status and the risk factors of cardiovascular diseases in retirees from a community in Shanghai. Observational study involved 9 943 retirees aged 50 and over in Shanghai. Both single factor and multi-factor analyses methods were used to describe the correlation between factors as:educational level, marital status, annual household income and risk of hypertension, coronary heart disease, stroke etc. A new defined compound index was used to assess the relevance of socioeconomic status on the risk of cardiovascular diseases, based on logistic regression model. After adjusted for age, the risk of cardiovascular diseases in these retirees was influenced by socioeconomic status. In general, opponent correlations in education levels and prevalence of hypertension were found between female and male. Compared with those having received college or higher education, the risk of hypertension increased in females when the education level declined, with OR as 1.08 (95% CI:0.89-1.30). For those having had senior high school junior high school or elementary education, the risks of hypertension were 1.26 (95%CI:1.05-1.51), 1.34 (95%CI:1.08-1.65), 0.72 (95%CI:0.59-0.87),0.78 (95%CI:0.64-0.94), and 0.70 (95%CI:0.52-0.92) for males, respectively. The risk of cardiovascular diseases increased with annual household income. Compared with high level of socioeconomic status, lower socioeconomic status might decline the risk of cardiovascular diseases in males by approximately 30%, with OR for medium being 0.72 (95%CI:0.61-0.84) and for lower ones it was 0.70 (95% CI:0.57-0.87). However, similar correlations were not found in females. No significant relationship was found between marital status and the prevalence of cardiovascular diseases in this study. The risks of cardiovascular diseases varied with different socioeconomic status, indicating that tailored interventions should be conducted in different socioeconomic groups.

Unraveling the Mechanisms of Cutaneous Graft-Versus-Host Disease

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Pedro Santos e Sousa

2018-05-01

Full Text Available The skin is the most common target organ affected by graft-versus-host disease (GVHD, with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies.

Unraveling the disease consequences and mechanisms of modular structure in animal social networks

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Sah, Pratha; Leu, Stephan T.; Cross, Paul C.; Hudson, Peter J.; Bansal, Shweta

2017-01-01

Disease risk is a potential cost of group living. Although modular organization is thought to reduce this cost in animal societies, empirical evidence toward this hypothesis has been conflicting. We analyzed empirical social networks from 43 animal species to motivate our study of the epidemiological consequences of modular structure in animal societies. From these empirical studies, we identified the features of interaction patterns associated with network modularity and developed a theoretical network model to investigate when and how subdivisions in social networks influence disease dynamics. Contrary to prior work, we found that disease risk is largely unaffected by modular structure, although social networks beyond a modular threshold experience smaller disease burden and longer disease duration. Our results illustrate that the lowering of disease burden in highly modular social networks is driven by two mechanisms of modular organization: network fragmentation and subgroup cohesion. Highly fragmented social networks with cohesive subgroups are able to structurally trap infections within a few subgroups and also cause a structural delay to the spread of disease outbreaks. Finally, we show that network models incorporating modular structure are necessary only when prior knowledge suggests that interactions within the population are highly subdivided. Otherwise, null networks based on basic knowledge about group size and local contact heterogeneity may be sufficient when data-limited estimates of epidemic consequences are necessary. Overall, our work does not support the hypothesis that modular structure universally mitigates the disease impact of group living.

Residential Arrangements and Children's School Engagement: The Role of the Parent-Child Relationship and Selection Mechanisms

Science.gov (United States)

Havermans, Nele; Sodermans, An Katrien; Matthijs, Koen

2017-01-01

The increase in shared residential arrangements is driven by the belief that it is in the best interest of the child. The maintenance of contact between child and parents can mitigate negative consequences of separation. However, selection mechanisms may account for a positive relationship between shared residential arrangements and child…

Dysphagia and sialorrhea: the relationship to Parkinson's disease.

Science.gov (United States)

Nicaretta, Denise Hack; Rosso, Ana Lucia; Mattos, James Pitágoras de; Maliska, Carmelindo; Costa, Milton M B

2013-01-01

Dysphagia and sialorrhea in patients with Parkinson's disease are both automatically accepted as dependent on this neurological disease. The aim were to establish if these two complaints are a consequence or associated manifestations of Parkinson's disease. Two Parkinson's diseases groups from the same outpatients' population were studied. Patients in the first group, with dysphagia, were studied by videofluoroscopy. The second, with sialorrhea, were studied by the scintigraphic method, Videofluoroscopic examination of the oral, pharyngeal and esophageal phases of swallowing showed that 94% of Parkinson's diseases patients present, structural causes, not related to Parkinson's diseases, able to produce or intensify the observed disphagia. The scintigraphic examination of Parkinson's diseases patients with sialorrhea showed that there is no increase of serous saliva production. Nevertheless, showed a significantly higher velocity of saliva excretion in the Parkinson's diseases patients. Dysphagia can be due to the muscular rigidity often present in the Parkinson's diseases patient, or more usually by non Parkinson's disease associated causes. In Parkinson's diseases patients, sialorrhea is produced by saliva retention. Nevertheless, sialorrhea can produce discomfort in swallowing, although without a formal complaint of dysphagia. In this case, subclinical dysphagia must be considered. Sialorrhea is indicative of dysphagia or at least of subclinical dysphagia. As final conclusion, Parkinson's diseases can be an isolated cause of dysphagia and/or sialorrhea, but frequently, a factor unrelated to Parkinson's diseases is the main cause of or at least aggravates the dysphagia.

