Measures of rheumatoid arthritis disease activity in Australian clinical practice.

PubMed

Taylor, Andrew; Bagga, Hanish

2011-01-01

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

Correlation between Epstein-Barr Virus Infection and Disease Activity of Systemic Lupus Erythematosus: a Cross-Sectional Study

PubMed

Piroozmand, Ahmad; Haddad Kashani, Hamed; Zamani, Batool

2017-02-01

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease for whose pathogenesis viral infections are important. The Epstein-Barr virus (EBV) is the main infectious etiological agent. This study aimed to quantitative evaluation of EBV in SLE patients. Materials and Methods: In this cross-sectional study, 40 patients with SLE diagnosed based on American College of Rheumatology criteria were selected using purposive sampling. All were included in the study after obtaining informed consent for participation. Whole blood samples were taken and buffy coat preparations were isolated to determine viral load using the real-time polymerase chain reaction method and assessment with the SLE disease activity index (SLE-DAI). Results: From a total of 40 patients, 37 cases (92.5%) were women. The EBV test was positive in 67.5% and mean viral load was 5396 ± 1891.9 copy/ml. Twenty of forty patients had active and 50% inactive disease, mean EBV viral loads being 6798 and 28.25 copy/ml, respectively (P-value = 0.003). In terms of the severity of disease activity, 17.5 % of female patients had mild to moderate activity, whilst 32.5% of them had severe activity, with respective viral loads of 5,803.3 and 29.73 copy/ml (P-value = 0.003). Conclusion: The Epstein-Barr viral load in SLE patients with active disease was found to be markedly higher than in inactive cases. Thus, EBV may have an important role in the pathogenesis and activity of SLE. Creative Commons Attribution License

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

PubMed Central

2012-01-01

Introduction The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA. Methods This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity. Conclusions This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity. PMID:23259466

Novel Ultrasound Joint Selection Methods Using a Reduced Joint Number Demonstrate Inflammatory Improvement when Compared to Existing Methods and Disease Activity Score at 28 Joints.

PubMed

Tan, York Kiat; Allen, John C; Lye, Weng Kit; Conaghan, Philip G; D'Agostino, Maria Antonietta; Chew, Li-Ching; Thumboo, Julian

2016-01-01

A pilot study testing novel ultrasound (US) joint-selection methods in rheumatoid arthritis. Responsiveness of novel [individualized US (IUS) and individualized composite US (ICUS)] methods were compared with existing US methods and the Disease Activity Score at 28 joints (DAS28) for 12 patients followed for 3 months. IUS selected up to 7 and 12 most ultrasonographically inflamed joints, while ICUS additionally incorporated clinically symptomatic joints. The existing, IUS, and ICUS methods' standardized response means were -0.39, -1.08, and -1.11, respectively, for 7 joints; -0.49, -1.00, and -1.16, respectively, for 12 joints; and -0.94 for DAS28. Novel methods effectively demonstrate inflammatory improvement when compared with existing methods and DAS28.

Association of diabetic peripheral arterial disease and objectively-measured physical activity: NHANES 2003-2004

PubMed Central

2014-01-01

Background Although much is known about the management of peripheral arterial disease among adults in the general population, the management of this disease among those with diabetes, and the effects of diabetic-induced peripheral arterial disease on objectively-measured physical activity, is unclear. Here, we examined the association between accelerometer-assessed physical activity and peripheral arterial disease among a national sample of U.S. adults with diabetes. Methods Data from the 2003–2004 National Health and Nutrition Examination Survey were used. Physical activity was measured using an accelerometer in 254 adults with diabetes. Peripheral arterial disease was assessed via ankle brachial index. Negative binomial regression analysis was used to examine the association between physical activity and peripheral arterial disease. Results Results were adjusted for age, gender, race-ethnicity, comorbidity index, smoking, HgbA1C, C-reactive protein, homocysteine, glomerular filtration rate, microalbuminuria, peripheral neuropathy, physical functioning, and medication use. After adjustments, participants with peripheral arterial disease engaged in 23% less physical activity (RR = 0.77, 95% CI: 0.62-0.96) than those without peripheral arterial disease. Conclusions These findings demonstrate an inverse association between accelerometer-assessed physical activity and peripheral arterial disease in a national sample of U.S adults with diabetes. PMID:24967220

Nutritional status in patients with active inflammatory bowel disease: prevalence of malnutrition and methods for routine nutritional assessment.

PubMed

Mijac, Dragana D; Janković, Goran L J; Jorga, Jagoda; Krstić, Miodrag N

2010-08-01

Malnutrition is a common feature of inflammatory bowel disease (IBD). There are numerous methods for the assessment of nutritional status, but the gold standard has not yet been established. The aims of the study were to estimate the prevalence of undernutrition and to evaluate methods for routine nutritional assessment of active IBD patients. Twenty-three patients with active Crohn disease, 53 patients with active ulcerative colitis and 30 controls were included in the study. The nutritional status was assessed by extensive anthropometric measurements, percentage of weight loss in the past 1-6 months and biochemical markers of nutrition. All investigated nutritional parameters were significantly different in IBD patients compared to control subjects, except MCV, tryglicerides and serum total protein level. Serum albumin level and body mass index (BMI) were the most predictive parameters of malnutrition. According to different assessment methods the prevalence of undernutrition and severe undernutrition in patients with active IBD were 25.0%-69.7% and 1.3%-31.6%, respectively, while in the control subjects no abnormalities have been detected. There was no statistically significant difference of nutritional parameters between UC and CD patients except lower mid-arm muscle circumference in UC group. Malnutrition is common in IBD patients. BMI and serum albumin are simple and convenient methods for the assessment of the nutritional status in IBD patients. Further studies with larger group of patients are necessary to elucidate the prevalence of malnutrition and the most accurate assessment methods in IBD patients.

NF-kappa B activation correlates with disease phenotype in Crohn’s disease

PubMed Central

Han, Yoo Min; Koh, Jaemoon; Lee, Changhyun; Koh, Seong-Joon; Kim, ByeongGwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung

2017-01-01

Background/Aims Unregulated activation of nuclear factor-κB (NF-κB) plays a critical role in the pathogenesis of Crohn’s disease. In this study, we investigated the clinical characteristics and disease outcome of Crohn’s disease patients with varying levels of the NF-κB activation. Methods Crohn’s disease patients who underwent surgical bowel resection were divided into two groups, based on the activation status of NF-κB. NF-κB activation was assessed by the immunoreactivity of nuclear NF-κB during immunohistochemical staining of bowel resection specimens. We compared the demographic, clinical and histologic characteristics between groups. Furthermore, the occurrence of reoperation, readmission, and medication change due to disease flare-up were investigated according to NF-κB activation status. Results Among 83 Crohn’s disease patients, 47 (56%) showed high NF-κB activity and 36 (44%) showed low NF-κB activity. Patients with high NF-κB activity had higher frequency of ileocolonic involvement (P = 0.028) and lower frequency of perianal involvement (P = 0.042) relative to those with low NF-κB activity. Total histologic scores were significantly higher in patients with high NF-κB activity than those with low NF-κB activity (P = 0.044). There was no significant difference in the frequency of reoperation, readmission, and medication change in relation to NF-κB activation status. Conclusions Crohn’s disease patients with high NF-κB activation showed specific clinical manifestations of higher frequency of ileocolonic involvement and lower frequency of perianal involvement relative to those with low NF-κB activation. High NF-κB activity was associated with higher histologic scores. However, the NF-κB activity did not affect the outcome and disease course after surgery. PMID:28753650

Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid

PubMed Central

Lee, Eui Hyung; Kim, Yeon Hee; Kim, Sinyoung; Kim, Song-ee

2012-01-01

Background Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease associated with autoantibodies against BP180 and BP230. Enzyme-linked immunosorbent assay (ELISA) is a sensitive tool for the detection of immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies. Objective The aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP. Methods We evaluated serum IgG levels of anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through retrospective review of the medical records, the clinical characteristics of BP including disease activity, duration, pruritus severity and peripheral blood eosinophil counts were assessed. Results The sensitivity of BP180 ELISA was 97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was 90.3%. BP180 ELISA scores showed strong associations with disease activity, pruritus severity, peripheral blood eosinophil counts, and disease duration, whereas BP230 ELISA scores did not. Conclusion BP180 and BP230 ELISAs are highly sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a sensitive tool for monitoring the disease activity of BP. PMID:22363155

Long-term health benefits of physical activity – a systematic review of longitudinal studies

PubMed Central

2013-01-01

Background The treatment of noncommunicable diseases (NCD), like coronary heart disease or type 2 diabetes mellitus, causes rising costs for the health system. Physical activity is supposed to reduce the risk for these diseases. Results of cross-sectional studies showed that physical activity is associated with better health, and that physical activity could prevent the development of these diseases. The purpose of this review is to summarize existing evidence for the long-term (>5 years) relationship between physical activity and weight gain, obesity, coronary heart disease, type 2 diabetes mellitus, Alzheimer’s disease and dementia. Methods Fifteen longitudinal studies with at least 5-year follow up times and a total of 288,724 subjects (>500 participants in each study), aged between 18 and 85 years, were identified using digital databases. Only studies published in English, about healthy adults at baseline, intentional physical activity and the listed NCDs were included. Results The results of these studies show that physical activity appears to have a positive long-term influence on all selected diseases. Conclusions This review revealed a paucity of long-term studies on the relationship between physical activity and the incidence of NCD. PMID:24010994

Fast detection of peroxidase (POD) activity in tomato leaves which infected with Botrytis cinerea using hyperspectral imaging

NASA Astrophysics Data System (ADS)

Kong, Wenwen; Liu, Fei; Zhang, Chu; Bao, Yidan; Yu, Jiajia; He, Yong

2014-01-01

Tomatoes are cultivated around the world and gray mold is one of its most prominent and destructive diseases. An early disease detection method can decrease losses caused by plant diseases and prevent the spread of diseases. The activity of peroxidase (POD) is very important indicator of disease stress for plants. The objective of this study is to examine the possibility of fast detection of POD activity in tomato leaves which infected with Botrytis cinerea using hyperspectral imaging data. Five pre-treatment methods were investigated. Genetic algorithm-partial least squares (GA-PLS) was applied to select optimal wavelengths. A new fast learning neural algorithm named extreme learning machine (ELM) was employed as multivariate analytical tool in this study. 21 optimal wavelengths were selected by GA-PLS and used as inputs of three calibration models. The optimal prediction result was achieved by ELM model with selected wavelengths, and the r and RMSEP in validation were 0.8647 and 465.9880 respectively. The results indicated that hyperspectral imaging could be considered as a valuable tool for POD activity prediction. The selected wavelengths could be potential resources for instrument development.

Point of Care- A Novel Approach to Periodontal Diagnosis-A Review

PubMed Central

Nayak, Prathibha Anand; Rana, Shivendra

2017-01-01

Periodontal disease, one of the prevalent oral diseases, is characterized by gingival inflammation and periodontal tissue destruction. Diagnosing this disease is challenging to the clinicians as the disease process is discontinuous and shows periods of exacerbation and remission. Traditional diagnostic methods basically tells about the past tissue destruction so new diagnostic methods are required which is able to detect the active state of the disease, determine the future progression and also estimates the response to the therapy, thereby helping in the better clinical management of the patient. Both saliva and Gingival crevicular fluid (GCF) are believed to be reliable medium to detect the biomarkers which plays a pivotal role in measuring the disease activity. Keeping these observations in mind rapid chairside tests are developed to diagnose periodontal disease called as Point of Care (POC) diagnostics which simplifies diagnosis and helps in improving the prognosis. This review article highlights about the biomarkers used in the diagnosis and throws light on the various available point of care diagnostic devices. PMID:28969294

A sensitive and reproducible fluorescent-based HPLC assay to measure the activity of acid as well as neutral beta-glucocerebrosidases.

PubMed

Hayashi, Yasuhiro; Zama, Kouta; Abe, Eriko; Okino, Nozomu; Inoue, Takehiko; Ohno, Kousaku; Ito, Makoto

2008-12-01

The activity of lysosomal acid beta-glucocerebrosidase (AGC, EC 3.2.1.45), which hydrolyzes the O-glycosidic linkage between D-glucose and ceramide of glucosylceramide (GlcCer), is a marker for the diagnosis of Gaucher disease because the disease is caused by dysfunction of AGC due to mutations in the gene. The activity of AGC is potently inhibited by conduritol B epoxide (CBE), whereas CBE-insensitive nonlysosomal neutral beta-glucocerebrosidase (NGC) activities have been found in various vertebrates, including humans. We report here a new reliable method to determine AGC as well as NGC activities using normal-phase high-performance liquid chromatography (HPLC) and NBD (4-nitrobenzo-2-oxa-1,3-diazole)- or BODIPY (4,4-difluoro-4-boro-3a,4a-diaza-s-indacene)-labeled GlcCer as a substrate. The reaction products of the enzymes, C6-NBD-ceramide and C12-BODIPY-ceramide, were clearly separated from the corresponding substrates on a normal-phase column within 5 min using a different solvent system. Reaction products could be detected quantitatively at concentrations ranging from 50 fmol to 50 pmol for C6-NBD-ceramide and from 10 fmol to 5 pmol for C12-BODIPY-ceramide. V(max)/K(m) values of human fibroblast AGC for fluorescent GlcCer were much higher than those for 4-methylumbelliferyl-beta-d-glucoside (4MU-Glc), which is used prevalently for Gaucher disease diagnosis. As a result, AGC activity was detected quantitatively using fluorescent GlcCer, but not 4MU-Glc, using 5 microl of human serum or 1 x 10(4) cultured human fibroblasts. The current method clearly showed the decrease of AGC activities in fibroblasts and serum from the patient with Gaucher disease compared with normal individuals, suggesting that the method is applicable for the diagnosis of Gaucher disease. Furthermore, this method was found to be useful for measuring the activities of nonlysosomal NGC of various cells and tissues in the presence of CBE.

Nailfold capillaroscopy in children and adolescents with rheumatic diseases.

PubMed

Piotto, Daniela Gerent Petry; Len, Cláudio Arnaldo; Hilário, Maria Odete Esteves; Terreri, Maria Teresa Ramos Ascensão

2012-10-01

To assess nailfold capillaroscopy in children and adolescents with autoimmune rheumatic diseases (juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma and mixed connective tissue disease) and relate it to clinical and laboratory findings and disease activity. Cross-sectional study assessing 147 patients by use of nailfold capillaroscopy as follows: 60 with juvenile idiopathic arthritis; 30 with systemic lupus erythematosus; 30 with juvenile dermatomyositis; 20 with localized scleroderma; four with systemic sclerosis; and three with mixed connective tissue disease. Clinical and laboratory tests and nailfold capillaroscopy were performed in all patients. The nailfold capillaroscopy was performed with an optical microscope (at 10- and 16-time magnifications) by the same observer. Most patients (76.2%) had normal nailfold capillaroscopy. The major changes in nailfold capillaroscopy, characterizing the scleroderma pattern, were observed in patients with juvenile dermatomyositis, systemic scleroderma and mixed connective tissue disease. There was no association between nailfold capillaroscopy and disease activity in patients with juvenile idiopathic arthritis, systemic lupus erythematosus and localized scleroderma. Disease activity and capillaroscopy were associated in patients with juvenile dermatomyositis. Nailfold capillaroscopy is a useful method to diagnose autoimmune rheumatic diseases and monitor disease activity.

Promotion of Physical Activity of Adolescents by Skill-Based Health Education

ERIC Educational Resources Information Center

Simbar, Masoumeh; Aarabi, Zeinab; Keshavarz, Zohreh; Ramezani-Tehrani, Fahimeh; Baghestani, Ahmad Reza

2017-01-01

Purpose: Insufficient physical activity leads to an increase in chronic diseases. Skills-based health education methods are supposed to be more successful than traditional methods to promote healthy behaviors. Skills-based health education is an approach to create healthy lifestyles and skills using participatory methods. The purpose of this paper…

Physical Activity and Modernization among Bolivian Amerindians

PubMed Central

Gurven, Michael; Jaeggi, Adrian V.; Kaplan, Hillard; Cummings, Daniel

2013-01-01

Background Physical inactivity is a growing public health problem, and the fourth leading risk factor for global mortality. Conversely, indigenous populations living traditional lifestyles reportedly engage in vigorous daily activity that is protective against non-communicable diseases. Here we analyze physical activity patterns among the Tsimane, forager-horticulturalists of Amazonian Bolivia with minimal heart disease and diabetes. We assess age patterns of adult activity among men and women, test whether modernization affects activity levels, and examine whether nascent obesity is associated with reduced activity. Methods and Findings A factorial method based on a large sample of behavioral observations was employed to estimate effects of age, sex, body mass index, and modernization variables on physical activity ratio (PAR), the ratio of total energy expenditure to basal metabolic rate. Accelerometry combined with heart rate monitoring was compared to the factorial method and used for nighttime sampling. Tsimane men and women display 24 hr physical activity level (PAL) of 2.02–2.15 and 1.73–1.85, respectively. Little time was spent “sedentary”, whereas most activity was light to moderate, rather than vigorous. Activity peaks by the late twenties in men, and declines thereafter, but remains constant among women after the early teens. Neither BMI, fat free mass or body fat percentage are associated with PAR. There was no negative effect of modernization on physical activity. Conclusions Tsimane display relatively high PALs typical of other subsistence populations, but of moderate intensity, and not outside the range of developed populations. Despite rapidly increasing socioeconomic change, there is little evidence that total activity has yet been affected. Overweight and obesity are more prevalent among women than men, and Spanish fluency is associated with greater obesity in women. The lack of cardiovascular disease among Tsimane is unlikely caused by activity alone; further study of diet, food intake and infectious disease is needed. PMID:23383262

Early Disease Activity or Clinical Response as Predictors of Long‐Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis

PubMed Central

Deodhar, A.; Fleischmann, R.; Mease, P. J.; Rudwaleit, M.; Nurminen, T.; Davies, O.

2017-01-01

Objective Early identification of patients unlikely to achieve good long‐term disease control with anti–tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat‐to‐target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol. Methods The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week‐48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C‐reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID‐axSpA and RAPID‐PsA trial data. Results A clear relationship between disease activity from week 2 to 12 and achievement of week‐48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week‐48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week‐12 ASDAS inactive disease. For PsA, week‐48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28‐CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week‐48 outcomes, though to a lesser extent than disease activity. Conclusion Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long‐term treatment goals. PMID:27696727

In vivo imaging of protease activity by Probody therapeutic activation

PubMed Central

Wong, Kenneth R.; Menendez, Elizabeth; Craik, Charles S.; Kavanaugh, W. Michael; Vasiljeva, Olga

2017-01-01

Probody™ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment. PMID:26546838

Diagnostic Accuracy of CT Enterography for Active Inflammatory Terminal Ileal Crohn Disease: Comparison of Full-Dose and Half-Dose Images Reconstructed with FBP and Half-Dose Images with SAFIRE.

PubMed

Gandhi, Namita S; Baker, Mark E; Goenka, Ajit H; Bullen, Jennifer A; Obuchowski, Nancy A; Remer, Erick M; Coppa, Christopher P; Einstein, David; Feldman, Myra K; Kanmaniraja, Devaraju; Purysko, Andrei S; Vahdat, Noushin; Primak, Andrew N; Karim, Wadih; Herts, Brian R

2016-08-01

Purpose To compare the diagnostic accuracy and image quality of computed tomographic (CT) enterographic images obtained at half dose and reconstructed with filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) with those of full-dose CT enterographic images reconstructed with FBP for active inflammatory terminal or neoterminal ileal Crohn disease. Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety subjects (45 with active terminal ileal Crohn disease and 45 without Crohn disease) underwent CT enterography with a dual-source CT unit. The reference standard for confirmation of active Crohn disease was active terminal ileal Crohn disease based on ileocolonoscopy or established Crohn disease and imaging features of active terminal ileal Crohn disease. Data from both tubes were reconstructed with FBP (100% exposure); data from the primary tube (50% exposure) were reconstructed with FBP and SAFIRE strengths 3 and 4, yielding four datasets per CT enterographic examination. The mean volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) at full dose were 13.1 mGy (median, 7.36 mGy) and 15.9 mGy (median, 13.06 mGy), respectively, and those at half dose were 6.55 mGy (median, 3.68 mGy) and 7.95 mGy (median, 6.5 mGy). Images were subjectively evaluated by eight radiologists for quality and diagnostic confidence for Crohn disease. Areas under the receiver operating characteristic curves (AUCs) were estimated, and the multireader, multicase analysis of variance method was used to compare reconstruction methods on the basis of a noninferiority margin of 0.05. Results The mean AUCs with half-dose scans (FBP, 0.908; SAFIRE 3, 0.935; SAFIRE 4, 0.924) were noninferior to the mean AUC with full-dose FBP scans (0.908; P < .003). The proportion of images with inferior quality was significantly higher with all half-dose reconstructions than with full-dose FBP (mean proportion: 0.117 for half-dose FBP, 0.054 for half-dose SAFIRE 3, 0.054 for half-dose SAFIRE 4, and 0.017 for full-dose FBP; P < .001). Conclusion The diagnostic accuracy of half-dose CT enterography with FBP and SAFIRE is statistically noninferior to that of full-dose CT enterography for active inflammatory terminal ileal Crohn disease, despite an inferior subjective image quality. (©) RSNA, 2016 Online supplemental material is available for this article.

Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

PubMed Central

Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

2016-01-01

INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC. PMID:27698971

Muscle strengthening activity associates with reduced all-cause mortality in COPD.

PubMed

Loprinzi, Paul D; Sng, Eveleen; Walker, Jerome F

2017-06-01

Objective Emerging research suggests that aerobic-based physical activity may help to promote survival among chronic obstructive pulmonary disease patients. However, the extent to which engagement in resistance training on survival among chronic obstructive pulmonary disease patients is relatively unknown. Therefore, the purpose of this study was to examine the independent associations of muscle strengthening activities on all-cause mortality among a national sample of U.S. adults with chronic obstructive pulmonary disease. We hypothesize that muscle strengthening activities will be inversely associated with all-cause mortality. Methods Data from the 2003-2006 NHANES were employed, with follow-up through 2011. Aerobic-based physical activity was objectively measured via accelerometry, muscle strengthening activities engagement was assessed via self-report, and chronic obstructive pulmonary disease was assessed via physician-diagnosis. Results Analysis included 385 adults (20 + yrs) with chronic obstructive pulmonary disease, who represent 13.3 million chronic obstructive pulmonary disease patients in the USA. The median follow-up period was 78 months (IQR=64-90), with 82 chronic obstructive pulmonary disease patients dying during this period. For a two muscle strengthening activity sessions/week increase (consistent with national guidelines), chronic obstructive pulmonary disease patients had a 29% reduced risk of all-cause mortality (HR=0.71; 95% CI: 0.51-0.99; P = 0.04). Conclusion Participation in muscle strengthening activities, independent of aerobic-based physical activity and other potential confounders, is associated with greater survival among chronic obstructive pulmonary disease patients.

Clean copy association of production diseases with motor activity-sensing devices and milk progesterone concentrations in dairy cows.

PubMed

Williams, J; Ntallaris, T; Routly, J E; Jones, D N; Cameron, J; Holman-Coates, A; Smith, R F; Humblot, P; Dobson, H

2018-05-31

We have previously established that the efficiency of identifying oestrus with activity-sensing devices can be compromised by common production diseases; the present study was undertaken to determine how these diseases may affect device readings. A total of 67 Holstein-Friesian cows, >20 days postpartum, were equipped with activity-sensing neck collars and pedometers, and simultaneous milk progesterone profiles were also monitored twice a week. The influences of common production stressors on maximum activity and progesterone values were analysed. Approximately 30% potential oestrus events (low progesterone value between two high values) remained unrecognised by both activity methods, and progesterone values in these animals were higher on the potential day of oestrus when both activity methods did not detect an event (0.043 ± 0.004 versus 0.029 ± 0.004 ng/mL; P = 0.03). Data from a subset of 45 cows (two events each) were subjected to mixed models and multiple regression modelling to investigate associations with production diseases. Cow motor activity was lower in lame cows. Maximum progesterone concentrations prior to oestrus increased as time postpartum and body condition score (BCS) increased. There were also fewer days of low progesterone prior to oestrus associated with increases in BCS and maximum progesterone concentrations prior to oestrus. In conclusion, lameness was associated with lower activity values, but this suppression was insufficient to account for lowered oestrus detection efficiency of either device. However, associations were identified between production diseases and progesterone profiles. Copyright © 2018. Published by Elsevier Inc.

Intakes of Vitamin B6 and Dietary Fiber and Clinical Course of Systemic Lupus Erythematosus: A Prospective Study of Japanese Female Patients

PubMed Central

Minami, Yuko; Hirabayashi, Yasuhiko; Nagata, Chisato; Ishii, Tomonori; Harigae, Hideo; Sasaki, Takeshi

2011-01-01

Background Intakes of selected vitamins and dietary fiber may influence the clinical course of systemic lupus erythematosus (SLE). Using a cohort study method, we investigated the associations of dietary intake of vitamin B6 and B12, folate, and dietary fiber with the risk of active disease and atherosclerotic vascular events in SLE. Methods The study included female SLE patients in the Miyagi Lupus Cohort, which was founded in 1995. Dietary nutrients at baseline were estimated by a semiquantitative food frequency questionnaire. The association of each nutrient intake with the risk of active disease was investigated in 216 patients who had inactive disease at baseline. The association with atherosclerotic vascular events was assessed in 196 women who had inactive disease and no history of atherosclerotic diseases at baseline. Results Forty-three cases of active disease were identified during 9966 person-months of follow-up (1995–1999). During 19 575 person-months of follow-up (1995–2005), 20 atherosclerotic vascular events were documented. The Cox proportional hazards model revealed an inverse association between vitamin B6 intake and the risk of active disease (hazard ratio for the highest as compared with the lowest tertile, 0.41; 95% confidence interval, 0.18–0.97; P for trend = 0.04). An inverse association was also found for dietary fiber intake (P for trend = 0.01). However, no significant association was observed between intakes of these nutrients and the risk of atherosclerotic vascular events. Conclusions Higher intake of vitamin B6 and dietary fiber may prevent the occurrence of active disease in SLE. PMID:21515941

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

NASA Astrophysics Data System (ADS)

Song, Yong-Ak; Melik, Rohat; Rabie, Amr N.; Ibrahim, Ahmed M. S.; Moses, David; Tan, Ara; Han, Jongyoon; Lin, Samuel J.

2011-12-01

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.

A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

PubMed

Li, Qian; Li, Xudong; Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-03-22

Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking.

A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

PubMed Central

Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-01-01

Background Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. Methodology We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. Conclusions This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking. PMID:21445339

Total polyphenols and antioxidant activity in different species of apples grown in Georgia.

PubMed

Gogia, N; Gongadze, M; Bukia, Z; Esaiashvili, M; Chkhikvishvili, I

2014-01-01

Many studies have shown that biologically active components in plant-based foods, particularly phytochemicals, have important potential to modulate many processes in the development of diseases, including cancer, cardiovascular disease, diabetes, pulmonary disorders, Alzheimer's disease, and other degenerative diseases. The aim of the our study was to provide an updated understanding and analysis of various apple sorts growing in Georgia by the compounds with a particular focus on their potential role(s) in disease risk and general human health. The Various sorts (Kekhura, Banany, Golden, Starty, Chempion, Aidaridy, Brotsky, Achabety, Sinapy, Jonagold and Antonovka,) of apples were investigated. The total phenolic content and antioxidant activity were studied in peel and flesh extracts and were measured by slightly modified method of Folin-Denis using Folin-Ciocalteu reagent and - 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method in those varieties of apples. Summarizing our data, we can conclude that, in accordance with the benefit to human health, the most prominent varieties of apples - Kekhura. It is rich with phenolic compounds, and also characterized by high scavenging activity. Also has good features Antonovka and Achabety. It should be noted that apple peel more helpful than the flesh, and therefore during consumption peeling of apples is unacceptable in terms of its usefulness.

Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis

PubMed Central

Shen, Yijing; Ramanujan, Saroja; Knowlton, Nicholas; Swan, Kathryn A.; Turner, Mary; Sutton, Chris; Smith, Dustin R.; Haney, Douglas J.; Chernoff, David; Hesterberg, Lyndal K.; Carulli, John P.; Taylor, Peter C.; Shadick, Nancy A.; Weinblatt, Michael E.; Curtis, Jeffrey R.

2013-01-01

Background Disease activity measurement is a key component of rheumatoid arthritis (RA) management. Biomarkers that capture the complex and heterogeneous biology of RA have the potential to complement clinical disease activity assessment. Objectives To develop a multi-biomarker disease activity (MBDA) test for rheumatoid arthritis. Methods Candidate serum protein biomarkers were selected from extensive literature screens, bioinformatics databases, mRNA expression and protein microarray data. Quantitative assays were identified and optimized for measuring candidate biomarkers in RA patient sera. Biomarkers with qualifying assays were prioritized in a series of studies based on their correlations to RA clinical disease activity (e.g. the Disease Activity Score 28-C-Reactive Protein [DAS28-CRP], a validated metric commonly used in clinical trials) and their contributions to multivariate models. Prioritized biomarkers were used to train an algorithm to measure disease activity, assessed by correlation to DAS and area under the receiver operating characteristic curve for classification of low vs. moderate/high disease activity. The effect of comorbidities on the MBDA score was evaluated using linear models with adjustment for multiple hypothesis testing. Results 130 candidate biomarkers were tested in feasibility studies and 25 were selected for algorithm training. Multi-biomarker statistical models outperformed individual biomarkers at estimating disease activity. Biomarker-based scores were significantly correlated with DAS28-CRP and could discriminate patients with low vs. moderate/high clinical disease activity. Such scores were also able to track changes in DAS28-CRP and were significantly associated with both joint inflammation measured by ultrasound and damage progression measured by radiography. The final MBDA algorithm uses 12 biomarkers to generate an MBDA score between 1 and 100. No significant effects on the MBDA score were found for common comorbidities. Conclusion We followed a stepwise approach to develop a quantitative serum-based measure of RA disease activity, based on 12-biomarkers, which was consistently associated with clinical disease activity levels. PMID:23585841

Certolizumab pegol in a heterogeneous population of patients with moderate-to-severe rheumatoid arthritis

PubMed Central

Soriano, Enrique R; Dellepiane, Analia; Salvatierra, Gabriela; Benítez, Cristian Alejandro; Salinas, Rodrigo Garcia; Baruzzo, Carlos

2018-01-01

Aim: To determine the efficacy and safety of certolizumab pegol for the treatment of rheumatoid arthritis in a real-world setting. Materials & methods: Patients with moderate-to-severe rheumatoid arthritis who initiated therapy with certolizumab were followed for 12 weeks. Response was assessed with Disease Activity Score of 28 joints, European Ligue Against Rheumatism criteria and Simplified Disease Activity Index. Predictors of response were analyzed with binary logistic regression models. Results: Statistically significant decreases in tender and swollen joint counts, laboratory parameters and use of corticosteroids and disease-modifying antirheumatic drugs were found. Disease activity also significantly diminished. Higher Disease Activity Score of 28 joints at baseline was the main predictor of response. No severe adverse events were reported. Conclusion: Certolizumab was effective and well tolerated, particularly in the subpopulation with higher inflammatory burden at baseline. PMID:29682324

Activities of daily living and manual hand dexterity in persons with idiopathic parkinson disease.

PubMed

Choi, Yoo-Im; Song, Chiang-Soon; Chun, Byung-Yoon

2017-03-01

[Purpose] The purpose of this study was to evaluate the relationship between daily activities and manual dexterity in persons with Parkinson disease. [Subjects and Methods] The study participants were 25 patients with idiopathic Parkinson disease. This study used two clinical tools, the box-and-block test and Schwab and England Activities of Daily Living scale, to investigate the relationship between manual dexterity and Schwab and England Activities of Daily Living score. [Results] A positive correlation was observed between the Schwab and England Activities of Daily Living and the box-and-block test scores on the more and less affected sides. Moreover, the Schwab and England Activities of Daily Living score had a greater correlation with the box-and-block test score on the less affected side than that on the more affected side. [Conclusion] Manual dexterity and activities of daily living showed a positive correlation in individuals with Parkinson disease. The results of this study suggest that manual dexterity is an important factor for predicting physical performance in daily living in persons with Parkinson disease.

Serum Analysis of Tryptophan Catabolism Pathway: Correlation with Crohn’s Disease Activity

PubMed Central

Gupta, Nitin K; Thaker, Ameet I; Kanuri, Navya; Riehl, Terrence E; Rowley, Christopher W; Stenson, William F; Ciorba, Matthew A

2011-01-01

BACKGROUND Indoleamine 2,3 dioxygenase 1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn’s disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine. METHODS Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. Montreal classification was used for disease phenotyping. Disease severity was categorized by physician’s global assessment. Serum tryptophan and kynurenine were measured by high pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks. RESULTS 25 CD patients and 11 controls were enrolled. 8 CD patients had serum collected at two different time points and levels of disease activity. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened. CONCLUSIONS IDO1 expression in Crohn’s disease is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve a reasonable objective marker of gut mucosal immune activation and surrogate for Crohn’s Disease activity. PMID:21823214

Active learning based segmentation of Crohns disease from abdominal MRI.

PubMed

Mahapatra, Dwarikanath; Vos, Franciscus M; Buhmann, Joachim M

2016-05-01

This paper proposes a novel active learning (AL) framework, and combines it with semi supervised learning (SSL) for segmenting Crohns disease (CD) tissues from abdominal magnetic resonance (MR) images. Robust fully supervised learning (FSL) based classifiers require lots of labeled data of different disease severities. Obtaining such data is time consuming and requires considerable expertise. SSL methods use a few labeled samples, and leverage the information from many unlabeled samples to train an accurate classifier. AL queries labels of most informative samples and maximizes gain from the labeling effort. Our primary contribution is in designing a query strategy that combines novel context information with classification uncertainty and feature similarity. Combining SSL and AL gives a robust segmentation method that: (1) optimally uses few labeled samples and many unlabeled samples; and (2) requires lower training time. Experimental results show our method achieves higher segmentation accuracy than FSL methods with fewer samples and reduced training effort. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

PubMed Central

Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars; Funch-Jensen, Peter; Gregersen, Hans

2006-01-01

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy. PMID:16718803

Physical activity and modernization among Bolivian Amerindians.

PubMed

Gurven, Michael; Jaeggi, Adrian V; Kaplan, Hillard; Cummings, Daniel

2013-01-01

Physical inactivity is a growing public health problem, and the fourth leading risk factor for global mortality. Conversely, indigenous populations living traditional lifestyles reportedly engage in vigorous daily activity that is protective against non-communicable diseases. Here we analyze physical activity patterns among the Tsimane, forager-horticulturalists of Amazonian Bolivia with minimal heart disease and diabetes. We assess age patterns of adult activity among men and women, test whether modernization affects activity levels, and examine whether nascent obesity is associated with reduced activity. A factorial method based on a large sample of behavioral observations was employed to estimate effects of age, sex, body mass index, and modernization variables on physical activity ratio (PAR), the ratio of total energy expenditure to basal metabolic rate. Accelerometry combined with heart rate monitoring was compared to the factorial method and used for nighttime sampling. Tsimane men and women display 24 hr physical activity level (PAL) of 2.02-2.15 and 1.73-1.85, respectively. Little time was spent "sedentary", whereas most activity was light to moderate, rather than vigorous. Activity peaks by the late twenties in men, and declines thereafter, but remains constant among women after the early teens. Neither BMI, fat free mass or body fat percentage are associated with PAR. There was no negative effect of modernization on physical activity. Tsimane display relatively high PALs typical of other subsistence populations, but of moderate intensity, and not outside the range of developed populations. Despite rapidly increasing socioeconomic change, there is little evidence that total activity has yet been affected. Overweight and obesity are more prevalent among women than men, and Spanish fluency is associated with greater obesity in women. The lack of cardiovascular disease among Tsimane is unlikely caused by activity alone; further study of diet, food intake and infectious disease is needed.

Comparative Effectiveness Research: A Roadmap for Physical Activity and Lifestyle

PubMed Central

Jakicic, John M.; Sox, Harold; Blair, Steven N.; Bensink, Mark; Johnson, William G.; King, Abby C.; Lee, I-Min; Nahum-Shani, Inbal; Sallis, James F.; Sallis, Robert E.; Craft, Lynette; Whitehead, James R.; Ainsworth, Barbara E.

2017-01-01

Purpose Comparative Effectiveness Research (CER) is designed to support informed decision making at both the individual, population, and policy levels. The American College of Sports Medicine and partners convened a conference with the focus of building an agenda for CER within the context of physical activity and non-pharmacological lifestyle approaches in the prevention and treatment of chronic disease. This report summarizes the conference content and consensus recommendations that culminated in a CER Roadmap for Physical Activity and Lifestyle approaches to reducing the risk of chronic disease. Methods This conference focused on presentations and discussion around the following topic areas: 1) defining CER, 2) identifying the current funding climate to support CER, 3) summarizing methods for conducting CER, and 4) identifying CER opportunities for physical activity. Results This conference resulted in consensus recommendations to adopt a CER Roadmap for Physical Activity and Lifestyle approaches to reducing the risk of chronic disease. In general, this roadmap provides a systematic framework by which CER for physical activity can move from a planning phase, to a phase of engagement in CER related to lifestyle factors with particular emphasis on physical activity, to a societal change phase that results in changes in policy, practice, and health. Conclusions It is recommended that physical activity researchers and healthcare providers use the roadmap developed from this conference as a method to systematically engage in and apply CER to the promotion of physical activity as a key lifestyle behavior that can be effective at impacting a variety of health-related outcomes. PMID:25426735

[Physical activity in the prevention and treatment of diseases of affluence--the key role of AMP-activated protein kinase (AMPK)].

PubMed

Grochowska, Ewa; Jarzyna, Robert

2014-09-12

In developed countries, we can observe an increasing number of people with obesity, type 2 diabetes, dyslipidemia, hypertension and arteriosclerosis. The main reason for this phenomenon is the abnormal energy balance due to sedentary lifestyles. Cardiovascular diseases are the leading cause of death in many countries around the world, nowadays. In this paper, the impact of physical activity on the effectiveness of treatment and prevention of metabolic diseases and cancer is considered. Exercise is one of the factors activating 5'AMP-activated protein kinase (AMPK). This enzyme is crucial in maintaining the energy balance of the cell and the entire organism, and its activation results in excluding the anabolic and switching on the catabolic processes. It is believed that the activation of AMPK is responsible for most of the positive effects resulting from physical exercise. Although there are pharmacological methods of activation of this enzyme, they seem to be not as effective as physical exercise. Therefore, physical activity should be the most important form of prevention and treatment of metabolic diseases.

A Method for Multiplexed Measurement of Mitochondrial Pyruvate Carrier Activity*

PubMed Central

Gray, Lawrence R.; Rauckhorst, Adam J.; Taylor, Eric B.

2016-01-01

The discovery that the MPC1 and MPC2 genes encode the protein components of the mitochondrial pyruvate carrier (MPC) has invigorated studies of mitochondrial pyruvate transport and its regulation in normal and disease states. Indeed, recent reports have demonstrated MPC involvement in the control of cell fate in cancer and gluconeogenesis in models of type 2 diabetes. Biochemical measurements of MPC activity are foundational for understanding the role of pyruvate transport in health and disease. We developed a 96-well scaled method of [14C]pyruvate uptake that markedly decreases sample requirements and increases throughput relative to previous techniques. This method was applied to determine the mouse liver MPC Km (28.0 ± 3.9 μm) and Vmax (1.08 ± 0.05 nmol/min/mg), which have not previously been reported. Km and Vmax of the rat liver MPC were found to be 71.2 ± 17 μm and 1.42 ± 0.14 nmol/min/mg, respectively. Additionally, we performed parallel pyruvate uptake and oxidation experiments with the same biological samples and show differential results in response to fasting, demonstrating the continued importance of a direct MPC activity assay. We expect this method will be of value for understanding the contribution of the MPC activity to health and disease states where pyruvate metabolism is expected to play a prominent role. PMID:26823462

Self-assessment of Rheumatoid Arthritis Disease Activity Using a Smartphone Application. Development and 3-month Feasibility Study.

PubMed

Nishiguchi, S; Ito, H; Yamada, M; Yoshitomi, H; Furu, M; Ito, T; Shinohara, A; Ura, T; Okamoto, K; Aoyama, T; Tsuboyama, Tadao

2016-01-01

This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". Rheumatoid arthritis (RA) is a progressive inflammatory disease that causes damage to multiple joints, decline in functional status, and premature mortality. Thus, effective and frequent objective assessments are necessary. Then, we developed a self-assessment system for RA patients based on a smartphone application. The purpose of this study was to investigate the feasibility of a self-assessment system for RA patients using a smartphone application. We measured daily disease activity in nine RA patients who used the smartphone application for a period of three months. A disease activity score (DAS28) predictive model was used and feedback comments relating to disease activity were shown to patients via the smartphone application each day. To assess participants' RA disease activity, the DAS28 based on the C-reactive protein level was measured by a rheumatologist during monthly clinical visits. The disease activity measured by the application correlated well with the patients' actual disease activity during the 3-month period, as assessed by clinical examination. Furthermore, most participants gave favourable responses to a questionnaire administered at the end of the 3-month period containing questions relating to the ease of use and usefulness of the system. The results of this feasibility study indicated that the DAS28 predictive model can longitudinally predict DAS28 and may be an acceptable and useful tool for assessment of RA disease activity for both patients and healthcare providers.

Intra-retinal segmentation of optical coherence tomography images using active contours with a dynamic programming initialization and an adaptive weighting strategy

NASA Astrophysics Data System (ADS)

Gholami, Peyman; Roy, Priyanka; Kuppuswamy Parthasarathy, Mohana; Ommani, Abbas; Zelek, John; Lakshminarayanan, Vasudevan

2018-02-01

Retinal layer shape and thickness are one of the main indicators in the diagnosis of ocular diseases. We present an active contour approach to localize intra-retinal boundaries of eight retinal layers from OCT images. The initial locations of the active contour curves are determined using a Viterbi dynamic programming method. The main energy function is a Chan-Vese active contour model without edges. A boundary term is added to the energy function using an adaptive weighting method to help curves converge to the retinal layer edges more precisely, after evolving of curves towards boundaries, in final iterations. A wavelet-based denoising method is used to remove speckle from OCT images while preserving important details and edges. The performance of the proposed method was tested on a set of healthy and diseased eye SD-OCT images. The experimental results, compared between the proposed method and the manual segmentation, which was determined by an optometrist, indicate that our method has obtained an average of 95.29%, 92.78%, 95.86%, 87.93%, 82.67%, and 90.25% respectively, for accuracy, sensitivity, specificity, precision, Jaccard Index, and Dice Similarity Coefficient over all segmented layers. These results justify the robustness of the proposed method in determining the location of different retinal layers.

Vitamin D in the Pathophysiology of Hypertension, Kidney Disease, and Diabetes: Examining the Relationship Between Vitamin D and the Renin-Angiotensin System in Human Diseases

PubMed Central

Vaidya, Anand; Williams, Jonathan S.

2011-01-01

Objective Vitamin D has been implicated in the pathophysiology of extra-skeletal conditions such as hypertension, kidney disease, and diabetes, via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. Methods Literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes. Results Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25(OH)2D mediated down-regulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β–cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well designed prospective human interventional studies to definitively assess clinical outcomes. Conclusion Animal studies implicate vitamin D receptor agonist therapy to lower RAS activity as a potential method to reduce the risk of hypertension, kidney disease, and diabetes. There is a need for more well designed prospective interventional studies to validate this hypothesis in human clinical outcomes. PMID:22075270

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

PubMed Central

Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid

2016-01-01

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428

Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus

PubMed Central

Chalikias, George; Tziakas, Dimitrios; Chizzolini, Carlo; Ribi, Camillo; Trendelenburg, Marten; Eisenberger, Ute; Hauser, Thomas; Pasch, Andreas; Huynh-Do, Uyen; Arampatzis, Spyridon

2018-01-01

Background Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations. Methods A total of 168 patients with ≥ 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort Study (SSCS) were included in this analysis. Serum calcification propensity was assessed using time-resolved nephelometry. Results The cohort mainly consisted of female (85%), middle-aged (43±14 years) Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum creatinine and serum protein levels explaining 43% of the variation at baseline. Integrating disease activity (SELENA-SLEDAI) into this multivariate model revealed a significant association between disease activity and T50 levels. In a subgroup analysis considering only patients with active disease (SELENA-SLEDAI score ≥4) we found a negative association between T50 and SELENA-SLEDAI score at baseline (Spearman’s rho -0.233, P = 0.02). Conclusions Disease activity and T50 are closely associated. Moreover, T50 levels identify a subgroup of SLE patients with ongoing systemic inflammation as mirrored by increased disease activity. T50 could be a promising biomarker reflecting SLE disease activity and might offer an earlier detection tool for high-risk patients. PMID:29364894

Multivariate inference of pathway activity in host immunity and response to therapeutics

PubMed Central

Goel, Gautam; Conway, Kara L.; Jaeger, Martin; Netea, Mihai G.; Xavier, Ramnik J.

2014-01-01

Developing a quantitative view of how biological pathways are regulated in response to environmental factors is central for understanding of disease phenotypes. We present a computational framework, named Multivariate Inference of Pathway Activity (MIPA), which quantifies degree of activity induced in a biological pathway by computing five distinct measures from transcriptomic profiles of its member genes. Statistical significance of inferred activity is examined using multiple independent self-contained tests followed by a competitive analysis. The method incorporates a new algorithm to identify a subset of genes that may regulate the extent of activity induced in a pathway. We present an in-depth evaluation of specificity, robustness, and reproducibility of our method. We benchmarked MIPA's false positive rate at less than 1%. Using transcriptomic profiles representing distinct physiological and disease states, we illustrate applicability of our method in (i) identifying gene–gene interactions in autophagy-dependent response to Salmonella infection, (ii) uncovering gene–environment interactions in host response to bacterial and viral pathogens and (iii) identifying driver genes and processes that contribute to wound healing and response to anti-TNFα therapy. We provide relevant experimental validation that corroborates the accuracy and advantage of our method. PMID:25147207

Validation of the Auto-Inflammatory Diseases Activity Index (AIDAI) for hereditary recurrent fever syndromes

PubMed Central

Piram, Maryam; Koné-Paut, Isabelle; Lachmann, Helen J; Frenkel, Joost; Ozen, Seza; Kuemmerle-Deschner, Jasmin; Stojanov, Silvia; Simon, Anna; Finetti, Martina; Sormani, Maria Pia; Martini, Alberto; Gattorno, Marco; Ruperto, Nicolino

2014-01-01

Objectives To validate the Auto-Inflammatory Diseases Activity Index (AIDAI) in the four major hereditary recurrent fever syndromes (HRFs): familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndromes (CAPS). Methods In 2010, an international collaboration established the content of a disease activity tool for HRFs. Patients completed a 1-month prospective diary with 12 yes/no items before a clinical appointment during which their physician assessed their disease activity by a questionnaire. Eight international experts in auto-inflammatory diseases evaluated the patient's disease activity by a blinded web evaluation and a nominal group technique consensus conference, with their consensus judgement considered the gold standard. Sensitivity/specificity/accuracy measures and the ability of the score to discriminate active from inactive patients via the best cut-off score were calculated by a receiver operating characteristic analysis. Results Consensus was achieved for 98/106 (92%) cases (39 FMF, 35 CAPS, 14 TRAPS and 10 MKD), with 26 patients declared as having inactive disease and 72 as having active disease. The median total AIDAI score was 14 (range=0–175). An AIDAI cut-off score ≥9 discriminated active from inactive patients, with sensitivity/specificity/accuracy of 89%/92%/90%, respectively, and an area under the curve of 98% (95% CI 96% to 100%). Conclusions The AIDAI score is a valid and simple tool for assessing disease activity in FMF/MKD/TRAPS/CAPS. This tool is easy to use in clinical practice and has the potential to be used as the standard efficacy measure in future clinical trials. PMID:24026675

Effective Diagnosis of Alzheimer's Disease by Means of Association Rules

NASA Astrophysics Data System (ADS)

Chaves, R.; Ramírez, J.; Górriz, J. M.; López, M.; Salas-Gonzalez, D.; Illán, I.; Segovia, F.; Padilla, P.

In this paper we present a novel classification method of SPECT images for the early diagnosis of the Alzheimer's disease (AD). The proposed method is based on Association Rules (ARs) aiming to discover interesting associations between attributes contained in the database. The system uses firstly voxel-as-features (VAF) and Activation Estimation (AE) to find tridimensional activated brain regions of interest (ROIs) for each patient. These ROIs act as inputs to secondly mining ARs between activated blocks for controls, with a specified minimum support and minimum confidence. ARs are mined in supervised mode, using information previously extracted from the most discriminant rules for centering interest in the relevant brain areas, reducing the computational requirement of the system. Finally classification process is performed depending on the number of previously mined rules verified by each subject, yielding an up to 95.87% classification accuracy, thus outperforming recent developed methods for AD diagnosis.

Improving inflammatory arthritis management through tighter monitoring of patients and the use of innovative electronic tools

PubMed Central

van Riel, Piet; Combe, Bernard; Abdulganieva, Diana; Bousquet, Paola; Courtenay, Molly; Curiale, Cinzia; Gómez-Centeno, Antonio; Haugeberg, Glenn; Leeb, Burkhard; Puolakka, Kari; Ravelli, Angelo; Rintelen, Bernhard; Sarzi-Puttini, Piercarlo

2016-01-01

Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists. PMID:27933206

Impact of persistence and non-persistence in leisure time physical activity on coronary heart disease and all-cause mortality: The Copenhagen City Heart Study.

PubMed

Schnohr, Peter; O'Keefe, James H; Lange, Peter; Jensen, Gorm Boje; Marott, Jacob Louis

2017-10-01

Aims The aim of this study was to investigate the impact of persistence and non-persistence in leisure time physical activity on coronary heart disease and all-cause mortality. Methods and results In the Copenhagen City Heart Study, we prospectively followed 12,314 healthy subjects for 33 years of maximum follow-up with at least two repeated measures of physical activity. The association between persistence and non-persistence in leisure time physical activity, coronary heart disease and all-cause mortality were assessed by multivariable Cox regression analyses. Coronary heart disease mortality for persistent physical activity in leisure compared to persistent sedentary activity were: light hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.63-0.92, moderate HR 0.52; 95% CI 0.41-0.67, and high physical activity HR 0.51; 95% CI, 0.30-0.88. The differences in longevity were 2.8 years for light, 4.5 years for moderate and 5.5 years for high physical activity. A substantial increase in physical activity was associated with lower coronary heart disease mortality (HR 0.75; 95% CI 0.52-1.08) corresponding to 2.4 years longer life, whereas a substantial decrease in physical activity was associated with higher coronary heart disease mortality (HR 1.61; 95% CI 1.11-2.33) corresponding to 4.2 years shorter life than the unchanged group. A similar pattern was observed for all-cause mortality. Conclusion We found inverse dose-response relationships between persistent leisure time physical activity and both coronary heart disease and all-cause mortality. A substantial increase in physical activity was associated with a significant gain in longevity, whereas a decrease in physical activity was associated with even greater loss of longevity.

[How to assess the economic cost of tropical diseases in a rural community].

PubMed

Guiguemde, T R

1986-01-01

Many tropical diseases cause disability and hinder the socio-economic development of the Third World countries where they rage. A method of assessment of the economic cost of these diseases during epidemiological studies has been suggested here. It calls on the following factors: the type of activity of the community, the gross income of the community, the cost of treatment and the types of the disability (degree of disability, length of disability in relation to the period of production, and the degree of men's activity).

National and international veterinary reference laboratories for infectious diseases.

PubMed

Edwards, S; Alexander, D

1998-08-01

Reference laboratories play an increasingly important role in the harmonisation of laboratory diagnostic tests and the standardisation of veterinary vaccines. This is particularly important in building confidence between international trading partners. The authors review aspects of the organisation, designation and support of reference laboratories for infectious diseases of animals and discuss the principal activities which such laboratories would normally perform. These activities include advice and consultancy, publications and communication, training, research, disease surveillance, maintenance of culture collections, evaluation of reference methods, preparation of reference materials and organisation of inter-laboratory comparisons.

Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review

PubMed Central

Block, Valerie A. J.; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A. C.; Allen, Diane D.; Gelfand, Jeffrey M.

2016-01-01

Objective To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Methods Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. Results 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. Conclusions These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability. PMID:27124611

IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity

PubMed Central

Colafrancesco, Serena; Priori, Roberta; Alessandri, Cristiano; Perricone, Carlo; Pendolino, Monica; Picarelli, Giovanna; Valesini, Guido

2012-01-01

Introduction. Immunological factors seem to play a pivotal role in Adult Onset Still's Disease (AOSD). Among all, IL-18 cytokine is overexpressed and drives the inflammatory process. Objective. We aimed to investigate the levels of IL-18 in sera of Italian patients with AOSD and to assess its possible role as a marker of disease activity. Methods. IL-18 serum levels were determined by ELISA in 26 Italian patients with AOSD. Disease activity was assessed using Pouchot's criteria. As controls, 21 patients with Rheumatoid Arthritis (RA), 21 patients with Sjogren's Syndrome (SS), 20 patients with Systemic Lupus Erythematosus (SLE), and 21 healthy subjects (normal human sera, NHS) were evaluated. Results. IL-18 serum levels were significantly higher in patients with active AOSD than in non-active (P = 0.001) and control groups (RA P = 0.0070, SS P = 0.0029, SLE P = 0.0032, NHS P = 0.0004). A significant correlation between IL-18 serum levels and disease activity (P < 0.0001), and laboratory parameters as ferritin (P = 0.0127) and C-reactive protein (P = 0.0032) was demonstrated. Conclusions. Higher levels of IL-18 are detected in active AODS patients and correlate with disease activity and inflammatory laboratory features. ROC-AUC analysis of the serum concentration of IL-18 suggests that it can be considered a diagnostic marker of AOSD. This paper supports the targeting of this cytokine as a possible therapeutic option in AOSD. PMID:22762008

The "Silent Cough" Method for Vocal Hyperfunction

ERIC Educational Resources Information Center

Zwitman, Daniel H.; Calcaterra, Thomas C.

1973-01-01

A method of silent coughing is recommended as an alternative to coughing and throat clearing which are described as vocally abusive activities that can be directly related to laryngeal disease. (Author/GW)

Methods for Determination of α-Glycosidase, β-Glycosidase, and α-Galactosidase Activities in Dried Blood Spot Samples.

PubMed

Sozmen, Eser Yıldırım; Sezer, Ebru Demirel

2017-01-01

The lysosomal storage diseases (LDSs) are a heterogeneous group of inherited genetic disorders caused by defects of lysosomal proteins. The accumulation of undigested substrates from different catabolic pathways leads to cellular dysfunction. LSDs generally presents during early childhood and have a devastating impact on the families and on public health. Over the years, approaches for treatment of some LSDs have been developed with different strategies. Increasing availability of treatments of these diseases has accelerated the development of new methods and techniques for rapid diagnosis in patients with clinical indication.The use of dried blood spot (DBS) test has been proposed as a first tier test to identify patients with Gaucher, Pompe, and Fabry diseases. DBS usage is advantageous for the purpose of screening as it is non-invasive, sensitive, has low-cost and fast turnaround time compared to measurements in leucocyte and/or fibroblast culture. This chapter focuses on the activity measurement of three lysosomal enzymes (α-glucosidase, β-glucosidase, and α galactosidase) in DBS samples by using fluorescent substrates and by the LC-MS/MS (liquid chromatography-mass spectrometry) method. All steps of the methods, from preparation of the solutions to calculation of the enzyme activity, will be explained in detail.

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

PubMed

Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E

2017-09-01

Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C 16:0 -ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C 16:0 -ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C 16:0 - and C 24:1 -hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

The pan-cancer pathological regulatory landscape

PubMed Central

Falco, Matias M.; Bleda, Marta; Carbonell-Caballero, José; Dopazo, Joaquín

2016-01-01

Dysregulation of the normal gene expression program is the cause of a broad range of diseases, including cancer. Detecting the specific perturbed regulators that have an effect on the generation and the development of the disease is crucial for understanding the disease mechanism and for taking decisions on efficient preventive and curative therapies. Moreover, detecting such perturbations at the patient level is even more important from the perspective of personalized medicine. We applied the Transcription Factor Target Enrichment Analysis, a method that detects the activity of transcription factors based on the quantification of the collective transcriptional activation of their targets, to a large collection of 5607 cancer samples covering eleven cancer types. We produced for the first time a comprehensive catalogue of altered transcription factor activities in cancer, a considerable number of them significantly associated to patient’s survival. Moreover, we described several interesting TFs whose activity do not change substantially in the cancer with respect to the normal tissue but ultimately play an important role in patient prognostic determination, which suggest they might be promising therapeutic targets. An additional advantage of this method is that it allows obtaining personalized TF activity estimations for individual patients. PMID:28000771

Interferon-alpha, immune activation and immune dysfunction in treated HIV infection

PubMed Central

Cha, Lilian; Berry, Cassandra M; Nolan, David; Castley, Allison; Fernandez, Sonia; French, Martyn A

2014-01-01

Type I interferons (IFNs) exert anti-viral effects through the induction of numerous IFN-stimulated genes and an immunomodulatory effect on innate and adaptive immune responses. This is beneficial in controlling virus infections but prolonged IFN-α activity in persistent virus infections, such as HIV infection, may contribute to immune activation and have a detrimental effect on the function of monocytes and T and B lymphocytes. Activation of monocytes, associated with increased IFN-α activity, contributes to atherosclerotic vascular disease, brain disease and other ‘age-related diseases' in HIV patients treated with long-term antiretroviral therapy (ART). In HIV patients receiving ART, the anti-viral effects of IFN-α therapy have the potential to contribute to eradication of HIV infection while IFN-α inhibitor therapy is under investigation for the treatment of immune activation. The management of HIV patients receiving ART will be improved by understanding more about the opposing effects of IFN-α on HIV infection and disease and by developing methods to assess IFN-α activity in clinical practice. PMID:25505958

Toward a Generation Free of Tuberculosis: TB Disease and Infection in Individuals of College Age in the United States

ERIC Educational Resources Information Center

Shah, N. S.; Flood-Bryzman, A.; Jeffries, C.; Scott, J.

2018-01-01

Objectives: To assess the magnitude of active TB disease and latent TB infection (LTBI) in young adults of college age. Participants: Individuals who were aged 18-24 years in 2011 were used as a proxy for college students. Methods: Active TB cases reported to the 2011 US National TB Surveillance System (NTSS) were included. LTBI prevalence was…

Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis

PubMed Central

Magee, Elizabeth A; Edmond, Laurie M; Tasker, Shiona M; Kong, San Choon; Curno, Richard; Cummings, John H

2005-01-01

Background The relapsing nature and varying geographical prevalence of ulcerative colitis (UC) implicates environmental factors such as diet in its aetiology. Methods In order to determine which foods might be related to disease activity in UC a new method of dietary analysis was developed and applied. Eighty-one UC patients were recruited at all stages of the disease process. Following completion of a 7 d diet diary, clinical assessment including a sigmoidoscopic examination (scale 0 (normal mucosa) to 6 (very active disease)) was conducted. Food weights for each person were adjusted (divided) by the person's calorific intake for the week. Each food consumed was given a food sigmoidoscopy score (FSS) calculated by summing the products of the (adjusted) weight of food consumed and sigmoidoscopy score for each patient and occurrence of food and dividing by the total (adjusted) weight of the food consumed by all 81 patients. Thus, foods eaten in large quantities by patients with very active disease have high FSSs and vice versa. Foods consumed by <10 people or weighing <1 kg for the whole group were excluded, leaving 75 foods. Results High FSS foods were characterized by high levels of the anti-thiamin additive sulfite (Mann-Whitney, p < 0.001), i.e. bitter, white wine, burgers, soft drinks from concentrates, sausages, lager and red wine. Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version. Beneficial foods (average intake per week) included pork (210 g), breakfast cereals (200 g), lettuce (110 g), apples and pears (390 g), milk (1250 ml), melon (350 g), bananas (350 g), bacon (120 g), beef and beef products (500 g), tomatoes (240 g), soup (700 g), citrus fruits (300 g), fish (290 g), yogurt (410 g), cheese (110 g), potatoes (710 g) and legumes (120 g). Conclusions The dietary analysis method described provides a new tool for establishing relationships between diet and disease and indicates a potentially therapeutic diet for UC. PMID:15705205

Risk of relapse after natalizumab withdrawal

PubMed Central

Vukusic, Sandra; Casey, Romain; Debard, Nadine; Stankoff, Bruno; Mrejen, Serge; Uhry, Zoe; Van Ganse, Eric; Castot, Anne; Clanet, Michel; Lubetzki, Catherine; Confavreux, Christian

2016-01-01

Objective: To assess disease activity within 12 months after natalizumab (NZ) discontinuation in a large French postmarketing cohort. Methods: In France, patients exposed at least once to NZ were included in the TYSEDMUS observational and multicenter cohort, part of the French NZ Risk Management Plan. Clinical disease activity during the year following NZ discontinuation was assessed in this cohort. Time to first relapse after NZ stop was analyzed using Kaplan-Meier method and potentially associated factors were studied using a multivariate Cox model. Results: Out of the 4,055 patients with multiple sclerosis (MS) included in TYSEDMUS, 1,253 discontinued NZ and 715 of them had relevant data for our study. The probability of relapse within the year after NZ stop was estimated at 45% (95% confidence interval 0.41–0.49). Conclusions: This large and systematic survey of patients with MS after NZ withdrawal allows quantifying the risk of increased disease activity following treatment discontinuation. This study provides large-scale, multicenter, systematic data after NZ cessation in real-life settings. PMID:27844037

Total flavonoid content and formulation antioxidant cream stem of jatropha multifida l.

NASA Astrophysics Data System (ADS)

Dwi Franyoto, Yuvianti; Kusmita, Lia; Mutmainah; Demma Angrena, Riega

2018-05-01

Free radical induced oxidative stress that influences the occurrence of various degenerative diseases such as cancer, coronary heart disease and premature aging. Stems of Jatropha multifida L are known to contain flavanoid compounds have antioxidant activity. A study has been carried out to determine antioxidant potential of stems of Jatropha multifida L. Initially, material was macerated gradually with ethanol. The extract obtained was filtered and evaporated. Determination of total flavanoid contents (TFC) using spectrophotometric methods. The antioxidant potential of this extract was evaluated by 2, 2-diphenyl-1- picrylhydrazyl (DPPH) radical scavenging assay. In the DPPH radical-scavenging activities, the extract had the antioxidant activity (IC50 = 72 ± 0.01 μg/ml). The results showed the extracts of Jatropha multifida L. could be considered as natural antioxidants and may be useful for curing diseases arising from oxidative deterioration. The formulation comprises with 5% of extract and was formulated using fusion method. The evaluation of the formulated cream showed good results and can be good potential for cosmetic product development.

Evaluation of the antioxidant, antibacterial, and antiproliferative activities of the acetone extract of the roots of Senna italica (Fabaceae).

PubMed

Masoko, P; Gololo, S S; Mokgotho, M P; Eloff, J N; Howard, R I; Mampuru, L J

2009-12-30

Senna italica, a member of the Fabaceae family (subfamily Caesalpinaceae), is widely used traditionally to treat a number of disease conditions, such as sexually transmitted diseases and some forms of intestinal complications. The roots of Senna italica were collected from Zebediela subregion, Limpopo province (S.A), powdered and extracted with acetone by cold/shaking extraction method. The phytochemical composition of the extract was determined by thin layer chromatography (TLC). The chromatograms were visualised with vanillin-sulphuric acid and p-anisaldehyde reagents. The total phenolic content of the extract was determined by Folin-Ciocalteu method and expressed as TAE/g dry weight. The extract was assayed for the in vitro anticancer activity using Jurkat T cells, antioxidant activity using DPPH assay and antibacterial activity by bioautographic method and the microtitre plate method. The acetone extract of the roots of Senna italica inhibited the growth of Jurkat T cells in a dose- and time-dependent manner. The extract also had free radical scavenging activity as well as reasonable antibacterial activity against Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli and Staphylococcus aureus with MICs ranging from 0,08 to 0.16 mg/ml in the same order as ampicillin the positive control. The biological activities observed in the acetone extract validated the ethnomedicinal use of Senna italica.

Activating STAT3 Alpha for Promoting Healing of Neurons

NASA Technical Reports Server (NTRS)

Conway, Greg

2008-01-01

A method of promoting healing of injured or diseased neurons involves pharmacological activation of the STAT3 alpha protein. Usually, injured or diseased neurons heal incompletely or not at all for two reasons: (1) they are susceptible to apoptosis (cell death); and (2) they fail to engage in axogenesis that is, they fail to re-extend their axons to their original targets (e.g., muscles or other neurons) because of insufficiency of compounds, denoted neurotrophic factors, needed to stimulate such extension. The present method (see figure) of treatment takes advantage of prior research findings to the effect that the STAT3 alpha protein has anti-apoptotic and pro-axogenic properties.

Harris-Benedict equation estimations of energy needs as compared to measured 24-h energy expenditure by indirect calorimetry in people with early to mid-stage Huntington's disease.

PubMed

Gaba, Ann; Zhang, Kuan; Moskowitz, Carol B; Boozer, Carol N; Marder, Karen

2008-10-01

Weight loss and energy metabolism are important clinical research areas in understanding the disease mechanisms in Huntington's disease. Having an accurate method to estimate expected total energy expenditure would likely facilitate the development of studies about these features of the disease. The Harris-Benedict equation is a formula commonly used to estimate basal energy expenditure of individuals, adjusted for height, weight, age and gender. This estimate is then multiplied by a physical activity factor to estimate total daily energy needs to maintain the given weight. Data from 24-h indirect calorimetry was utilized to derive an adjustment formula for the physical activity factor of the Harris-Benedict equation for 13 early to mid-stage Huntington's disease patients. The adjusted activity factor provided the most accurate estimate of energy needs. This adjusted formula can be used in clinical assessments of Huntington's disease patients, as well as in research studies when indirect calorimetry has not been performed.

Usefulness of C-Reactive Protein as a Disease Activity Marker in Crohn’s Disease according to the Location of Disease

PubMed Central

Yang, Dong-Hoon; Yang, Suk-Kyun; Park, Sang Hyoung; Lee, Ho-Su; Boo, Sun-Jin; Park, Jae-Ho; Na, Soo Young; Jung, Kee Wook; Kim, Kyung-Jo; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Kim, Jin-Ho

2015-01-01

Background/Aims C-reactive protein (CRP) is a serologic activity marker in Crohn’s disease (CD), but it may be less useful in evaluating CD activity in ileal CD patients. We aimed to investigate the usefulness of CRP as a disease activity marker in CD according to disease location. Methods Korean CD patients in a single hospital were evaluated. Factors associated with elevated CRP concentration at the time of diagnosis of CD and the association between the physician’s prediction regarding upcoming surgery and the sites of the lesions directly related to surgery were analyzed. Results Of 435 CD patients, 25.7%, 6.9%, and 67.4% had ileal, colonic, and ileocolonic CD, respectively. Multivariate analysis revealed that an elevated erythrocyte sedimentation rate, reduced serum albumin, CD activity index (CDAI) >220, and ileocolonic/colonic location were associated with an elevated CRP level and that the CRP level was significantly correlated with the CDAI in all CD patients (γ=0.466, p<0.01). However, the correlation coefficient was dependent on the location, with values of 0.395, 0.456, and 0.527 in patients with an ileal, ileocolonic, and colonic disease location, respectively. Surgery for ileal lesions was less predictable than surgery for ileocolonic or colonic lesions during follow-up. Conclusions CRP is less useful as a disease activity marker in patients with ileal CD than those with ileocolonic or colonic CD. PMID:25170056

HIV Type 1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels

PubMed Central

Eller, Michael A.; Opollo, Marc S.; Liu, Michelle; Redd, Andrew D.; Eller, Leigh Anne; Kityo, Cissy; Kayiwa, Joshua; Laeyendecker, Oliver; Wawer, Maria J.; Milazzo, Mark; Kiwanuka, Noah; Gray, Ronald H.; Serwadda, David; Sewankambo, Nelson K.; Quinn, Thomas C.; Michael, Nelson L.; Wabwire-Mangen, Fred; Sandberg, Johan K.; Robb, Merlin L.

2015-01-01

Background. Untreated human immunodeficiency virus type 1 (HIV) infection is associated with persistent immune activation, which is an independent driver of disease progression in European and United States cohorts. In Uganda, HIV-1 subtypes A and D and recombinant AD viruses predominate and exhibit differential rates of disease progression. Methods. HIV-1 seroconverters (n = 156) from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow-up. Results. The frequency of activated T cells was increased in HIV-1–infected Ugandans, compared with community matched uninfected individuals, but did not differ significantly between viral subtypes. Higher HIV-1 load, subtype D, older age, and high T-cell activation levels were associated with faster disease progression to AIDS or death. In a multivariate Cox regression analysis, HIV-1 load was the strongest predictor of progression, with subtype also contributing. T-cell activation did not emerge an independent predictor of disease progression from this particular cohort. Conclusions. These findings suggest that the independent contribution of T-cell activation on morbidity and mortality observed in European and North American cohorts may not be directly translated to the HIV epidemic in East Africa. In this setting, HIV-1 load appears to be the primary determinant of disease progression. PMID:25404522

Participation of general practitioners in disease management: experiences from the Netherlands

PubMed Central

Steuten, L.M.G.; Vrijhoef, H.J.M.; Spreeuwenberg, C.; Van Merode, G.G.

