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

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

PubMed

Magee, Kelsey E; Kelsey, Christina E; Kurzinski, Katherine L; Ho, Jonhan; Mlakar, Logan R; Feghali-Bostwick, Carol A; Torok, Kathryn S

2013-01-01

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. 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). 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. 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.

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

Natural selection to sports, later physical activity habits, and coronary heart disease

PubMed Central

Kujala, U.; Sarna, S.; Kaprio, J.; Tikkanen, H.; Koskenvuo, M.

2000-01-01

Objectives—To investigate the associations between natural selection to sports at a young age, continuity of physical activity, and occurrence of coronary heart disease. Design—Prospective cohort study. Setting—Finland. Participants—Former top level male athletes participating at a young age (1920–1965) in different types of sport (endurance (n = 166), power speed (n = 235), "other" (n = 834)) and controls healthy at the age of 20 years (n = 743). Main outcome measures—Data on the occurrence of coronary heart disease were obtained from death certificates, three nationwide registers, and questionnaire studies in 1985 and 1995, and data on later physical activity were obtained from the questionnaires. Results—In 1985 all groups of former athletes were more physically active than controls (p<0.001). Despite similar total volumes of physical activity, compared with power speed athletes, former endurance athletes participated more often in vigorous activity (p = 0.006) and had less coronary heart disease (adjusted odds ratio 0.34, 95% confidence interval 0.17 to 0.73; p = 0.004). In 1985 and 1995, both endurance and other athletes had less coronary heart disease than controls. From 1986 to 1995, the incidence of new coronary heart disease was lower among those who participated in vigorous physical activity in 1985. Conclusions—Both a previous aptitude for endurance athletic events and continuity of vigorous physical activity seem to be associated with protection against coronary heart disease, but an aptitude for power speed events does not give protection against coronary heart disease. Key Words: coronary heart disease; fitness; genetic selection; physical activity PMID:11131233

Reduced cortical activation in inferior frontal junction in Unverricht-Lundborg disease (EPM1) - A motor fMRI study.

PubMed

Könönen, Mervi; Danner, Nils; Koskenkorva, Päivi; Kälviäinen, Reetta; Hyppönen, Jelena; Mervaala, Esa; Karjalainen, Pasi; Vanninen, Ritva; Niskanen, Eini

2015-03-01

Unverricht-Lundborg disease (EPM1) is characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia. Several disease-related alterations in cortical structure and excitability have been associated with the motor symptoms of EPM1. This study aimed to elucidate possible alterations in cortical activation related to motor performance in EPM1. Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex underwent motor functional MRI. Group differences in activations were evaluated in the primary and supplementary motor cortices and sensory cortical areas. Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated with the severity of the motor symptoms. The EPM1-patients exhibited decreased activation in the left inferior frontal junction (IFJ) during right hand voluntary motor task when compared with controls. In the quantitative analysis, EPM1-patients had significantly weaker activation than controls in the hand knob and supplementary motor areas (SMA). The volume of activation in M1 decreased with age and duration of disease in the patient group, whereas the volume increased with age in controls. Negative correlations were observed between fMRI parameters of SMA and disease duration or age in patients but not in controls. The weaker motor fMRI activation observed in EPM1 patients parallels previous neurophysiological findings and correlates with the motor symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1 patients may be associated with the difficulties in initiation or termination of motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect the progressive nature of this disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of QT and P wave dispersion and mean platelet volume among inflammatory bowel disease patients.

PubMed

Dogan, Yuksel; Soylu, Aliye; Eren, Gulay A; Poturoglu, Sule; Dolapcioglu, Can; Sonmez, Kenan; Duman, Habibe; Sevindir, Isa

2011-01-01

In inflammatory bowel disease (IBD) number of thromboembolic events are increased due to hypercoagulupathy and platelet activation. Increases in mean platelet volume (MPV) can lead to platelet activation, this leads to thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT-dispersion and P-wave dispersion are predictors of ventricular arrhythmias and atrial fibrilation; MPV is accepted as a risk factor for acute coronary syndromes, we aimed at evaluating the correlations of these with the duration of disease, its localization and activity. The study group consisted of 69 IBD (Ulcerative colitis n: 54, Crohn's Disease n: 15) patients and the control group included 38 healthy individuals. Disease activity was evaluated both endoscopically and clinically. Patients with existing cardiac conditions, those using QT prolonging medications and having systemic diseases, anemia and electrolyte imbalances were excluded from the study. QT-dispersion, P-wave dispersion and MPV values of both groups were compared with disease activity, its localization, duration of disease and the antibiotics used. The P-wave dispersion values of the study group were significantly higher than those of the control group. Duration of the disease was not associated with QT-dispersion, and MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were similar between the active and in mild ulcerative colitis patients. QT-dispersion levels were similar between IBD patients and the control group. No difference was observed between P-wave dispersion, QT-dispersion and MPV values; with regards to disease duration, disease activity, and localization in the study group (p>0.05). P-wave dispersion which is accepted as a risk factor for the development of atrial fibirilation was found to be high in our IBD patients. This demonstrates us that the risk of developing atrial fibrillation may be high in patients with IBD. No significant difference was found in the QT-dispersion, and in the MPV values when compared to the control group.

Disease control operations

USGS Publications Warehouse

Friend, M.; Franson, J.C.

1999-01-01

Individual disease outbreaks have killed many thousands of animals on numerous occasions. Tens of thousands of migratory birds have died in single die-offs with as many as 1,000 birds succumbing in 1 day. The ability to successfully combat such explosive situations is highly dependent on the readiness of field personnel to deal with them. Because many disease agents can spread through wildlife populations very quickly, advance preparation is essential for preventing infected animals from spreading disease to additional species and locations. Carefully thought-out disease contingency plans should be developed as practical working documents for field personnel and updated as necessary. Well-designed plans can prove invaluable in minimizing wildlife losses and the costs associated with disease control activities.Although requirements for disease control operations vary and must be tailored to each situation, all disease contingency planning involves general concepts and basic biological information. This chapter, which is intended to be a practical guide, identifies the major activities and needs of disease control operations, and relates them to disease contingency planning.

Do women with fibromyalgia present higher cardiovascular disease risk profile than healthy women? The al-Ándalus project.

PubMed

Acosta-Manzano, Pedro; Segura-Jiménez, Víctor; Estévez-López, Fernando; Álvarez-Gallardo, Inmaculada C; Soriano-Maldonado, Alberto; Borges-Cosic, Milkana; Gavilán-Carrera, Blanca; Delgado-Fernández, Manuel; Aparicio, Virginia A

2017-01-01

To analyse the cardiovascular disease risk profile of women with fibromyalgia and compare it with control women; and to test whether physical activity is associated with the cardiovascular disease risk profile in this population. This cross-sectional study comprised 436 women with fibromyalgia (51.4±7.5 years old) and 217 controls (48.4±9.6 years old) from Andalusia, Spain. Clinical data, waist circumference, body fat percentage, resting heart rate, blood pressure and cardiorespiratory fitness were assessed. Moderate-to-vigorous physical activity was objectively assessed with accelerometry. A clustering of individual cardiovascular disease risk factors was represented by the number of cigarettes/day, adiposity, mean arterial pressure, resting heart rate and cardiorespiratory fitness. Women with fibromyalgia presented higher waist circumference and body fat percentage, greater number of cigarettes/day consumption and lower levels of cardiorespiratory fitness after controlling for age, marital status, educational level, occupational status, medication for cholesterol and monthly regular menstruation (all, p<.05). Women with fibromyalgia showed higher clustered cardiovascular disease risk than control women after controlling for the potential confounders described above (p<.001). Women with fibromyalgia who did not meet moderate-to-vigorous physical activity recommendations showed increased clustered cardiovascular disease risk after adjusting for the potential confounders described above (p<.001). Women with fibromyalgia may present higher risk of cardiovascular disease than controls. Inadequate levels of moderate-to-vigorous physical activity may play a significant role as an additional predisposing factor for cardiovascular disease risk in this population.

Self-managed eHealth Disease Monitoring in Children and Adolescents with Inflammatory Bowel Disease: A Randomized Controlled Trial.

PubMed

Carlsen, Katrine; Jakobsen, Christian; Houen, Gunnar; Kallemose, Thomas; Paerregaard, Anders; Riis, Lene B; Munkholm, Pia; Wewer, Vibeke

2017-03-01

To evaluate the impact of eHealth on disease activity, the need for hospital contacts, and medical adherence in children and adolescents with inflammatory bowel disease (IBD). Furthermore, to assess eHealth's influence on school attendance and quality of life (QoL). Patients with IBD, 10 to 17 years attending a public university hospital, were prospectively randomized to a 2-year open label case-controlled eHealth intervention. The eHealth-group used the web-application young.constant-care.com (YCC) on a monthly basis and in case of flare-ups, and were seen at one annual preplanned outpatient visit. The control-group continued standard visits every third month. Every 3 months, both groups had blood and fecal calprotectin tested and the following were assessed: escalation in medication, disease activity, hospital contacts, medical adherence, school absence, and QoL. Fifty-three patients in nonbiological treatment were included (27 eHealth/26 control). We found no differences between the groups regarding escalation in treatment and disease activity (symptoms, fecal calprotectin, and blood). The number of total outpatient visits (mean: eHealth 3.26, SEM 0.51; control 7.31, SEM 0.69; P < 0.0001) and IBD-related school absence (mean days: eHealth 1.6, SEM 0.5; control 16.5, SEM 4.4; P < 0.002) was significantly lower in the eHealth-group. No differences in medical adherence and QoL were found. Adherence to YCC was 81% (384 of the 475 expected entries). None of the patients or parents felt unsafe using the eHealth system. The use of eHealth in children and adolescents with IBD is feasible, does not lead to impaired disease control, and can be managed by the patients without risk of increased disease activity.

Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis.

PubMed

Gracie, David J; Irvine, Andrew J; Sood, Ruchit; Mikocka-Walus, Antonina; Hamlin, P John; Ford, Alexander C

2017-03-01

Inflammatory bowel disease is associated with psychological comorbidity and impaired quality of life. Psychological comorbidity could affect the natural history of inflammatory bowel disease. Psychological therapies might therefore have beneficial effects on disease activity, mood, and quality of life in patients with inflammatory bowel disease. We did a systematic review and meta-analysis examining these issues. In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for articles published between 1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients with inflammatory bowel disease aged at least 16 years that compared psychological therapy with a control intervention or usual treatment were eligible. We pooled dichotomous data to obtain relative risks of induction of remission in active disease or prevention of relapse of quiescent disease, with 95% CIs. We pooled continuous data to estimate standardised mean differences in disease activity indices, anxiety, depression, perceived stress, and quality-of-life scores in patients dichotomised into those with clinically active or quiescent disease, with 95% CIs. We extracted data from published reports and contacted the original investigators of studies for which the required data were not available. We pooled all data using a random-effects model. The search identified 1824 studies, with 14 RCTs of 1196 patients eligible for inclusion. The relative risk of relapse of quiescent inflammatory bowel disease with psychological therapy versus control was 0·98 (95% CI 0·77-1·24; p=0·87; I 2 =50%; six trials; 518 patients). We observed a significant difference in depression scores (standardised mean difference -0·17 [-0·33 to -0·01]; p=0·04; I 2 =0%; seven trials; 605 patients) and quality of life (0·30 [0·07-0·52]; p=0·01; I 2 =42%; nine trials; 578 patients) with psychological therapy versus control at the end of therapy for patients with quiescent disease. However, these beneficial effects were lost at final point of follow-up (depression scores -0·11 [-0·27 to 0·05], p=0·17, I 2 =0%, eight trials, 593 patients; quality of life 0·15 [-0·05 to 0·34], p=0·14, I 2 =22%, ten trials, 577 patients). When we assessed the effect of individual physiological therapies on quality of life, only cognitive behavioural therapy had any significant beneficial effect (0·37 [0·02-0·72]). We noted no effect on disease activity indices or other psychological wellbeing scores when compared with control in patients with quiescent disease. Dichotomous data for induction of remission and continuous data for change in clinical disease activity indices, depression, anxiety, and perceived stress scores were only reported in one RCT of patients with active disease. Quality of life was assessed in two RCTs of patients with active disease, but was not significantly different between intervention and control groups (0·27 [-0·05 to 0·59]). Psychological therapies, and cognitive behavioural therapy in particular, might have small short-term beneficial effects on depression scores and quality of life in patients with inflammatory bowel disease. Further RCTs of these interventions in patients with coexistent psychological distress are required. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE.

PubMed

Işikay, Sedat; Hizli, Şamil; Çoşkun, Serkan; Yilmaz, Kutluhan

2015-12-01

Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. A total of 175 children with the diagnosis of celiac disease (study group) and 99 age- and sex-matched healthy children as controls (control group) were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3%) of newly diagnosed and in 2 (1.5%) of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0%) of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively). We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients, clinicians should be aware of this association and be alert about any neurological symptoms.

The Public Health Perspective in Health Promotion and Disability Prevention for Older Adults: The Role of the Centers for Disease Control and Prevention.

ERIC Educational Resources Information Center

Hennessy, Catherine Hagan; Buchner, David M.; Jordan, Joanne M.; Leveille, Suzanne G.; Shefer, Abigail M.; Stevens, Judy A.

2001-01-01

The Centers for Disease Control and Prevention works with public health agencies and other organizations to address chronic disease prevention and risk reduction in older adults. Efforts in the areas of physical activity, osteoarthritis, and chronic illness self-management are described. Other activities include older adult immunization programs…

Platelet monoamine oxidase B and plasma β-phenylethylamine in Parkinson's disease

PubMed Central

Zhou, G; Miura, Y; Shoji, H; Yamada, S; Matsuishi, T

2001-01-01

OBJECTIVE—To evaluate the correlation between changes in platelet monoamine oxidase type B (MAO-B) activity and plasma β-phenylethylamine (PEA) concentrations in patients with Parkinson's disease and controls.
METHODS—Platelet MAO-B activity and plasma PEA were measured with gas chromatography-mass spectrometry (GC-MS) in patients with Parkinson's disease treated with levodopa (12 men and 12 women) or selegiline (three men and three women), and physically healthy subjects as a control group (10 men and 10women).
RESULTS—Platelet MAO-B activity was significantly higher in the Parkinson's disease group (mean 542 (SD 318) pmol/107 platelets/30 min) than in the control group (mean 349 (SD 307) pmol/107 platelets/30 min) (p<0.05). By contrast, the plasma PEA concentrations in patients with Parkinson's disease were significantly lower than in the control group (mean 532 (SD 243) pg/ml; 931 (SD 560) pg/ml) (p<0.01). The plasma PEA concentrations in patients with Parkinson's disease treated with selegiline were prominently higher than in patients with no selegiline treatment (p<0.001). There was a significantly negative correlation between platelet MAO-B activity and plasma PEA concentrations in patients (n=24, r=−0.466, p<0.001).
CONCLUSIONS—The increase in platelet MAO-B activity and decrease in plasma PEA concentrations in patients with Parkinson's disease may be involved in the pathophysiological processes of the disease, and these changes are reversed by treatment with selegiline.

 PMID:11160474

Metabolic and cardiovascular outcomes in patients with Cushing's syndrome of different aetiologies during active disease and 1 year after remission.

PubMed

Giordano, Roberta; Picu, Andreea; Marinazzo, Elisa; D'Angelo, Valentina; Berardelli, Rita; Karamouzis, Ioannis; Forno, Daniela; Zinnà, Domenico; Maccario, Mauro; Ghigo, Ezio; Arvat, Emanuela

2011-09-01

Cushing's syndrome is associated with several comorbidities responsible for the increased cardiovascular risk, not only during the active phase but also after disease remission. In 29 patients with Cushing's syndrome (14 Cushing's diseases and 15 adrenal adenomas), waist circumference, fasting and 2-h glucose after oral glucose tolerance test (OGTT), lipid profile and blood pressure were evaluated during the active disease and 1 year after remission and compared with those in 29 sex-, age- and BMI-matched controls. During the active disease, waist circumference, 2-h glucose after OGTT, total and LDL cholesterol were higher in patients with Cushing's syndrome than in controls (P < 0·001) but similar in Cushing's disease and adrenal adenomas. The prevalence of impaired glucose tolerance (IGT), diabetes mellitus, dyslipidaemia and hypertension was higher (P < 0·001) in patients with Cushing's syndrome (27%, 24%, 59% and 72%) than in controls (10%, 0%, 21% and 10%), with no significant difference between Cushing's disease and adrenal adenomas. One year following hormonal remission, waist circumference persisted higher than in controls (P < 0·05) in both Cushing's disease and adrenal adenomas. Metabolic and cardiovascular abnormalities were still present in both groups, although with a lower prevalence, as well as with a more marked decrease in adrenal adenomas (P < 0·05 vs active disease for IGT, dyslipidaemia and hypertension). These results show that chronic hypercortisolism, independently of its aetiology, contributes to metabolic impairment and increased cardiovascular risk, while these abnormalities mostly persist in patients with previous Cushing's disease after hormonal remission. Pituitary hormonal deficiencies, hormonal replacement treatments and/or incomplete cure from Cushing's disease may account for these findings. © 2011 Blackwell Publishing Ltd.

Comparison between Alzheimer's disease and subcortical vascular dementia: attentional cortex study in functional magnetic resonance imaging.

PubMed

Li, C; Zheng, J; Wang, J; Gui, L

2011-01-01

Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and the Stroop test were used to assess attentional cortex activation in patients with Alzheimer's disease, subcortical vascular dementia, and normal control subjects. Patients with Alzheimer's disease and subcortical vascular dementia demonstrated similar locations of cortical activation, including the bilateral middle and inferior frontal gyri, anterior cingulate and inferior parietal lobule in response to Stroop colour word stimuli. This activation was distinctly decreased in patients with dementia compared with normal control subjects. Different regions of the brain were activated in patients with Alzheimer's disease and subcortical vascular dementia compared with normal controls. fMRI is a useful tool for the study of dementia in humans and has some potential diagnostic value. Further studies with larger numbers of participants are required.

Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

PubMed

van der Valk, Eline S; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J

2016-09-01

Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. © 2016 John Wiley & Sons Ltd.

78 FR 72088 - Agency Information Collection Activities; Proposals, Submissions, and Approvals; Withdrawal

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [60 Day-14-0770] Agency Information Collection Activities; Proposals, Submissions, and Approvals; Withdrawal AGENCY: Centers for Disease Control and Prevention (CDC) Center for HIV, Hepatitis, STD, and TB Prevention...

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.

[Quality of life and physical activity of patients with inflammatory bowel diseases].

PubMed

Nowak, Agata; Kucio, Cezary

2015-01-01

Estimation of the quality of life of patients with inflammatory bowel diseases and comparison these results with control group. A group of 16 patients with inflammatory bowel diseases and 13 healthy persons as a control group. In orderto estimate the quality of life, polish version of Inflammatory Bowel Disease Questionnaire (IBDQ) was used. The Second questionnaire that was used is WHOQOL-BREF (The World Health Organization Quality of Life). To assess the level of physical activity was applied the Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ). All the results have been correlated to answer the question if there is any relationship between the quality of life and physical activity and if level of these parameters is different in control group. In the group of patients the lowest level of functioning were stated on bowel ailments field and emotional field. The most important roles in patients life are social relationship and sanity. The higher level of the caloric consumption was stated in the group of patients with inflammatory bowel diseases in comparison to control group. There was no significant difference in caloric consumption related with the recreation and house works. Because of the fact that all of the patients were in the remission period, it was impossible to verify if there is any relationship between quality of life and the stage of disease. The results of researches have not proved relationship between the level of physical activity and the quality of life among the patients as well as in the control group.

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

Objectively Assessed Physical Activity and its Association with Balance, Physical Function and Dyskinesia in Parkinson's Disease.

PubMed

Nero, Håkan; Benka Wallén, Martin; Franzén, Erika; Conradsson, David; Ståhle, Agneta; Hagströmer, Maria

2016-10-19

The desirable effects of physical activity in individuals with Parkinson's disease are well-known, although according to results from previous studies factors associated with objectively assessed physical activity are not fully investigated. To investigate demographic, disease-related and mobility-related factors that associate with objectively measured physical activity, in a sample of older adults with mild to moderate Parkinson's disease. Demographic, disease-related and mobility-related factors were gathered by interview from a total of 91 older adults with Parkinson's disease, followed by an evaluation of balance control using the Mini-BESTest. After initial testing, participants wore a tri-axial accelerometer during a week of free-living. Correlation analysis and multiple linear regression was used to investigate factors associated with total PA, represented by total activity counts, and time in brisk walking. Motor impairment, physical function, body mass index and dyskinesia contributed to the variance of total physical activity, explaining 34 % of the variance, while physical function and balance control were significant factors associated with brisk walking, explaining 22 %. This study identified factors that have not been shown to associate with objectively measured physical activity previously, such as dyskinesia, balance control and self-rated physical function. The findings also demonstrated that associated factors differ, depending on the activity behavior being investigated. However, other factors than those included in this study may also be of importance.

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial.

PubMed

Scheltens, Philip; Kamphuis, Patrick J G H; Verhey, Frans R J; Olde Rikkert, Marcel G M; Wurtman, Richard J; Wilkinson, David; Twisk, Jos W R; Kurz, Alexander

2010-01-01

To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's Disease Assessment Scale-cognitive subscale at week 12. At 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated. Supplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials. 2010 The Alzheimer's Association. All rights reserved.

Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency.

PubMed

Wang, X; Qiao, Y; Yang, L; Song, S; Han, Y; Tian, Y; Ding, M; Jin, H; Shao, F; Liu, A

2017-11-01

Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.

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.

75 FR 7283 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-18

... Interface Activities for Avian Influenza and Other Zoonotic Diseases, Funding Opportunity Announcement (FOA... Interface Activities for Avian Influenza and other Zoonotic Diseases, FOA CK10-001.'' Contact Person for...

Platelets Toll-like receptor-4 in Crohns disease.

PubMed

Schmid, Werner; Novacek, Gottfried; Vogelsang, Harald; Papay, Pavol; Primas, Christian; Eser, Alexander; Panzer, Simon

2017-02-01

Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry. Levels of HNPs were higher in patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD in remission). Likewise, neutrophils with adhering platelets were higher in patients with active CD than in controls (P = 0.004). Binding of the TLR-4 antibody in patients with active CD was similar to that in controls, while patients in remission had significantly higher binding capacities (P = 0.59 and P = 0.003). Incubation of plasma from patients with active disease or patients in remission with platelets from healthy controls confirmed lower binding of the TLR-4 antibody in the presence of plasma from active diseased patients compared to controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as suggested by high levels of sCD14 and lipoprotein binding protein. Our study indicates involvement of platelet TLR-4 in enhancing the secretion of antimicrobial peptides from neutrophils. While platelet aggregation can be due to a variety of mechanisms in inflammatory disease, the mutual activation of platelets and neutrophils may augment host defense. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

Paraoxonase activity and dementia.

PubMed

Wehr, Hanna; Bednarska-Makaruk, Małgorzata; Graban, Ałła; Lipczyńska-Łojkowska, Wanda; Rodo, Maria; Bochyńska, Anna; Ryglewicz, Danuta

2009-08-15

Paraoxonase activity, homocysteine level and lipids were determined in 120 patients with dementia (51 with Alzheimer disease, 28 with dementia of vascular origin, 41 with mixed dementia), 45 with mild cognitive impairment and in 61 age and sex matched controls without dementia. Paraoxonase activity was decreased in Alzheimer disease and in mixed dementia as compared with control group. In the same forms of dementia homocysteine levels were increased. In Alzheimer disease paraoxonase activity was negatively correlated with homocysteine levels. Minimental State Examination results showed positive correlation with paraoxonase activity. The results suggest an important role of oxidative stress in the development of the forms of dementia with prevailing neurodegeneration.

Effects of inflammatory bowel disease on students' adjustment to college.

PubMed

Almadani, S Bashar; Adler, Jeremy; Browning, Jeff; Green, Elan H; Helvie, Karla; Rizk, Rafat S; Zimmermann, Ellen M

2014-12-01

Successful adjustment to college is required for academic success. We investigated whether inflammatory bowel disease (IBD) activity affects this adjustment process. We created an online survey that included a Student Adaptation to College Questionnaire (SACQ), a general quality of life survey (SF-12), a disease-specific short IBD quality of life survey (SIBDQ), and disease activity indices. Undergraduate students across the United States were recruited via social media. Surveys were completed by 65 students with Crohn's disease (CD), 28 with ulcerative colitis, and 214 healthy students (controls). Disease-specific quality of life (SIBDQ results) correlated with IBD disease activity (rho = -0.79; P < .0001). High college adjustment scores (SACQ results) were associated with high SIBDQ scores. Students with IBD had lower mean SACQ scores than controls (307 vs 290; P < .0001). There was a modest inverse correlation between CD activity and SACQ (rho = -0.24; P < .04). Disease activity in students with CD was associated strongly with their self-reported ability to keep up with academic work (P < .0089) and confidence in their ability to meet future academic challenges (P < .0015). Students with active IBD reported feeling as if they were not academically successful (P < .018), and students with ulcerative colitis reported irregular class attendance (P < .043). Students with IBD do not adjust to college as well as healthy students. Disease activity affects their adjustment and attitudes about academics-especially among students with CD. Successful adjustment is important for academic success, affecting graduation rates and future economic success. Strategies to increase disease control and provide social and emotional support during college could improve adjustment to college and academic performance, and increase patients' potential. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

A study of physical activity comparing people with Charcot-Marie-Tooth disease to normal control subjects.

PubMed

Ramdharry, Gita M; Pollard, Alexander J; Grant, Robert; Dewar, Elizabeth L; Laurá, Matilde; Moore, Sarah A; Hallsworth, Kate; Ploetz, Thomas; Trenell, Michael I; Reilly, Mary M

2017-08-01

Charcot Marie Tooth disease (CMT) describes a group of hereditary neuropathies that present with distal weakness, wasting and sensory loss. Small studies indicate that people with CMT have reduced daily activity levels. This raises concerns as physical inactivity increases the risk of a range of co- morbidities, an important consideration in the long-term management of this disease. This study aimed to compare physical activity, patterns of sedentary behavior and overall energy expenditure of people with CMT and healthy matched controls. We compared 20 people with CMT and 20 matched controls in a comparison of physical activity measurement over seven days, using an activity monitor. Patterns of sedentary behavior were explored through a power law analysis. Results showed a decrease in daily steps taken in the CMT group, but somewhat paradoxically, they demonstrate shorter bouts of sedentary activity and more frequent transitions from sedentary to active behaviors. No differences were seen in energy expenditure or time spent in sedentary, moderate or vigorous activity. The discrepancy between energy expenditure and number of steps could be due to higher energy requirements for walking, but also may be due to an over-estimation of energy expenditure by the activity monitor in the presence of muscle wasting. Alternatively, this finding may indicate that people with CMT engage more in activities or movement not related to walking. Implications for Rehabilitation Charcot-Marie-Tooth disease: • People with Charcot-Marie-Tooth disease did not show a difference in energy expenditure over seven days compared to healthy controls, but this may be due to higher energy costs of walking, and/or an over estimation of energy expenditure by the activity monitor in a population where there is muscle wasting. This needs to be considered when interpreting activity monitor data in people with neuromuscular diseases. • Compared to healthy controls, people with Charcot-Marie-Tooth disease had a lower step count over seven days, but exhibited more frequent transitions from sedentary to active behaviors • High Body Mass Index and increased time spent sedentary were related factors that have implications for general health status. • Understanding the profile of physical activity and behavior can allow targeting of rehabilitation interventions to address mobility and fitness.