Lifelong Bilingualism and Neural Reserve against Alzheimer’s disease: A Review of Findings and Potential Mechanisms

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Gold, Brian T.

2014-01-01

Alzheimer’s disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. PMID:25496781

Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

Science.gov (United States)

Roncal-Jimenez, C; Lanaspa, M A; Jensen, T; Sanchez-Lozada, L G; Johnson, R J

2015-01-01

Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health. © 2015 S. Karger AG, Basel.

Adipokines and the cardiovascular system: mechanisms mediating health and disease.

Science.gov (United States)

Northcott, Josette M; Yeganeh, Azadeh; Taylor, Carla G; Zahradka, Peter; Wigle, Jeffrey T

2012-08-01

This review focuses on the role of adipokines in the maintenance of a healthy cardiovascular system, and the mechanisms by which these factors mediate the development of cardiovascular disease in obesity. Adipocytes are the major cell type comprising the adipose tissue. These cells secrete numerous factors, termed adipokines, into the blood, including adiponectin, leptin, resistin, chemerin, omentin, vaspin, and visfatin. Adipose tissue is a highly vascularised endocrine organ, and different adipose depots have distinct adipokine secretion profiles, which are altered with obesity. The ability of many adipokines to stimulate angiogenesis is crucial for adipose tissue expansion; however, excessive blood vessel growth is deleterious. As well, some adipokines induce inflammation, which promotes cardiovascular disease progression. We discuss how these 7 aforementioned adipokines act upon the various cardiovascular cell types (endothelial progenitor cells, endothelial cells, vascular smooth muscle cells, pericytes, cardiomyocytes, and cardiac fibroblasts), the direct effects of these actions, and their overall impact on the cardiovascular system. These were chosen, as these adipokines are secreted predominantly from adipocytes and have known effects on cardiovascular cells.

Genetic characterization and disease mechanism of retinitis pigmentosa; current scenario.

Science.gov (United States)

Ali, Muhammad Umar; Rahman, Muhammad Saif Ur; Cao, Jiang; Yuan, Ping Xi

2017-08-01

Retinitis pigmentosa is a group of genetically transmitted disorders affecting 1 in 3000-8000 individual people worldwide ultimately affecting the quality of life. Retinitis pigmentosa is characterized as a heterogeneous genetic disorder which leads by progressive devolution of the retina leading to a progressive visual loss. It can occur in syndromic (with Usher syndrome and Bardet-Biedl syndrome) as well as non-syndromic nature. The mode of inheritance can be X-linked, autosomal dominant or autosomal recessive manner. To date 58 genes have been reported to associate with retinitis pigmentosa most of them are either expressed in photoreceptors or the retinal pigment epithelium. This review focuses on the disease mechanisms and genetics of retinitis pigmentosa. As retinitis pigmentosa is tremendously heterogeneous disorder expressing a multiplicity of mutations; different variations in the same gene might induce different disorders. In recent years, latest technologies including whole-exome sequencing contributing effectively to uncover the hidden genesis of retinitis pigmentosa by reporting new genetic mutations. In future, these advancements will help in better understanding the genotype-phenotype correlations of disease and likely to develop new therapies.

Relationship between Inflammation and Cardiovascular Diseases

OpenAIRE

Riddhi Patel; Henish Patel; Rachana Sarawade

2013-01-01

Inflammation is a part of complex biological response of vascular tissue to harmful stimuli such as pathogens, damaged cells or irritants. Recent advance in basic science have established a fundamental role for inflammation immediating all stages of cardiovascular diseases from initiation, progression and complications. Inflammation is thread linking to cardiovascular diseases. Clinical studies have shown that this emerging biology of inflammation play important role in pathogenesis of acute ...