2002-01-01

Abstract Objective To investigate the extent to which GPs in the Netherlands participate in disease management and how personal opinions, impeding and promoting incentives as well as physician characteristics influence their attitude towards disease management. Methods The attitude-model of Fishbein and Ajzen was used to describe the attitude of GPs towards disease management and main influencing factors. After interviewing seventeen representatives of the GPs and testing a questionnaire, the final questionnaire was sent to all GPs in the Netherlands (7680 GPs) barring those involved in the testing of the questionnaire. Results At least 10.4% of all Dutch GPs are active in disease management. The main factors predicting a positive attitude towards disease management are the following: GPs' opinion that they are improving quality and efficiency of care when executing disease management, presence of a good quality network between actors involved prior to the start of disease management, working in a health centre, and performing sideline activities besides their daily activities as GPs. The main factors predicting a negative attitude are: GPs' opinion that the investment-time is too high, lack of reimbursement for disease management activities, working in a solo practice, and not performing any sideline activities beside their daily activities as GP. Conclusions The factors predicting a negative attitude of Dutch GPs towards disease management dominate the factors predicting a positive attitude. The arguments in favour of disease management are matters of belief, for example concerning improvements in the quality of care, while arguments against are more concrete barriers e.g. high workload and financial reimbursement. Placed on the innovation timeline, the 10.4% participation might be taken to represent the start of a trend. PMID:16896373

Segmentation of the Globus Pallidus Internus Using Probabilistic Diffusion Tractography for Deep Brain Stimulation Targeting in Parkinson Disease.

PubMed

Middlebrooks, E H; Tuna, I S; Grewal, S S; Almeida, L; Heckman, M G; Lesser, E R; Foote, K D; Okun, M S; Holanda, V M

2018-06-01

Although globus pallidus internus deep brain stimulation is a widely accepted treatment for Parkinson disease, there is persistent variability in outcomes that is not yet fully understood. In this pilot study, we aimed to investigate the potential role of globus pallidus internus segmentation using probabilistic tractography as a supplement to traditional targeting methods. Eleven patients undergoing globus pallidus internus deep brain stimulation were included in this retrospective analysis. Using multidirection diffusion-weighted MR imaging, we performed probabilistic tractography at all individual globus pallidus internus voxels. Each globus pallidus internus voxel was then assigned to the 1 ROI with the greatest number of propagated paths. On the basis of deep brain stimulation programming settings, the volume of tissue activated was generated for each patient using a finite element method solution. For each patient, the volume of tissue activated within each of the 10 segmented globus pallidus internus regions was calculated and examined for association with a change in the Unified Parkinson Disease Rating Scale, Part III score before and after treatment. Increasing volume of tissue activated was most strongly correlated with a change in the Unified Parkinson Disease Rating Scale, Part III score for the primary motor region (Spearman r = 0.74, P = .010), followed by the supplementary motor area/premotor cortex (Spearman r = 0.47, P = .15). In this pilot study, we assessed a novel method of segmentation of the globus pallidus internus based on probabilistic tractography as a supplement to traditional targeting methods. Our results suggest that our method may be an independent predictor of deep brain stimulation outcome, and evaluation of a larger cohort or prospective study is warranted to validate these findings. © 2018 by American Journal of Neuroradiology.

Ultrasonographic imaging of inflammatory bowel disease in pediatric patients

PubMed Central

Chiorean, Liliana; Schreiber-Dietrich, Dagmar; Braden, Barbara; Cui, Xin-Wu; Buchhorn, Reiner; Chang, Jian-Min; Dietrich, Christoph F

2015-01-01

Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases in pediatric patients. Choosing the optimal imaging modality for the assessment of gastrointestinal disease in pediatric patients can be challenging. The invasiveness and patient acceptance, the radiation exposure and the quality performance of the diagnostic test need to be considered. By reviewing the literature regarding imaging in inflammatory bowel disease the value of ultrasound in the clinical management of pediatric patients is highlighted. Transabdominal ultrasound is a useful, noninvasive method for the initial diagnosis of IBD in children; it also provides guidance for therapeutic decisions and helps to characterize and predict the course of the disease in individual patients. Ultrasound techniques including color Doppler imaging and contrast-enhanced ultrasound are promising imaging tools to determine disease activity and complications. Comparative studies between different imaging methods are needed. PMID:25954096

Identification of Antipathogenic Bacterial Coral Symbionts Against Porites Ulcerative White Spots Disease

NASA Astrophysics Data System (ADS)

Sa'adah, Nor; Sabdono, Agus; Diah Permata Wijayanti, dan

2018-02-01

Coral reef ecosystems are ecosystems that are vulnerable and susceptible to damage due to the exploitation of ocean resources. One of the factors that cause coral damage is the disease that attacks the coral. Porites Ulcerative White Spots (PUWS) is a coral disease found in Indonesia and attacks the coral genera Porites allegedly caused by pathogenic microbial attacks. The purpose of this study was to identify the symbiotic bacteria on healthy coral that have antipatogenic potency against PUWS. The method used in this research was descriptive explorative. Sampling was done in Kemujan Island, Karimunjawa. Bacteria were isolated from healthy coral and coral affected by PUWS disease. Streak method was used to purify coral bacteria, while overlay and agar diffusion were used to test antipathogenic activity. Bacterial identification was carried out based on polyphasic approach. The results of this study showed that coral bacterial symbionts have antipathogenic activity against PUWS disease. The selected bacteria NM 1.2, NM 1.3 and KPSH 5. NM1.2 were closely related to Pseudoalteromonas piscicida, Pseudoalteromonas flavipulchra and Bacillus flexus, respectively.

A Structured Peer-Mentoring Method for Physical Activity Behavior Change among Adolescents

ERIC Educational Resources Information Center

Smith, Laureen H.; Petosa, Rick L.

2016-01-01

Despite national guidelines for regular physical activity, most adolescents are not physically active. Schools serve an estimated 60 million youth and provide an educational environment to meet the current physical activity guidelines. The obesity epidemic and chronic disease comorbidities associated with physical inactivity are not likely to be…

Disparity in Physical Activity among Urban Youth: An Ecologically Guided Assessment

ERIC Educational Resources Information Center

Lenhart, Clare M.; Patterson, Freda; Brown, Michael D.; O'Brien, Matthew J.; Nelson, Deborah B.

2014-01-01

Background: Insufficient physical activity among urban youth increases risk of chronic disease.Purpose:This study assessed reported physical activity to determine when disparities in participation emerge and what ecologically guided factors are linked with high activity. Methods:We administered a cross-sectional survey to a diverse sample of 321…

Practice of Iranian Adolescents with Hemophilia in Prevention of Complications of Hemophilia

PubMed Central

Valizadeh, Leila; Hosseini, Fahimeh Alsadat; Zamanzadeh, Vahid; Heidarnezhad, Fatemeh; Jasemi, Madineh; Lankarani, Kamran Bagheri

2015-01-01

Background: Prerequisite for management of a chronic disease involves knowledge about its complications and their prevention. Hemophilia in adolescents influences all the aspects of their lives and thier performance. Objectives: The present study aimed to determine the performance of Iranian hemophilic adolescents in prevention of disease complications. Patients and Methods: In this descriptive-analytical study, 108 adolescents with hemophilia were selected through convenience sampling. Their performance in preventing the complications of hemophilia was evaluated by sending a semi-structured questionnaire to their addresses throughout Iran. Then, the data was analysed using the Statistical Package for Social Sciences (SPSS) software (v. 13) and descriptive and interferential statistics were used. Results: Overall, 32.1% of the participants controlled bleeding during the 1st hour. Inaccessibility of coagulation products was mainly responsible for inhibiting timely and proper bleeding control. In order to relieve bleeding associated pain, only 39.0% of the adolescents used analgesics. On the other hand, 19.8% of the subjects used nonpharmacological methods to relieve pain. The majority of the adolescents did not participate in sport activities (65.4%) others allocated less than 5 hours a week to physical activities (70.5%). In addition, the participants did not have favorable dietary patterns, exercise habits, and dental care. The results showed a significant relationship between the adolescents’ preventive practice with coagulation disorders and utilization of pharmacological pain relief methods. Also, significant relationships were found between severity of the disease; participating in physical activities, number of hours of physical activities; and disease complications. Conclusions: Iranian adolescents did not exhibit favorable practices towards complication prevention. PMID:26600702

New technologies in predicting, preventing and controlling emerging infectious diseases.

PubMed

Christaki, Eirini

2015-01-01

Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance tools and epidemic intelligence methods, used by all major public health institutions, are intended to facilitate risk assessment and timely outbreak detection. In this review, we present new methods for regional and global infectious disease surveillance and advances in epidemic modeling aimed to predict and prevent future infectious diseases threats.

New technologies in predicting, preventing and controlling emerging infectious diseases

PubMed Central

Christaki, Eirini

2015-01-01

Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance tools and epidemic intelligence methods, used by all major public health institutions, are intended to facilitate risk assessment and timely outbreak detection. In this review, we present new methods for regional and global infectious disease surveillance and advances in epidemic modeling aimed to predict and prevent future infectious diseases threats. PMID:26068569

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases

PubMed Central

Rossel, Jean-Benoît; Biedermann, Luc; Frei, Pascal; Zeitz, Jonas; Spalinger, Marianne; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R.; Rogler, Gerhard

2017-01-01

Background Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications. Objectives Identifying risk factors for gallstones and kidney stones in IBD patients. Methods Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses. Results Out of 2323 IBD patients, 104 (7.8%) Crohn’s disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001). Conclusion The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD. PMID:29023532

Whole-Genome Sequencing in Outbreak Analysis

PubMed Central

Turner, Stephen D.; Riley, Margaret F.; Petri, William A.; Hewlett, Erik L.

2015-01-01

SUMMARY In addition to the ever-present concern of medical professionals about epidemics of infectious diseases, the relative ease of access and low cost of obtaining, producing, and disseminating pathogenic organisms or biological toxins mean that bioterrorism activity should also be considered when facing a disease outbreak. Utilization of whole-genome sequencing (WGS) in outbreak analysis facilitates the rapid and accurate identification of virulence factors of the pathogen and can be used to identify the path of disease transmission within a population and provide information on the probable source. Molecular tools such as WGS are being refined and advanced at a rapid pace to provide robust and higher-resolution methods for identifying, comparing, and classifying pathogenic organisms. If these methods of pathogen characterization are properly applied, they will enable an improved public health response whether a disease outbreak was initiated by natural events or by accidental or deliberate human activity. The current application of next-generation sequencing (NGS) technology to microbial WGS and microbial forensics is reviewed. PMID:25876885

Relationship Between Markers of Platelet Activation and Inflammation with Disease Activity in Wegener’s Granulomatosis

PubMed Central

TOMASSON, GUNNAR; LAVALLEY, MICHAEL; TANRIVERDI, KAHRAMAN; FINKIELMAN, JAVIER D.; DAVIS, JOHN C.; HOFFMAN, GARY S.; McCUNE, W. JOSEPH; St. CLAIR, E. WILLIAM; SPECKS, ULRICH; SPIERA, ROBERT; STONE, JOHN H.; FREEDMAN, JANE E.; MERKEL, PETER A.

2013-01-01

Objective There remains a need for biomarkers to guide therapy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our objective was to determine whether measures of platelet activation or inflammation are associated with disease activity in Wegener’s granulomatosis (WG). Methods Study subjects were participants in a clinical trial. Soluble CD40 ligand (sCD40L), C-reactive protein, interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), P-selectin, vascular endothelial growth factor, and proteinase 3 (PR3)-specific ANCA were measured by ELISA using plasma samples obtained at baseline (active disease), at remission, and prior to, during, and after first flares. Disease activity was assessed by the Birmingham Vasculitis Activity Score for WG (BVAS/WG). Association of biomarkers with disease activity was determined with conditional logistic and linear regression. Results Over a mean followup of 27 months, 180 subjects underwent 2044 visits; markers were measured in 563 samples. Longitudinally, all markers other than IL-6 were associated with disease activity. The strongest associations for active disease at baseline versus remission were observed for sCD40L (OR 4.72, 95% CI 2.47–9.03), P-selectin (OR 6.26, 95% CI 2.78–14.10), PR3-ANCA (OR 9.41, 4.03–21.99), and inversely for MCP-1 (OR 0.36, 95% CI 0.22–0.57). BVAS/WG increased by 0.80 (95% CI 0.44–1.16), 0.83 (95% CI 0.42–1.25), and 0.81 (95% CI 0.48–1.15) per unit-increase in PR3-ANCA, sCD40L, and P-selectin, respectively; and decreased by 1.54 (95% CI 0.96–2.12) per unit-increase in MCP-1. Conclusion Cytokines arising from within the circulation, including those of platelet activation, correlate with disease activity in WG. PMID:21411717

Inhibitory activities of venom alkaloids of Red Imported Fire Ant against Clavibacter michiganensis subsp. michiganensis in vitro and the application of piperidine alkaloids to manage symptom development..

USDA-ARS?s Scientific Manuscript database

Bacterial canker of tomato caused by Clavibacter michiganensis subsp. michiganensis (CMM) is a highly destructive disease and has caused major economic losses in tomato production worldwide. There are limited methods available to manage this disease. In searching for disease management alternatives,...

QUEST‐RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries

PubMed Central

Sokka, Tuulikki; Kautiainen, Hannu; Toloza, Sergio; Mäkinen, Heidi; Verstappen, Suzan M M; Hetland, Merete Lund; Naranjo, Antonio; Baecklund, Eva; Herborn, Gertraud; Rau, Rolf; Cazzato, Massimiliano; Gossec, Laure; Skakic, Vlado; Gogus, Feride; Sierakowski, Stanislaw; Bresnihan, Barry; Taylor, Peter; McClinton, Catherine; Pincus, Theodore

2007-01-01

Objective To conduct a cross‐sectional review of non‐selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. Methods The review included current disease activity using data from clinical assessment and a patient self‐report questionnaire, which was translated into each language. Data on demographic, disease and treatment‐related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28‐joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. Results Between January 2005 and October 2006, the QUEST‐RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 ⩽3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1. Conclusions This international multicentre cross‐sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005–6 including countries that are infrequently involved in clinical research projects. PMID:17412740

Disease Activity in Rheumatoid Arthritis and the Risk of Cardiovascular Events

PubMed Central

Solomon, DH; Reed, G; Kremer, JM; Curtis, JR; Farkouh, ME; Harrold, LR; Hochberg, MC; Tsao, P; Greenberg, J

2015-01-01

Background Use of several immunomodulatory agents has been associated with reduced cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease activity in RA correlates with CV events. Methods We studied patients with RA followed in a longitudinal US-based registry. Time-averaged disease activity was assessed using the area under the curve of the Clinical Disease Activity Index, a validated measure of rheumatoid arthritis disease activity, assessed during follow-up. Age, gender, diabetes, hypertension, hyperlipidemia, body mass index, family history of myocardial infarction (MI), aspirin use, NSAID use presence of CV disease, and baseline immunomodulator use were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV endpoint that included MI, stroke, and CV death. Results 24,989 subjects followed for a median of 2.7 years were included in these analyses. During follow-up, we observed 422 confirmed CV endpoints for an incidence rate of 9.08 (95% confidence interval, CI, 7.90 – 10.26) per 1,000 person-years. In models adjusting for variables noted above, a 10-point reduction in time-averaged Clinical Disease Activity Index was associated with a 26% reduction in CV risk (95% confidence interval 17-34%). These results were robust in subgroup analyses stratified by presence of CV disease, use of corticosteroids, use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors, change in RA treatment, and also when restricted to events adjudicated as definite or probable. Conclusions Reduced time-averaged disease activity in RA is associated with fewer CV events. PMID:25776112

Simultaneous Treatment with Subcutaneous Injection of Golimumab and Intra-articular Injection of Triamcinolone Acetonide (K-Method) in Patients with Rheumatoid Arthritis Undergoing Switching of Biologics: Retrospective Case–Control Study

PubMed Central

Kanbe, Katsuaki; Chiba, Junji; Inoue, Yasuo; Taguchi, Masashi; Yabuki, Akiko; Deguchi, Tomohiko

2016-01-01

BACKGROUND Tight control of severe rheumatoid arthritis (RA) in patients with high disease activity, even when using biologics, is sometimes difficult using a treat-to-target strategy. Switching from one biologic to another is associated with lower efficacy than that in treatment-naive cases. We developed the K-method that involves simultaneous treatment with golimumab and intra-articular joint injection of triamcinolone acetonide (TA) in patients undergoing switching of biologics. We performed this retrospective case–control study to investigate the efficacy of achieving an immediate treatment response using the K-method. METHODS This study involved 20 patients with RA (control group, 10 patients; K-method group, 10 patients). Patients in the control group were switched to golimumab from other biologics without intra-articular injection of TA. The K-method involved injection of 1 mL of TA (40 mg/mL) and 2 mL of 1% lidocaine hydrochloride into swollen or painful joints on the same day as golimumab treatment. A quick response one day after treatment was compared between the two groups according to the disease activity score 28 based on C-reactive protein (DAS28 CRP), clinical disease activity index (CDAI), simplified disease activity index (SDAI), European League Against Rheumatism (EULAR) response, and remission rate. These parameters were investigated for 24 weeks. RESULTS The K-method group showed significant improvements in DAS28 CRP, CDAI, and SDAI at one day, 12 weeks, and 24 weeks compared with the control group. The number of swollen and tender joints and the patient and doctor global visual analog scale scores were also significantly different between the two groups. The remission rates based on DAS28 CRP were 30% at one day, 50% at 12 weeks, and 60% at 24 weeks in the K-method group. The EULAR good/moderate response rates were 80% at one day, 90% at 12 weeks, and 90% at 24 weeks in the K-method group; however, these rates were only 10%, 40%, and 40%, respectively, in the control group. No adverse events occurred in either group. CONCLUSION Simultaneous treatment with biologics and intra-articular injection of TA is useful for cases involving switching of biologics for RA. This strategy is safe and practical for RA treatment. PMID:27081319

Developing community-driven quality improvement initiatives to enhance chronic disease care in Indigenous communities in Canada: the FORGE AHEAD program protocol.

PubMed

Naqshbandi Hayward, Mariam; Paquette-Warren, Jann; Harris, Stewart B

2016-07-26

Given the dramatic rise and impact of chronic diseases and gaps in care in Indigenous peoples in Canada, a shift from the dominant episodic and responsive healthcare model most common in First Nations communities to one that places emphasis on proactive prevention and chronic disease management is urgently needed. The Transformation of Indigenous Primary Healthcare Delivery (FORGE AHEAD) Program partners with 11 First Nations communities across six provinces in Canada to develop and evaluate community-driven quality improvement (QI) initiatives to enhance chronic disease care. FORGE AHEAD is a 5-year research program (2013-2017) that utilizes a pre-post mixed-methods observational design rooted in participatory research principles to work with communities in developing culturally relevant innovations and improved access to available services. This intensive program incorporates a series of 10 inter-related and progressive program activities designed to foster community-driven initiatives with type 2 diabetes mellitus as the action disease. Preparatory activities include a national community profile survey, best practice and policy literature review, and readiness tool development. Community-level intervention activities include community and clinical readiness consultations, development of a diabetes registry and surveillance system, and QI activities. With a focus on capacity building, all community-level activities are driven by trained community members who champion QI initiatives in their community. Program wrap-up activities include readiness tool validation, cost-analysis and process evaluation. In collaboration with Health Canada and the Aboriginal Diabetes Initiative, scale-up toolkits will be developed in order to build on lessons-learned, tools and methods, and to fuel sustainability and spread of successful innovations. The outcomes of this research program, its related cost and the subsequent policy recommendations, will have the potential to significantly affect future policy decisions pertaining to chronic disease care in First Nations communities in Canada. Current ClinicalTrial.gov protocol ID NCT02234973 . Date of Registration: July 30, 2014.

Contraceptive Use and Unintended Pregnancy in Women With Congenital Heart Disease.

PubMed

Lindley, Kathryn J; Madden, Tessa; Cahill, Alison G; Ludbrook, Philip A; Billadello, Joseph J

2015-08-01

To identify patterns of contraceptive use and pregnancy in an academic adult congenital cardiology practice. In this cross-sectional study, from October 2013 through March 2014, 100 women with congenital heart disease aged 18-45 years were recruited from an academic congenital heart disease clinic and administered a survey regarding pregnancy history, contraception use, and understanding of pregnancy-related and contraceptive-related risk. The primary outcome was current use of long-acting reversible contraception, including intrauterine devices or subdermal implants. Of 83 sexually active women, 63 (75.9%, 95% confidence interval [CI] 65.3-85.1) reported currently using any contraceptive method, including 30 of 83 (36.1%, 95% CI 25.9-47.4) using tier I methods (typical-use failure rates of less than 1% per year) and 20 of 83 (24.1%, 95% CI 15.4-34.7) using tier II methods (typical-use failure rates of 6-12% per year). Nine of 83 (10.8%, 95% CI 5.1-19.6) reported currently using long-acting reversible contraception. Sixty-four of 141 total pregnancies (45.4%, 95% CI 31.9-58.9) were self-reported by participants as "unexpected" rather than "planned." Only one (1.6%, 95% CI 0-4.6) of the 64 unintended pregnancies occurred when the woman was using a tier I method of contraception at the time of conception. Most women with congenital heart disease of childbearing age are sexually active. The high incidence of unintended pregnancy in this group may be related to underuse of highly effective methods of contraception. Specific counseling on tier I methods may reduce unintended pregnancies in women with congenital heart disease. III.

Changes in Novel Biomarkers of Disease Activity in Juvenile and Adult Dermatomyositis are Sensitive Biomarkers of Disease Course

PubMed Central

Reed, Ann M.; Peterson, Erik; Bilgic, Hatice; Ytterberg, Steven R.; Amin, Shreyasee; Hein, Molly S.; Crowson, Cynthia S.; Ernste, Floranne; Gillespie, Emily Baechler

2012-01-01

Objective Muscle enzyme levels are insensitive markers of disease activity in juvenile and adult dermatomyositis (DM), especially during the active treatment phase. To improve our ability to monitor DM disease activity longitudinally, especially in the presence of immune modulating agents, we prospectively evaluated whether IFN-dependent peripheral blood gene and chemokine signatures could serve as sensitive and responsive biomarkers for change in disease activity in adult and juvenile DM. Methods Peripheral blood and clinical data were collected from 51 juvenile and adult DM subjects prospectively over 2 study visits. Disease activity measures, whole-blood type I IFN gene and chemokine score were collected. We also measured serum levels of other pro-inflammatory cytokines, including IL-6. Results Changes in juvenile and adult DM global disease activity correlated positively and significantly with changes in the type I IFN gene score before (r=0.33, p=0.023) and IFN chemokine score before and after adjustment for medication use (r=0.53, p<0.001 and r=0.50, p=<0.001). Changes in muscle and extramuscular VAS subscales positively correlated with change in IFN gene and chemokine score (p=0.002). Serum levels of IL-6, IL-8 and TNFα were positively correlated with changes in global, muscle and extra-muscular VAS before and after adjustment for medications (p<0.05). Conclusion Our findings suggest that changes in type I IFN gene and chemokine scores as well as levels of IL-6, IL-8 and TNFα may serve as sensitive and responsive longitudinal biomarkers of change in disease activity in juvenile and adult DM, even in the presence of immunosuppressant use. PMID:22886447

Use of Pneumococcal Disease Epidemiology to Set Policy and Prevent Disease during 20 Years of the Emerging Infections Program.

PubMed

Moore, Matthew R; Whitney, Cynthia G

2015-09-01

Two decades ago, the Emerging Infections Program of the US Centers for Disease Control and Prevention implemented what seemed like a simple yet novel idea: a population- and laboratory-based surveillance system designed to identify and characterize invasive bacterial infections, including those caused by Streptococcus pneumoniae. This system, known as Active Bacterial Core surveillance, has since served as a flexible platform for following trends in invasive pneumococcal disease and studying vaccination as the most effective method for prevention. We report the contributions of Active Bacterial Core surveillance to every pneumococcal vaccine policy decision in the United States during the past 20 years.

Early Changes by 18Fluorodeoxyglucose Positron Emission Tomography Coregistered with Computed Tomography Predict Outcome after Mycobacterium tuberculosis Infection in Cynomolgus Macaques

PubMed Central

Coleman, M. Teresa; Maiello, Pauline; Tomko, Jaime; Frye, Lonnie James; Fillmore, Daniel; Janssen, Christopher; Klein, Edwin

2014-01-01

Cynomolgus macaques infected with low-dose Mycobacterium tuberculosis develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection. 18Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished active-disease and latent outcomes. Macaques (n = 10) were infected with low-dose M. tuberculosis with FDG PET/CT performed during infection. At 24 weeks postinfection, animals were classified as having active disease (n = 3) or latent infection (n = 6), with one “percolator” monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size, mineralization, and distribution of lesions) were compared among active and latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were observed in animals that would later develop active disease than in those that would develop latent infection. Over time, new lesions developed in active-disease animals but not in latent animals. Granulomas and mediastinal lymph nodes from active-disease but not latent animals consistently increased in metabolic activity at early time points. The presence of fewer lesions at 3 weeks and the lack of new lesion development in animals with latent infection suggest that innate and rapid adaptive responses are critical to preventing active tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of adaptive responses, especially in the airway, should be emphasized in newer vaccine strategies. PMID:24664509

Glutathione Peroxidase Enzyme Activity in Aging

PubMed Central

Espinoza, Sara E.; Guo, Hongfei; Fedarko, Neal; DeZern, Amy; Fried, Linda P.; Xue, Qian-Li; Leng, Sean; Beamer, Brock; Walston, Jeremy D.

2010-01-01

Background It is hypothesized that free radical damage contributes to aging. Age-related decline in activity of the antioxidant enzyme glutathione peroxidase (GPx) may contribute to increased free radicals. We hypothesized that GPx activity decreases with age in a population of older women with disability. Methods Whole blood GPx activity was measured in baseline stored samples from participants in the Women's Health and Aging Study I, a cohort of disabled community-dwelling older women. Linear regression was used to determine cross-sectional associations between GPx activity and age, adjusting for hemoglobin, coronary disease, diabetes, selenium, and body mass index. Results Six hundred one participants had complete demographic, disease, and laboratory information. An inverse association was observed between GPx and age (regression coefficient = −2.9, p < .001), indicating that for each 1-year increase in age, GPx activity decreased by 2.9 μmol/min/L. This finding remained significant after adjustment for hemoglobin, coronary disease, diabetes, and selenium, but not after adjustment for body mass index and weight loss. Conclusion This is the first study to examine the association between age and GPx activity in an older adult cohort with disability and chronic disease. These findings suggest that, after age 65, GPx activity declines with age in older women with disability. This decline does not appear to be related to diseases that have been previously reported to alter GPx activity. Longitudinal examination of GPx activity and other antioxidant enzymes in diverse populations of older adults will provide additional insight into age- and disease-related changes in these systems. PMID:18511755

Some potentials and limits of the leucocrit test as a fish health assessment method

USGS Publications Warehouse

Wedemeyer, G.A.; Gould, R.W.; Yasutake, W.T.

1983-01-01

The sensitivity of the leucocrit as a stress tolerance and fish health assessment method was evaluated by subjecting juvenile coho salmon, Oncorhynchus kisutch, or steelhead trout, Salmo gairdneri, to standardized crowding, handling, temperature and disease challenges. The leucocrit was a sensitive indicator of the physiological stress resulting from crowding at population densities of 0·2–0·4 kg l−1, and to the stress of handling and to temperature changes. It was relatively insensitive to physiological sampling procedures which supports its continued development as a stress assessment method.In the case of fish diseases, subclinical or active Renibacterium salmoninarum and Yersinia ruckeriinfections had essentially no effect on leucocrit values. In contrast, active Aeromonas salmonicidainfections significantly depressed the leucocrit. However, no change was seen during the subclinical (incubation) phase prior to the development of an epizootic. Thus, the potential of the leucocrit as a fish health assessment method appears limited.

Prescribing of Electronic Activity Monitors in Cardiometabolic Diseases: Qualitative Interview-Based Study

PubMed Central

Macé, Sandrine; Oppert, Jean-Michel

2017-01-01

Background The prevalence of noncommunicable diseases, including those such as type 2 diabetes, obesity, dyslipidemia, and hypertension, so-called cardiometabolic diseases, is high and is increasing worldwide. Strong evidence supports the role of physical activity in management of these diseases. There is general consensus that mHealth technology, including electronic activity monitors, can potentially increase physical activity in patients, but their use in clinical settings remains limited. Practitioners’ requirements when prescribing electronic activity monitors have been poorly described. Objective The aims of this qualitative study were (1) to explore how specialist physicians prescribe electronic activity monitors to patients presenting with cardiometabolic conditions, and (2) to better understand their motivation for and barriers to prescribing such monitors. Methods We conducted qualitative semistructured interviews in March to May 2016 with 11 senior physicians from a public university hospital in France with expertise in management of cardiometabolic diseases (type 1 and type 2 diabetes, obesity, hypertension, and dyslipidemia). Interviews lasted 45 to 60 minutes and were audiotaped, transcribed verbatim, and analyzed using directed content analysis. We report our findings following the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Results Most physicians we interviewed had never prescribed electronic activity monitors, whereas they frequently prescribed blood glucose or blood pressure self-monitoring devices. Reasons for nonprescription included lack of interest in the data collected, lack of evidence for data accuracy, concern about work overload possibly resulting from automatic data transfer, and risk of patients becoming addicted to data. Physicians expected future marketing of easy-to-use monitors that will accurately measure physical activity duration and intensity and provide understandable motivating feedback. Conclusions Features of electronic activity monitors, although popular among the general public, do not meet the needs of physicians. In-depth understanding of physicians’ expectations is a first step toward designing technologies that can be widely used in clinical settings and facilitate physical activity prescription. Physicians should have a role, along with key health care stakeholders—patients, researchers, information technology firms, the public, and private payers—in developing the most effective methods for integrating activity monitors into patient care. PMID:28947415

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations

PubMed Central

Caprilli, R; Gassull, M A; Escher, J C; Moser, G; Munkholm, P; Forbes, A; Hommes, D W; Lochs, H; Angelucci, E; Cocco, A; Vucelic, B; Hildebrand, H; Kolacek, S; Riis, L; Lukas, M; de Franchis, R; Hamilton, M; Jantschek, G; Michetti, P; O'Morain, C; Anwar, M M; Freitas, J L; Mouzas, I A; Baert, F; Mitchell, R; Hawkey, C J

2006-01-01

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease. PMID:16481630

Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus: Association with Disease Activity

PubMed Central

Choi, Jin-Young; Ho, John Hsi-en; Pasoto, Sandra G; Bunin, Viviane; Kim, Sangtaek; Carrasco, Solange; Borba, Eduardo F; Gonçalves, Celio R; Costa, Priscila R; Kallas, Esper G; Bonfa, Eloisa; Craft, Joe

2015-01-01

Objective To assess circulating follicular helper-like CD4+ T (cTfh-like) cells in systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods We analyzed blood samples from SLE patients, and as controls, Behçet’s disease (BD) patients and healthy individuals. We used flow cytometry to enumerate cTfh-like cells using as markers the C-X-C chemokine receptor type 5 (CXCR5), inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PCDC1, PD-1), and secretion of interleukin-21 (IL-21). We compared the frequency of cTfh-like cells with that of circulating plasmablasts (CD19+IgD−CD38+) and evaluated their possible association with disease activity. Results cTfh-like T cells, identified as CXCR5hiICOShiPD-1hi, were expanded in the blood of SLE patients compared to BD and healthy controls. Such cells produced IL-21 with lower expression of CCR7, compared to circulating CXCR5hi central memory (Tcm) cells, enabling their distinction. PD-1, not ICOS or CXCR5, expression was significantly elevated in cTfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5hi cTfh-like cells correlated with disease activity, circulating plasmablasts, and anti-dsDNA antibody positivity, but not disease duration nor past organ injury; rather, it reflected current active disease. Conclusion We found that cTfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T-B cell collaboration with a causal relationship central to disease pathogenesis. These findings also suggest that cTfh-like cells provide a surrogate for aberrant GC activity in SLE, and that their PD-1 expression offers a tool for following disease activity and response to therapies. PMID:25581113

Association of sleep quality in Behcet disease with disease activity, depression, and quality of life in Korean population

PubMed Central

Lee, Jimin; Kim, Sung-Soo; Jeong, Hye-Jin; Son, Chang-Nam; Kim, Ji-Min; Cho, Yong-Won; Kim, Sang-Hyon

2017-01-01

Background/Aims Sleep disturbance is prime concern in patients with Behcet disease. The purpose of this study was to find out the effects of sleep quality, in Korean patients suffering from Behcet disease. We further investigated the relationship between depression, quality of life and the clinical findings of Behcet disease. Methods The study was performed by the cross-sectional design. Sleep quality was assessed by the Korean version of Pittsburgh sleep quality index (PSQI). Disease activity of Behcet disease was evaluated by Behcet disease current activity form (BDCAF). Depression was assessed by the Korean version of Beck depression inventory second edition (BDI-2). Quality of life was assessed by the Korean version of the Leeds Behcet disease quality of life measure (BDQoL). Results Among the 100 patients studied, 42% reported poor sleep quality (PSQI ≥ 9). These patients have a higher BDI-2, total BDCAF and pain visual analogue scale (VAS) score (p < 0.001, p = 0.022, and p = 0.005). Considering BDCAF, the frequency of genital ulcer was significantly higher (p = 0.01). Behcet was higher in females. The BDQoL was lower in poor sleeper group (p = 0.004 and p < 0.001). Among 7 PSQI components, daytime dysfunction was higher in patients with high disease activity (p = 0.03). Total PSQI score were strongly correlated with BDCAF, BDI-2, BDQoL, and pain VAS score (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). Conclusions Low sleep quality is directly associated with disease activity, depression, and quality of life in Korean patients with Behcet disease. PMID:28192886

The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

PubMed

Smolinska, A; Bodelier, A G L; Dallinga, J W; Masclee, A A M; Jonkers, D M; van Schooten, F-J; Pierik, M J

2017-05-01

To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C-reactive protein <5 mg/L and faecal calprotectin <100 μg/g) were included for cross-sectional analysis. Non-UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC. © 2017 John Wiley & Sons Ltd.

Psychological distress, iron deficiency, active disease and female gender are independent risk factors for fatigue in patients with ulcerative colitis

PubMed Central

Jonefjäll, Börje; Simrén, Magnus; Lasson, Anders; Öhman, Lena; Strid, Hans

2017-01-01

Background Patients with ulcerative colitis often report fatigue. Objectives To investigate prevalence of and risk factors for fatigue in patients with ulcerative colitis with active disease and during deep remission. Methods In this cross-sectional study, disease activity was evaluated with endoscopy and calprotectin, and patients were classified as having active disease (n = 133) or being in deep remission (n = 155). Blood samples were analysed to assess anaemia, iron deficiency and systemic immune activity. Patients completed questionnaires to assess fatigue, psychological distress, gastrointestinal symptoms and quality of life. Results The prevalence of high fatigue (general fatigue ≥ 13, Multidimensional Fatigue Inventory) was 40% in the full study population. Among patients with high fatigue, female gender and iron deficiency were more prevalent, and these patients had more severe disease activity and reported higher levels of anxiety, depression and decreased quality of life compared with patients with no/mild fatigue. A logistic regression analysis identified probable psychiatric disorder (odds ratio (OR) (confidence interval) 6.1 (3.1–12.2)), iron deficiency (OR 2.5 (1.2–5.1)), active disease (OR 2.2 (1.2–3.9)) and female gender (OR 2.1 (1.1–3.7)) as independent risk factors for high fatigue. Similar results were found concerning psychological distress, gender and quality of life, but immune markers did not differ in patients in deep remission with high vs. no/mild fatigue. Conclusions Probable psychiatric disorder, iron deficiency, active disease and female gender are independent risk factors for high fatigue in patients with ulcerative colitis. Low-grade immune activity does not seem to be the cause of fatigue among patients in deep remission. PMID:29435325

Evaluation of differential disaccharide excretion in urine for non-invasive investigation of altered intestinal disaccharidase activity caused by alpha-glucosidase inhibition, primary hypolactasia, and coeliac disease.

PubMed Central

Bjarnason, I; Batt, R; Catt, S; Macpherson, A; Maxton, D; Menzies, I S

1996-01-01

BACKGROUND/AIM: The reliability of a quantitative method for the non-invasive assessment of intestinal disaccharide hydrolysis was assessed. METHODS: Differential excretion of intact disaccharide, expressed as ratios of lactulose to appropriate hydrolysable disaccharides in urine collected following combined ingestion, has been investigated in healthy volunteers with drug induced alpha-glucosidase inhibition, in subjects with primary hypolactasia, and patients with coeliac disease. RESULTS: Oral administration of the alpha-glucosidase inhibitor 'Acarbose' (BAY g 5421, 200 mg) together with sucrose and lactulose increased the urinary sucrose/lactulose excretion ratios (% dose/10 h) fivefold. The effect was quantitatively reproducible, a higher dose of 'Acarbose' (500 mg) increasing the excretion ratio to about 1.0 indicating complete inhibition of intestinal sucrase activity. The suitability of the method for measuring differences in dose/response and duration of action was assessed by comparing three different alpha-glucosidase inhibitors (BAY g 5421, BAY m 1099, and BAY o 1248) and found to be satisfactory. Subjects with primary adult hypolactasia had urine lactose/lactulose excretion ratios raised to values indicating reduced rather than complete absence of lactase activity whereas sucrose/lactulose ratios were not significantly affected. 'Whole' intestinal disaccharidase activity assessed by this method demonstrated impairment of lactase, sucrase, and isomaltase in eight, one, and seven, respectively, of 20 patients with coeliac disease. By contrast in vitro assay of jejunal biopsy tissue indicated pan-disaccharidase deficiency in all but five of these patients. This shows the importance of distinguishing between 'local' and 'whole' intestinal performance. CONCLUSIONS: Differential urinary excretion of ingested disaccharides provides a reliable, quantitative, and non-invasive technique for assessing profiles of intestinal disaccharidase activity. PMID:8949640

Developing Fine-Grained Actigraphies for Rheumatoid Arthritis Patients from a Single Accelerometer Using Machine Learning

PubMed Central

Garcia-Gancedo, Luis; Van der Drift, Anniek; Powell, Adam; Hamy, Valentin; Keller, Thomas; Yang, Guang-Zhong

2017-01-01

In addition to routine clinical examination, unobtrusive and physical monitoring of Rheumatoid Arthritis (RA) patients provides an important source of information to enable understanding the impact of the disease on quality of life. Besides an increase in sedentary behaviour, pain in RA can negatively impact simple physical activities such as getting out of bed and standing up from a chair. The objective of this work is to develop a method that can generate fine-grained actigraphies to capture the impact of the disease on the daily activities of patients. A processing methodology is presented to automatically tag activity accelerometer data from a cohort of moderate-to-severe RA patients. A study of procesing methods based on machine learning and deep learning is provided. Thirty subjects, 10 RA patients and 20 healthy control subjects, were recruited in the study. A single tri-axial accelerometer was attached to the position of the fifth lumbar vertebra (L5) of each subject with a tag prediction granularity of 3 s. The proposed method is capable of handling unbalanced datasets from tagged data while accounting for long-duration activities such as sitting and lying, as well as short transitions such as sit-to-stand or lying-to-sit. The methodology also includes a novel mechanism for automatically applying a threshold to predictions by their confidence levels, in addition to a logical filter to correct for infeasible sequences of activities. Performance tests showed that the method was able to achieve around 95% accuracy and 81% F-score. The produced actigraphies can be helpful to generate objective RA disease-specific markers of patient mobility in-between clinical site visits. PMID:28906437

Developing Fine-Grained Actigraphies for Rheumatoid Arthritis Patients from a Single Accelerometer Using Machine Learning.

PubMed

Andreu-Perez, Javier; Garcia-Gancedo, Luis; McKinnell, Jonathan; Van der Drift, Anniek; Powell, Adam; Hamy, Valentin; Keller, Thomas; Yang, Guang-Zhong

2017-09-14

In addition to routine clinical examination, unobtrusive and physical monitoring of Rheumatoid Arthritis (RA) patients provides an important source of information to enable understanding the impact of the disease on quality of life. Besides an increase in sedentary behaviour, pain in RA can negatively impact simple physical activities such as getting out of bed and standing up from a chair. The objective of this work is to develop a method that can generate fine-grained actigraphies to capture the impact of the disease on the daily activities of patients. A processing methodology is presented to automatically tag activity accelerometer data from a cohort of moderate-to-severe RA patients. A study of procesing methods based on machine learning and deep learning is provided. Thirty subjects, 10 RA patients and 20 healthy control subjects, were recruited in the study. A single tri-axial accelerometer was attached to the position of the fifth lumbar vertebra (L5) of each subject with a tag prediction granularity of 3 s. The proposed method is capable of handling unbalanced datasets from tagged data while accounting for long-duration activities such as sitting and lying, as well as short transitions such as sit-to-stand or lying-to-sit. The methodology also includes a novel mechanism for automatically applying a threshold to predictions by their confidence levels, in addition to a logical filter to correct for infeasible sequences of activities. Performance tests showed that the method was able to achieve around 95% accuracy and 81% F-score. The produced actigraphies can be helpful to generate objective RA disease-specific markers of patient mobility in-between clinical site visits.

Using ontology-based annotation to profile disease research

PubMed Central

Coulet, Adrien; LePendu, Paea; Shah, Nigam H

2012-01-01

Background Profiling the allocation and trend of research activity is of interest to funding agencies, administrators, and researchers. However, the lack of a common classification system hinders the comprehensive and systematic profiling of research activities. This study introduces ontology-based annotation as a method to overcome this difficulty. Analyzing over a decade of funding data and publication data, the trends of disease research are profiled across topics, across institutions, and over time. Results This study introduces and explores the notions of research sponsorship and allocation and shows that leaders of research activity can be identified within specific disease areas of interest, such as those with high mortality or high sponsorship. The funding profiles of disease topics readily cluster themselves in agreement with the ontology hierarchy and closely mirror the funding agency priorities. Finally, four temporal trends are identified among research topics. Conclusions This work utilizes disease ontology (DO)-based annotation to profile effectively the landscape of biomedical research activity. By using DO in this manner a use-case driven mechanism is also proposed to evaluate the utility of classification hierarchies. PMID:22494789

Uncovering the hidden: complexity and strategies for diagnosing latent tuberculosis.

PubMed

Flores-Valdez, Mario Alberto

2017-10-24

Tuberculosis produces two clinical manifestations: active and latent (non-apparent) disease. The latter is estimated to affect one-third of the world population and constitutes a source of continued transmission should the disease emerge from its hidden state (reactivation). Methods to diagnose latent TB have been evolving and aim to detect the disease in people who are truly infected with M. tuberculosis , versus those where other mycobacteria, or even other pathologies not related to TB, are present. The current use of proteomic and transcriptomic approaches may lead to improved detection methods in the coming years.

Experience with a cholinesterase histochemical technique for rectal suction biopsies in the diagnosis of Hirschsprung's disease

PubMed Central

Trigg, P. H.; Belin, R.; Haberkorn, S.; Long, W. J.; Nixon, H. H.; Plaschkes, J.; Spitz, L.; Willital, G. H.

1974-01-01

Cryostat sections from 160 rectal suction biopsies were stained for cholinesterases by the method of Karnovsky and Roots (1964) in an attempt to facilitate the diagnosis of Hirschsprung's disease. The method proved at least as reliable as experienced assessment of paraffin haematoxylin-eosin sections, and appeared to offer the advantages of reduced scanning fatigue and superior demonstration of the increased cholinesterase-positive nerves in Hirschprung's disease. Contrary to the findings of Meier-Ruge (1971) it was not possible to base a diagnosis on mucosal cholinesterase activity. Images PMID:4832300

Hyperthyroid vs hypothyroid eye disease: the same severity and activity

PubMed Central

Kashkouli, M B; Pakdel, F; Kiavash, V; Heidari, I; Heirati, A; Jam, S

2011-01-01

Purpose To compare demographics, severity, and activity of thyroid eye disease (TED) in patients with hyperthyroidism (Hr-TED) vs primary hypothyroidism (Ho-TED). Patients and Methods In a cross-sectional study, demographics, complete eye examination, severity score (NOSPECS, total hundred eye score), clinical activity score, and Rundle grading were recorded for patients with TED and different thyroid disorders referred from an endocrinology clinic from 2003 to 2006. Results TED was clinically found in 303 patients (303/851, 35.6%). The majority of them (280/303, 92.4%) had Graves' hyperthyroidism and 23 (23/303, 7.5%) had primary hypothyroidism. Mean age, gender, mean severity score, mean activity score, Rundle grade, unilateral presentation of TED, smoking habit, mean duration of eye disease, and mean interval time of thyroid to TED were not significantly different between the two groups (0.06

Myths about oral contraceptives. Does OC availability result in increased sexual activity among teens?

PubMed

Chaney

1993-11-01

Parents, educators, public health officials, health-care providers, religious organizations, and advocacy groups are very concerned about the rise in teenage pregnancy and the increase in sexually transmitted diseases among the young. Some say the increased availability and acceptance of oral contraceptives is directly related to an increase in sexual activity among teens. Less than 50% of women use a contraceptive method at first intercourse. Use is much lower in Hispanic and African-American women than among White women; women with low socioeconomic status, living in one-parent households, or having sex at an early age are the least likely to use a contraceptive method at first intercourse. According to the National Survey of Family Growth, teens engaging in sexual intercourse for the first time, who use a contraceptive method, typically choose the condom. Oral contraceptive use is very low and use at first intercourse has not increased over time. It is only after the establishment of routine sexual intercourse that the pill becomes the preferred method. The use of a condom has more than doubled for the period from 1982 to 1988. Adolescents under age 16 are at greatest risk for unintended pregnancies because this group is the least likely to use any method of contraception. The increase in teen sexual activity over the years does not coincide with an increase in pill use. Education must begin in elementary schools, stressing abstinence, but also include facts about sex, contraception, and disease prevention, because 40% of teens are sexually active by 9th grade. Skills can focus on changing behavior, such as learning to delay intercourse, building self-esteem as well as proper use of contraceptives. Easy, nonthreatening access to medical care can prevent many unintended pregnancies and the spread of sexually transmitted diseases.

Measurement of motor disability in MPTP-treated macaques using a telemetry system for estimating circadian motor activity.

PubMed

Barcia, C; De Pablos, V; Bautista-Hernández, V; Sanchez-Bahillo, A; Fernández-Barreiro, A; Poza, M; Herrero, M T

2004-03-15

The parkinsonian symptoms of primates after MPTP exposure can be measured by several visual methods (classical motor scores). However, these methods have a subjective bias, especially as regards the evaluation of the motor activity. Computerized monitoring systems represent an unbiased method for measuring the motor disability of monkeys after MPTP administration. In this work the motor activity of monkeys before and after MPTP administration is measured and compared with the activity of a control intact group by means of a telemetry system. A pronounced decrease in motor activity was observed after MPTP administration. These results suggest the monitoring method used is suited for characterizing the motor incapacity and possible improvements following treatments to test different therapies to control Parkinson's disease in MPTP models involving primates.

Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance and disease activity in systemic lupus erythematosus: a cross-sectional human study.

PubMed

Sahebari, M; Roshandel, G; Saadati, N; Saghafi, M; Abdolahi, N; Rezaieyazdi, Z

2017-08-01

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 ( P = 0.01, standardized beta -0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis.

Thiol/disulfide homeostasis in patients with ankylosing spondylitis

PubMed Central

Dogru, Atalay; Balkarli, Ayse; Cetin, Gozde Yildirim; Neselioglu, Salim; Erel, Ozcan; Tunc, Sevket Ercan; Sahin, Mehmet

2016-01-01

Ankylosing spondylitis (AS) is a chronic inflammatory disease. In many inflammatory diseases, increased production of pro-inflammatory cytokines is associated with an increase in oxidative stress mediators. Thiol/disulfide homeostasis is a marker for oxidative stress. The aim of this study was to examine the dynamic thiol/disulfide homeostasis in AS. Sixty-nine patients with AS and 60 age- and sex-matched controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and visual analogue scale (VAS) were used to determine the disease activity. Native thiol, total thiol, and disulfide levels were measured with a novel automated method recently described by Erel and Neselioglu. The aforementioned method is also optionally manual spectrophotometric assay. The total thiol levels were significantly lower in the AS group compared with the control group (p = 0.03). When the patients were divided into active (n = 35) and inactive (n = 34) subgroups using BASDAI scores, the native plasma thiol and total thiol levels were significantly lower in the active AS patients compared to the inactive AS patients (p = 0.02, p = 0.03 respectively). There was a negative correlation between the plasma native thiol levels and VAS, BASDAI scores. Thiol/disulfide homeostasis may be used for elucidating the effects of oxidative stress in AS. Understanding the role of thiol/disulfide homeostasis in AS might provide new therapeutic intervention strategies for patients. PMID:27186972

Diverse Functional Properties of Wilson Disease ATP7B Variants

PubMed Central

Huster, Dominik; Kühne, Angelika; Bhattacharjee, Ashima; Raines, Lily; Jantsch, Vanessa; Noe, Johannes; Schirrmeister, Wiebke; Sommerer, Ines; Sabri, Osama; Berr, Frieder; Mössner, Joachim; Stieger, Bruno; Caca, Karel; Lutsenko, Svetlana

2012-01-01

BACKGROUND & AIMS Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper (64Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS Variants in ATP7B associated with Wilson disease disrupt the protein’s transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype–phenotype correlation and mechanisms of disease pathogenesis. PMID:22240481

Counting Steps in Activities of Daily Living in People With a Chronic Disease Using Nine Commercially Available Fitness Trackers: Cross-Sectional Validity Study

PubMed Central

Beekman, Emmylou; Theunissen, Kyra; Braun, Susy; Beurskens, Anna J

2018-01-01

Background Measuring physical activity with commercially available activity trackers is gaining popularity. People with a chronic disease can especially benefit from knowledge about their physical activity pattern in everyday life since sufficient physical activity can contribute to wellbeing and quality of life. However, no validity data are available for this population during activities of daily living. Objective The aim of this study was to investigate the validity of 9 commercially available activity trackers for measuring step count during activities of daily living in people with a chronic disease receiving physiotherapy. Methods The selected activity trackers were Accupedo (Corusen LLC), Activ8 (Remedy Distribution Ltd), Digi-Walker CW-700 (Yamax), Fitbit Flex (Fitbit inc), Lumoback (Lumo Bodytech), Moves (ProtoGeo Oy), Fitbit One (Fitbit inc), UP24 (Jawbone), and Walking Style X (Omron Healthcare Europe BV). In total, 130 persons with chronic diseases performed standardized activity protocols based on activities of daily living that were recorded on video camera and analyzed for step count (gold standard). The validity of the trackers’ step count was assessed by correlation coefficients, t tests, scatterplots, and Bland-Altman plots. Results The correlations between the number of steps counted by the activity trackers and the gold standard were low (range: –.02 to .33). For all activity trackers except for Fitbit One, a significant systematic difference with the gold standard was found for step count. Plots showed a wide range in scores for all activity trackers; Activ8 showed an average overestimation and the other 8 trackers showed underestimations. Conclusions This study showed that the validity of 9 commercially available activity trackers is low measuring steps while individuals with chronic diseases receiving physiotherapy engage in activities of daily living. PMID:29610110

Antibacterial activity of plant defensins against alfalfa crown rot pathogens

USDA-ARS?s Scientific Manuscript database

Alfalfa (Medicago sativa) is the fourth most widely grown crop in the United States. Alfalfa crown rot is a disease complex that severely decreases alfalfa stand density and productivity in all alfalfa-producing areas. Currently, there are no viable methods of disease control. Plant defensins are sm...

In Celiac Disease, a Subset of Autoantibodies against Transglutaminase Binds Toll-Like Receptor 4 and Induces Activation of Monocytes

PubMed Central

Tridente, Giuseppe; Bason, Caterina; Sivori, Simona; Beri, Ruggero; Dolcino, Marzia; Valletta, Enrico; Corrocher, Roberto; Puccetti, Antonio

2006-01-01

Background Celiac disease is a small intestine inflammatory disorder with multiple organ involvement, sustained by an inappropriate immune response to dietary gluten. Anti-transglutaminase antibodies are a typical serological marker in patients with active disease, and may disappear during a gluten-free diet treatment. Involvement of infectious agents and innate immunity has been suggested but never proven. Molecular mimicry is one of the mechanisms that links infection and autoimmunity. Methods and Findings In our attempt to clarify the pathogenesis of celiac disease, we screened a random peptide library with pooled sera of patients affected by active disease after a pre-screening with the sera of the same patients on a gluten-free diet. We identified a peptide recognized by serum immunoglobulins of patients with active disease, but not by those of patients on a gluten-free diet. This peptide shares homology with the rotavirus major neutralizing protein VP-7 and with the self-antigens tissue transglutaminase, human heat shock protein 60, desmoglein 1, and Toll-like receptor 4. We show that antibodies against the peptide affinity-purified from the sera of patients with active disease recognize the viral product and self-antigens in ELISA and Western blot. These antibodies were able to induce increased epithelial cell permeability evaluated by transepithelial flux of [3H] mannitol in the T84 human intestinal epithelial cell line. Finally, the purified antibodies induced monocyte activation upon binding Toll-like receptor 4, evaluated both by surface expression of activation markers and by production of pro-inflammatory cytokines. Conclusions Our findings show that in active celiac disease, a subset of anti-transglutaminase IgA antibodies recognize the viral protein VP-7, suggesting a possible involvement of rotavirus infection in the pathogenesis of the disease, through a mechanism of molecular mimicry. Moreover, such antibodies recognize self-antigens and are functionally active, able to increase intestinal permeability and induce monocyte activation. We therefore provide evidence for the involvement of innate immunity in the pathogenesis of celiac disease through a previously unknown mechanism of engagement of Toll-like receptor 4. PMID:16984219

Evaluation of traditional Chinese medicinal plants for anti-MRSA activity with reference to the treatment record of infectious diseases.

PubMed

Zuo, Guo-Ying; Zhang, Xin-Juan; Yang, Cui-Xian; Han, Jun; Wang, Gen-Chun; Bian, Zhong-Qi

2012-03-09

The in vitro antimicrobial activities of 30 Chinese medicinal plants were evaluated with reference to the treatment record of infectious diseases in the Traditional Chinese Medicine (TCM) literature. The plant materials were extracted with 80% ethanol and the extracts were primarily screened against conventional clinical pathogens like Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans by the agar diffusion method. Their inhibition zone diameters (IZDs, mm, 50 mg/mL) ranged from 2,048 by the standard broth microdilution method. The seven extracts from M. yunnanensis, S. sinensis, G. morella, E. daneillii, M. squamulata, S. arborescens and B. hancei were determined as the most active extracts, with MICs of 8-64 μg/mL. The results were in good agreement with their traditional applications in skin and other infections.

Three-dimensional quantitative structure-activity relationship studies on c-Src inhibitors based on different docking methods.

PubMed

Bairy, Santhosh Kumar; Suneel Kumar, B V S; Bhalla, Joseph Uday Tej; Pramod, A B; Ravikumar, Muttineni

2009-04-01

c-Src kinase play an important role in cell growth and differentiation and its inhibitors can be useful for the treatment of various diseases, including cancer, osteoporosis, and metastatic bone disease. Three dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on quinazolin derivatives inhibiting c-Src kinase. Molecular field analysis (MFA) models with four different alignment techniques, namely, GLIDE, GOLD, LIGANDFIT and Least squares based methods were developed. glide based MFA model showed better results (Leave one out cross validation correlation coefficient r(2)(cv) = 0.923 and non-cross validation correlation coefficient r(2)= 0.958) when compared with other models. These results help us to understand the nature of descriptors required for activity of these compounds and thereby provide guidelines to design novel and potent c-Src kinase inhibitors.

MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate

PubMed Central

González-Mercado, Mirna Gisel; Rivas, Fernando; Gallegos-Arreola, M. Patricia; Morán-Moguel, M. Cristina; Salazar-Páramo, Mario; González-López, Laura; Gámez-Nava, J. Iván; Muñoz-Valle, J. Francisco; Medina-Coss y León, Ricardo; González-Mercado, Anahí; Aceves, Mario A.; Dávalos, Nory O.; Macías-Chumacera, Agustín

2017-01-01

Aim: To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Materials and Methods: Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction. Results: Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations. Conclusion: Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA. PMID:28994615

Quantitative Comparison of Active and Latent Tuberculosis in the Cynomolgus Macaque Model▿ †

PubMed Central

Lin, Philana Ling; Rodgers, Mark; Smith, Le'kneitah; Bigbee, Matthew; Myers, Amy; Bigbee, Carolyn; Chiosea, Ion; Capuano, Saverio V.; Fuhrman, Carl; Klein, Edwin; Flynn, JoAnne L.

2009-01-01

We previously described that low-dose Mycobacterium tuberculosis infection in cynomolgus macaques results in a spectrum of disease similar to that of human infection: primary disease, latent infection, and reactivation tuberculosis (S. V. Capuano III, D. A. Croix, S. Pawar, A. Zinovik, A. Myers, P. L. Lin, S. Bissel, C. Fuhrman, E. Klein, and J. L. Flynn, Infect. Immun. 71:5831-5844, 2003). This is the only established model of latent infection, and it provides a unique opportunity to understand host and pathogen differences across of range of disease states. Here, we provide a more extensive and detailed characterization of the gross pathology, microscopic histopathology, and immunologic characteristics of monkeys in each clinical disease category. The data underscore the similarities between human and nonhuman primate M. tuberculosis infection. Furthermore, we describe novel methods of quantifying gross pathology and bacterial burden that distinguish between active disease and latent infection, and we extend the usefulness of this model for comparative studies. Early in infection, an abnormal chest X ray, M. tuberculosis growth by gastric aspirate, and increased mycobacterium-specific gamma interferon (IFN-γ) in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells were associated with the development of active disease. At necropsy, disease was quantified with respect to pathology and bacterial numbers. Microscopically, a spectrum of granuloma types are seen and differ with disease type. At necropsy, monkeys with active disease had more lung T cells and more IFN-γ from PBMC, BAL, and mediastinal lymph nodes than monkeys with latent infection. Finally, we have observed a spectrum of disease not only in monkeys with active disease but also in those with latent infection that provides insight into human latent tuberculosis. PMID:19620341

Immunopathology of childhood celiac disease—Key role of intestinal epithelial cells

PubMed Central

Hedberg, Maria; Sjöberg, Veronika; Sandström, Olof; Hernell, Olle; Hammarström, Sten

2017-01-01

Background & Aims Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria. Methods Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells. Results More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells. Conclusion A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease. PMID:28934294

Expressive Behavior in Parkinson's Disease as a Function of Interview Context

PubMed Central

Takahashi, Kayoko; Tickle-Degnen, Linda; Coster, Wendy J.; Latham, Nancy K.

2010-01-01

OBJECTIVE Parkinson's disease affects the ability to express motivation through face, body, and voice; contextual factors may facilitate or inhibit expressive behavior. The purpose of this study was to determine whether qualities of the interview context are associated with client motivational behavior in Parkinson's disease. METHOD Men and women with Parkinson's disease (N = 106) discussed 2 topics (enjoyable activity vs. frustrating activity) during an assessment with a female or male interviewer. From videotaped clips, displays of 4 categories of motivation and 12 verbal and 18 nonverbal behavioral patterns were rated. RESULTS During the discussion of enjoyable activities, participants used more positive words, smiled more, and were more facially expressive. Participants were less talkative about their negative feelings and appeared to be more apathetic with the same-gender interviewer. CONCLUSION Occupational therapy practitioners should vary the emotional tone of their questions to improve the validity of motivation assessments. PMID:20608279

Quantification of mevalonate-5-phosphate using UPLC-MS/MS for determination of mevalonate kinase activity.

PubMed

Reitzle, Lukas; Maier, Barbara; Stojanov, Silvia; Teupser, Daniel; Muntau, Ania C; Vogeser, Michael; Gersting, Søren W

2015-08-01

Mevalonate kinase deficiency, a rare autosomal recessive autoinflammatory disease, is caused by mutations in the MVK gene encoding mevalonate kinase (MK). MK catalyzes the phosphorylation of mevalonic acid to mevalonate-5-phosphate (MVAP) in the pathway of isoprenoid and sterol synthesis. The disease phenotype correlates with residual activity ranging from <0.5% for mevalonic aciduria to 1-7% for the milder hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Hence, assessment of loss-of-function requires high accuracy measurements. We describe a method using isotope dilution UPLC-MS/MS for precise and sensitive determination of MK activity. Wild-type MK and the variant V261A, which is associated with HIDS, were recombinantly expressed in Escherichia coli. Enzyme activity was determined by formation of MVAP over time quantified by isotope dilution UPLC-MS/MS. The method was validated according to the FDA Guidance for Bioanalytical Method Validation. Sensitivity for detection of MAVP by UPLC-MS/MS was improved by derivatization with butanol-HCl (LLOQ, 5.0 fmol) and the method was linear from 0.5 to 250 μmol/L (R(2) > 0.99) with a precision of ≥ 89% and an accuracy of ± 2.7%. The imprecision of the activity assay, including the enzymatic reaction and the UPLC-MS/MS quantification, was 8.3%. The variant V261A showed a significantly decreased activity of 53.1%. Accurate determination of MK activity was enabled by sensitive and reproducible detection of MVAP using UPLC-MS/MS. The novel method may improve molecular characterization of MVK mutations, provide robust genotype-phenotype correlations, and accelerate compound screening for drug candidates restoring variant MK activity. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis

PubMed Central

Ishiuji, Y.; Coghill, R.C.; Patel, T.S.; Oshiro, Y.; Kraft, R.A.; Yosipovitch, G.

2009-01-01

Summary Background Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. Objectives To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). Methods Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. Results We found significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. Conclusions Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity. PMID:19663870

Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

PubMed Central

Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

2013-01-01

Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

Profile of patients with chronic obstructive pulmonary disease classified as physically active and inactive according to different thresholds of physical activity in daily life

PubMed Central

Furlanetto, Karina C.; Pinto, Isabela F. S.; Sant’Anna, Thais; Hernandes, Nidia A.; Pitta, Fabio

2016-01-01

ABSTRACT Objective To compare the profiles of patients with chronic obstructive pulmonary disease (COPD) considered physically active or inactive according to different classifications of the level of physical activity in daily life (PADL). Method Pulmonary function, dyspnea, functional status, body composition, exercise capacity, respiratory and peripheral muscle strength, and presence of comorbidities were assessed in 104 patients with COPD. The level of PADL was quantified with a SenseWear Armband activity monitor. Three classifications were used to classify the patients as physically active or inactive: 30 minutes of activity/day with intensity >3.2 METs, if age ≥65 years, and >4 METs, if age <65 years; 30 minutes of activity/day with intensity >3.0 METs, regardless of patient age; and 80 minutes of activity/day with intensity >3.0 METs, regardless of patient age. Results In all classifications, when compared with the inactive group, the physically active group had better values of anthropometric variables (higher fat-free mass, lower body weight, body mass index and fat percentage), exercise capacity (6-minute walking distance), lung function (forced vital capacity) and functional status (personal care domain of the London Chest Activity of Daily Living). Furthermore, patients classified as physically active in two classifications also had better peripheral and expiratory muscle strength, airflow obstruction, functional status, and quality of life, as well as lower prevalence of heart disease and mortality risk. Conclusion In all classification methods, physically active patients with COPD have better exercise capacity, lung function, body composition, and functional status compared to physically inactive patients. PMID:27683835

Physical Activity And Risk Of End Stage Kidney Disease In The Singapore Chinese Health Study

PubMed Central

Jafar, Tazeen Hasan; Jin, Aizhen; Koh, Woon-Puay; Yuan, Jian-Min; Chow, Khuan Yew

2015-01-01

Background Physical inactivity is a modifiable risk factor for cardiovascular disease. However, the relationship between physical activity and risk of end-stage kidney disease (ESKD) is not clear. Methods We analyzed data on a prospective cohort of 59,552 Chinese adults aged 45-74 years enrolled in the Singapore Chinese Health Study. Information on physical activity was collected with a structured questionnaire. Physically active individuals were defined as those who engaged in any moderate activities for 2 hours or more per week, and any strenuous activities 30 minutes or more per week. Incident ESKD was identified via record linkage with the Singapore Registry of Birth and Death and Singapore Renal Registry. Cox proportional hazards regression method was used for analysis for risk of incident ESKD alone or ESKD plus death associated with physical activity. Multivariable models were used to account for the potential confounding effect of sociodemographic, life style factors, and known co-morbidites on the physical activity-ESKD risk association. Results During a median follow-up of 15.3 years, a total of 642 incident ESKD occurred, and 9808 study participants died. A 24% lower adjusted risk of ESKD [hazard ratio (HR): 0.76; 95% confidence interval (CI): 0.62-0.93] was associated with moderate or strenuous physical activities compared to no regular physical activity. This association appeared to be dose dependent with the lowest risk for subjects at highest intensity of physical activity (p trend <0.003). Similar results were observed for risk of ESKD plus death. Conclusions Higher levels of physical activity are associated with lower risk of ESKD. Our findings highlight the role of physical activity for prevention of ESKD, which deserves further evaluation in intervention trials. PMID:25346108

Objectively assessed physical activity and lower limb function and prospective associations with mortality and newly diagnosed disease in UK older adults: an OPAL four-year follow-up study

PubMed Central

Fox, Kenneth R.; Ku, Po-Wen; Hillsdon, Melvyn; Davis, Mark G.; Simmonds, Bethany A. J.; Thompson, Janice L.; Stathi, Afroditi; Gray, Selena F.; Sharp, Deborah J.; Coulson, Joanne C.

2015-01-01

Background: objective measures of physical activity and function with a diverse cohort of UK adults in their 70s and 80s were used to investigate relative risk of all-cause mortality and diagnoses of new diseases over a 4-year period. Participants: two hundred and forty older adults were randomly recruited from 12 general practices in urban and suburban areas of a city in the United Kingdom. Follow-up included 213 of the baseline sample. Methods: socio-demographic variables, height and weight, and self-reported diagnosed diseases were recorded at baseline. Seven-day accelerometry was used to assess total physical activity, moderate-to-vigorous activity and sedentary time. A log recorded trips from home. Lower limb function was assessed using the Short Physical Performance Battery. Medical records were accessed on average 50 months post baseline, when new diseases and deaths were recorded. Analyses: ANOVAs were used to assess socio-demographic, physical activity and lower limb function group differences in diseases at baseline and new diseases during follow-up. Regression models were constructed to assess the prospective associations between physical activity and function with mortality and new disease. Results: for every 1,000 steps walked per day, the risk of mortality was 36% lower (hazard ratios 0.64, 95% confidence interval (CI) 0.44–0.91, P = 0.013). Low levels of moderate-to-vigorous physical activity (incident rate ratio (IRR) 1.67, 95% CI 1.04–2.68, P = 0.030) and low frequency of trips from home (IRR 1.41, 95% CI 0.98–2.05, P = 0.045) were associated with diagnoses of more new diseases. Conclusion: physical activity should be supported for adults in their 70s and 80s, as it is associated with reduced risk of mortality and new disease development. PMID:25377744

In Vitro Screening for Anti-Cholinesterase and Antioxidant Activity of Methanolic Extracts of Ayurvedic Medicinal Plants Used for Cognitive Disorders

PubMed Central

Mathew, Maya; Subramanian, Sarada

2014-01-01

Inhibition of Acetylcholinesterase (AChE) is still considered as the main therapeutic strategy against Alzheimer’s disease (AD). Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman’s microplate colorimetric method. Out of 20 extracts, Emblica officinalis, Nardostachys jatamansi, Nelumbo nucifera, Punica granatum and Raulfia Serpentina showed IC50 values <100 µg/ml for acetylcholinesterase inhibitory activity. Antioxidant activities of these plants were assessed by DPPH scavenging assay. Among the extracts used, antioxidant activity was highest for Terminalia chebula and Emblica officinalis with IC50 values <10 µg/ml. Considering the complex multifactorial etiology of AD, these plant extracts will be safer and better candidates for the future disease modifying therapies against this devastating disease. PMID:24466247

In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders.

PubMed

Mathew, Maya; Subramanian, Sarada

2014-01-01

Inhibition of Acetylcholinesterase (AChE) is still considered as the main therapeutic strategy against Alzheimer's disease (AD). Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman's microplate colorimetric method. Out of 20 extracts, Emblica officinalis, Nardostachys jatamansi, Nelumbo nucifera, Punica granatum and Raulfia Serpentina showed IC50 values <100 µg/ml for acetylcholinesterase inhibitory activity. Antioxidant activities of these plants were assessed by DPPH scavenging assay. Among the extracts used, antioxidant activity was highest for Terminalia chebula and Emblica officinalis with IC50 values <10 µg/ml. Considering the complex multifactorial etiology of AD, these plant extracts will be safer and better candidates for the future disease modifying therapies against this devastating disease.

[In vitro activity of doripenem against strains from pediatric diseases and strains causing purulent meningitis].

PubMed

Ohta, Merime; Toba, Shinsuke; Ito, Akinobu; Nakamura, Rio; Tsuji, Masakatsu

2012-12-01

This study evaluated the in vitro activity of doripenem (DRPM) against 200 Streptococcus pneumoniae and 197 Haemophilus influenzae from children and adults in 2007, 50 H. influenzae type b in 2006, 20 Listeria monocytogenes in 1990-2005, 23 Neisseria meningitidis in 2007-2009 and 83 Bordetella pertussis in 1989-2003. All strains were isolated from Japanese clinical facilities. We also investigated in vitro activity of other carbapenems (meropenem, imipenem, panipenem, biapenem), cephems (ceftriaxone, cefotaxime), ampicillin and clarithromycin. The all MICs were determined by a broth micro dilution method or an agar dilution method according to CLSI. The MIC90(s) of DRPM against S. pneumoniae and H. influenzae from children were 0.25 microg/mL, 1 microg/mL, respectively, which were similar to strains from adults. These results suggested that antibacterial activity of DRPM is not variable by patient's age. DRPM also showed excellent activities against H. influenzae type b, L. monocytogenes and N. meningitidis, which cause purulent meningitis, and B. pertussis causing whooping cough more than the other carbapenems. DRPM showed superior activities against serious strains of pediatric infection diseases.

Making the invisible visible: bioelectrical impedance analysis demonstrates unfavourable body composition in rheumatoid arthritis patients in clinical practice.