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

A randomized controlled study to evaluate the effect of pharmacist-led educational intervention on glycemic control, self-care activities and disease knowledge among type 2 diabetes patients: A consort compliant study protocol.

PubMed

Bukhsh, Allah; Nawaz, Muhammad Sarfraz; Ahmed, Hafiz Sajjad; Khan, Tahir Mehmood

2018-03-01

Diabetes self-care activities, like, healthy diet, regular exercise, self-monitoring of blood glucose, and rational use of medicines are considered to play a vital role in establishing euglycemia. Health literacy among type 2 diabetes mellitus (T2DM) patients in Pakistan is very low, which is the most likely cause for poor clinical outcomes. This study is designed to investigate the impact of pharmacist-led educational intervention on glycemic control, self-care activities and disease knowledge among T2DM patients in Pakistan. In this randomized controlled trail, effectiveness of a 6-month pharmacist-led educational intervention will be examined on glycemic control, diabetes self-care activities and disease knowledge of 80 adult T2DM patients (age >30 years) with poorly controlled T2DM (HbA1c> 7%), after randomizing them into intervention and control groups, at diabetes care clinic of Capital Hospital Islamabad, Pakistan. The primary outcome is change in patients' HbA1c, whereas, changes in self-care activities and patients' disease knowledge are the secondary outcomes. After baseline assessment of their self-care activities and disease knowledge by using validated Urdu versions of Diabetes Self-management Questionnaire (DSMQ) and Diabetes Knowledge Questionnaire (DKQ), respectively, interventional group patients will be supplemented with a face-to-face pharmacist-led educational intervention, whereas, the control group will receive usual care. Intervention arm patients will be educated successively at their first follow-up visit (12th week) and telephonically after every 4 weeks. All assessments will be made at baseline and end of trail for both intervention and control groups. Multivariate general linear model will be applied to analyze the effects of the intervention. Glycemic control in T2DM patients requires optimum self-care activities. This study is an attempt to improve self-care behaviors among poorly controlled T2DM patients who are at higher risk of diabetes-associated late complications.

In vivo assessment of plant extracts for control of plant diseases: A sesquiterpene ketolactone isolated from Curcuma zedoaria suppresses wheat leaf rust.

PubMed

Han, Jae Woo; Shim, Sang Hee; Jang, Kyoung Soo; Choi, Yong Ho; Dang, Quang Le; Kim, Hun; Choi, Gyung Ja

2018-02-01

As an alternative to synthetic pesticides, natural materials such as plant extracts and microbes have been considered to control plant diseases. In this study, methanol extracts of 120 plants were explored for in vivo antifungal activity against Rhizoctonia solani, Botrytis cinerea, Phytophthora infestans, Puccinia triticina, and Blumeria graminis f. sp. hordei. Of the 120 plant extracts, eight plant extracts exhibited a disease control efficacy of more than 90% against at least one of five plant diseases. In particular, a methanol extract of Curcuma zedoaria rhizomes exhibited strong activity against wheat leaf rust caused by P. triticina. When the C. zedoaria methanol extracts were partitioned with various solvents, the layers of n-hexane, methylene chloride, and ethyl acetate showed disease control values of 100, 80, and 43%, respectively, against wheat leaf rust. From the C. zedoaria rhizome extracts, an antifungal substance was isolated and identified as a sesquiterpene ketolactone based on the mass and nuclear magnetic resonance spectral data. The active compound controlled the development of rice sheath blight, wheat leaf rust, and tomato late blight. Considering the in vivo antifungal activities of the sesquiterpene ketolactone and the C. zedoaria extracts, these results suggest that C. zedoaria can be used as a potent fungicide in organic agriculture.

Disease control operations

USGS Publications Warehouse

Friend, Milton; Franson, J. Christian

1987-01-01

Individual disease outbreaks have killed many thousands of animals on numerous occasions. Tens of thousands of migratory birds have died in single die-offs with as many as 1,000 birds succumbing in 1 day. In mammals, individual disease outbreaks have killed hundreds to thousands of animals with, for example, hemorrhagic disease in white-tailed deer, distemper in raccoon, Errington's disease in muskrat, and sylvatic plague in wild rodents. The ability to successfully combat such explosive situations is highly dependent n the readiness of field personnel to deal with them. Because many disease agents can spread though wildlife populations very fast, advance preparation is essential in preventing infected animals from spreading disease to additional species and locations. Carefully though-out disease contingency plans should be developed as practical working documents for field personnel and updated as necessary. Such well-designed plans can prove invaluable in minimizing wildlife losses and costs associated with disease control activities. Although requirements for disease control operations vary and must be tailored to each situation, all disease contingency planning involved general concepts and basic biological information. This chapter, intended as a practical guide, identifies the major activities and needs of disease control operations, and relates them to disease contingency planning.

CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activity.

PubMed

Khattab, Sahar S; El-Saied, Amany M; Mohammed, Rehab A; Mohamed, Eman E

2016-06-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls. Copyright© by the Egyptian Association of Immunologists.

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.

Correlation between IL-17A/F, IL-23, IL-35 and IL-12/-23 (p40) levels in peripheral blood lymphocyte cultures and disease activity in Behcet's patients.

PubMed

Sonmez, Cemile; Yucel, Aysegul Atak; Yesil, Turan Hilmi; Kucuk, Hamit; Sezgin, Berna; Mercan, Ridvan; Yucel, Ahmet Eftal; Demirel, Gulderen Yanikkaya

2018-03-20

Behcet's disease is a chronic multisystemic disease with remissions and relapses. Several studies have shown that immune mechanisms play an important role in the development of the disease. In order to assess the association of disease activity with IL-17A/F, IL-23, IL-12/23 (p40) and IL-35 expression, we aimed to investigate production of these cytokines in peripheral blood mononuclear cells (PBMCs) from Behcet's patients and normal controls. Furthermore, we included Systemic Lupus Erythematosus (SLE) as disease control to evaluate the specificity of our data for immunopathogenesis of BD. Totally 15 active, 15 inactive Behcet's patients, 12 active and 12 inactive SLE patients and 12 healthy volunteers were enrolled in the study. Peripheral blood mononuclear cells were separated, lymphocyte cultures were performed and IL-17A/F, IL-12/23 p(40), IL-23, IL-35 cytokine levels were measured by ELISA in culture supernatants in the presence or absence of phytohemagglutinin (PHA) on time-dependent manner. IL-17 A/F levels increased parallel to IL-23 levels in Behcet's and SLE patients. Compared to healthy controls, IL-17 A/F levels were higher in active Behcet's and SLE patients; on the contrary, levels of IL-35 were lower. IL-17A/F, IL-12/23 (p40) and IL-23 levels were detectable most frequently in active Behcet's patients followed by active SLE patients. Our results indicate that IL-17 A/F, IL-23 and IL-12/23 (p40) may play role in the immunopathogenesis of BD so as Th17 and Th1 cell responses. Since IL-35 levels were lower in active Behcet's patients compared to inactive patients and healthy controls, there may be a plasticity between Th17 and Treg cells according to the state of disease activity.

Schistosomiasis and soil-transmitted helminthiasis control in Cameroon and Côte d'Ivoire: implementing control on a limited budget.

PubMed

Tchuenté, L A Tchuem; N'goran, E K

2009-11-01

Schistosomiasis and soil-transmitted helminthiasis occur throughout the developing world and remain a major public health problem in the poorest communities with enormous consequences for development. The extent of the problem has long been neglected because these diseases rarely kill at a young age and also because of their insidious nature. Today there exists a momentum and an unprecedented opportunity for a cost-effective control of these neglected tropical diseases. The control of these diseases has become a priority on the agenda of many governments, donors and international agencies. This paper highlights the progress made and future control activities in Cameroon and Côte d'Ivoire, where schistosomiasis and soil-transmitted helminthiasis control measures have been implemented over the past decade with limited budgets. In Cameroon, deworming activities were increased to encompass all ten regions in 2007 as a result of a co-ordinated effort of the Ministry of Health and the Ministry of Education with national and international partners. In Côte d'Ivoire, focal control activities were achieved with support from various partners. Prospects, opportunities and challenges for the control of neglected tropical diseases in these two countries are discussed.

Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity.