Do payers value rarity? : An analysis of the relationship between disease rarity and orphan drug prices in Europe

NARCIS (Netherlands)

Medic, Goran; Korchagina, Daria; Young, Katherine Eve; Toumi, Mondher; Postma, Maarten Jacobus; Wille, Micheline; Hemels, Michiel

2017-01-01

Background and Objective: Orphan drugs have been a highlight of discussions due to their higher prices than non-orphan drugs. There is currently no European consensus on the method of value assessment for orphan drugs. This study assessed the relationship between the prevalence of rare diseases and

INCIDENCE OF STUNTING AND ITS RELATIONSHIP WITH FOOD INTAKE, INFECTIOUS DISEASES, AND ECONOMIC STATUS IN KENDARI, SOUTHEAST SULAWESI, INDONESIA

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Akhmad

2016-12-01

Full Text Available Background: Stunting is characterized by inhibition of growth in children that lead to failure in getting normal heights and healthy child's age. It is a public health problem in the working area of Public Health Center of Mata, Kelurahan Mangga Dua in Kendari in 2016. Objective: This study aims to examine the relationship between food intake, infectious diseases, economic status and the incidence of stunting in Kendari, Southeast Sulawesi, Indonesia Methods: This was a descriptive cross sectional study with retrospective approach. This research was conducted in Public Health Center of Mata. There were 41 respondents were selected as the samples. Data were collected by questionnaires, observation, and documentation. Data were analyzed using Chi-Square test. Results: The results showed that there were significant associations between food intake (p= 0.001, infectious diseases (p= 0.000, economic status (p= 0.000, and the incidence of stunting in infants. Conclusions: It can be concluded that there is a relationship between food intake, infectious diseases and economic status with the incidence of stunting in children aged 2-4 years in the working area of Public Health Center of Mata, Kendari. Therefore, good food intake is needed for the growth and development of the child. Moreover, changing the behavior of parents by doing the healthy and clean behavior in the household to prevent infectious diseases in children infectious diseases is also very important. Economic status however also plays key role in the incidence of stunting in children

Insight into the mechanisms regulating immune homeostasis in health and disease.

Science.gov (United States)

Sirisinha, Stitaya

2011-03-01

Innate and adaptive immune systems consist of cells and molecules that work together in concert to fight against microbial infection and maintain homeostasis. Hosts encounter microbes / exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) all the time and they must have proper mechanisms to counteract the danger such that appropriate responses (e.g., degree of inflammation and types of mediators induced) can be mounted in different scenarios. Increasing numbers of endogenous danger signals of host origin are being identified including, for example, uric acid and cholesterol crystals, high mobility group box1 (HMGB1) protein, oxidized LDL, vesicans, heat shock proteins (HSPs) and self DNA. Many of these endogenous ligands have been shown to be associated with inflammation-related diseases like atherosclerosis, gout and type 2 diabetes. Several DAMPs appear to have the ability to interact with more than one receptor. We are now beginning to understand how the immune system can distinguish infection from endogenous ligands elaborated following cellular insults and tissue damage. Appropriate responses to maintain the homeostatic state in health and disease depend largely on the recognition and response to these stimuli by germline encoded pattern-recognition receptors (PRRs) present on both immune and non-immune cells. These receptors are, for example, Toll-like receptors (TLRs), C-type lectin receptors (CLRs) and cytosolic receptors (e.g., RLRs, NLRs and some intracellular DNA sensors). Atypical PRR "danger" receptors, like the receptor for advanced glycation end products (RAGE) and their ligands have been identified. A proper response to maintain homeostasis relies on specific negative regulators and regulatory pathways to dampen its response to tissue injury while maintaining the capacity to eliminate infection and induce proper tissue repair. Moreover, some PRRs (e.g., TLR2,TLR4 and NLRP3) and atypical

The integrated disease network.

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Sun, Kai; Buchan, Natalie; Larminie, Chris; Pržulj, Nataša

2014-11-01

The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases.

Family health history communication networks of older adults: importance of social relationships and disease perceptions.

Science.gov (United States)

Ashida, Sato; Kaphingst, Kimberly A; Goodman, Melody; Schafer, Ellen J

2013-10-01

Older individuals play a critical role in disseminating family health history (FHH) information that can facilitate disease prevention among younger family members. This study evaluated the characteristics of older adults and their familial networks associated with two types of communication (have shared and intend to share new FHH information with family members) to inform public health efforts to facilitate FHH dissemination. Information on 970 social network members enumerated by 99 seniors (aged 57 years and older) at 3 senior centers in Memphis, Tennessee, through face-to-face interviews was analyzed. Participants shared FHH information with 27.5% of the network members; 54.7% of children and 24.4% of siblings. Two-level logistic regression models showed that participants had shared FHH with those to whom they provided emotional support (odds ratio [OR] = 1.836) and felt close to (OR = 1.757). Network-members were more likely to have received FHH from participants with a cancer diagnosis (OR = 2.617) and higher familiarity with (OR = 1.380) and importance of sharing FHH with family (OR = 1.474). Participants intended to share new FHH with those who provide tangible support to (OR = 1.804) and were very close to them (OR = 2.112). Members with whom participants intend to share new FHH were more likely to belong to the network of participants with higher perceived severity if family members encountered heart disease (OR = 1.329). Many first-degree relatives were not informed of FHH. Perceptions about FHH and disease risk as well as quality of social relationships may play roles in whether seniors communicate FHH with their families. Future studies may consider influencing these perceptions and relationships.