PubMed

Konijn, N P C; van Tuyl, L H D; Bultink, I E M; Lems, W F; Earthman, C P; van Bokhorst-de van der Schueren, M A E

2014-01-01

To examine differences between the assessment of body composition by body mass index (BMI) and bioelectrical impedance analysis (BIA) in patients with rheumatoid arthritis (RA). The body composition of RA patients was assessed during their visit to the outpatient department of a Dutch academic hospital using BMI, fat-free mass index (FFMI), and fat mass index (FMI). FFMI and FMI were determined by single-frequency BIA. Sixty-five consecutive RA patients (83% women, mean age 58 years, median disease duration 7 years) with moderately active disease [mean Disease Activity Score using 28 joint counts (DAS28) = 3.40; mean Rheumatoid Arthritis Disease Activity Index (RADAI) score = 3.49] and moderate disability [mean Health Assessment Questionnaire (HAQ) score = 0.87] were included. Based on BMI, 2% of our study population were underweight, 45% had a healthy body composition, and 54% were overweight or obese. Based on BIA, 18% of the patients showed a low FFMI and 74% had a high or very high FMI. Low FFMI was found in 44% of the women with a normal BMI, and high FMI was found in 40% of the women and 75% of the men with a normal BMI. A high frequency of unfavourable body composition, predominantly reduced FFMI and elevated FMI, was found in a cohort of RA patients with moderately active disease, turning BMI into an unreliable method for assessment of body composition in RA. BIA, however, might be the preferred method to assess FFMI and FMI in RA patients in clinical practice, as it is easy to use and relatively inexpensive.

Hepatic fat quantification using the two-point Dixon method and fat color maps based on non-alcoholic fatty liver disease activity score.

PubMed

Hayashi, Tatsuya; Saitoh, Satoshi; Takahashi, Junji; Tsuji, Yoshinori; Ikeda, Kenji; Kobayashi, Masahiro; Kawamura, Yusuke; Fujii, Takeshi; Inoue, Masafumi; Miyati, Tosiaki; Kumada, Hiromitsu

2017-04-01

The two-point Dixon method for magnetic resonance imaging (MRI) is commonly used to non-invasively measure fat deposition in the liver. The aim of the present study was to assess the usefulness of MRI-fat fraction (MRI-FF) using the two-point Dixon method based on the non-alcoholic fatty liver disease activity score. This retrospective study included 106 patients who underwent liver MRI and MR spectroscopy, and 201 patients who underwent liver MRI and histological assessment. The relationship between MRI-FF and MR spectroscopy-fat fraction was used to estimate the corrected MRI-FF for hepatic multi-peaks of fat. Then, a color FF map was generated with the corrected MRI-FF based on the non-alcoholic fatty liver disease activity score. We defined FF variability as the standard deviation of FF in regions of interest. Uniformity of hepatic fat was visually graded on a three-point scale using both gray-scale and color FF maps. Confounding effects of histology (iron, inflammation and fibrosis) on corrected MRI-FF were assessed by multiple linear regression. The linear correlations between MRI-FF and MR spectroscopy-fat fraction, and between corrected MRI-FF and histological steatosis were strong (R 2  = 0.90 and R 2  = 0.88, respectively). Liver fat variability significantly increased with visual fat uniformity grade using both of the maps (ρ = 0.67-0.69, both P < 0.001). Hepatic iron, inflammation and fibrosis had no significant confounding effects on the corrected MRI-FF (all P > 0.05). The two-point Dixon method and the gray-scale or color FF maps based on the non-alcoholic fatty liver disease activity score were useful for fat quantification in the liver of patients without severe iron deposition. © 2016 The Japan Society of Hepatology.

Company Profile: Selventa, Inc.

PubMed

Fryburg, David A; Latino, Louis J; Tagliamonte, John; Kenney, Renee D; Song, Diane H; Levine, Arnold J; de Graaf, David

2012-08-01

Selventa, Inc. (MA, USA) is a biomarker discovery company that enables personalized healthcare. Originally founded as Genstruct, Inc., Selventa has undergone significant evolution from a technology-based service provider to an active partner in the development of diagnostic tests, functioning as a molecular dashboard of disease activity using a unique platform. As part of that evolution, approximately 2 years ago the company was rebranded as Selventa to reflect its new identity and mission. The contributions to biomedical research by Selventa are based on in silico, reverse-engineering methods to determine biological causality. That is, given a set of in vitro or in vivo biological observations, which biological mechanisms can explain the measured results? Facilitated by a large and carefully curated knowledge base, these in silico methods generated new insights into the mechanisms driving a disease. As Selventa's methods would enable biomarker discovery and be directly applicable to generating novel diagnostics, the scientists at Selventa have focused on the development of predictive biomarkers of response in autoimmune and oncologic diseases. Selventa is presently building a portfolio of independent, as well as partnered, biomarker projects with the intention to create diagnostic tests that predict response to therapy.

Research and Operational Support for the Study of Militarily Relevant Infectious Diseases of Interest to the United States Army and the Royal Thai Army

DTIC Science & Technology

2008-01-01

funding support for Royal Thai Army at Armed Forces Research Institute of Medical Sciences (AFRIMS) engaged in research activities in collaboration with... Active and Passive Protection of Mice against Japanese Encephalitis Virus 55 (a) Investigators 55 (b) Objectives 55 (c) Methods 55 (d) Results...Research Project: Sentinel Surveillance for Emerging Diseases Causing Dengue-like or Acute Encephalitis Syndrome in the Philippines (SEDP) 83 (a

Dynamic Neuro-Cognitive Imagery Improves Mental Imagery Ability, Disease Severity, and Motor and Cognitive Functions in People with Parkinson's Disease

PubMed Central

Hart, Ariel; Andrade, Isaac; Hackney, Madeleine E.

2018-01-01

People with Parkinson's disease (PD) experience kinesthetic deficits, which affect motor and nonmotor functions, including mental imagery. Imagery training is a recommended, yet underresearched, approach in PD rehabilitation. Dynamic Neuro-Cognitive Imagery (DNI™) is a codified method for imagery training. Twenty subjects with idiopathic PD (Hoehn and Yahr stages I–III) were randomly allocated into DNI training (experimental; n = 10) or in-home learning and exercise program (control; n = 10). Both groups completed at least 16 hours of training within two weeks. DNI training focused on anatomical embodiment and kinesthetic awareness. Imagery abilities, disease severity, and motor and nonmotor functions were assessed pre- and postintervention. The DNI participants improved (p < .05) in mental imagery abilities, disease severity, and motor and spatial cognitive functions. Participants also reported improvements in balance, walking, mood, and coordination, and they were more physically active. Both groups strongly agreed they enjoyed their program and were more mentally active. DNI training is a promising rehabilitation method for improving imagery ability, disease severity, and motor and nonmotor functions in people with PD. This training might serve as a complementary PD therapeutic approach. Future studies should explore the effect of DNI on motor learning and control strategies. PMID:29725348

Efficient mining of association rules for the early diagnosis of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Chaves, R.; Górriz, J. M.; Ramírez, J.; Illán, I. A.; Salas-Gonzalez, D.; Gómez-Río, M.

2011-09-01

In this paper, a novel technique based on association rules (ARs) is presented in order to find relations among activated brain areas in single photon emission computed tomography (SPECT) imaging. In this sense, the aim of this work is to discover associations among attributes which characterize the perfusion patterns of normal subjects and to make use of them for the early diagnosis of Alzheimer's disease (AD). Firstly, voxel-as-feature-based activation estimation methods are used to find the tridimensional activated brain regions of interest (ROIs) for each patient. These ROIs serve as input to secondly mine ARs with a minimum support and confidence among activation blocks by using a set of controls. In this context, support and confidence measures are related to the proportion of functional areas which are singularly and mutually activated across the brain. Finally, we perform image classification by comparing the number of ARs verified by each subject under test to a given threshold that depends on the number of previously mined rules. Several classification experiments were carried out in order to evaluate the proposed methods using a SPECT database that consists of 41 controls (NOR) and 56 AD patients labeled by trained physicians. The proposed methods were validated by means of the leave-one-out cross validation strategy, yielding up to 94.87% classification accuracy, thus outperforming recent developed methods for computer aided diagnosis of AD.

Application of biosensors to detection of epidemic diseases in animals.

PubMed

Du, Xin; Zhou, Jun

2018-06-01

Epidemic diseases are the leading cause of animal mortality, resulting in significant losses to the agricultural economy. These economic impacts have generated a strong interest in advancing methods for the diagnosis and control of epidemic diseases in animals. Conventional methods are often time-consuming (typically result is available in 2-10 days), expensive, and require both large-scale equipment and experienced personnel. However, the advent of biosensor technology has ushered in a new and promising approach for the diagnosis of animal diseases. With advantages that include simplicity, real -time analysis, high sensitivity, miniaturization, rapid detection time, and low cost, biosensor technologies are under active development for the diagnosis of epidemic diseases in animals. Here, we summarize recent developments in biological sensing technologies used to detect infectious viral, bacterial, and parasitic diseases. Additionally, we discuss research challenges and future prospects for this field of study. Copyright © 2018 Elsevier Ltd. All rights reserved.

Techniques for chronic monitoring of brain activity in freely moving sheep using wireless EEG recording.

PubMed

Perentos, N; Nicol, A U; Martins, A Q; Stewart, J E; Taylor, P; Morton, A J

2017-03-01

Large mammals with complex central nervous systems offer new possibilities for translational research into basic brain function. Techniques for monitoring brain activity in large mammals, however, are not as well developed as they are in rodents. We have developed a method for chronic monitoring of electroencephalographic (EEG) activity in unrestrained sheep. We describe the methods for behavioural training prior to implantation, surgical procedures for implantation, a protocol for reliable anaesthesia and recovery, methods for EEG data collection, as well as data pertaining to suitability and longevity of different types of electrodes. Sheep tolerated all procedures well, and surgical complications were minimal. Electrode types used included epidural and subdural screws, intracortical needles and subdural disk electrodes, with the latter producing the best and most reliable results. The implants yielded longitudinal EEG data of consistent quality for periods of at least a year, and in some cases up to 2 years. This is the first detailed methodology to be described for chronic brain function monitoring in freely moving unrestrained sheep. The developed method will be particularly useful in chronic investigations of brain activity during normal behaviour that can include sleep, learning and memory. As well, within the context of disease, the method can be used to monitor brain pathology or the progress of therapeutic trials in transgenic or natural disease models in sheep. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthetic Nucleic Acids and Treatment of Neurological Diseases.

PubMed

Corey, David R

2016-10-01

The ability to control gene expression with antisense oligonucleotides (ASOs) could provide a new treatment strategy for disease. To review the use of ASOs for the treatment of neurological disorders. Articles were identified through a search of PubMed references from 2000 to 2016 for articles describing the use of ASOs to treat disease, with specific attention to neurological disease. We concentrated our review on articles pertaining to activation of frataxin expression (Friedreich's ataxia) and production of active survival motor neuron 2 (SMN2, spinal muscular atrophy). Many neurological diseases are caused by inappropriate expression of a protein. Mutations may reduce expression of a wild-type protein, and strategies to activate expression may provide therapeutic benefit. For other diseases, a mutant protein may be expressed too highly and methods that reduce mutant protein expression might form the basis for drug development. Synthetic ASOs can recognize cellular RNA and control gene expression. Antisense oligonucleotides are not a new concept, but successful clinical development has proceeded at a slow pace. Advances in ASO chemistry, biological understanding, and clinical design are making successful applications more likely. Both laboratory and clinical studies are demonstrating the potential of ASOs as a source of drugs to treat neurological disease.

Fecal volatile organic compounds: a novel, cheaper method of diagnosing inflammatory bowel disease?

PubMed

Probert, Chris S J; Reade, Sophie; Ahmed, Iftikhar

2014-09-01

The investigation of a novel, cheaper method of diagnosing inflammatory bowel disease (IBD) is an area of active research. Recently, investigations into the metabolomic profile of IBD patients and animal models of colitis compared to healthy controls has begun to receive considerable attention and correlations between the fecal volatile organic compound (VOC) metabolome and IBD is merging. Patients and clinicians have often reported a change in odor of feces during relapse of IBD. Therefore, this article will focus specifically on the fecal VOC metabolome and its potential role in identifying a novel diagnostic method for IBD.

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

PubMed Central

2013-01-01

Introduction The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS. PMID:24499523

Vital Signs: Disability and Physical Activity — United States, 2009–2012

PubMed Central

Carroll, Dianna D.; Courtney-Long, Elizabeth A.; Stevens, Alissa C.; Sloan, Michelle L.; Lullo, Carolyn; Visser, Susanna N.; Fox, Michael H.; Armour, Brian S.; Campbell, Vincent A.; Brown, David R.; Dorn, Joan M.

2014-01-01

Background Adults with disabilities are less active and have higher rates of chronic disease than the general population. Given the health benefits of physical activity, understanding physical activity, its relationship with chronic disease, and health professional recommendations for physical activity among young to middle-age adults with disabilities could help increase the effectiveness of health promotion efforts. Methods Data from the 2009–2012 National Health Interview Survey (NHIS) were used to estimate the prevalence of, and association between, aerobic physical activity (inactive, insufficiently active, or active) and chronic diseases (heart disease, stroke, diabetes, and cancer) among adults aged 18–64 years by disability status and type (hearing, vision, cognitive, and mobility). The prevalence of, and association between, receiving a health professional recommendation for physical activity and level of aerobic physical activity was assessed using 2010 data. Results Overall, 11.6% of U.S. adults aged 18–64 years reported a disability, with estimates for disability type ranging from 1.7% (vision) to 5.8% (mobility). Compared with adults without disabilities, inactivity was more prevalent among adults with any disability (47.1% versus 26.1%) and for adults with each type of disability. Inactive adults with disabilities were 50% more likely to report one or more chronic diseases than those who were physically active. Approximately 44% of adults with disabilities received a recommendation from a health professional for physical activity in the past 12 months. Conclusions Almost half of adults with disabilities are physically inactive and are more likely to have a chronic disease. Among adults with disabilities who visited a health professional in the past 12 months, the majority (56%) did not receive a recommendation for physical activity. Implications for Public Health These data highlight the need for increased physical activity among persons with disabilities, which might require support across societal sectors, including government and health care. PMID:24807240

Fecal Calprotectin in Ileal Crohn's Disease: Relationship with Magnetic Resonance Enterography and a Pathology Score.

PubMed

Cerrillo, Elena; Beltrán, Belén; Pous, Salvador; Echarri, Ana; Gallego, Jose Carlos; Iborra, Marisa; Pamies, Jose; Nos, Pilar

2015-07-01

Magnetic resonance enterography (MRE) is an effective method of assessing small bowel Crohn's disease (CD). Fecal calprotectin (FC) correlates well with endoscopic disease activity. We aimed to evaluate the correlation between FC and disease activity according to MRE and surgical pathology in small bowel CD. One hundred twenty consecutive patients with ileal CD who underwent MRE assessment were included. Clinical data, C-reactive protein and FC, radiological and histological variables were obtained. Clinical activity was evaluated by the Harvey-Bradshaw Index and FC by enzyme-linked immunosorbent assay. MRE activity was assessed by means of the Magnetic Resonance Index of Activity score. Chiorean's score was used to grade pathological inflammation in surgical specimens. Seventy-five patients (62.5%) were in clinical remission (Harvey-Bradshaw Index < 5) and 45 (37.5%) had active disease (Harvey-Bradshaw Index ≥ 5). The Magnetic Resonance Index of Activity score was significantly associated with FC levels (P < 0.01), with a moderate overall correlation (Spearman's r = 0.56, P < 0.001). FC reflected MRE inflammatory activity with an area under the receiver operating characteristic curve of 0.914 (confidence interval, 0.849-0.958; P < 0.001). A cutoff value of 166.50 μg/g had 90% sensitivity, 74% specificity, 89% positive predictive value, and 76% negative predictive value for diagnosis of inflammation. Twenty-eight of 120 patients were operated. Surgical pathology showed a good agreement with FC for moderate (P = 0.03) and severe (P = 0.01) Chiorean's index. No relationship was detected for C-reactive protein. FC correlates with the degree of MRE inflammatory activity and with surgical pathology damage in ileal CD. Thus, FC could be a surrogate marker of disease control used to select patients for MRE assessment and therapeutic adjustment.

Comparative study to evaluate the anti-viral efficacy of Glycyrrhiza glabra extract and ribavirin against the Newcastle disease virus

PubMed Central

Omer, Muhammad Ovais; AlMalki, Waleed Hassan; Shahid, Imran; Khuram, Shahzada; Altaf, Imran; Imran, Saeed

2014-01-01

Background: The Newcastle disease represents as one of the most infectious viral disease, which afflicts almost every species of the birds. The causative agent of the disease is a single-stranded RNA virus with rapid replication capability. Objective: This study was performed to evaluate the comparative anti-viral efficacy and toxicity of Glycyrrhiza glabra aqueous extract and ribavirin against the Newcastle disease virus. Materials and Methods: The embryonated eggs were divided into six groups (A, B, C, D, E and F). Groups A, B, C, and D were further subdivided into three subgroups. The virus was identified by hemagglutination inhibition test. Spot hemagglutination test and viability of embryos were also evaluated. Three different concentrations i-e., 30 mg/100 ml, 60 mg/100 ml, and 120 mg/100 ml of the Glycyrrhiza aqueous extract and 10 μg/ml, 20 μg/ml, and 40 μg/ml ribavirin in deionized water were evaluated for their toxicity and anti-viral activity in the embryonated eggs. Results: 60 mg/100 ml concentration of Glycyrrhiza extract did not produce any toxicity in the embryonated eggs and showed anti-viral activity against the virus. Similarly, 20 μg/ml ribavirin was non-toxic in the embryonated eggs and contained anti-viral activity. Conclusion: It may conclude from the presented study that 60 mg/100 ml Glycyrrhiza extract inhibits replication of Newcastle disease virus and is non-toxic in the embryonated eggs. So, Glycyrrhiza glabra extract may be further evaluated in future to determine the potentially active compounds for their anti-viral activity against Newcastle disease virus. Furthermore, the mechanism of action of these active phytochemicals as an antiviral agent would be helpful to elucidate the pathogenesis of the disease. PMID:24497736

Novel diagnostic techniques for celiac disease.

PubMed

Kurppa, Kalle; Taavela, Juha; Saavalainen, Päivi; Kaukinen, Katri; Lindfors, Katri

2016-07-01

The diagnosis of celiac disease has long been based on the demonstration of gluten-induced small-bowel mucosal damage. However, due to the constantly increasing disease prevalence and limitations in the histology-based criteria there is a pressure towards more serology-based diagnostics. The serological tools are being improved and new non-invasive methods are being developed, but the constantly refined endoscopic and histologic techniques may still prove helpful. Moreover, growing understanding of the disease pathogenesis has led researchers to suggest completely novel approaches to celiac disease diagnostics regardless of disease activity. In this review, we will elucidate the most recent development and possible future innovations in the diagnostic techniques for celiac disease.

An Automatic User-Adapted Physical Activity Classification Method Using Smartphones.

PubMed

Li, Pengfei; Wang, Yu; Tian, Yu; Zhou, Tian-Shu; Li, Jing-Song

2017-03-01

In recent years, an increasing number of people have become concerned about their health. Most chronic diseases are related to lifestyle, and daily activity records can be used as an important indicator of health. Specifically, using advanced technology to automatically monitor actual activities can effectively prevent and manage chronic diseases. The data used in this paper were obtained from acceleration sensors and gyroscopes integrated in smartphones. We designed an efficient Adaboost-Stump running on a smartphone to classify five common activities: cycling, running, sitting, standing, and walking and achieved a satisfactory classification accuracy of 98%. We designed an online learning method, and the classification model requires continuous training with actual data. The parameters in the model then become increasingly fitted to the specific user, which allows the classification accuracy to reach 95% under different use environments. In addition, this paper also utilized the OpenCL framework to design the program in parallel. This process can enhance the computing efficiency approximately ninefold.

Disparity between Physical Capacity and Participation in Seniors with Chronic Disease

PubMed Central

Ashe, Maureen C.; Eng, Janice J.; Miller, William C.; Soon, Judith A.

2011-01-01

Consistently low rates of physical activity are reported for older adults and there is even lower participation if a chronic disease is present. Purpose To explore the predictors of physical capacity and participation in older community-dwelling individuals living with multiple chronic diseases. Methods This was a descriptive cross-sectional investigation of physical capacity (physiological potential) and physical activity participation (recorded engagement in physical activity). Multiple regression and odds ratios were used to investigate determinants of physical capacity (6 Minute Walk Test) and physical activity participation (Physical Activity Scale for Individuals with Physical Disabilities Questionnaire; pedometer steps/day). Results 200 community dwelling ambulatory participants living with 2 or more chronic disease were assessed. Sixty-five percent (65%) were women and the mean age was 74 ± 6 years (range 65–90 years). Mobility (Timed Up and Go) was a consistent determinant across all 3 primary outcomes. For the Six Minute Walk Test, determinants included mobility, BMI, grip strength, number of medications, leg strength, balance and Chronic Disease Management Self Efficacy Scale (r2=0.58; P=.000). The determinants for the self-reported participation measure (Physical Activity Scale for Individuals with Physical Disabilities Questionnaire) was mobility (r2=0.04; P=.007). For the mean daily pedometer steps, the determinants included mobility, body mass index (BMI), age and Chronic Disease Management Self-Efficacy Scale (r2=0.27; P=.000). There were higher risks for inactivity associated with impairments compared with the presence of a chronic disease. In addition, over 1/3 of participants had sufficient physical capacity, but did not meet minimal recommendations of physical activity. Conclusion This study suggests that it is easier to predict an individual’s physical capacity than their actual physical participation. PMID:17596782

MS disease activity in RESTORE

PubMed Central

Cree, Bruce A.C.; De Sèze, Jerome; Gold, Ralf; Hartung, Hans-Peter; Jeffery, Douglas; Kappos, Ludwig; Kaufman, Michael; Montalbán, Xavier; Weinstock-Guttman, Bianca; Anderson, Britt; Natarajan, Amy; Ticho, Barry; Duda, Petra

2014-01-01

Objective: RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab. Methods: Eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon β-1a [IM IFN-β-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks. Results: Patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-β-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-β-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%–29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4–8 weeks (n = 2 in weeks 4–8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity. Conclusions: MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies. Classification of evidence: This study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab. PMID:24682966

Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus: No association with subclinical viral reactivations or lupus disease activity.

PubMed

Rondaan, C; van Leer, C C; van Assen, S; Bootsma, H; de Leeuw, K; Arends, S; Bos, N A; Westra, J

2018-07-01

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia.

Pilot surveillance for childhood encephalitis in Australia using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network.

PubMed

Britton, P N; Dale, R C; Elliott, E; Festa, M; Macartney, K; Booy, R; Jones, C A

2016-07-01

We aimed to assess the performance of active surveillance for hospitalized childhood encephalitis in New South Wales (NSW) using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network to inform methodology for the nationwide Australian childhood encephalitis (ACE) study. We piloted active surveillance for suspected encephalitis from May to December 2013 at the Children's Hospital at Westmead, Sydney, NSW. Cases were ascertained using four screening methods: weekday nurse screening of admission records (PAEDS), cerebrospinal fluid (CSF) microscopy records, magnetic resonance imaging (MRI) reports, and pharmacy dispensing records. Comprehensive clinical data were prospectively collected on consented participants and subsequently reviewed by an expert panel. Cases were categorized as confirmed encephalitis or 'not encephalitis'; encephalitis cases were sub-categorized as infectious, immune-mediated or unknown. We performed an ICD-10 diagnostic code audit of hospitalizations for the pilot period. We compared case ascertainment in the four screening methods and with the ICD code audit. Forty-eight cases of suspected encephalitis were identified by one or more methods. PAEDS was the most efficient mechanism (yield 34%), followed by MRI, CSF, and pharmacy audits (yield 14%, 12%, and 7% respectively). Twenty-five cases met the criteria for confirmed encephalitis. PAEDS was the most sensitive of the mechanisms for confirmed encephalitis (92%) with a positive predictive value (PPV) of 72%. The ICD audit was moderately sensitive (64%) but poorly specific (Sp 9%, PPV 14%). Of the 25 confirmed encephalitis cases, 19 (76%) were sub-categorized as infectious, three (12%) were immune-mediated, and three (12%) were 'unknown'. We identified encephalitis cases associated with two infectious disease outbreaks (enterovirus 71, parechovirus 3). PAEDS is an efficient, sensitive and accurate surveillance mechanism for detecting cases of childhood encephalitis including those associated with emerging infectious diseases. Active surveillance significantly increases the ascertainment of encephalitis cases compared with passive approaches.

Actigraphy monitoring of symptoms in patients with Parkinson's disease.

PubMed

Pan, Weidong; Kwak, Shin; Li, Fuzhong; Wu, Chunlan; Chen, Yiyun; Yamamoto, Yoshiharu; Cai, Dingfang

2013-07-02

Although the Unified Parkinson's Disease Rating Scale (UPDRS) is the "gold-standard" tool in assessing the severity of symptoms in patients with Parkinson's disease (PD), not all activity-related disease symptoms can be accurately captured by the well-established clinical rating scale. Using an alternative approach, this study examined the level of physical activity measured by actigraphy over time and whether change in physical activity was associated with disease severity assessed by UPDRS. We used a longitudinal design in which physical activity and disease severity were assessed repeatedly during a 4-month interval, over a 3-year observational period, in a sample of 61 patients with idiopathic PD and a control group of 32 neurologically intact individuals. Physical activity data during awake-time were analyzed using the power-law exponent (PLE) method. Correlational relationships between changes in maxima values of PLE and scores of total UPDRS, UPDRS-part II (Activities of Daily Living), and UPDRS-part III (Motor Examination) in patients with PD were examined. Results show an increase in maxima values of PLE and the UPDRS total score in PD patients and that there is a positive association between changes in maxima values and total UPDRS score (r=0.746, p=0.032), UPDRS-part II score (r=0.687, p=0.027), and UPDRS-part III score (r=0.893, p=0.018). There was no significant change in the level of physical activity over time for the controls. Findings from this study indicate that change in physical activity, as captured by actigraphy, is associated with increased severity in patients' clinical symptoms of PD over time. Thus, these data suggest that, when used in conjunction with the conventional UPDRS measure, an actigraphic measure of physical activity may provide clinicians an adjunct measurement approach to monitor patients' activity-based disease progression or responses to treatment in outpatient clinic settings. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Assessment of leg muscle activity using toe tapping in patients with Parkinson's disease: comparison of two types of toe tapping.

PubMed

Taniguchi, Seira; Peper, Ferdinand; Shimokawa, Tetsuya

2018-05-01

[Purpose] This study investigates two types of toe tapping, i.e., "closed," with both feet on the floor, and "open," in which the foot does not touch the ground, and evaluates their usefulness in combination with monitoring of muscle activity during toe tapping. [Subjects and Methods] The study enrolled 11 patients with Parkinson's disease (PD) and 9 controls (Controls). The tibialis anterior (TA) and gastrocnemius (GS) muscle activity during toe tapping was measured using surface electromyography. [Results] In closed tapping, the minima in GS activation with the first tap was significantly higher in patients with PD than in Controls. In open tapping, the coefficient of variation (CV) of local maxima in TA activation was significantly higher in patients with PD than in Controls. In both types of tapping, the CV of extrema in GS activities increased with disease duration, but this may be due to the long-term administration of Levodopa, which itself tends to cause excessive GS activities. [Conclusion] Closed tapping is suitable for the assessment of GS activity and can detect excessive activities, which is observed as visible movement. Open tapping, on the other hand, is suitable for assessment of TA activity.

Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

PubMed Central

Curtis, Jeffrey R; van der Helm-van Mil, Annette H; Knevel, Rachel; Huizinga, Tom W; Haney, Douglas J; Shen, Yijing; Ramanujan, Saroja; Cavet, Guy; Centola, Michael; Hesterberg, Lyndal K; Chernoff, David; Ford, Kerri; Shadick, Nancy A; Hamburger, Max; Fleischmann, Roy; Keystone, Edward; Weinblatt, Michael E

2012-01-01

Objective Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Methods Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti–tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. Results The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6–12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02). Conclusion Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition. PMID:22736476

Association of weight loss with improved disease activity in patients with rheumatoid arthritis: A retrospective analysis using electronic medical record data

PubMed Central

Kreps, David J.; Halperin, Florencia; Desai, Sonali P.; Zhang, Zhi Z.; Losina, Elena; Olson, Amber T.; Karlson, Elizabeth W.; Bermas, Bonnie L.; Sparks, Jeffrey A.

2018-01-01

Objective To evaluate the association between weight loss and rheumatoid arthritis (RA) disease activity. Methods We conducted a retrospective cohort study of RA patients seen at routine clinic visits at an academic medical center, 2012–2015. We included patients who had ≥2 clinical disease activity index (CDAI) measures. We identified visits during follow-up where the maximum and minimum weights occurred and defined weight change and CDAI change as the differences of these measures at these visits. We defined disease activity improvement as CDAI decrease of ≥5 and clinically relevant weight loss as ≥5 kg. We performed logistic regression analyses to establish the association between improved disease activity and weight loss and baseline BMI category (≥25 kg/m2 or <25 kg/m2). We built linear regression models to investigate the association between continuous weight loss and CDAI change among patients who were overweight/obese at baseline and who lost weight during follow-up. Results We analyzed data from 174 RA patients with a median follow-up of 1.9 years (IQR 1.3–2.4); 117 (67%) were overweight/obese at baseline, and 53 (31%) lost ≥5 kg during follow-up. Patients who were overweight/obese and lost ≥5 kg had three-fold increased odds of disease activity improvement compared to those who did not (OR 3.03, 95%CI 1.18–7.83). Among those who were overweight/obese at baseline, each kilogram weight loss was associated with CDAI improvement of 1.15 (95%CI 0.42–1.88). Our study was limited by using clinical data from a single center without fixed intervals for assessments. Conclusion Clinically relevant weight loss (≥5 kg) was associated with improved RA disease activity in the routine clinical setting. Further studies are needed for replication and to evaluate the effect of prospective weight loss interventions on RA disease activity. PMID:29606976

Quantifying bone marrow edema in the rheumatoid cervical spine using magnetic resonance imaging.

PubMed

Suppiah, Ravi; Doyle, Anthony; Rai, Raylynne; Dalbeth, Nicola; Lobo, Maria; Braun, Jürgen; McQueen, Fiona M

2010-08-01

To determine the reliability and feasibility of a new magnetic resonance imaging (MRI) score to quantify bone marrow edema (BME), synovitis, and erosions in the cervical spine of patients with rheumatoid arthritis (RA); and to investigate the correlations among neck pain, clinical markers of RA disease activity, and MRI features of disease activity in the cervical spine. Thirty patients with RA (50% with neck pain) and a Disease Activity Score 28-joint count > 3.2 had an MRI scan of their cervical spine. STIR, VIBE, and T1-weighted postcontrast sequences were used to quantify BME. MRI scans were scored for total BME, synovitis, and erosions using a new scoring method developed by the authors and assessed for reliability and feasibility. Associations between neck pain and clinical markers of disease activity were investigated. BME was present in 14/30 patients; 9/14 (64%) had atlantoaxial BME, 10/14 (71%) had subaxial BME, and 5/14 (36%) had both. Interobserver reliability for total cervical BME score was moderate [intraclass correlation coefficient (ICC) = 0.51]. ICC improved to 0.67 if only the vertebral bodies and dens were considered. There was no correlation between neck pain or clinical measures of RA disease activity and the presence of any MRI features including BME, synovitis, or erosions. Current RA disease activity scores do not identify activity in the cervical spine. An MRI score that quantifies BME, synovitis, and erosions in the cervical spine may provide useful information regarding inflammation and damage. This could alert clinicians to the presence of significant pathology and influence management.

Single-Cell Sequencing of the Healthy and Diseased Heart Reveals Ckap4 as a New Modulator of Fibroblasts Activation.

PubMed

Gladka, Monika M; Molenaar, Bas; de Ruiter, Hesther; van der Elst, Stefan; Tsui, Hoyee; Versteeg, Danielle; Lacraz, Grègory P A; Huibers, Manon M H; van Oudenaarden, Alexander; van Rooij, Eva

2018-01-31

Background -Genome-wide transcriptome analysis has greatly advanced our understanding of the regulatory networks underlying basic cardiac biology and mechanisms driving disease. However, so far, the resolution of studying gene expression patterns in the adult heart has been limited to the level of extracts from whole tissues. The use of tissue homogenates inherently causes the loss of any information on cellular origin or cell type-specific changes in gene expression. Recent developments in RNA amplification strategies provide a unique opportunity to use small amounts of input RNA for genome-wide sequencing of single cells. Methods -Here, we present a method to obtain high quality RNA from digested cardiac tissue from adult mice for automated single-cell sequencing of both the healthy and diseased heart. Results -After optimization, we were able to perform single-cell sequencing on adult cardiac tissue under both homeostatic conditions and after ischemic injury. Clustering analysis based on differential gene expression unveiled known and novel markers of all main cardiac cell types. Based on differential gene expression we were also able to identify multiple subpopulations within a certain cell type. Furthermore, applying single-cell sequencing on both the healthy and the injured heart indicated the presence of disease-specific cell subpopulations. As such, we identified cytoskeleton associated protein 4 ( Ckap4 ) as a novel marker for activated fibroblasts that positively correlates with known myofibroblast markers in both mouse and human cardiac tissue. Ckap4 inhibition in activated fibroblasts treated with TGFβ triggered a greater increase in the expression of genes related to activated fibroblasts compared to control, suggesting a role of Ckap4 in modulating fibroblast activation in the injured heart. Conclusions -Single-cell sequencing on both the healthy and diseased adult heart allows us to study transcriptomic differences between cardiac cells, as well as cell type-specific changes in gene expression during cardiac disease. This new approach provides a wealth of novel insights into molecular changes that underlie the cellular processes relevant for cardiac biology and pathophysiology. Applying this technology could lead to the discovery of new therapeutic targets relevant for heart disease.

Thermographic venous blood flow characterization with external cooling stimulation

NASA Astrophysics Data System (ADS)

Saxena, Ashish; Ng, E. Y. K.; Raman, Vignesh

2018-05-01

Experimental characterization of blood flow in a human forearm is done with the application of continuous external cooling based active thermography method. Qualitative and quantitative detection of the blood vessel in a thermal image is done, along with the evaluation of blood vessel diameter, blood flow direction, and velocity in the target blood vessel. Subtraction based image manipulation is performed to enhance the feature contrast of the thermal image acquired after the removal of external cooling. To demonstrate the effect of occlusion diseases (obstruction), an external cuff based occlusion is applied after the removal of cooling and its effect on the skin rewarming is studied. Using external cooling, a transit time method based blood flow velocity estimation is done. From the results obtained, it is evident that an external cooling based active thermography method can be used to develop a diagnosis tool for superficial blood vessel diseases.

Participatory epidemiology at the neotropics: study of diseases of backyard livestock and description of hunting patterns in Uaxactún, Maya Reserve Biosphere, Guatemala.

PubMed

Mérida Ruíz, Samuel Alberto; Guerra Centeno, Dennis Sigfried; Bailey Leonardo, Edgar Leonel; Rohn, Karl; Kösters, Sarah; Kreienbrock, Lothar

2016-04-07

The intention of the following study was to describe the interrelationship between villagers, domestic animals and wildlife at the Community Forestry Concession of Uaxactún, Guatemala by means of participatory epidemiological methods. The main focus was generating information regarding different livestock diseases considered important by villagers and their relevance, as well as obtaining knowledge concerning hunting activities and cooking methods to gain a better understanding of the interrelationship of people and animals and the diseases of their animals. For poultry, an overall prevalence of 41% of Newcastle disease was found by means of the ELISA test by antibody detection, chicken being the most affected species in the village. No samples were positive to avian influenza with the HI test. No virus was isolated by means of the tracheal or cloaca swabbing of ducks. All species could be hunted by chance at any time of the year. There was a difference in species hunted between seasons, peccaries being more frequently hunted during the dry season and in contrast, deer and wild avian during the rainy season. Villagers did not consume any raw meat. The cooking methods depended on the species. Stewing was the most favoured method for peccaries, wild birds, tepezcuintle and domestic poultry, whereas grilling was preferable for deer, roasting for armadillos and marinating for pork. According to the generated information, the most important domestic livestock species in the village are chickens and pigs, chickens being the most affected by diseases. No evident health problems on pigs were observed in this study. Hunting was shown as an activity enhanced by poverty and the lack of employment opportunities in the village and was mostly directed at larger species such as deer and peccaries. From the viewpoint of a transmission of zoonoses from animals to humans cooking methods mostly reflected a protective factor as no raw meat was eaten, stews and broths being the most common forms of cooking, involving an exposure of meat to high temperatures. Nonetheless, both agricultural and hunting activities represent a risk factor for the spread of diseases as hunters may act as mechanical vectors for different pathogens within domestic and wild animal populations.

Nonstationary time series analysis of surface water microbial pathogen population dynamics using cointegration methods

EPA Science Inventory

Background/Question/Methods Bacterial pathogens in surface water present disease risks to aquatic communities and for human recreational activities. Sources of these pathogens include runoff from urban, suburban, and agricultural point and non-point sources, but hazardous micr...

Biological Evaluation and Molecular Docking of Protocatechuic Acid from Hibiscus sabdariffa L. as a Potent Urease Inhibitor by an ESI-MS Based Method.

PubMed

Hassan, Sherif T S; Švajdlenka, Emil

2017-10-11

Studies on enzyme inhibition remain a crucial area in drug discovery since these studies have led to the discoveries of new lead compounds useful in the treatment of several diseases. In this study, protocatechuic acid (PCA), an active compound from Hibiscus sabdariffa L. has been evaluated for its inhibitory properties against jack bean urease (JBU) as well as its possible toxic effect on human gastric epithelial cells (GES-1). Anti-urease activity was evaluated by an Electrospray Ionization-Mass Spectrometry (ESI-MS) based method, while cytotoxicity was assayed by the MTT method. PCA exerted notable anti-JBU activity compared with that of acetohydroxamic acid (AHA), with IC 50 values of 1.7 and 3.2 µM, respectively. PCA did not show any significant cytotoxic effect on (GES-1) cells at concentrations ranging from 1.12 to 3.12 µM. Molecular docking study revealed high spontaneous binding ability of PCA to the active site of urease. Additionally, the anti-urease activity was found to be related to the presence of hydroxyl moieties of PCA. This study presents PCA as a natural urease inhibitor, which could be used safely in the treatment of diseases caused by urease-producing bacteria.

Quality of life in inflammatory bowel disease patients: A cross-sectional study.

PubMed

Habibi, Farzaneh; Habibi, Mohammad Emadoddin; Gharavinia, Ali; Mahdavi, Sadegh Baradaran; Akbarpour, Mohammad Javad; Baghaei, Abdolmehdi; Emami, Mohammad Hassan

2017-01-01

Inflammatory bowel disease (IBD) has a significant impact on health-related quality of life (HRQOL). This study aims to investigate the variables which can be attributed to HRQOL in IBD patients. Seventy-one patients filled in IBD questionnaire (IBDQ-32), Pittsburgh sleep quality index questionnaire, and sociodemographic questionnaire. Disease activity was assessed by Crohn's disease activity index (CDAI) and ulcerative colitis activity index (UCAI). The correlations of sleep quality, sociodemographic variables, and disease characteristics with IBDQ were investigated. IBDQ-32 mean score was lower in patients who had hospitalization ( P = 0.01), poor sleep quality ( P < 0.001), anemia ( P = 0.03), more severe disease ( P = 0.01), and those who had not consumed folic acid ( P = 0.01) relative to their counterparts. A multivariate regression analysis identified the predictors of decreased HRQOL as not consuming folic acid ( P = 0.008), poor sleep quality ( P = 0.014), and disease severity ( P = 0.043). Impaired HRQOL was significantly associated with poor sleep quality, lack of folic acid consumption, and disease severity in IBD patients. Therefore, evaluation of folic acid level and efficacy of its supplementation in prospective studies is recommended. Treatment of sleep disturbance with pharmacological agents and nonpharmacological methods should be kept in mind as well.

Activity assessment of microbial fibrinolytic enzymes.

PubMed

Kotb, Essam

2013-08-01

Conversion of fibrinogen to fibrin inside blood vessels results in thrombosis, leading to myocardial infarction and other cardiovascular diseases. In general, there are four therapy options: surgical operation, intake of antiplatelets, anticoagulants, or fibrinolytic enzymes. Microbial fibrinolytic enzymes have attracted much more attention than typical thrombolytic agents because of the expensive prices and the side effects of the latter. The fibrinolytic enzymes were successively discovered from different microorganisms, the most important among which is the genus Bacillus. Microbial fibrinolytic enzymes, especially those from food-grade microorganisms, have the potential to be developed as functional food additives and drugs to prevent or cure thrombosis and other related diseases. There are several assay methods for these enzymes; this may due to the insolubility of substrate, fibrin. Existing assay methods can be divided into three major groups. The first group consists of assay of fibrinolytic activity with natural proteins as substrates, e.g., fibrin plate methods. The second and third groups of assays are suitable for kinetic studies and are based on the determination of hydrolysis of synthetic peptide esters. This review will deal primarily with the microorganisms that have been reported in literature to produce fibrinolytic enzymes and the first review discussing the methods used to assay the fibrinolytic activity.

Disease Monitoring and Health Campaign Evaluation Using Google Search Activities for HIV and AIDS, Stroke, Colorectal Cancer, and Marijuana Use in Canada: A Retrospective Observational Study

PubMed Central

2016-01-01

Background Infodemiology can offer practical and feasible health research applications through the practice of studying information available on the Web. Google Trends provides publicly accessible information regarding search behaviors in a population, which may be studied and used for health campaign evaluation and disease monitoring. Additional studies examining the use and effectiveness of Google Trends for these purposes remain warranted. Objective The objective of our study was to explore the use of infodemiology in the context of health campaign evaluation and chronic disease monitoring. It was hypothesized that following a launch of a campaign, there would be an increase in information seeking behavior on the Web. Second, increasing and decreasing disease patterns in a population would be associated with search activity patterns. This study examined 4 different diseases: human immunodeficiency virus (HIV) infection, stroke, colorectal cancer, and marijuana use. Methods Using Google Trends, relative search volume data were collected throughout the period of February 2004 to January 2015. Campaign information and disease statistics were obtained from governmental publications. Search activity trends were graphed and assessed with disease trends and the campaign interval. Pearson product correlation statistics and joinpoint methodology analyses were used to determine significance. Results Disease patterns and online activity across all 4 diseases were significantly correlated: HIV infection (r=.36, P<.001), stroke (r=.40, P<.001), colorectal cancer (r= −.41, P<.001), and substance use (r=.64, P<.001). Visual inspection and the joinpoint analysis showed significant correlations for the campaigns on colorectal cancer and marijuana use in stimulating search activity. No significant correlations were observed for the campaigns on stroke and HIV regarding search activity. Conclusions The use of infoveillance shows promise as an alternative and inexpensive solution to disease surveillance and health campaign evaluation. Further research is needed to understand Google Trends as a valid and reliable tool for health research. PMID:27733330

[Clinical interest of fMRI and functional exploration methods of brain activity and interactivity: physical and neurophysiological considerations].

PubMed

de Marco, G; Menuel, C; Guillevin, R; Vallée, J-N; Lehmann, P; Fall, S; Quaglino, V; Bourdin, B; Devauchelle, B; Chiras, J

2008-07-01

After having provided a brief reminder of the principle of the blood oxygen level-dependent (BOLD) contrast effect, the physiological bases of brain activity and the concepts of functional integration and effective connectivity, we describe the most recent approaches, which permit to explore brain activity and putative networks of interconnected active areas in order to examine the normal brain physiology and its dysfunctions. We present various methods and studies of brain activity analysis clinically applicable, and we detail the concepts of functional and effective connectivity, which allow to study the cerebral plasticity which occurs at the child's during the maturation (e.g., dyslexia), at the adult during the ageing (e.g., Alzheimer disease), or still in schizophrenia or Parkinson disease. The study of specific circuits in networks has to allow defining in a more realistic way the dynamic of the central nervous system, which underlies various cerebral functions, both in physiological and pathological conditions. This connectivity approach should improve the diagnostic and facilitate the development of new therapeutic strategies.

Pharmacological and phytochemical screening of Palestinian traditional medicinal plants Erodium laciniatum and Lactuca orientalis.

PubMed

Jaradat, Nidal; AlMasri, Motasem; Zaid, Abdel Naser; Othman, Dua'a Ghazi

2017-09-01

Various epidemiological studies showed that herbal remedies containing polyphenols may protect against various diseases such as cancers, vascular diseases and inflammatory pathologies. Currently, such groups of bioactive compounds have become a subject of many antimicrobials and antioxidant investigations. Accordingly, the current study aimed to conduct biological and phytochemical screening for two Palestinian traditional medicinal plants, Erodium laciniatum and Lactuca orientalis. Current plants phytoconstituents and their antioxidant activities were evaluated by using standard phytochemical methods; meanwhile, antimicrobial activities were estimated by using several types of American Type Culture Collection and multidrug resistant clinical isolates by using agar diffusion well-variant, agar diffusion disc-variant and broth microdilution methods. Phytochemical screenings showed that L. orientalis and E. laciniatum contain mixtures of secondary and primary metabolites Moreover, total flavonoid, tannins and phenols content in E. laciniatum extract were higher than the L. orientalis extracts with almost the same antioxidant potentials. Additionally, both plants organic and aqueous extracts showed various potentials of antimicrobial activity Conclusions: Overall, the studied species have a mixture of phytochemicals, flavonoids, phenols and tannins also have antioxidant and antimicrobial activities which approved their folk uses in treatments of infectious and Alzheimer diseases and simultaneously can be used as therapeutic agents in the pharmaceutical industries.

Role for positron emission tomography in skeletal diseases.

PubMed

Duet, Michèle; Pouchot, Jacques; Lioté, Frédéric; Faraggi, Marc

2007-01-01

Imaging plays a prominent role in the diagnosis and management of rheumatic diseases. Conventional imaging methods provide high-resolution structural information but usually fail to distinguish between active lesions and residual changes. Positron emission tomography (PET) with the tracer 18F-fluorodeoxyglucose (18F-FDG) was recently introduced into clinical practice as a means of obtaining information on both structure and metabolic activity. 18F-FDG-PET is widely used in oncology and may be valuable in patients with infections or inflammatory diseases, most notably vasculitis. Although encouraging results have been published, the number of studies remains small, as 18F-FDG-PET is an expensive investigation that is not available everywhere. Further work is needed to determine the cost-effectiveness ratio of 18F-FDG-PET in patients with infections or inflammatory diseases. Imaging plays a prominent role in the diagnosis and management of many musculoskeletal diseases. Although considerable progress has been made recently, the structural information supplied by conventional imaging methods is inadequate in some patients. Positron emission tomography (PET) after injection of 18fluorodeoxyglucose (18F-FDG) provides information on tissue metabolism. The usefulness of 18F-FDG-PET in oncology is now widely recognized. Other uses are emerging, in part thanks to the development of new cameras that combine dedicated detectors and an X-scanner in order to ensure accurate three-dimensional localization of metabolically active lesions. However, the exact role for 18F-FDG-PET needs to be studied in larger populations of patients.

Cardiovascular effects of variations in habitual levels of physical activity

NASA Technical Reports Server (NTRS)

Blomqvist, C. G.; Mitchell, J. H.

1975-01-01

Mechanisms involved in human cardiovascular adaption to stress, particularly adaption to different levels of physical activity are determined along with quantitative noninvasive methods for evaluation of cardiovascular function during stess in normal subjects and in individuals with latent or manifest cardiovascular disease. Results are summarized.

Nano-sized Contrast Agents to Non-Invasively Detect Renal Inflammation by Magnetic Resonance Imaging

PubMed Central

Thurman, Joshua M.; Serkova, Natalie J.

2013-01-01

Several molecular imaging methods have been developed that employ nano-sized contrast agents to detect markers of inflammation within tissues. Renal inflammation contributes to disease progression in a wide range of autoimmune and inflammatory diseases, and a biopsy is currently the only method of definitively diagnosing active renal inflammation. However, the development of new molecular imaging methods that employ contrast agents capable of detecting particular immune cells or protein biomarkers will allow clinicians to evaluate inflammation throughout the kidneys, and to assess a patient's response to immunomodulatory drugs. These imaging tools will improve our ability to validate new therapies and to optimize the treatment of individual patients with existing therapies. This review describes the clinical need for new methods of monitoring renal inflammation, and recent advances in the development of nano-sized contrast agents for detection of inflammatory markers of renal disease. PMID:24206601

"There's nothing I can't do – I just put my mind to anything and I can do it": a qualitative analysis of how children with chronic disease and their parents account for and manage physical activity

PubMed Central

Fereday, Jennifer; MacDougall, Colin; Spizzo, Marianne; Darbyshire, Philip; Schiller, Wendy

2009-01-01

Background This paper reports the findings of a South Australian qualitative, exploratory study of children and young people living with a chronic disease, and their perceptions and experiences of physical activity. The perceptions and experiences of their parents were also explored. The chronic diseases were type 1 diabetes, asthma and cystic fibrosis. Methods Multiple qualitative data collection techniques were used to elicit the children and young people's perspectives and experiences of physical activity, including focus groups, maps, photos and 'traffic light posters'. The children's parents were interviewed separately to ascertain their views of their child's participation in physical activities. Results Children and young people described their active participation in a wide variety of physical activities including organised sports and play, but made very little mention of any negative influence or impact due to their disease. Their parents' stories described the diligent background planning and management undertaken to enable their child to participate in a wide range of physical activities. Conclusion The results of this study suggest that for these children and young people, having a chronic disease was not perceived as a barrier to participation in organised sport and recreational activities. They were physically active and perceived themselves to be no different from their peers. Their positive beliefs were shared by their parents and the level of participation described was enabled by the high level of parental support and background planning involved in managing their child's health care needs. PMID:19117528

Use of Activity Space in a Tuberculosis Outbreak: Bringing Homeless Persons Into Spatial Analyses.

PubMed

Worrell, Mary Claire; Kramer, Michael; Yamin, Aliya; Ray, Susan M; Goswami, Neela D

2017-01-01

Tuberculosis (TB) causes significant morbidity and mortality in US cities, particularly in poor, transient populations. During a TB outbreak in Fulton County, Atlanta, GA, we aimed to determine whether local maps created from multiple locations of personal activity per case would differ significantly from traditional maps created from single residential address. Data were abstracted for patients with TB disease diagnosed in 2008-2014 and receiving care at the Fulton County Health Department. Clinical and activity location data were abstracted from charts. Kernel density methods, activity space analysis, and overlay with homeless shelter locations were used to characterize case spatial distribution when using single versus multiple addresses. Data were collected for 198 TB cases, with over 30% homeless US-born cases included. Greater spatial dispersion of cases was found when utilizing multiple versus single addresses per case. Activity spaces of homeless and isoniazid (INH)-resistant cases were more spatially congruent with one another than non-homeless and INH-susceptible cases ( P < .0001 and P < .0001, respectively). Innovative spatial methods allowed us to more comprehensively capture the geography of TB-infected homeless persons, who made up a large portion of the Fulton County outbreak. We demonstrate how activity space analysis, prominent in exposure science and chronic disease, supports that routine capture of multiple location TB data may facilitate spatially different public health interventions than traditional surveillance maps. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Crude Extract from Ziziphus Jujuba Fruits, a Weapon against Pediatric Infectious Disease

PubMed Central

Daneshmand, F; Zare-Zardini, H; Tolueinia, B; Hasani, Z; Ghanbari, T

2013-01-01

Background Pediatric infectious disease is one of the main problems in cancerous children that treat by chemotherapy drugs. Thus, study in this regard is necessary. The aim of this study was to evaluate antimicrobial properties of ethanolic extract of Ziziphus Jujuba fruits against different infectious pathogens. Materials and Methods This study is descriptive. In vitro antimicrobial activity of extract was assessed on gram negative and gram positive bacteria as well as fungi. The antimicrobial activity was tested by Radial Diffusion Assay (RDA) and Minimal Inhibitory Concentration (MIC) methods. Results The results showed a wide antimicrobial activity of the extract against the microbes studied. Escherichia coli was the most susceptible to the extracts among tested microorganisms for which the MIC was 0.65±0.22 mg/ml. Amongst the bacterial strains investigated, Staphylococcus aureus was the most resistant strain with MIC of 2.26±0.68 mg/ml. The ethanolic extract also showed antimicrobial activity on the fungi studied as no growth was observed in 2.35±0.38 and 2.86±0.7 mg/ml concentration for Candida albicans and Aspergillus fumigatus, respectively. The results of qualitive and quantitative test are well indicative of the extract effective activity against the microbes mentioned. Conclusion Confirming the potential antimicrobial activities of crude extract of Ziziphus Jujuba fruits, this study suggested that ethanolic extracts of this plant is appropriate candidate for treatment of microbial infections, especially pediatric infectious diseases. PMID:24575267

Trajectory data analyses for pedestrian space-time activity study.

PubMed

Qi, Feng; Du, Fei

2013-02-25

It is well recognized that human movement in the spatial and temporal dimensions has direct influence on disease transmission(1-3). An infectious disease typically spreads via contact between infected and susceptible individuals in their overlapped activity spaces. Therefore, daily mobility-activity information can be used as an indicator to measure exposures to risk factors of infection. However, a major difficulty and thus the reason for paucity of studies of infectious disease transmission at the micro scale arise from the lack of detailed individual mobility data. Previously in transportation and tourism research detailed space-time activity data often relied on the time-space diary technique, which requires subjects to actively record their activities in time and space. This is highly demanding for the participants and collaboration from the participants greatly affects the quality of data(4). Modern technologies such as GPS and mobile communications have made possible the automatic collection of trajectory data. The data collected, however, is not ideal for modeling human space-time activities, limited by the accuracies of existing devices. There is also no readily available tool for efficient processing of the data for human behavior study. We present here a suite of methods and an integrated ArcGIS desktop-based visual interface for the pre-processing and spatiotemporal analyses of trajectory data. We provide examples of how such processing may be used to model human space-time activities, especially with error-rich pedestrian trajectory data, that could be useful in public health studies such as infectious disease transmission modeling. The procedure presented includes pre-processing, trajectory segmentation, activity space characterization, density estimation and visualization, and a few other exploratory analysis methods. Pre-processing is the cleaning of noisy raw trajectory data. We introduce an interactive visual pre-processing interface as well as an automatic module. Trajectory segmentation(5) involves the identification of indoor and outdoor parts from pre-processed space-time tracks. Again, both interactive visual segmentation and automatic segmentation are supported. Segmented space-time tracks are then analyzed to derive characteristics of one's activity space such as activity radius etc. Density estimation and visualization are used to examine large amount of trajectory data to model hot spots and interactions. We demonstrate both density surface mapping(6) and density volume rendering(7). We also include a couple of other exploratory data analyses (EDA) and visualizations tools, such as Google Earth animation support and connection analysis. The suite of analytical as well as visual methods presented in this paper may be applied to any trajectory data for space-time activity studies.

Light and sound - emerging imaging techniques for inflammatory bowel disease

PubMed Central

Knieling, Ferdinand; Waldner, Maximilian J

2016-01-01

Patients with inflammatory bowel disease are known to have a high demand of recurrent evaluation for therapy and disease activity. Further, the risk of developing cancer during the disease progression is increasing from year to year. New, mostly non-radiant, quick to perform and quantitative methods are challenging, conventional endoscopy with biopsy as gold standard. Especially, new physical imaging approaches utilizing light and sound waves have facilitated the development of advanced functional and molecular modalities. Besides these advantages they hold the promise to predict personalized therapeutic responses and to spare frequent invasive procedures. Within this article we highlight their potential for initial diagnosis, assessment of disease activity and surveillance of cancer development in established techniques and recent advances such as wide-view full-spectrum endoscopy, chromoendoscopy, autofluorescence endoscopy, endocytoscopy, confocal laser endoscopy, multiphoton endoscopy, molecular imaging endoscopy, B-mode and Doppler ultrasound, contrast-enhanced ultrasound, ultrasound molecular imaging, and elastography. PMID:27433080

Diuretics Prime Plant Immunity in Arabidopsis thaliana

PubMed Central

Noutoshi, Yoshiteru; Ikeda, Mika; Shirasu, Ken

2012-01-01

Plant activators are agrochemicals that activate the plant immune system, thereby enhancing disease resistance. Due to their prophylactic and durable effects on a wide spectrum of diseases, plant activators can provide synergistic crop protection when used in combination with traditional pest controls. Although plant activators have achieved great success in wet-rice farming practices in Asia, their use is still limited. To isolate novel plant activators applicable to other crops, we screened a chemical library using a method that can selectively identify immune-priming compounds. Here, we report the isolation and characterization of three diuretics, bumetanide, bendroflumethiazide and clopamide, as immune-priming compounds. These drugs upregulate the immunity-related cell death of Arabidopsis suspension-cultured cells induced with an avirulent strain of Pseudomonas syringae pv. tomato in a concentration-dependent manner. The application of these compounds to Arabidopsis plants confers disease resistance to not only the avirulent but also a virulent strain of the pathogen. Unlike salicylic acid, an endogenous phytohormone that governs disease resistance in response to biotrophic pathogens, the three diuretic compounds analyzed here do not induce PR1 or inhibit plant growth, showing potential as lead compounds in a practical application. PMID:23144763

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study

PubMed Central

Salustri, C.; Tecchio, F.; Zappasodi, F.; Tomasevic, L.; Ercolani, M.; Moffa, F.; Cassetta, E.; Rossini, P. M.; Squitti, R.

2013-01-01

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity. Results. Patients' sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission. Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD. Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia. PMID:24416615

The Oxidant and Antioxidant Status in Pityriasis Rosea

PubMed Central

Emre, Selma; Akoglu, Gulsen; Metin, Ahmet; Demirseren, Duriye Deniz; Isikoglu, Semra; Oztekin, Aynure; Erel, Ozcan

2016-01-01

Background: Pityriasis rosea (PR) is usually an asymptomatic and self-limiting papulosquamous skin disease with acute onset. The etiology has not been clarified yet. Recently, increased oxidative stress was found to play a role in etiopathogenesis of multiple cutaneous diseases with T cell-mediated immune response. However, there are no studies demonstrating the oxidative stress status in PR. Aim: The aim of the study is to determine the status of oxidative stress (OS) and paraoxonase (PON) 1/arylesterase enzyme activities in PR. Materials and Methods: Study included 51 patients with active PR lesions, and 45 healthy volunteers. Serum levels of total oxidant status (TOS), total antioxidant status (TAS), and PON1/arylesterase (ARES) activity were determined and oxidative stress index (OSI) was calculated in all patients and controls. Results: TAS levels and ARES activities in the patient group were significantly lower than the control group. On the other hand, TOS and OSI levels were significantly higher in patients compared with controls. There was no significant correlation between the duration of disease and TAS, TOS, OSI levels, and ARES activities. Conclusion: A systemic oxidative stress exists in PR, which suggests that OS may be involved in the etiopathogenesis of disease. PMID:26955119

Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis.

PubMed

Huffman, K M; Pieper, C F; Hall, K S; St Clair, E W; Kraus, W E

2015-01-01

Until recently, reports of physical activity in rheumatoid arthritis (RA) were limited to self-report methods and/or leisure-time physical activity. Our objectives were to assess, determine correlates of, and compare to well-matched controls both exercise and sedentary time in a typical clinical cohort of RA. Persons with established RA (seropositive or radiographic erosions; n = 41) without diabetes or cardiovascular disease underwent assessments of traditional and disease-specific correlates of physical activity and 7 days of triaxial accelerometry. Twenty-seven age, gender, and body mass index (BMI)-matched controls were assessed. For persons with RA, objectively measured median (25th-75th percentile) exercise time was 3 (1-11) min/day; only 10% (n = 4) of participants exercised for ≥ 30 min/day. Time spent in sedentary activities was 92% (89-95%). Exercise time was not related to pain but was inversely related to disease activity (r = -0.3, p < 0.05) and disability (r = -0.3, p < 0.05) and positively related to self-efficacy for endurance activity (r = 0.4, p < 0.05). Sedentary activity was related only to self-efficacy for endurance activity (r = -0.4, p < 0.05). When compared to matched controls, persons with RA exhibited poorer self-efficacy for physical activity but similar amounts of exercise and sedentary time. For persons with RA and without diabetes or cardiovascular disease, time spent in exercise was well below established guidelines and activity patterns were predominantly sedentary. For optimal care in RA, in addition to promoting exercise, clinicians should consider assessing sedentary behaviour and self-efficacy for exercise. Future interventions might determine whether increased self-efficacy can increase physical activity in RA.

The biospeckle method for early damage detection of fruits

NASA Astrophysics Data System (ADS)

Yan, Lei; Liu, Jiaxin; Men, Sen

2017-07-01

In the field of fruits damage assessment, biospeckle activity is considered relevant to quality properties of plants, such us damage, aging, or diseases. In this paper, biospeckle technique was applied to identify the early bruising of apples. Then a total of 50 undamaged apples were determined to be artificially bruised as samples. Three methods (Fujii, GD, and LSTCA) were used to extract effective information from these speckle images for measuring the intensity of biospeckle activity. The results showed that for all of three methods, the biospeckle activities of the undamaged areas in apple were similar; after the hit, the damaged area showed a lower biospeckle activity. It can be concluded that early bruising can be identified by biospeckle technique.

Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study

PubMed Central

Sokka, Tuulikki; Toloza, Sergio; Cutolo, Maurizio; Kautiainen, Hannu; Makinen, Heidi; Gogus, Feride; Skakic, Vlado; Badsha, Humeira; Peets, Tõnu; Baranauskaite, Asta; Géher, Pál; Újfalussy, Ilona; Skopouli, Fotini N; Mavrommati, Maria; Alten, Rieke; Pohl, Christof; Sibilia, Jean; Stancati, Andrea; Salaffi, Fausto; Romanowski, Wojciech; Zarowny-Wierzbinska, Danuta; Henrohn, Dan; Bresnihan, Barry; Minnock, Patricia; Knudsen, Lene Surland; Jacobs, Johannes WG; Calvo-Alen, Jaime; Lazovskis, Juris; Pinheiro, Geraldo da Rocha Castelar; Karateev, Dmitry; Andersone, Daina; Rexhepi, Sylejman; Yazici, Yusuf; Pincus, Theodore

2009-01-01

Introduction Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). Methods The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. Results Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. Conclusions In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself. PMID:19144159

Quantitative Evaluation of the Use of Actigraphy for Neurological and Psychiatric Disorders

PubMed Central

Song, Yu; Kwak, Shin; Yoshida, Sohei; Yamamoto, Yoshiharu

2014-01-01

Quantitative and objective evaluation of disease severity and/or drug effect is necessary in clinical practice. Wearable accelerometers such as an actigraph enable long-term recording of a patient's movement during activities and they can be used for quantitative assessment of symptoms due to various diseases. We reviewed some applications of actigraphy with analytical methods that are sufficiently sensitive and reliable to determine the severity of diseases and disorders such as motor and nonmotor disorders like Parkinson's disease, sleep disorders, depression, behavioral and psychological symptoms of dementia (BPSD) for vascular dementia (VD), seasonal affective disorder (SAD), and stroke, as well as the effects of drugs used to treat them. We believe it is possible to develop analytical methods to assess more neurological or psychopathic disorders using actigraphy records. PMID:25214709

Employees on the Move!

ERIC Educational Resources Information Center

Levin, Sarah

This paper describes a method for designing, implementing, and evaluating a work-site physical activity campaign aimed at employees who are currently sedentary in their leisure time. Inactivity is a major but modifiable risk factor for coronary heart disease. Increasing the activity levels of underactive adults would have a positive impact on…

The cost of changing physical activity behaviour: evidence from a "physical activity pathway" in the primary care setting

PubMed Central

2011-01-01

Background The 'Physical Activity Care Pathway' (a Pilot for the 'Let's Get Moving' policy) is a systematic approach to integrating physical activity promotion into the primary care setting. It combines several methods reported to support behavioural change, including brief interventions, motivational interviewing, goal setting, providing written resources, and follow-up support. This paper compares costs falling on the UK National Health Service (NHS) of implementing the care pathway using two different recruitment strategies and provides initial insights into the cost of changing physical activity behaviour. Methods A combination of a time driven variant of activity based costing, audit data through EMIS and a survey of practice managers provided patient-level cost data for 411 screened individuals. Self reported physical activity data of 70 people completing the care pathway at three month was compared with baseline using a regression based 'difference in differences' approach. Deterministic and probabilistic sensitivity analyses in combination with hypothesis testing were used to judge how robust findings are to key assumptions and to assess the uncertainty around estimates of the cost of changing physical activity behaviour. Results It cost £53 (SD 7.8) per patient completing the PACP in opportunistic centres and £191 (SD 39) at disease register sites. The completer rate was higher in disease register centres (27.3% vs. 16.2%) and the difference in differences in time spent on physical activity was 81.32 (SE 17.16) minutes/week in patients completing the PACP; so that the incremental cost of converting one sedentary adult to an 'active state' of 150 minutes of moderate intensity physical activity per week amounts to £ 886.50 in disease register practices, compared to opportunistic screening. Conclusions Disease register screening is more costly than opportunistic patient recruitment. However, additional costs come with a higher completion rate and better outcomes in terms of behavioural change in patients completing the care pathway. Further research is needed to rigorously evaluate intervention efficiency and to assess the link between behavioural change and changes in quality adjusted life years (QALYs). PMID:21605400

[Screening of anti-aging active ingredients and mechanism analysis based on molecular docking technology].

PubMed

Du, Ran-Feng; Zhang, Xiao-Hua; Ye, Xiao-Tong; Yu, Wen-Kang; Wang, Yun

2016-07-01

Dampness evil is the source of all diseases, which is easy to cause disease and promote aging, while aging could also promote the occurence and development of diseases. In this paper, the relationship between the dampness evil and aging would be discussed, to find the anti-aging active ingredients in traditional Chinese medicine (TCM), and analyze the anti-aging mechanism of dampness eliminating drug. Molecular docking technology was used, with aging-related mammalian target of rapamycin as the docking receptors, and chemical components of Fuling, Sangzhi, Mugua, Yiyiren and Houpo as the docking molecules, to preliminarily screen the anti-aging active ingredients in dampness eliminating drug. Through the comparison with active drugs already on the market (temsirolimus and everolimus), 12 kinds of potential anti-aging active ingredients were found, but their drug gability still needs further study. The docking results showed that various components in the dampness eliminating drug can play anti-aging activities by acting on mammalian target of rapamycin. This result provides a new thought and direction for the method of delaying aging by eliminating dampness. Copyright© by the Chinese Pharmaceutical Association.

Inhibition of c-Jun N-terminal kinase activation reverses Alzheimer disease phenotypes in APPswe/PS1dE9 mice.

PubMed

Zhou, Qiong; Wang, Man; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Li, Zhuyi; Miao, Jianting

2015-04-01

Growing evidence indicates that the activation of c-Jun N-terminal kinase (JNK) is implicated in the multiple major pathological features of Alzheimer disease (AD). However, whether specific inhibition of JNK activation could prevent disease progression in adult transgenic AD models at moderate stage remains unknown. Here we first investigated the potential disease-modifying therapeutic effect of systemic administration of SP600125, a small-molecule JNK-specific inhibitor, in middle-aged APPswe/PS1dE9 mice. Using behavioral, histological, and biochemical methods, outcomes of SP600125 treatment on neuropathology and cognitive deficits were studied in APPswe/PS1dE9 mice. Compared with vehicle-treated APPswe/PS1dE9 mice, chronic treatment of SP600125 for 12 weeks potently inhibited JNK activation, which resulted in a marked improvement of behavioral measures of cognitive deficits and a dramatic reduction in amyloid plaque burden, β-amyloid production, tau hyperphosphorylation, inflammatory responses, and synaptic loss in these transgenic animals. In particular, we found that SP600125 treatment strongly promoted nonamyloidogenic amyloid precursor protein (APP) processing and inhibited amyloidogenic APP processing via regulating APP-cleavage secretase expression (ie, ADAM10, BACE1, and PS1) in APPswe/PS1dE9 mice. Our findings demonstrate that chronic SP600125 treatment is powerfully effective in slowing down disease progression by markedly reducing multiple pathological features and ameliorating cognitive deficits associated with AD. This study highlights the concept that active JNK actually contributes to the development of the disease, and provides critical preclinical evidence that specific inhibition of JNK activation by SP600125 treatment may be a novel promising disease-modifying therapeutic strategy for the treatment of AD. © 2015 American Neurological Association.

Milk fat globule E-8 and interleukin 17 in systemic lupus erythematosus: partners in crime?

PubMed Central

Elgengehy, Fatema; Niazy, Marwa; Ghoneim, Shada

2016-01-01

Objectives Systemic lupus erythematosus (SLE) is a multi-factorial, autoimmune disease with a wide array of manifestations. The pro-inflammatory cytokine interleukin (IL)-17 has been implicated in the inflammatory response and tissue damage in SLE; however, its correlation with disease activity is still questionable. Meanwhile, efficient clearance of apoptotic cells is required for immune tolerance. An abnormally low or high level of milk fat globule (MFG-E8) can result in impaired apoptotic cell clearance and the subsequent autoimmune response. In this study, we endeavoured to compare the levels of MFG-E8 and IL-17 in SLE patients and healthy controls and to reveal the alleged association of these levels with SLE disease activity. Material and methods Serum samples from 57 SLE patients and 30 healthy control subjects were examined for quantitation of MFG-E8 and IL-17 levels using ELISA. Systemic lupus erythematosus disease activity was calculated using the SLE Disease Activity Index (SLEDAI). Clinical manifestations and laboratory findings of the patients were also recorded. Results We report that serum MFG-E8 levels were significantly elevated in the sera of SLE patients compared to healthy controls (p-value = 0.019). Likewise, IL-17 levels were higher in SLE patients (p-value < 0.001). A positive correlation was revealed between MFG-E8 level and proteinuria. Surprisingly, there was a poor correlation between disease activity and the levels of either IL-17 or MFG-E8. Conclusions Although serum MFG-E8 and IL-17 levels were higher in SLE patients than in normal controls, our results indicate that they cannot accurately reflect the disease activity. Meanwhile, further studies are needed to assess MFG-E8 and IL-17 as potential therapeutic targets in SLE patients. PMID:27407263

EHealth: self-management in inflammatory bowel disease and in irritable bowel syndrome using novel constant-care web applications. EHealth by constant-care in IBD and IBS.