PubMed

Doss, Reham William; El-Rifaie, Abdel-Aziz A; Abdel-Wahab, Amr M; Gohary, Yasser M; Rashed, Laila A

2016-01-01

Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis. The aim of this study was to map the level of HSP-70 in vitiligo lesions to declare its role in the pathogenesis and activity of vitiligo. The study included thirty patients with vitiligo and 30 age- and sex-matched healthy controls. Vitiligo patients were divided as regards to the disease activity into highly active, moderately active, and inactive vitiligo groups. Skin biopsies were taken from the lesional and nonlesional skin of patients and from the normal skin of the controls. HSP-70 messenger RNA (mRNA) expression was estimated using quantitative real-time polymerase chain reaction. Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease. HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.

78 FR 13678 - Board of Scientific Counselors, Office of Infectious Diseases (BSC, OID)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Board of Scientific Counselors, Office of Infectious Diseases (BSC, OID) Notice of Cancellation: A notice was... management activities, for both the Centers for Disease Control and Prevention and the Agency for Toxic...

Cytokine profiling reveals decreased serum levels of CCL2 in active ocular toxoplasmosis.

PubMed

Rey, Amanda; Molins, Blanca; Llorenç, Victor; Pelegrín, Laura; Mesquida, Marina; Adán, Alfredo

2013-10-01

Toxoplasma gondii infection is an important cause of ocular disease. Although parasite-mediated host cell lysis is probably the principal cause of tissue destruction in immunodeficiency states, hypersensitivity and inflammatory responses may underlie severe disease in otherwise immunocompetent individuals. The purpose of the current investigation was to study the cytokine profiles in serum from patients with ocular toxoplasmosis and to compare them with those obtained from healthy control subjects. Using a multiplex assay, we determined the serum concentration of granulocyte colony-stimulating factor (GCSF), interferon γ (IFNγ), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, chemokine (C-C motif) ligand 2 (CCL2) and tumour necrosis factor α (TNFα) in patients with inactive ocular toxoplasmosis (n=48), active ocular toxoplasmosis (n=21), and an age-matched and sex-matched healthy control group (n=25). In a subgroup of 17 patients with active disease, a second serum sample was obtained when the disease was inactive. Cytokine profiles were correlated with disease activity, severity and visual outcome. Levels of CCL2 were significantly reduced in patients with active ocular toxoplasmosis compared to the control group (564 ± 42 pg/mL vs 455 ± 35 pg/mL, p<0.05). Moreover, CCL2 levels were significantly lower during active ocular toxoplasmosis compared to inactive disease (569 ± 32 pg/mL vs 433 ± 32 pg/mL, p<0.01). GCSF and TNFα were elevated in patients with toxoplasmosis with poor visual outcome. No significant correlations were found with specific cytokine profiles and disease severity. Decreased serum levels of CCL2 may be associated with active ocular toxoplasmosis and could therefore serve as a marker of disease activity.

Accelerometry-based monitoring of daily physical activity in children with juvenile idiopathic arthritis.

PubMed

Nørgaard, M; Twilt, M; Andersen, L B; Herlin, T

2016-01-01

Juvenile idiopathic arthritis (JIA) may cause functional impairment, reduced participation in physical activity (PA) and, over time, physical deconditioning. The aim of this study was to objectively monitor daily free-living PA in 10-16-year-old children with JIA using accelerometry with regard to disease activity and physical variables and to compare the data with those from healthy age- and gender-matched controls. Patients underwent an evaluation of disease activity, functional ability, physical capacity, and pain. Accelerometer monitoring was assessed using the GT1M ActiGraph. Normative data from two major studies on PA in Danish schoolchildren were used for comparison. Data of accelerometry were available for 61 JIA patients and 2055 healthy controls. Of the JIA patients, 57% showed below-average values of maximal physical capacity (fitness level). JIA patients showed low disease activity and pain and were physically well functioning. Accelerometer counts were lower in JIA patients than in controls. Accelerometer measurements were negatively correlated with disease activity, erythrocyte sedimentation rate (ESR), and number of joints with swelling and/or limited range of motion (ROM). No correlation was found between PA and pain scores, functional ability, and hypermobility. Patients with involvement of ankles or hips demonstrated significantly lower levels of PA. Children with JIA are less physically active and have lower physical capacity and fitness than their age- and gender-matched healthy peers despite good disease control. The involvement of hips or ankles is associated with lower PA.

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

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

Temporal prolongation of decreased skin blood flow causes cold limbs in Parkinson's disease.

PubMed

Shindo, Kazumasa; Kobayashi, Fumikazu; Miwa, Michiaki; Nagasaka, Takamura; Takiyama, Yoshihisa; Shiozawa, Zenji

2013-03-01

To unravel the pathogenesis of cold limbs in Parkinson's disease, we evaluated cutaneous vasomotor neural function in 25 Parkinson's disease patients with or without cold limbs and 20 healthy controls. We measured resting skin sympathetic nerve activity, as well as reflex changes of skin blood flow and skin sympathetic nerve activity after electrical stimulation, with the parameters including skin sympathetic nerve activity frequency at rest, the amplitude of reflex bursts, the absolute decrease and percent reduction of blood flow, and the recovery time which was calculated as the interval from the start of blood flow reduction until the return to baseline cutaneous blood flow. The resting frequency of skin sympathetic nerve activity was significantly lower in patients with Parkinson's disease than in controls (p < 0.01). There were no significant differences between the patients and controls with respect to the amplitude of skin sympathetic nerve activity and the absolute decrease or percent reduction of blood flow volume. In the controls, the recovery time (9.4 ± 1.2), which was similar to Parkinson's disease patients without cold limbs (9.0 ± 0.7), while the recovery time ranged (15.7 ± 3.2) in Parkinson's disease patients with cold limbs. Recovery was significantly slower in these patients compared with the other groups (p < 0.05). It is possible that cold limbs might arise due to impaired circulation based on prolonged vasoconstriction by peripheral autonomic impairments, in addition to central autonomic dysfunction in Parkinson's disease.

Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

PubMed

Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

2017-05-25

In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate <3.2). Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease.

PubMed

Maiuri, Luigi; Ciacci, Carolina; Ricciardelli, Ida; Vacca, Loredana; Raia, Valeria; Auricchio, Salvatore; Picard, Jean; Osman, Mohamed; Quaratino, Sonia; Londei, Marco

2003-07-05

The adaptive immune system is central to the development of coeliac disease. Adaptive immune responses are, however, controlled by a preceding activation of the innate immune system. We investigated whether gliadin, a protein present in wheat flour, could activate an innate as well as an adaptive immune response in patients with coeliac disease. Duodenal biopsy samples from 42 patients with untreated coeliac disease, 37 treated patients, and 18 controls, were cultured in vitro for 3 h or 24 h, in the presence of either immunodominant gliadin epitopes (p(alpha)-2 and p(alpha)-9) or a non-immunodominant peptide (p31-43) known to induce small intestine damage in coeliac disease. We also incubated biopsy samples from nine untreated and six treated patients with a non-immunodominant peptide for 3 h, before incubation with immunodominant gliadin epitopes. Different combinations of interleukin-15 or signal transduction inhibitors were added to selected incubations. Only the non-immunodominant peptide induced rapid expression of interleukin-15, CD83, cyclo-oxygenase (COX)-2, and CD25 by CD3- cells (p=0.005 vs medium alone) and enterocyte apoptosis (p<0.0001). Only the non-immunodominant peptide induced p38 MAP kinase activation in CD3- cells. Pre-incubation with the non-immunodominant peptide enabled immunodominant epitopes to induce T-cell activation (p=0.001) and enterocyte apoptosis. Inhibition of interleukin-15 or of p38 MAP kinase controlled such activity. A gliadin fragment can activate the innate immune system, affecting the in situ T-cell recognition of dominant gliadin epitopes. Although our findings emphasise the key role of gliadin-specific T cells, they suggest a complex pathogenic situation, and show that inhibition of interleukin-15 or p38 MAP kinase might have the potential to control coeliac disease.

Mid-frontal theta activity is diminished during cognitive control in Parkinson's disease.

PubMed

Singh, Arun; Richardson, Sarah Pirio; Narayanan, Nandakumar; Cavanagh, James F

2018-05-23

Mid-frontal theta activity underlies cognitive control. These 4-8 Hz rhythms are modulated by cortical dopamine and can be abnormal in patients with Parkinson's disease (PD). Here, we investigated mid-frontal theta deficits in PD patients during a task explicitly involving cognitive control. We collected scalp EEG from high-performing PD patients and demographically matched controls during performance of a modified Simon reaction-time task. This task involves cognitive control to adjudicate response conflict and error-related adjustments. Task performance of PD patients was indistinguishable from controls, but PD patients had less mid-frontal theta modulations around cues and responses. Critically, PD patients had attenuated mid-frontal theta activity specifically associated with response conflict and post-error processing. These signals were unaffected by medication or motor scores. Post-error mid-frontal theta activity was correlated with disease duration. Classification of control vs. PD from these data resulted in a specificity of 69% and a sensitivity of 72%. These findings help define the scope of mid-frontal theta aberrations during cognitive control in PD, and may provide insight into the nature of PD-related cognitive dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit.