Is periodontal disease a reason or result for premature birth?

Directory of Open Access Journals (Sweden)

Turgut Demir

2012-01-01

Full Text Available Introduction: It is a known fact that there is a connection between periodontal disease and certain systemic conditions. Even though there are some contradictory results in the conducted studies, periodontal disease has been accepted as a risk factor affecting the negative terminations of pregnancy in recent years (premature birth [PB], low birth weight. This consideration is associated with a positive correlation between two conditions in some studies. The Hypothesis: Although there is such a relationship between periodontal disease and PB, the linking mechanism has not been explained as presence of the relation cannot reveal the cause-effect relationship. It should be discussed whether or not this positive connection is caused by the fact that periodontal disease is an independent risk factor for PB, or the change (hormonal, inflammatory in the systemic condition in PB cases causes a risk for periodontal disease. Evaluation of the Hypothesis: The fact that in PB cases the changes in steroid hormone levels might increase the incidence and severity of periodontal disease as in pregnancy, or there could be a common risk factor that may cause both cases, has not been revealed yet and should be taken into consideration.

Action mechanisms of transcranial direct current stimulation in Alzheimer´s disease and memory loss

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Niels eHansen

2012-05-01

Full Text Available The pharmacological treatment of Alzheimer´s disease (AD is often limited and accompanied by drug side effects. Thus alternative therapeutic strategies such as non-invasive brain stimulation are needed. Few studies have demonstrated that transcranial direct current stimulation (tDCS, a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilitation in depressive patients, Parkinson´s disease and stroke. TDCS improves working and visual recognition memory in humans and object-recognition learning in the elderly. Neurobiological mechanisms of AD comprise changes in neuronal activity and the cerebral blood flow caused by altered microvasculature, synaptic dysregulation from ß-amyloid peptide accumulation, altered neuromodulation by degeneration of modulatory amine transmitter systems, altered brain oscillations, and changes in network connectivity. tDCS alters (i neuronal activity and (ii human cerebral blood flow, (iii has synaptic and non-synaptic after-effects (iv, can modify neurotransmitters polarity-dependently, (v and alter oscillatory brain activity and (vi functional connectivity patterns in the brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it improves cognitive function in manner based on a disease mechanism. Moreover, it might prove valuable in other types of dementia. Future large-scale clinical and mechanism-oriented studies may enable to identify its therapeutic validity in other types of demential disorders.

Molecular Mechanisms of Insulin Resistance in Chronic Kidney Disease

Science.gov (United States)

Thomas, Sandhya S.; Zhang, Liping; Mitch, William E.

2015-01-01

Insulin resistance refers to reduced sensitivity of organs to insulin-initiated biologic processes that result in metabolic defects. Insulin resistance is common in patients with end-stage renal disease but also occurs in patients with chronic kidney disease (CKD), even when the serum creatinine is minimally increased. Following insulin binding to its receptor, auto-phosphorylation of the insulin receptor is followed by kinase reactions that phosphorylate insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt. In fact, low levels of Akt phosphorylation (p-Akt) identifies the presence of the insulin resistance that leads to metabolic defects in insulin-initiated metabolism of glucose, lipids and muscle proteins. Besides CKD, other complex conditions (e.g., inflammation, oxidative stress, metabolic acidosis, aging and excess angiotensin II) reduce p-Akt resulting in insulin resistance. Insulin resistance in each of these conditions is due to activation of different, E3 ubiquitin ligases which specifically conjugate ubiquitin to IRS-1 marking it for degradation in the ubiquitin-proteasome system (UPS). Consequently, IRS-1 degradation suppresses insulin-induced intracellular signaling, causing insulin resistance. Understanding mechanisms of insulin resistance could lead to therapeutic strategies that improve the metabolism of patients with CKD. PMID:26444029

The synthesis, structure-toxicity relationship of cisplatin derivatives for the mechanism research of cisplatin-induced nephrotoxicity.

Science.gov (United States)

Hu, Jing; Wu, Tian-Ming; Li, Hong-Ze; Zuo, Ze-Ping; Zhao, Ying-Lan; Yang, Li

2017-08-01

Cisplatin is a widely used antineoplastic drug, while its nephrotoxicity limits the clinical application. Although several mechanisms contributing to nephrotoxicity have been reported, the direct protein targets are unclear. Herein we reported the synthesis of 29 cisplatin derivatives and the structure-toxicity relationship (STR) of these compounds with MTT assay in human renal proximal tubule cells (HK-2) and pig kidney epithelial cells (LLC-PK1). To the best of our knowledge, this study represented the first report regarding the structure-toxicity relationship (STR) of cisplatin derivatives. The potency of biotin-pyridine conjugated derivative 3 met the requirement for target identification, and the preliminary chemical proteomics results suggested that it is a promising tool for further target identification of cisplatin-induced nephrotoxicity. Copyright © 2017. Published by Elsevier Ltd.