PubMed

Pedersen, Natalia

2015-12-01

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders of unknown aetiology of increasing incidence and changing disease activity or severity. Approximately 60-80% of IBD patients suffer from IBS. Monitoring and treatment goals of IBD are to optimise the disease course by prolonging remission periods and preventing or shortening periods of active disease. Constant-care web-monitoring and treatment approaches with active patient involvement have been proven effective in UC, increasing patients' adherence and improving the disease outcomes.   To assess the feasibility and efficacy of the novel constant-care eHealth applications in: i) CD patients treated with infliximab (IFX), ii) UC patients with active disease on mesalazine, iii) IBS patients and iv) IBD patients with IBS on a low FODMAP diet (LFD).   New constant-care web applications www.cd.constant-care.dk, www.meza.constant-care.dk and www.ibs.constant-care.dk in IBD patients were developed and assessed in this thesis. An integrated inflammatory burden measure of disease activity, consisting of a subjective (clinical indices) and of an objective (faecal calprotectin) part and a treatment guide to drug doses and intervals, was incorporated into the web applications and used by patients. Web-guided IFX treatment in CD demonstrated patients' inter- and intra-individual variability in infusion intervals and provided patients with individualised treatment according to their needs. Web-guided treatment with multimatrix mesalazine was efficacious in a majority of UC patients with mild-to-moderate disease activity. Web-guided IBS-monitoring in IBD and in IBS patients on LFD was shown to be a feasible method that actively involved patients in their disease management and had a positive short-term impact on the disease. Moreover, the new constant-care concepts were demonstrated to be safe and to have a positive impact on quality of life and adherence to treatment and helped to reduce the costs.   The novel constant-care web applications have proven feasible in improving the disease outcomes in CD patients on IFX, in UC patients on mesalazine, and in monitoring IBS. These applications are expected to be implemented in the clinical practice of gastroenterology in Denmark in the coming years. Future studies will help to assess whether the natural disease course can be improved in the long-term.

How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?

PubMed

Auray-Blais, Christiane; Ntwari, Aimé; Clarke, Joe T R; Warnock, David G; Oliveira, João Paulo; Young, Sarah P; Millington, David S; Bichet, Daniel G; Sirrs, Sandra; West, Michael L; Casey, Robin; Hwu, Wuh-Liang; Keutzer, Joan M; Zhang, X Kate; Gagnon, René

2010-12-14

Fabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb(3)), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb(3)), is increased in patients with the disease. Until now, lyso-Gb(3) was not detectable in urine, possibly because of the presence of interfering compounds. We undertook to: 1) characterize lyso-Gb(3) in urine; 2) develop a method to quantitate urinary lyso-Gb(3) by mass spectrometry; 3) evaluate urinary lyso-Gb(3) as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb(3) is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb(3) from 83 Fabry patients and 77 healthy age-matched controls. The intraday and interday bias and precision of the method were <15%. Increases in lyso-Gb(3)/creatinine correlated with the concentrations of Gb(3) (r(2)=0.43), type of mutations (p=0.0006), gender (p<0.0001) and enzyme replacement therapy status (p=0.0012). Urine from healthy controls contained no detectable lyso-Gb(3). Lyso-Gb(3) did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb(3) of Fabry patients correlated well with a number of indicators of disease severity. Lyso-Gb(3) is a reliable independent biomarker for clinically important characteristics of Fabry disease. Copyright © 2010 Elsevier B.V. All rights reserved.

Improving Response Inhibition in Parkinson’s Disease with Atomoxetine

PubMed Central

Ye, Zheng; Altena, Ellemarije; Nombela, Cristina; Housden, Charlotte R.; Maxwell, Helen; Rittman, Timothy; Huddleston, Chelan; Rae, Charlotte L.; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.; Rowe, James B.

2015-01-01

Background Dopaminergic drugs remain the mainstay of Parkinson’s disease therapy but often fail to improve cognitive problems such as impulsivity. This may be due to the loss of other neurotransmitters, including noradrenaline, which is linked to impulsivity and response inhibition. We therefore examined the effect of the selective noradrenaline reuptake inhibitor atomoxetine on response inhibition in a stop-signal paradigm. Methods This pharmacological functional magnetic resonance imaging study used a double-blinded randomized crossover design with low-frequency inhibition trials distributed among frequent Go trials. Twenty-one patients received 40 mg atomoxetine or placebo. Control subjects were tested on no-drug. The effects of disease and drug on behavioral performance, regional brain activity, and functional connectivity were analyzed using general linear models. Anatomical connectivity was examined using diffusion-weighted imaging. Results Patients with Parkinson’s disease had longer stop-signal reaction times, less stop-related activation in the right inferior frontal gyrus (RIFG), and weaker functional connectivity between the RIFG and striatum compared with control subjects. Atomoxetine enhanced stop-related RIFG activation in proportion to disease severity. Although there was no overall behavioral benefit from atomoxetine, analyses of individual differences revealed that enhanced response inhibition by atomoxetine was associated with increased RIFG activation and functional frontostriatal connectivity. Improved performance was more likely in patients with higher structural frontostriatal connectivity. Conclusions This study suggests that enhanced prefrontal cortical activation and frontostriatal connectivity by atomoxetine may improve response inhibition in Parkinson’s disease. These results point the way to new stratified clinical trials of atomoxetine to treat impulsivity in selected patients with Parkinson’s disease. PMID:24655598

The Scope of Global Health Training in U.S. Obstetrics and Gynecology Residency Programs

PubMed Central

Hung, Kristin J.; Tsai, Alexander C.; Johnson, Timothy R.B.; MD, MPH, Rochelle P.; Bangsberg, David R.; Kerry, Vanessa B.

2013-01-01

Objective To enumerate global health training activities in U.S. obstetrics and gynecology residency programs, and to examine the worldwide distribution of programmatic activity relative to the maternal and perinatal disease burden. Methods Using a systematic, Web-based protocol, we searched for global health training opportunities at all U.S. obstetrics and gynecology residency programs. Country-level data on disability-adjusted life years due to maternal and perinatal conditions were obtained from the Global Burden of Disease study. We calculated Spearman’s rank correlation coefficients to estimate the cross-country association between programmatic activity and disease burden. Results Of the 243 accredited U.S. obstetrics and gynecology residency programs, we identified 41 (17%) with one of several possible predefined categories of programmatic activity. Thirty-three residency programs offered their residents opportunities to participate in one or more elective-based rotations, eight offered extended field-based training, and 18 offered research activities. A total of 128 programmatic activities were dispersed across 64 different countries. At the country level, the number of programmatic activities had a statistically significant association with the total disease burden due to maternal (Spearman’s ρ=0.37; 95% confidence interval [CI], 0.14-0.57) and perinatal conditions (ρ=0.34; 95% CI, 0.10-0.54) but not gynecologic cancers (ρ=−0.24; 95% CI, −0.46 to 0.01). Conclusions There are few global health training opportunities for U.S. obstetrics and gynecology residents. These activities are disproportionately distributed among countries with greater burdens of disease. PMID:24104785

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma

PubMed Central

Torok, Kathryn S.; Kurzinski, Katherine; Kelsey, Christina; Yabes, Jonathan; Magee, Kelsey; Vallejo, Abbe N.; Medsger, Thomas; Feghali-Bostwick, Carol A.

2015-01-01

Objective To evaluate peripheral blood T-helper (TH) cell associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. Methods A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. Results Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. Conclusion This is the first time that multiple cytokines and chemokines have been examined simultaneously LS. In general, a TH-1 (IFN-γ) and TH-17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN–γ signature with elevated IP-10, MCP-1 and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting. PMID:26254121

The Effect of Positive Family History of Autoimmunity in Juvenile Idiopathic Arthritis Characteristics; a Case Control Study

PubMed Central

Khani, Mehdi; Ziaee, Vahid; Moradinejad, Mohamad-Hassan; Parvaneh, Nima

2013-01-01

Objective To compare Juvenile Idiopathic Arthritis (JIA) patients with and without family history of autoimmune disease with respect to clinical features and laboratory data. Methods Sixteen JIA patients with family history of autoimmune disease were identified during study, 32 patients were chosen for comparative group from referred patients to the rheumatology clinic according to the date of referral. Two groups were compared with respect to age of onset, sex, subtype, disease activity, duration of active disease and laboratory variables. Findings The age of onset was significantly lower in JIA patients with family history of autoimmunity (4.7 years vs. 7.0 years; P=0.02), polyarthicular subtype was more frequent in patients with positive family history (50% vs.25%; P=0.04) most of JIA patients with positive family history were in the active phase at the time of study (64% vs 25%; P=0.02) and had a longer duration of active disease (21.0 months vs 12.3 months; P=0.04). Patients with positive family history had more positive ANA (43.5%% vs 12.5%; P=0.01) and also more positive ADA (75% vs 20.8%; P=0.002). Two groups were similar according to sex, and other laboratory variables. Conclusion JIA patients with family history of autoimmune disease seem to have a more severe disease than patients without such family history, they are younger at the onset, and have mostly poyarthicular subtype. They also have more ANA and ADA positivity. These findings are different from familial JIA case-control studies according to active disease duration, subtype, and ANA positivity. PMID:24800019

Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

PubMed Central

Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

2010-01-01

Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

Cross-cultural adaptation and validation of the Behcet’s Disease Current Activity Form in Korea

PubMed Central

Choi, Hyo Jin; Seo, Mi Ryoung; Ryu, Hee Jung; Baek, Han Joo

2015-01-01

Background/Aims: This study was undertaken to perform a cross-cultural adaptation of the Behcet’s Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet’s disease (BD). Methods: A cross-cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF questionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing κ statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient’s/clinician’s perception of disease activity and the Korean version of the Behcet’s Disease Quality of Life (BDQOL). Results: For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Significant correlations were obtained between the total BDCAF score with the BDQOL and the patient’s/clinician’s perception of disease activity p < 0.05). Conclusions: The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients. PMID:26354066

[Immunochemistry of eukaryotic ribosomes].

PubMed

Lopaczyński, W; Gałasiński, W

1990-01-01

Immunochemical investigations of ribosomes should correlate with basic knowledge of the function, structure and activity of organelles in the cell processes. Our paper presents data of immunochemical methods used to determine the structure, function and differences of ribosomes. We present the usefulness of immunochemical methods to test human ribosomes, diagnosis and therapy of many diseases.

In-Vitro, Anti-Bacterial Activities of Aqueous Extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo Against Gram Positive and Gram Negative Bacteria

PubMed Central

Dashtdar, Mehrab; Dashtdar, Mohammad Reza; Dashtdar, Babak; shirazi, Mohammad khabaz; Khan, Saeed Ahmad

2013-01-01

Objective: Evaluations of the in-vitro anti-bacterial activities of aqueous extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and Shilajita mumiyo against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) and gram-negative bacteria (Escherichia coli, klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa) are reasonable since these ethnomedicinal plants have been used in Persian folk medicine for treating skin diseases, venereal diseases, respiratory problems and nervous disorders for ages. Methods: The well diffusion method (KB testing) with a concentration of 250 μg/disc was used for evaluating the minimal inhibitory concentrations (MIC). Maximum synergistic effects of different combinations of components were also observed. Results: A particular combination of Acacia catechu (L.F.) Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo extracts possesses an outstanding anti-bacterial activity. It's inhibiting effect on microorganisms is significant when compared to the control group (P< 0.05). Staphylococcus aureus was the most sensitive microorganism. The highest antibacterial activity against gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) or gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis and Pseudomonas aeruginosa) was exerted by formula number 2 (Table1). Conclusion: The results reveal the presence of antibacterial activities of Acacia catechu, Castanea sativa husk, Ephedra sp. and Mumiyo against gram-positive and gram-negative bacteria. Synergistic effects in a combined formula, especially in formula number 2 (ASLANⓇ) can lead to potential sources of new antiseptic agents for treatment of acute or chronic skin ulcers. These results considering the significant antibacterial effect of the present formulation, support ethno-pharmacological uses against diarrheal and venereal diseases and demonstrate use of these plants to treat infectious diseases. PMID:25780663

Impact of bariatric surgery on patients with rheumatoid arthritis

PubMed Central

Sparks, Jeffrey A.; Halperin, Florencia; Karlson, Jonathan C.; Karlson, Elizabeth W.; Bermas, Bonnie L.

2015-01-01

Objective We investigated the effect of weight loss after bariatric surgery among patients with rheumatoid arthritis (RA). Methods We conducted a retrospective cohort study of RA patients who underwent bariatric surgery (Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or sleeve gastrectomy) at two medical centers. We obtained anthropometrics, laboratory values, RA disease activity, and medication use at baseline (prior to surgery), at six and twelve months post-surgery, and at most recent follow-up visits. RA disease activity was determined by clinical or validated measures. At each post-surgical visit, characteristics were compared to baseline. Results We identified 53 RA patients who underwent bariatric surgery. At baseline prior to surgery, mean body mass index was 47.8 kg/m2 (SD 7.7), mean weight was 128.2 kg (SD 24.1), and 57% had moderate/high RA disease activity. Twelve months post-surgery, subjects lost a mean of 41.0 kg (SD 17.3), 70% (SD 24) of excess weight (P<0.001). RA disease activity significantly improved at post-surgical visits (P<0.001). At 12 months post-surgery, 6% had moderate/high disease activity compared to 57% at baseline (P<0.001). At most recent follow-up (mean 5.8 years [SD 3.2] after surgery), 74% were in remission compared to 26% at baseline (P<0.001). Subjects had significantly lower erythrocyte sedimentation rate, C-reactive protein, and RA-related medication use at follow-up visits compared to baseline (P<0.05). Conclusion After substantial weight loss from bariatric surgery, RA patients had lower disease activity, decreased serum inflammatory markers, and less RA-related medication usage. Weight loss may be an important non-pharmacologic strategy to reduce RA disease activity. However, other factors, such as improved efficacy of medications, improved physical activity, and metabolic changes, may also have contributed to these post-surgical improvements. PMID:26018243

Vascular endothelial growth factor in systemic lupus erythematosus - correlations with disease activity and nailfold capillaroscopy changes.

PubMed

Bărbulescu, Andreea Lili; Vreju, Ananu Florentin; Bugă, Ana Maria; Sandu, Raluca Elena; Criveanu, Cristina; Tudoraşcu, Diana Rodica; Gheonea, Ioana Andreea; Ciurea, Paulina Lucia

2015-01-01

Our study aimed to quantify serum VEGF (vascular endothelial growth factor) and its inter-relation with the severity of microvascular damage, assessed by nailfold capillaroscopy (NC), and to establish the possible relationship with disease activity score. We included 18 patients, diagnosed with systemic lupus erythematosus (SLE) and 17 gender and age-matched control subjects. For determining serum VEGF, we used a Human VEGF Assay kit-IBL. NC was performed, according to the standard method, using a video-capillaroscope Videocap 3.0, DS Medica, by the same examiner, blinded to clinical and laboratory data. Serum VEGF registered a mean value of 68.99±71.06 pg/mL for SLE patients and 31.84±11.74 pg/mL for controls, differences statistically significant; depending on disease activity, we found a mean value of 60.11±57.74 pg/mL, for patients with moderate disease activity vs. 30.96±11.51 pg/mL for the ones with a low activity (p=0.014). We found a moderately positive correlation, statistically significant (p=0.015), between serum level of VEGF and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Performing NC, we found changes in 88.88% of the patients; the most frequent were increased tortuosity, dilated capillaries, an increased length and a prominent subpapillary plexus. The presence of nailfold capillaroscopy changes and serum level of VEGF, correlated moderately, positive. Since serum levels of VEGF are higher in SLE patients, compared to controls, significantly different according to disease activity degree, and directly inter-related to abnormal NC patterns and a more active disease, we can include these accessible parameters in the routine evaluation, in order to better quantify the systemic damage, individualize the treatment, improve the outcome and life quality for these patients.

Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

PubMed Central

Yüksel, Meral; Okur, Hacer Kuzu; Pelin, Zerrin; Öğünç, Ayliz Velioğlu; Öztürk, Levent

2014-01-01

OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels. PMID:24714832

Short health scale: A valid measure of health-related quality of life in Korean-speaking patients with inflammatory bowel disease

PubMed Central

Park, Soo-Kyung; Ko, Bong Min; Goong, Hyeon Jeong; Seo, Jeong Yeon; Lee, Sang Hyuk; Baek, Hae Lim; Lee, Moon Sung; Park, Dong Il

2017-01-01

AIM To evaluate the short health scale (SHS), a new, simple, four-part visual analogue scale questionnaire that is designed to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQOL), in Korean-speaking patients with IBD. METHODS The SHS was completed by 256 patients with Crohn’s disease (CD) and ulcerative colitis (UC). Individual SHS items were correlated with inflammatory bowel disease questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability, responsiveness and patient or disease characteristics with probable association with high SHS scores were analyzed. RESULTS Of 256 patients with IBD, 139 (54.3%) had UC and 117 (45.7%) had CD. The correlation coefficients between SHS questions about “symptom burden”, “activities of daily living”, and “disease-related worry” and their corresponding dimensions in the IBDQ ranged from 0.62 to 0.71, compared with correlation coefficients ranging from -0.45 to -0.61 for their non-corresponding dimensions. There was a stepwise increase in SHS scores, with increasing disease activity in both CD and UC (all P values < 0.001). Reliability was confirmed with test-retest correlations ranging from 0.68 to 0.90 (all P values < 0.001). Responsiveness was confirmed with the patients who remained in remission. Their SHS scores remained unchanged, except for the SHS dimension “disease-related worry”. In the multivariate analysis, female sex was associated with worse “general well-being” (OR = 2.28, 95%CI: 1.02-5.08) along with worse disease activity. CONCLUSION The SHS is a valid and reliable measure of HRQOL in Korean-speaking patients with IBD. PMID:28596689

Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients.

PubMed

Karci, Alper Cagri; Canturk, Zeynep; Tarkun, Ilhan; Cetinarslan, Berrin

2017-07-01

During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients. In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40). Serum matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B levels were measured by the enzyme-linked immunosorbent assay method. The mean serum matrix metalloproteinase-2 level was significantly higher in the active acromegaly patients than in the controlled acromegaly patients (150.1 ± 54.5 ng/mL vs. 100.2 ± 44.6 ng/mL; p < 0.0001). There was no significant difference between the active and controlled acromegaly patients regarding serum matrix metalloproteinase-9 and cathepsin B levels (p = 0.205 and p = 0.598, respectively). Serum matrix metalloproteinase-2 levels of 118.3 ng/mL and higher had a sensitivity of 75% and a specificity of 77.5% in determining active disease. The risk of active acromegaly was 3.3 fold higher in the patients with a matrix metalloproteinase-2 level of >118.3 ng/mL than in the patients with a matrix metalloproteinase-2 level of <118.3 ng/mL. In this study, serum matrix metalloproteinase-2 level is increased in the active acromegaly patients and a threshold value in determining active disease was defined for serum matrix metalloproteinase-2 level. This study is the first to compare acromegaly patients having active or controlled disease in terms of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels. The results need to be confirmed by a study that will be conducted in a larger patient group also including a healthy control group to demonstrate the value of this novel marker in disease activity.

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

PubMed Central

López-Mejías, Raquel; Rueda-Gotor, Javier; Miranda-Filloy, José A.; Ubilla, Begoña; Carnero-López, Beatriz; Palmou-Fontana, Natalia; Gómez-Acebo, Inés; Blanco, Ricardo; Pina, Trinitario; Ochoa, Rodrigo; González-Juanatey, Carlos; González-Gay, Miguel A.

2014-01-01

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients. PMID:24976690

Functional Assessment of Disease-Associated Regulatory Variants In Vivo Using a Versatile Dual Colour Transgenesis Strategy in Zebrafish

PubMed Central

Bhatia, Shipra; Gordon, Christopher T.; Foster, Robert G.; Melin, Lucie; Abadie, Véronique; Baujat, Geneviève; Vazquez, Marie-Paule; Amiel, Jeanne; Lyonnet, Stanislas; van Heyningen, Veronica; Kleinjan, Dirk A.

2015-01-01

Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function. PMID:26030420

PSEA: Kinase-specific prediction and analysis of human phosphorylation substrates

NASA Astrophysics Data System (ADS)

Suo, Sheng-Bao; Qiu, Jian-Ding; Shi, Shao-Ping; Chen, Xiang; Liang, Ru-Ping

2014-03-01

Protein phosphorylation catalysed by kinases plays crucial regulatory roles in intracellular signal transduction. With the increasing number of kinase-specific phosphorylation sites and disease-related phosphorylation substrates that have been identified, the desire to explore the regulatory relationship between protein kinases and disease-related phosphorylation substrates is motivated. In this work, we analysed the kinases' characteristic of all disease-related phosphorylation substrates by using our developed Phosphorylation Set Enrichment Analysis (PSEA) method. We evaluated the efficiency of our method with independent test and concluded that our approach is reliable for identifying kinases responsible for phosphorylated substrates. In addition, we found that Mitogen-activated protein kinase (MAPK) and Glycogen synthase kinase (GSK) families are more associated with abnormal phosphorylation. It can be anticipated that our method might be helpful to identify the mechanism of phosphorylation and the relationship between kinase and phosphorylation related diseases. A user-friendly web interface is now freely available at http://bioinfo.ncu.edu.cn/PKPred_Home.aspx.

Low angle light scattering analysis: a novel quantitative method for functional characterization of human and murine platelet receptors.

PubMed

Mindukshev, Igor; Gambaryan, Stepan; Kehrer, Linda; Schuetz, Claudia; Kobsar, Anna; Rukoyatkina, Natalia; Nikolaev, Viacheslav O; Krivchenko, Alexander; Watson, Steve P; Walter, Ulrich; Geiger, Joerg

2012-07-01

Determinations of platelet receptor functions are indispensable diagnostic indicators of cardiovascular and hemostatic diseases including hereditary and acquired receptor defects and receptor responses to drugs. However, presently available techniques for assessing platelet function have some disadvantages, such as low sensitivity and the requirement of large sample sizes and unphysiologically high agonist concentrations. Our goal was to develop and initially characterize a new technique designed to quantitatively analyze platelet receptor activation and platelet function on the basis of measuring changes in low angle light scattering. We developed a novel technique based on low angle light scattering registering changes in light scattering at a range of different angles in platelet suspensions during activation. The method proved to be highly sensitive for simultaneous real time detection of changes in size and shape of platelets during activation. Unlike commonly-used methods, the light scattering method could detect platelet shape change and aggregation in response to nanomolar concentrations of extracellular nucleotides. Furthermore, our results demonstrate that the advantages of the light scattering method make it a choice method for platelet receptor monitoring and for investigation of both murine and human platelets in disease models. Our data demonstrate the suitability and superiority of this new low angle light scattering method for comprehensive analyses of platelet receptors and functions. This highly sensitive, quantitative, and online detection of essential physiological, pathophysiological and pharmacological-response properties of human and mouse platelets is a significant improvement over conventional techniques.

A Structured Peer-Mentoring Method for Physical Activity Behavior Change Among Adolescents.

PubMed

Smith, Laureen H; Petosa, Rick L

2016-10-01

Despite national guidelines for regular physical activity, most adolescents are not physically active. Schools serve an estimated 60 million youth and provide an educational environment to meet the current physical activity guidelines. The obesity epidemic and chronic disease comorbidities associated with physical inactivity are not likely to be reversed without a strong contribution from local schools. This article describes how a structured peer-mentoring method provides a feasible, flexible, and tailored means to meet the current guidelines for best practice in a school setting. Structured peer mentoring using trained high school mentors to support behavior change in younger peers is an innovative method to meeting the School Health Guidelines to Promote Healthy Eating and Physical Activity Through structured peer mentoring, adolescents are provided consistent social support in a caring and personalized manner. This support builds skills and competencies enhancing self-efficacy to sustain a lifetime of physical activity behavior. © The Author(s) 2016.

A Structured Peer-Mentoring Method for Physical Activity Behavior Change Among Adolescents

PubMed Central

Smith, Laureen H.; Petosa, Rick L.

2016-01-01

Despite national guidelines for regular physical activity, most adolescents are not physically active. Schools serve an estimated 60 million youth and provide an educational environment to meet the current physical activity guidelines. The obesity epidemic and chronic disease comorbidities associated with physical inactivity are not likely to be reversed without a strong contribution from local schools. This article describes how a structured peer-mentoring method provides a feasible, flexible, and tailored means to meet the current guidelines for best practice in a school setting. Structured peer mentoring using trained high school mentors to support behavior change in younger peers is an innovative method to meeting the School Health Guidelines to Promote Healthy Eating and Physical Activity. Through structured peer mentoring, adolescents are provided consistent social support in a caring and personalized manner. This support builds skills and competencies enhancing self-efficacy to sustain a lifetime of physical activity behavior. PMID:27257081

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

PubMed

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk

PubMed Central

Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

2015-01-01

Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease. PMID:26057532

Lifestyle Factors and Alzheimer's Disease in People with Down Syndrome

ERIC Educational Resources Information Center

Kenshole, Athena V.; Gallichan, Deanna; Pahl, Sabine; Clibbens, John

2017-01-01

Background: Lifestyle has previously been associated with the onset of Alzheimer's disease (AD) in the typically developing population, but research investigating this association in Down syndrome (DS) is limited. Method: Adults with DS and AD (n = 27) were compared to adults with DS without AD (n = 30) on physical activity, diet, weight, where…

Automatic counting of microglial cell activation and its applications

PubMed Central

Gallego, Beatriz I.; de Gracia, Pablo

2016-01-01

Glaucoma is a multifactorial optic neuropathy characterized by the damage and death of the retinal ganglion cells. This disease results in vision loss and blindness. Any vision loss resulting from the disease cannot be restored and nowadays there is no available cure for glaucoma; however an early detection and treatment, could offer neuronal protection and avoid later serious damages to the visual function. A full understanding of the etiology of the disease will still require the contribution of many scientific efforts. Glial activation has been observed in glaucoma, being microglial proliferation a hallmark in this neurodegenerative disease. A typical project studying these cellular changes involved in glaucoma often needs thousands of images - from several animals - covering different layers and regions of the retina. The gold standard to evaluate them is the manual count. This method requires a large amount of time from specialized personnel. It is a tedious process and prone to human error. We present here a new method to count microglial cells by using a computer algorithm. It counts in one hour the same number of images that a researcher counts in four weeks, with no loss of reliability. PMID:27651757

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment. PMID:23940611

Progress of pancreatitis disease biomarker alpha amylase enzyme by new nano optical sensor.

PubMed

Attia, M S; Al-Radadi, Najlaa S

2016-12-15

A new nano optical sensor binuclear Pd-(2-aminothiazole) (urea), Pd(atz,ur) complex was prepared and characterized for the assessment of the activity of alpha amylase enzyme in urine and serum samples for early diagnosis of Pancreatitis disease. The assessment of alpha amylase activity is carried out by the quenching of the luminescence intensity of the nano optical sensor binuclear Pd(atz,ur) complex at 457nm by the 2-chloro-4-nitrophenol (2-CNP) which produced from the reaction of the enzyme with 2-chloro-4-nitrophenyl-α-d-maltotrioside (CNPG3) substrate. The remarkable quenching of the luminescence intensity at 457nm of nano Pd(atz,ur) doped in sol-gel matrix by various concentrations of the 2-CNP was successfully used as an optical sensor for the assessment of α-amylase activity. The calibration plot was achieved over the concentration range 8.5×10(-6) to 1.9×10(-9)molL(-1) 2-CNP with a correlation coefficient of (0.999) and a detection limit of (7.4×10(-10)molL(-1)). The method was used satisfactorily for the assessment of the α-amylase activity over activity range (3-321U/L) in different urine and serum samples of pancreatitis patients. The assessment of the alpha amylase biomarker by the proposed method increases its sensitivity (96.88%) and specificity (94.41%) for early diagnosis of pancreatitis diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

The Diagnostic Role of Magnetic Resonance Enterography as a Complementary Test to Colonoscopy in Active Crohn's Disease.

PubMed

Aryan, Arvin; Azizi, Zahra; Teimouri, Azam; Ebrahimi Daryani, Nasser; Aletaha, Najme; Jahanbakhsh, Ali; Nouritaromlou, Mohammad Kazem; Alborzi, Forough; Mami, Masoud; Basirat, Vahid; Javid Anbardan, Sanam

2016-04-01

BACKGROUND According to recent studies comparing magnetic resonance enterography (MRE) with ileocolonoscopy for assessing inflammation of small bowel and colonic segments in adults with active Crohn's disease (CD), we aimed to compare the accuracy of these two diagnostic methods in Iranian population. METHODS During 2013-2014 a follow-up study was done on 30 patients with active CD in a gastroenterology clinic affiliated to Tehran University of Medical Sciences. MRE and ileocolonoscopy were performed for all the patients. All statistical analyses were performed using SPSS (version 18) and p-value<0.05 was considered as statistically significant. RESULTS Of the 30 patients with active CD, 11(36.7%) were men and 19 (63.3%) were women with mean age of 37.30±13.66 years (range: 19-67 years). MRE had sensitivity and specificity of 50% and 90% with positive predictive value (PPV) and negative predictive value (NPV) of 71.43 and 78.26, respectively for localizing sigmoid lesions and ileum had sensitivity and specificity of 84.21 and 45.45 with PPV and NPV of 72.73 and 62.50, respectively. CONCLUSION While moderate sensitivity and high specificity of MRE in localizing colonic lesions makes it an appropriate confirmatory test after colonoscopy, the reported high sensitivity and moderate specificity of MRE versus colonoscopy in detecting ileal lesions makes it a suitable screening test for ileal lesions. Finally we can conclude that MRE can be an important complementary test to colonoscopy in detecting active disease.

Physical Activity Behaviors and Emotional Self-Efficacy: Is There a Relationship for Adolescents?

ERIC Educational Resources Information Center

Valois, Robert F.; Umstattd, M. Renee; Zullig, Keith J.; Paxton, Raheem J.

2008-01-01

Background: This study explored relationships between physical activity (PA) behaviors and emotional self-efficacy (ESE) in a statewide sample of public high school adolescents in South Carolina (n = 3836). Methods: The Center for Disease Control Youth Risk Behavior Survey PA items and an adolescent ESE scale were used. Logistic regression…

Secretory phospholipase A2 activity in blood serum: the challenge to sense.

PubMed

Alekseeva, A S; Korotaeva, A A; Samoilova, E V; Volynsky, P E; Vodovozova, E L; Boldyrev, I A

2014-11-07

Excess levels of secretory phospholipase A2 (sPLA2) is known to contribute to several inflammatory diseases including vascular inflammation correlating with coronary events in coronary artery disease. Thus a method to monitor sPLA2 activity in blood serum is urgently needed. Such method is still a challenge since existing fluorescent probes do not allow to monitor sPLA2 activity directly in blood serum. Here we analyze and overcome barriers in sPLA2 sensing methodology and report a fluorescent probe and a kinetic model of its hydrolysis by sPLA2. New probe is designed with a fluorophore and a quencher not interfering binding to the enzyme. At the same time phospholipid matrix bearing the probe promotes efficient initial quenching of the fluorophore. Kinetic model of probe hydrolysis takes into account signal change due to the side processes. The probe and the kinetic model applied together prove the concept that the activity of sPLA can be measured directly in blood serum. Copyright © 2014 Elsevier Inc. All rights reserved.

A rapid fluorescence assay for sphingosine-1-phosphate lyase enzyme activity.

PubMed

Bandhuvula, Padmavathi; Fyrst, Henrik; Saba, Julie D

2007-12-01

Sphingosine-1-phosphate (S1P) lyase (SPL) catalyzes the conversion of S1P to ethanolamine phosphate and hexadecenal. This enzyme plays diverse roles in physiology and disease and, thus, may be useful as a disease marker and/or drug target. Unfortunately, the radioisotope-based assay currently used to quantify SPL activity is suboptimal. We have devised an assay using a commercially available omega(7-nitro-2-1,3-benzoxadiazol-4-yl)-d-erythro (NBD)-labeled fluorescent substrate. Alternatively, we provide a method for synthesis of the substrate from NBD-sphingosine. Enzyme activity is determined by following the formation of NBD-aldehyde product, which is isolated from unreacted substrate by lipid extraction and quantified after separation by HPLC using a C18 column. A fluorescent NBD-C18-sphingosine internal standard is used to control for extraction efficiency. The reaction is linear over 20 min and total protein concentrations of 20-200 mg/l. The sensitivity of the fluorescence assay is comparable to or better than that of the radioactive assay, and SPL levels as low as 8 pmol/mg/min were readily detected. Semicarbazide, a nonspecific SPL inhibitor, reduced SPL activity in vitro by approximately 70% using both standard and fluorescence methods. Product inhibition was not observed using ethanolamine phosphate and a commercially available source of hexadecenal. This method is suitable for quantifying SPL activity in a variety of cell and tissue sources.

Antioxidant activity of Syzygium cumini leaf gall extracts

PubMed Central

Eshwarappa, Ravi Shankara Birur; Iyer, Raman Shanthi; Subbaramaiah, Sundara Rajan; Richard, S Austin; Dhananjaya, Bhadrapura Lakkappa

2014-01-01

Introduction: Free radicals are implicated in several metabolic diseases and the medicinal properties of plants have been explored for their potent antioxidant activities to counteract metabolic disorders. This research highlights the chemical composition and antioxidant potential of leaf gall extracts (aqueous and methanol) of Syzygium cumini (S. cumini), which have been extensively used in traditional medications to treat various metabolic diseases. Methods: The antioxidant activities of leaf gall extracts were examined using diphenylpicrylhydrazyl (DPPH), nitric oxide scavenging, hydroxyl scavenging and ferric reducing power (FRAP) methods. Results: In all the methods, the methanolic extract showed higher antioxidant potential than the standard ascorbic acid. The presence of phenolics, flavonoids, phytosterols, terpenoids, and reducing sugars was identified in both the extracts. When compared, the methanol extract had the highest total phenolic and flavonoid contents at 474±2.2 mg of GAE/g d.w and 668±1.4 mg of QUE/g d.w, respectively. The significant high antioxidant activity can be positively correlated to the high content of total polyphenols/flavonoids of the methanol extract. Conclusion: The present study confirms the folklore use of S. cumini leaves gall extracts as a natural antioxidant and justifies its ethnobotanical use. Further, the result of antioxidant properties encourages the use of S. cumini leaf gall extracts for medicinal health, functional food and nutraceuticals applications. PMID:25035854

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology

PubMed Central

Lee, Bradford W.; Kumar, Virender B.; Biswas, Pooja; Ko, Audrey C.; Alameddine, Ramzi M.; Granet, David B.; Ayyagari, Radha; Kikkawa, Don O.; Korn, Bobby S.

2018-01-01

Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents. PMID:29760827

Deterministic SLIR model for tuberculosis disease mapping

NASA Astrophysics Data System (ADS)

Aziz, Nazrina; Diah, Ijlal Mohd; Ahmad, Nazihah; Kasim, Maznah Mat

2017-11-01

Tuberculosis (TB) occurs worldwide. It can be transmitted to others directly through air when active TB persons sneeze, cough or spit. In Malaysia, it was reported that TB cases had been recognized as one of the most infectious disease that lead to death. Disease mapping is one of the methods that can be used as the prevention strategies since it can displays clear picture for the high-low risk areas. Important thing that need to be considered when studying the disease occurrence is relative risk estimation. The transmission of TB disease is studied through mathematical model. Therefore, in this study, deterministic SLIR models are used to estimate relative risk for TB disease transmission.

Practice of Physical Activity among Future Doctors: A Cross Sectional Analysis

PubMed Central

Rao, Chythra R; Darshan, BB; Das, Nairita; Rajan, Vinaya; Bhogun, Meemansha; Gupta, Aditya

2012-01-01

Background: Non communicable diseases (NCD) will account for 73% of deaths and 60% of the global disease burden by 2020. Physical activity plays a major role in the prevention of these non-communicable diseases. The stress involved in meeting responsibilities of becoming a physician may adversely affect the exercise habits of students. So, the current study aimed to study the practice of physical activity among undergraduate medical students. Methods: A cross sectional study was conducted among 240 undergraduate medical students. Quota sampling method was used to identify 60 students from each of the four even semesters. A pre-tested, semi-structured questionnaire was used to collect the data. Statistical Package for Social Sciences (SPSS) version 16 was used for data entry and analysis and results are expressed as percentages and proportions. Results: In our study, 55% were 20 to 22 years old. Over half of the students were utilizing the sports facilities provided by the university in the campus. Majority of students 165 (69%) had normal body mass index (BMI), (51) 21% were overweight, while 7 (3%) were obese. Of the 62% who were currently exercising, the practice of physical activity was more among boys as compared to girls (62% v/s 38%). Lack of time 46 (60.5%), laziness (61.8%), and exhaustion from academic activities (42%) were identified as important hindering factors among medical students who did not exercise. Conclusion: A longitudinal study to follow-up student behavior throughout their academic life is needed to identify the factors promoting the practice of physical activity among students. PMID:22708033

Immunocapture and microplate-based activity and quantity measurement of pyruvate dehydrogenase in human peripheral blood mononuclear cells.

PubMed

Liu, Xiaowen; Pervez, Hira; Andersen, Lars W; Uber, Amy; Montissol, Sophia; Patel, Parth; Donnino, Michael W

2015-01-01

Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). RESULTS/METHODOLOGY: We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects. Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease.

Behçet Syndrome Manifestations and Activity in the United States versus Turkey — A Cross-sectional Cohort Comparison

PubMed Central

Sibley, Cailin; Yazici, Yusuf; Tascilar, Koray; Khan, Nafiz; Bata, Yasmin; Yazici, Hasan; Goldbach-Mansky, Raphaela; Hatemi, Gulen

2015-01-01

Objective To compare clinical manifestations and activity of Behçet syndrome (BS) in the United States versus Turkey using validated outcome measures. Methods Consecutive patients with BS from the US National Institutes of Health (NIH), New York University, and the University of Istanbul were evaluated. Disease activity was measured using the Behçet’s Syndrome Activity Scale (BSAS) and the Behçet’s Disease Current Activity Form (BDCAF) with quality of life measured by the Behçet Disease Quality of Life (BDQOL) form. One-way ANOVA, t-tests, and multivariate regression analyses were performed. Results Mean age did not differ between sites; however, more women were seen in the United States versus in Turkey (p < 0.001), and disease duration was longer in the United States (p = 0.02). Organ manifestations were similar for oral and genital ulcers, skin disease, arthralgia, eye disease, and thrombosis. However, more gastrointestinal (p < 0.001) and neurologic disease (p = 0.003) was seen in the United States. BSAS and BDCAF scores were worse in the United States compared to Turkey (p = 0.013 and < 0.001, respectively). Worse mean BDQOL scores were observed at the NIH compared to Istanbul (not significant). Multivariable regression models showed worse scores in ethnically atypical patients for BSAS and BDCAF (p = 0.04 and p = 0.001), American patients for BDCAF (p = 0.01), older age for BDCAF (p = 0.005), and women for BDQOL (p = 0.01). Conclusion Demographic and clinical manifestations of BS differ between sites with higher disease activity in the United States compared to Turkey. Referral patterns, age, sex, ethnicity, and country of origin may be important in these differences. These observations raise the question of whether pathogenic mechanisms differ in Turkish and American patients. PMID:24931953

Superoxide dismutase activity of Cu-bound prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Lu, Wenchang; Bernholc, Jerry

2009-03-01

Misfolding of the prion protein, PrP, has been linked to a group of neurodegenerative diseases, including the mad cow disease in cattle and the Creutzfeldt-Jakob disease in humans. The normal function of PrP is still unknown, but it was found that the PrP can efficiently bind Cu(II) ions. Early experiments suggested that Cu-PrP complex possesses significant superoxide dismutase (SOD) activity, but later experiments failed to confirm it and at present this issue remains unresolved. Using a recently developed hybrid DFT/DFT method, which combines Kohn-Sham DFT for the solute and its first solvation shells with orbital-free DFT for the remainder of the solvent, we have investigated SOD activity of PrP. The PrP is capable of incorporating Cu(II) ions in several binding modes and our calculations find that each mode has a different SOD activity. The highest activity found is comparable to those of well-known SOD proteins, suggesting that the conflicting experimental results may be due to different bindings of Cu(II) in those experiments.

Examining the Disability Model From the International Classification of Functioning, Disability, and Health Using a Large Data Set of Community-Dwelling Malaysian Older Adults

PubMed Central

Loke, Seng Cheong; Lim, Wee Shiong; Someya, Yoshiko; Hamid, Tengku A.; Nudin, Siti S. H.

2015-01-01

Objective: This study examines the International Classification of Functioning, Disability, and Health model (ICF) using a data set of 2,563 community-dwelling elderly with disease-independent measures of mobility, physical activity, and social networking, to represent ICF constructs. Method: The relationship between chronic disease and disability (independent and dependent variables) was examined using logistic regression. To demonstrate variability in activity performance with functional impairment, graphing was used. The relationship between functional impairment, activity performance, and social participation was examined graphically and using ANOVA. The impact of cognitive deficits was quantified through stratifying by dementia. Results: Disability is strongly related to chronic disease (Wald 25.5, p < .001), functional impairment with activity performance (F = 34.2, p < .001), and social participation (F= 43.6, p < .001). With good function, there is considerable variability in activity performance (inter-quartile range [IQR] = 2.00), but diminishes with high impairment (IQR = 0.00) especially with cognitive deficits. Discussion: Environment modification benefits those with moderate functional impairment, but not with higher grades of functional loss. PMID:26472747

Pentraxin-3 levels are associated with vasculitis and disease activity in childhood-onset systemic lupus erythematosus.

PubMed

Sahin, S; Adrovic, A; Barut, K; Durmus, S; Gelisgen, R; Uzun, H; Kasapcopur, O

2017-09-01

Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune disease characterized by inflammatory organ damage by means of vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory processes, predominantly from endothelial cells. In adult studies, PTX3 has shown to be an indicator of active vasculitis both in large-vessel and small-vessel vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated with disease activity, and with some of the clinical manifestations and laboratory parameters. We aimed to ascertain if PTX3 might be a significant mediator in cSLE and if it might indicate active vasculitis during the course of the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and 41 healthy subjects. We have investigated its relation with disease activity, damage, clinical features, laboratory parameters and medications. Results Serum levels of PTX3 were found to be increased in cSLE compared to healthy controls (mean ± SD; 10.6 ± 8.2 ng/mL vs 2.7 ± 1.3 ng/mL, p < 0.001). PTX3 concentrations were also in correlation with SLEDAI-2K ( r = 0.57, p < 0.001). When viewed from the clinical perspective, serum PTX3 levels were significantly higher only in patients with active vasculitis ( p < 0.001), Raynaud phenomenon ( p = 0.006) and mucocutaneous manifestations ( p < 0.001). However, an association between PTX3 and age, age at disease onset, disease duration, complement levels, PedSDI score (pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected. Conclusions Patients with cSLE have increased levels of serum PTX3 compared to healthy controls. Thus, serum PTX-3 level might be a significant mediator in cSLE. Apart from these, the results support that PTX3 reflects active cutaneous vasculitis in cSLE and correlates with disease activity.

Flares assessed weekly in patients with rheumatoid arthritis or axial spondyloarthritis and relationship with physical activity measured using a connected activity tracker: a 3-month study

PubMed Central

Jacquemin, Charlotte; Molto, Anna; Servy, Hervé; Sellam, Jérémie; Foltz, Violaine; Gandjbakhch, Frédérique; Hudry, Christophe; Mitrovic, Stéphane; Granger, Benjamin; Fautrel, Bruno; Gossec, Laure

2017-01-01

Background The evolution of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is marked by flares, although their frequency is unclear. Flares may impact physical activity. Activity can be assessed objectively using activity trackers. The objective was to assess longitudinally the frequency of flares and the association between flares and objective physical activity. Methods This prospective observational study (ActConnect) included patients with definite clinician-confirmed RA or axSpA, owning a smartphone. During 3 months, physical activity was assessed continuously by number of steps/day, using an activity tracker, and disease flares were self-assessed weekly using a specific flare question and, if relevant, the duration of the flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models. Results In all, 170/178 patients (91 patients with RA and 79 patients with axSpA; 1553 time points) were analysed: mean age was 45.5±12.4 years, mean disease duration was 10.3±8.7 years, 60 (35.3%) were men and 90 (52.9%) received biologics. The disease was well-controlled (mean Disease Activity Score 28: 2.3±1.2; mean Bath Ankylosing Spondylitis Disease Activity Index score: 3.3±2.1). Patients self-reported flares in 28.2%±28.1% of the weekly assessments. Most flares (78.9%±31.4%) lasted ≤3 days. Persistent flares lasting more than 3 days were independently associated with less weekly physical activity (p=0.03), leading to a relative decrease of 12%–21% and an absolute decrease ranging from 836 to 1462 steps/day. Conclusion Flares were frequent but usually of short duration in these stable patients with RA and axSpA. Persistent flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares. PMID:28879046

SAFETY AND TOLERABILITY OF LOW DOSE NALTREXONE THERAPY IN CHILDREN WITH MODERATE TO SEVERE CROHN’S DISEASE: A PILOT STUDY

PubMed Central

Smith, Jill P.; Field, Douglas; Bingaman, Sandra; Evans, Robert; Mauger, David

2012-01-01

Background There is an unmet need for safe and effective medicines to treat children with Crohn’s disease. Recently, investigations have shown an association between endogenous opioid peptides and inflammatory cells. Aims The aims of this study were to evaluate the safety and tolerability of an opioid antagonist, naltrexone, in children with moderate to severe Crohn’s disease. Methods A pilot clinical trial was conducted in children with moderate to severe Crohn’s disease. Fourteen subjects with a mean age of 12.3 years (8–17, range) were enrolled. Children were randomized to placebo or naltrexone 0.1 mg/kg orally for 8 weeks followed by open-labeled treatment with 8 additional weeks of naltrexone. Safety and toxicity were monitored by physical examinations and blood chemistries. Clinical activity was assessed by the PCDAI (Pediatric Crohn’s Disease Activity Index) and Quality of life was monitored by the Impact III survey. Results Oral naltrexone was well tolerated without any serious adverse events in children with moderate to severe Crohn’s disease. PCDAI scores significantly decreased from pretreatment values (34.2±3.3) with an eight-week course of naltrexone therapy (21.7±3.9) (p=0.005). Twenty-five percent of those treated with naltrexone were considered in remission (score < 10) and 67% had improved with mild disease activity (decrease PCDAI score by at least 10 points) at the end of the study. Systemic and social quality of life improved with naltrexone treatment (p=0.035). Conclusions Naltrexone therapy appears safe with limited toxicity when given to children with Crohn’s disease and may reduce disease activity. PMID:23188075

Factors associated with disease expression patterns in systemic lupus erythematosus patients: results from LUMINA (LXXVII), a multiethnic US cohort.

PubMed

Ugarte-Gil, M F; Pimentel-Quiroz, V R; Vilá, L M; Reveille, J D; McGwin, G; Alarcón, G S

2017-05-01

Objective The objective of this study was to determine the association of disease expression patterns with demographic and clinical characteristics in SLE. Methods Patients from a multi-ethnic SLE cohort were included. Disease expression patterns were defined as acute SLE and insidious SLE; this group was divided into those who accrued three ACR criteria and then accrued the fourth (insidious pattern A) and those who have one or two and then accrued four criteria (insidious pattern B). Disease activity was ascertained with the SLAM-R and disease damage with SLICC/ACR damage index. Variables were compared using analysis of variance for numeric variables and χ 2 for categorical variables. Multivariable analyses adjusting for possible confounders were performed. Results Six hundred and forty patients were included; the most frequent pattern was the insidious pattern B, with 415 (64.8%) patients, followed by the acute SLE group with 115 (18.0%) and the insidious pattern A with 110 (17.2%) patients. Patients from the insidious pattern A were older at diagnosis (pattern A: 39.8 vs pattern B: 36.7 vs acute: 32.4 years; p < 0.0001), more educated (13.6 vs 13.1 vs 12.1; p = 0.0008) and with a less active disease at baseline (8.8 vs 9.2 vs 10.7; p = 0.0227). Caucasian and Hispanic (Puerto Rico) ethnicities were overrepresented in this group (40.0% vs 27.7% vs 19.1% and 18.2% vs 17.1% vs 9.6%; p = 0.0003). Conclusions More insidious onset is associated with older age, Caucasian ethnicity, higher level of education, and lower disease activity than those with acute onset. However, after multivariable analyses, disease activity was not associated with any disease expression pattern.

In vitro antioxidant and cholinesterase inhibitory activities of Elatostema papillosum leaves and correlation with their phytochemical profiles: a study relevant to the treatment of Alzheimer's disease.

PubMed

Ali Reza, A S M; Hossain, Mohammad Shahadat; Akhter, Sharmin; Rahman, Md Rezanur; Nasrin, Mst Samima; Uddin, Md Josim; Sadik, Golam; Khurshid Alam, A H M

2018-04-05

Alzheimer's disease (AD), one of the major causes of dementia, is an overwhelming neurodegenerative disease that particularly affects the brain, leading to memory loss and impairment of language and judgment capacity. The aim of the present study was to investigate the antioxidant and anticholinesterase properties of the leaves of Elatostema papillosum (EPL) and correlate with their phytochemical profiles, which are relevant to the treatment of AD. The dried coarse powder of EPL was extracted with 80% methanol (EPL-M80) by cold extraction method. The resultant EPL-M80 was assessed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity by the Ellman method. The antioxidant activity was determined by DPPH (1, 1-diphenyl-2-picrylhydrazyl) and hydroxyl radical scavenging assays. Quantitative phytochemical (phenolic and flavonoid contents) analysis of endogenous substances in EPL-M80 was performed by standard spectrophotometric methods. EPL-M80 significantly (p < 0.05) inhibited AChE and BChE activity with IC 50 of 165.40 ± 4.01 and 213.81 ± 3.57 μg/mL, respectively in a dose-dependent manner. Additionally, EPL-M80 exhibited strong radical scavenging activity against DPPH (IC 50 = 32.35 ± 0.68 μg/mL) and hydroxyl radical (IC 50 = 19.67 ± 1.42 μg/mL) when compared to that of standards. EPL-M80 was found to be rich in phenolic (23.74 mg gallic acid equivalent/g of dry extract) and flavonoid (31.18 mg quercetin equivalent/g of dry extract) content. Furthermore, a positive correlation (p < 0.001) was observed between the total phenolics and antioxidant as well as the anticholinesterase potential. The marked inhibition of AChE and BChE, and potent antioxidant activity of the leaves of Elatostema papillosum highlight its potential to provide an effective treatment for AD.

Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis

PubMed Central

Chi, Shuhong; Yu, Yunxia; Shi, Juan; Zhang, Yurong; Yang, Jijuan; Yang, Lijuan; Liu, Xiaoming

2015-01-01

Objective. An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. Methods. The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. Results. The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. Conclusion. Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease. PMID:26549923

Leisure in Children and Adolescents with Juvenile Idiopathic Arthritis: A Systematic Review

PubMed Central

Cavallo, Sabrina; April, Karine Toupin; Grandpierre, Viviane; Majnemer, Annette; Feldman, Debbie Ehrmann

2014-01-01

The aim of this systematic review is to describe participation in social and physical leisure activities among children and adolescents with JIA, as well as identify potential determinants of leisure participation. Methods Electronic databases were systematically searched for articles published up until June 2013 pertaining to participation in leisure activities among youth with JIA and other rheumatic diseases. Studies were included if they measured involvement in either social or physical leisure activities. Selection and quality appraisal of articles were completed independently by two authors. Results Eight hundred and ninety-three articles were found through electronic and reference search. One hundred and nine full articles were reviewed to assess for eligibility. Twelve articles met inclusion criteria and findings were reviewed. Most focused on describing participation in physical rather than social activities. Results suggest that youth with JIA participated less in both social and physical leisure activities as compared to healthy peers, and those with JIA did not meet national recommendations for physical activity. Potential determinants of leisure participation were socio-demographic (age, sex), anthropometric (height, weight) and disease-related (JIA subtype, disease duration, pain, number of swollen or painful joints, stiffness, fatigue, well-being) factors. Conclusion Characterization of leisure activity remains limited and mostly focused on physical activity in JIA. Assessment of more comprehensive outcome measures is warranted to obtain a better description of leisure in this population. Evidence of the influence of contextual factors as potential determinants of involvement in leisure among children with pediatric rheumatologic diseases is needed. PMID:25329390

Antibacterial Activity of Marine and Black Band Disease Cyanobacteria against Coral-Associated Bacteria

PubMed Central

Gantar, Miroslav; Kaczmarsky, Longin T.; Stanić, Dina; Miller, Aaron W.; Richardson, Laurie L.

2011-01-01

Black band disease (BBD) of corals is a cyanobacteria-dominated polymicrobial disease that contains diverse populations of heterotrophic bacteria. It is one of the most destructive of coral diseases and is found globally on tropical and sub-tropical reefs. We assessed ten strains of BBD cyanobacteria, and ten strains of cyanobacteria isolated from other marine sources, for their antibacterial effect on growth of heterotrophic bacteria isolated from BBD, from the surface mucopolysaccharide layer (SML) of healthy corals, and three known bacterial coral pathogens. Assays were conducted using two methods: co-cultivation of cyanobacterial and bacterial isolates, and exposure of test bacteria to (hydrophilic and lipophilic) cyanobacterial cell extracts. During co-cultivation, 15 of the 20 cyanobacterial strains tested had antibacterial activity against at least one of the test bacterial strains. Inhibition was significantly higher for BBD cyanobacteria when compared to other marine cyanobacteria. Lipophilic extracts were more active than co-cultivation (extracts of 18 of the 20 strains were active) while hydrophilic extracts had very limited activity. In some cases co-cultivation resulted in stimulation of BBD and SML bacterial growth. Our results suggest that BBD cyanobacteria are involved in structuring the complex polymicrobial BBD microbial community by production of antimicrobial compounds. PMID:22073011

Histone Deacetylase Adaptation in Single Ventricle Heart Disease and a Young Animal Model of Right Ventricular Hypertrophy

PubMed Central

Blakeslee, Weston W.; Demos-Davies, Kimberly M.; Lemon, Douglas D.; Lutter, Katharina M.; Cavasin, Maria A.; Payne, Sam; Nunley, Karin; Long, Carlin S.; McKinsey, Timothy A.; Miyamoto, Shelley D.

2017-01-01

Background Histone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac disease. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle heart disease of right ventricular morphology (SV), as well as in a rodent model of right ventricular hypertrophy (RVH). Methods Homogenates of RV explants from non-failing controls and SV children were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day old rat pups were placed in hypoxic conditions and echocardiographic analysis, gene expression, HDAC catalytic activity and isoform expression studies of the RV were performed. Results Class I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in hearts of SV children. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression and elevated class I and class IIb HDAC catalytic activity and protein expression in the RV compared to control. Conclusions These data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. While further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for pre-clinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies. PMID:28549058

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study.

PubMed

Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-05-26

BACKGROUND This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). MATERIAL AND METHODS Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). RESULTS The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. CONCLUSIONS The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients.

Antioxidant and α-glucosidase activities of benzoic acid derivate from the bark of Myristica fatua Houtt

NASA Astrophysics Data System (ADS)

Megawati, Darmawan, Akhmad; Fajriah, Sofa; Primahana, Gian; Dewi, Rizna Triana; Minarti, Meiliawati, Lia

2017-11-01

Myrictica fatua Houtt widely used in Indonesian as one of the traditional medicinal plants. Cancer and diabetic mellitus (DM) type 2 are two degenerative diseases caused by the presence of excessive free radicals in the body. Antioxidant and anti-diabetic active compounds were needed to reduce the risk of the diseases. One of the chemical compound groups that can be used as antioxidant and antidiabetic is phenolic compound. Isolation of the methanolic extract of the bark of M. fatua Houtt using chromatography methods led to the isolation of phenolic compound. Methyl 3,4-dihydroxybenzoate showed antioxidant and antidiabetic activities through DPPH free radicals scavenger and α-glucosidase inhibitions activities test showed IC50 value 7.96 and 7.68 ug / mL, respectively

Is Moderate Red Wine Consumption Safe in Inactive Inflammatory Bowel Disease?

PubMed Central

Swanson, Garth R.; Tieu, Vanessa; Shaikh, Maliha; Forsyth, Chris; Keshavarzian, Ali

2011-01-01

Background Alcohol consumption is a potential trigger for inflammatory bowel disease (IBD) flare because of alcohol-induced oxidative stress and its deleterious effects on gut barrier function. Additionally, we have recently shown that alcohol consumption is associated with more symptoms in IBD. However, it is not known whether moderate daily alcohol consumption can modify IBD disease activity. To test what effects alcohol may have on patients with IBD, we evaluated the effect of moderate daily red wine for 1 week on two factors associated with recurrent IBD disease activity: intestinal permeability and stool calprotectin. Methods To assess the effects of moderate daily alcohol consumption on intestinal permeability and inflammation, we recruited 21 patients: 8 with inactive ulcerative colitis (UC), 6 with inactive Crohn's disease (CD), and 7 healthy controls. All participants with IBD completed a validated questionnaire on disease activity (Crohn's disease activity index or ulcerative colitis clinical activity index), to confirm they had inactive disease. All subjects then underwent a baseline assessment that included a blood draw, urine collection after sugar challenge, and stool collection. Subjects then consumed 1–3 glasses of red wine a day for 1 week (approx. 0.4 g EtOH/kg), and repeated the three measures. Results No subjects flared during the study. Moderate alcohol consumption did not significantly change either clinical disease activity scores or C-reactive protein. In contrast to healthy subjects, daily consumption of red wine significantly (1) decreased stool calprotectin in IBD subjects from baseline (p = 0.001) and (2) increased intestinal permeability as measured by urinary lactulose/mannitol excretion (marker of small bowel permeability) in CD (p = 0.028) or urinary sucralose secretion (marker of large bowel permeability) in UC (p = 0.012). Conclusions One week of moderate consumption of red wine in inactive IBD was associated with a significant decrease in stool calprotectin and a significant increase in intestinal permeability. Our data suggests that patients with inactive IBD who drink red wine daily may be at an increased long-term risk for disease relapse. PMID:21876358

Bilateral versus unilateral thyroid eye disease

PubMed Central

Kashkouli, Mohsen Bahmani; Kaghazkanani, Reza; Heidari, Iraj; Ketabi, Nooshin; Jam, Sara; Azarnia, Shahrzad; Pakdel, Farzad

2011-01-01

Aims: The aim of this study was to compare demographics, clinical manifestations, associated systemic and ocular factors, severity and activity of patients with unilateral thyroid eye disease (U-TED) versus bilateral thyroid eye disease (B-TED). Materials and Methods: In a cross-sectional study, all patients with Graves’ hyperthyroidism and primary hypothyroidism seen in an endocrinology clinic were included from September 2003 to July 2006. Demographics, complete eye examination, severity score (NOSPECS, total eye score), and clinical activity score were recorded and compared in the B-TED and U-TED groups of patients. Results: From 851 patients with thyroid disorders, 303 (35.6%) had TED. Thirty-two patients (32/ 303, 10.56%) were found to have U-TED. Patients with U-TED (mean age 31.6 ± 11.6 years) were significantly younger than patients with B-TED (mean age 37.7 ± 14.7 years). Monovariate analysis (Chi-square and independent sample t-test) showed a significantly higher severity score in B-TED (U-TED 4.09±4.05, B-TED: 6.7±6.3; P= 0.002) and more activity score in B-TED (U-TED= 1.03±0.96, B-TED: 1.74±1.6, P= 0.001). However, multivariate analysis did not show any significant difference between the two groups in terms of age, gender, type of thyroid disease, duration of thyroid disease and TED, severity and activity of TED, smoking habit, and presentation of TED before or after the presentation of thyroid disease (0.1

Photodynamic therapy for the treatment of osteoarthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trauner, Kenneth; Hasan, Tayyaba

A method of treating a patient who has osteoarthritic disease by administering a therapeutic composition containing a photoactivatable compound, or a precursor thereof, and administering light of a photoactivating wavelength that activates the compound.

Carotid intima-media thickness and arterial stiffness in pediatric systemic lupus erythematosus.

PubMed

Su-Angka, N; Khositseth, A; Vilaiyuk, S; Tangnararatchakit, K; Prangwatanagul, W

2017-08-01

Objectives The carotid intima-media thickness (CIMT) and carotid arterial stiffness index (CASI) act as the surrogate markers of atherosclerosis. We aim to assess CIMT and CASI in pediatric systemic lupus erythematosus (SLE). Methods Patients ≤ 20 years old fulfilling diagnostic criteria for SLE were enrolled. Patients with active smoking, coronary heart disease, cerebrovascular disease, arterial thrombosis, family history of hypercholesterolemia, chronic liver disease, or other chronic severe diseases were excluded. The patients were categorized into four groups: active SLE, age- and sex-matched control (control A), inactive SLE, and age- and sex-matched control (control I), according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). All subjects underwent ultrasound of carotid arteries to evaluate CIMT and CASI. Results One hundred and two SLE patients (26 active and 76 inactive) and one hundred and three healthy controls (26 control A and 77 control I) were enrolled. The median CIMT in all groups were not significantly different (0.43, 0.41-0.44; 0.43, 0.41-0.44; 0.42, 0.41-0.43; and 0.42, 0.41-0.43 mm, respectively).The CASI in active SLE (13.5, 11.4-17.3) was significantly higher than in control A (8.2, 7.2-9.2) ( p < 0.0001), whereas CASI in inactive SLE (12.7, 10.9-15.7) was significantly higher than in control I (8.9, 7.6-9.8). However, the CASI in active and inactive SLE was not significantly different. Conclusions The higher CASI in active and inactive pediatric SLE, implying functional change of carotid arteries, may be early evidence of increased atherosclerosis in pediatric SLE. This functional dysfunction has been found both in inactive and active SLE.

Nailfold capillaroscopic changes in patients with systemic lupus erythematosus: correlations with disease activity, skin manifestation and nephritis.

PubMed

Shenavandeh, S; Habibi, S

2017-08-01

Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p < 0.002). A higher incidence of microhaemorrhages was seen in patients with active SLE disease ( p < 0.04). In SLE patients with active skin involvement, the disturbed distribution ( p < 0.004) was more frequent and subtle changes ( p < 0.009) were less frequently observed as compared with patients without active skin involvement. In the group of SLE patients with renal involvement, no correlation was found between the capillary abnormalities and the presence of renal involvement ( p > 0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.

Koebner phenomenon in alopecia areata: rapid appearance after trichogram. Implications for the pathogenesis and therapy.

PubMed

D'Ovidio, R

2013-04-01

Anecdotical experiences indicate that Koebner phenomenon (KP) can also be observed in alopecia areata (AA). The present short report gives an account of what has been observed in some patients with remitting-relapsing AA in multiple patches, in whom the phenomenon was accidentally caused by perilesional Trichogram. The almost immediate appearance of relapses of the disease (1-7 days) and their evolution can be useful to understand the physiopathology of AA and and emphasize the compelling need for a rapid and appropriate diagnosis and treatment in the acute phase of AA, even with the active participation of the patient adequately trained. The method of trichogram should be reserved for cases in which non-invasive methods such as the Pull Test or Trichoscopy are not sufficient to verify the activity of the disease.

Biological Activities of Polyphenols from Grapes

PubMed Central

Xia, En-Qin; Deng, Gui-Fang; Guo, Ya-Jun; Li, Hua-Bin

2010-01-01

The dietary consumption of grape and its products is associated with a lower incidence of degenerative diseases such as cardiovascular disease and certain types of cancers. Most recent interest has focused on the bioactive phenolic compounds in grape. Anthocyanins, flavanols, flavonols and resveratrol are the most important grape polyphenols because they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, antiaging and antimicrobial properties. This review summarizes current knowledge on the bioactivities of grape phenolics. The extraction, isolation and identification methods of polyphenols from grape as well as their bioavailability and potential toxicity also are included. PMID:20386657

Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis

PubMed Central

Tsuji, Sosuke; Takatani, Ayuko; Shimizu, Toshimasa; Fukui, Shoichi; Umeda, Masataka; Nishino, Ayako; Horai, Yoshiro; Koga, Tomohiro; Kawashiri, Shin-ya; Aramaki, Toshiyuki; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Terada, Kaoru; Origuchi, Tomoki; Eguchi, Katsumi; Ueki, Yukitaka; Kawakami, Atsushi

2017-01-01

Objective We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) in a real-world setting. Methods Seventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS)28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks. Results Fifty-eight patients (82.9%) continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (P<0.0001, vs. baseline). 15 AEs including 5 herpes zoster infection occurred during tofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX) or patients whose treatment with tocilizumab (TCZ) failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs) previously used was independently associated with achievement of DAS-low disease activity. Conclusions Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs. PMID:28472115

Transcription of PR3 and Related Myelopoiesis Genes in Peripheral Blood Mononuclear Cells in Active Wegener's Granulomatosis

PubMed Central

Cheadle, Chris; Berger, Alan E.; Andrade, Felipe; James, Regina; Johnson, Kristen; Watkins, Tonya; Park, Jin Kyun; Chen, Yu-Chi; Ehrlich, Eva; Mullins, Marissa; Chrest, Francis; Barnes, Kathleen C.; Levine, Stuart M.

2010-01-01

Objective Wegener's granulomatosis (WG) is a systemic inflammatory disease causing substantial morbidity. This study seeks to understand the biology underlying WG, and to discover markers of disease activity useful in prognosis and treatment guidance. Methods Gene expression profiling was performed using total RNA from PBMC and granulocyte fractions from 41 WG patients and 23 healthy controls. Gene set enrichment analysis (GSEA) was performed to search for candidate WG-associated molecular pathways and disease activity biomarkers. Principal component analysis (PCA) was used to visualize relationships between subgroups of WG patients and controls. Longitudinal changes in PR3 expression were evaluated using RT-PCR, and clinical outcomes including remission status and disease activity were determined using the BVAS-WG. Results We identified 86 genes significantly up-regulated in WG PBMCs and 40 in WG PMNs relative to controls. Genes up-regulated in WG PBMCs were involved in myeloid differentiation, and included the WG autoantigen, PR3. The coordinated regulation of myeloid differentiation genes was confirmed by gene set analysis. Median expression values of the 86 WG PBMC genes were associated with disease activity (p=1.3 × 10−4), and patients expressing these genes at a lower level were only modestly different from healthy controls (p=0.07). PR3 transcription was significantly up-regulated in the PBMCs (p=1.3 ×10−5, FDR=0.002), but not in the PMNs (p=0.03, FDR=0.28) of WG patients, and changes in BVAS-WG tracked with PBMC PR3 RNA levels in a preliminary longitudinal analysis. Conclusion Transcription of PR3 and related myeloid differentiation genes in PBMCs may represent novel markers of disease activity in WG. PMID:20155833

Apps for People With Rheumatoid Arthritis to Monitor Their Disease Activity: A Review of Apps for Best Practice and Quality

PubMed Central

Townsley, Hermaleigh; White, Bonnie; Langlotz, Tobias; Taylor, William J

2017-01-01

Background Rheumatoid arthritis (RA) is a chronic inflammatory arthritis requiring long-term treatment with regular monitoring by a rheumatologist to achieve good health outcomes. Since people with RA may wish to monitor their own disease activity with a smartphone app, it is important to understand the functions and quality of apps for this purpose. Objective The aim of our study was to assess the features and quality of apps to assist people to monitor their RA disease activity by (1) summarizing the available apps, particularly the instruments used for measurement of RA disease activity; (2) comparing the app features with American College of Rheumatology and European League against Rheumatism (ACR and EULAR) guidelines for monitoring of RA disease activity; and (3) rating app quality with the Mobile App Rating Scale (MARS). Methods Systematic searches of the New Zealand iTunes and Google Play app stores were used to identify all apps for monitoring of RA disease activity that could be used by people with RA. The apps were described by both key metadata and app functionality. App adherence with recommendations for monitoring of RA disease activity in clinical practice was evaluated by identifying whether apps included calculation of a validated composite disease activity measure and recorded results for future retrieval. App quality was assessed by 2 independent reviewers using the MARS. Results The search identified 721 apps in the Google Play store and 216 in the iTunes store, of which 19 unique apps met criteria for inclusion (8 from both app stores, 8 iTunes, and 3 Google Play). In total, 14 apps included at least one validated instrument measuring RA disease activity; 7 of 11 apps that allowed users to enter a joint count used the standard 28 swollen and tender joint count; 8 apps included at least one ACR and EULAR-recommended RA composite disease activity (CDA) measure; and 10 apps included data storage and retrieval. Only 1 app, Arthritis Power, included both an RA CDA measure and tracked data, but this app did not include the standard 28 tender and swollen joint count. The median overall MARS score for apps was 3.41/5. Of the 6 apps that scored ≥4/5 on the overall MARS rating, only 1 included a CDA score endorsed by ACR and EULAR; however, this app did not have a data tracking function. Conclusions This review found a lack of high-quality apps for longitudinal assessment of RA disease activity. Current apps fall into two categories: simple calculators primarily for rheumatologists and data tracking tools for people with RA. The latter do not uniformly collect data using validated instruments or composite disease activity measures. There is a need for appropriate, high-quality apps for use by rheumatologists and patients together in co-management of RA. PMID:28223263

Laser-based optoelectronic system for therapy by medical treatment of cardiovascular diseases

NASA Astrophysics Data System (ADS)

Chtchoupak, Oleg S.; Shpilevoj, Boris N.; Zapaeva, Natlia L.

1996-01-01

The method and design of a system for the laser treatment of ischemic heart disease is presented. Our conceptual approach to the development of the system is based on the theoretical and experimental works of the east and west scientists about positive influence of low intensity laser irradiation in the near infrared range by treatment of cardiovascular diseases. The method and system allow active influence on the subepicardial collateral blood circulation with near infrared (NIR) laser irradiation in wavelength ranges of 0.86-1.06 mkm. The presented technique makes it possible to achieve a higher effectiveness of treatment due to individual choice of radiation parameters on the basis of analysis of the patient conditions before and after laser therapy and due to simultaneous affection at several points of the human body. Finally, results of the tests are presented, which prove given methods.

Activation of cellular immune response in acute pancreatitis.