PubMed Central

Coimbra, T.; Wiggins, R.; Noh, J. W.; Merritt, S.; Phan, S. H.

1991-01-01

The purpose of this study was to assay for the presence of collagen synthesis stimulatory activity in the kidney during immune-induced renal injury that results in severe fibrosis in both glomerular and interstitial compartments. A model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on day 0 by the injection of anti-GBM antibody and renal cortex tissues were then sampled at various time points. Only conditioned media prepared from diseased renal cortical samples showed collagen synthesis stimulatory activity when tested on rabbit mesangial cells. The activity had an estimated molecular weight range of 16 to 25 kd and was neutralized by antibody to transforming growth factor-beta (TGF-beta). A standard assay for TGF-beta using a mink lung epithelial cell line confirmed the increase in TGF-beta activity in conditioned media of diseased cortex from day 7 and day 14 animals, which was not significantly activated by previous acidification. This suggests that most of the TGF-beta present in renal conditioned media was in the active form. The increase in renal cortical secretion of active TGF-beta was accompanied by increases in renal cortical TGF-beta mRNA content on days 4 and 7 after induction, with subsequent return to control levels. A similar increase in TGF-beta activity was present in nonacidified conditioned media of purified glomeruli from diseased days 7 and 14 animals, which was also accompanied by significant increases in TGF-beta mRNA. However with acidification no significant differences were noted between control and diseased samples, suggesting the presence of substantial latent TGF-beta activity in control glomerular conditioned media. These same control-conditioned media contained inhibitor activity for added exogenous TGF-beta. These results support the conclusion that the association between increased TGF-beta secretion and increased renal cortical collagen synthesis in this model is consistent with a role for this cytokine in directing fibrogenesis in the kidney. Images Figure 6 PMID:1987768

The control of Asian rust by glyphosate in glyphosate-resistant soybeans.

PubMed

Feng, Paul C C; Clark, Celeste; Andrade, Gabriella C; Balbi, Maria C; Caldwell, Pat

2008-04-01

Glyphosate is a widely used broad-spectrum herbicide. Recent studies in glyphosate-resistant (GR) crops have shown that, in addition to its herbicidal activity, glyphosate exhibits activity against fungi, thereby providing disease control benefits. In GR wheat, glyphosate has shown both preventive and curative activities against Puccinia striiformis f. sp. tritici (Erikss) CO Johnston and Puccinia triticina Erikss, which cause stripe and leaf rusts respectively. Laboratory studies confirmed earlier observations that glyphosate has activity against Phakopsora pachyrhizi Syd & P Syd which causes Asian soybean rust (ASR) in GR soybeans. The results showed that glyphosate at rates between 0.84 and 1.68 kg ha(-1) delayed the onset of ASR in GR soybeans. However, field trials conducted in Argentina and Brazil under natural infestations showed variable ASR control from application of glyphosate in GR soybeans. Further field studies are ongoing to define the activity of glyphosate against ASR. These results demonstrate the disease control activities of glyphosate against rust diseases in GR wheat and GR soybeans. Copyright (c) 2007 Society of Chemical Industry.

Insect and disease activity (2003)

Treesearch

John W. Coulston

2007-01-01

Why Are Insects and Diseases Important? Native insects and diseases are a natural part of ecosystems and are essential to the ecological balance in natural forests (Castello and others 1995). In contrast, nonnative insects and diseases can pose a particular threat because ecosystems often lack natural internal controls of these agents. The activity of both native and...

The Relationships between Television Viewing in Midlife and the Development of Alzheimer's Disease in a Case-Control Study

ERIC Educational Resources Information Center

Lindstrom, H.A.; Fritsch, T.; Petot, G.; Smyth, K.A.; Chen, C.H.; Debanne, S.M.; Lerner, A.J.; Friedland, R.P.

2005-01-01

The relationship between leisure activities and development of cognitive impairment in aging has been the subject of recent research. We examined television viewing in association with risk of developing Alzheimer's disease (AD) in a case-control study. Given recent focus on the importance of intellectually stimulating activities as preventive…

The Association between Funding for Statewide Programs and Enactment of Obesity Legislation

ERIC Educational Resources Information Center

Hersey, James; Lynch, Christina; Williams-Piehota, Pamela; Rooks, Adrienne; Hamre, Robin; Chappelle, Eileen F.; Roussel, Amy; O'Toole, Terry; Grasso, Tamara; Hannan, Casey

2010-01-01

Objective: As part of a national effort to prevent and control obesity, the Centers for Disease Control and Prevention's (CDC's) Nutrition and Physical Activity Program to Prevent Obesity and Other Chronic Diseases (NPAO) provides funding to states to improve access to healthful food and increase opportunities for physical activity. The CDC also…

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis.

PubMed

Jalal, Diana; McFadden, Molly; Dwyer, Jamie P; Umanath, Kausik; Aguilar, Erwin; Yagil, Yoram; Greco, Barbara; Sika, Mohammed; Lewis, Julia B; Greene, Tom; Goral, Simin

2017-04-01

Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown. We conducted a post-hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed. There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group. Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence. © 2016 International Society for Hemodialysis.

The correlation of serum bilirubin levels with disease activity in patients with rheumatoid arthritis.

PubMed

Peng, You-Fan; Wang, Jun-Li; Pan, Guo-Gang

2017-06-01

We investigated the relationship between serum bilirubin and disease activity in patients with rheumatoid arthritis (RA). We included a total of 173 consecutive RA patients without steroid treatment and 346 healthy subjects; the disease activity score in 28 joints (DAS28) was used to assess disease activity in patients with RA. Serum bilirubin concentrations were significantly lower in RA patients than in controls. Serum bilirubin was found to be negatively correlated with C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in patients with RA. There was a negative correlation between the serum bilirubin and DAS28 score (r=-0.331, P<0.001). Serum bilirubin was independently associated with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression analysis. Serum bilirubin concentrations are lower in patients with RA compared to controls and correlate with disease activity in patients with RA. Copyright © 2017. Published by Elsevier B.V.

Proteomic profiling of eccrine sweat reveals its potential as a diagnostic biofluid for active tuberculosis.

PubMed

Adewole, Olanisun Olufemi; Erhabor, Greg Efosa; Adewole, Temitayo Oluwatoyin; Ojo, Abiodun Oluwasesan; Oshokoya, Harriet; Wolfe, Lisa M; Prenni, Jessica E

2016-05-01

Excessive sweating is a common symptom of the disease and an unexplored biofluid for TB diagnosis; we conducted a proof-of-concept study to identify potential diagnostic biomarkers of active TB in eccrine sweat. We performed a global proteomic profile of eccrine sweat sampled from patients with active pulmonary TB, other lung diseases (non-TB disease), and healthy controls. A comparison of proteomics between Active-TB, Non-TB, and Healthy Controls was done in search for potential biomarkers of active TB. Sweat specimens were pooled from 32 active TB patients, 27 patients with non-TB diseases, and 24 apparently healthy controls, all were negative for HIV. Over 100 unique proteins were identified in the eccrine sweat of all three groups. Twenty-six proteins were exclusively detected in the sweat of patients with active TB while the remaining detected proteins overlapped between three groups. Gene ontology evaluation indicated that the proteins detected uniquely in sweat of active TB patients were involved in immune response and auxiliary protein transport. Gene products for cellular components (e.g. ribosomes) were detected only in active TB patients. Data are available via ProteomeXchange with identifier PXD003224. Proteomics of sweat from active TB patients is a viable approach for biomarker identification, which could be used to develop a nonsputum-based test for detection of active TB. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Control of Citrus Huanglongbing via Trunk Injection of Plant Defense Activators and Antibiotics.

PubMed

Hu, J; Jiang, J; Wang, N

2018-02-01

Citrus huanglongbing (HLB) or greening is a devastating disease of citrus worldwide and no effective control measure is currently available. Plant defense activators environmentally friendly compounds capable of inducing resistance against many plant pathogens. Earlier studies showed that foliar spray of plant defense inducers could slow down HLB disease progress. In this study, eight plant defense activators and three antibiotics were evaluated in three field trials for their effect to control HLB by trunk injection of young and mature sweet orange trees. Results showed that four trunk injections of several activators, including salicylic acid, oxalic acid, acibenzolar-S-methyl, and potassium phosphate, provided significant control of HLB by suppressing 'Candidatus Liberibacter asiaticus' titer and disease progress. Trunk injection of penicillin, streptomycin, and oxytetracycline hydrochloride resulted in excellent control of HLB. In general, antibiotics were more effective in reduction of 'Ca. L. asiaticus' titer and HLB symptom expressions than plant defense activators. These treatments also resulted in increased yield and better fruit quality. Injection of both salicylic acid and acibenzolar-S-methyl led to significant induction of pathogenesis-related (PR) genes PR-1 and PR-2 genes. Meanwhile, injection of either potassium phosphate or oxalic acid resulted in significant induction of PR-2 or PR-15 gene expression, respectively. These results suggested that HLB diseased trees remained inducible for systemic acquired resistance under field conditions. In summary, this study presents information regarding controlling HLB via trunk injection of plant defense activators and antibiotics, which helps citrus growers in decision making regarding developing an effective HLB management program.