Contribution of Neuroepigenetics to Huntington's Disease.

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Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine

2017-01-01

Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process.

Ubiquitination in Periodontal Disease: A Review.

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Tsuchida, Sachio; Satoh, Mamoru; Takiwaki, Masaki; Nomura, Fumio

2017-07-10

Periodontal disease (periodontitis) is a chronic inflammatory condition initiated by microbial infection that leads to gingival tissue destruction and alveolar bone resorption. The periodontal tissue's response to dental plaque is characterized by the accumulation of polymorphonuclear leukocytes, macrophages, and lymphocytes, all of which release inflammatory mediators and cytokines to orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is achieved by a mechanism that involves a number of factors, including an ubiquitin-activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin-protein ligase. Ubiquitination is a post-translational modification restricted to eukaryotes that are involved in essential host processes. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Increasing numbers of recent reports have provided evidence that many approaches are delivering promising reports for discovering the relationship between ubiquitination and periodontal disease. The scope of this review was to investigate recent progress in the discovery of ubiquitinated protein in diseased periodontium and to discuss the ubiquitination process in periodontal diseases.

Knowledge of medical doctors in Turkey about the relationship between periodontal disease and systemic health

OpenAIRE

TAŞDEMIR,Zekeriya; ALKAN,Banu Arzu

2015-01-01

Understanding the relationship between periodontal disease (PD) and systemic health (SH) is necessary for the accurate diagnosis and treatment of both. The aim of this study was to evaluate the knowledge of medical doctors in Turkey with regard to the association between PD and SH. This study was carried out using self-reported questionnaires that were sent to medical doctors who work at various universities and public and private hospitals in different cities in Turkey. The questionnaires co...

The mechanism of anemia in 4 patients with Hodgkin's disease: a study simultaneously using radioiron and radiochromium

International Nuclear Information System (INIS)

Ditu Mpandamadi

1981-01-01

To investigate the mechanism of anemias during the course of Hodgkin's disease, a study utilizing blood labeled simultaneously with radioiron (Fe 59 ) and radiochromium (Cr 51 ) was undertaken in 4 patients: 1 male and 3 females 18, 18, 29, 33 years old. The results obtained in this study were compared with those of the relevant literature. It is concluded that the mechanism of anemias, in patients suffering from Hodgkin's disease, combines and increased rate of red cell destruction with abnormalities of iron metabolism. This investigation shows the interest of evaluating the pathogenesis of anemias with an isotope technique simultaneously utilizing Fe 59 and Cr 51

Quality of life in people with Parkinson's disease: the relevance of social relationships and communication.

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Takahashi, Kayoko; Kamide, Naoto; Suzuki, Makoto; Fukuda, Michinari

2016-01-01

[Purpose] Maintaining high quality of life is crucial for the rehabilitation of patients with Parkinson's disease. The quality of life scales currently in use do not assess all quality of life domains or their importance for each individual. Therefore, a new quality of life measure, the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting, was used to investigate quality of life in people with Parkinson's disease. [Subjects and Methods] Fifteen people with idiopathic Parkinson's disaese (average age = 80.0 years, standard deviation = 10.3 years, Hoehn & Yahr stages 1-4) were interviewed using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting. Its quality of life constructs were tested by comparing them against disease-specific quality of life (39-items Parkinson's Disease Questionnaire), motor functioning (Unified Parkinson's Disease Rating Scale Part III), and activities of daily living (Barthel Index). [Results] Social connections such as "family" and "friends" were revealed as important constructs of life satisfaction. The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting was not significantly correlated with the 39-items Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale Part III, or Barthel Index but was significantly correlated with the "communication" dimension of the 39-items Parkinson's Disease Questionnaire. [Conclusion] The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting detected various domains of quality of life, especially social relationships with family and friends. "Being heard" was also revealed as an essential component of life satisfaction, as it provides patients with a feeling of acceptance and assurance, possibly resulting in better quality of life.

Mechanical Energy Recovery during Walking in Patients with Parkinson Disease.

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Mariangela Dipaola

Full Text Available The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD. The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64±9 years with bilateral symptoms (H&Y ≥II if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs. Ten healthy subjects (mean age 62±3 years walked both at their 'preferred' and 'slow' speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM of hip, knee and ankle joint angles. We also measured kinetic (Wk, potential (Wp, total (WtotCM energy variations and the energy recovery index (ER. Along with PD progression, we found a significant correlation of WtotCM and Wp with knee ROM and in particular with knee extension in terminal stance phase. Wk and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both Wp and WtotCM. Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait-related energetic components.