PubMed Central

Mora, A; Pérez-Mateo, M; Viedma, J A; Carballo, F; Sánchez-Payá, J; Liras, G

1997-01-01

BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity. PMID:9245935

Inflammation associated anemia and ferritin as disease markers in SLE

PubMed Central

2012-01-01

Introduction In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. Methods A protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed. Results Protein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced. Conclusion Urine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE. PMID:22871034

Risk Factors for Nursing Home Placement in Alzheimer's Disease: A Longitudinal Study of Cognition, ADL, Service Utilization, and Cholinesterase Inhibitor Treatment

ERIC Educational Resources Information Center

Wattmo, Carina; Wallin, Asa K.; Londos, Elisabet; Minthon, Lennart

2011-01-01

Purpose of the Study: To identify risk factors for early nursing home placement (NHP) in Alzheimer's disease (AD), focusing on the impact of longitudinal change in cognition, activities of daily living (ADL), service utilization, and cholinesterase inhibitor treatment (ChEI). Design and Methods: In an open, 3-year, prospective, multicenter study…

Reliability and validity of a videotape method to describe expressive behavior in persons with Parkinson's disease.

PubMed

Lyons, Kathleen Doyle; Tickle-Degnen, Linda

2005-01-01

The ability to effectively communicate thoughts, feelings, and identity to others is an important aspect of occupational performance. The symptoms of Parkinson's disease can impair a person's ability to verbally and non-verbally communicate with others. In order to better understand issues of communication functioning for this population, research tools to describe expressive and communicative behavior during occupation and social interaction are needed. In this study, six persons with Parkinson's disease participated in individual, videotaped interviews focused on problem solving during daily activities. Three trained graduate students viewed edited clips from the videotapes and completed a rating scale of expressive behavior designed by the authors. Data support the reliability and construct validity of the behavioral rating scale, suggesting that measures of expressive behavior of persons with Parkinson's disease can be effectively derived using short segments of videotaped activity.

Is Phosphoproteomics Ready for Clinical Research?

PubMed Central

Iliuk, Anton B.; Tao, W. Andy

2012-01-01

Background For many diseases such as cancer where phosphorylation-dependent signaling is the foundation of disease onset and progression, single-gene testing and genomic profiling alone are not sufficient in providing most critical information. The reason for this is that in these activated pathways the signaling changes and drug resistance are often not directly correlated with changes in protein expression levels. In order to obtain the essential information needed to evaluate pathway activation or the effects of certain drugs and therapies on the molecular level, the analysis of changes in protein phosphorylation is critical. Methods Existing approaches do not differentiate clinical disease subtypes on the protein and signaling pathway level, and therefore hamper the predictive management of the disease and the selection of therapeutic targets. Conclusions The mini-review examines the impact of emerging systems biology tools and the possibility of applying phosphoproteomics to clinical research. PMID:23159844

Health-related quality of life in end-stage renal disease patients: the effects of renal rehabilitation.

PubMed

Kouidi, E

2004-05-01

Health-related quality of life (HRQoL) consists of a number of components like functional status, psychological and social functioning, cognition and disease and treatment-related symptoms. End-stage renal disease (ESRD) patients display emotional disturbances, as well as non-adherence to treatment and fluid and food intake, depression, anxiety, social withdrawal and cardiovascular and other co-existing disease morbidity. They have very low functional capacity and physical limitations in their daily activities that affect their mortality and morbidity. Exercise training in ESRD patients is effective in increasing work related activities and important components of their daily life and improving physical functioning. A physical rehabilitation program also leads to a reduction in depression and improvement in family and social interactions. Therefore, renal rehabilitation should be considered as an important therapeutic method for improving physical fitness, social function, well-being and thus health-adjusted quality of life in ESRD patients.

Evaluation of occupational allergic contact dermatitis and its related factors in Iran.

PubMed

Nassiri-Kashani, Mansour; Nassiri-Kashani, Mohammad Hassan; Ghafari, Mostafa

2016-01-01

Background: Occupational contact dermatitis, especially in hand, is one of the most common occupational disorders. The present study aimed at evaluating patients with occupational allergic contact dermatitis (ACD) caused by common allergens based on occupation type and disease history. Methods: This cross-sectional study aimed at evaluating the data of the patients with probable diagnosis of ACD in Center for Research and Training in Skin Diseases and Leprosy (CRTSDL) in Iran. In the present study, 946 patients were assessed from different regions of Iran. One hundred fifty-one cases with positive patch test and relevant exposure were entered into the study; data related to their occupation and disease activity history were evaluated and recorded. Then, factors related to disease activity history were assessed considering the occupational groups and common exposures. Results: Nickel sulphate was the most common allergen in the 151 patients. Disease activity was constant in 29.8% of the patients; it increased in 27.8%, and decreased just before doing the patch test in 42.4%. Of the patients, 52.3% were getting worse during the working days. Occupational groups were significantly different in age and gender. Disease duration was also different in the occupational groups (p=0.001). The least disease duration was observed in healthcare workers, and the most in service workers. Lesions in the foot were related to period of employment. In administrative work group, (teachers, technicians and housewives) disease activity was decreased in the most cases, while it was increased in most patients of service workers (p=0.086). Conclusion: The present study, similar to previous reports, revealed that nickel sulphate is the most common allergen in ACD cases. Moreover, it was found that the symptoms of disease activity remained constant or increased in a significant proportion of the cases during the working days. Therefore, these workers should seriously follow up on this matter and change their occupation, or limit the exposure to allergens.

Generalized query-based active learning to identify differentially methylated regions in DNA.

PubMed

Haque, Md Muksitul; Holder, Lawrence B; Skinner, Michael K; Cook, Diane J

2013-01-01

Active learning is a supervised learning technique that reduces the number of examples required for building a successful classifier, because it can choose the data it learns from. This technique holds promise for many biological domains in which classified examples are expensive and time-consuming to obtain. Most traditional active learning methods ask very specific queries to the Oracle (e.g., a human expert) to label an unlabeled example. The example may consist of numerous features, many of which are irrelevant. Removing such features will create a shorter query with only relevant features, and it will be easier for the Oracle to answer. We propose a generalized query-based active learning (GQAL) approach that constructs generalized queries based on multiple instances. By constructing appropriately generalized queries, we can achieve higher accuracy compared to traditional active learning methods. We apply our active learning method to find differentially DNA methylated regions (DMRs). DMRs are DNA locations in the genome that are known to be involved in tissue differentiation, epigenetic regulation, and disease. We also apply our method on 13 other data sets and show that our method is better than another popular active learning technique.

Free radical scavenging capacity, anticandicidal effect of bioactive compounds from Sida Cordifolia L., in combination with nystatin and clotrimazole and their effect on specific immune response in rats

PubMed Central

2012-01-01

Background Infectious diseases caused by fungi are still a major threat to public health, despite numerous efforts by researchers. Use of ethnopharmacological knowledge is one attractive way to reduce empiricism and enhance the probability of success in new drug-finding efforts. In this work, the total alkaloid compounds (AC) from Sida cordifolia L. (Malvaceae) have been investigated for their free radical scavenging capacity, antifungal and immunostimulatory properties. Method The antifungal activity was investigated against five candida strains using the microplate dilution method and the Fractional Inhibitory Concentration Index (FICI) of compounds was evaluated. The antioxidant activity of the samples was evaluate using three separate methods, at last, the immunostimulatory effect on immunosuppressed wistar rats was performed. Results As for the antifungal activity, result varied according to microorganism. The results obtained in this antifungal activity were interesting and indicated a synergistic effect between alkaloid compounds and the antifungal references such as Nystatin and Clotrimazole. Antioxidant capacity noticed that the reduction capacity of DPPH radicals obtained the best result comparatively to the others methods of free radical scavenging. Our results showed a low immunostimulatory effect and this result could be explained by the lack of biologically active antioxidants such as polyphenol compounds lowly contained in the alkaloid compounds. Conclusion The results of this study showed that alkaloid compounds in combination with antifungal references (Nystatin and Clotrimazole) exhibited antimicrobial effects against candida strains tested. The results supported the utilization of these plants in infectious diseases particularly in treatment of candida infections. PMID:23268761

Nonlinear analysis of human physical activity patterns in health and disease.

PubMed

Paraschiv-Ionescu, A; Buchser, E; Rutschmann, B; Aminian, K

2008-02-01

The reliable and objective assessment of chronic disease state has been and still is a very significant challenge in clinical medicine. An essential feature of human behavior related to the health status, the functional capacity, and the quality of life is the physical activity during daily life. A common way to assess physical activity is to measure the quantity of body movement. Since human activity is controlled by various factors both extrinsic and intrinsic to the body, quantitative parameters only provide a partial assessment and do not allow for a clear distinction between normal and abnormal activity. In this paper, we propose a methodology for the analysis of human activity pattern based on the definition of different physical activity time series with the appropriate analysis methods. The temporal pattern of postures, movements, and transitions between postures was quantified using fractal analysis and symbolic dynamics statistics. The derived nonlinear metrics were able to discriminate patterns of daily activity generated from healthy and chronic pain states.

Indigenous perspectives on active living in remote Australia: a qualitative exploration of the socio-cultural link between health, the environment and economics

PubMed Central

2013-01-01

Background The burden of chronic disease in Indigenous Australia is more than double that of non-Indigenous populations and even higher in remote Northern Territory (NT) communities. Sufficient levels of physical activity are known to reduce the risk of chronic disease and improve the health of those already suffering from chronic disease. It has been identified that effective promotion of physical activity in Indigenous settings requires the diverse cultural perspectives and participation of Indigenous people. However, Indigenous concepts of physical activity are not represented in the public health literature and examples of Indigenous involvement in physical activity promotion are scarce. This study aimed to explore and describe local perspectives, experiences and meanings of physical activity in two remote NT Indigenous communities. Methods Qualitative research methods guided by ethnographic and participatory action research principles were used. Semi-structured interviews conducted with 23 purposively selected community members were the main source of data, augmented by five commissioned paintings by community-based artists and observations recorded in a journal by the first author. Results The findings reveal that in this cultural context the meaning of physical activity is embedded in socially significant and economically necessary physical engagement with the environment. Participants described physical activities associated with Indigenous natural and cultural resource management, customary spaces, seasonal timing and traditional education as creating and protecting health. These activities were viewed not only as culturally appropriate physical activities that contribute to health but as legitimate, physically active forms of social organisation, education and employment that help to build and maintain relationships, wealth, resources and the environment. Conclusion This different construction of physical activity in remote Indigenous communities highlights the importance of involving Indigenous people in the development and implementation of physical activity promotion. Physical activities associated with traditional Indigenous cultural practices and being active ‘on country’ need to be viewed as legitimate health promotion activities. Exploring further ways to enable Indigenous people in remote NT to be involved in creating viable active livelihoods on ‘traditional country’ needs to be considered as imperative to health improvement. PMID:23672247

The Understanding and Interpretation of Innovative Technology-Enabled Multidimensional Physical Activity Feedback in Patients at Risk of Future Chronic Disease

PubMed Central

Western, Max J.; Peacock, Oliver J.; Stathi, Afroditi; Thompson, Dylan

2015-01-01

Background Innovative physical activity monitoring technology can be used to depict rich visual feedback that encompasses the various aspects of physical activity known to be important for health. However, it is unknown whether patients who are at risk of chronic disease would understand such sophisticated personalised feedback or whether they would find it useful and motivating. The purpose of the present study was to determine whether technology-enabled multidimensional physical activity graphics and visualisations are comprehensible and usable for patients at risk of chronic disease. Method We developed several iterations of graphics depicting minute-by-minute activity patterns and integrated physical activity health targets. Subsequently, patients at moderate/high risk of chronic disease (n=29) and healthcare practitioners (n=15) from South West England underwent full 7-days activity monitoring followed by individual semi-structured interviews in which they were asked to comment on their own personalised visual feedback Framework analysis was used to gauge their interpretation and of personalised feedback, graphics and visualisations. Results We identified two main components focussing on (a) the interpretation of feedback designs and data and (b) the impact of personalised visual physical activity feedback on facilitation of health behaviour change. Participants demonstrated a clear ability to understand the sophisticated personal information plus an enhanced physical activity knowledge. They reported that receiving multidimensional feedback was motivating and could be usefully applied to facilitate their efforts in becoming more physically active. Conclusion Multidimensional physical activity feedback can be made comprehensible, informative and motivational by using appropriate graphics and visualisations. There is an opportunity to exploit the full potential created by technological innovation and provide sophisticated personalised physical activity feedback as an adjunct to support behaviour change. PMID:25938455

Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Tetsuhiro, E-mail: atetsu@mail.ecc.u-tokyo.ac.jp; Shimizu, Ayano; Takahashi, Kazutoshi

2014-08-15

Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrialmore » dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ{sup 0} cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.« less

Mining geographic variations of Plasmodium vivax for active surveillance: a case study in China.

PubMed

Shi, Benyun; Tan, Qi; Zhou, Xiao-Nong; Liu, Jiming

2015-05-27

Geographic variations of an infectious disease characterize the spatial differentiation of disease incidences caused by various impact factors, such as environmental, demographic, and socioeconomic factors. Some factors may directly determine the force of infection of the disease (namely, explicit factors), while many other factors may indirectly affect the number of disease incidences via certain unmeasurable processes (namely, implicit factors). In this study, the impact of heterogeneous factors on geographic variations of Plasmodium vivax incidences is systematically investigate in Tengchong, Yunnan province, China. A space-time model that resembles a P. vivax transmission model and a hidden time-dependent process, is presented by taking into consideration both explicit and implicit factors. Specifically, the transmission model is built upon relevant demographic, environmental, and biophysical factors to describe the local infections of P. vivax. While the hidden time-dependent process is assessed by several socioeconomic factors to account for the imported cases of P. vivax. To quantitatively assess the impact of heterogeneous factors on geographic variations of P. vivax infections, a Markov chain Monte Carlo (MCMC) simulation method is developed to estimate the model parameters by fitting the space-time model to the reported spatial-temporal disease incidences. Since there is no ground-truth information available, the performance of the MCMC method is first evaluated against a synthetic dataset. The results show that the model parameters can be well estimated using the proposed MCMC method. Then, the proposed model is applied to investigate the geographic variations of P. vivax incidences among all 18 towns in Tengchong, Yunnan province, China. Based on the geographic variations, the 18 towns can be further classify into five groups with similar socioeconomic causality for P. vivax incidences. Although this study focuses mainly on the transmission of P. vivax, the proposed space-time model is general and can readily be extended to investigate geographic variations of other diseases. Practically, such a computational model will offer new insights into active surveillance and strategic planning for disease surveillance and control.

Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

PubMed Central

Kishi, Taro; Iwata, Nakao

2015-01-01

Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer’s disease. Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Results: Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=−0.13), activity of daily living scores (standardized mean difference=−0.10), and global assessment scores (standardized mean difference=−0.15). In addition, cognitive function scores (standardized mean difference=−0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer’s disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer’s disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. PMID:25548104

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis

PubMed Central

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof

2017-01-01

Introduction Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. Material and methods We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. Results There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04–2.28; p = 0.035). Conclusions The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity. PMID:28883856

Education, leisure activities and cognitive and functional ability of Alzheimer's disease patients: A follow-up study

PubMed Central

Sobral, Margarida; Paúl, Constança

2013-01-01

Education and participation in leisure activities appear to be highly relevant variables in Alzheimer's disease (AD) and usually form the basis of the Cognitive Reserve construct. OBJECTIVE [A] To determine the association between education, cognitive and functional ability of AD patients; [B] To determine the association between participation in leisure activities and cognitive and functional ability of AD patients; [C] To evaluate the association of education and participation in leisure activities in the course of AD. METHODS Functional and neuropsychological abilities of 120 outpatients with probable AD were evaluated at baseline, at 36 and 54 months. Data collected at baseline included socio-demographics, clinical variables, education and frequency of participation in leisure activities throughout life. All participants and/or caregivers answered the questionnaire, "Participation in leisure activities throughout life" while patients completed the MMSE, the Clinical Dementia Rating scale, neuropsychological tests from the Lisbon Screening for Dementia Assessment, Barthel Index and Lawton and Brody's Index. RESULTS AD patients with higher levels of education achieved better results on cognitive tests. The participants with higher participation in leisure activities exhibited better results on cognitive and functional tests than those with lower participation. The disease progression was linear and progressed similarly regardless of the level of education of participants. However, the results suggest a slower disease progression in patients with a higher level of participation in leisure activities throughout their lives. CONCLUSION AD patients with high education and high participation in leisure activities may benefit from a slower cognitive and functional decline after diagnosis of AD. PMID:29213838

Factors associated with health-related quality of life in Peruvian patients with systemic lupus erythematosus.

PubMed

Elera-Fitzcarrald, Claudia; Alva, Magaly; Gamboa-Cardenas, Rocío; Mora-Trujillo, Claudia S; Zevallos, Francisco; García-Poma, Augusto; Medina, Mariela; Rodriguez-Bellido, Zoila; Perich-Campos, Risto A; Pastor-Asurza, César A; Segami, María I; Ugarte-Gil, Manuel F

2018-05-01

Objective In this paper, we aim to define factors associated with health-related quality of life (HRQoL) in Mestizo patients with systemic lupus erythematosus (SLE). Methods We evaluated patients with SLE from Peru's two largest hospitals between October 2012 and July 2015 to ascertain HRQoL. Using a standard protocol, we incorporated demographic characteristics, clinical manifestations and treatment in our analysis. HRQoL was measured with the LupusQoL, disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage was appraised with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI). The associations between the LupusQoL and these variables were examined using linear regression models. Model selection was based on backward elimination. Results A total of 277 patients fit the inclusion criterion. Of these, 254 (91.7%) were female, the median (interquartile range, IQR) age at diagnosis was 41.5 (33.8-51.8) years, disease duration was 6.5 (2.7-11.3) years. The HRQoL domains most affected were the following: burden to others, fatigue, and intimate relationships. Through multivariate analysis, we determined that older age at diagnosis, higher disease activity, damage, and immunosuppressive drug use were negatively associated with HRQoL. Further, we found that higher socioeconomic status, disease duration, and antimalarial use were positively associated with HRQoL. Conclusion Age at diagnosis, disease activity, damage, and use of immunosuppressive drugs were negatively associated with HRQoL; high socioeconomic status, disease duration, and use of antimalarials were positively associated with HRQoL.

A Diet, Physical Activity, and Stress Reduction Intervention in Men with Rising Prostate-Specific Antigen (PSA) after Treatment for Prostate Cancer

PubMed Central

Hébert, James R.; Hurley, Thomas G.; Harmon, Brook E.; Heiney, Sue; Hebert, Christine J.; Steck, Susan E.

2011-01-01

Background Nearly 35% of men treated for prostate cancer (PrCA) will experience biochemically defined recurrence, noted by a rise in PSA, within ten years of definitive therapy. Diet, physical activity, and stress reduction may affect tumor promotion and disease progression. Methods A randomized trial of an intensive diet, physical activity, and meditation intervention was conducted in men with rising post-treatment PSA after definitive treatment for PrCA. Intention-to-treat methods were used to compare usual care to the intervention in 47 men with complete data. Signal detection methods were used to identify dietary factors associated with PSA change. Results The intervention and control groups did not differ statistically on any demographic or disease-related factor. Although the intervention group experienced decreases of 39% in intakes of saturated fatty acid (SFA as percent of total calories) (p<0.0001) and 12% in total energy intake (218 kcal/day p<0.05)], no difference in PSA change was observed by intervention status. Signal detection methods indicated that in men increasing their consumption of fruit, 56% experienced no rise in PSA (vs. 29% in men who did not increase their fruit intake). Among men who increased fruit and fiber intakes, PSA increased in 83% of participants who also increased saturated fatty acid intake (vs. 44% in participants who decreased or maintained saturated fatty acid intake). Conclusion Results are discussed in the context of conventional treatment strategies that were more aggressive when this study was being conducted in the mid-2000s. Positive health changes in a number of lifestyle parameters were observed with the intervention, and both increased fruit and reduced saturated fat intakes were associated with maintaining PSA levels in men with biochemically recurrent disease. PMID:22018935

ENVIRONMENTAL PCB EXPOSURE AND RISK OF ENDOMETRIOSIS

EPA Science Inventory

BACKGROUND: Hormonally active environmental agents recently have been associated with the development of endometriosis. METHODS: We undertook a study to assess the relation between endometriosis, an estrogen dependent gynecologic disease, and 62 individual polychlorinated biphe...

Classification of optical coherence tomography images for diagnosing different ocular diseases

NASA Astrophysics Data System (ADS)

Gholami, Peyman; Sheikh Hassani, Mohsen; Kuppuswamy Parthasarathy, Mohana; Zelek, John S.; Lakshminarayanan, Vasudevan

2018-03-01

Optical Coherence tomography (OCT) images provide several indicators, e.g., the shape and the thickness of different retinal layers, which can be used for various clinical and non-clinical purposes. We propose an automated classification method to identify different ocular diseases, based on the local binary pattern features. The database consists of normal and diseased human eye SD-OCT images. We use a multiphase approach for building our classifier, including preprocessing, Meta learning, and active learning. Pre-processing is applied to the data to handle missing features from images and replace them with the mean or median of the corresponding feature. All the features are run through a Correlation-based Feature Subset Selection algorithm to detect the most informative features and omit the less informative ones. A Meta learning approach is applied to the data, in which a SVM and random forest are combined to obtain a more robust classifier. Active learning is also applied to strengthen our classifier around the decision boundary. The primary experimental results indicate that our method is able to differentiate between the normal and non-normal retina with an area under the ROC curve (AUC) of 98.6% and also to diagnose the three common retina-related diseases, i.e., Age-related Macular Degeneration, Diabetic Retinopathy, and Macular Hole, with an AUC of 100%, 95% and 83.8% respectively. These results indicate a better performance of the proposed method compared to most of the previous works in the literature.

British isles lupus assessment group 2004 index is valid for assessment of disease activity in systemic lupus erythematosus

PubMed Central

Yee, Chee-Seng; Farewell, Vernon; Isenberg, David A; Rahman, Anisur; Teh, Lee-Suan; Griffiths, Bridget; Bruce, Ian N; Ahmad, Yasmeen; Prabu, Athiveeraramapandian; Akil, Mohammed; McHugh, Neil; D'Cruz, David; Khamashta, Munther A; Maddison, Peter; Gordon, Caroline

2007-01-01

Objective To determine the construct and criterion validity of the British Isles Lupus Assessment Group 2004 (BILAG-2004) index for assessing disease activity in systemic lupus erythematosus (SLE). Methods Patients with SLE were recruited into a multicenter cross-sectional study. Data on SLE disease activity (scores on the BILAG-2004 index, Classic BILAG index, and Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), investigations, and therapy were collected. Overall BILAG-2004 and overall Classic BILAG scores were determined by the highest score achieved in any of the individual systems in the respective index. Erythrocyte sedimentation rates (ESRs), C3 levels, C4 levels, anti–double-stranded DNA (anti-dsDNA) levels, and SLEDAI-2K scores were used in the analysis of construct validity, and increase in therapy was used as the criterion for active disease in the analysis of criterion validity. Statistical analyses were performed using ordinal logistic regression for construct validity and logistic regression for criterion validity. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results Of the 369 patients with SLE, 92.7% were women, 59.9% were white, 18.4% were Afro-Caribbean and 18.4% were South Asian. Their mean ± SD age was 41.6 ± 13.2 years and mean disease duration was 8.8 ± 7.7 years. More than 1 assessment was obtained on 88.6% of the patients, and a total of 1,510 assessments were obtained. Increasing overall scores on the BILAG-2004 index were associated with increasing ESRs, decreasing C3 levels, decreasing C4 levels, elevated anti-dsDNA levels, and increasing SLEDAI-2K scores (all P < 0.01). Increase in therapy was observed more frequently in patients with overall BILAG-2004 scores reflecting higher disease activity. Scores indicating active disease (overall BILAG-2004 scores of A and B) were significantly associated with increase in therapy (odds ratio [OR] 19.3, P < 0.01). The BILAG-2004 and Classic BILAG indices had comparable sensitivity, specificity, PPV, and NPV. Conclusion These findings show that the BILAG-2004 index has construct and criterion validity. PMID:18050213

Reconsidering the methodology of “stress” research in inflammatory bowel disease

PubMed Central

Keefer, Laurie; Keshavarzian, Ali; Mutlu, Ece

2009-01-01

Background and Aims The goals of this paper are: 1) to critically review and analyze the methodology of the studies since 1990 linking stress to inflammatory bowel disease; and 2) to make recommendations for future research in this area of research. Methods Articles were restricted to empirical reports in the English language with human subjects. Eleven empirical articles were able to answer “How is psychological stress related to inflammation and/or the expression or course of inflammatory bowel disease?” Results Studies varied by choice of participant groups, method for classifying disease activity, choice of design, and definition and measurement of stress. Only half of the studies supported the hypothesis that stress affected IBD in some way. Conclusions Current methodological limitations in the stress and gut inflammation research have made it difficult for us to ascertain the role of stress in inflammatory bowel disease. Authors provide a checklist of items to consider when designing future studies. PMID:21172210

Quality of Life in Swiss Paediatric Inflammatory Bowel Disease Patients: Do Patients and Their Parents Experience Disease in the Same Way?

PubMed Central

Mueller, Rebekka; Ziade, Farah; Pittet, Valérie; Fournier, Nicolas; Ezri, Jessica; Schoepfer, Alain; Schibli, Susanne; Spalinger, Johannes; Braegger, Christian

2016-01-01

Background and Aims: Inflammatory bowel diseases (IBDs) may impair quality of life (QoL) in paediatric patients. We aimed to evaluate in a nationwide cohort whether patients experience QoL in a different way when compared with their parents. Methods: Sociodemographic and psychosocial characteristics were prospectively acquired from paediatric patients and their parents included in the Swiss IBD Cohort Study. Disease activity was evaluated by the Paediatric Crohn’s Disease Activity Index (PCDAI) and the Paediatric Ulcerative Colitis Activity Index (PUCAI). We assessed QoL using the KIDSCREEN questionnaire. The QoL domains were analysed and compared between children and parents according to type of disease, parents’ age, origin, education and marital status. Results: We included 110 children and parents (59 Crohn’s disease [CD], 45 ulcerative colitis [UC], 6 IBD unclassified [IBDU]). There was no significant difference in QoL between CD and UC/IBDU, whether the disease was active or in remission. Parents perceived overall QoL, as well as ‘mood’, ‘family’ and ‘friends’ domains, lower than the children themselves, independently of their place of birth and education. However, better concordance was found on ‘school performance’ and ‘physical activity’ domains. Marital status and age of parents significantly influenced the evaluation of QoL. Mothers and fathers being married or cohabiting perceived significantly lower mood, family and friends domains than their children, whereas mothers living alone had a lower perception of the friends domain; fathers living alone had a lower perception of family and mood subscores. Conclusion: Parents of Swiss paediatric IBD patients significantly underestimate overall QoL and domains of QoL of their children independently of origin and education. PMID:26519462

Differences in Long-Term Disease Activity and Treatment of Adult Patients With Childhood-and Adult-Onset Systemic Lupus Erythematosus

PubMed Central

Hersh, Aimee O.; von Scheven, Emily; Yazdany, Jinoos; Panopalis, Pantelis; Trupin, Laura; Julian, Laura; Katz, Patricia; Criswell, Lindsey A.; Yelin, Edward

2009-01-01

Objective To compare differences in long-term outcome between adults with childhood-onset (age at diagnosis <18 years) systemic lupus erythematosus (SLE) and with adult-onset SLE. Methods Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 885 adult subjects with SLE (90 childhood-onset [cSLE], 795 adult-onset [aSLE]). Baseline and 1-year followup data were obtained via structured 1-hour telephone interviews conducted between 2002 and 2006. Using self-report data, differences in organ involvement and disease morbidity, current disease status and activity, past and current medication use, and number of physician visits were compared, based on age at diagnosis of SLE. Results Average disease duration for the cSLE and aSLE subgroups was 16.5 and 13.4 years, respectively, and mean age at followup was 30.5 and 49.9 years, respectively. When compared with aSLE subjects, cSLE subjects had a higher frequency of SLE-related renal disease, whereas aSLE subjects were more likely to report a history of pulmonary disease. Rates of clotting disorders, seizures, and myocardial infarction were similar between the 2 groups. At followup, cSLE subjects had lower overall disease activity, but were more likely to be taking steroids and other immunosuppressive therapies. The total number of yearly physician visits was similar between the 2 groups, although cSLE subjects had a higher number of nephrology visits. Conclusion This study demonstrates important differences in the outcomes of patients with cSLE and aSLE, and provides important prognostic information about long-term SLE disease activity and treatment. PMID:19116979

Colocalization recognition-activated cascade signal amplification strategy for ultrasensitive detection of transcription factors.

PubMed

Zhu, Desong; Wang, Lei; Xu, Xiaowen; Jiang, Wei

2017-03-15

Transcription factors (TFs) bind to specific double-stranded DNA (dsDNA) sequences in the regulatory regions of genes to regulate the process of gene transcription. Their expression levels sensitively reflect cell developmental situation and disease state. TFs have become potential diagnostic markers and therapeutic targets of cancers and some other diseases. Hence, high sensitive detection of TFs is of vital importance for early diagnosis of diseases and drugs development. The traditional exonucleases-assisted signal amplification methods suffered from the false positives caused by incomplete digestion of excess recognition probes. Herein, based on a new recognition way-colocalization recognition (CR)-activated dual signal amplification, an ultrasensitive fluorescent detection strategy for TFs was developed. TFs-induced the colocalization of three split recognition components resulted in noticeable increases of local effective concentrations and hybridization of three split components, which activated the subsequent cascade signal amplification including strand displacement amplification (SDA) and exponential rolling circle amplification (ERCA). This strategy eliminated the false positive influence and achieved ultra-high sensitivity towards the purified NF-κB p50 with detection limit of 2.0×10 -13 M. Moreover, NF-κB p50 can be detected in as low as 0.21ngμL -1 HeLa cell nuclear extracts. In addition, this proposed strategy could be used for the screening of NF-κB p50 activity inhibitors and potential anti-NF-κB p50 drugs. Finally, our proposed strategy offered a potential method for reliable detection of TFs in medical diagnosis and treatment research of cancers and other related diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis

PubMed Central

Viatte, Sebastien; Lee, James C.; Fu, Bo; Espéli, Marion; Lunt, Mark; De Wolf, Jack N. E.; Wheeler, Lily; Reynolds, John A.; Castelino, Madhura; Symmons, Deborah P. M.; Lyons, Paul A.

2016-01-01

Objective Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte‐driven inflammation through a transforming growth factor β1–dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis. Methods Collagen‐induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss‐of‐function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C‐reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA. Results Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin‐6 in the blood. Similarly, rs12212067 (a single‐nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores. Conclusion Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage. PMID:27214848

Manzamine alkaloids: isolation, cytotoxicity, antimalarial activity and SAR studies.

PubMed

Ashok, Penta; Ganguly, Swastika; Murugesan, Sankaranarayanan

2014-11-01

The infectious disease Malaria is caused by different species of the genus Plasmodium. Resistance to quinoline antimalarial drugs and decreased susceptibility to artemisinin-based combination therapy have increased the need for novel antimalarial agents. Historically, natural products have been used for the treatment of infectious diseases. Identification of natural products and their semi-synthetic derivatives with potent antimalarial activity is an important method for developing novel antimalarial agents. Manzamine alkaloids are a unique group of β-carboline alkaloids isolated from various species of marine sponge displaying potent antimalarial activity against drug-sensitive and -resistant strains of Plasmodium. In this review, we demonstrate antimalarial potency, cytotoxicity and antimalarial SAR of manzamine alkaloids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nutritional Strategies in the Management of Adult Patients with Inflammatory Bowel Disease: Dietary Considerations from Active Disease to Disease Remission.

PubMed

Nguyen, Douglas L; Limketkai, Berkeley; Medici, Valentina; Saire Mendoza, Mardeli; Palmer, Lena; Bechtold, Matthew

2016-10-01

Inflammatory bowel disease (IBD) is a group of chronic, lifelong, and relapsing illnesses, such as ulcerative colitis and Crohn's disease, which involve the gastrointestinal tract. There is no cure for these diseases, but combined pharmacological and nutritional therapy can induce remission and maintain clinical remission. Malnutrition and nutritional deficiencies among IBD patients result in poor clinical outcomes such as growth failure, reduced response to pharmacotherapy, increased risk for sepsis, and mortality. The aim of this review is to highlight the consequences of malnutrition in the management of IBD and describe nutritional interventions to facilitate induction of remission as well as maintenance; we will also discuss alternative delivery methods to improve nutritional status preoperatively.

Targeting CD4+ T cells for the treatment of sarcoidosis: a promising strategy?

PubMed Central

Celada, Lindsay J; Drake, Wonder P

2017-01-01

Sarcoidois is an inflammatory disease of unknown origin characterized by the abnormal accumulation of noncaseating granulomas at sites of disease activity in multiple organs throughout the body with a predilection for the lungs. Because the exact trigger that leads to disease activity is still under investigation, current treatment options are contingent on the organ or organs affected. Corticosteroids are the therapy of choice, but antimalarials and TNF-α antagonists are also commonly prescribed. Recent findings provide evidence for the use of CD20 B-cell-depleting therapy as an alternative method of choice. However, because sarcoidosis is predominantly a T-helper cell-driven disorder, an overwhelming amount of compelling evidence exists for the use of CD4+ T-cell targeted therapy. PMID:25572480

Immunocapture and microplate-based activity and quantity measurement of pyruvate dehydrogenase in human peripheral blood mononuclear cells

PubMed Central

Liu, Xiaowen; Pervez, Hira; Andersen, Lars W; Uber, Amy; Montissol, Sophia; Patel, Parth; Donnino, Michael W

2015-01-01

Background Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). Results/Methodology We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects. Conclusion Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease. PMID:25826140

Ecological Immunology through the Lens of Exercise Immunology: New Perspective on the Links between Physical Activity and Immune Function and Disease Susceptibility in Wild Animals.

PubMed

van Dijk, Jacintha G B; Matson, Kevin D

2016-08-01

Locomotion and other physical activities by free-living animals may influence immune function and disease susceptibility. This influence may be a consequence of energetic trade-offs or other mechanisms that are often, but not always, inseparably linked to an animal's life history (e.g., flight and migration). Ecological immunology has mainly focused on these life-history trade-offs, overlooking the possible effects of physical activity per se on immune function and disease susceptibility. In this review, we explore the field of exercise immunology, which examines the impact of exercise on immune function and disease susceptibility in humans, with the aim of presenting new perspectives that might be transferable to ecological immunology. First, we explore key concepts in exercise immunology that could be extended to animals. Next, we investigate the concept "exercise" in animals, and propose the use of "physical activity" instead. We briefly discuss methods used in animals to quantify physical activity in terms of energy expenditure and summarize several examples of animals engaging in physical activity. Then, we highlight potential consequences of physical activity on immune function and disease susceptibility in animals, together with an overview of animal studies that examine these links. Finally, we explore and discuss the potential for incorporating perspectives from exercise immunology into ecological immunology. Such integration could help advance our understanding of human and animal health and contribute new ideas to budding "One Health" initiatives. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Intestinal protozoa infections among patients with ulcerative colitis: prevalence and impact on clinical disease course.

PubMed

Yamamoto-Furusho, Jesús K; Torijano-Carrera, Emma

2010-01-01

Epidemiological and microbiologic studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of inflammatory bowel disease. To explore the prevalence of intestinal protozoa in patients with ulcerative colitis (UC) and its impact on clinical disease course. A total of 215 patients with definitive diagnosis of UC were studied. Fresh feces samples taken from all UC patients were examined immediately using trichrome-staining methods. A total of 103 female and 112 male UC patients were analyzed. The mean age at diagnosis was 30.5 +/- 10.8 years. The prevalence of overall parasitic infections was 24% and distributed as follows: Blastocystis hominis in 22 patients (10%), Endolimax nana in 19 cases (9%), and Entamoebahistolytica in 11 cases (5%). A significantly increased frequency of protozoa infection was found in those patients with persistent activity and intermittent activity as compared to active than inactive group (p = 1 x 10(-7), OR 13.05, 95% CI 4.28-42.56, and p = 0.003, OR 1.42-14.47, respectively). Interestingly, this association remained significant when we compared the persistent activity group versus intermittent activity group (p = 0.003, OR 2.97, 95% CI 1.35-6.59). Subgroup analysis showed no association between protozoa infection (E. histolytica, B. hominis, and E. nana) and other clinical variables such as gender, extent of disease, extraintestinal complications, medical treatment and grade of disease activity. The prevalence of intestinal protozoa infections in Mexican UC patients was 24% and these microorganisms could be a contributing cause of persistent activity despite medical treatment in our population. 2010 S. Karger AG, Basel.

Disease course and long-term outcome of juvenile localized scleroderma: Experience from a single pediatric rheumatology Centre and literature review.

PubMed

Martini, Giorgia; Fadanelli, Gloria; Agazzi, Anna; Vittadello, Fabio; Meneghel, Alessandra; Zulian, Francesco

2018-05-03

Juvenile Localized Scleroderma (JLS) is a rare disorder that may cause severe aesthetic sequelae and functional disability. To date, data on natural history and long-term outcome are discordant and difficult to compare due to the heterogeneity of clinical subtypes, treatments and methods to evaluate activity and outcome in previous studies. A retrospective and cross-sectional study including 133 patients followed between January 1991 and December 2016 was conducted at our Pediatric Rheumatology Centre. Disease course was drawn by retrospective analysis of patients' clinical features, treatment, disease course and outcome at the last evaluation. Disease activity and severity of tissue damage were assessed by using parameters derived from the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and thermography. Most patients achieved complete remission, as only 12.5%, all with the linear subtype, had still active disease after over 10 years of follow-up. At least one disease relapse occurred in 22.2% of patients and first flare was observed 20 months after first treatment discontinuation. Mild tissue damage was observed in more than half of patients, in 25.4% was moderate and in 23.0% severe; 19.8% presented a functional limitation. The entity of skin and subcutaneous fat loss established at the early stages of the disease as 27.8% of patients with shorter disease duration had severe damage and the rates remained constant in patients with longer follow-up. The delay in start of systemic treatment was associated with longer disease activity and higher relapse rate. Patients with linear scleroderma (LS), pansclerotic morphea (PM) and mixed subtype (MS) presented more severe aesthetic and functional damage but did not differ from other subtypes as for rate of complete remission. JLS in some patients can be a very aggressive disease with persistent activity after >10 years and/or several disease relapses. As tissue damage establishes early in disease course a prompt diagnosis and start of appropriate treatment is crucial to control inflammation, to limit and stabilize damage, before it become irreversible. Clinicians must be aware that children with JLS may present disease reactivation so it is important to closely follow-up patients, particularly in the first 2 years after discontinuation of treatment when disease relapses may occur more frequently. Copyright © 2018 Elsevier B.V. All rights reserved.

Activity-based protein profiling for biochemical pathway discovery in cancer

PubMed Central

Nomura, Daniel K.; Dix, Melissa M.; Cravatt, Benjamin F.

2011-01-01

Large-scale profiling methods have uncovered numerous gene and protein expression changes that correlate with tumorigenesis. However, determining the relevance of these expression changes and which biochemical pathways they affect has been hindered by our incomplete understanding of the proteome and its myriad functions and modes of regulation. Activity-based profiling platforms enable both the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When integrated with other large-scale profiling methods, activity-based proteomics can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and illuminate new strategies for disease diagnosis and treatment. PMID:20703252

Antibacterial activity of crude extracts of prasaprohyai formula and its components against pathogenic bacteria.

PubMed

Sattaponpan, Chisanucha; Kondo, Sumalee

2011-12-01

Prasaprohyai formula is a Thai Traditional Medicine which has been used for reducing feverish in child. Fever is a symptom resulting from various infections and diseases. The major cause of fever is bacterial and viral infections. The Prasaprohyai formula and its components potentially have biological activities including antipyretic and antimicrobial activities. It is in a hope to develop the formula and its components for an alternative medicine of infectious diseases. To study antibacterial activity of Prasaprohyai formula and its components against pathogenic bacteria. Prasaprohyai formula and its components were extracted by different methods, A: maceration with 95% ethanol followed by evaporation (ET), B: ET followed by freeze drying (EF) and C: water distillation (VO). All extracts were tested against clinical isolates from Thammasat University Hospital, Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. Disk diffusion and broth dilution methods were performed. Crude extracts of ET had higher yield of extraction than other methods. The results showed that the crude extract from different methods of Syzygium aromaticum (Linn) Merr & Perry (Flower) was effective against all bacterial strains with the inhibition zone ranging from 9 to 19 mm. The VO extract of Prasaprohyai formula showed antibacterial activity against most of the pathogenic bacteria in the present study. The activity against Streptococcus pyogenes was found in the VO extract of some components. The ET extracts of Lepidium sativum Linn, Myristica fragrans Houtt (seed) and Myristica fragrans Houtt (aril) had no antibacterial activity against all microorganism. However the EF extracts of this formula and some components were able to mostly inhibit Gram positive bacteria. The results indicated that Prasaprohyai formula and its components were able to inhibit the growth of both Gram positive and Gram negative bacteria including multiresistant strains. The volatile oil extracts seemed to play an important role in antimicrobial activities. The development of Prasaprohyai formula for alternative medicine will be approached in future.

Development and Application of Advanced Ophthalmic Imaging Technology to Enhance Military Ocular Health Capabilities

DTIC Science & Technology

2009-04-01

active military personnel and veterans, are affected by three major blinding diseases of the retina and optic nerve: diabetic retinopathy , age-related...disease is detected early. New advanced detection methods are available, but are only interpretable by very experienced specialists. The goal of this...consist of several steps [1-3]: feature detection ; transform model estimation; optimization function design; and optimization strategies. We do not

Muscle Activation During Grasping With and Without Motor Imagery in Healthy Volunteers and Patients After Stroke or With Parkinson's Disease

PubMed Central

Kobelt, Manuela; Wirth, Brigitte; Schuster-Amft, Corina

2018-01-01

Introduction: The present study assessed whether motor imagery (MI) produces electromyographic activation in specific muscles of the upper limb during a hand grasping and arm-lifting task in healthy volunteers, patients after stroke, or with Parkinson's disease. Electromyographic (EMG) activation was compared under three conditions: MI, physical execution (PE), and rest. The task is clinically relevant unilateral executed movement using open muscle chains. Methods: In a cross-sectional study EMG activation was measured in four muscles: M. deltoideus pars clavicularis, M. biceps brachii, M. extensor digitorum, M. flexor carpi radialis. MI ability was evaluated with mental rotation, mental chronometry and the Kinaesthetic and Visual Imagery Questionnaire. Cognitive performance was screened with the Mini-Mental State Examination. Results: Twenty-two participants (11 females, age 52.6 ±15.8, age range 21 to 72) were included: ten healthy volunteers, seven patients after stroke (time after stroke onset 16.3 ± 24.8 months), and five patients with Parkinson's disease (disease duration 60.4 ± 24.5 months). Overall Mini-Mental State Examination scores ranged between 27 and 30. An increased EMG activation during MI compared to rest condition was observed in M. deltoideus pars clavicularis and M. biceps brachii across all participants (p-value = 0.001, p = 0.007). Seven participants (two healthy volunteers, three patients after stroke and two patients with Parkinson's disease) showed a EMG activation during MI of the hand grasping and arm-lifting task in at least one of the target muscles. No correlation between EMG activation during MI and scores of three MI ability assessments were found. Conclusions: The findings suggest that MI can yield subliminal EMG activation. However, that might vary on individual basis. It remains unclear what parameters contribute to or inhibit an EMG activation during MI. Future investigations should determine factors that influence EMG activation, e.g. MI instructions, tasks to imagine, amount of MI training, and longitudinal changes after an MI training period. PMID:29740377

[Precision nutrition in the era of precision medicine].

PubMed

Chen, P Z; Wang, H

2016-12-06

Precision medicine has been increasingly incorporated into clinical practice and is enabling a new era for disease prevention and treatment. As an important constituent of precision medicine, precision nutrition has also been drawing more attention during physical examinations. The main aim of precision nutrition is to provide safe and efficient intervention methods for disease treatment and management, through fully considering the genetics, lifestyle (dietary, exercise and lifestyle choices), metabolic status, gut microbiota and physiological status (nutrient level and disease status) of individuals. Three major components should be considered in precision nutrition, including individual criteria for sufficient nutritional status, biomarker monitoring or techniques for nutrient detection and the applicable therapeutic or intervention methods. It was suggested that, in clinical practice, many inherited and chronic metabolic diseases might be prevented or managed through precision nutritional intervention. For generally healthy populations, because lifestyles, dietary factors, genetic factors and environmental exposures vary among individuals, precision nutrition is warranted to improve their physical activity and reduce disease risks. In summary, research and practice is leading toward precision nutrition becoming an integral constituent of clinical nutrition and disease prevention in the era of precision medicine.

Role of Artificial Intelligence Techniques (Automatic Classifiers) in Molecular Imaging Modalities in Neurodegenerative Diseases.

PubMed

Cascianelli, Silvia; Scialpi, Michele; Amici, Serena; Forini, Nevio; Minestrini, Matteo; Fravolini, Mario Luca; Sinzinger, Helmut; Schillaci, Orazio; Palumbo, Barbara

2017-01-01

Artificial Intelligence (AI) is a very active Computer Science research field aiming to develop systems that mimic human intelligence and is helpful in many human activities, including Medicine. In this review we presented some examples of the exploiting of AI techniques, in particular automatic classifiers such as Artificial Neural Network (ANN), Support Vector Machine (SVM), Classification Tree (ClT) and ensemble methods like Random Forest (RF), able to analyze findings obtained by positron emission tomography (PET) or single-photon emission tomography (SPECT) scans of patients with Neurodegenerative Diseases, in particular Alzheimer's Disease. We also focused our attention on techniques applied in order to preprocess data and reduce their dimensionality via feature selection or projection in a more representative domain (Principal Component Analysis - PCA - or Partial Least Squares - PLS - are examples of such methods); this is a crucial step while dealing with medical data, since it is necessary to compress patient information and retain only the most useful in order to discriminate subjects into normal and pathological classes. Main literature papers on the application of these techniques to classify patients with neurodegenerative disease extracting data from molecular imaging modalities are reported, showing that the increasing development of computer aided diagnosis systems is very promising to contribute to the diagnostic process.

Systematic review of surveillance systems and methods for early detection of exotic, new and re-emerging diseases in animal populations.

PubMed

Rodríguez-Prieto, V; Vicente-Rubiano, M; Sánchez-Matamoros, A; Rubio-Guerri, C; Melero, M; Martínez-López, B; Martínez-Avilés, M; Hoinville, L; Vergne, T; Comin, A; Schauer, B; Dórea, F; Pfeiffer, D U; Sánchez-Vizcaíno, J M

2015-07-01

In this globalized world, the spread of new, exotic and re-emerging diseases has become one of the most important threats to animal production and public health. This systematic review analyses conventional and novel early detection methods applied to surveillance. In all, 125 scientific documents were considered for this study. Exotic (n = 49) and re-emerging (n = 27) diseases constituted the most frequently represented health threats. In addition, the majority of studies were related to zoonoses (n = 66). The approaches found in the review could be divided in surveillance modalities, both active (n = 23) and passive (n = 5); and tools and methodologies that support surveillance activities (n = 57). Combinations of surveillance modalities and tools (n = 40) were also found. Risk-based approaches were very common (n = 60), especially in the papers describing tools and methodologies (n = 50). The main applications, benefits and limitations of each approach were extracted from the papers. This information will be very useful for informing the development of tools to facilitate the design of cost-effective surveillance strategies. Thus, the current literature review provides key information about the advantages, disadvantages, limitations and potential application of methodologies for the early detection of new, exotic and re-emerging diseases.

Physical activity and pediatric multiple sclerosis: Developing a research agenda.

PubMed

Yeh, E Ann; Kinnett-Hopkins, Dominique; Grover, Stephanie A; Motl, Robert W

2015-11-01

Three-quarters of children with multiple sclerosis (MS) experience fatigue or depression, and progressive neurocognitive decline may be seen as early as two years after MS diagnosis. Furthermore, a higher magnetic resonance imaging disease burden is seen in pediatric-onset MS compared with adult-onset MS. To date, limited knowledge exists regarding behavioral methods for managing symptoms and disease progression in pediatric MS. To that end, this paper builds an evidence-based argument for the possible symptomatic and disease-modifying effects of exercise and physical activity in pediatric MS. This will be accomplished through: (a) a review of pediatric MS and its consequences; (b) a brief overview of physical activity and its consequences in children and adults with MS; and (c) a selective review of research on the neurological benefits of physical activity in pediatric populations. This topical review concludes with a list of 10 questions to guide future research on physical activity and pediatric MS. The objective of this paper is the provision of a research interest, focus and agenda involving pediatric MS and its lifelong management though exercise and physical activity behavior. Such an agenda is critical as the effects and maintenance of physical activity and exercise track across the lifespan, particularly when developed in the early stages of life. © The Author(s), 2015.

Functional analysis of variant lysosomal acid glycosidases of Anderson-Fabry and Pompe disease in a human embryonic kidney epithelial cell line (HEK 293 T).

PubMed

Ebrahim, Hatim Y; Baker, Robert J; Mehta, Atul B; Hughes, Derralynn A

2012-03-01

The functional significance of missense mutations in genes encoding acid glycosidases of lysosomal storage disorders (LSDs) is not always clear. Here we describe a method of investigating functional properties of variant enzymes in vitro using a human embryonic kidney epithelial cell line. Site-directed mutagenesis was performed on the parental plasmids containing cDNA encoding for alpha-galactosidase A (α-Gal A) and acid maltase (α-Glu) to prepare plasmids encoding relevant point mutations. Mutant plasmids were transfected into HEK 293 T cells, and transient over-expression of variant enzymes was measured after 3 days. We have illustrated the method by examining enzymatic activities of four unknown α-Gal A and one α-Glu variants identified in our patients with Anderson-Fabry disease and Pompe diseases respectively. Comparison with control variants known to be either pathogenic or non-pathogenic together with over-expression of wild-type enzyme allowed determination of the pathogenicity of the mutation. One leader sequence novel variant of α-Gal A (p.A15T) was shown not to significantly reduce enzyme activity, whereas three other novel α-Gal A variants (p.D93Y, p.L372P and p.T410I) were shown to be pathogenic as they resulted in significant reduction of enzyme activity. A novel α-Glu variant (p.L72R) was shown to be pathogenic as this significantly reduced enzyme activity. Certain acid glycosidase variants that have been described in association with late-onset LSDs and which are known to have variable residual plasma and leukocyte enzyme activity in patients appear to show intermediate to low enzyme activity (p.N215S and p.Q279E α-Gal A respectively) in the over-expression system.

A simple screening method for determining knowledge of the appropriate levels of activity and risk behaviour in young people with congenital cardiac conditions.

PubMed

Kendall, Lynne; Parsons, Jonathan M; Sloper, Patricia; Lewin, Robert J P

2007-04-01

To assess a novel method for assessing risk and providing advice about activity to children and young people with congenital cardiac disease and their parents. Questionnaire survey in outpatient clinics at a tertiary centre dealing with congenital cardiac disease, and 6 peripheral clinics. Children or their parents completed a brief questionnaire. If this indicated a desire for help, or a serious mismatch between advised and real level of activity, they were telephoned by a physiotherapist. MAIN MEASURES OF OUTCOME: Knowledge about appropriate levels of activity, and identification of the number exercising at an unsafe level, the number seeking help, and the type of help required. 253/258 (98.0%) questionnaires were returned, with 119/253 (47.0%) showing incorrect responses in their belief about their advised level of exercise; 17/253 (6.7%) had potentially dangerous overestimation of exercise. Asked if they wanted advice 93/253 (36.8%) said "yes", 43/253 (17.0%) "maybe", and 117/253 (46.2%) "no". Of those contacted by phone to give advice, 72.7% (56/77) required a single contact and 14.3% (11/77) required an intervention that required more intensive contact lasting from 2 up to 12 weeks. Of the cohort, 3.9% (3/77) were taking part in activities that put them at significant risk. There is a significant lack of knowledge about appropriate levels of activity, and a desire for further advice, in children and young people with congenital cardiac disease. A few children may be at very significant risk. These needs can be identified, and clinical risk reduced, using a brief self-completed questionnaire combined with telephone follow-up from a suitably knowledgeable physiotherapist.

Anti-inflammatory, anticholinesterase and antioxidant activity of leaf extracts of twelve plants used traditionally to alleviate pain and inflammation in South Africa.

PubMed

Dzoyem, J P; Eloff, J N

2015-02-03

Oxidative stress and inflammatory conditions are among the pathological features associated with the central nervous system in Alzheimer׳s disease. Traditionally, medicinal plants have been used to alleviate inflammation, pains and also other symptoms possibly associated with Alzheimer׳s disease. Therefore, the present study was designed to determine the in vitro anti-inflammatory, antioxidant and anticholinesterase activity of twelve South African medicinal plants traditionally used to alleviate pain and inflammation. Nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages and 15-lipoxygenase (LOX) inhibitory assay were used to evaluate the anti-inflammatory activity. Acetylcholinesterase inhibition was assessed by using a modification of the Ellman׳s method. Antioxidant activity, total phenolic and total flavonoids contents were determined using standard in vitro methods. The extract of Burkea africana had the highest anti-15-lipoxygenase activity with 85.92% inhibition at 100µg/mL. All the extracts tested inhibited nitric oxide (NO) production in a dose dependant manner in LPS-stimulated RAW 264.7 macrophages. However, extracts from Leucaena leucocephala, Lippia javanica inhibited the production of NO by 97% at a concentration of 25µg/mL. In addition, both Leucaena leucocephala and Englerophytum magaliesmontanum had strong activity against acetylcholinesterase with IC50 values of 118µg/mL and 160µg/mL respectively. Hight levels of phenolics and flavonoids were found in Leucaena leucocephala, Lippia javanica and Burkea africana. The correlation with antioxidant activities was not strong indicating that other metabolites may also be involved in antioxidant activity. The results obtained in this study validate the use of leaf extracts of these plants in South African traditional medicine against inflammation. Extracts of these plants species might be of value in the management of various diseases emerging from oxidative stress and related degenerative disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Size-dependent antibacterial activities of silver nanoparticles against oral anaerobic pathogenic bacteria.

PubMed

Lu, Zhong; Rong, Kaifeng; Li, Ju; Yang, Hao; Chen, Rong

2013-06-01

Dental caries and periodontal disease are widespread diseases for which microorganism infections have been identified as the main etiology. Silver nanoparticles (Ag Nps) were considered as potential control oral bacteria infection agent due to its excellent antimicrobial activity and non acute toxic effects on human cells. In this work, stable Ag Nps with different sizes (~5, 15 and 55 nm mean values) were synthesized by using a simple reduction method or hydrothermal method. The Nps were characterized by powder X-ray diffraction, transmission electron microscopy and UV-vis absorption spectroscopy. The antibacterial activities were evaluated by colony counting assay and growth inhibition curve method, and corresponding minimum inhibitory concentration (MIC) against five anaerobic oral pathogenic bacteria and aerobic bacteria E. coli were determined. The results showed that Ag Nps had apparent antibacterial effects against the anaerobic oral pathogenic bacteria and aerobic bacteria. The MIC values of 5-nm Ag against anaerobic oral pathogenic bacteria A. actinomycetemcomitans, F. nuceatum, S. mitis, S. mutans and S. sanguis were 25, 25, 25, 50 and 50 μg/mL, respectively. The aerobic bacteria were more susceptible to Ag NPs than the anaerobic oral pathogenic bacteria. In the mean time, Ag NPs displayed an obvious size-dependent antibacterial activity against the anaerobic bacteria. The 5-nm Ag presents the highest antibacterial activity. The results of this work indicated a potential application of Ag Nps in the inhibition of oral microorganism infections.

Photodynamic therapy for the treatment of osteoarthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trauner, K.; Hasan, T.

A method is disclosed of treating a patient who has osteoarthritic disease by administering a therapeutic composition containing a photoactivatable compound, or a precursor thereof, and administering light of a photoactivating wavelength that activates the compound. 5 figs.

Photodynamic therapy for the treatment of osteoarthritis

DOEpatents

Trauner, K.; Hasan, T.

1999-08-24

A method is disclosed of treating a patient who has osteoarthritic disease by administering a therapeutic composition containing a photoactivatable compound, or a precursor thereof, and administering light of a photoactivating wavelength that activates the compound. 5 figs.

Laser methods of caries prophylaxis

NASA Astrophysics Data System (ADS)

Kunin, Anatoly A.; Dergunova, Elvira I.; Kazmina, Svetlana G.

1996-01-01

Low intensive laser irradiation is widely used for the treatment of many stomatological diseases. The caries static activity of HNL light and infrared lasers, its influence on the activation of microcirculation of the pulp enzyme system and on the increase of enamel permeability became clear. These data allow us to suppose that the low intensive laser irradiation may potent the activity of the initial caries by the increase of teeth stability to the factors provoking the caries.

Are three generations of quantitative molecular methods sufficient in medical virology? Brief review.

PubMed

Clementi, Massimo; Bagnarelli, Patrizia

2015-10-01

In the last two decades, development of quantitative molecular methods has characterized the evolution of clinical virology more than any other methodological advancement. Using these methods, a great deal of studies has addressed efficiently in vivo the role of viral load, viral replication activity, and viral transcriptional profiles as correlates of disease outcome and progression, and has highlighted the physio-pathology of important virus diseases of humans. Furthermore, these studies have contributed to a better understanding of virus-host interactions and have sharply revolutionized the research strategies in basic and medical virology. In addition and importantly from a medical point of view, quantitative methods have provided a rationale for the therapeutic intervention and therapy monitoring in medically important viral diseases. Despite the advances in technology and the development of three generations of molecular methods within the last two decades (competitive PCR, real-time PCR, and digital PCR), great challenges still remain for viral testing related not only to standardization, accuracy, and precision, but also to selection of the best molecular targets for clinical use and to the identification of thresholds for risk stratification and therapeutic decisions. Future research directions, novel methods and technical improvements could be important to address these challenges.

Novel Nrf2 activators from microbial transformation products inhibit blood-retinal barrier permeability in rabbits.

PubMed

Nakagami, Yasuhiro; Masuda, Kayoko; Hatano, Emiko; Inoue, Tatsuya; Matsuyama, Takuya; Iizuka, Mayumi; Ono, Yasunori; Ohnuki, Takashi; Murakami, Yoko; Iwasaki, Masaru; Yoshida, Kazuhiro; Kasuya, Yuji; Komoriya, Satoshi

2015-03-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well-known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator. The potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase-1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen-induced retinopathy in rats and glycated albumin-induced blood-retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation. Bardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2-targeted genes was observed at a one-tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively. Nrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease. © 2014 The British Pharmacological Society.

Novel Nrf2 activators from microbial transformation products inhibit blood–retinal barrier permeability in rabbits

PubMed Central

Nakagami, Yasuhiro; Masuda, Kayoko; Hatano, Emiko; Inoue, Tatsuya; Matsuyama, Takuya; Iizuka, Mayumi; Ono, Yasunori; Ohnuki, Takashi; Murakami, Yoko; Iwasaki, Masaru; Yoshida, Kazuhiro; Kasuya, Yuji; Komoriya, Satoshi

2015-01-01

Background and Purpose Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well-known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator. Experimental Approach The potent novel Nrf2 activator, RS9, was obtained from microbial transformation products. Its Nrf2 activity was evaluated by determining NADPH:quinone oxidoreductase-1 induction activity in Hepa1c1c7 cells. We also investigated the effects of RS9 on oxygen-induced retinopathy in rats and glycated albumin-induced blood–retinal barrier permeability in rabbits because many ocular diseases are associated with oxidative stress and inflammation. Key Results Bardoxolone methyl doubled the specific activity of Nrf2 in Hepa1c1c7 cells at a much higher concentration than RS9. Moreover, the induction of Nrf2-targeted genes was observed at a one-tenth lower concentration of RS9. Interestingly, the cytotoxicity of RS9 was substantially reduced compared with bardoxolone methyl. Oral and intravitreal administration of RS9 ameliorated the pathological scores and leakage in the models of retinopathy in rats and ocular inflammation in rabbits respectively. Conclusion and Implications Nrf2 activators are applicable for treating ocular diseases and novel Nrf2 activators have potential as a unique method for prevention and treatment of retinovascular disease. PMID:25363737

US medical specialty global health training and the global burden of disease

PubMed Central

Kerry, Vanessa B.; Walensky, Rochelle P.; Tsai, Alexander C.; Bergmark, Regan W.; Bergmark, Brian A.; Rouse, Chaturia; Bangsberg, David R.

2013-01-01

Background Rapid growth in global health activity among US medical specialty education programs has lead to heterogeneity in types of activities and global health training models. The breadth and scope of this activity is not well chronicled. Methods Using a standardized search protocol, we examined the characteristics of US medical residency global health programs by number of programs, clinical specialty, nature of activity (elective, research, extended curriculum based field training), and geographic location across seven different clinical medical residency education specialties. We tabulated programmatic activity by clinical discipline, region and country. We calculated the Spearman's rank correlation coefficient to estimate the association between programmatic activity and country–level disease burden. Results Of the 1856 programs assessed between January and June 2011, there were 380 global health residency training programs (20%) working in 141 countries. 529 individual programmatic activities (elective–based rotations, research programs, extended curriculum–based field training, or other) occurred at 1337 specific sites. The majority of the activities consisted of elective–based rotations. At the country level, disease burden had a statistically significant association with programmatic activity (Spearman's ρ = 0.17) but only explained 3% of the total variation between countries. Conclusions There were a substantial number of US medical specialty global health programs, but a relative paucity of surgical and mental health programs. Elective–based programs were more common than programs that offer longitudinal experiences. Despite heterogeneity, there was a small but statistically significant association between program location and the global burden of disease. Areas for further study include the degree to which US–based programs develop partnerships with their program sites, the significance of this activity for training, and number and breadth of programs in medical specialty global health education in other countries around the world. PMID:24363924

Presymptomatic detection of Parkinson's disease.

PubMed

Jenner, P

1993-01-01

Presymptomatic detection of Parkinson's disease is necessary if neuroprotective therapies are to be utilized in its treatment. Various methods (PET, electrophysiology, enzyme assays, olfactory function) may be applicable but none has been rigorously evaluated. Other possible approaches are now considered. Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral dopamine function. However, there are no detectable differences in pHVA between newly diagnosed and untreated parkinsonian patients and control subjects. Compensatory increases in dopamine turnover may mask a decrease in pHVA in the early stages of the disease. So, at present this technique could not be used as a diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide clues to biochemical markers indicative of nigral pathology. Mitochondrial complex I activity is reduced in substantia nigra in Parkinson's disease and it was reported also to be markedly reduced in blood platelets. However, subsequent studies suggest that the difference in platelet complex I activity is too small to be diagnostic of Parkinson's disease. There are also selective reductions in brain glutathione levels in Parkinson's disease restricted to substantia nigra, which do not occur in other neurodegenerative disorders and are not due to drug treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's disease) nigral glutathione levels are reduced to the same degree as in advanced Parkinson's disease. So, some peripheral index of altered glutathione function may be valuable in the early detection of the disease process.

Relationship between physician-based assessment of disease activity, quality of life, and costs of ulcerative colitis in Poland

PubMed Central

Stawowczyk, Ewa

2018-01-01

Introduction Ulcerative colitis (UC) is an idiopathic inflammatory bowel disorder, which requires lifelong treatment. It generates substantial direct and indirect costs, and significantly affects the quality of life, especially in the active state of the disease. Aim To evaluate the direct and indirect costs of UC as well as to assess disease activity and quality of life reported by patients with UC in Polish settings. Material and methods A questionnaire, cross-sectional study among UC patients as well as physicians involved in the therapy of the patients was conducted. The Clinical Activity Index (CAI) was used to assess disease activity, and the WPAI questionnaire to assess productivity loss. The quality of life was presented as utility calculated using the EQ-5D-3L questionnaire. Indirect costs included absenteeism, presenteeism, and informal care were assessed with the Human Capital Approach and expressed in euros (€). The productivity loss among informal caregivers was valuated with the average wage in Poland. Correlations were presented using the Spearman’s coefficient, and the between-group difference was assessed with Mann-Whitney U-test. Results One hundred and forty-seven patients participated in the study, including 95 working persons. Mean cost of absenteeism and presenteeism was €1615.2 (95% CI: 669.5–2561.0) and €3684.4 (95% CI: 2367.8–5001.1), respectively, per year per patient with a disease in remission. The mean yearly cost of productivity loss due to informal care was estimated to be €256.6 (range: 0.0–532.6). The corresponding values for patients with active disease were: €8,913.3 (95% CI: 6223.3–11,603.3), €4325.1 (95% CI: 2282.4–6367.8), and €2396.1 (95% CI: 402.0–4390.3). The between-group difference in total indirect costs, cost of absenteeism, and cost of informal care was statistically significant (p < 0.05). The average weighted monthly costs of therapy with particular drugs categories (e.g. mesalazine or biologic drugs) differed significantly between active disease or remission patients. The difference in utility values between patients with a disease in remission (0.898 ±0.126) and patients with an active disease (0.646 ±0.302) was statistically significant. Conclusions Our study revealed the social burden of UC and high dependency of direct and indirect costs as well as quality of life on the severity of UC in Poland. The statistically significant differences were identified in total direct and indirect cost, cost of absenteeism, cost of informal care, and health-related quality of life among patients with an active disease compared to patients with a disease in remission. PMID:29657613

A unique dual recognition hairpin probe mediated fluorescence amplification method for sensitive detection of uracil-DNA glycosylase and endonuclease IV activities.

PubMed

Wu, Yushu; Yan, Ping; Xu, Xiaowen; Jiang, Wei

2016-03-07

Uracil-DNA glycosylase (UDG) and endonuclease IV (Endo IV) play cooperative roles in uracil base-excision repair (UBER) and inactivity of either will interrupt the UBER to cause disease. Detection of UDG and Endo IV activities is crucial to evaluate the UBER process in fundamental research and diagnostic application. Here, a unique dual recognition hairpin probe mediated fluorescence amplification method was developed for sensitively and selectively detecting UDG and Endo IV activities. For detecting UDG activity, the uracil base in the probe was excised by the target enzyme to generate an apurinic/apyrimidinic (AP) site, achieving the UDG recognition. Then, the AP site was cleaved by a tool enzyme Endo IV, releasing a primer to trigger rolling circle amplification (RCA) reaction. Finally, the RCA reaction produced numerous repeated G-quadruplex sequences, which interacted with N-methyl-mesoporphyrin IX to generate an enhanced fluorescence signal. Alternatively, for detecting Endo IV activity, the uracil base in the probe was first converted into an AP site by a tool enzyme UDG. Next, the AP site was cleaved by the target enzyme, achieving the Endo IV recognition. The signal was then generated and amplified in the same way as those in the UDG activity assay. The detection limits were as low as 0.00017 U mL(-1) for UDG and 0.11 U mL(-1) for Endo IV, respectively. Moreover, UDG and Endo IV can be well distinguished from their analogs. This method is beneficial for properly evaluating the UBER process in function studies and disease prognoses.

Therapeutic target for protozoal diseases

DOEpatents

Rathore, Dharmendar [Blacksburg, VA; Jani, Dewal [Blacksburg, VA; Nagarkatti, Rana [Blacksburg, VA

2008-10-21

A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

Research priority setting in childhood chronic disease: a systematic review.

PubMed

Odgers, Harrison Lindsay; Tong, Allison; Lopez-Vargas, Pamela; Davidson, Andrew; Jaffe, Adam; McKenzie, Anne; Pinkerton, Ross; Wake, Melissa; Richmond, Peter; Crowe, Sally; Caldwell, Patrina Ha Yuen; Hill, Sophie; Couper, Jennifer; Haddad, Suzy; Kassai, Behrouz; Craig, Jonathan C

2018-04-11

To evaluate research priority setting approaches in childhood chronic diseases and to describe the priorities of stakeholders including patients, caregivers/families and health professionals. We conducted a systematic review of MEDLINE, Embase, PsycINFO and CINAHL from inception to 16 October 2016. Studies that elicited stakeholder priorities for paediatric chronic disease research were eligible for inclusion. Data on the prioritisation process were extracted using an appraisal checklist. Generated priorities were collated into common topic areas. We identified 83 studies (n=15 722). Twenty (24%) studies involved parents/caregivers and four (5%) children. The top three health areas were cancer (11%), neurology (8%) and endocrine/metabolism (8%). Priority topic areas were treatment (78%), disease trajectory (48%), quality of life/psychosocial impact (48%), disease onset/prevention (43%), knowledge/self-management (33%), prevalence (30%), diagnostic methods (28%), access to healthcare (25%) and transition to adulthood (12%). The methods included workshops, Delphi techniques, surveys and focus groups/interviews. Specific methods for collecting and prioritising research topics were described in only 60% of studies. Most reviewed studies were conducted in high-income nations. Research priority setting activities in paediatric chronic disease cover many discipline areas and have elicited a broad range of topics. However, child/caregiver involvement is uncommon, and the methods often lack clarity. A systematic and explicit process that involves patients and families in partnership may help to inform a more patient and family-relevant research agenda in paediatric chronic disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A pilot study examining the relationship among Crohn disease activity, glucagon-like peptide-2 signalling and intestinal function in pediatric patients

PubMed Central

Sigalet, David L; Kravarusic, Dragan; Butzner, Decker; Hartmann, Bolette; Holst, Jens J; Meddings, Jon

2013-01-01

BACKGROUND/OBJECTIVES: The relationship between the enteroendocrine hormone glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2 promotes mucosal growth, decreases permeability and reduces inflammation in the intestine; physiological stimulation of GLP-2 release is triggered by nutrient contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2 release. METHODS: With ethics board approval, pediatric patients hospitalized with CD were studied; controls were recruited from local schools. Inclusion criteria were endoscopy-confirmed CD (primarily of the small intestine) with a disease activity index >150. Fasting and post-prandial GLP-2 levels and quantitative urinary recovery of orally administered 3-O-methyl-glucose (active transport) and lactulose/mannitol (passive) were quantified during the acute and remission phases. RESULTS: Seven patients (mean [± SD] age 15.3±1.3 years) and 10 controls (10.3±1.6 years) were studied. In patients with active disease, fasting levels of GLP-2 remained stable but postprandial levels were reduced. Patients with active disease exhibited reduced glucose absorption and increased lactulose/mannitol recovery; all normalized with disease remission. The change in the lactulose/mannitol ratio was due to both reduced lactulose and increased mannitol absorption. CONCLUSIONS: These findings suggest that pediatric patients with acute ileal CD have decreased postprandial GLP-2 release, reduced glucose absorption and increased intestinal permeability. Healing of CD resulted in normalization of postprandial GLP-2 release and mucosal functioning (nutrient absorption and permeability), the latter due to an increase in mucosal surface area. These findings have implications for the use of GLP-2 and feeding strategies as a therapy in CD patients; further studies of the effects of inflammation and the GLP-2 axis are recommended. PMID:24106731

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

PubMed Central

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-01-01

Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID:19643759

The ethanolic extract of ashitaba stem (Angelica keskei [Miq.] Koidz) as future antituberculosis

PubMed Central

Kusuma, Sri Agung Fitri; Iskandar, Yoppi; Dewanti, Mutiara Ayu

2018-01-01

Considering the easy contagion of tuberculosis (TB) disease spread and the emergence of multidrug-resistant TB, which directly impacts the failure of therapeutic goals and mortality rates increasing, TB disease control remains to be the main concern of continuous health development effort. Therefore, the discovery of new TB drug is needed. This research assessed the new natural anti-TB drug from the ethanolic extract of Angelica keiskei stem obtained from Lombok, Indonesia. The objectives of this study were to evaluate the sensitivity of Mycobacterium tuberculosis (Mtb) H37Rv strain to A. keiskei stem extract and to determine its minimum inhibitory concentration (MIC). The extraction methods of A. keiskei stem were done using a maceration method. In addition to phytochemical screening and water content analysis using standard method, the phytochemical parameters were analyzed by thin-layer chromatography. Ethanolic extract of A. keiskei stem was assayed for their Mtb inhibitory activity using the proportion method. The phytochemical analysis result showed that the secondary metabolites contain in the extract were flavonoid, polyphenol, tannin, monoterpenoid and sesquiterpen, quinon, and saponin. The anti-TB test result showed the active activity of ethanolic extract of A. keiskei against Mtb H37Rv strain with MIC ranging from 6% to 8% w/v. In conclusion, ethanolic extract of A. keiskei is a prospective natural anti-TB for the future. PMID:29441323

Perceived stress and reported cognitive symptoms among Georgia patients with systemic lupus erythematosus.