Increased levels of circulating platelet derived microparticles in Crohn's disease patients.

PubMed

Tziatzios, Georgios; Polymeros, Dimitrios; Spathis, Aris; Triantafyllou, Maria; Gkolfakis, Paraskevas; Karakitsos, Petros; Dimitriadis, George; Triantafyllou, Konstantinos

2016-10-01

Platelet activation is a consistent feature in inflammatory bowel disease. However, the role of circulating platelet derived microparticles (PDMPs) and the effects of disease activity and treatment on their levels has not been clarified yet in this disorder. Using flow cytometry, we measured platelet derived microparticles and platelet derived microparticles expressing Annexin V in platelet rich plasma from 47 Crohn's disease and 43 ulcerative colitis patients and 24 healthy controls. Crohn's disease patients have greater PDMPs (0.31% ± 0.07% versus 0.14% ± 0.04%, p = 0.02) and PDMPs expressing Annexin V (27% ± 2.6% versus 14.6% ± 2.7%, p = 0.002) levels in comparison with healthy controls; however, both microparticles levels are not related with disease activity. Crohn's disease patients on 5-ASA therapy show lower levels of PDMPs in comparison with those on no 5-ASA (0.30% ± 0.07% versus 0.32% ± 0.09%, p = 0.048). Ulcerative colitis patients have similar PDMPs and PDMPs expressing Annexin V levels, compared to healthy controls (p = 0.06 and p = 0.2, respectively) and there is no correlation of both microparticles expression with disease activity. 5-ASA has no effect on both microparticles levels in ulcerative colitis patients. Anti-TNF-α treatment has no effect on study's microparticles expression in Crohn's and ulcerative colitis patients. Circulating levels of platelet derived microparticles are increased only in Crohn's patients, but they do not correlate with disease activity. 5-ASA treatment is associated with lower levels of PDMPs only in Crohn's, while anti-TNF-α treatment does not influence expression of microparticles in inflammatory bowel disease patients.

Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1β Pathway in Systemic Lupus Erythematosus.

PubMed

Nhek, Sokha; Clancy, Robert; Lee, Kristen A; Allen, Nicole M; Barrett, Tessa J; Marcantoni, Emanuela; Nwaukoni, Janet; Rasmussen, Sara; Rubin, Maya; Newman, Jonathan D; Buyon, Jill P; Berger, Jeffrey S

2017-04-01

Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet-endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.1±12.8 years; 82% female; 37% white) with age- and sex-matched controls. Platelets were coincubated with human umbilical vein endothelial cells (HUVECs) and changes to gene expression assessed by an RNA array and quantitative reverse transcription polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1±3.9). Compared with controls, patients with SLE had significantly increased monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with SLE platelets found a platelet-mediated effect on endothelial gene pathways involved in cell activation. Sera from SLE versus control subjects significantly increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3) platelet-induced HUVEC gene expression of interleukin-8, and intercellular adhesion molecule 1; and (4) proinflammatory gene expression in HUVECs, mediated by interleukin-1β-dependent pathway. Incubation of SLE-activated platelets with an interleukin-1β-neutralizing antibody or HUVECs pretreated with interleukin-1 receptor antibodies attenuated the platelet-mediated activation of endothelial cells. Platelet activity measurements and subsequent interleukin-1β-dependent activation of the endothelium are increased in subjects with SLE. Platelet-endothelial interactions may play a role in the pathogenesis of cardiovascular disease in patients with SLE. © 2017 American Heart Association, Inc.

Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1β Pathway in Systemic Lupus Erythematosus

PubMed Central

Nhek, Sokha; Clancy, Robert; Lee, Kristen A.; Allen, Nicole M.; Barrett, Tessa J.; Marcantoni, Emanuela; Nwaukoni, Janet; Rasmussen, Sara; Rubin, Maya; Newman, Jonathan D.; Buyon, Jill P.; Berger, Jeffrey S.

2017-01-01

Objective Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet–endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. Approach and Results Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.1±12.8 years; 82% female; 37% white) with age- and sex-matched controls. Platelets were coincubated with human umbilical vein endothelial cells (HUVECs) and changes to gene expression assessed by an RNA array and quantitative reverse transcription polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1±3.9). Compared with controls, patients with SLE had significantly increased monocyte and leukocyte–platelet aggregation and platelet aggregation in response to submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with SLE platelets found a platelet-mediated effect on endothelial gene pathways involved in cell activation. Sera from SLE versus control subjects significantly increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3) platelet-induced HUVEC gene expression of interleukin-8, and intercellular adhesion molecule 1; and (4) proinflammatory gene expression in HUVECs, mediated by interleukin-1β–dependent pathway. Incubation of SLE-activated platelets with an interleukin-1β–neutralizing antibody or HUVECs pretreated with interleukin-1 receptor antibodies attenuated the platelet-mediated activation of endothelial cells. Conclusions Platelet activity measurements and subsequent interleukin-1β–dependent activation of the endothelium are increased in subjects with SLE. Platelet–endothelial interactions may play a role in the pathogenesis of cardiovascular disease in patients with SLE. PMID:28153882

Selective serotonin reuptake inhibition modulates response inhibition in Parkinson’s disease

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.

2014-01-01

Impulsivity is common in Parkinson’s disease even in the absence of impulse control disorders. It is likely to be multifactorial, including a dopaminergic ‘overdose’ and structural changes in the frontostriatal circuits for motor control. In addition, we proposed that changes in serotonergic projections to the forebrain also contribute to response inhibition in Parkinson’s disease, based on preclinical animal and human studies. We therefore examined whether the selective serotonin reuptake inhibitor citalopram improves response inhibition, in terms of both behaviour and the efficiency of underlying neural mechanisms. This multimodal magnetic resonance imaging study used a double-blind randomized placebo-controlled crossover design with an integrated Stop-Signal and NoGo paradigm. Twenty-one patients with idiopathic Parkinson’s disease (46–76 years old, 11 male, Hoehn and Yahr stage 1.5–3) received 30 mg citalopram or placebo in addition to their usual dopaminergic medication in two separate sessions. Twenty matched healthy control subjects (54–74 years old, 12 male) were tested without medication. The effects of disease and drug on behavioural performance and regional brain activity were analysed using general linear models. In addition, anatomical connectivity was examined using diffusion tensor imaging and tract-based spatial statistics. We confirmed that Parkinson’s disease caused impairment in response inhibition, with longer Stop-Signal Reaction Time and more NoGo errors under placebo compared with controls, without affecting Go reaction times. This was associated with less stop-specific activation in the right inferior frontal cortex, but no significant difference in NoGo-related activation. Although there was no beneficial main effect of citalopram, it reduced Stop-Signal Reaction Time and NoGo errors, and enhanced inferior frontal activation, in patients with relatively more severe disease (higher Unified Parkinson’s Disease Rating Scale motor score). The behavioural effect correlated with the citalopram-induced enhancement of prefrontal activation and the strength of preserved structural connectivity between the frontal and striatal regions. In conclusion, the behavioural effect of citalopram on response inhibition depends on individual differences in prefrontal cortical activation and frontostriatal connectivity. The correlation between disease severity and the effect of citalopram on response inhibition may be due to the progressive loss of forebrain serotonergic projections. These results contribute to a broader understanding of the critical roles of serotonin in regulating cognitive and behavioural control, as well as new strategies for patient stratification in clinical trials of serotonergic treatments in Parkinson’s disease. PMID:24578545

Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly.

PubMed

van der Lely, Aart J; Gomez, Roy; Pleil, Andreas; Badia, Xavier; Brue, Thierry; Buchfelder, Michael; Burman, Pia; Clemmons, David; Ghigo, Ezio; Jørgensen, Jens Otto Lunde; Luger, Anton; van der Lans-Bussemaker, Joli; Webb, Susan M; Strasburger, Christian J

2017-12-01

Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient's perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.

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

The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves' Disease.

PubMed

Cho, Sun Wook; Bae, Jae Hyun; Noh, Gyeong Woon; Kim, Ye An; Moon, Min Kyong; Park, Kyoung Un; Song, Junghan; Yi, Ka Hee; Park, Do Joon; Chung, June-Key; Cho, Bo Youn; Park, Young Joo

2015-01-01

Osteoporosis-related fractures are one of the complications of Graves' disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves' disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves' disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves' disease.

Assessment of Diet and Physical Activity in Paediatric Non-Alcoholic Fatty Liver Disease Patients: A United Kingdom Case Control Study.