Relationships between Mechanical Variables in the Traditional and Close-Grip Bench Press.

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Lockie, Robert G; Callaghan, Samuel J; Moreno, Matthew R; Risso, Fabrice G; Liu, Tricia M; Stage, Alyssa A; Birmingham-Babauta, Samantha A; Stokes, John J; Giuliano, Dominic V; Lazar, Adrina; Davis, DeShaun L; Orjalo, Ashley J

2017-12-01

The study aim was to determine relationships between mechanical variables in the one-repetition maximum (1RM) traditional bench press (TBP) and close-grip bench press (CGBP). Twenty resistance-trained men completed a TBP and CGBP 1RM. The TBP was performed with the preferred grip; the CGBP with a grip width of 95% biacromial distance. A linear position transducer measured: lift distance and duration; work; and peak and mean power, velocity, and force. Paired samples t-tests (p velocity was greater for the CGBP (d = 0.50-1.29). The 1RM TBP correlated with CGBP 1RM, power, and force (r = 0.685-0.982). TBP work correlated with CGBP 1RM, lift distance, power, force, and work (r = 0.542-0.931). TBP power correlated with CGBP 1RM, power, force, velocity, and work (r = 0.484-0.704). TBP peak and mean force related to CGBP 1RM, power, and force (r = 0.596-0.980). Due to relationships between the load, work, power, and force for the TBP and CGBP, the CGBP could provide similar strength adaptations to the TBP with long-term use. The velocity profile for the CGBP was different to that of the TBP. The CGBP could be used specifically to improve high-velocity, upper-body pushing movements.

Estrogen-related and other disease diagnoses preceding Parkinson's disease

DEFF Research Database (Denmark)

Latourelle, Jeanne C; Dybdal, Merete; Destefano, Anita L

2010-01-01

Estrogen exposure has been associated with the occurrence of Parkinson's disease (PD), as well as many other disorders, and yet the mechanisms underlying these relations are often unknown. While it is likely that estrogen exposure modifies the risk of various diseases through many different...... mechanisms, some estrogen-related disease processes might work in similar manners and result in association between the diseases. Indeed, the association between diseases need not be due only to estrogen-related factors, but due to similar disease processes from a variety of mechanisms....

The longitudinal relationship between mental health disorders and chronic disease for older adults: a population-based study.

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Chen, Chun-Min; Lee, I-Chen; Su, Yung-Yu; Mullan, Judy; Chiu, Herng-Chia

2017-09-01

Although mental health disorders in older adults are common, their relationship with chronic disease and the influence of chronic disease on the development of mental health disorders over time is not well understood. This longitudinal study investigated the change in status of mental health disorders and chronic disease, as well as their interrelationships, over time. Participants included community-dwelling older adults living in Taiwan, aged 65 years or older, who completed six waves of survey interviews. Mental health disorders were scored using the Short Psychiatric Evaluation Schedule, and chronic disease(s) status was recorded during consecutive biennial data collection waves. The autoregressive latent trajectory model and parallel latent growth curve model were used for data analysis. The study findings suggest that in older people pre-existing mental health disorders and/or chronic disease(s) will predispose them to developing significantly more mental health disorders and/or chronic diseases respectively. The study findings also suggest that pre-existing mental health disorders can significantly contribute to the development of chronic disease over time, and that pre-existing chronic disease(s) significantly can contribute to the development of mental health disorders over time, indicating a reciprocal interrelationship. Our study findings suggest that it in addition to monitoring and treating chronic disease(s) in older people, it is also important to monitor and treat their mental health disorders. Doing so will result in overall better health outcomes and will facilitate a better quality of life as they age. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The independent relationship between triglycerides and coronary heart disease.

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Morrison, Alan; Hokanson, John E

2009-01-01

The aim was to review epidemiologic studies to reassess whether serum levels of triglycerides should be considered independently of high-density lipoprotein-cholesterol (HDL-C) as a predictor of coronary heart disease (CHD). We systematically reviewed population-based cohort studies in which baseline serum levels of triglycerides and HDL-C were included as explanatory variables in multivariate analyses with the development of CHD (coronary events or coronary death) as dependent variable. A total of 32 unique reports describing 38 cohorts were included. The independent association between elevated triglycerides and risk of CHD was statistically significant in 16 of 30 populations without pre-existing CHD. Among populations with diabetes mellitus or pre-existing CHD, or the elderly, triglycerides were not significantly independently associated with CHD in any of 8 cohorts. Triglycerides and HDL-C were mutually exclusive predictors of coronary events in 12 of 20 analyses of patients without pre-existing CHD. Epidemiologic studies provide evidence of an association between triglycerides and the development of primary CHD independently of HDL-C. Evidence of an inverse relationship between triglycerides and HDL-C suggests that both should be considered in CHD risk estimation and as targets for intervention.

Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease.

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Kanatsu, Kunihiko; Tomita, Taisuke

2017-01-01

Alzheimer disease (AD) is a neurodegenerative disease characterized by the extensive deposition of senile plaques and neurofibrillary tangles. Until recently, only the APOE gene had been known as a genetic risk factor for late-onset AD (LOAD), which accounts for more than 95% of all AD cases. However, in addition to this well-established genetic risk factor, genome-wide association studies have identified several single nucleotide polymorphisms as genetic risk factors of LOAD, such as PICALM and BIN1 . In addition, whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, including TREM2 . We review the recent findings related to the molecular mechanisms by which these genetic risk factors contribute to AD, and our perspectives regarding the etiology of AD for the development of therapeutic agents.

Using a Treat-to-Target Management Strategy to Improve the Doctor-Patient Relationship in Inflammatory Bowel Disease.

Science.gov (United States)

Rubin, David T; Krugliak Cleveland, Noa

2015-09-01

The doctor-patient relationship (DPR) in inflammatory bowel disease (IBD) has been facing new challenges, in part due to the substantial progress in medical and surgical management and also due to the rapid expansion of patient access to medical information. Not surprisingly, the complexity of IBD care and heterogeneity of the disease types may lead to conflict between a physician's therapeutic recommendations and the patient's wishes. In this commentary, we propose that the so-called "treat-to-target" approach of objective targets of disease control and serial adjustments to therapies can also strengthen the DPR in IBD by enabling defined trials of alternative approaches, followed by a more objective assessment and reconsideration of treatments. We contend that such respect for patient autonomy and the use of objective markers of disease activity improves the DPR by fostering trust and both engaging and empowering patients and physicians with the information necessary to make shared decisions about therapies.

Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies

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Jean-Paul Lasserre

2015-06-01

Full Text Available Mitochondrial diseases are severe and largely untreatable. Owing to the many essential processes carried out by mitochondria and the complex cellular systems that support these processes, these diseases are diverse, pleiotropic, and challenging to study. Much of our current understanding of mitochondrial function and dysfunction comes from studies in the baker's yeast Saccharomyces cerevisiae. Because of its good fermenting capacity, S. cerevisiae can survive mutations that inactivate oxidative phosphorylation, has the ability to tolerate the complete loss of mitochondrial DNA (a property referred to as ‘petite-positivity’, and is amenable to mitochondrial and nuclear genome manipulation. These attributes make it an excellent model system for studying and resolving the molecular basis of numerous mitochondrial diseases. Here, we review the invaluable insights this model organism has yielded about diseases caused by mitochondrial dysfunction, which ranges from primary defects in oxidative phosphorylation to metabolic disorders, as well as dysfunctions in maintaining the genome or in the dynamics of mitochondria. Owing to the high level of functional conservation between yeast and human mitochondrial genes, several yeast species have been instrumental in revealing the molecular mechanisms of pathogenic human mitochondrial gene mutations. Importantly, such insights have pointed to potential therapeutic targets, as have genetic and chemical screens using yeast.

The relationship between mean platelet volume and neutrophil/lymphocyte ratio with inflammation and proteinuria in chronic kidney disease

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Gulay Yilmaz

2017-01-01

Full Text Available Atherosclerosis, which develops as a result of inflammation, is the most important cause of morbidity and mortality in chronic kidney disease (CKD. In this study, we investigated the relationship of mean platelet volume (MPV and neutrophil/lymphocyte ratio (NLR with inflammation and proteinuria in patients with CKD Stage 3-4. Healthy individuals who applied to nephrology clinic for checkup purposes acted as controls. Fifty-three patients and 30 healthy controls were included in the study. Patients with diabetes mellitus, active infection, malignancy, and coronary artery disease were excluded from the study. Biochemistry values and hemograms were recorded for all patients and for control group. NLR was calculated. The relationship between MPV/NLR and protein, fibrinogen, and proteinuria was evaluated. Our study showed a statistically significant difference between CKD group and healthy control (HC group in uric acid, fibrinogen, C-reactive protein, and NLR values (P <0.01, P <0.01, P = 0.01, P <0.01, respectively. No statistically significant difference was found between CKD and HC groups for MPV (P = 0.307. Correlation analysis revealed a statistically significant relationship between NLR and creatinine (P <0.00, r = 0.571, uric acid (P <0.00, r = 0.436, glomerular filtration rate (P <0.00, r = −0.418, 24 h urine protein (P = 0.004, r = 0.311, and 24 h urine microalbumin (P = 0.001, r = 0.354. A statistically significant relationship was detected between MPV and platelet count (P <0.001, r = −0.422, age (P = 0.004, r = −0.312, uric acid (P = 0.04, r = −0.226, and fibrinogen (P = 0.023, r = −0.249. Whereas, a statistically significant relationship was detected between NLR and microalbuminuria/proteinuria, there was no statistically significant relationship between MPV and microalbuminuria/proteinuria. Our study showed that the NLR is high in CKD group and is correlated with uric acid and proteinuria, which are known to be associated

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

DEFF Research Database (Denmark)

Louveau, Antoine; Plog, Benjamin A; Antila, Salli

2017-01-01

to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege...... and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems....