PubMed

Plantinga, L; Lim, S S; Bowling, C B; Drenkard, C

2017-09-01

Objective To examine associations of perceived stress with cognitive symptoms among adults with systemic lupus erythematosus (SLE). Methods Among 777 adult (≥18 years) SLE patients, the association of Perceived Stress Scale (PSS) scores with two self-reported cognitive symptoms was examined: forgetfulness (severe/moderate vs. mild/none; from the Systemic Lupus Activity Questionnaire) and difficulty concentrating (all/most vs. some/little/none of the time; from the Lupus Impact Tracker). The study used multivariable logistic regression to estimate the odds ratios (ORs) per minimal important difference (MID = 0.5*SD) of PSS score and cognitive symptoms. Results Forgetfulness and difficulty concentrating were reported by 41.7% and 29.5%, respectively. Women and those with less education and high disease activity had higher PSS scores and were more likely to report cognitive symptoms than their counterparts. With adjustment for age, race, sex, education, and disease activity, each MID increase in PSS score was associated with higher prevalence of forgetfulness (OR = 1.43, 95% CI 1.29-1.47) and difficulty concentrating (OR = 2.19, 95% CI 1.90-2.52). No substantial differences in this association by age, race, sex, or disease activity were noted. Conclusions SLE patients, particularly those with high disease activity, report a high burden of cognitive symptoms, for which stress may be a modifiable risk factor.

Exploiting the potential of vector control for disease prevention.

PubMed

Townson, H; Nathan, M B; Zaim, M; Guillet, P; Manga, L; Bos, R; Kindhauser, M

2005-12-01

Although vector control has proven highly effective in preventing disease transmission, it is not being used to its full potential, thereby depriving disadvantaged populations of the benefits of well tried and tested methods. Following the discovery of synthetic residual insecticides in the 1940s, large-scale programmes succeeded in bringing many of the important vector-borne diseases under control. By the late 1960s, most vector-borne diseases--with the exception of malaria in Africa--were no longer considered to be of primary public health importance. The result was that control programmes lapsed, resources dwindled, and specialists in vector control disappeared from public health units. Within two decades, many important vector-borne diseases had re-emerged or spread to new areas. The time has come to restore vector control to its key role in the prevention of disease transmission, albeit with an increased emphasis on multiple measures, whether pesticide-based or involving environmental modification, and with a strengthened managerial and operational capacity. Integrated vector management provides a sound conceptual framework for deployment of cost-effective and sustainable methods of vector control. This approach allows for full consideration of the complex determinants of disease transmission, including local disease ecology, the role of human activity in increasing risks of disease transmission, and the socioeconomic conditions of affected communities.

Exploiting the potential of vector control for disease prevention.

PubMed Central

Townson, H.; Nathan, M. B.; Zaim, M.; Guillet, P.; Manga, L.; Bos, R.; Kindhauser, M.

2005-01-01

Although vector control has proven highly effective in preventing disease transmission, it is not being used to its full potential, thereby depriving disadvantaged populations of the benefits of well tried and tested methods. Following the discovery of synthetic residual insecticides in the 1940s, large-scale programmes succeeded in bringing many of the important vector-borne diseases under control. By the late 1960s, most vector-borne diseases--with the exception of malaria in Africa--were no longer considered to be of primary public health importance. The result was that control programmes lapsed, resources dwindled, and specialists in vector control disappeared from public health units. Within two decades, many important vector-borne diseases had re-emerged or spread to new areas. The time has come to restore vector control to its key role in the prevention of disease transmission, albeit with an increased emphasis on multiple measures, whether pesticide-based or involving environmental modification, and with a strengthened managerial and operational capacity. Integrated vector management provides a sound conceptual framework for deployment of cost-effective and sustainable methods of vector control. This approach allows for full consideration of the complex determinants of disease transmission, including local disease ecology, the role of human activity in increasing risks of disease transmission, and the socioeconomic conditions of affected communities. PMID:16462987

Health Cobenefits and Transportation-Related Reductions in Greenhouse Gas Emissions in the San Francisco Bay Area

PubMed Central

Woodcock, James; Co, Sean; Ostro, Bart; Fanai, Amir; Fairley, David

2013-01-01

Objectives. We quantified health benefits of transportation strategies to reduce greenhouse gas emissions (GHGE). Methods. Statistics on travel patterns and injuries, physical activity, fine particulate matter, and GHGE in the San Francisco Bay Area, California, were input to a model that calculated the health impacts of walking and bicycling short distances usually traveled by car or driving low-emission automobiles. We measured the change in disease burden in disability-adjusted life years (DALYs) based on dose–response relationships and the distributions of physical activity, particulate matter, and traffic injuries. Results: Increasing median daily walking and bicycling from 4 to 22 minutes reduced the burden of cardiovascular disease and diabetes by 14% (32 466 DALYs), increased the traffic injury burden by 39% (5907 DALYS), and decreased GHGE by 14%. Low-carbon driving reduced GHGE by 33.5% and cardiorespiratory disease burden by less than 1%. Conclusions: Increased physical activity associated with active transport could generate a large net improvement in population health. Measures would be needed to minimize pedestrian and bicyclist injuries. Together, active transport and low-carbon driving could achieve GHGE reductions sufficient for California to meet legislative mandates. PMID:23409903

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study

PubMed Central

Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-01-01

Background This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). Material/Methods Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). Results The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. Conclusions The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients. PMID:28548078

Prion protein degradation by lichens of the genus Cladonia

USGS Publications Warehouse

Bennett, James P.; Rodriguez, Cynthia M.; Johnson, Christopher J.

2012-01-01

It has recently been discovered that lichens contain a serine protease capable of degrading the pathogenic prion protein, the etiological agent of prion diseases such as sheep scrapie and cervid chronic wasting disease. Limited methods are available to degrade or inactivate prion disease agents, especially in the environment, and lichens or their serine protease could prove important for management of these diseases. Scant information is available regarding the presence or absence of the protease responsible for degrading prion protein (PrP) in lichen species and, in this study, we tested the hypothesis that PrP degradation activity in lichens is phylogenetically-based by testing 44 species of Cladonia lichens, a genus for which a significant portion of the phylogeny is well established. We categorized PrP degradation activity among the 44 species (high, moderate, low or none) and found that activity in Cladonia species did not correspond with phylogenetic position of the species. Degradation of PrP did correspond, however, with three classical taxonomic characters within the genus: species with brown apothecia, no usnic acid, and the presence of a cortex. Of the 44 species studied, 18 (41%) had either high or moderate PrP degradation activity, suggesting the protease may be frequent in this genus of lichens.

Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions.

PubMed

Reddy, Rallabandi Harikrishna; Kim, Hackyoung; Cha, Seungbin; Lee, Bongsoo; Kim, Young Jun

2017-05-28

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

Mean Platelet Volume in Ocular Behçet's Disease

PubMed Central

Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Çınar, Yasin; Akkurt, Meltem; Şahin, Muhammed; Özkurt, Zeynep; Şahin, Alparslan; Çaça, İhsan

2013-01-01

Objective. To determine whether mean platelet volume (MPV) is an indicator of disease severity in ocular Behçet's Disease (BD). Materials and Methods. The study population was 30 newly diagnosed ocular BD patients who presented with active uveitis. These patients had no past history of smoking, drug use, or systemic diseases including diabetes mellitus, hypertension, cardiovascular disease, and renal disease. A control group consisting of 34 healthy individuals was included for comparison. MPV measurements were performed serially upon presentation with active uveitis and at one and three month thereafter in BD group whereas only at presentation in the controls. Results. Upon presentation with active uveitis, the mean MPV levels were 7.88 ± 1.14 femtoliters (fL) for BD group. During the posttreatment follow-up period at first and third months, BD patients demonstrated a mean MPV level of 7.71 ± 1.12 fL and 7.65 ± 1.04 fL, respectively. The mean MPV value of control group, was 8.39 ± 0.66 fL at presentation. Fluctuations in MPV values were not significant in the BD group, while there was a significant difference between the initial measurements of the BD and control groups. Conclusion. MPV measurement in ocular BD is not a predictive laboratory test to determine the clinical improvement in early stages following classical immunosuppressive treatment. PMID:24250258

In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development.

PubMed

Ozerov, Ivan V; Lezhnina, Ksenia V; Izumchenko, Evgeny; Artemov, Artem V; Medintsev, Sergey; Vanhaelen, Quentin; Aliper, Alexander; Vijg, Jan; Osipov, Andreyan N; Labat, Ivan; West, Michael D; Buzdin, Anton; Cantor, Charles R; Nikolsky, Yuri; Borisov, Nikolay; Irincheeva, Irina; Khokhlovich, Edward; Sidransky, David; Camargo, Miguel Luiz; Zhavoronkov, Alex

2016-11-16

Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. The iPANDA method combines precalculated gene coexpression data with gene importance factors based on the degree of differential gene expression and pathway topology decomposition for obtaining pathway activation scores. Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. We successfully apply iPANDA for stratifying breast cancer patients according to their sensitivity to neoadjuvant therapy.

In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development

PubMed Central

Ozerov, Ivan V.; Lezhnina, Ksenia V.; Izumchenko, Evgeny; Artemov, Artem V.; Medintsev, Sergey; Vanhaelen, Quentin; Aliper, Alexander; Vijg, Jan; Osipov, Andreyan N.; Labat, Ivan; West, Michael D.; Buzdin, Anton; Cantor, Charles R.; Nikolsky, Yuri; Borisov, Nikolay; Irincheeva, Irina; Khokhlovich, Edward; Sidransky, David; Camargo, Miguel Luiz; Zhavoronkov, Alex

2016-01-01

Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. The iPANDA method combines precalculated gene coexpression data with gene importance factors based on the degree of differential gene expression and pathway topology decomposition for obtaining pathway activation scores. Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. We successfully apply iPANDA for stratifying breast cancer patients according to their sensitivity to neoadjuvant therapy. PMID:27848968

Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

PubMed

Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Antibacterial activity of Aquilaria crassna leaf extract against Staphylococcus epidermidis by disruption of cell wall

PubMed Central

2013-01-01

Background Aquilaria crassna Pierre ex Lecomte has been traditionally used in Thailand for treatment of infectious diseases such as diarrhoea and skin diseases for a long time. The main objectives of this study were to examine antibacterial activity of the Aquilaria crassna leaf extract against Staphylococcus epidermidis and its underlying mechanism. The antioxidant activity and acute toxicity were studied as well. Methods Antioxidant activities were examined by FRAP, ABTS and DPPH scavenging methods. Antibacterial activity was conducted using disc diffusion assay and the minimum inhibitory concentration (MIC) was determined by dilution method. The minimum bactericidal concentration (MBC) was reported as the lowest concentration producing no growth of microbes in the subcultures. Morphological changes of the microbe were observed by scanning electron microscopy, while an inhibitory effect on biofilm formation was evaluated by phase contrast microscopic analysis. Bacterial cell wall integrity was assessed by transmission electron microscopy. Acute toxicity was conducted in accordance with the OECD for Testing of Chemicals (2001) guidelines. Results The extract exhibited considerable antioxidant activity. Staphylococcus epidermidis was susceptible to the extract with the MIC and MBC of 6 and 12 mg/ml, respectively. The extract caused swelling and distortion of bacterial cells and inhibited bacterial biofilm formation. Rupture of bacterial cell wall occurred after treated with the extract for 24 h. Acute toxicity test in mice showed no sign of toxicity or death at the doses of 2,000 and 15,000 mg/kg body weight. Conclusion The aqueous extract of Aquilaria crassna leaves possesses an in vitro antibacterial activity against Staphylococcus epidermidis, with no sign of acute oral toxicity in mice, probably by interfering with bacterial cell wall synthesis and inhibiting biofilm formation. PMID:23962360

β-Cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore extract against alloxan-induced oxidative stress via regulation of apoptosis and reactive oxygen species (ROS).

PubMed

Bahar, Entaz; Akter, Kazi-Marjahan; Lee, Geum-Hwa; Lee, Hwa-Young; Rashid, Harun-Or; Choi, Min-Kyung; Bhattarai, Kashi Raj; Hossain, Mir Mohammad Monir; Ara, Joushan; Mazumder, Kishor; Raihan, Obayed; Chae, Han-Jung; Yoon, Hyonok

2017-03-29

Medicinal plants are becoming more popular in the treatment of various diseases because of the adverse effects of the current therapy, especially antioxidant plant components such as phenols and flavonoids have a protective role against oxidative stress-induced degenerative diseases like diabetes. Thus, the purpose of this study was to investigate β-cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. The in-vitro study was conducted by the pancreatic β-cell culture and α-amylase inhibition technique which includes two methods, namely starch-iodine method and 3,5-dinitrosalicylic acid (DNSA) method. On the other hand, the in-vivo study was performed by oral glucose tolerance test (OGTT) method and alloxan-induced diabetes method by using Wistar albino rat. At the end pancreatic specimens were removed and processed for histopathological study. The plant extract showed significant (*p < 0.05, **p < 0.01) effect on hyperglycemia as compared to standard (Gliclazide) in OGTT. The plant extract showed efficient protection activity of pancreatic β-cell from cell death in INS-1 cell line by significantly reduced (*p < 0.05, **p < 0.01) the levels alloxan-induced apoptosis and intracellular reactive oxygen species (ROS) accumulation. In addition, the plant extract showed a significant (*p < 0.05, **p < 0.01) effect on hyperglycemia by increases in percent of β-cells present in each islet (45% - 60%) compared to the diabetic group. The result showed that C. crepidioides had β-cell protection and antidiabetic activities in pancreatic β-cell culture and Wistar albino rat.

Is gardening a stimulating activity for people with advanced Huntington's disease?

PubMed

Spring, Josephine A; Viera, Marc; Bowen, Ceri; Marsh, Nicola

2014-11-01

This study evaluated adapted gardening as an activity for people with advanced Huntington's disease (HD) and explored its therapeutic aspects. Visitors and staff completed a questionnaire and participated in structured interviews to capture further information, whereas a pictorial questionnaire was designed for residents with communication difficulties. Staff reported that gardening was a constructive, outdoor activity that promoted social interaction, physical activity including functional movement and posed cognitive challenges. Half the staff thought the activity was problem free and a third used the garden for therapy. Visitors used the garden to meet with residents socially. Despite their disabilities, HD clients enjoyed growing flourishing flowers and vegetables, labelling plants, being outside in the sun and the quiet of the garden. The garden is valued by all three groups. The study demonstrates the adapted method of gardening is a stimulating and enjoyable activity for people with advanced HD. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Epidemiological surveillance methods for vector-borne diseases.

PubMed

Thompson, P N; Etter, E

2015-04-01

Compared with many other diseases, the ever-increasing threat of vector-borne diseases (VBDs) represents a great challenge to public and animal health managers. Complex life cycles, changing distribution ranges, a variety of potential vectors and hosts, and the possible role of reservoirs make surveillance for VBDs a grave concern in a changing environment with increasing economic constraints. Surveillance activities may have various specific objectives and may focus on clinical disease, pathogens, vectors, hosts and/or reservoirs, but ultimately such activities should improve our ability to predict, prevent and/or control the diseases concerned. This paper briefly reviews existing and newly developed tools for the surveillance of VBDs. A range of examples, by no means exhaustive, illustrates that VBD surveillance usually involves a combination of methods to achieve its aims, and is best accomplished when these techniques are adapted to the specific environment and constraints of the region. More so than any other diseases, VBDs respect no administrative boundaries; in addition, animal, human and commodity movements are increasing dramatically, with illegal or unknown movements difficult to quantify. Vector-borne disease surveillance therefore becomes a serious issue for local and national organisations and is being conducted more and more at the regional and international level through multidisciplinary networks. With economic and logistical constraints, tools for optimising and evaluating the performance of surveillance systems are essential and examples of recent developments in this area are included. The continuous development of mapping, analytical and modelling tools provides us with an enhanced ability to interpret, visualise and communicate surveillance results. This review also demonstrates the importance of the link between surveillance and research, with interactions and benefits in both directions.

The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study.

PubMed

Liu, Shu-Ying; Wile, Daryl J; Fu, Jessie Fanglu; Valerio, Jason; Shahinfard, Elham; McCormick, Siobhan; Mabrouk, Rostom; Vafai, Nasim; McKenzie, Jess; Neilson, Nicole; Perez-Soriano, Alexandra; Arena, Julieta E; Cherkasova, Mariya; Chan, Piu; Zhang, Jing; Zabetian, Cyrus P; Aasly, Jan O; Wszolek, Zbigniew K; McKeown, Martin J; Adam, Michael J; Ruth, Thomas J; Schulzer, Michael; Sossi, Vesna; Stoessl, A Jon

2018-04-01

Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease. Between June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N- 11 C-methyl-piperidin-4-yl propionate to scan for acetylcholinesterase activity. The primary outcome measure was rate of acetylcholinesterase hydrolysis, calculated using the striatal input method. We compared acetylcholinesterase hydrolysis rates between groups using ANCOVA, with adjustment for age based on the results of linear regression analysis. We recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation carriers without Parkinson's disease, eight patients with idiopathic Parkinson's disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0·009, default mode network-related regions p=0·006, limbic network-related regions p=0·020) and the thalamus (p=0·008). LRRK2 mutation carriers without Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0·046). Patients with LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0·043, default mode network-related regions p=0·021) and the thalamus (thalamus p=0·004) compared with individuals with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy controls were correlated inversely with age. LRRK2 mutations are associated with significantly increased cholinergic activity in the brain in mutation carriers without Parkinson's disease compared with healthy controls and in LRRK2 mutation carriers with Parkinson's disease compared with individuals with idiopathic disease. Changes in cholinergic activity might represent early and sustained attempts to compensate for LRRK2-related dysfunction, or alteration of acetylcholinesterase in non-neuronal cells. Michael J Fox Foundation, National Institutes of Health, and Pacific Alzheimer Research Foundation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human jagged polypeptide, encoding nucleic acids and methods of use

DOEpatents

Li, Linheng; Hood, Leroy

2000-01-01

The present invention provides an isolated polypeptide exhibiting substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the polypeptide does not have the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. The invention further provides an isolated nucleic acid molecule containing a nucleotide sequence encoding substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the nucleotide sequence does not encode the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. Also provided herein is a method of inhibiting differentiation of hematopoietic progenitor cells by contacting the progenitor cells with an isolated JAGGED polypeptide, or active fragment thereof. The invention additionally provides a method of diagnosing Alagille Syndrome in an individual. The method consists of detecting an Alagille Syndrome disease-associated mutation linked to a JAGGED locus.

Methods of diagnosing alagille syndrome

DOEpatents

Li, Linheng; Hood, Leroy; Krantz, Ian D.; Spinner, Nancy B.

2004-03-09

The present invention provides an isolated polypeptide exhibiting substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the polypeptide does not have the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. The invention further provides an isolated nucleic acid molecule containing a nucleotide sequence encoding substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the nucleotide sequence does not encode the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. Also provided herein is a method of inhibiting differentiation of hematopoietic progenitor cells by contacting the progenitor cells with an isolated JAGGED polypeptide, or active fragment thereof. The invention additionally provides a method of diagnosing Alagille Syndrome in an individual. The method consists of detecting an Alagille Syndrome disease-associated mutation linked to a JAGGED locus.

External trial deep brain stimulation device for the application of desynchronizing stimulation techniques.

PubMed

Hauptmann, C; Roulet, J-C; Niederhauser, J J; Döll, W; Kirlangic, M E; Lysyansky, B; Krachkovskyi, V; Bhatti, M A; Barnikol, U B; Sasse, L; Bührle, C P; Speckmann, E-J; Götz, M; Sturm, V; Freund, H-J; Schnell, U; Tass, P A

2009-12-01

In the past decade deep brain stimulation (DBS)-the application of electrical stimulation to specific target structures via implanted depth electrodes-has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.

Reduction of sitting time has a positive effect on the decrease of insulin resistance in patients with non-alcoholic fatty liver disease

PubMed Central

Sabinicz, Anna; Maciejewska, Dominika; Kaczorowska, Małgorzata; Ryterska, Karina; Jamioł-Milc, Dominika; Wyszomirska-Raszeja, Joanna; Gutowska, Izabela

2016-01-01

Introduction Non-alcoholic fatty liver disease (NAFLD) affects a large part of the human population. One of the major environmental factors associated with the risk of NAFLD is the lack of physical activity. Aim To compare the level of physical activity and the insulin resistance in NAFLD patients. Material and methods Thirty patients with NAFLD underwent a six-month dietary intervention based on the principles of classical dietetics. Data about diet and physical activity was based on 72-hour nutrition diaries and International Physical Activity Questionnaire (IPAQ). Standard blood biochemical analyses were carried out before and after diet at the University Hospital Laboratory. Results The study showed that total physical activity and physical activity in leisure time are negatively correlated with insulin resistance (HOMA-IR) (p < 0.05). Insulin (p < 0.05), body weight (p < 0.05), and waist-hip ratio (WHR) (p < 0.05) were also negatively correlated with physical activity in free time. In addition, we noticed a positive correlation between sitting time and the risk of insulin resistance, in the case of HOMA-IR and insulin concentration (p < 0.05). Conclusions Dietary intervention and a physical activity plan are important factors in the treatment of non-alcoholic fatty liver disease. Taking regular exercise increases insulin sensitivity and prevents further development of the disease. It seems that diet and physical activity are not the only one risk factors of NAFLD. Our study reveals that the reduction of sitting time has a positive effect on the level of insulin and it reduces insulin resistance in patients with NAFLD. PMID:28053680

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

PubMed Central

Rowe, James B.; Winder-Rhodes, Sophie E.; Hampshire, Adam; Owen, Adrian M.; Breen, David P.; Duncan, Gordon W.; Khoo, Tien K.; Yarnall, Alison J.; Firbank, Michael J.; Chinnery, Patrick F.; Robbins, Trevor W.; O’Brien, John T.; Brooks, David J.; Burn, David J.; Barker, Roger A.

2014-01-01

Parkinson’s disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the ‘Dual Syndrome’ hypothesis for cognitive impairment in Parkinson’s disease, which distinguishes an executive syndrome (affecting the frontostriatal regions due to dopaminergic deficits) from a posterior cortical syndrome (affecting visuospatial, mnemonic and semantic functions related to Lewy body pathology and secondary cholinergic loss). An incident Parkinson’s disease cohort (n = 168, median 8 months from diagnosis to participation) and matched control group (n = 85) were recruited to a neuroimaging study at two sites in the UK. All participants underwent clinical, neuropsychological and functional magnetic resonance imaging assessments. The three neuroimaging tasks (Tower of London, Spatial Rotations and Memory Encoding Tasks) were designed to probe executive, visuospatial and memory encoding domains, respectively. Patients were also genotyped for three polymorphisms associated with cognitive change in Parkinson’s disease and related disorders: (i) rs4680 for COMT Val158Met polymorphism; (ii) rs9468 for MAPT H1 versus H2 haplotype; and (iii) rs429358 for APOE-ε2, 3, 4. We identified performance deficits in all three cognitive domains, which were associated with regionally specific changes in cortical activation. Task-specific regional activations in Parkinson’s disease were linked with genetic variation: the rs4680 polymorphism modulated the effect of levodopa therapy on planning-related activations in the frontoparietal network; the MAPT haplotype modulated parietal activations associated with spatial rotations; and APOE allelic variation influenced the magnitude of activation associated with memory encoding. This study demonstrates that neurocognitive deficits are common even in recently diagnosed patients with Parkinson’s disease, and that the associated regional brain activations are influenced by genotype. These data further support the dual syndrome hypothesis of cognitive change in Parkinson’s disease. Longitudinal data will confirm the extent to which these early neurocognitive changes, and their genetic factors, influence the long-term risk of dementia in Parkinson’s disease. The combination of genetics and functional neuroimaging provides a potentially useful method for stratification and identification of candidate markers, in future clinical trials against cognitive decline in Parkinson’s disease. PMID:25080285

Protecting Bone Health in Pediatric Rheumatic Diseases: Pharmacological Considerations.

PubMed

Zhang, Yujuan; Milojevic, Diana

2017-06-01

Bone health in children with rheumatic conditions may be compromised due to several factors related to the inflammatory disease state, delayed puberty, altered life style, including decreased physical activities, sun avoidance, suboptimal calcium and vitamin D intake, and medical treatments, mainly glucocorticoids and possibly some disease-modifying anti-rheumatic drugs. Low bone density or even fragility fractures could be asymptomatic; therefore, children with diseases of high inflammatory load, such as systemic onset juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, and those requiring chronic glucocorticoids may benefit from routine screening of bone health. Most commonly used assessment tools are laboratory testing including serum 25-OH-vitamin D measurement and bone mineral density measurement by a variety of methods, dual-energy X-ray absorptiometry as the most widely used. Early disease control, use of steroid-sparing medications such as disease-modifying anti-rheumatic drugs and biologics, supplemental vitamin D and calcium, and promotion of weight-bearing physical activities can help optimize bone health. Additional treatment options for osteoporosis such as bisphosphonates are still controversial in children with chronic rheumatic diseases, especially those with decreased bone density without fragility fractures. This article reviews common risk factors leading to compromised bone health in children with chronic rheumatic diseases and discusses the general approach to prevention and treatment of bone fragility.

Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease.

PubMed

Yang, Hua-Li; Cai, Pei; Liu, Qiao-Hong; Yang, Xue-Lian; Fang, Si-Qiang; Tang, Yan-Wei; Wang, Cheng; Wang, Xiao-Bing; Kong, Ling-Yi

2017-11-01

A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-β (Aβ) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Aβ 1-42 aggregation (91.3±2.1%, 25μM), inhibition of hMAO-B (IC 50 , 1.73±0.39μM), antioxidant effects (43.4±2.6μM of IC 50 by DPPH method, 0.67±0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs. Copyright © 2017. Published by Elsevier Ltd.

The Effects of an Oral Supplement Enriched With Fish Oil, Prebiotics, and Antioxidants on Nutrition Status in Crohn’s Disease Patients

PubMed Central

Wiese, Dawn M.; Lashner, Bret A.; Lerner, Edith; DeMichele, Stephen J.; Seidner, Douglas L.

2015-01-01

Background Research in the treatment of Crohn’s disease (CD) supports anti-inflammatory benefits of n-3 fatty acids from fish oil, prebiotics, and antioxidants. A nutritionally balanced inflammatory bowel disease nutrition formula (IBDNF) enriched with these compounds has the potential to improve nutrition status and disease activity in CD. Methods This is an open-label pilot study investigating the effects of IBDNF on nutrition status in CD patients. Twenty-eight patients with active CD on stable medication were asked to consume 16 oz of IBDNF/d for 4 months. Nutrition status was assessed with dual-energy X-ray absorptiometry scans and serum micronutrient levels. Disease activity and quality of life were measured using the Crohn’s Disease Activity Index (CDAI) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Results Twenty patients completed the final visit. After 4 months, there was a significant decrease in plasma phospholipid levels of arachidonic acid with increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid. Ten patients had a final EPA concentration of >2%. There was improvement in fat-free and fat mass in patients with final EPA >2% (P = .014 and P = .05). Vitamin D (25-OH) levels improved in all patients (18.5–25.9 ng/mL, P < .001). Those with EPA >2% had significantly lower CDAI (116 ± 94.5 vs 261.8 ± 86.5; P = .005) and higher IBDQ (179.1 ± 26.6 vs 114.6 ± 35.9, P < .001) compared to those with EPA <2%. Conclusions IBDNF has the potential to deposit fat-free and fat mass, improve vitamin D status, and improve quality of life in CD patients. PMID:21775642

Brain activity related to phonation in young patients with adductor spasmodic dysphonia.

PubMed

Kiyuna, Asanori; Maeda, Hiroyuki; Higa, Asano; Shingaki, Kouta; Uehara, Takayuki; Suzuki, Mikio

2014-06-01

This study investigated the brain activities during phonation of young patients with adductor spasmodic dysphonia (ADSD) of relatively short disease duration (<10 years). Six subjects with ADSD of short duration (mean age: 24. 3 years; mean disease duration: 41 months) and six healthy controls (mean age: 30.8 years) underwent functional magnetic resonance imaging (fMRI) using a sparse sampling method to identify brain activity during vowel phonation (/i:/). Intragroup and intergroup analyses were performed using statistical parametric mapping software. Areas of activation in the ADSD and control groups were similar to those reported previously for vowel phonation. All of the activated areas were observed bilaterally and symmetrically. Intergroup analysis revealed higher brain activities in the SD group in the auditory-related areas (Brodmann's areas [BA] 40, 41), motor speech areas (BA44, 45), bilateral insula (BA13), bilateral cerebellum, and middle frontal gyrus (BA46). Areas with lower activation were in the left primary sensory area (BA1-3) and bilateral subcortical nucleus (putamen and globus pallidus). The auditory cortical responses observed may reflect that young ADSD patients control their voice by use of the motor speech area, insula, inferior parietal cortex, and cerebellum. Neural activity in the primary sensory area and basal ganglia may affect the voice symptoms of young ADSD patients with short disease duration. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Development of fluorescent methods for DNA methyltransferase assay

NASA Astrophysics Data System (ADS)

Li, Yueying; Zou, Xiaoran; Ma, Fei; Tang, Bo; Zhang, Chun-yang

2017-03-01

DNA methylation modified by DNA methyltransferase (MTase) plays an important role in regulating gene transcription, cell growth and proliferation. The aberrant DNA MTase activity may lead to a variety of human diseases including cancers. Therefore, accurate and sensitive detection of DNA MTase activity is crucial to biomedical research, clinical diagnostics and therapy. However, conventional DNA MTase assays often suffer from labor-intensive operations and time-consuming procedures. Alternatively, fluorescent methods have significant advantages of simplicity and high sensitivity, and have been widely applied for DNA MTase assay. In this review, we summarize the recent advances in the development of fluorescent methods for DNA MTase assay. These emerging methods include amplification-free and the amplification-assisted assays. Moreover, we discuss the challenges and future directions of this area.

Serum creatine kinase isoenzymes and macroenzymes in dogs with different neurologic diseases.

PubMed

Paltrinieri, Saverio; Pintore, Laura; Balducci, Federica; Giordano, Alessia; Costabile, Annaluce; Bernardini, Marco

2017-03-01

Increased serum activity of CK isoenzymes and macroenzymes, and in particular of the brain isoenzyme (CK-BB) has been reported in dogs with central nervous system (CNS) disorders. However, no studies on the possible differences in serum activities of CK iso- or macroenzymes (Macro-CK1 and Macro-CK2) in different neurologic diseases are available. The aim of this study was to describe the electrophoretic distribution of CK iso- and macroenzymes in dogs with CNS disorders in order to assess whether this distribution depends on a specific neurologic disease. This study was done on sera from 45 dogs with neurologic diseases (degenerative, n = 7; idiopathic epilepsy [IE], n = 14; inflammatory, n = 16; space occupying lesions [SOL], n = 8) and from 10 clinically healthy dogs. The separation of serum CK isoenzymes and macroenzymes was performed using an automated electrophoretic method already validated in dogs. Compared with healthy dogs, dogs with CNS disorders had significantly higher total CK and CK-BB activities, and a significantly lower Macro-CK2 activity (P < .001). Comparison of pathologic subgroups and healthy dogs revealed significant differences (P < .01) in dogs with IE and inflammatory disorders for total CK activity, in all the subgroups for CK-BB (P < .01), and in dogs with IE and SOL for Macro-CK2 (P < .01). The results of this study suggest that CK-BB is released by neurons damaged by inflammatory or degenerative conditions or due to compressive effects of SOL. However, the neurologic diseases cannot be differentiated based on CK-BB or Macro-CK2 activities, unless further studies allow the definition of diagnostic thresholds. © 2017 American Society for Veterinary Clinical Pathology.

Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn’s disease

PubMed Central

Oh, Eun Hye; Ko, Dae-Hyun; Seo, Hyungil; Chang, Kiju; Kim, Gwang-Un; Song, Eun Mi; Seo, Myeongsook; Lee, Ho-Su; Hwang, Sung Wook; Yang, Dong-Hoon; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun; Park, Sang Hyoung

2017-01-01

AIM To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn’s disease (CD) patients in Asian countries. METHODS IFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician’s judgment of patients’ clinical status at enrollment. The impact of concomitant immunomodulators was also investigated. RESULTS This study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083). CONCLUSION IFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice. PMID:28293096

Contrast-enhanced ultrasonography (CEUS) vs. MRI of the small bowel in the evaluation of Crohn's disease activity.

PubMed

Malagò, R; D'Onofrio, M; Mantovani, W; D'Alpaos, G; Foti, G; Pezzato, A; Caliari, G; Cusumano, D; Benini, L; Pozzi Mucelli, R

2012-03-01

The presence of disease activity in Crohn's disease (CD) is one of the main parameters used to establish whether optimal therapy should be drug therapy or surgery. However, a major problem in monitoring CD is the common mismatch between the patient's symptoms and imaging objective signs of disease activity. Bowel ultrasonography (US) has emerged as a low-cost, noninvasive technique in the diagnosis and follow-up of patients with CD. Accordingly, the use of contrast-enhanced US (CEUS) has made possible an evaluation of the vascular enhancement pattern, similar to the use of magnetic resonance imaging (MRI). The aim of our study was to evaluate the role of CEUS in comparison with small-bowel MRI for assessing Crohn's disease activity. We prospectively enrolled 30 consecutive patients with known CD. Clinical and laboratory data were compared with imaging findings obtained from MRI and CEUS of the small bowel. MRI was performed with a 1.5-T system using phased-array coils and biphasic orally administered contrast agent prior to and after gadolinium chelate administration. We performed US with a 7.5-MHz linear-array probe and a second-generation contrast agent. The parameters analysed in both techniques were the following: lesion length, wall thickness, layered wall appearance, comb sign, fibroadipose proliferation, presence of enlarged lymph nodes and stenosis. We classified parietal enhancement curves into two types in relation to the contrast pattern obtained with the time-intensity curves at MRI and CEUS: (1) quick washin, quick washout, (2) slow washin, plateau with a slow washout. Comparison between Crohn's disease activity index (CDAI) and MRI showed a low correlation, with an rho=0.398; correlation between CDAI-laboratory data and CEUS activity was low, with rho=0.354; correlation between MRI activity and CEUS activity was good, with rho = 0.791; high correlation was found between CEUS and MRI of the small bowel when assessing wall-thickness, lymph nodes and comb sign; good correlation was fund when assessing layered wall appearance, disease extension and fibroadipose proliferation. At MRI, time-intensity curves for 12/30 patients were active, compared with for 14/30 patients at CEUS; therefore there was a poor correlation between curve on CEUS and curve on MRI (r=0.167; p=0.36). The use of CEUS can be recommended if there is a discrepancy between MRI and clinical/laboratory parameters. MRI of the small bowel remains the most accurate method for evaluating disease activity.

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

PubMed Central

Nikiphorou, Elena; Norton, Sam; Young, Adam; Carpenter, Lewis; Dixey, Josh; Walsh, David Andrew; Kiely, Patrick

2016-01-01

Objectives To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6–3.2), low-moderate (LMDAS≥3.2–4.19), high-moderate (HMDAS 4.2–5.1) and high (HDAS>5.1). Results Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients. PMID:26979104

PDTCM: a systems pharmacology platform of traditional Chinese medicine for psoriasis.

PubMed

Wang, Dongmei; Gu, Jiangyong; Zhu, Wei; Luo, Fang; Chen, Lirong; Xu, Xiaojie; Lu, Chuanjian

2017-12-01

Psoriasis is a refractory skin disorder, and usually requires a lifetime control. Traditional Chinese medicine (TCM) is effective and safe for this disease. However, the cellular and molecular mechanisms of TCM remedies for psoriasis are still not fully understood. TCM contains numerous natural products. Natural products have historically been invaluable as a resource of therapeutic agents. Yet, there is no integrated information about active compounds of TCM for psoriasis. We use systems pharmacology methods to develop the Psoriasis Database of Traditional Chinese Medicine (PDTCM). The database covered a number of psoriasis-related information (formulas, TCM, compounds, target proteins, diseases and biomarkers). With these data information, an online platform was constructed Results: PDTCM comprises 38 empirical therapeutic formulas, 34373 compounds from 1424 medicinal plants, 44 psoriasis-related proteins and 76 biomarkers from 111 related diseases. On this platform, users can screen active compounds for a psoriasis-related target and explore molecular mechanisms of TCM. Accordingly, users can also download the retrieved structures and data information with a defined value set. In addition, it helps to get a better understanding of Chinese prescriptions in disease treatment. With the systems pharmacology-based data, PDTCM would become a valuable resource for TCM in psoriasis-related research. Key messages PDTCM platform comprises a great deal of data on TCM and psoriasis. On this platform, users can retrieve and get needed information with systems pharmacology methods, such as active compounds screening, target prediction and molecular mechanisms exploration. It is a tool for psoriasis-related research on natural drugs systematically.

Body mass index and the rheumatoid arthritis swollen joint count: an observational study

PubMed Central

Caplan, Liron; Davis, Lisa A.; Bright, Christina M.; Kerr, Gail S.; Lazaro, Deana M.; Khan, Nasim A.; Richards, J. Steuart; Johnson, Dannette S.; Cannon, Grant W.; Reimold, Andreas M.; Mikuls, Ted R.

2012-01-01

Objective Obesity is a prevalent condition and a serious health concern. The relationship between obesity and RA disease activity and severity has not been adequately examined, and there are concerns that periarticular adipose tissue may reduce the utility of the joint examination. Methods We used a cross-sectional study to compare the performance of swollen joint count (SJC) in subjects with rheumatoid arthritis (RA) across body mass index (BMI) strata. Specifically, regression techniques tested for associations of SJC and seven RA disease activity/severity measures (including high sensitivity c-reactive protein, radiographic changes, and multi-dimensional health assessment questionnaire scores) within BMI quartiles. We also evaluated the association of BMI with radiographic evidence of RA in multivariate analyses and the association of BMI with SJC. Clinical and laboratory data from 980 Veterans Affairs Rheumatoid Arthritis (VARA) registry participants were analyzed using linear and logistic regression. Results Associations were evident between SJC and six of the seven examined RA disease activity/severity measures. SJC predicts RA disease activity/severity at least as well in more obese subjects as in subjects with lower BMIs, and there was a trend towards better performance in higher BMI individuals. Subjects with higher BMIs were marginally less likely to be characterized by radiographic changes (O.R. 0.98, p=0.051). We found no association between BMI and SJC. Conclusions BMI does not obscure the relationship of SJC and objective disease activity measures. There is a borderline association of higher BMI and likelihood of radiographic changes characteristic of RA after controlling for clinical characteristics. PMID:22623288

Comparative analysis of gingival crevicular fluid β-glucuronidase levels in health, chronic gingivitis and chronic periodontitis.

PubMed

Sanara, P P; Shereef, Mohammed; Hegde, Shashikanth; Rajesh, K S; Arun Kumar, M S; Mohamed, Shabeer

2015-08-01

Current methods available for periodontal disease diagnosis are seriously deficient in terms of accuracy, in the ability to predict ongoing or future disease activity and indeed in determining whether previously diseased sites are in an arrested phase or still active. One area that is receiving a great deal of attention is the biochemical investigation of gingival crevicular fluid (GCF). β-glucuronidase (βG) is one of the enzymes found in GCF that is involved in degradation of the ground substance and fibrillar components of host connective tissue. GCF βG activity might be a good indicator or predictor of periodontal disease activity. This study was conducted to estimate and compare the GCF βG levels in patients with healthy periodontium, chronic gingivitis, and chronic periodontitis. Subjects were classified into three groups of 20 patients each; healthy individuals, chronic gingivitis, and chronic periodontitis. After recording the plaque index, gingival index and probing pocket depth, 1 μL GCF was collected by placing a calibrated microcapillary pipette extracrevicularly and transferred to sterile plastic vials containing 350 μL of normal saline with 1% bovine serum albumin. Analysis of βG was done by spectrophotometry. βG levels in GCF were significantly higher in chronic periodontitis group (mean value - 2.04743), followed by chronic gingivitis group (mean - 1.11510) and healthy group (0.53643). Increased βG levels were observed in patients with increased periodontal destruction, hence GCF βG levels can be used as biochemical marker for periodontal disease activity.

Advances in physical activity monitoring and lifestyle interventions in obesity: a review.

PubMed

Bonomi, A G; Westerterp, K R

2012-02-01

Obesity represents a strong risk factor for developing chronic diseases. Strategies for disease prevention often promote lifestyle changes encouraging participation in physical activity. However, determining what amount of physical activity is necessary for achieving specific health benefits has been hampered by the lack of accurate instruments for monitoring physical activity and the related physiological outcomes. This review aims at presenting recent advances in activity-monitoring technology and their application to support interventions for health promotion. Activity monitors have evolved from step counters and measuring devices of physical activity duration and intensity to more advanced systems providing quantitative and qualitative information on the individuals' activity behavior. Correspondingly, methods to predict activity-related energy expenditure using bodily acceleration and subjects characteristics have advanced from linear regression to innovative algorithms capable of determining physical activity types and the related metabolic costs. These novel techniques can monitor modes of sedentary behavior as well as the engagement in specific activity types that helps to evaluate the effectiveness of lifestyle interventions. In conclusion, advances in activity monitoring have the potential to support the design of response-dependent physical activity recommendations that are needed to generate effective and personalized lifestyle interventions for health promotion.

[Using cluster analysis for evaluation of sensitivity to antibiotics of pathogens isolated from women with genital inflammatory diseases].

PubMed

Tsyganenko, A Ia; Kon', E V

2007-01-01

The study was conducted to evaluate sensitivity to 44 antibiotics of pathogens isolated from 183 women with genital inflammatory diseases and to offer schemes of antibacterial treatment. The pathogens (66.8%) were in associations. The probability of isolation of main bacteria and sexually transmitted microorganisms in different associations was estimated in the work. Using the methods of clustering analysis all the tested antibiotics were divided into 3 groups, depending on their antimicrobial activity toward bacteria isolated both in monoculture and in associations. Furagin, cefotaxime, gentamicin, cefoperazon, ceftriaxon, ciprofloxacin, pefloxacin, as well as, cefazolin, zoxan, ofloxacin, and lomefloxacin were shown to be the most effective antibiotics in vitro. The least activity was diplayed by ectericid, chlorophillipt, and ampiox. These data should be considered when choosing the antibacterial treatment of genital inflammatory diseases.

An ex vivo evaluation of the efficacy of andrographolide in modulating differential expression of transcription factors and target genes in periodontal cells and its potential role in treating periodontal diseases.

PubMed

Ambili R; Janam, Prasanthila; Saneesh Babu, P S; Prasad, Manu; Vinod, D; Anil Kumar, P R; Kumary, T V; Asha Nair, S; Radhakrishna Pillai, M

2017-01-20

Andrographolide is a herbal extract traditionally used in South Asian countries for treating inflammatory diseases. To evaluate the efficacy of andrographolide in management of periodontal disease which is a highly prevalent oral disease. Periodontal ligament fibroblasts (PDLF) were cultured from healthy and diseased periodontium using explant culture methods. The safe dose of AG was determined using MTT assay. LPS (lipopolysaccharide) of the most important periodontopathogen, P gingivalis was used to activate NF-κB and STAT3 in PDLF. The efficacy of AG in inhibiting NF-κB and STAT3 was analyzed using immunofluorescence. Down regulation of expression of target genes of these transcription factors related to inflammation and bone resorption were analyzed using real time PCR. AG up to the concentration of 25μM was found to be safe as determined by MTT assay. Statistically significant activation of NF-κB and STAT3 in cultured PDLF was observed in diseased group compared to healthy controls before and after LPS challenge. 5μM AG pretreatment significantly inhibited activation of NF-κB and STAT3 and down regulated expression of inflammatory and bone resorptive genes in cultured PDLF. The findings of the present study propose the adjunctive use of a novel herbal drug andrographolide as a promising host modulation agent for periodontal therapy by inhibiting NF-κB and STAT3 activation and inhibition of inflammation and bone resorption related genes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Alzheimer Disease Alters the Relationship of Cardiorespiratory Fitness With Brain Activity During the Stroop Task

PubMed Central

Gayed, Matthew R.; Honea, Robyn A.; Savage, Cary R.; Hobbs, Derek; Burns, Jeffrey M.

2013-01-01

Background Despite mounting evidence that physical activity has positive benefits for brain and cognitive health, there has been little characterization of the relationship between cardiorespiratory (CR) fitness and cognition-associated brain activity as measured by functional magnetic resonance imaging (fMRI). The lack of evidence is particularly glaring for diseases such as Alzheimer disease (AD) that degrade cognitive and functional performance. Objective The aim of this study was to describe the relationship between regional brain activity during cognitive tasks and CR fitness level in people with and without AD. Design A case-control, single-observation study design was used. Methods Thirty-four individuals (18 without dementia and 16 in the earliest stages of AD) completed maximal exercise testing and performed a Stroop task during fMRI. Results Cardiorespiratory fitness was inversely associated with anterior cingulate activity in the participants without dementia (r=−.48, P=.05) and unassociated with activation in those with AD (P>.7). Weak associations of CR fitness and middle frontal cortex were noted. Limitations The wide age range and the use of a single task in fMRI rather than multiple tasks challenging different cognitive capacities were limitations of the study. Conclusions The results offer further support of the relationship between CR fitness and regional brain activity. However, this relationship may be attenuated by disease. Future work in this area may provide clinicians and researchers with interpretable and dependable regional fMRI biomarker signatures responsive to exercise intervention. It also may shed light on mechanisms by which exercise can support cognitive function. PMID:23559521

Advances in the analytical methods for determining the antioxidant properties of honey: a review.

PubMed

Moniruzzaman, M; Khalil, M I; Sulaiman, S A; Gan, S H

2012-01-01

Free radicals and reactive oxygen species (ROS) have been implicated in contributing to the processes of aging and disease. In an effort to combat free radical activity, scientists are studying the effects of increasing individuals' antioxidant levels through diet and dietary supplements. Honey appears to act as an antioxidant in more ways than one. In the body, honey can mop up free radicals and contribute to better health. Various antioxidant activity methods have been used to measure and compare the antioxidant activity of honey. In recent years, DPPH (Diphenyl-1-picrylhydrazyl), FRAP (Ferric Reducing Antioxidant Power), ORAC (The Oxygen Radical Absorbance Capacity), ABTS [2, 2-azinobis (3ehtylbenzothiazoline-6-sulfonic acid) diamonium salt], TEAC [6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (Trolox)-equivalent antioxidant capacity] assays have been used to evaluate antioxidant activity of honey. The antioxidant activity of honey is also measured by ascorbic acid content and different enzyme assays like Catalase (CAT), Glutathione Peroxidase (GPO), Superoxide Dismutase (SOD). Among the different methods available, methods that have been validated, standardized and widely reported are recommended.

[Detection of respiratory tract diseases among rural population during the team-work mass screening].

PubMed

Abramson, E Z; Galkin, V B; Stepanova, G Ia

1990-01-01

A screening complex for the examination of the rural population has been worked out to detect bronchopulmonary pathology and form groups of risk for respiratory diseases. The complex of methods included compulsory questionnaires and ++fluoro-functional examination, spirometry if indicated and bacterial tests. Out of 1, 131 persons examined, 328 were found to have respiratory diseases. Chronic non-specific respiratory diseases were detected in 103 subjects, including 62 of them having obstructive bronchitis. A risk group developing chronic non-specific respiratory diseases, including 202 persons with disturbed ventilation activity of the lungs, post-tuberculous inadequate changes and other pathology. Pulmonary tuberculosis was registered in 7 subjects. The given data indicate the necessity of a complex examination of the population.

Satellite cell proliferation in adult skeletal muscle

NASA Technical Reports Server (NTRS)

Morrison, Paul R. (Inventor); Thomason, Donald B. (Inventor); Stancel, George M. (Inventor); Booth, Frank W. (Inventor)

1995-01-01

Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

The progress in the cholinesterase quantification methods.

PubMed

Holas, Ondrej; Musilek, Kamil; Pohanka, Miroslav; Kuca, Kamil

2012-12-01

Determination of acetylcholinesterase and butyrylcholinesterase activity has become an important tool in drug design and discovery as well as in medicine and toxicology. There are a large number of compounds that are able to modulate cholinesterase activity. These compounds can be used for pharmacological management of various disorders (e.g., Alzheimer's disease, myasthenia Gravis). Moreover, organophosphate poisoning is frequently diagnosed via a cholinesterase activity assay. This broad variety of methods has been developed over the past decades for cholinesterase activity quantification. This review provides a summary of the methods that are based on specific properties of cholinesterases and their interactions with native or artificial substrates. The authors also aim to provide an overview of different techniques used for the determination of quantitative cholinesterase activity. Specifically, the authors describe and discuss the manometric, potentiometric, titrimetric, photometric, fluorometric, and radioisotopic methods. Existing methods are able to cover most of the problems that arise during cholinesterase activity determination. Colorimetry according to Ellman has proved to be the most useful and versatile approach. It may be used in various protocols for the determination of pesticide or nerve agent exposure or for the development of new drugs. Its possible improvement lies in optimization of hemoglobin-rich samples. The progress of the most common methods (including Ellman) depends on miniaturization and modern physical platforms (e.g., optical fibers, chip methods, or nanotechnologies).

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

PubMed

Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

2018-03-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

PubMed Central

Gray, Alan; Neyton, Lucile P. A.; Barrett, Jeffrey; Stahl, Eli A.; Tenesa, Albert; Andersson, Robin; Brown, J. Ben; Faulkner, Geoffrey J.; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Kawaji, Hideya; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A.; Hacohen, Nir; Freeman, Thomas C.; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Hume, David A.

2018-01-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits. PMID:29494619

INFLUENCE OF EXERCISE TESTING IN GASTROESOPHAGEAL REFLUX IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE

PubMed Central

MENDES-FILHO, Antonio Moreira; MORAES-FILHO, Joaquim Prado Pinto; NASI, Ary; EISIG, Jaime Natan; RODRIGUES, Tomas Navarro; BARBUTTI, Ricardo Correa; CAMPOS, Josemberg Marins; CHINZON, Décio

2014-01-01

Background Gastroesophageal reflux disease is a worldwide prevalent condition that exhibits a large variety of signs and symptoms of esophageal or extra-esophageal nature and can be related to the esophagic adenocarcinoma. In the last few years, greater importance has been given to the influence of physical exercises on it. Some recent investigations, though showing conflicting results, point to an exacerbation of gastroesophageal reflux during physical exercises. Aim To evaluate the influence of physical activities in patients presenting with erosive and non erosive disease by ergometric stress testing and influence of the lower esophageal sphincter tonus and body mass index during this situation. Methods Twenty-nine patients with erosive disease (group I) and 10 patients with non-erosive disease (group II) were prospectively evaluated. All the patients were submitted to clinical evaluation, followed by upper digestive endoscopy, manometry and 24 h esophageal pH monitoring. An ergometric testing was performed 1 h before removing the esophageal pH probe. During the ergometric stress testing, the following variables were analyzed: test efficacy, maximum oxygen uptake, acid reflux duration, gastroesophageal reflux symptoms, influence of the lower esophageal sphincter tonus and influence of body mass index in the occurrence of gastroesophageal reflux during these physical stress. Results Maximum oxigen consumption or VO 2 max, showed significant correlation when it was 70% or higher only in the erosive disease group, evaluating the patients with or without acid reflux during the ergometric testing (p=0,032). The other considered variables didn't show significant correlations between gastroesophageal reflux and physical activity (p>0,05). Conclusions 1) Highly intensive physical activity can predispose the occurrence of gastroesophageal reflux episodes in gastroesophageal reflux disease patients with erosive disease; 2) light or short sessions of physical activity have no influence on reflux, regardless of body mass index; 3) the lower esophageal sphincter tonus does not influence the occurrence of reflux disease episodes during exercise testing. PMID:24676289

A novel method to identify herds with an increased probability of disease introduction due to animal trade.

PubMed

Frössling, Jenny; Nusinovici, Simon; Nöremark, Maria; Widgren, Stefan; Lindberg, Ann

2014-11-15

In the design of surveillance, there is often a desire to target high risk herds. Such risk-based approaches result in better allocation of resources and improve the performance of surveillance activities. For many contagious animal diseases, movement of live animals is a main route of transmission, and because of this, herds that purchase many live animals or have a large contact network due to trade can be seen as a high risk stratum of the population. This paper presents a new method to assess herd disease risk in animal movement networks. It is an improvement to current network measures that takes direction, temporal order, and also movement size and probability of disease into account. In the study, the method was used to calculate a probability of disease ratio (PDR) of herds in simulated datasets, and of real herds based on animal movement data from dairy herds included in a bulk milk survey for Coxiella burnetii. Known differences in probability of disease are easily incorporated in the calculations and the PDR was calculated while accounting for regional differences in probability of disease, and also by applying equal probability of disease throughout the population. Each herd's increased probability of disease due to purchase of animals was compared to both the average herd and herds within the same risk stratum. The results show that the PDR is able to capture the different circumstances related to disease prevalence and animal trade contact patterns. Comparison of results based on inclusion or exclusion of differences in risk also highlights how ignoring such differences can influence the ability to correctly identify high risk herds. The method shows a potential to be useful for risk-based surveillance, in the classification of herds in control programmes or to represent influential contacts in risk factor studies. Copyright © 2014 Elsevier B.V. All rights reserved.

An unusual white blood cell scan in a child with inflammatory bowel disease: a case report.

PubMed

Porn, U; Howman-Giles, R; O'Loughlin, E; Uren, R; Chaitow, J

2000-10-01

Technetium-99m-labeled leukocyte (WBC) imaging is a valuable screening method for inflammatory bowel disease, especially in children, because of its high rate of sensitivity, low cost, and ease of preparation. A 14-year-old girl is described who had juvenile arthritis and iritis complicated by inflammatory bowel disease. She was examined for recurrent abdominal pain. A Tc-99m stannous colloid WBC scan was performed, and tracer accumulation was seen in the small bowel in the region of the distal ileum on the initial 1-hour image. Delayed imaging at 3 hours also revealed tracer accumulation in the cecum and ascending colon, which was not seen on the early image. A biopsy of the colon during endoscopy showed no evidence of active inflammation in the colon. The small bowel was not seen. Computed tomography revealed changes suggestive of inflammatory bowel disease in the distal ileum. The appearance on the WBC study was most likely a result of inflammatory bowel disease involving the distal ileum, with transit of luminal activity into the large bowel.

Low dose radiation adaptive protection to control neurodegenerative diseases.

PubMed

Doss, Mohan

2014-05-01

Concerns have been expressed recently regarding the observed increased DNA damage from activities such as thinking and exercise. Such concerns have arisen from an incomplete accounting of the full effects of the increased oxidative damage. When the effects of the induced adaptive protective responses such as increased antioxidants and DNA repair enzymes are taken into consideration, there would be less endogenous DNA damage during the subsequent period of enhanced defenses, resulting in improved health from the thinking and exercise activities. Low dose radiation (LDR), which causes oxidative stress and increased DNA damage, upregulates adaptive protection systems that may decrease diseases in an analogous manner. Though there are ongoing debates regarding LDR's carcinogenicity, with two recent advisory committee reports coming to opposite conclusions, data published since the time of the reports have overwhelmingly ruled out its carcinogenicity, paving the way for consideration of its potential use for disease reduction. LDR adaptive protection is a promising approach to control neurodegenerative diseases, for which there are no methods of prevention or cure. Preparation of a compelling ethics case would pave the way for LDR clinical studies and progress in dealing with neurodegenerative diseases.

Improving Value for Patients with Eczema.

PubMed

Block, Julie

2018-04-01

Chronic diseases now represent a cost majority in the United States health care system. Contributing factors to rising costs include expensive novel and emerging therapies, under-treatment of disease, under-management of comorbidities, and patient dissatisfaction with care results. Critical to identifying replicable improvement methods is a reliable model to measure value. If we understand value within healthcare consumerism to be equal to a patient's health outcome improvement over costs associated with care (Value=Outcomes/Costs), we can use this equation to measure the improvement of value. Research and literature show that patient activation-the skills and confidence that equip patients to become actively engaged in their health care-impact health outcomes, costs, and patient experience. Reaching patient activation through engagement methods including shared decision-making (SDM) lead to improved value of care received. The National Eczema Association (NEA) Shared Decision-Making Resource Center can be a transformative strategy to measure and evaluate value of health care interventions for eczema patients to advance a value-driven health care system in the United States. Through this Resource Center, NEA will measure patient value through their own perceptions using validated PRO instruments and other patient-generated health data. Assessment of this data will reveal findings that can assist researchers in evaluating the impact this care framework on patient-perceived value across other chronic diseases. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Designing Culturally Relevant Physical Activity Programs for African American Women: A Framework for Intervention Development

PubMed Central

Keller, Colleen; Affuso, Oliva; Ainsworth, Barbara E.

2016-01-01

Background African American women perform low levels of physical activity and are disproportionally burdened by associated cardiometabolic disease conditions (i.e. 57% are obese, 49% have cardiovascular disease) The marked health disparities among African American women indicate the need for innovative strategies to promote physical activity to help attenuate the chronic disease health disparities in this high-risk population. Culturally tailoring PA programs to address the sociocultural norms, values, beliefs, and behaviors of African American women is an advantageous strategy to enhance physical activity promotion efforts. The purpose of this article is to discuss critical aspects for researchers to consider when designing physical activity programs for African American women and to present a conceptual framework to guide intervention development. Methods Development of the framework was based on our previous physical activity research with African American women, seminal literature on the topics of cultural adaptation and health promotion, sociological and theoretical perspectives on the role of women in African American culture, and key determinants of physical activity engagement among African American women. Results Three key concepts are discussed in the conceptual framework: 1) Developmental milestones and life stage transitions of African American women, 2) Historical, social and cultural influences associated with physical activity engagement, and 3) Intervention delivery strategies. Discussion Using the framework to guide intervention development has the potential to enhance the physical activity and health outcomes of a physical activity program for African American women. PMID:27178447

[Serum anticholinergic activity: relationship with clinical symptoms in Alzheimer's disease and proposal of new biological marker].

PubMed

Hori, Koji; Konishi, Kimiko; Hachisu, Mitsugu

2011-06-01

We reviewed the importance of measuring serum anticholinergic activity (SAA) in patients with Alzheimer's disease (AD). Since Tune and Coyle reported a simple method for assessing SAA using radioreceptor-binding assay, SAA is assumed to be the cumulative activity of parent medications and their metabolites and its relationship with delirium and cognitive functions has been debated. However, we evaluated the SAA in AD patients and SAA was correlated with prescription of antipsychotic medications, cognitive dysfunctions, severity of AD and psychotic symptoms, especially, with delusion and diurnal rhythm disturbance. From these results, we should not only pay attention to avoiding the prescription of medications with anticholinergic activity but also we speculated that AA appeared endogenously in AD and accelerated AD pathology. Moreover, there might be the possibility that SAA has predictive value for assessing the progressiveness of AD and as a biological marker for AD.

How medicine has become a science?

PubMed

Zieliński, Andrzej

2014-01-01

The historical review of medical activities draws attention how late in its very long history therapies of proven effectiveness were introduced. Author attributes it to the late development of methods which would be capable to determine the causal relations which would scientifically justified identification the causes and risk factors of diseases as well as checking the effectiveness of preventive and therapeutic procedures. Among the fundamental tools for scientific knowledge of the causes and mechanisms of diseases, the author indicates: achievements of basic science and the development of epidemiological methods used to study causal relationships. In the author's opinion the results of basic research are an essential source of variables among which, with an increased likelihood could be found the causes and risk factors of studied conditions, including diseases. The author also stresses the role of medical technology, which is the primary source of potential medicines, other therapeutic procedures and diagnostic methods whose effectiveness is tested in experimental epidemiological studies. Medical technologies create also tools for the development of basic sciences.

Development of the Korean Academy of Medical Sciences Guideline for Rating the Impairment in the Brain Injured and Brain Diseased Persons with Motor Dysfunction

PubMed Central

Baik, Jong Sam; Jang, Seong Ho; Park, Dong Sik

2009-01-01

To develop an objective and scientific method to evaluate the brain injured and brain diseased persons with motor dysfunction, American Medical Association's Guides to the Evaluation of Permanent Impairment was used as an exemplar. After the motor dysfunction due to brain injury or brain disease was confirmed, active range of motion and muscle strength of affected extremities were measured. Also, the total function of extremities was evaluated through the assessment of activities of daily living, fine coordination of hand, balance and gait. Then, the total score of manual muscle test and functional assessment of impaired upper and lower extremity were added, respectively. Spasticity of upper and lower extremity was used as minus factors. Patients with movement disorder such as Parkinson's disease were assessed based on the degree of dysfunction in response to medication. We develop a new rating system based on the concept of total score. PMID:19503680

Emerging diagnostic and therapeutic molecular imaging applications in vascular disease

PubMed Central

Eraso, Luis H; Reilly, Muredach P; Sehgal, Chandra; Mohler, Emile R

2013-01-01

Assessment of vascular disease has evolved from mere indirect and direct measurements of luminal stenosis to sophisticated imaging methods to depict millimeter structural changes of the vasculature. In the near future, the emergence of multimodal molecular imaging strategies may enable robust therapeutic and diagnostic (‘theragnostic’) approaches to vascular diseases that comprehensively consider structural, functional, biological and genomic characteristics of the disease in individualized risk assessment, early diagnosis and delivery of targeted interventions. This review presents a summary of recent preclinical and clinical developments in molecular imaging and theragnostic applications covering diverse atherosclerosis events such as endothelial activation, macrophage infammatory activity, plaque neovascularization and arterial thrombosis. The main focus is on molecular targets designed for imaging platforms commonly used in clinical medicine including magnetic resonance, computed tomography and positron emission tomography. A special emphasis is given to vascular ultrasound applications, considering the important role this imaging platform plays in the clinical and research practice of the vascular medicine specialty. PMID:21310769

Nitric Oxide Homeostasis in Neurodegenerative Diseases.

PubMed

Hannibal, Luciana

2016-01-01

The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases (NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.

Bioinformatics in protein kinases regulatory network and drug discovery.

PubMed

Chen, Qingfeng; Luo, Haiqiong; Zhang, Chengqi; Chen, Yi-Ping Phoebe

2015-04-01

Protein kinases have been implicated in a number of diseases, where kinases participate many aspects that control cell growth, movement and death. The deregulated kinase activities and the knowledge of these disorders are of great clinical interest of drug discovery. The most critical issue is the development of safe and efficient disease diagnosis and treatment for less cost and in less time. It is critical to develop innovative approaches that aim at the root cause of a disease, not just its symptoms. Bioinformatics including genetic, genomic, mathematics and computational technologies, has become the most promising option for effective drug discovery, and has showed its potential in early stage of drug-target identification and target validation. It is essential that these aspects are understood and integrated into new methods used in drug discovery for diseases arisen from deregulated kinase activity. This article reviews bioinformatics techniques for protein kinase data management and analysis, kinase pathways and drug targets and describes their potential application in pharma ceutical industry. Copyright © 2015 Elsevier Inc. All rights reserved.

Correlation between clinical severity of central nervous system (CNS) lupus and findings on single photon emission computed tomographic (SPECT) images of the brain; preliminary results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silverman, I.E.; Zeit, R.M.; Von Feldt, J.M.

1994-05-01

Systemic Lupus Erythematosis (SLE) commonly causes significant neuropsychiatric disorders. The purpose of this study was to review the brain SPECT studies of SLE patients with clinical evidence of CNS involvement and determine whether there is a correlation between the findings on SPECT images and the clinical manifestations of this serious phase of the disease. We enrolled 19 SLE patients and 12 normal controls in this study. The level of each patient`s disease activity was determined by the SLE Disease Activity Index (SLEDAI), an established method of scoring disease severity which is heavily weighted toward neuropsychiatric symptomatology, for 15 of themore » 19 SLE patients. The SLEDAI was calculated within a 10 day window of the date when the SPECT scan was obtained. SPECT scans were performed 30 minutes following the intravenous administration of 99mTc-HMPAO. Results are discussed.« less

Generic protease detection technology for monitoring periodontal disease.

PubMed

Zheng, Xinwei; Cook, Joseph P; Watkinson, Michael; Yang, Shoufeng; Douglas, Ian; Rawlinson, Andrew; Krause, Steffi

2011-01-01

Periodontal diseases are inflammatory conditions that affect the supporting tissues of teeth and can lead to destruction of the bone support and ultimately tooth loss if untreated. Progression of periodontitis is usually site specific but not uniform, and currently there are no accurate clinical methods for distinguishing sites where there is active disease progression from sites that are quiescent. Consequently, unnecessary and costly treatment of periodontal sites that are not progressing may occur. Three proteases have been identified as suitable markers for distinguishing sites with active disease progression and quiescent sites: human neutrophil elastase, cathepsin G and MMP8. Generic sensor materials for the detection of these three proteases have been developed based on thin dextran hydrogel films cross-linked with peptides. Degradation of the hydrogel films was monitored using impedance measurements. The target proteases were detected in the clinically relevant range within a time frame of 3 min. Good specificity for different proteases was achieved by choosing appropriate peptide cross-linkers.

Correlation between disease severity and brain electric LORETA tomography in Alzheimer's disease.

PubMed

Gianotti, Lorena R R; Künig, Gabriella; Lehmann, Dietrich; Faber, Pascal L; Pascual-Marqui, Roberto D; Kochi, Kieko; Schreiter-Gasser, Ursula

2007-01-01

To compare EEG power spectra and LORETA-computed intracortical activity between Alzheimer's disease (AD) patients and healthy controls, and to correlate the results with cognitive performance in the AD group. Nineteen channel resting EEG was recorded in 21 mild to moderate AD patients and in 23 controls. Power spectra and intracortical LORETA tomography were computed in seven frequency bands and compared between groups. In the AD patients, the EEG results were correlated with cognitive performance (Mini Mental State Examination, MMSE). AD patients showed increased power in EEG delta and theta frequency bands, and decreased power in alpha2, beta1, beta2 and beta3. LORETA specified that increases and decreases of power affected different cortical areas while largely sparing prefrontal cortex. Delta power correlated negatively and alpha1 power positively with the AD patients' MMSE scores; LORETA tomography localized these correlations in left temporo-parietal cortex. The non-invasive EEG method of LORETA localized pathological cortical activity in our mild to moderate AD patients in agreement with the literature, and yielded striking correlations between EEG delta and alpha1 activity and MMSE scores in left temporo-parietal cortex. The present data support the hypothesis of an asymmetrical progression of the Alzheimer's disease.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PubMed

Maruyama, Hiroki; Miyata, Kaori; Mikame, Mariko; Taguchi, Atsumi; Guili, Chu; Shimura, Masaru; Murayama, Kei; Inoue, Takeshi; Yamamoto, Saori; Sugimura, Koichiro; Tamita, Koichi; Kawasaki, Toshihiro; Kajihara, Jun; Onishi, Akifumi; Sugiyama, Hitoshi; Sakai, Teiko; Murata, Ichijiro; Oda, Takamasa; Toyoda, Shigeru; Hanawa, Kenichiro; Fujimura, Takeo; Ura, Shigehisa; Matsumura, Mimiko; Takano, Hideki; Yamashita, Satoshi; Matsukura, Gaku; Tazawa, Ryushi; Shiga, Tsuyoshi; Ebato, Mio; Satoh, Hiroshi; Ishii, Satoshi

2018-03-15

PurposePlasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females.MethodsBetween 1 July 2014 and 31 December 2015, we screened 2,360 patients (1,324 males) referred from 169 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively.ResultsOf 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml -1 ) and low α-Gal A activity (≤4.0 nmol h -1  ml -1 ), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 15 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 8 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance).ConclusionPlasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.Genet Med advance online publication, 15 March 2018; doi:10.1038/gim.2018.31.

Children with chronic disease and extracurricular activities: training needs

PubMed

Desserprix, Agnès; Marchand, Claire; Crozet, Cyril

2016-10-19

Background: ln the current context of increasing numbers of children living with a chronic disease and increasing numbers of people supervising extracurricular activities, difficulties appear to persist despite the Personalised Core Project (PCP). This study explores the accessibility and usefulness of the information provided by the Personalised Care Project and the value of complementary support. Methods: Based on the key messages identified by experts in the four most common chronic diseases, a questionnaire was deve/oped and sent to people supervising extracurricular activities in three districts of the Saône-et-Loire department. Descriptive statistical analysis was performed. Results: 55 people participated in the study. 30 (54.5%) had already supervised children with a chronic disease, 21 (70%) of them had been able to read the PCP and 17 (57%) had participated in an information meeting. 23 out of 28 (82%) considered thot the information contained in the PCP was helpful and 21 (81%) expressed their needs for further information. 98% of respondents thought thot additional support would be useful. Their main needs corresponded to 3 main self-core ski/Js: to recognize, analyse and measure; to deal with and decide; to resolve prevention problems. Conclusion: This study confirms the value of the PCP, but also the Jack of preparation of people supervising extracurricu/ar activ ities. lt highlights the need for training to allow these people to ensure the safety of chi /dren living with chronic diseases.

Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Yang, Guoyan; Wang, Yuyi; Tian, Jinzhou; Liu, Jian-Ping

2013-01-01

Background Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease. Methods We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249) Results 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A. Conclusions Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials. PMID:24086396

18F-Labelled catecholamine type radiopharmaceuticals in the diagnosis of neurodegenerative diseases and neuroendocrine tumours: approaches to synthesis and development prospects

NASA Astrophysics Data System (ADS)

Vatsadze, S. Z.; Eremina, O. E.; Veselova, I. A.; Kalmykov, S. N.; Nenajdenko, V. G.

2018-04-01

The pathogenesis of many socially significant diseases such as neurodegenerative dementias and neuroendocrine tumours involves imbalance of neurotransmitters. Among the known neuroimaging methods, positron emission tomography (PET) is the most perfect and informative technique for diagnosing these diseases. The potential of PET is largely determined by the inventory of available radiopharmaceuticals, that is, biologically active molecules containing short-lived nuclides with positron decay. This review gives a systematic account of the application of fluorine-18-labelled catecholamine type radiopharmaceuticals in clinical investigations of the sympathetic and central nervous systems. The methods for the synthesis of these agents and existing problems are considered. The material is arranged according to the mechanisms of reactions that underlie the synthetic approaches: electrophilic, nucleophilic and metal-catalyzed reactions. The bibliography includes 198 references.

[Latest progress on diagnosis and treatment of glenohumeral instability].

PubMed

Zhao, Gang; Liu, Yu-Jie

2014-02-01

As a common and frequently-occurring disease,glenohumeral instability is become one of disease which restrict upper limb activity. The diagnosis of this disease is easy, but it is very difficult to assess the degree of periarticular soft tissue injuries. With the development of magnetic resonance imaging and arthroscopy, MRA become the gold standard for evaluation of glenoid labrum, joint capsule and ligaments injury. The traditional manual reduction is a fast, simple method, but often can cause adverse consequences,such as rotator cuff tear,ligament relaxation,and habitual dislocation. Open operation can rebuild stability of joint,but with many new treatment methods,especially the arthroscopic reconstruction has gradually replaced the open operation, and become the mainstream trend, but for the long-term effect of capsular tightening surgery, rotator cuff gap closure is not clear,it is need further follow-up observation.

Methicillin-Resistant Staphylococcus aureus Control in the 21st Century: Laboratory Involvement Affecting Disease Impact and Economic Benefit from Large Population Studies

PubMed Central

Schora, Donna M.

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a global health care problem. Large studies (e.g., >25,000 patients) show that active surveillance testing (AST) followed by contact precautions for positive patients is an effective approach for MRSA disease control. With this approach, the clinical laboratory will be asked to select what AST method(s) to use and to provide data monitoring outcomes of the infection prevention interventions. This minireview summarizes evidence for MRSA disease control, reviews the involvement of the laboratory, and provides examples of how to undertake a program cost analysis. Health care organizations with total MRSA clinical infections of >0.3/1,000 patient days or bloodstream infections of >0.03/1,000 patient days should implement a MRSA control plan. PMID:27307459

Evidence of Secular Changes in Physical Activity and Fitness, but Not Adiposity and Diet, in Welsh 12-13 Year Olds

ERIC Educational Resources Information Center

Thomas, Non E.; Williams, D. R. R.; Rowe, David A.; Davies, Bruce; Baker, Julien S.

2010-01-01

Objective: The aim of the present study was to investigate secular trends in selected cardiovascular disease risk factors (namely adiposity, physical activity, physical fitness and diet) in a sample of Welsh 12-13 year olds between 2002 and 2007. Design: Cross-sectional. Setting: A secondary school based in South West Wales. Method: Two studies in…

Ileal Crohn disease: mural microvascularity quantified with contrast-enhanced US correlates with disease activity.

PubMed

De Franco, Antonio; Di Veronica, Alessandra; Armuzzi, Alessandro; Roberto, Italia; Marzo, Manuela; De Pascalis, Barbara; De Vitis, Italo; Papa, Alfredo; Bock, Enrico; Danza, Francesco M; Bonomo, Lorenzo; Guidi, Luisa

2012-02-01

To quantitatively assess microvascular activation in the thickened ileal walls of patients with Crohn disease (CD) by using contrast-enhanced ultrasonography (US) and evaluate its correlation with widely used indexes of CD activity. This prospective study was approved by the ethics committee, and written informed consent was obtained from all patients. The authors examined 54 consecutively enrolled patients (mean age, 35.29 years; age range, 18-69 years; 39 men, 15 women) with endoscopically confirmed CD of the terminal ileum. Ileal wall segments thicker than 3 mm were examined with low-mechanical-index contrast-enhanced US and a second-generation US contrast agent. The authors analyzed software-plotted time-enhancement intensity curves to determine the maximum peak intensity (MPI) and wash-in slope coefficient (β) and evaluated their correlation with (a) the composite index of CD activity (CICDA), (b) the CD activity index (CDAI), and (c) the simplified endoscopic score for CD (SES-CD, evaluated in 37 patients) for the terminal ileum. Statistical analysis was performed with the Mann-Whitney test, Spearman rank test, and receiver operating characteristic (ROC) analysis. MPI and β coefficients were significantly increased in the 36 patients with a CICDA indicative of active disease (P<.0001 for both), the 33 patients with a CDAI of at least 150 (P<.032 and P<.0074, respectively), and the 26 patients with an SES-CD of at least 1 (P<.0001 and P<.002, respectively). ROC analysis revealed accurate identification (compared with CICDA) of active CD with an MPI threshold of 24 video intensity (VI) (sensitivity, 97%; specificity, 83%) and a β coefficient of 4.5 VI/sec (sensitivity, 86%; specificity, 83%). Contrast-enhanced US of the ileal wall is a promising method for objective, reproducible assessment of disease activity in patients with ileal CD. © RSNA, 2011

Mito-magneto: A Tool for Nanoparticle Mediated Mitochondria Isolation†

PubMed Central

Banik, Bhabatosh; Askins, Brett W.; Dhar, Shanta

2016-01-01

The field of intracellular organelle targeting using nanoparticles (NPs) is mushrooming rapidly. Thus, the area of nanotechnology-enabled targeting of mitochondrion, the cellular powerhouse, for diseases characterized by mitochondrial dysfunctions such as cancer, diseases of the central nervous system, cardiovascular diseases is also growing at a rapid pace. Optimization of NP’s ability to target the mitochondria requires quantification of the particles in this subcellular organelle and isolation of mitochondria from cells. Conventional gradient centrifugation used in currently available methods may not be appropriate for NP containing mitochondria isolation as these particles undergo Brownian motion under centrifugal forces yielding irreproducible results. There is only one method for centrifugation free mitochondria isolation, however this method requires immune-precipitation. Thus, a reliable centrifugation and immune-precipitation free method is urgently needed to support this growing field of nanotechnology-based mitochondria targeting. Here, we report a mitochondria-targeted magnetic NP, Mito-magneto, to avoid centrifugation and immune precipitation methods for isolation of functional, respiration active pure mitochondria which can be used to analyze and quantify mitochondria targeting properties of various NPs to provide an important tool for the growing field of “mitochondrial nanomedicine”. PMID:27735003

Aggressive periodontitis: case definition and diagnostic criteria.

PubMed

Albandar, Jasim M

2014-06-01

Aggressive periodontitis is a destructive disease characterized by the following: the involvement of multiple teeth with a distinctive pattern of periodontal tissue loss; a high rate of disease progression; an early age of onset; and the absence of systemic diseases. In some patients periodontal tissue loss may commence before puberty, whereas in most patients the age of onset is during or somewhat after the circumpubertal period. Besides infection with specific microorganisms, a host predisposition seems to play a key role in the pathogenesis of aggressive periodontitis, as evidenced by the familial aggregation of the disease. In this article we review the historical background of the diagnostic criteria of aggressive periodontitis, present a contemporary case definition and describe the clinical parameters of the disease. At present, the diagnosis of aggressive periodontitis is achieved using case history, clinical examination and radiographic evaluation. The data gathered using these methods are prone to relatively high measurement errors. Besides, this diagnostic approach measures past disease history and may not reliably measure existing disease activity or accurately predict future tissue loss. A diagnosis is often made years after the onset of the disease, partly because current assessment methods detect established disease more readily and reliably than they detect incipient or initial lesions where the tissue loss is minimal and usually below the detection threshold of present examination methods. Future advancements in understanding the pathogenesis of this disease may contribute to an earlier diagnosis. Insofar, future case definitions may involve the identification of key etiologic and risk factors, combined with high-precision methodologies that enable the early detection of initial lesions. This may significantly enhance the predictive value of these tests and detect cases of aggressive periodontitis before significant tissue loss develops. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Effects of bilateral deep brain stimulation in the subthalamic nucleus using two methods of target structure verification].

PubMed

Goubareva, N N; Fedorova, N V; Bril', E V; Tomskiy, A A; Gamaleya, A A; Poddubskaya, A A; Shabalov, V A; Omarova, S M

To evaluate the efficacy of deep brain stimulation in the subthalamic nucleus (DBS STN) in patients with Parkinson's disease (PD) using different methods of targeting according to the dynamics of motor symptoms of PD. The study involved 90 patients treated with DBS STN. In 30 cases intraoperative microelectrode recording (MER) was used. MER was not performed in 30 patients of the comparison group. The control group consisted of 30 patients with PD who received conservative treatment. Hoehn and Yahr scale, Tinetti Balance and Mobility Scale (TBMS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Quality of Life-39 Scoring System (РDQ-39), Schwab & England ADL Scale were used. Levodopa equivalent daily dose (LEDD, 2010) was calculated for each patient. The effect of DBS STN using intraoperative microelectrode recording on the main motor symptoms, motor complications, walking as well as indicators of quality of life and daily activities was shown. In both DBS STN groups, there was a significant reduction in the LEDD and marked improvement of the control of motor symptoms of PD. A significant reduction in the severity of motor fluctuations (50%) and drug-induced dyskinesia (51%) was observed. Quality of life and daily activity in off-medication condition were significantly improved in both DBS STN groups of patients, irrespective of the method of target planning (75-100%), compared with the control group.

Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

PubMed Central

Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

2016-01-01

Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced stages of Parkinson’s disease. PMID:27776130

Disease evolution in late-onset and early-onset systemic lupus erythematosus.

PubMed

Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

2017-10-01

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

Immunomodulation: the future cure for allergic diseases.

PubMed

Tsitoura, Daphne C; Tassios, Yannis

2006-11-01

Allergies are the result of aberrant immune reactivity against common innocuous environmental proteins (allergens). A pivotal component of allergic pathogenesis is the generation of allergen-specific Th cells with an effector phenotype. These Th cells activate a complex immune cascade that triggers the release of potent mediators and enhances the mobilization of several inflammatory cells types, which in turn elicit the acute allergic reactions and promote the development of chronic inflammation. The current therapies for allergic diseases focus primarily on pharmacological control of symptoms and suppression of inflammation. This approach is beneficial, but not curative, since the underlying immune pathology is not inhibited. In an attempt to develop more effective therapeutic strategies, the scientific interest has been directed toward methods down-modulating the immune mechanisms that initiate and maintain the allergic cascade. Today, the only widely used disease-modifying form of allergy treatment is the specific immunotherapy with allergen extracts. More recently the use of anti-IgE has been approved for patients with allergic asthma. Other immunomodulatory methods being currently explored are the administration of microbial adjuvants that inhibit Th2 reactivity and the design of molecules that interrupt the activity of key allergic cytokines, chemokines, or other Th2 effector mediators.

The Pharmacological Chaperone Isofagomine Increases Activity of the Gaucher Disease L444P Mutant Form of β-Glucosidase

PubMed Central

Khanna, Richie; Benjamin, Elfrida R.; Pellegrino, Lee; Schilling, Adriane; Rigat, Brigitte A.; Soska, Rebecca; Nafar, Hadis; Ranes, Brian E.; Feng, Jessie; Lun, Yi; Powe, Allan C.; Palling, David J.; Wustman, Brandon A.; Schiffmann, Raphael; Mahuran, Don J.; Lockhart, David J.; Valenzano, Kenneth J.

2010-01-01

SUMMARY Gaucher disease is caused by mutations in the gene that encodes the lysosomal enzyme acid β-glucosidase (GCase). We have shown previously that the small molecule pharmacological chaperone isofagomine (IFG) binds and stabilizes N370S GCase, resulting in increased lysosomal trafficking and cellular activity. In this study, we investigated the effect of IFG on L444P GCase. Incubation of Gaucher patient-derived lymphoblastoid cell lines (LCLs) or fibroblasts with IFG led to approximately 3.5- and 1.3-fold increases in L444P GCase activity, respectively, as measured in cell lysates. The effect in fibroblasts was increased approximately 2-fold using glycoprotein-enrichment, GCase-immunocapture, or by incubating cells overnight in IFG-free media prior to assay, methods designed to maximize GCase activity by reducing IFG carryover and inhibition in the enzymatic assay. IFG incubation also increased the lysosomal trafficking and in situ activity of L444P GCase in intact cells, as measured by reduction in endogenous glucosylceramide levels. Importantly, this reduction was seen only following three-day incubation in IFG-free media, underscoring the importance of IFG removal to restore lysosomal GCase activity. In mice expressing murine L444P GCase, oral administration of IFG resulted in significant increases (2- to 5-fold) in GCase activity in disease-relevant tissues, including brain. Additionally, eight-week IFG administration significantly lowered plasma chitin III and IgG levels, and 24-week administration significantly reduced spleen and liver weights. Taken together, these data suggest that IFG can increase the lysosomal activity of L444P GCase in cells and tissues. Moreover, IFG is orally available and distributes into multiple tissues, including brain, and may thus merit therapeutic evaluation for patients with neuronopathic and non-neuronopathic Gaucher disease. PMID:20148966

The Alberta moving beyond breast cancer (AMBER) cohort study: a prospective study of physical activity and health-related fitness in breast cancer survivors

PubMed Central

2012-01-01

Background Limited research has examined the association between physical activity, health-related fitness, and disease outcomes in breast cancer survivors. Here, we present the rationale and design of the Alberta Moving Beyond Breast Cancer (AMBER) Study, a prospective cohort study designed specifically to examine the role of physical activity and health-related fitness in breast cancer survivorship from the time of diagnosis and for the balance of life. The AMBER Study will examine the role of physical activity and health-related fitness in facilitating treatment completion, alleviating treatment side effects, hastening recovery after treatments, improving long term quality of life, and reducing the risks of disease recurrence, other chronic diseases, and premature death. Methods/Design The AMBER Study will enroll 1500 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a 5 year period. Assessments will be made at baseline (within 90 days of surgery), 1 year, and 3 years consisting of objective and self-reported measurements of physical activity, health-related fitness, blood collection, lymphedema, patient-reported outcomes, and determinants of physical activity. A final assessment at 5 years will measure patient-reported data only. The cohort members will be followed for an additional 5 years for disease outcomes. Discussion The AMBER cohort will answer key questions related to physical activity and health-related fitness in breast cancer survivors including: (1) the independent and interactive associations of physical activity and health-related fitness with disease outcomes (e.g., recurrence, breast cancer-specific mortality, overall survival), treatment completion rates, symptoms and side effects (e.g., pain, lymphedema, fatigue, neuropathy), quality of life, and psychosocial functioning (e.g., anxiety, depression, self-esteem, happiness), (2) the determinants of physical activity and health-related fitness including demographic, medical, social cognitive, and environmental variables, (3) the mediators of any observed associations between physical activity, health-related fitness, and health outcomes including biological, functional, and psychosocial, and (4) the moderators of any observed associations including demographic, medical, and biological/disease factors. Taken together, these data will provide a comprehensive inquiry into the outcomes, determinants, mechanisms, and moderators of physical activity and health-related fitness in breast cancer survivors. PMID:23153358

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

PubMed Central

Draborg, Anette H.; Lydolph, Magnus C.; Westergaard, Marie; Olesen Larsen, Severin; Nielsen, Christoffer T.; Duus, Karen; Jacobsen, Søren; Houen, Gunnar

2015-01-01

Objective In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs’ association with Epstein-Barr virus (EBV) antibodies was examined. Methods Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance. Results Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001) also after adjusting for Ig levels (p<0.0001). The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI)) score of the SLE patients (r = 0.399, p = 0.007). Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009), and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA) concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation) whereas EBV-directed antibodies reflect the extent of previous infection/reactivations. Conclusion SLE patients have elevated concentrations of serum FLCs that correlate with global disease activity scores and especially serologic markers for active disease. These findings are suggestive of circulating FLCs having potential as a new supplementary serologic biomarker in SLE. PMID:26402865

Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated

PubMed Central

Almeida, Beverley; Campanilho‐Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A.; Wedderburn, Lucy R.; Armon, Kate; Briggs, Vanja; Ellis‐Gage, Joe; Roper, Holly; Watts, Joanna; Baildam, Eileen; Hanna, Louise; Lloyd, Olivia; McCann, Liza; Roberts, Ian; McGovern, Ann; Riley, Phil; Al‐Abadi, Eslam; Ryder, Clive; Scott, Janis; Southwood, Taunton; Thomas, Beverley; Amin, Tania; Burton, Deborah; Jackson, Gillian; Van Rooyen, Vanessa; Wood, Mark; Wyatt, Sue; Browne, Michael; Davidson, Joyce; Ferguson, Sue; Gardner‐Medwin, Janet; Martin, Neil; Waxman, Liz; Foster, Helen; Friswell, Mark; Jandial, Sharmila; Qiao, Lisa; Sen, Ethan; Smith, Eve; Stevenson, Vicky; Swift, Alison; Wade, Debbie; Watson, Stuart; Crate, Lindsay; Frost, Anna; Jordan, Mary; Mosley, Ellen; Satyapal, Rangaraj; Stretton, Elizabeth; Venning, Helen; Warrier, Kishore; Almeida, Beverley; Arnold, Katie; Beard, Laura; Brown, Virginia; Campanilho‐Marques, Raquel; Enayat, Elli; Glackin, Yvonne; Halkon, Elizabeth; Hasson, Nathan; Juggins, Audrey; Kassoumeri, Laura; Lunt, Sian; Maillard, Sue; Nistala, Kiran; Pilkington, Clarissa; Simou, Stephanie; Smith, Sally; Varsani, Hemlata; Wedderburn, Lucy; Murray, Kevin; Ioannou, John; Suffield, Linda; Al‐Obaidi, Muthana; Leach, Sam; Lee, Helen; Smith, Helen; Inness, Emma; Kendall, Eunice; Mayers, David; Wilkinson, Nick; Clinch, Jacqui; Pluess‐Hall, Helen

2015-01-01

Objective The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. Methods We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. Results At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). Conclusion There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met the other 3 criteria. Incorporating PGA as an essential criterion for clinically inactive disease helps prevent the misclassification of patients with active skin disease. PMID:25988361

Computational Modeling of Interventions and Protective Thresholds to Prevent Disease Transmission in Deploying Populations

PubMed Central

2014-01-01

Military personnel are deployed abroad for missions ranging from humanitarian relief efforts to combat actions; delay or interruption in these activities due to disease transmission can cause operational disruptions, significant economic loss, and stressed or exceeded military medical resources. Deployed troops function in environments favorable to the rapid and efficient transmission of many viruses particularly when levels of protection are suboptimal. When immunity among deployed military populations is low, the risk of vaccine-preventable disease outbreaks increases, impacting troop readiness and achievement of mission objectives. However, targeted vaccination and the optimization of preexisting immunity among deployed populations can decrease the threat of outbreaks among deployed troops. Here we describe methods for the computational modeling of disease transmission to explore how preexisting immunity compares with vaccination at the time of deployment as a means of preventing outbreaks and protecting troops and mission objectives during extended military deployment actions. These methods are illustrated with five modeling case studies for separate diseases common in many parts of the world, to show different approaches required in varying epidemiological settings. PMID:25009579

Computational modeling of interventions and protective thresholds to prevent disease transmission in deploying populations.

PubMed

Burgess, Colleen; Peace, Angela; Everett, Rebecca; Allegri, Buena; Garman, Patrick

2014-01-01

Military personnel are deployed abroad for missions ranging from humanitarian relief efforts to combat actions; delay or interruption in these activities due to disease transmission can cause operational disruptions, significant economic loss, and stressed or exceeded military medical resources. Deployed troops function in environments favorable to the rapid and efficient transmission of many viruses particularly when levels of protection are suboptimal. When immunity among deployed military populations is low, the risk of vaccine-preventable disease outbreaks increases, impacting troop readiness and achievement of mission objectives. However, targeted vaccination and the optimization of preexisting immunity among deployed populations can decrease the threat of outbreaks among deployed troops. Here we describe methods for the computational modeling of disease transmission to explore how preexisting immunity compares with vaccination at the time of deployment as a means of preventing outbreaks and protecting troops and mission objectives during extended military deployment actions. These methods are illustrated with five modeling case studies for separate diseases common in many parts of the world, to show different approaches required in varying epidemiological settings.

Endotoxin Neutralization as a Biomonitor for Inflammatory Bowel Disease

PubMed Central

Champion, Keith; Chiu, Laura; Ferbas, John; Pepe, Michael

2013-01-01

Gram-negative bacterial endotoxin is a potent immunostimulant implicated in the development and/or progression of a variety of diseases. The mammalian immune system has both innate and adaptive immune responses to neutralize endotoxin. In this study, a system was developed to monitor bacterial exposure by measuring the extent and nature of endotoxin neutralization in plasma. In control patients, females had higher levels of endotoxin neutralization than males, mirroring clinical outcomes from bacterial infection and sepsis. In addition to the total amount of neutralization, we used inactivation techniques to elucidate the nature of this activity and develop a system to compare early and late immune responses. Using this method to monitor patients with inflammatory bowel disease, we found a more robust total response that relies more on long-term, adaptive components of the immune system and less on early, innate components. Our results indicate that endotoxin neutralization is a valuable method to discern inflammatory bowel disease patients from a control population. Additionally, the nature of neutralization may be valuable in monitoring disease severity and/or the role of medication. PMID:23826338

Drug-Target Interactions: Prediction Methods and Applications.

PubMed

Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

2018-01-01

Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Increased myelopepoxidase activity is a risk factor for ishemic heart disease in patients with diabetes mellitus].

PubMed

Gorudko, I V; Kostevich, A V; Sokolov, A V; Konstatinova, E É; Tsapaeva, N L; Mironova, E V; Zakharova, E T; Vasil'ev, V B; Cherenkevich, S N; Panasenko, A M

2012-01-01

Using previously developed spectro-photonmetrical method (Bioorg. Khim. 2009. V. 35. pp. 629-639), a significant increase of myeloperoxidase (MPO) activity was found in blood plasma of patients with type 2 diabetes mellitus (DM2) without of cardiovascular complications, as well as with ischemic heart disease (IHD). Plasma MPO concentration measured by an enzyme-linked immunosorbent assay was significantly higher only in blood plasma of patient with DM2 and IHD. A direct and significant correlation between MPO activity and MPO concentration was observed only in blood plasma samples from healthy donors. Increased MPO activity did not correlate with MPO concentration in blood plasma of patients with DM2 and DM2 with IHD. Taken together, these results highlight the necessity for studying of the MPO role in the development of pathological processes to determine both the amount of enzyme and its peroxidase activity in the blood. The proposed approach gives comprehensive information about the relationship between MPO activity and MPO concentration in patient blood. Since the high concentration of MPO is a diagnostically significant parameter in the prediction of endothelial dysfunction and cardiovascular disease development, the obtained results evidence the contribution of MPO-dependent reactions in cardiovascular complications associated with diabetes. MPO activity may serve as an additional diagnostic criterion for determination of risk of IHD in DM patients.

Free radical scavenging capacity, anticandicidal effect of bioactive compounds from Sida cordifolia L., in combination with nystatin and clotrimazole and their effect on specific immune response in rats.

PubMed

Ouédraogo, Maurice; Konaté, Kiessoun; Lepengué, Alexis Nicaise; Souza, Alain; M'Batchi, Bertrand; Sawadogo, Laya L

2012-12-26

Infectious diseases caused by fungi are still a major threat to public health, despite numerous efforts by researchers. Use of ethnopharmacological knowledge is one attractive way to reduce empiricism and enhance the probability of success in new drug-finding efforts. In this work, the total alkaloid compounds (AC) from Sida cordifolia L. (Malvaceae) have been investigated for their free radical scavenging capacity, antifungal and immunostimulatory properties. The antifungal activity was investigated against five candida strains using the microplate dilution method and the Fractional Inhibitory Concentration Index (FICI) of compounds was evaluated. The antioxidant activity of the samples was evaluate using three separate methods, at last, the immunostimulatory effect on immunosuppressed wistar rats was performed. As for the antifungal activity, result varied according to microorganism. The results obtained in this antifungal activity were interesting and indicated a synergistic effect between alkaloid compounds and the antifungal references such as Nystatin and Clotrimazole. Antioxidant capacity noticed that the reduction capacity of DPPH radicals obtained the best result comparatively to the others methods of free radical scavenging. Our results showed a low immunostimulatory effect and this result could be explained by the lack of biologically active antioxidants such as polyphenol compounds lowly contained in the alkaloid compounds. The results of this study showed that alkaloid compounds in combination with antifungal references (Nystatin and Clotrimazole) exhibited antimicrobial effects against candida strains tested. The results supported the utilization of these plants in infectious diseases particularly in treatment of candida infections.

Tuberculosis beliefs among recent Vietnamese refugees in New York State.

PubMed Central

Carey, J W; Oxtoby, M J; Nguyen, L P; Huynh, V; Morgan, M; Jeffery, M

1997-01-01

OBJECTIVE: To identify newly arrived Vietnamese refugees' beliefs about tuberculosis (TB) and TB education needs. METHODS: In 1994, the New York State Health Department and the Centers for Disease Control and Prevention conducted a survey of 51 newly arrived adult Vietnamese refugees in two New York counties. After being trained in interview methods, two bilingual researchers asked 32 open-ended questions on the causes of TB, TB treatment, and the disease's impact on work and social relationships. RESULTS: Respondents correctly viewed TB as an infectious lung disease with symptoms such as cough, weakness, and weight loss. Hard manual labor, smoking, alcohol consumption, and poor nutrition were believed to be risk factors. Many respondents incorrectly believed that asymptomatic latent infection is not possible and that infection inevitably leads to disease. Nearly all respondents anticipated that having tuberculosis would adversely impact their work, family, and community activities and relationships. CONCLUSIONS: Targeted patient education is needed to address misconceptions about TB among Vietnamese refugees and to help ensure adherence to prescribed treatment regimens. PMID:9018292

Back propagation artificial neural network for community Alzheimer's disease screening in China.

PubMed

Tang, Jun; Wu, Lei; Huang, Helang; Feng, Jiang; Yuan, Yefeng; Zhou, Yueping; Huang, Peng; Xu, Yan; Yu, Chao

2013-01-25

Alzheimer's disease patients diagnosed with the Chinese Classification of Mental Disorders diagnostic criteria were selected from the community through on-site sampling. Levels of macro and trace elements were measured in blood samples using an atomic absorption method, and neurotransmitters were measured using a radioimmunoassay method. SPSS 13.0 was used to establish a database, and a back propagation artificial neural network for Alzheimer's disease prediction was simulated using Clementine 12.0 software. With scores of activities of daily living, creatinine, 5-hydroxytryptamine, age, dopamine and aluminum as input variables, the results revealed that the area under the curve in our back propagation artificial neural network was 0.929 (95% confidence interval: 0.868-0.968), sensitivity was 90.00%, specificity was 95.00%, and accuracy was 92.50%. The findings indicated that the results of back propagation artificial neural network established based on the above six variables were satisfactory for screening and diagnosis of Alzheimer's disease in patients selected from the community.

Back propagation artificial neural network for community Alzheimer's disease screening in China★

PubMed Central

Tang, Jun; Wu, Lei; Huang, Helang; Feng, Jiang; Yuan, Yefeng; Zhou, Yueping; Huang, Peng; Xu, Yan; Yu, Chao

2013-01-01

Alzheimer's disease patients diagnosed with the Chinese Classification of Mental Disorders diagnostic criteria were selected from the community through on-site sampling. Levels of macro and trace elements were measured in blood samples using an atomic absorption method, and neurotransmitters were measured using a radioimmunoassay method. SPSS 13.0 was used to establish a database, and a back propagation artificial neural network for Alzheimer's disease prediction was simulated using Clementine 12.0 software. With scores of activities of daily living, creatinine, 5-hydroxytryptamine, age, dopamine and aluminum as input variables, the results revealed that the area under the curve in our back propagation artificial neural network was 0.929 (95% confidence interval: 0.868–0.968), sensitivity was 90.00%, specificity was 95.00%, and accuracy was 92.50%. The findings indicated that the results of back propagation artificial neural network established based on the above six variables were satisfactory for screening and diagnosis of Alzheimer's disease in patients selected from the community. PMID:25206598

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

PubMed Central

Xing, Jihong; Li, Jianhua

2017-01-01

Background/Aims Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex. Methods A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues were obtained to examine the protein levels of PAR2 using western blot analysis. Current responses induced by activation of TRPA1 in skeletal muscle DRG neurons were characterized using whole-cell patch clamp methods. The blood pressure response to static exercise (i.e., muscle contraction) and stimulation of TRPA1 was also examined after a blockade of PAR2. Results The expression of PAR2 was amplified in DRG neurons of the occluded limb, and PAR2 activation with SL-NH2 (a PAR2 agonist) increased the amplitude of TRPA1 currents to a greater degree in DRG neurons of the occluded limb. Moreover, FSLLRY-NH2 (a PAR antagonist) injected into the arterial blood supply of the hindlimb muscles significantly attenuated the pressor response to muscle contraction and TRPA1 stimulation in rats with occluded limbs. Conclusions The PAR2 signal in muscle sensory nerves contributes to the amplified exercise pressor reflex via TRPA1 mechanisms in rats with femoral artery ligation. These findings provide a pathophysiological basis for autonomic responses during exercise activity in PAD, which may potentially aid in the development of therapeutic approaches for improvement of blood flow in this disease. PMID:29131007

Surveillance for Neisseria meningitidis Disease Activity and Transmission Using Information Technology

PubMed Central

Ahmed, S. Sohail; Oviedo-Orta, Ernesto; Mekaru, Sumiko R.; Freifeld, Clark C.; Tougas, Gervais; Brownstein, John S.

2015-01-01

Background While formal reporting, surveillance, and response structures remain essential to protecting public health, a new generation of freely accessible, online, and real-time informatics tools for disease tracking are expanding the ability to raise earlier public awareness of emerging disease threats. The rationale for this study is to test the hypothesis that the HealthMap informatics tools can complement epidemiological data captured by traditional surveillance monitoring systems for meningitis due to Neisseria meningitides (N. meningitides) by highlighting severe transmissible disease activity and outbreaks in the United States. Methods Annual analyses of N. meningitides disease alerts captured by HealthMap were compared to epidemiological data captured by the Centers for Disease Control’s Active Bacterial Core surveillance (ABCs) for N. meningitides. Morbidity and mortality case reports were measured annually from 2010 to 2013 (HealthMap) and 2005 to 2012 (ABCs). Findings HealthMap N. meningitides monitoring captured 80-90% of alerts as diagnosed N. meningitides, 5-20% of alerts as suspected cases, and 5-10% of alerts as related news articles. HealthMap disease alert activity for emerging disease threats related to N. meningitides were in agreement with patterns identified historically using traditional surveillance systems. HealthMap’s strength lies in its ability to provide a cumulative “snapshot” of weak signals that allows for rapid dissemination of knowledge and earlier public awareness of potential outbreak status while formal testing and confirmation for specific serotypes is ongoing by public health authorities. Conclusions The underreporting of disease cases in internet-based data streaming makes inadequate any comparison to epidemiological trends illustrated by the more comprehensive ABCs network published by the Centers for Disease Control. However, the expected delays in compiling confirmatory reports by traditional surveillance systems (at the time of writing, ABCs data for 2013 is listed as being provisional) emphasize the helpfulness of real-time internet-based data streaming to quickly fill gaps including the visualization of modes of disease transmission in outbreaks for better resource and action planning. HealthMap can also contribute as an internet-based monitoring system to provide real-time channel for patients to report intervention-related failures. PMID:25992552

Synthesis of 1-indanones with a broad range of biological activity

PubMed Central

Turek, Marika; Szczęsna, Dorota; Koprowski, Marek

2017-01-01

This comprehensive review describes methods for the preparation of 1-indanones published in original and patent literature from 1926 to 2017. More than 100 synthetic methods utilizing carboxylic acids, esters, diesters, acid chlorides, ketones, alkynes, alcohols etc. as starting materials, have been performed. This review also covers the most important studies on the biological activity of 1-indanones and their derivatives which are potent antiviral, anti-inflammatory, analgesic, antimalarial, antibacterial and anticancer compounds. Moreover, they can be used in the treatment of neurodegenerative diseases and as effective insecticides, fungicides and herbicides. PMID:28382183

Regulation of defensive function on gingival epithelial cells can prevent periodontal disease.

PubMed

Fujita, Tsuyoshi; Yoshimoto, Tetsuya; Kajiya, Mikihito; Ouhara, Kazuhisa; Matsuda, Shinji; Takemura, Tasuku; Akutagawa, Keiichi; Takeda, Katsuhiro; Mizuno, Noriyoshi; Kurihara, Hidemi

2018-05-01

Periodontal disease is a bacterial biofilm-associated inflammatory disease that has been implicated in many systemic diseases. A new preventive method for periodontal disease needs to be developed in order to promote the health of the elderly in a super-aged society. The gingival epithelium plays an important role as a mechanical barrier against bacterial invasion and a part of the innate immune response to infectious inflammation in periodontal tissue. The disorganization of cell-cell interactions and subsequent inflammation contribute to the initiation of periodontal disease. These make us consider that regulation of host defensive functions, epithelial barrier and neutrophil activity, may become novel preventive methods for periodontal inflammation. Based on this concept, we have found that several agents regulate the barrier function of gingival epithelial cells and suppress the accumulation of neutrophils in the gingival epithelium. We herein introduce the actions of irsogladine maleate, azithromycin, amphotericin B, and Houttuynia cordata (dokudami in Japanese), which is commonly used in traditional medicine, on the epithelial barrier and neutrophil migration in gingival epithelial cells in vivo and in vitro , in order to provide support for the clinical application of these agents to the prevention of periodontal inflammation.

Cost-of-illness studies: concepts, scopes, and methods

PubMed Central

2014-01-01

Liver diseases are one of the main causes of death, and their ever-increasing prevalence is threatening to cause significant damage both to individuals and society as a whole. This damage is especially serious for the economically active population in Korea. From the societal perspective, it is therefore necessary to consider the economic impacts associated with liver diseases, and identify interventions that can reduce the burden of these diseases. The cost-of-illness study is considered to be an essential evaluation technique in health care. By measuring and comparing the economic burdens of diseases to society, such studies can help health-care decision-makers to set up and prioritize health-care policies and interventions. Using economic theories, this paper introduces various study methods that are generally applicable to most disease cases for estimating the costs of illness associated with mortality, morbidity, disability, and other disease characteristics. It also presents concepts and scopes of costs along with different cost categories from different research perspectives in cost estimations. By discussing the epidemiological and economic grounds of the cost-of-illness study, the reported results represent useful information about several evaluation techniques at an advanced level, such as cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis. PMID:25548737

Twin methodology in epigenetic studies.

PubMed

Tan, Qihua; Christiansen, Lene; von Bornemann Hjelmborg, Jacob; Christensen, Kaare

2015-01-01

Since the final decades of the last century, twin studies have made a remarkable contribution to the genetics of human complex traits and diseases. With the recent rapid development in modern biotechnology of high-throughput genetic and genomic analyses, twin modelling is expanding from analysis of diseases to molecular phenotypes in functional genomics especially in epigenetics, a thriving field of research that concerns the environmental regulation of gene expression through DNA methylation, histone modification, microRNA and long non-coding RNA expression, etc. The application of the twin method to molecular phenotypes offers new opportunities to study the genetic (nature) and environmental (nurture) contributions to epigenetic regulation of gene activity during developmental, ageing and disease processes. Besides the classical twin model, the case co-twin design using identical twins discordant for a trait or disease is becoming a popular and powerful design for epigenome-wide association study in linking environmental exposure to differential epigenetic regulation and to disease status while controlling for individual genetic make-up. It can be expected that novel uses of twin methods in epigenetic studies are going to help with efficiently unravelling the genetic and environmental basis of epigenomics in human complex diseases. © 2015. Published by The Company of Biologists Ltd.

Cost-of-illness studies: concepts, scopes, and methods.

PubMed

Jo, Changik

2014-12-01

Liver diseases are one of the main causes of death, and their ever-increasing prevalence is threatening to cause significant damage both to individuals and society as a whole. This damage is especially serious for the economically active population in Korea. From the societal perspective, it is therefore necessary to consider the economic impacts associated with liver diseases, and identify interventions that can reduce the burden of these diseases. The cost-of-illness study is considered to be an essential evaluation technique in health care. By measuring and comparing the economic burdens of diseases to society, such studies can help health-care decision-makers to set up and prioritize health-care policies and interventions. Using economic theories, this paper introduces various study methods that are generally applicable to most disease cases for estimating the costs of illness associated with mortality, morbidity, disability, and other disease characteristics. It also presents concepts and scopes of costs along with different cost categories from different research perspectives in cost estimations. By discussing the epidemiological and economic grounds of the cost-of-illness study, the reported results represent useful information about several evaluation techniques at an advanced level, such as cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis.

Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

PubMed Central

Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

2013-01-01

Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

Novel roles of complement in renal diseases and their therapeutic consequences.

PubMed

Wada, Takehiko; Nangaku, Masaomi

2013-09-01

The complement system functions as a part of the innate immune system. Inappropriate activation of the complement pathways has a deleterious effect on kidneys. Recent advances in complement research have provided new insights into the pathogenesis of glomerular and tubulointerstitial injury associated with complement activation. A new disease entity termed 'C3 glomerulopathy' has recently been proposed and is characterized by isolated C3 deposition in glomeruli without positive staining for immunoglobulins. Genetic and functional studies have demonstrated that several different mutations and disease variants, as well as the generation of autoantibodies, are potentially associated with its pathogenesis. The data from comprehensive analyses suggest that complement dysregulation can also be associated with hemolytic uremic syndrome and more common glomerular diseases, such as IgA nephropathy and diabetic kidney disease. In addition, animal studies utilizing genetically modified mice have begun to elucidate the molecular pathomechanisms associated with the complement system. From a diagnostic point of view, a noninvasive, MRI-based method for detecting C3 has recently been developed to serve as a novel tool for diagnosing complement-mediated kidney diseases. While novel therapeutic tools related to complement regulation are emerging, studies evaluating the precise roles of the complement system in kidney diseases will still be useful for developing new therapeutic approaches.

Helminths as an alternative therapy for intestinal diseases.

PubMed

Sipahi, Aytan Miranda; Baptista, Daniel Machado

2017-09-07

Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity, altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings, such as inflammatory bowel disease (IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies, we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use, but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs, since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease, such as the importance of the specific species of helminths used, appropriate dosing regimens, optimal timing of treatment, the role of host genetics, diet, environment, and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method, especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.

Safe and effective prescription of exercise in acute exacerbations of chronic obstructive pulmonary disease: rationale and methods for an integrated knowledge translation study.

PubMed

Camp, Pat; Reid, W Darlene; Yamabayashi, Cristiane; Brooks, Dina; Goodridge, Donna; Chung, Frank; Marciniuk, Darcy D; Neufeld, Andrea; Hoens, Alsion

2013-01-01

Patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) engage in low levels of activity, putting them at risk for relapse and future readmissions. There is little direction for health care providers regarding the parameters for safe exercise during an AECOPD that is effective for increasing activity tolerance before discharge from hospital, especially for patients with associated comorbid conditions. To report the rationale for and methods of a study to develop evidence-informed care recommendations that guide health care providers in the assessment, prescription, monitoring and progression of exercise for patients hospitalized with AECOPD. The present study was a multicomponent knowledge translation project incorporating evidence from systematic reviews of exercise involving populations with chronic obstructive pulmonary disease and⁄or common comorbidities. A Delphi process was then used to obtain expert opinion from clinicians, academics and patients to identify the parameters of safe and effective exercise for patients with AECOPD. Clinical decision-making tool(s) for patients and practitioners supported by a detailed knowledge dissemination, implementation and evaluation framework. The present study addressed an important knowledge gap: the lack of availability of parameters to guide safe and effective exercise prescription for hospitalized patients with AECOPD, with or without comorbid conditions. In the absence of such parameters, health care professionals may adopt an 'activity as tolerated' approach, which may not improve physical activity levels in their patients. The present study synthesizes the best available evidence and expert opinion, and will generate decision-making tools for use by patients and their health care providers.

Antifungal study of the resinous exudate and of meroterpenoids isolated from Psoralea glandulosa (Fabaceae).

PubMed

Madrid, Alejandro; Espinoza, Luis; González, Cesar; Mellado, Marco; Villena, Joan; Santander, Rocío; Silva, Viviana; Montenegro, Iván

2012-12-18

Psoralea glandulosa L. (Fabaceae) is a medicinal resinous shrub used in Chilean folk medicine as antiseptic in treatment of infections and skin diseases caused by bacteria and fungus. To evaluate the in vitro antifungal activity of the resin and the active components from P. glandulosa against clinical yeast isolates. Active compounds were obtained of the resinous exudate from aerial parts of P. glandulosa. Eight species of yeast were exposed to the resin and two major compounds. Minimum inhibitory concentration (MIC(80)) was determined according to the standard broth microdilution method. Bakuchiol and 3-hydroxy-bakuchiol demonstrated potent activity with the MIC(80) ranging from 4 to >16 and 0.125 to 16 μg/mL, respectively. The resin had some degree of antifungal activity. The overall results provided important information for the potential application of the 3-hydroxy-bakuchiol from P. glandulosa in the therapy of serious infection and skin diseases caused by clinical yeast. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014

PubMed Central

Schneider, Lon S.; Mangialasche, Francesca; Andreasen, Niels; Feldman, Howard; Giacobini, Ezio; Jones, Roy; Mantua, Valentina; Mecocci, Patrizia; Pani, Luca; Winblad, Bengt; Kivipelto, Miia

2014-01-01

The modern era of drug development for Alzheimer’s disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer’s disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here we review the development of treatments for Alzheimer’s disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer’s disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild to moderate Alzheimer’s disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer’s disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6 to 12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early-stage Alzheimer’s disease trial samples by using biomarkers and phase-specific outcomes. In conclusion, validated drug targets for Alzheimer’s disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late-phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods. PMID:24605808

Osteochondroses: Diseases of Growth Centers.

ERIC Educational Resources Information Center

Pappas, Arthur M.

1989-01-01

Many growth center disorders may be associated with athletic activities like Little League baseball and year-round gymnastics. Osteochondroses are developmental disorders usually diagnosed in growing children and associated with anatomic sites undergoing transition from cartilage to bone. Radiographic methods of diagnosing these problems are…

Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

PubMed Central

Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

2013-01-01

Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

Cost Analysis of Selected Patient Categories within a Dermatology Department Using an ABC Approach

PubMed Central

Papadaki, Šárka; Popesko, Boris

2016-01-01

Background: Present trends in hospital management are facilitating the utilization of more accurate costing methods, which potentially results in superior cost-related information and improved managerial decision-making. However, the Activity-Based Costing method (ABC), which was designed for cost allocation purposes in the 1980s, is not widely used by healthcare organizations. This study analyzes costs related to selected categories of patients, those suffering from psoriasis, varicose ulcers, eczema and other conditions, within a dermatology department at a Czech regional hospital. Methods: The study was conducted in a hospital department where both inpatient and outpatient care are offered. Firstly, the diseases treated at the department were identified. Further costs were determined for each activity using ABC. The study utilized data from managerial and financial accounting, as well as data obtained through interviews with departmental staff. Using a defined cost-allocation procedure makes it possible to determine the cost of an individual patient with a given disease more accurately than via traditional costing procedures. Results: The cost analysis focused on the differences between the costs related to individual patients within the selected diagnoses, variations between inpatient and outpatient treatments and the costs of activities performed by the dermatology department. Furthermore, comparing the costs identified through this approach and the revenue stemming from the health insurance system is an option. Conclusions: Activity-Based Costing is more accurate and relevant than the traditional costing method. The outputs of ABC provide an abundance of additional information for managers. The benefits of this research lie in its practically-tested outputs, resulting from calculating the costs of hospitalization, which could prove invaluable to persons involved in hospital management and decision-making. The study also defines the managerial implications of the performed cost analysis for the hospital management. Based on the analysis results, it is possible to standardize activities and performance appraisal (Benchmarking), and provide all necessary information for hospital budgeting practices, especially Activity-Based Budgeting (ABB). PMID:26755477

Fermentation of Foc TR4-infected bananas and Trichoderma spp.

PubMed

Yang, J; Li, B; Liu, S W; Biswas, M K; Liu, S; Wei, Y R; Zuo, C W; Deng, G M; Kuang, R B; Hu, C H; Yi, G J; Li, C Y

2016-10-17

Fusarium wilt (also known as Panama disease) is one of the most destructive banana diseases, and greatly hampers the global production of bananas. Consequently, it has been very detrimental to the Chinese banana industry. An infected plant is one of the major causes of the spread of Fusarium wilt to nearby regions. It is essential to develop an efficient and environmentally sustainable disease control method to restrict the spread of Fusarium wilt. We isolated Trichoderma spp from the rhizosphere soil, roots, and pseudostems of banana plants that showed Fusarium wilt symptoms in the infected areas. Their cellulase activities were measured by endoglucanase activity, β-glucosidase activity, and filter paper activity assays. Safety analyses of the Trichoderma isolates were conducted by inoculating them into banana plantlets. The antagonistic effects of the Trichoderma spp on the Fusarium pathogen Foc tropical Race 4 (Foc TR4) were tested by the dual culture technique. Four isolates that had high cellulase activity, no observable pathogenicity to banana plants, and high antagonistic capability were identified. The isolates were used to biodegrade diseased banana plants infected with GFP-tagged Foc TR4, and the compost was tested for biological control of the infectious agent; the results showed that the fermentation suppressed the incidence of wilt and killed the pathogen. This study indicates that Trichoderma isolates have the potential to eliminate the transmission of Foc TR4, and may be developed into an environmentally sustainable treatment for controlling Fusarium wilt in banana plants.

The Catalonian Expert Patient Programme for Chagas Disease: An Approach to Comprehensive Care Involving Affected Individuals.

PubMed

Claveria Guiu, Isabel; Caro Mendivelso, Johanna; Ouaarab Essadek, Hakima; González Mestre, Maria Asunción; Albajar-Viñas, Pedro; Gómez I Prat, Jordi

2017-02-01

The Catalonian Expert Patient Programme on Chagas disease is a initiative, which is part of the Chronic Disease Programme. It aims to boost responsibility of patients for their own health and to promote self-care. The programme is based on nine sessions conducted by an expert patient. Evaluation was focusing in: habits and lifestyle/self-care, knowledge of disease, perception of health, self-esteem, participant satisfaction, and compliance with medical follow-up visits. Eighteen participants initiated the programme and 15 completed it. The participants were Bolivians. The 66.7 % of them had been diagnosed with chagas disease in Spain. The 100 % mentioned that they would participate in this activity again and would recommend it to family and friends. The knowledge about disease improve after sessions. The method used in the programme could serve as a key strategy in the field of comprehensive care for individuals with this disease.

Hypoxic Tumor Kinase Signaling Mediated by STAT5A in Development of Castration-Resistant Prostate Cancer

PubMed Central

Røe, Kathrine; Bratland, Åse; Vlatkovic, Ljiljana; Ragnum, Harald Bull; Saelen, Marie Grøn; Olsen, Dag Rune; Marignol, Laure; Ree, Anne Hansen

2013-01-01

In this study, we hypothesized that androgen-deprivation therapy (ADT) in prostate cancer, although initially efficient, induces changes in the tumor kinome, which subsequently promote development of castration-resistant (CR) disease. Recognizing the correlation between tumor hypoxia and poor prognosis in prostate cancer, we further hypothesized that such changes might be influenced by hypoxia. Microarrays with 144 kinase peptide substrates were applied to analyze CWR22 prostate carcinoma xenograft samples from ADT-naïve, androgen-deprived (AD), long-term AD (ADL), and CR disease stages. The impact of hypoxia was assessed by matching the xenograft kinase activity profiles with those acquired from hypoxic and normoxic prostate carcinoma cell cultures, whereas the clinical relevance was evaluated by analyzing prostatectomy tumor samples from patients with locally advanced disease, either in ADT-naïve or early CR disease stages. By using this novel peptide substrate microarray method we revealed high kinase activity mediated by signal transducer and activator of transcription 5A (STAT5A) in CR prostate cancer. Additionally, we uncovered high STAT5A kinase activity already in regressing ADL xenografts, before renewed CR growth was evidenced. Finally, since increased STAT5A kinase activity also was detected after exposing prostate carcinoma cells to hypoxia, we propose long-term ADT to induce tumor hypoxia and stimulate STAT5A kinase activity, subsequently leading to renewed CR tumor growth. Hence, the study detected STAT5A as a candidate to be further investigated for its potential as marker of advanced prostate cancer and as possible therapeutic target protein. PMID:23675504

Relationship between Self-efficacy and Physical Activity, Medication Adherence in Chronic Disease Patients

PubMed Central

Daniali, Seyde Shahrbanoo; Darani, Firooze Mostafavi; Eslami, Ahmad Ali; Mazaheri, Mohammad

2017-01-01

Background: The global epidemic of unhealthy lifestyle causes to increase chronic disease. It has been proven that psychological factors such as self-efficacy are responsible to success in the process of lifestyle change. Low self-efficacy is usually related to low level of physical activity and medication adherence. Objective of the study was to investigate the effects of self-efficacy, other physical symptoms on physical activity and medication adherence in patients with chronic illness in public health centers. Materials and Methods: A cross-sectional study was conducted on 483 patients with chronic diseases attended to governmental health care centers in Isfahan. Participants were chosen by systematic random sampling. Inclusion criteria were having a chronic illness at least 6-month ago while prescription of medication and willing to take part in the survey. The parts of Stanford Self-management Questionnaire were used. Data were analyzed by SPSS 18 software using the descriptive and analytic statistics. P < 0.05 was considered significant. Results: Mean age of participants was 54.8 (7.22) years. The half of participants had low self-efficacy and 87.2% had low physical activity. Nearly 80% of patients had a good medication adherence. There was a significant relationship between self-efficacy and physical activity (P = 0.336, β = 1.01, P < 0.001). Conclusion: Although chronic disease patients had a good medication adherence, other self-care behaviors such as physical activity has been neglected. It is seemed that concentration on psychological factors such as self-efficacy should be considered as a proximal factor to improve self-care. PMID:28603704

Typical cerebral metabolic patterns in neurodegenerative brain diseases.

PubMed

Teune, Laura K; Bartels, Anna L; de Jong, Bauke M; Willemsen, Antoon T M; Eshuis, Silvia A; de Vries, Jeroen J; van Oostrom, Joost C H; Leenders, Klaus L

2010-10-30

The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.We have studied patients who had an FDG-PET scan on clinical grounds at an early disease stage and included those with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria. Ninety-six patients could be included of which 20 patients with Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17 progressive supranuclear palsy (PSP), 10 corticobasal degeneration (CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD), and 7 frontotemporal dementia (FTD). FDG PET images of each patient group were analyzed and compared to18 healthy controls using Statistical Parametric Mapping (SPM5).Disease-specific patterns of relatively decreased metabolic activity were found in PD (contralateral parietooccipital and frontal regions), MSA (bilateral putamen and cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus, thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB (occipital and parietotemporal regions), AD (parietotemporal regions), and FTD (frontotemporal regions).The integrated method addressing a spectrum of various neurodegenerative brain diseases provided means to discriminate patient groups also at early disease stages. Clinical follow-up enabled appropriate patient inclusion. This implies that an early diagnosis in individual patients can be made by comparing each subject's metabolic findings with a complete database of specific disease related patterns.

A review of antiviral drugs and other compounds with activity against feline herpesvirus-1

PubMed Central

Thomasy, S. M.; Maggs, D. J.

2016-01-01

Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. However, many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally-inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise review of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats. PMID:27091747

Bacopa monnieri Phytochemicals Mediated Synthesis of Platinum Nanoparticles and Its Neurorescue Effect on 1-Methyl 4-Phenyl 1,2,3,6 Tetrahydropyridine-Induced Experimental Parkinsonism in Zebrafish

PubMed Central

Nellore, Jayshree; Pauline, Cynthia; Amarnath, Kanchana

2013-01-01

Current discovery demonstrates the rapid formation of platinum nanoparticles using leaf extract of a neurobeneficial plant, Bacopa monnieri (BmE). The nanoparticles (BmE-PtNPs) were stabilized and then coated with varied phytochemicals present within the leaf extract. These nanoparticles demonstrated the same activity of Complex I, as that of oxidizing NADH to NAD+ using a spectrophotometric method. This suggests that BmE-PtNPs are a potential medicinal substance for oxidative stress mediated disease with suppressed mitochondrial complex I, namely, Parkinson's disease (PD). Hence, the neuroprotective potentials of the phytochemical coated nanoparticle were explored in 1-methyl 4-phenyl 1,2,3,6 tetrahydropyridine- (MPTP-)induced experimental Parkinsonism in zebrafish model. BmE-PtNPs pretreatment significantly reversed toxic effects of MPTP by increasing the levels of dopamine, its metabolites, GSH and activities of GPx, catalase, SOD and complex I, and reducing levels of MDA along with enhanced locomotor activity. Taken together, these findings suggest that BmE-PtNPs have protective effect in MPTP-induced neurotoxicity in this model of Parkinson's disease via their dual functions as mitochondrial complex I and antioxidant activity. PMID:26317003

Optimization model using Markowitz model approach for reducing the number of dengue cases in Bandung

NASA Astrophysics Data System (ADS)

Yong, Benny; Chin, Liem

2017-05-01

Dengue fever is one of the most serious diseases and this disease can cause death. Currently, Indonesia is a country with the highest cases of dengue disease in Southeast Asia. Bandung is one of the cities in Indonesia that is vulnerable to dengue disease. The sub-districts in Bandung had different levels of relative risk of dengue disease. Dengue disease is transmitted to people by the bite of an Aedesaegypti mosquito that is infected with a dengue virus. Prevention of dengue disease is by controlling the vector mosquito. It can be done by various methods, one of the methods is fogging. The efforts made by the Health Department of Bandung through fogging had constraints in terms of limited funds. This problem causes Health Department selective in fogging, which is only done for certain locations. As a result, many sub-districts are not handled properly by the Health Department because of the unequal distribution of activities to prevent the spread of dengue disease. Thus, it needs the proper allocation of funds to each sub-district in Bandung for preventing dengue transmission optimally. In this research, the optimization model using Markowitz model approach will be applied to determine the allocation of funds should be given to each sub-district in Bandung. Some constraints will be added to this model and the numerical solution will be solved with generalized reduced gradient method using Solver software. The expected result of this research is the proportion of funds given to each sub-district in Bandung correspond to the level of risk of dengue disease in each sub-district in Bandung so that the number of dengue cases in this city can be reduced significantly.

[Medical and surgical health care for congenital heart disease: a panoramic vision of the reality in Mexico. Inquiry 2009].

PubMed

Calderón-Colmenero, Juan; De-la-Llata, Manuel; Vizcaíno, Alfredo; Ramírez, Samuel; Bolio, Alejandro

2011-01-01

The only way to characterize the Mexican problem related to congenital heart disease care is promoting the creation of a national database for registering the organization, resources, and related activities. The Health Secretary of Mexico adopted a Spanish registration model to design a survey for obtaining a national Mexican reference in congenital heart disease. This survey was distributed to all directors of medical and/or surgical health care centers for congenital heart disease in Mexico. This communication presents the results obtained in relation to organization, resources and activities performed during the last year 2009. From the 22 health care centers which answered the survey 10 were reference centers (45%) and 12 were assistant centers (55%). All of them are provided with cardiologic auxiliary diagnostic methods. Except one, all centers have at least one bidimentional echocardiography apparatus. There is a general deficit between material and human resources detected in our study. Therapeutic actions for congenital heart disease (70% surgical and 30% therapeutical interventionism) show a clear centralization tendency for this kind of health care in Mexico City, Monterrey and finally Guadalajara. Due to the participation of almost all cardiac health centers in Mexico, our study provides an important information related to organization, resources, and medical and/or surgical activities for congenital heart disease. The data presented not only show Mexican reality, but allows us to identify better the national problematic for establishing priorities and propose solution alternatives.

Health, lifestyle, belief and knowledge differences between two ethnic groups with specific reference to tobacco, diet and physical activity.

PubMed

Anthony, Denis; Baggott, Rob; Tanner, Judith; Jones, Kathryn; Evans, Hala; Perkins, Gill; Palmer, Hilary

2012-11-01

  To compare physical activity levels, body mass index, habitual diet, tobacco use and prevalence of non-communicable disease between the two ethnic groups and to identify predictors for differences between groups.   Tobacco use, poor diet and physical inactivity are major lifestyle risk factors for chronic cardiovascular diseases, certain cancers, diabetes and chronic lung diseases. There are higher risk and incidence of these diseases in some ethnic groups, for example Asians have higher incidence of diabetes.   Cross sectional survey.   Cross sectional survey of Asians of Indian descent and white British adults conducted between October-December 2009. Main outcome variables were lifestyle behaviours and BMI. Self-reported disease diagnosis was also collected. In a regression analysis, predictors of outcome variables were demographic variables and beliefs/attitudes/knowledge towards lifestyle behaviours.   Body mass index, tobacco use and non-communicable disease (except diabetes) were lower in Indians. Indians reported lower physical activity levels and greater salt use than Whites. Tobacco use was higher in Whites, but knowledge, attitudes and beliefs were similar between Whites and Indians.   Health risk behaviour and morbidity are different between the two ethnic groups. Gender, age, educational level, beliefs, attitudes and knowledge do not explain these differences. Health promotion that aims to improve knowledge will probably not work and innovative methods are needed to improve health in high risk groups. © 2012 Blackwell Publishing Ltd.

Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases.

PubMed

Ishida, Kentaro; Gee, Peter; Hotta, Akitsu

2015-10-16

Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9.

Serum level of vitamin D3 in cutaneous melanoma

PubMed Central

de Oliveira, Renato Santos; de Oliveira, Daniel Arcuschin; Martinho, Vitor Augusto Melão; Antoneli, Célia Beatriz Gianotti; Marcussi, Ludmilla Altino de Lima; Ferreira, Carlos Eduardo dos Santos

2014-01-01

Objective To compare the level of vitamin D3 in cutaneous melanoma patients, with or without disease activity, with reference values and with patients from a general hospital. Methods The serum levels of vitamin D3 were measured in cutaneous melanoma patients, aged 20 to 88 years, both genders, from January 2010 to December 2013. The samples from the general group were processed at Hospital Israelita Albert Einstein (control group). Data analysis was performed using the Statistics software. Results A total of 100 patients were studied, 54 of them men, with mean age of 54.67 years, and 95 Caucasian. Out of these 100 patients, 17 had active disease. The average levels of vitamin D3 in the melanoma patients were lower than the level considered sufficient, but above the average of the control group. Both groups (with or without active disease) of patients showed a similar distribution of vitamin D3 deficiency. Conclusion Vitamin D3 levels in melanoma patients were higher than those of general patients and lower than the reference level. If the reference values are appropriate, a large part of the population had insufficient levels of vitamin D, including those with melanoma, or else, this standard needs to be reevaluated. No difference in vitamin D3 levels was found among melanoma patients with or without active disease. More comprehensive research is needed to assess the relation between vitamin D and melanoma. PMID:25628199

Synergistic Action of Flavonoids, Baicalein, and Daidzein in Estrogenic and Neuroprotective Effects: A Development of Potential Health Products and Therapeutic Drugs against Alzheimer's Disease

PubMed Central

Choi, Roy C. Y.; Zhu, Judy T. T.; Yung, Amanda W. Y.; Lee, Pinky S. C.; Xu, Sherry L.; Guo, Ava J. Y.; Zhu, Kevin Y.; Dong, Tina T. X.; Tsim, Karl W. K.

2013-01-01

Despite the classical hormonal effect, estrogen has been reported to mediate neuroprotection in the brain, which leads to the searching of estrogen-like substances for treating neurodegenerative diseases. Flavonoids, a group of natural compounds, are well known to possess estrogenic effects and used to substitute estrogen, that is, phytoestrogen. Flavonoid serves as one of the potential targets for the development of natural supplements and therapeutic drugs against different diseases. The neuroprotection activity of flavonoids was chosen for a possible development of anti-Alzheimer's drugs or food supplements. The estrogenic activity of two flavonoids, baicalein and daidzein, were demonstrated by their strong abilities in stimulating estrogen receptor phosphorylation and transcriptional activation of estrogen responsive element in MCF-7 breast cells. The neuroprotection effects of flavonoids against β-amyloid (Aβ) were revealed by their inhibition effects on in vitro Aβ aggregation and Aβ-induced cytotoxicity in PC12 neuronal cells. More importantly, the estrogenic and neuroprotective activities of individual flavonoid could be further enhanced by the cotreatment in the cultures. Taken together, this synergistic effect of baicalein and daidzein might serve as a method to improve the therapeutic efficacy of different flavonoids against Aβ, which might be crucial in developing those flavonoidsin treating Alzheimer's disease in the future. PMID:24058373

Legg-Calvé-Perthes disease.

PubMed

Schoenecker, P L

1986-09-01

Legg-Calvé-Perthes disease, or osteochondrosis of the femoral head, occurs predominantly in boys 4 to 7 years of age. The disease progresses through synovitis, necrosis, fragmentation, and a residual stage. Outcome can be affected by age at disease onset, the extent of femoral head involvement as determined by x-ray, and the degree to which normal range of motion is maintained. The goal of treatment is to minimize residual deformity of the femoral head and acetabulum. This is accomplished by containing the femoral head well within the acetabulum and maintaining range of motion while the disease process runs its course. In extremely young patients, containment is often achieved during normal daily living activities. Containment treatment methods include abduction casting or orthosis; surgical containment can be accomplished by femoral or innominate osteotomy.

Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis.

PubMed

Suzuki, Hitoshi

2018-05-08

IgA nephropathy (IgAN) is the most prevalent glomerular disease worldwide and is associated with a poor prognosis. Development of curative treatment strategies and approaches for early diagnosis is necessary. Renal biopsy is the gold standard for the diagnosis and assessment of disease activity. However, reliable biomarkers are needed for the noninvasive diagnosis of this disease and to more fully delineate the risk of progression. With regard to the pathogenesis of IgAN, the multi-hit hypothesis, including production of galactose-deficient IgA1 (Gd-IgA1; Hit 1), IgG or IgA autoantibodies that recognize Gd-IgA1 (Hit 2), and their subsequent immune complexes formation (Hit 3) and glomerular deposition (Hit 4), has been widely supported by many studies. Although the prognostic values of several biomarkers have been discussed, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of Gd-IgA1 and Gd-IgA1-containing immune complexes. In addition, urinary Gd-IgA1 may represent a disease-specific biomarker for IgAN. We also confirmed that there is a significant correlation between serum levels of these effector molecules and disease activity, suggesting that each can be considered a practical surrogate marker of therapeutic response. Thus, these disease-oriented specific serum and urine biomarkers may be useful for screening of potential IgAN with isolated hematuria, earlier diagnosis, disease activity, and eventually, response to treatment. In this review, we discuss these concepts, with a focus on potential clinical applications of these biomarkers.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome

PubMed Central

Bertsias, G K; Agmon-Levin, N; Brown, S; Cervera, R; Costedoat-Chalumeau, N; Doria, A; Fischer-Betz, R; Forger, F; Moraes-Fontes, M F; Khamashta, M; King, J; Lojacono, A; Marchiori, F; Meroni, P L; Mosca, M; Motta, M; Ostensen, M; Pamfil, C; Raio, L; Schneider, M; Svenungsson, E; Tektonidou, M; Yavuz, S; Boumpas, D; Tincani, A

2017-01-01

Objectives Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. Results Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. Conclusions Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus. PMID:27457513

Communications strategies for on-ship CDPC systems.

PubMed

Jerome, Carlos

2012-01-01

Individual countries and international organisations have worked on standardising methods for on-ship prevention and control of communicable disease (CDPC). A number of voices have called for integrating the various aspects of maritime CDPC. The purpose of this article is to further conceptualise the totality of on-ship CDPC activity as an integrated system and to suggest a few strategies for communications in such systems. The methods used to summarise standardisation and integration of ship-board CDPC procedures included a scientific literature review and a web search. The fields of the review were maritime, health, and technology sources. Special attention was paid to material dealing with communications methods and issues related to ship-board systems and methods to manage communicable diseases. Effective communications strategies are vital for the success of CDPC systems. I suggest some specific viewpoints and strategies to improve communications: (i) It is sometimes helpful to view the Constituent Relations Management (CRM) team as a system component. This view highlights the fact that an on-ship CDPC system will be well designed and maintained only if constituent relations are well designed and maintained. (ii) For rapid communications with appropriate groups of constituents, it is important to structure groups of constituents, with the ability to rapidly apply set-theoretic operations to those groups. (iii) Optimistic concurrency control is generally the appropriate general strategy for synchronisation of on-ship CDPC data locations and data storage types. This may be modified in special situations, in particular with a latest-update-wins policy for disease contraction data in an epidemic. (iv) To encourage traveller cooperation with CDPC efforts, cultural activities may be helpful.

Gastrointestinal Behçet's disease: A review

PubMed Central

Skef, Wasseem; Hamilton, Matthew J; Arayssi, Thurayya

2015-01-01

Behçet’s disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet’s disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time. PMID:25852265

Low dynamic muscle strength and its associations with fatigue, functional performance, and quality of life in premenopausal patients with systemic lupus erythematosus and low disease activity: a case–control study

PubMed Central

2013-01-01

Background The purpose of the present study was to compare dynamic muscle strength, functional performance, fatigue, and quality of life in premenopausal systemic lupus erythematosus (SLE) patients with low disease activity versus matched-healthy controls and to determine the association of dynamic muscle strength with fatigue, functional performance, and quality of life in SLE patients. Methods We evaluated premenopausal (18–45 years) SLE patients with low disease activity (Systemic lupus erythematosus disease activity index [SLEDAI]: mean 1.5 ± 1.2). The control (n = 25) and patient (n = 25) groups were matched by age, physical characteristics, and the level of physical activities in daily life (International Physical Activity Questionnaire IPAQ). Both groups had not participated in regular exercise programs for at least six months prior to the study. Dynamic muscle strength was assessed by one-repetition maximum (1-RM) tests. Functional performance was assessed by the Timed Up and Go (TUG), in 30-s test a chair stand and arm curl using a 2-kg dumbbell and balance test, handgrip strength and a sit-and-reach flexibility test. Quality of life (SF-36) and fatigue were also measured. Results The SLE patients showed significantly lower dynamic muscle strength in all exercises (leg press 25.63%, leg extension 11.19%, leg curl 15.71%, chest press 18.33%, lat pulldown 13.56%, 1-RM total load 18.12%, P < 0.001-0.02) compared to the controls. The SLE patients also had lower functional performance, greater fatigue and poorer quality of life. In addition, fatigue, SF-36 and functional performance accounted for 52% of the variance in dynamic muscle strength in the SLE patients. Conclusions Premenopausal SLE patients with low disease activity showed lower dynamic muscle strength, along with increased fatigue, reduced functional performance, and poorer quality of life when compared to matched controls. PMID:24011222

Positive correlation between inflammation on sacroiliac joint MRI and serum C-terminal telopeptide of type-I collagen in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis.

PubMed

Kang, Kwi Young; Jung, Joon-Yong; Hong, Yeon Sik; Ju, Ji Hyeon; Park, Sung-Hwan

2017-01-01

To identify the clinical disease activity scores and laboratory markers that best reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). This cross-sectional study included all consecutive patients who presented with axial spondyloarthritis in 2013-2015. All underwent SIJ MRI. The bone marrow oedema in the inflammatory lesions on MRI was scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide of type-I collagen (sCTX-I), and inflammatory markers were measured. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were assessed. The correlations between the MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables were evaluated. Of the 81 patients with axSpA, 45 had AS and 36 had nr-axSpA. The AS and nr-axSpA groups did not differ in terms of disease activity scores, physical functional index, or MRI-determined SIJ inflammation. Erythrocyte sedimentation rate, C-reactive protein, and ASDAS correlated with MRI inflammatory scores in nr-axSpA but not in AS. sCTX-I correlated with MRI-determined SIJ inflammatory scores in AS only. BASDAI and BALP levels did not associate with MRI inflammatory scores in either group. Multivariate analysis showed that sCTX-I associated independently with MRI inflammatory score in AS (β=17.047, p=0.038). Inflammatory markers and ASDAS correlated with active sacroiliitis on MRI in nr-axSpA only. In AS, only sCTX-I correlated with active inflammation on SIJ MRI. sCTX-I may be useful as a marker of objective inflammation in AS.