Mechanisms of body weight fluctuations in Parkinson’s disease

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Andrea eKistner

2014-06-01

Full Text Available Typical body weight changes are known to occur in PD. Weight loss has been reported in early stages as well as in advanced disease and malnutrition may worsen the clinical state of the patient. On the other hand an increasing number of patients show weight gain under dopamine replacement therapy or after surgery. These weight changes are multifactorial and involve changes in energy expenditure, perturbation of homeostatic control, and eating behavior modulated by dopaminergic treatment. Comprehension of the different mechanisms contributing to body weight is a prerequisite for the management of body weight and nutritional state of an individual PD patient. This review summarizes the present knowledge and highlights the necessity of evaluation of body weight and related factors, as eating behavior, energy intake and expenditure in PD.

PERCEPTIONS OF CLOSE AND GROUP RELATIONSHIPS MEDIATE THE RELATIONSHIP BETWEEN ANXIETY AND DEPRESSION OVER A DECADE LATER.

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Jacobson, Nicholas C; Newman, Michelle G

2016-01-01

Previous research has demonstrated that anxiety reliably predicts later depression, but little has been uncovered about the mechanism underlying this connection. Interpersonal relationships appear to be a viable mechanism of the association as anxiety has been shown to predict later deficits in both close (e.g., "best friendships") and group relationships (e.g., classroom peer groups), and deficits in both close and group relationships have been linked to later depressive symptoms. The current study examined close and group relationships as potential mediators between anxiety and depression 12-14 years later. In a nationally representative sample of adolescents (N = 6,504), anxiety was measured at baseline, perceptions of close relationships (i.e., feeling loved) and perceptions of group relationships (i.e., feeling part of a group) were measured 6 months later, and depression levels and diagnosis were measured 12-14 years later. Using structural equation models, the results showed that adolescent perceptions of both close and group relationships significantly mediated the relationship between adolescent anxiety and adult levels of depression. Furthermore, perceptions of not being accepted/loved in close relationships significantly mediated the relationship between adolescent anxiety and clinical depression in adulthood. These results suggest that a perception of not being accepted in group relationships may be a mechanism by which heightened anxiety in adolescents leads to heightened nonclinical depression in adulthood. On the other hand, adolescent perceptions of not feeling loved or accepted in close relationships may be a mechanism by which heightened anxiety in adolescence leads to clinical depression--in adulthood. © 2015 Wiley Periodicals, Inc.

Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease.

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Guo, Rui; Liong, Emily C; So, Kwok Fai; Fung, Man-Lung; Tipoe, George L

2015-04-01

Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneficial effects of aerobic exercise on NAFLD. We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing intrahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptor gamma expression levels; (ii) decreasing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inflammation via the inhibition of pro-inflammatory mediators such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. Aerobic exercise, via different mechanisms, significantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

The temporal relationship between reduction of early imitative responses and the development of attention mechanisms

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Benga Oana

2003-12-01

Full Text Available Abstract Background To determine whether early imitative responses fade out following the maturation of attentional mechanisms, the relationship between primitive imitation behaviors and the development of attention was examined in 4-month-old infants. They were divided into high and low imitators, based on an index of imitation. The status of attention was assessed by studying inhibition of return (IOR. Nine-month-old infants were also tested to confirm the hypothesis. Results The IOR latency data replicate previous results that infants get faster to produce a covert shift of attention with increasing age. However, those 4-month-olds who showed less imitation had more rapid saccades to the cue before target presentation. Conclusion The cortical control of saccade planning appears to be related to an apparent drop in early imitation. We interpret the results as suggesting a relationship between the status of imitation and the neural development of attention-related eye movement.

Understanding gene functions and disease mechanisms

DEFF Research Database (Denmark)

Fuchs, Helmut; Aguilar-Pimentel, Juan Antonio; Amarie, Oana V.

2018-01-01

Since decades, model organisms have provided an important approach for understanding the mechanistic basis of human diseases. The German Mouse Clinic (GMC) was the first phenotyping facility that established a collaboration-based platform for phenotype characterization of mouse lines. In order...... to address individual projects by a tailor-made phenotyping strategy, the GMC advanced in developing a series of pipelines with tests for the analysis of specific disease areas. For a general broad analysis, there is a screening pipeline that covers the key parameters for the most relevant disease areas...