Saint John's wort, an herbal inducer of the cytochrome P4503A4 isoform, may alleviate symptoms of Willis-Ekbom's disease

PubMed Central

Pereira, José Carlos; Pradella-Hallinan, Márcia; Alves, Rosana Cardoso

2013-01-01

OBJECTIVE: Certain drug classes alleviate the symptoms of Willis-Ekbom's disease, whereas others aggravate them. The pharmacological profiles of these drugs suggest that drugs that alleviate Willis-Ekbom's disease inhibit thyroid hormone activity, whereas drugs that aggravate Willis-Ekbom's disease increase thyroid hormone activity. These different effects may be secondary to the opposing actions that drugs have on the CYP4503A4 enzyme isoform. Drugs that worsen the symptoms of the Willis-Ekbom's disease inhibit the CYP4503A4 isoform, and drugs that ameliorate the symptoms induce CYP4503A4. The aim of this study is to determine whether Saint John's wort, as an inducer of the CYP4503A4 isoform, diminishes the severity of Willis-Ekbom's disease symptoms by increasing the metabolism of thyroid hormone in treated patients. METHODS: In an open-label pilot trial, we treated 21 Willis-Ekbom's disease patients with a concentrated extract of Saint John's wort at a daily dose of 300 mg over the course of three months. RESULTS: Saint John's wort reduced the severity of Willis-Ekbom's disease symptoms in 17 of the 21 patients. CONCLUSION: Results of this trial suggest that Saint John's wort may benefit some Willis-Ekbom's disease patients. However, as this trial was not placebo-controlled, the extent to which Saint John's wort is effective as a Willis-Ekbom's disease treatment will depend on future, blinded placebo-controlled studies. PMID:23778343

Neutrophil-Related Gene Expression And Low-Density Granulocytes Associated with Disease Activity and Response to Treatment in ANCA-Associated Vasculitis

PubMed Central

Grayson, Peter C.; Carmona-Rivera, Carmelo; Xu, Lijing; Lim, Noha; Gao, Zhong; Asare, Adam L.; Specks, Ulrich; Stone, John H.; Seo, Philip; Spiera, Robert F.; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St Clair, E. William; Tchao, Nadia K.; Ytterberg, Steven R.; Phippard, Deborah J.; Merkel, Peter A.; Kaplan, Mariana J.; Monach, Paul A.

2015-01-01

Objectives To discover biomarkers involved in the pathophysiology of ANCA-associated vasculitis (AAV) and determine if low-density granulocytes (LDGs) contribute to gene expression signatures in AAV. Methods The source of clinical data and linked biospecimens was a randomized controlled treatment trial in AAV. RNA-sequencing of whole blood from patients with AAV was performed during active disease at the baseline visit (BL) and during remission 6 months later (6M). Gene expression was compared between patients who met versus did not meet the primary trial outcome of clinical remission at 6M (responders vs. nonresponders). Measurement of neutrophil-related gene expression was confirmed in PBMCs to validate findings in whole blood. A negative selection strategy isolated LDGs from PBMC fractions. Results Differential expression between responders (n=77) and nonresponders (n=35) was detected in 2,346 transcripts at BL visit (p<0.05). Unsupervised hierarchical clustering demonstrated a cluster of granulocyte-related genes, including myeloperoxidase (MPO) and proteinase 3 (PR3). A granulocyte multi-gene composite score was significantly higher in nonresponders than responders (p<0.01) and during active disease compared to remission (p<0.01). This signature strongly overlapped an LDG signature identified previously in lupus (FDRGSEA<0.01). Transcription of PR3 measured in PBMCs was associated with active disease and treatment response (p<0.01). LDGs isolated from patients with AAV spontaneously formed neutrophil extracellular traps containing PR3 and MPO. Conclusions In AAV an increased expression of a granulocyte gene signature is associated with disease activity and decreased response to treatment. The source of this signature is likely LDGs, a potentially pathogenic cell type in AAV. PMID:25891759

Calculating the ankylosing spondylitis disease activity score if the conventional c-reactive protein level is below the limit of detection or if high-sensitivity c-reactive protein is used: an analysis in the DESIR cohort.

PubMed

Machado, Pedro; Navarro-Compán, Victoria; Landewé, Robert; van Gaalen, Floris A; Roux, Christian; van der Heijde, Désirée

2015-02-01

The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite measure of disease activity in axial spondyloarthritis. The aims of this study were to determine the most appropriate method for calculating the ASDAS using the C-reactive protein (CRP) level when the conventional CRP level was below the limit of detection, to determine how low CRP values obtained by high-sensitivity CRP (hsCRP) measurement influence ASDAS-CRP results, and to test agreement between different ASDAS formulae. Patients with axial spondyloarthritis who had a conventional CRP level below the limit of detection (5 mg/liter) were selected (n = 257). The ASDAS–conventional CRP with 11 different imputations for the conventional CRP value (range 0–5 mg/liter, at 0.5-mg/liter intervals) was calculated. The ASDAS-hsCRP and ASDAS using the erythrocyte sedimentation rate (ESR) were also calculated. Agreement between the ASDAS formulae was tested. The ASDAS-hsCRP showed better agreement with the ASDAS-CRP calculated using the conventional CRP imputation values of 1.5 and 2.0 mg/liter and with the ASDAS-ESR than with other imputed formulae. Disagreement occurred mainly in lower disease activity states (inactive/moderate disease activity). When the CRP value was <2 mg/liter, the resulting ASDAS-CRP scores may have been inappropriately low. When the conventional CRP level is below the limit of detection or when the hsCRP level is <2 mg/liter, the constant value of 2 mg/liter should be used to calculate the ASDAS-CRP score. There is good agreement between the ASDAS-hsCRP and ASDAS-ESR; however, formulae are not interchangeable.

Foot function is well preserved in children and adolescents with juvenile idiopathic arthritis who are optimally managed

PubMed Central

Hendry, Gordon J.; Rafferty, Danny; Barn, Ruth; Gardner-Medwin, Janet; Turner, Debbie E.; Woodburn, James

2013-01-01

Purpose The objective of this study was to compare disease activity, impairments, disability, foot function and gait characteristics between a well described cohort of juvenile idiopathic arthritis (JIA) patients and normal healthy controls using a 7-segment foot model and three-dimensional gait analysis. Methods Fourteen patients with JIA (mean (standard deviation) age of 12.4 years (3.2)) and a history of foot disease and 10 healthy children (mean (standard deviation) age of 12.5 years (3.4)) underwent three-dimensional gait analysis and plantar pressure analysis to measure biomechanical foot function. Localised disease impact and foot-specific disease activity were determined using the juvenile arthritis foot disability index, rear- and forefoot deformity scores, and clinical and musculoskeletal ultrasound examinations respectively. Mean differences between groups with associated 95% confidence intervals were calculated using the t distribution. Results Mild-to-moderate foot impairments and disability but low levels of disease activity were detected in the JIA group. In comparison with healthy subjects, minor trends towards increased midfoot dorsiflexion and reduced lateral forefoot abduction within a 3–5° range were observed in patients with JIA. The magnitude and timing of remaining kinematic, kinetic and plantar pressure distribution variables during the stance phase were similar for both groups. Conclusion In children and adolescents with JIA, foot function as determined by a multi-segment foot model did not differ from that of normal age- and gender-matched subjects despite moderate foot impairments and disability scores. These findings may indicate that tight control of active foot disease may prevent joint destruction and associated structural and functional impairments. PMID:23142184

Combined mepacrine-hydroxychloroquine treatment in patients with systemic lupus erythematosus and refractory cutaneous and articular activity.

PubMed

Ugarte, A; Porta, S; Ríos, R; Martinez-Zapico, A; Ortego-Centeno, N; Agesta, N; Ruiz-Irastorza, G

2018-01-01

Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such patients.

Total antioxidant activity and antimicrobial potency of the essential oil and oleoresin of Zingiber officinale Roscoe

PubMed Central

Bellik, Yuva

2014-01-01

Objective To compare in vitro antioxidant and antimicrobial activities of the essential oil and oleoresin of Zingiber officinale Roscoe. Methods The antioxidant activity was evaluated based on the ability of the ginger extracts to scavenge ABTS°+ free radical. The antimicrobial activity was studied by the disc diffusion method and minimal inhibitory concentration was determined by using the agar incorporation method. Results Ginger extracts exerted significant antioxidant activity and dose-depend effect. In general, oleoresin showed higher antioxidant activity [IC50=(1.820±0.034) mg/mL] when compared to the essential oil [IC50=(110.14±8.44) mg/mL]. In terms of antimicrobial activity, ginger compounds were more effective against Escherichia coli, Bacillus subtilis and Staphylococcus aureus, and less effective against Bacillus cereus. Aspergillus niger was least, whereas, Penicillium spp. was higher sensitive to the ginger extracts; minimal inhibitory concentrations of the oleoresin and essential oil were 2 mg/mL and 869.2 mg/mL, respectively. Moreover, the studied extracts showed an important antifungal activity against Candida albicans. Conclusions The study confirms the wide application of ginger oleoresin and essential oil in the treatment of many bacterial and fungal diseases.

Screening of lysosomal storage disorders: application of the online trapping-and-cleanup liquid chromatography/mass spectrometry method for mucopolysaccharidosis I.

PubMed

Ombrone, Daniela; Malvagia, Sabrina; Funghini, Silvia; Giocaliere, Elisa; Della Bona, Maria Luisa; Forni, Giulia; De Luca, Alessio; Villanelli, Fabio; Casetta, Bruno; Guerrini, Renzo; la Marca, Giancarlo

2013-01-01

In recent years, new treatments have become available to treat some lysosomal storage disorders (LSDs) and many studies suggest that there is a benefit with starting therapy early. Newborn screening should detect diseases early enough for prompt treatment. Some countries include additional conditions, such as some LSDs, into their newborn screening panels. Mucopolysaccharidosis Type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase (IDUA) activity. Currently, enzyme replacement therapy (ERT) or bone marrow transplantation is available and this has raised a growing interest for the development of a newborn screening test. In 2009, we reported a new fast and simplified tandem mass spectrometry-based method for quantifying five enzyme activities on dried blood spots. Here, we describe the inclusion of IDUA activity determination for the simultaneous detection of six lysosomal storage diseases. We have defined reference normal ranges by testing 680 healthy newborns and 240 adults. The assay was checked through three confirmed MPS I patients whose IDUA activity was below the normal range. Reproducibility of the assays has been established by assessing the intra-day and inter-day assay imprecisions. This quick assay has been devised to be implemented in newborn screening by liquid chromatography tandem mass spectrometry.

Preventing Cognitive Decline in Older African Americans with Mild Cognitive Impairment: Design and Methods of a Randomized Clinical Trial

PubMed Central

Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Leiby, Benjamin E.

2012-01-01

Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

Characterisation of an epigenetically altered CD4+ CD28+ Kir+ T cell subset in autoimmune rheumatic diseases by multiparameter flow cytometry

PubMed Central

Strickland, Faith M; Patel, Dipak; Somers, Emily; Robida, Aaron M; Pihalja, Michael; Swartz, Richard; Marder, Wendy; Richardson, Bruce

2016-01-01

Objectives Antigen-specific CD4+ T cells epigenetically modified with DNA methylation inhibitors overexpress genes normally suppressed by this mechanism, including CD11a, CD70, CD40L and the KIR gene family. The altered cells become autoreactive, losing restriction for nominal antigen and responding to self-class II major histocompatibility complex (MHC) molecules without added antigen, and are sufficient to cause a lupus-like disease in syngeneic mice. T cells overexpressing the same genes are found in patients with active lupus. Whether these genes are co-overexpressed on the same or different cells is unknown. The goal of this study was to determine whether these genes are overexpressed on the same or different T cells and whether this subset of CD4+ T cells is also present in patients with lupus and other rheumatic diseases. Methods Multicolour flow cytometry was used to compare CD11a, CD70, CD40L and KIR expression on CD3+CD4+CD28+ T cells to their expression on experimentally demethylated CD3+CD4+CD28+ T cells and CD3+CD4+CD28+ T cells from patients with active lupus and other autoimmune diseases. Results Experimentally demethylated CD4+ T cells and T cells from patients with active lupus have a CD3+CD4+CD28+CD11ahiCD70+CD40LhiKIR+ subset, and the subset size is proportional to lupus flare severity. A similar subset is found in patients with other rheumatic diseases including rheumatoid arthritis, systemic sclerosis and Sjögren's syndrome but not retroperitoneal fibrosis. Conclusions Patients with active autoimmune rheumatic diseases have a previously undescribed CD3+CD4+CD28+CD11ahiCD70+CD40LhiKIR+ T cell subset. This subset may play an important role in flares of lupus and related autoimmune rheumatic diseases, provide a biomarker for disease activity and serve as a novel therapeutic target for the treatment of lupus flares. PMID:27099767

Grading of inflammatory disease activity in the sacroiliac joints with magnetic resonance imaging: comparison between short-tau inversion recovery and gadolinium contrast-enhanced sequences.

PubMed

Madsen, Karen Berenth; Egund, Niels; Jurik, Anne Grethe

2010-02-01

We investigated the potential concordance of 2 different magnetic resonance (MR) sequences - short-tau inversion recovery (STIR) and fat-saturated T1-weighted spin-echo after application of gadolinium (Gd) contrast medium to detect active bone marrow abnormalities at the sacroiliac joints (SIJ) in patients with spondyloarthritis (SpA). Blinded and using the Danish scoring method, we evaluated transaxial MR images of the 2 sequences in 40 patients with SpA with disease duration of 3-14 years. Both the cartilaginous and ligamentous portions of the SIJ were analyzed. There was a significant positive correlation between the activity scores obtained by STIR and Gd-enhanced sequences (p < 0.0001). Agreement in the detection of bone marrow abnormalities occurred in 60 of the 80 joints, 35 with and 25 without signs of active disease. Discordance with STIR-positive marrow activity scores occurred in only 11 joints; Gd-enhanced positive scores in 9 joints. The STIR sequence detected remnants of marrow activity in the periphery of chronic fatty replacement not seen or partly obscured on the Gd sequence. Small subchondral enhancing lesions may not be scored on the STIR sequence, mostly because of reduced image resolution. Active bone marrow abnormalities were detected nearly equally well with STIR and Gd-enhanced fat-suppressed T1 sequences in patients with SpA, with STIR being most sensitive to visualize active abnormalities in the periphery of chronic changes.

Vital Signs: Prevalence of Doctor-Diagnosed Arthritis and Arthritis-Attributable Activity Limitation — United States, 2013–2015

PubMed Central

Helmick, Charles G.; Boring, Michael; Brady, Teresa J.

2017-01-01

Background In the United States, doctor-diagnosed arthritis is a common and disabling chronic condition. Arthritis can lead to severe joint pain and poor physical function, and it can negatively affect quality of life. Methods CDC analyzed 2013–2015 data from the National Health Interview Survey, an annual, nationally representative, in-person interview survey of the health status and behaviors of the noninstitutionalized civilian U.S. adult population, to update previous prevalence estimates of arthritis and arthritis-attributable activity limitations. Results On average, during 2013–2015, 54.4 million (22.7%) adults had doctor-diagnosed arthritis, and 23.7 million (43.5% of those with arthritis) had arthritis-attributable activity limitations (an age-adjusted increase of approximately 20% in the proportion of adults with arthritis reporting activity limitations since 2002 [p-trend <0.001]). Among adults with heart disease, diabetes, and obesity, the prevalences of doctor-diagnosed arthritis were 49.3%, 47.1%, and 30.6%, respectively; the prevalences of arthritis-attributable activity limitations among adults with these conditions and arthritis were 54.5% (heart disease), 54.0% (diabetes), and 49.0% (obesity). Conclusions and Comments The prevalence of arthritis is high, particularly among adults with comorbid conditions, such as heart disease, diabetes, and obesity. Furthermore, the prevalence of arthritis-attributable activity limitations is high and increasing over time. Approximately half of adults with arthritis and heart disease, arthritis and diabetes, or arthritis and obesity are limited by their arthritis. Greater use of evidence-based physical activity and self-management education interventions can reduce pain and improve function and quality of life for adults with arthritis and also for adults with other chronic conditions who might be limited by their arthritis. PMID:28278145

Azasugar inhibitors as pharmacological chaperones for Krabbe disease

DOE PAGES

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

2015-03-23

Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe amore » new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.« less

Occupational physical activity assessment for chronic disease prevention and management: A review of methods for both occupational health practitioners and researchers.

PubMed

Scott, Kenneth A; Browning, Raymond C

2016-01-01

Occupational physical activity (OPA) is an occupational exposure that impacts worker health. OPA is amenable to measurement and modification through the hierarchy of controls. Occupational exposure scientists have roles in addressing inadequate physical activity, as well as excessive or harmful physical activity. Occupational health researchers can contribute to the development of novel OPA exposure assessment techniques and to epidemiologic studies examining the health impacts of physical activity at work. Occupational health practitioners stand to benefit from understanding the strengths and limitations of physical activity measurement approaches, such as accelerometers in smartphones, which are already ubiquitous in many workplaces and in some worksite health programs. This comprehensive review of the literature provides an overview of physical activity monitoring for occupational exposure scientists. This article summarizes data on the public health implications of physical activity at work, highlighting complex relationships with common chronic diseases. This article includes descriptions of several techniques that have been used to measure physical activity at work and elsewhere, focusing in detail on pedometers, accelerometers, and Global Positioning System technology. Additional subjective and objective measurement strategies are described as well.

A Practical Green Synthesis and Biological Evaluation of Benzimidazoles Against Two Neglected Tropical Diseases: Chagas and Leishmaniasis.

PubMed

Bandyopadhyay, Debashis; Samano, Selina; Villalobos-Rocha, Juan Carlos; Sanchez-Torres, Luvia Enid; Nogueda-Torres, Benjamin; Rivera, Gildardo; Banik, Bimal K

2017-01-01

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas' disease and leishmaniasis. Chagas' disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and millions of people are infected. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. On the other hand, Leishmaniasis represents complex diseases with an important clinical and epidemiological diversity. It is endemic in 88 countries 72 of which are developing countries and it has been estimated that are 12 million people infected and 350 million are in areas with infection risk. On this basis, research on organic compounds that can be used against these two diseases is an important target. A very simple, green, and efficient protocol is developed in which bismuth nitrate pentahydrate is employed as a Lewis acid catalyst in aqueous media under microwave irradiation for the synthesis of various 2-aryl substituted benzimidazoles from aldehydes and o-phenylenediamine. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and no wastes. Nine 1H-benzimidazole derivatives (1-9) with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by spectroscopic methods. The compounds were screened to identify whether they posses pharmacological activity against Chagas' disease and leishmaniasis. Compound 8 showed better activity than the control Nifurtimox against INC-5 Trypanosoma cruzi strain whereas compounds 3 and 9 have demonstrated potent leshmanicidal activity. A systematic green synthetic procedure and in vitro biological evaluation of nine 1H-benzimidazoles are described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Disease activity in longstanding ankylosing spondylitis: a correlation of clinical and magnetic resonance imaging findings.

PubMed

Goh, L; Suresh, P; Gafoor, A; Hughes, P; Hickling, P

2008-04-01

We evaluated magnetic resonance imaging (MRI) changes in ankylosing spondylitis (AS) patients with longstanding disease and investigated whether there is any relationship between MRI findings and validated methods of disease assessment. A total of 34 AS patients with disease duration greater than 10 years were included in this observational cross-sectional study (26 men, 8 women). The main outcome measures were Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Global assessment (BASG), Bath Ankylosing Spondylitis Metrology Index (BASMI), MRI of the thoracic and lumbar spine (AS spi MRI A) and measurement of serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasma viscosity (PV) and immunoglobulin A (Ig A). The median scores for the acute lesions based on AS spi MRI A scoring system was 2.5 (0-4.12). The respective mean ESR and CRP were 36 (SD, 24.00) mm/h and 14.19 (SD, 24.00) mg/l with the median PV of 1.8 (1.75-1.87). The median BASG, BASFI and BASDAI were 4.55 (2.37-5.55), 4.40(2.31-5.47) and 4.32 (3.07-6.48), respectively. No significant correlations were found between the acute MRI scores and each of the clinical instruments and laboratory markers of inflammation. In this study, majority of AS patients with longstanding disease had very low AS spi MRI A scores or no evidence of spinal inflammatory lesions. Our study would suggest that MRI should be used along with other measures of disease activity in the assessment of symptomatic AS patients with longstanding disease.

A Place-Based Community Health Worker Program: Feasibility and Early Outcomes, New York City, 2015

PubMed Central

Lopez, Priscilla M.; Islam, Nadia; Feinberg, Alexis; Myers, Christa; Seidl, Lois; Drackett, Elizabeth; Riley, Lindsey; Mata, Andrea; Pinzon, Juan; Benjamin, Elisabeth; Wyka, Katarzyna; Dannefer, Rachel; Lopez, Javier; Trinh-Shevrin, Chau; Maybank, Karen Aletha; Thorpe, Lorna E.

2017-01-01

Introduction This study examined feasibility of a place-based community health worker (CHW) and health advocate (HA) initiative in five public housing developments selected for high chronic disease burden and described early outcomes. Methods This intervention was informed by a mixed-method needs assessment performed December 2014–January 2015 (representative telephone survey, n=1,663; six focus groups, n=55). Evaluation design was a non-randomized, controlled quasi-experiment. Intake and 3-month follow-up data were collected February–December 2015 (follow-up response rate, 93%) on 224 intervention and 176 comparison participants, and analyzed in 2016. All participants self-reported diagnoses of hypertension, diabetes, or asthma. The intervention consisted of chronic disease self-management and goal setting through six individual CHW-led health coaching sessions, instrumental support, and facilitated access to insurance/clinical care navigation from community-based HAs. Feasibility measures included CHW service satisfaction and successful goal setting. Preliminary outcomes included clinical measures (blood pressure, BMI); disease management behaviors and self-efficacy; and preventive behaviors (physical activity). Results At the 3-month follow-up, nearly all intervention participants reported high satisfaction with their CHW (90%) and HA (76%). Intervention participants showed significant improvements in self-reported physical activity (p=0.005) and, among hypertensive participants, self-reported routine blood pressure self-monitoring (p=0.013) compared with comparison participants. No improvements were observed in self-efficacy or clinical measures at the 3-month follow-up. Conclusions Housing-based initiatives involving CHW and HA teams are acceptable to public housing residents and can be effectively implemented to achieve rapid improvements in physical activity and chronic disease self-management. At 3-month assessment, additional time and efforts are required to improve clinical outcomes. PMID:28215382

Evaluation of a novel Serious Game based assessment tool for patients with Alzheimer's disease.

PubMed

Vallejo, Vanessa; Wyss, Patric; Rampa, Luca; Mitache, Andrei V; Müri, René M; Mosimann, Urs P; Nef, Tobias

2017-01-01

Despite growing interest in developing ecological assessment of difficulties in patients with Alzheimer's disease new methods assessing the cognitive difficulties related to functional activities are missing. To complete current evaluation, the use of Serious Games can be a promising approach as it offers the possibility to recreate a virtual environment with daily living activities and a precise and complete cognitive evaluation. The aim of the present study was to evaluate the usability and the screening potential of a new ecological tool for assessment of cognitive functions in patients with Alzheimer's disease. Eighteen patients with Alzheimer's disease and twenty healthy controls participated to the study. They were asked to complete six daily living virtual tasks assessing several cognitive functions: three navigation tasks, one shopping task, one cooking task and one table preparation task following a one-day scenario. Usability of the game was evaluated through a questionnaire and through the analysis of the computer interactions for the two groups. Furthermore, the performances in terms of time to achieve the task and percentage of completion on the several tasks were recorded. Results indicate that both groups subjectively found the game user friendly and they were objectively able to play the game without computer interactions difficulties. Comparison of the performances between the two groups indicated a significant difference in terms of percentage of achievement of the several tasks and in terms of time they needed to achieve the several tasks. This study suggests that this new Serious Game based assessment tool is a user-friendly and ecological method to evaluate the cognitive abilities related to the difficulties patients can encounter in daily living activities and can be used as a screening tool as it allowed to distinguish Alzheimer's patient's performance from healthy controls.

Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases

PubMed Central

2010-01-01

Background Endometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility. This disease has been associated to development of different types of malignancies; therefore new blood vessels are essential for the survival of the endometrial implant. Our previous observations on humans showed that angiogenesis is predominantly found in rectosigmoid endometriosis, a deeply infiltrating disease. In this study, we have established the experimental model of rat peritoneal endometriosis to evaluate the process of angiogenesis and to compare with eutopic endometrium. Methods We have investigated the morphological characteristics of these lesions and the vascular density, VEGF and its receptor Flk-1 and MMP-9 expression, and activated macrophage distribution, using immunohistochemistry and RT-PCR. Results As expected, the auto-transplantation of endometrium pieces into the peritoneal cavity is a well-established method for endometriosis induction in rats. The lesions were cystic and vascularized, and demonstrated histological hallmarks of human pathology, such as endometrial glands and stroma. The vascular density and the presence of VEGF and Flk-1 and MMP-9 were significantly higher in endometriotic lesions than in eutopic endometrium, and confirmed the angiogenic potential of these lesions. We also observed an increase in the number of activated macrophages (ED-1 positive cells) in the endometriotic lesions, showing a positive correlation with VEGF. Conclusion The present endometriosis model would be useful for investigation of the mechanisms of angiogenesis process involved in the peritoneal attachment of endometrial cells, as well as of the effects of therapeutic drugs, particularly with antiangiogenic activity. PMID:20085636

Male fertility potential alteration in rheumatic diseases: a systematic review

PubMed Central

Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfá, Eloisa; Srougi, Miguel; Clovis, A

2016-01-01

ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy. PMID:27120778

Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly

PubMed Central

Mendoza-Núñez, Víctor Manuel; Martínez-Maldonado, María de la Luz; Correa-Muñoz, Elsa

2009-01-01

Background World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm. Methods/Design A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators (gerontological nuclei) and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i) therapeutic adherence; (ii) the incidence of the main chronic diseases in old age; (iii) life expectancy without chronic diseases at 60 years of age; (iv) disability adjusted life years lost; (v) years of life lost due to premature mortality, and (vi) years lived with disability. Discussion We propose that the implementation of the model active aging framework will permits the empowerment of older adults, which constitutes basic social capital for chronic disease prevention and control in old age. PMID:19706199

A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

PubMed

Alai, Milind; Lin, Wen Jen

2013-01-01

The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

The place of human values in the language of science: Kuhn, Saussure, and structuralism.

PubMed

Psaty, B M; Inui, T S

1991-12-01

The current paradigm in medicine generally distinguishes between genetic and environmental causes of disease. Although the word "paradigm" has become a commonplace, the theories of Thomas Kuhn have not received much attention in the journals of medicine. Kuhn's structuralist method differs radically from the daily activities of the scientific method itself. Using linguistic theory, this essay offers a structuralist reading of Thomas Kuhn's The Structure of Scientific Revolutions. Our purpose is to highlight the similarities between these structuralist models of science and language. In part, we focus on the logic that enables Kuhn to assert the priority of perception over interpretation in the history of science. To illustrate some of these issues, we refer to the distinction between environmental and genetic causes of disease. While the activity of scientific research results in the revision of concepts in science, the production of significant differences that shape our knowledge is in part a social and linguistic process.

Physical Activity Monitoring in Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Liao, Shu-Yi; Benzo, Roberto; Ries, Andrew L.; Soler, Xavier

2014-01-01

Reduced physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality (e.g. exacerbations) and eventually leads to disability, depression, and social and physical isolation. Measuring PA in this population is important to accurately characterize COPD and to help clinicians during a baseline evaluation and patient follow-up. Also, it may help increase adherence to PA programs. There are reliable objective and subjective methods available to measure PA. Recently, several new monitors have been developed that have improved accuracy of such measurements. Because these devices provide real-time feedback, they may help to improve participant self-motivation strategies and reinforce daily lifestyle modifications, one of the main goals in COPD management. This review focuses on describing available instruments to measure PA, specifically in patients with COPD. The reliability, validity, advantages, limitations, and clinical applications of questionnaires, pedometers, and accelerometers are discussed. Finally, based on current published literature, we propose recommendations about which methods may be most useful in different research or clinical settings. PMID:28848818

[Evaluation of the factorial and metric equivalence of the Sexual Assertiveness Scale (SAS) by sex].

PubMed

Sierra, Juan Carlos; Santos-Iglesias, Pablo; Vallejo-Medina, Pablo

2012-05-01

Sexual assertiveness refers to the ability to initiate sexual activity, refuse unwanted sexual activity, and use contraceptive methods to avoid sexually transmitted diseases, developing healthy sexual behaviors. The Sexual Assertiveness Scale (SAS) assesses these three dimensions. The purpose of this study is to evaluate, using structural equation modeling and differential item functioning, the equivalence of the scale between men and women. Standard scores are also provided. A total of 4,034 participants from 21 Spanish provinces took part in the study. Quota sampling method was used. Results indicate a strict equivalent dimensionality of the Sexual Assertiveness Scale across sexes. One item was flagged by differential item functioning, although it does not affect the scale. Therefore, there is no significant bias in the scale when comparing across sexes. Standard scores show similar Initiation assertiveness scores for men and women, and higher scores on Refusal and Sexually Transmitted Disease Prevention for women. This scale can be used on men and women with sufficient psychometric guarantees.

Neurocognitive Dysfunction in Systemic Lupus Erythematosus: Association with Antiphospholipid Antibodies, Disease Activity and Chronic Damage

PubMed Central

Conti, Fabrizio; Alessandri, Cristiano; Perricone, Carlo; Scrivo, Rossana; Rezai, Soheila; Ceccarelli, Fulvia; Spinelli, Francesca Romana; Ortona, Elena; Marianetti, Massimo; Mina, Concetta; Valesini, Guido

2012-01-01

Introduction Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. Methods Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs). Results Nineteen percent of patients had mild GCDs impairment (GCDs 2–3), 7% moderate (GCDs 4–5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = −0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment. Conclusions Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients. PMID:22461897

Tibetan medicine "RNSP" in treatment of Alzheimer disease.

PubMed

Shi, Jing-Ming; He, Xue; Lian, Hui-Juan; Yuan, Dong-Ya; Hu, Qun-Ying; Sun, Zheng-Qi; Li, Yan-Song; Zeng, Yu-Wen

2015-01-01

Alzheimer disease (Alzheimer Disease, AD) is one of the most common type in senile dementia. Its main pathological features were that a large number of senile plaques gathered in brain extracellular and tangles fibrosis appeared in nerve cells. Currently, the pathogenesis of AD is still uncertain, and scale investigation and combined brain CT, MRI data were analyzed mainly for clinical diagnosis. Mitigation and improvement of the nervous system activity to interfere with the subsequent behavior of the patients are the main methods for treatment. In clinical no drug can really prevent and cure AD. From the view point of Tibetan medicine studies, Tibetan medicine RNSP has effect on improving memory and repairing the neurons in the brain. In this study, we combined the characteristics of AD pathology, pathogenesis, diagnosis and treatment methods to explore the feasibility of Tibetan medicine RNSP for the treatment of AD to provide new ideas for the diagnosis and treatment of AD.

Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener's granulomatosis

PubMed Central

Slart, R; Jager, P; Poot, L; Piers, D; Cohen, T; Stegeman, C

2003-01-01

Background: Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear. Objective: To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions. Methods: Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity. Results: WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections. Conclusion: Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower. PMID:12810430

Rare disease surveillance: An international perspective

PubMed Central

Elliott, Elizabeth J; Nicoll, Angus; Lynn, Richard; Marchessault, Victor; Hirasing, Remy; Ridley, Greta

2001-01-01

BACKGROUND: The International Network of Paediatric Surveillance Units (INoPSU) was established in 1998 and met formally for the first time in Ottawa, Ontario in June 2000. OBJECTIVES: To document the methodology and activities of existing national paediatric surveillance units; the formation of INoPSU; the diseases studied by INoPSU members; and the impact of such studies on education, public health and paediatric practice. METHODS: Directors of paediatric surveillance units in Australia, Britain, Canada, Germany, the Netherlands, Latvia, Malaysia, Papua New Guinea, New Zealand and Switzerland were asked to provide information on each unit’s affiliations, funding and staffing; the method of case ascertainment, the mailing list and response rates; and diseases studied. Original articles that reported data derived from units were identified by a search of an electronic database (MEDLINE), and additional information was obtained from units’ annual reports. RESULTS: Worldwide, 10 units (established from 1986 to 1997), use active national surveillance of more than 8500 clinicians each month to identify cases of rare or uncommon diseases in a childhood population (younger than 15 years of age) of over 47 million (monthly response rate 73% to 98%). By January 1999, units had initiated 147 studies on 103 different conditions, and 63 studies were completed. CONCLUSION: INoPSU enhances collaboration among units from four continents, providing a unique opportunity for simultaneous cross-sectional studies of rare diseases in populations with diverse geographical and ethnic characteristics. It facilitates the sharing of ideas regarding current methodology, ethics, the most appropriate means of evaluating units and their potential application. PMID:20084246

Research and Operational Support for the Study of Militarily Relevant Infectious Diseases of Interest to the United States Army and the Royal Thai Army

DTIC Science & Technology

2009-01-01

to provide funding support for Royal Thai Army at Armed Forces Research Institute of Medical Sciences (AFRIMS) engaged in research activities in...City, Philippines (WRAIR #1385) 77 (a) Investigators 77 (b) Objectives 77 12 (c) Methods 78 (d) Results 78 (e) Future Plans 79 10...Title of Research Project: Sentinel Surveillance for Emerging Diseases Causing Hospitalized Dengue-like Illness in Cebu, Philippines (SEDC) 79

Conservative treatment of sickle cell avascular necrosis of the femoral head.

PubMed

Washington, E R; Root, L

1985-01-01

Treatment of avascular necrosis of the femoral head in adolescents with sickle cell anemia has not yet been standardized. In this study we review the literature and report on three patients with the Legg-Perthes-type avascular necrosis associated with sickle cell disease. These patients were successfully treated by partial weight-bearing with crutches and active range-of-motion exercises. We have examined physiologic and anatomic factors in this specific disease syndrome, which suggest that this may be the preferred method of treatment.

Vaccine therapy for HIV: a historical review of the treatment of infectious diseases by active specific immunization with microbe-derived antigens.

PubMed

Burke, D S

1993-01-01

A review of the history of 'vaccine therapy' for infectious diseases is presented. The concept originated when Auzias-Turenne introduced 'syphilitic vaccination' or 'syphilization' as a treatment for syphilis in Paris in the mid-1800s; his clinical studies probably influenced Pasteur's successful rabies postexposure vaccine trials. Robert Koch in Berlin in the 1890s observed that inoculation of tuberculin into patients with tuberculosis induced an inflammatory response in affected tissues, and advocated 'tuberculin therapy'. Sir Almroth Wright in London in the early 20th century devised methods to measure changes in serum 'opsonizing' activity in response to therapeutic inoculations with microbe-derived vaccines. Since the advent of antibiotics, active specific immunization with microbe-derived antigens (vaccine therapy) has been largely forgotten as a strategy for treatment of infectious diseases. Advances in antigen production and in molecular immunology now permit new tactics to probe, analyse and selectively alter in vivo human immune responses to infectious microbes. Our recent demonstration that vaccine therapy can boost natural immunity to HIV in infected patients should rekindle interest in this approach.

Hyper-activation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2

PubMed Central

Douse, Christopher H.; Roberts, Rhys C.; Dougan, Gordon; Kingston, Robert E.; Modis, Yorgo; Lehner, Paul J.

2017-01-01

Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR/Cas9-mediated forward genetic screen, we identify MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploit a new method – Differential Viral Accessibility (DIVA) – to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common mutation affecting the ATPase domain found in CMT patients (R252W) hyper-activates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease. PMID:28581500

Antimicrobial activity of bark extracts of Syzygium jambos (L.) alston (Myrtaceae).

PubMed

Djipa, C D; Delmée, M; Quetin-Leclercq, J

2000-07-01

Syzygium jambos (L.) Alston (Myrtaceae) is a widespread medicinal plant traditionally used in sub-Saharan Africa to treat infectious diseases. Acetone and aqueous extracts from the bark of S. jambos were tested for antimicrobial activity in vitro by the agar dilution method in petri dishes. Both extracts showed some activity against the tested micro-organisms. They proved to be particularly effective on Staphylococcus aureus, Yersinia enterocolitica and coagulase negative staphylococci among which Staphylococcus hominis, Staphylococcus cohnii and Staphylococcus warneri. These properties seem to be related to the high tannin content of S. jambos extracts (77 and 83% for the aqueous and acetone extracts, respectively, determined according to the European Pharmacopoeia method) which were generally more active than Hamamelis virginiana, Krameria triandra, Alchemilla vulgaris and Rubus fruticosus extracts containing 48, 44, 46 and 28% tannins, respectively. Furthermore, elimination of tannins totally suppressed these antimicrobial activities.

Physical activity in subjects with multiple sclerosis with focus on gender differences: a survey

PubMed Central

2014-01-01

Background There is increasing research that examines gender-issues in multiple sclerosis (MS), but little focus has been placed on gender-issues regarding physical activity. The aim of the present study was to describe levels of physical activity, self-efficacy for physical activity, fall-related self-efficacy, social support for physical activity, fatigue levels and the impact of MS on daily life, in addition to investigating gender differences. Methods The sample for this cross-sectional cohort study consisted of 287 (84 men; 29.3%) adults with MS recruited from the Swedish Multiple Sclerosis Registry. A questionnaire was sent to the subjects consisting of the self-administrated measurements: Physical Activity Disability Survey – Revised, Exercise Self-Efficacy Scale, Falls- Efficacy Scale (Swedish version), Social Influences on Physical Activity, Fatigue Severity Scale and Multiple Sclerosis Impact Scale. Response rate was 58.2%. Results Men were less physically active, had lower self-efficacy for physical activity and lower fall-related self-efficacy than women. This was explained by men being more physically affected by the disease. Men also received less social support for physical activity from family members. The level of fatigue and psychological consequences of the disease were similar between the genders in the total sample, but subgroups of women with moderate MS and relapsing remitting MS experienced more fatigue than men. Conclusions Men were less physically active, probably a result of being more physically affected by the disease. Men being more physically affected explained most of the gender differences found in this study. However, the number of men in the subgroup analyses was small and more research is needed. A gender perspective should be considered in strategies for promoting physical activity in subjects with MS, e.g. men may need more support to be physically active. PMID:24612446

The regulation of catalase activity by PPAR γ is affected by α-synuclein

PubMed Central

Yakunin, Eugenia; Kisos, Haya; Kulik, Willem; Grigoletto, Jessica; Wanders, Ronald J A; Sharon, Ronit

2014-01-01

Objective While evidence for oxidative injury is frequently detected in brains of humans affected by Parkinson's disease (PD) and in relevant animal models, there is uncertainty regarding its cause. We tested the potential role of catalase in the oxidative injury that characterizes PD. Methods Utilizing brains of A53T α-Syn and ntg mice, and cultured cells, we analyzed catalase activity and expression, and performed biochemical analyses of peroxisomal metabolites. Results Lower catalase expression and lower activity levels were detected in A53T α-Syn brains and α-Syn-expressing cells. The effect on catalase activity was independent of disease progression, represented by mouse age and α-Syn mutation, suggesting a potential physiological function for α-Syn. Notably, catalase activity and expression were unaffected in brains of mice modeling Alzheimer's disease. Moreover, we found that α-Syn expression downregulate the peroxisome proliferator-activated receptor (PPAR)γ, which controls catalase transcription. Importantly, activation of either PPARγ2, PPARα or retinoic X receptor eliminated the inhibiting effect of α-Syn on catalase activity. In addition, activation of these nuclear receptors enhanced the accumulation of soluble α-Syn oligomers, resulting in a positive association between the degree of soluble α-Syn oligomers and catalase activity. Of note, a comprehensive biochemical analysis of specific peroxisomal metabolites indicated no signs of dysfunction in specific peroxisomal activities in brains of A53T α-Syn mice. Interpretation Our results suggest that α-Syn expression may interfere with the complex and overlapping network of nuclear receptors transcription activation. In result, catalase activity is affected through mechanisms involved in the regulation of soluble α-Syn oligomers. PMID:25356396

[Change in the activity of natural killer cells in normal subjects and in virus diseases on exposure to interferon in vitro].

PubMed

Petrov, R V; Saidov, M Z; Koval'chuk, L V; Sorokin, A M; Kaganov, B S

1984-04-01

The activity of natural killers was examined in peripheral blood of healthy subjects and patients with chronic hepatitis and disseminated sclerosis. An attempt was made to correct natural killer activity by human leukocyte interferon in vitro. To assess the activity of natural killers, use was made of the method of serial dilutions. An optimal effector/target ratio was employed in experiments. The patients with chronic hepatitis and disseminated sclerosis demonstrated a reduction in the activity of natural killers whatever the effector/target ratio. The action of interferon in vitro is specific immunomodulatory in nature. Administration of interferon in a dose of 250 Units/ml raises the magnitude of the cytotoxic index in healthy donors and in patients with chronic hepatitis and disseminated sclerosis, making the shape of the killer activity curve approach that of normal. Such an approach can be used for preliminary assessment of the sensitivity of natural killers to interferon in viral diseases of man. The potentialities and efficacy of interferon in clinical medicine are discussed.

The Effect of Online Chronic Disease Personas on Activation: Within-Subjects and Between-Groups Analyses

PubMed Central

2015-01-01

Background Although self-management of chronic disease is important, engaging patients and increasing activation for self-care using online tools has proven difficult. Designing more tailored interventions through the application of condition-specific personas may be a way to increase engagement and patient activation. Personas are developed from extensive interviews with patients about their shared values and assumptions about their health. The resulting personas tailor the knowledge and skills necessary for self-care and guide selection of the self-management tools for a particular audience. Objective Pre-post changes in self-reported levels of activation for self-management were analyzed for 11 chronic health personas developed for 4 prevalent chronic diseases. Methods Personas were created from 20 to 25 hour-long nondirected interviews with consumers with a common, chronic disease (eg, diabetes). The interviews were transcribed and coded for behaviors, feelings, and beliefs using the principles of grounded theory. A second group of 398 adults with self-reported chronic disease were recruited for online testing of the personas and their impact on activation. The activation variables, based on an integrated theory of health behavior, were knowledge of a given health issue, perceived self-management skills, confidence in improving health, and intention to take action in managing health. Pre-post changes in activation were analyzed with a mixed design with 1 within-subjects factor (pre-post) and 1 between-group factor (persona) using a general linear model with repeated measures. Results Sixteen pre-post changes for 4 measures of activation were analyzed. All but 2 of the within-subjects effects were statistically significant and all changes were in the direction of increased activation scores at posttest. Five significant differences between personas were observed, showing which personas performed better. Of low activation participants, 50% or more shifted to high activation across the 4 measures with minimal changes (≤5%) in the reverse direction. Conclusions The majority of participants using a persona-tailored learning path reported high levels of satisfaction with their online user experience and increased levels of activation about their own health. In the body of work on patient activation, the current study adds to understanding of both short-term impact and the content of a brief, online intervention for engagement of specific groups in self-management. PMID:25720676

Guidelines for the field evaluation of desert tortoise health and disease

USGS Publications Warehouse

Berry, Kristin H.; Christopher, Mary M.

2001-01-01

Field evaluation of free-ranging wildlife requires the systematic documentation of a variety of environmental conditions and individual parameters of health and disease, particularly in the case of rare or endangered species. In addition, defined criteria are needed for the humane salvage of ill or dying animals. The purpose of this paper is to describe, in detail, the preparation, procedures, and protocols we developed and tested for the field evaluation of wild desert tortoises (Gopherus agassizii). These guidelines describe: preparations for the field, including developing familiarity with tortoise behavior and ecology, and preparation of standardized data sheets; journal notes to document background data on weather conditions, temperature, rainfall, locality, and historic and recent human activities; procedures to prevent the spread of disease and parasites; data sheets for live tortoises to record tortoise identification, location, sex, body measurements and activity; health profile forms for documenting and grading physical abnormalities of tortoise posture and movements, general condition (e.g., lethargy, cachexia), external parasites, and clinical abnormalities associated with shell and upper respiratory diseases; permanent photographic records for the retrospective analysis of progression and regression of upper respiratory and eye diseases, analysis of shell lesions and evaluation of growth and age; and indications and methods for salvaging ill or dying tortoises for necropsy evaluation. These guidelines, tested on 5,000 to 20,000 tortoises over a 10 to 27 yr period, were designed to maximize acquisition of data for demographic, ecological, health and disease research projects; to reduce handling and stress of individual animals; to avoid spread of infectious disease; to promote high quality and consistent data sets; and to reduce the duration and number of field trips. The field methods are adapted for desert tortoise life cycle, behavior, anatomy, physiology, and pertinent disease; however the model is applicable to other species of reptiles. Comprehensive databases of clinical signs of disease and health are crucial to research endeavors and essential to decisions on captive release, epidemiology of disease, translocation of wild tortoises, breeding programs, and euthanasia.

Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study

PubMed Central

2014-01-01

Introduction Disease activity, severity and comorbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in patients with early disease. Methods In this study, 950 RA patients were followed regularly from the time of inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or swollen joints, Visual Analogue Scale pain and global scores, and Disease Activity Score in 28 joints (DAS28)) and function (Health Assessment Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of the hands and feet (erosions based on Larsen score), extraarticular disease, nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs) were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid factor, antinuclear antibodies and antibodies against cyclic citrullinated peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analysed at the time of inclusion. Data were stratified as young-onset RA (YORA) and late-onset RA (LORA), which were defined as being below or above the median age at the time of onset of RA (58 years). Results LORA was associated with lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01), but with greater disease activity at the time of inclusion measured on the basis of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24 months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA patients. At baseline and 24 months, LORA was more often associated with erosions (P < 0.01 for both) and higher Larsen scores (P < 0.001 for both). LORA was more often treated with corticosteroids (P < 0.01) and less often with methotrexate (P < 0.001) and biologics (P < 0.001). YORA was more often associated with early DMARD treatment (P < 0.001). The results of multiple regression analyses supported our findings regarding the impact of age on chosen treatment. Conclusion YORA patients were more frequently ACPA-positive than LORA patients. LORA was more often associated with erosions, higher Larsen scores, higher disease activity and higher HAQ scores at baseline. Nevertheless, YORA was treated earlier with DMARDs, whilst LORA was more often treated with corticosteroids and less often with DMARDs in early-stage disease. These findings could have implications for the development of comorbidities. PMID:24731866

Anti-trypanosomal effects of some compounds isolated from the extracts of Warburgia ugandensis.

PubMed

Kioy, D W; Murilla, G; Kofi-Tsekpo, M W; Mukhongo, M; Okwara, J

1998-02-01

The plant kingdom has been used as a source of compounds employed in the treatment of many disease conditions for many years. Even with the new technology in synthetic chemistry, plants are still being used as a source of lead compounds in drug development. In the treatment of trypanosomiasis, the drugs that are currently in the market were developed between 1950-1960's. These drugs are expensive and associated with a number of toxic effects, therefore there is still need to develop newer drugs in the management of trypanosomiasis. The plant Warburgia ugandansis is a common plant that has been used traditionally to treat many disease conditions. The crude and pure compounds from this plant were tested against trypanosomes: T. congolense, T. evansi and T. bruceL In vitro tests using tissue culture method and in vivo tests using mice were carried out The results of the in vitro method indicated that the pure compound was more active than the crude extract The in vivo method indicated that the total extract was not effective, while one of the pure compounds was too toxic, and the other one showed activity. The two compounds investigated were basically of the same structure type with a slight difference on the functional groups. These preliminary results indicate that there is a possibility of finding active compounds against Trypanosomes in plants.

Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases

NASA Astrophysics Data System (ADS)

Fornaguera, C.; Feiner-Gracia, N.; Calderó, G.; García-Celma, M. J.; Solans, C.

2015-07-01

Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases.Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03474d

Physical activity perceptions and behaviors among young adults with congenital heart disease: A mixed-methods study.

PubMed

McKillop, Adam; McCrindle, Brian W; Dimitropoulos, Gina; Kovacs, Adrienne H

2018-03-01

A physically active lifestyle can help maintain positive physical and psychosocial health outcomes among adults with congenital heart disease (CHD). This study explored the physical activity perceptions and behaviors among young adults with CHD. This was a cross-sectional, mixed-methods study that included objectively measured physical activity assessment (accelerometer), individual semistructured interviews, and psychosocial questionnaires. Fifteen participants (67% male; 21 ± 3 years old) with moderate (n = 10) or complex (n = 5) CHD were recruited from an outpatient adult CHD clinic. Participants accumulated 26 ± 16 minutes of moderate-to-vigorous physical activity per day, and reported a high quality of life, moderate self-efficacy for exercise, and low cardiac-focused anxiety. Qualitative data indicated that participants reported more positive perceptions toward activity if their family members encouraged physical activity participation, including siblings that engaged in physical activity alongside participants. Participants described parents as supportive rather than overprotective. Activity precautions were perceived by participants as being instructions from cardiologists rather than restrictions by parents. Participants described some physical limitations compared to peers, but managed challenges by either working within their limitations or choosing activities that met their expectations and/or in which they could fully participate. Participants often described childhood physical activity in the context of school, physical education, and organized sports. Whereas physical activity in childhood was viewed as recreational, the cardiac health-promoting aspects became more prominent in adulthood. Activities performed during one's employment were considered sufficient to meet physical activity recommendation levels, and participants reported limited time and/or energy to participate in activity outside of work. The influence of family appeared to help participants adopt a positive perception toward activity participation in childhood that was carried forward to young adulthood. Future clinical work should target adolescents with CHD with less social supports and/or negative perceptions toward physical activity. © 2017 Wiley Periodicals, Inc.

Physician-patient communication in rheumatology: a systematic review.

PubMed

Georgopoulou, Sofia; Prothero, Louise; D'Cruz, David P

2018-05-01

The nature of physician-patient interaction can have a significant impact on patient outcomes through information-sharing and disease-specific education that can enhance patients' active involvement in their care. The aim of this systematic review was to examine all the empirical evidence pertaining to aspects of physician-patient communication and its impact on patient outcomes. A systematic search of five electronic databases (MEDLINE, PsycINFO, EMBASE, CINAHL, and Web of Science) was undertaken from earliest record to December 2016. Studies were eligible if they: (1) included adult participants (18 years or over) with a diagnosis of a rheumatic condition; (2) were of quantitative, qualitative or mixed methods design; (4) were surveys, observational and interventional studies; (5) were published in the English language; and (6) reported findings on either various physician-patient communication aspects alone or in combination with physical and psychological outcomes. Searches identified 455 papers. Following full-text retrieval and assessment for eligibility and quality, ten studies were included in the review; six quantitative, one mixed methods, and three qualitative papers. Higher levels of trust in the physician and active patient participation in the medical consultation were linked to lower disease activity, better global health, less organ damage accrual, greater treatment satisfaction with fewer side effects from the medication, more positive beliefs about control over the disease, and about current and future health. Future research could focus on the design and implementation of interventions incorporating communications skills and patient-education training.

Neuraminidase as an enzymatic marker for detecting airborne Influenza virus and other viruses.

PubMed

Turgeon, Nathalie; Toulouse, Marie-Josée; Ho, Jim; Li, Dongqing; Duchaine, Caroline

2017-02-01

Little information is available regarding the effectiveness of air samplers to collect viruses and regarding the effects of sampling processes on viral integrity. The neuraminidase enzyme is present on the surface of viruses that are of agricultural and medical importance. It has been demonstrated that viruses carrying this enzyme can be detected using commercial substrates without having to process the sample by methods such as RNA extraction. This project aims at evaluating the effects of 3 aerosol-sampling devices on the neuraminidase enzyme activity of airborne viruses. The purified neuraminidase enzymes from Clostridium perfringens, a strain of Influenza A (H1N1) virus, the FluMist influenza vaccine, and the Newcastle disease virus were used as models. The neuraminidase models were aerosolized in aerosol chambers and sampled with 3 different air samplers (SKC BioSampler, 3-piece cassettes with polycarbonate filters, and Coriolis μ) to assess the effect on neuraminidase enzyme activity. Our results demonstrated that Influenza virus and Newcastle disease virus neuraminidase enzymes are resistant to aerosolization and sampling with all air samplers tested. Moreover, we demonstrated that the enzymatic neuraminidase assay is as sensitive as RT-qPCR for detecting low concentrations of Influenza virus and Newcastle disease virus. Therefore, given the sensitivity of the assay and its compatibility with air sampling methods, viruses carrying the neuraminidase enzyme can be rapidly detected from air samples using neuraminidase activity assay without having to preprocess the samples.

The Webcam system: a simple, automated, computer-based video system for quantitative measurement of movement in nonhuman primates.

PubMed

Togasaki, Daniel M; Hsu, Albert; Samant, Meghana; Farzan, Bijan; DeLanney, Louis E; Langston, J William; Di Monte, Donato A; Quik, Maryka

2005-06-30

Investigations using models of neurologic disease frequently involve quantifying animal motor activity. We developed a simple method for measuring motor activity using a computer-based video system (the Webcam system) consisting of an inexpensive video camera connected to a personal computer running customized software. Images of the animals are captured at half-second intervals and movement is quantified as the number of pixel changes between consecutive images. The Webcam system allows measurement of motor activity of the animals in their home cages, without devices affixed to their bodies. Webcam quantification of movement was validated by correlation with measures simultaneously obtained by two other methods: measurement of locomotion by interruption of infrared beams; and measurement of general motor activity using portable accelerometers. In untreated squirrel monkeys, correlations of Webcam and locomotor activity exceeded 0.79, and correlations with general activity counts exceeded 0.65. Webcam activity decreased after the monkeys were rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but the correlations with the other measures of motor activity were maintained. Webcam activity also correlated with clinical ratings of parkinsonism. These results indicate that the Webcam system is reliable under both untreated and experimental conditions and is an excellent method for quantifying motor activity in animals.

Sexual Behavior and Contraceptive Use at Brown University: 1975-2011.

PubMed

Peipert, Benjamin J; Scott, Dana Marie; Matteson, Kristen A; Clark, Melissa A; Zhao, Qiuhong; Peipert, Jeffrey F

2016-01-01

To assess sexual behaviors and contraceptive use in a sample of Brown University students. A total of 255 undergraduate students responded to an anonymous online survey in May 2011. The survey addressed level of sexual activity, behaviors, and contraceptive use. Female responders were compared to results from surveys conducted in 1975, 1986, 1989, and 1995. Of the surveyed undergraduates 62% were sexually active. Sexual activity among women was similar to that of previous survey years. Contraceptive pills were the most common primary contraceptive method, reported by 59% of students, and 32% used dual method contraceptive use for sexually transmitted disease (STD) and pregnancy prevention. We observed a plateau in condom use among women in 2011 after an increase from 1975-1995. Use of long-acting reversible contraception (LARC) was uncommon (3%). Educational efforts should emphasize the effectiveness of LARC and dual method contraceptive use to reduce the risk of STDs and unintended pregnancies.

Anti-microbial Activity of Tulsi {Ocimum Sanctum (Linn.)} Extract on a Periodontal Pathogen in Human Dental Plaque: An Invitro Study

PubMed Central

Devaraj, C.G.; Agarwal, Payal

2016-01-01

Introduction Tulsi is a popular healing herb in Ayurvedic medicine. It is widely used in the treatment of several systemic diseases because of its anti-microbial property. However, studies documenting the effect of Tulsi on oral disease causing organisms are rare. Hence, an attempt was made to determine the effect of Tulsi on a periodontal microorganism in human dental plaque. Aim To determine if Ocimum sanctum (Linn.) has an anti-microbial activity (Minimum Inhibitory Concentration and zone of inhibition) against Actinobacillus actinomycetemcomitans in human dental plaque and to compare the antimicrobial activity of Ocimum sanctum(Linn.) extract with 0.2% chlorhexidine as the positive control and dimethyl sulfoxide as the negative control. Materials and Methods A lab based invitro experimental study design was adopted. Ethanolic extract of Ocimum sanctum (Linn.) was prepared by the cold extraction method. The extract was diluted with an inert solvent, dimethyl sulfoxide, to obtain ten different concentrations (1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%) of extract. Plaque sample was collected from 05 subjects diagnosed with periodontal disease. Isolation of Actinobacillus actinomycetemcomitans from plaque samples was done using Tryptic Soy Serum Bacitracin Vancomycin agar (TSBV) medium. Identification of Actinobacillus actinomycetemcomitans was done based on cultural, microscopic, biochemical characterization and multiple drug resistance patterns. Anti-microbial activity of Ocimum sanctum (Linn.) extract was tested by agar well-diffusion method against 0.2% chlorhexidine as a positive control and dimethyl sulfoxide as a negative control. The zone of inhibition was measured in millimeters using Vernier callipers. Results At the 6% w/v concentration of Ocimum sanctum (Linn.) extract, a zone of inhibition of 22 mm was obtained. This was the widest zone of inhibition observed among all the 10 different concentrations tested. The zone of inhibition for positive control was 25mm and no zone of inhibition was observed around the negative control. Conclusion Ocimum sanctum (Linn.) extract demonstrated an antimicrobial activity against Actinobacillus actinomycetemcomitans. The maximum antimicrobial potential was observed at the 6% concentration level. PMID:27135002

Redefining Racial Residential Segregation and its Association With Physical Activity Among African Americans 50 years and Older: A Mixed Methods Approach

PubMed Central

Armstrong-Brown, Janelle; Eng, Eugenia; Hammond, Wizdom Powell; Zimmer, Catherine; Bowling, J. Michael

2016-01-01

Physical inactivity is one of the factors contributing to disproportionate disease rates among older African Americans. Previous literature indicates that older African Americans are more likely to live in racially segregated neighborhoods and that racial residential segregation is associated with limited opportunities for physical activity. A cross-sectional mixed methods study was conducted guided by the concept of therapeutic landscapes. Multilevel regression analyses demonstrated that racial residential segregation was associated with more minutes of physical activity and greater odds of meeting physical activity recommendations. Qualitative interviews revealed the following physical activity related themes: aging of the neighborhood, knowing your neighbors, feeling of safety, and neighborhood racial identity. Perceptions of social cohesion enhanced participants’ physical activity, offering a plausible explanation to the higher rates of physical activity found in this population. Understanding how social cohesion operates within racially segregated neighborhoods can help to inform the design of effective interventions for this population. PMID:24812201

Leisure activities following a lower limb amputation.

PubMed

Couture, Mélanie; Caron, Chantal D; Desrosiers, Johanne

2010-01-01

The aim of this study was to describe leisure activities, leisure satisfaction and constraints on participation in leisure following a unilateral lower limb amputation due to vascular disease. This study used a mixed-method approach where 15 individuals with lower limb amputation completed the individual leisure profile 2-3 months post-discharge from rehabilitation. A subsample (n = 8) also participated in semi-structured interviews analysed using the Miles and Huberman analytic method. Results show that participants were involved in 12 different leisure activities on average. Compared to before the amputation, a decrease in participation was observed in all categories of leisure activity, and especially crafts, nature and outdoor activities, mechanics, sports and physical activities. Nonetheless, overall satisfaction was high. The most important constraints on participation in leisure were lack of accessibility, material considerations, functional abilities, affective constraints and social constraints. A decrease in leisure activity participation and the presence of constraints do not automatically translate into low levels of leisure satisfaction.

Resident training in microbiology.

PubMed

Haller, Barbara L

2007-06-01

To meet the challenges of diagnosis and management of infectious diseases, clinical pathology residents must receive comprehensive training in microbiology, learn to think critically, develop problem-solving skills, and take active roles as laboratory consultants. Residents well trained in clinical microbiology become capable laboratory professionals, developing cost-effective testing strategies, decreasing risk for medical errors, and improving patient care. Newer methods for diagnosing infectious disease, such as real-time polymerase chain reaction, microarrays for pathogen detection, and rapid assays for antigen or antibody detection, have become standard. Knowledge of infectious disease principles, drug therapeutic options, and drug resistance is also important. Suggestions for training and for assessing resident competency in clinical microbiology are presented.

[Psychogenetic neurological disorders in draft age personnel].

PubMed

Akhmetianov, L A; Ovchinnikov, A V

2012-07-01

The tendency of psychogenetic neurological disorders increases with predominance in young persons being students of high schools, students of military, technical and other lyceum was shown. The origin of diseases are psychotraumas (family, work), stress. Also genetic and hereditary factors take place that are indicative for individual rehabilitation organization. The basics of psychosomatic diseases pathogenesis are the disintegration mechanisms in brain structure activity,the disorders of integrative apparatus which provides the relationship between somatic, emotional and vegetative functions. The confirmation of brain work disintegration is achieved by modern computer diagnostic systems. As psychogenic diseases increase the need in methods of computer electroencephalography, evoked potentials, and rheoencephalography application is more actual.

Robust method for TALEN-edited correction of pF508del in patient-specific induced pluripotent stem cells.

PubMed

Camarasa, María Vicenta; Gálvez, Víctor Miguel

2016-02-09

Cystic fibrosis is one of the most frequent inherited rare diseases, caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. Apart from symptomatic treatments, therapeutic protocols for curing the disease have not yet been established. The regeneration of genetically corrected, disease-free epithelia in cystic fibrosis patients is envisioned by designing a stem cell/genetic therapy in which patient-derived pluripotent stem cells are genetically corrected, from which target tissues are derived. In this framework, we present an efficient method for seamless correction of pF508del mutation in patient-specific induced pluripotent stem cells by gene edited homologous recombination. Gene edition has been performed by transcription activator-like effector nucleases and a homologous recombination donor vector which contains a PiggyBac transposon-based double selectable marker cassette.This new method has been designed to partially avoid xenobiotics from the culture system, improve cell culture efficiency and genome stability by using a robust culture system method, and optimize timings. Overall, once the pluripotent cells have been amplified for the first nucleofection, the procedure can be completed in 69 days, and can be easily adapted to edit and change any gene of interest.

Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis

PubMed Central

Nishikawa, Hiroki; Osaki, Yukio

2015-01-01

The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes. PMID:26494949

Awareness of chronic disease related health benefits of physical activity among residents of a rural South Indian region: a cross-sectional study

PubMed Central

2014-01-01

Background Physical activity trends for a lower-middle income country like India suggest a gradual decline in work related physical activity and no concomitant increase in leisure time physical activity. Perceived health benefits of physical activity and intention to increase physical activity have been established as independent correlates of physical activity status. In India, not much is known about peoples’ perceptions of health benefits of physical activity and their intention to increase physical activity levels. This study was performed to understand peoples’ perceptions and awareness about health benefits of physical activity in a rural South Indian region. Methods This cross-sectional study was conducted using a multistage cluster sampling design. A content validated, field tested questionnaire was administered in person by a trained interviewer in the participants’ native language. The questionnaire assessed the participants’ perceptions about their lifestyle (active or sedentary), health benefits of physical activity and need for increasing their physical activity. In addition, the participant’s physical activity was assessed using version 2 of global physical activity questionnaire. Frequencies and percentages were used to summarise perceived health benefits of physical activity and other categorical variables. Age and body mass index were summarised using mean ± SD, whereas physical activity (MET.min.wk −1) was summarised using median and interquartile range. Results Four hundred fifty members from 125 randomly selected households were included in the study, of which 409 members participated. 89% (364) of participants felt they lead an active lifestyle and 83.1% (340) of participants did not feel a need to increase their physical activity level. 86.1%, (352) of the participants were physically active. Though 92.4% (378) of participants felt there were health benefits of physical activity, majority of them (75.1%) did not report any benefit related to chronic diseases. None mentioned health benefits related to heart disease or stroke. Conclusion There is low awareness of chronic disease related benefits of physical activity and participants do not see a need to increase their physical activity level. Public health awareness programs on importance and health benefits of physical activity would be useful to counter the anticipated decline in physical activity. PMID:24575767

Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes.

PubMed

Piantoni, S; Regola, F; Zanola, A; Andreoli, L; Dall'Ara, F; Tincani, A; Airo', P

2018-01-01

Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann-Whitney test. Bonferroni correction was applied to adjust for multiple comparisons ( p adj ). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls ( p = .04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K ≥ 6 ( n = 13) had a higher percentage of circulating CD4+ T-cells with CD28- phenotype ( p adj  = .005) as well as those with an effector memory ( p adj  = .004) and TDEM ( p adj  = .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02), in comparison with patients with low disease activity ( n = 38). Patients with damage (SDI ≥ 1) tended to show an expansion of TDEM among CD4+ T-cells as compared with patients with no damage ( p = .01). In SLE patients an inverse correlation was found between the percentages of TREGs and those of TDEM ( p < .01) or CD4 + CD28- ( p < .01) T-cells. Conclusions CD4+ T-cell subpopulations displaying phenotype characteristics of effector lymphocytes are proportionally expanded in patients with active SLE and a higher damage index. These findings may suggest a role of effector T-cells in the pathogenesis of the disease and in the mechanisms of damage in SLE.

Clinical Significance of Thyrotrophin Binding Inhibitor Immunoglobulins in Patients with Graves’ Disease and Various Types of Thyroiditis

PubMed Central

Lee, Chong Suk; Kim, Doo Man; Kim, Chong Soon; Yoo, Hyung Joon

1987-01-01

It is well known that thyrotrophin receptor antibodies are present in the sera of patients with autoimmune thyroid disease. There is now compelling evidence that the hyperthyroidism of Graves’ disease is due to antibodies to the thyrotrophin (TSH) receptor. The measurement of these antibodies is valuable in the diagnosis and monitoring of Graves’ disease and in predicting the outcome of treatment. In the present study, thyrotrophin binding inhibitor immunoglobulin (TBII) activites were measured by radioreceptor assay, according to the method of Shewring and Smith1), in 30 patients with Graves’ disease, 13 patients with Hashimoto’s thyroiditis, 20 patients with lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (LT-SRH), 5 patients with postpartum thyroiditis, and 7 patients with subacute thyroiditis. The TBII activity results a mean of 3.0±3.0% in normal controls, 44.8±8.7% in Graves’ disease, 8.69±8.06% in Hashimoto’s thyroiditis, 7.63±2.32% in LT-SRH, 3.33±1.16% in postpartum thyroiditis, and 2.67±2.33% in subacute thyroiditis respectively. These clinical and laboratory findings show that TBII also plays a role in the pathogenesis of Graves’ disease. The levels of the TBII activties in Hashimoto’s thyroiditis and LT-SRH, suggest a pathognomic role similar to that of Graves’ disease in above mentioned two disease, but that TBII activity is not significant in postpartum or subacute thyroiditis. PMID:2908728

75 FR 989 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

...-3121 or [email protected] for more information. Diamidine Inhibitors of Tdp1 as Anti-Cancer Agents.... diamidine derivatives have the potential to enhance the anti-neoplastic activity of Top1 inhibitors, by... applications. Method of Preventing and Treating Metastatic Disease Description of Technology: Cancer that...

Connecting Neuronal Cell Protective Pathways and Drug Combinations in a Huntington's Disease Model through the Application of Quantitative Systems Pharmacology.

PubMed

Pei, Fen; Li, Hongchun; Henderson, Mark J; Titus, Steven A; Jadhav, Ajit; Simeonov, Anton; Cobanoglu, Murat Can; Mousavi, Seyed H; Shun, Tongying; McDermott, Lee; Iyer, Prema; Fioravanti, Michael; Carlisle, Diane; Friedlander, Robert M; Bahar, Ivet; Taylor, D Lansing; Lezon, Timothy R; Stern, Andrew M; Schurdak, Mark E

2017-12-19

Quantitative Systems Pharmacology (QSP) is a drug discovery approach that integrates computational and experimental methods in an iterative way to gain a comprehensive, unbiased understanding of disease processes to inform effective therapeutic strategies. We report the implementation of QSP to Huntington's Disease, with the application of a chemogenomics platform to identify strategies to protect neuronal cells from mutant huntingtin induced death. Using the STHdh Q111 cell model, we investigated the protective effects of small molecule probes having diverse canonical modes-of-action to infer pathways of neuronal cell protection connected to drug mechanism. Several mechanistically diverse protective probes were identified, most of which showed less than 50% efficacy. Specific combinations of these probes were synergistic in enhancing efficacy. Computational analysis of these probes revealed a convergence of pathways indicating activation of PKA. Analysis of phospho-PKA levels showed lower cytoplasmic levels in STHdh Q111 cells compared to wild type STHdh Q7 cells, and these levels were increased by several of the protective compounds. Pharmacological inhibition of PKA activity reduced protection supporting the hypothesis that protection may be working, in part, through activation of the PKA network. The systems-level studies described here can be broadly applied to any discovery strategy involving small molecule modulation of disease phenotype.

ACADEMIC OUTCOMES IN CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS

PubMed Central

Zelko, Frank; Beebe, Dean; Baker, Aimee; Nelson, Shannen M; Ali, Aisha; Cedeno, Adlin; Dina, Blair; Klein-Gitelman, Marisa S; Ying, Jun; Brunner, Hermine I

2012-01-01

Objective To explore academic outcomes in childhood-onset systemic lupus erythematosus (cSLE) and their relationship to variables such as demographic and socioeconomic status, neurocognitive functioning, behavioral/emotional adjustment, and cSLE disease status. Methods Forty pairs of children diagnosed with cSLE and healthy best-friend controls were rated by parents on a standardized scale of school competence. Information about participants’ demographic and socioeconomic status was obtained, along with measures of cSLE disease activity and damage. All participants received formal neurocognitive testing and were also rated on standardized scales of behavioral/emotional adjustment and executive functioning. Results Compared to healthy controls, school competence was rated as lower in the cSLE group, although the groups did not differ significantly on indices of cognitive, behavioral, emotional, or executive functioning. School competence ratings were correlated with reading and mathematics achievement test scores in both groups, and with ratings of mental self-regulation in the cSLE group. School competence ratings were correlated with measures of cSLE disease activity and treatment intensity. Conclusion cSLE is associated with inferior parent-rated academic outcomes compared to those noted in demographically-matched peers, despite similar neurocognitive function. The adverse academic outcomes which distinguish children with cSLE from their demographically-matched peers appear to be mediated by SLE disease activity and treatment. PMID:22807373