PubMed

Gibson, Philippa S; Lang, Sarah; Gilbert, Marianne; Kamat, Deepa; Bansal, Sanjay; Ford-Adams, Martha E; Desai, Ashish P; Dhawan, Anil; Fitzpatrick, Emer; Moore, J Bernadette; Hart, Kathryn H

2015-11-26

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children, with prevalence rising alongside childhood obesity rates. This study aimed to characterise the habitual diet and activity behaviours of children with NAFLD compared to obese children without liver disease in the United Kingdom (UK). Twenty-four biopsy-proven paediatric NAFLD cases and eight obese controls without biochemical or radiological evidence of NAFLD completed a 24-h dietary recall, a Physical Activity Questionnaire (PAQ), a Dutch Eating Behavior Questionnaire (DEBQ) and a 7-day food and activity diary (FAD), in conjunction with wearing a pedometer. Groups were well matched for age and gender. Obese children had higher BMI z-scores (p = 0.006) and BMI centiles (p = 0.002) than participants with NAFLD. After adjusting for multiple hypotheses testing and controlling for differences in BMI, no differences in macro- or micronutrient intake were observed as assessed using either 24-h recall or 7-day FAD (p > 0.001). Under-reporting was prevalent (NAFLD 75%, Obese Control 87%: p = 0.15). Restrained eating behaviours were significantly higher in the NAFLD group (p = 0.005), who also recorded more steps per day than the obese controls (p = 0.01). In conclusion, this is the first study to assess dietary and activity patterns in a UK paediatric NAFLD population. Only a minority of cases and controls were meeting current dietary and physical activity recommendations. Our findings do not support development of specific dietary/ physical activity guidelines for children with NAFLD; promoting adherence with current general paediatric recommendations for health should remain the focus of clinical management.

A Randomized, Double-blind, Placebo-controlled Clinical Trial Examining the Effects of Green Tea Extract on Systemic Lupus Erythematosus Disease Activity and Quality of Life.

PubMed

Shamekhi, Z; Amani, R; Habibagahi, Z; Namjoyan, F; Ghadiri, Ata; Saki Malehi, A

2017-07-01

Antiinflammatory and immunomodulatory benefit of green tea (Camellia sinensis) in autoimmune disease has been proven in recent studies. The objective of this study was to assess the effects of green tea on disease activity and quality of life in systemic lupus erythematosus patients. A randomized controlled trial on subjects with lupus was conducted, and 68 patients in the age range of 39.1 ± 10.3 years and body mass index of 25.7 ± 5.21 kg/m 2 completed the 12-week study. Patients were randomly divided into two groups of intervention (1000 mg green tea extract, two capsules/day) and control (1000 mg of starch, two capsules/day). Main outcome measure, systemic lupus erythematosus disease activity, was assessed by the systemic lupus erythematosus disease activity index at the first and after 3 months of intervention. In addition, patient's quality of life was evaluated by short form of quality-of-life questionnaire at baseline and after 3 months. Green tea extract supplementation significantly reduced disease activity in lupus patients (p < 0.004); in addition, it significantly increased the vitality (p < 0.006) and general health (p < 0.01). This study showed that daily consumption of green tea extracts for 12 weeks improves the systemic lupus erythematosus disease activity as well as some aspects of quality of life. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

An early and late peak in microglial activation in Alzheimer's disease trajectory.

PubMed

Fan, Zhen; Brooks, David J; Okello, Aren; Edison, Paul

2017-03-01

Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease. Thirty subjects (eight mild cognitive impairment, eight Alzheimer's disease and 14 controls) aged between 54 and 77 years underwent 11C-(R)PK11195, 11C-PIB positron emission tomography and magnetic resonance imaging scans. Patients were followed-up after 14 ± 4 months. Region of interest and Statistical Parametric Mapping analysis were used to determine longitudinal alterations. Single subject analysis was performed to evaluate the individualized pathological changes over time. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed using Biological Parametric Mapping. We demonstrated that both baseline and follow-up microglial activation in the mild cognitive impairment cohort compared to controls were increased by 41% and 21%, respectively. There was a longitudinal reduction of 18% in microglial activation in mild cognitive impairment cohort over 14 months, which was associated with a mild elevation in fibrillar amyloid load. Cortical clusters of microglial activation and amyloid deposition spatially overlapped in the subjects with mild cognitive impairment. Baseline microglial activation was increased by 36% in Alzheimer's disease subjects compared with controls. Longitudinally, Alzheimer's disease subjects showed an increase in microglial activation. In conclusion, this is one of the first longitudinal positron emission tomography studies evaluating longitudinal changes in microglial activation in mild cognitive impairment and Alzheimer's disease subjects. We found there is an initial longitudinal reduction in microglial activation in subjects with mild cognitive impairment, while subjects with Alzheimer's disease showed an increase in microglial activation. This could reflect that activated microglia in mild cognitive impairment initially may adopt a protective activation phenotype, which later change to a cidal pro-inflammatory phenotype as disease progresses and amyloid clearance fails. Thus, we speculate that there might be two peaks of microglial activation in the Alzheimer's disease trajectory; an early protective peak and a later pro-inflammatory peak. If so, anti-microglial agents targeting the pro-inflammatory phenotype would be most beneficial in the later stages of the disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of Tai Chi-based cardiac rehabilitation on aerobic endurance, psychosocial well-being, and cardiovascular risk reduction among patients with coronary heart disease: A systematic review and meta-analysis.

PubMed

Liu, Ting; Chan, Aileen Wk; Liu, Yun Hong; Taylor-Piliae, Ruth E

2018-04-01

Tai Chi is an attractive exercise to improve cardiovascular health. This review aimed to synthesize articles written both in Chinese and in English to evaluate the effects of Tai Chi-based cardiac rehabilitation on aerobic endurance, psychosocial well-being and cardiovascular diseases risk reduction for coronary heart diseases patients. PRISMA guidelines were used to search major health databases to identify randomized controlled trials or non-randomized controlled clinical trials that evaluated Tai Chi intervention compared with active or non-active control groups in coronary heart disease patients. When suitable, data were pooled using a random-effects meta-analysis model. Thirteen studies met the inclusion criteria. Tai Chi groups showed a large and significant improvement in aerobic endurance compared with both active and non-active control interventions (standard mean difference (SMD) 1.12; 95% confidence interval (CI): 0.58-1.66; p <0.001). Tai Chi groups also showed a significantly lower level of anxiety (SMD=9.28; CI: 17.46-1.10; p=0.03) and depression (SMD=9.42; CI: 13.59-5.26; p <0.001), and significantly better quality of life (SMD=0.73; 95% CI: 0.39-1.08; p <0.001) compared with non-active control groups. Significant effects of Tai Chi have been found in improving aerobic endurance and psychosocial well-being among coronary heart disease patients. Tai Chi could be a cost-effective and safe exercise option in cardiac rehabilitation. However, the effect of Tai Chi on cardiovascular disease risk reduction has not been amply investigated among coronary heart disease patients. Caution is also warranted in view of a small number of studies for this meta-analysis and potential heterogeneity in differences in the varied designs of Tai Chi intervention.

Mean platelet volume in ocular Behçet's disease.

PubMed

Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Cınar, Yasin; Akkurt, Meltem; Sahin, Muhammed; Ozkurt, Zeynep; Sahin, Alparslan; Caça, Ihsan

2013-01-01

To determine whether mean platelet volume (MPV) is an indicator of disease severity in ocular Behçet's Disease (BD). 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. 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. MPV measurement in ocular BD is not a predictive laboratory test to determine the clinical improvement in early stages following classical immunosuppressive treatment.

Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

PubMed

Lee, Hyeonjeong; Shin, Miyoung

2017-01-01

The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into distinctive associations between pathway activities in case and control samples.

Reserve-building activities in multiple sclerosis patients and healthy controls: a descriptive study.

PubMed

Schwartz, Carolyn E; Ayandeh, Armon; Ramanathan, Murali; Benedict, Ralph; Dwyer, Michael G; Weinstock-Guttman, Bianca; Zivadinov, Robert

2015-08-12

Cognitive reserve has been implicated as a possible protective factor in multiple sclerosis (MS) but to date no study has compared reserve-building activities across disease course or to healthy controls. This study aims to describe differences in reserve-building activities across the MS disease course and healthy controls. Secondary analysis of a cross-sectional cohort study that included 276 healthy controls, and subjects with clinically isolated syndrome (CIS; n = 67), relapsing-remitting MS (RRMS; n = 358) and secondary progressive MS (PMS; n = 109). Past reserve-building activities were operationalized as occupational attainment and education. Current activities comprised 6 strenuous and 6 non-strenuous activities, including 5 reserve-building activities and television-watching. Multivariate Analysis of Variance models examined group differences in past and current activities, after adjusting for covariates. There were group differences in past and current reserve-building activities. SPMS patients had lower past reserve-building activities than healthy controls. All forms of MS engaged in fewer strenuous current reserve-building pursuits than healthy controls. RRMS read less than healthy controls. SPMS engaged in fewer job-related non-strenuous activities. All MS groups watched more television than healthy controls. MS patients show significantly fewer past and present reserve-building activities. Although it is difficult to establish causality without future prospective studies, lifestyle-modifying interventions should prioritize expanding MS patients' repertoire of strenuous and non-strenuous activities.

RNA Interference of Endochitinases in the Sugarcane Endophyte Trichoderma virens 223 Reduces Its Fitness as a Biocontrol Agent of Pineapple Disease

PubMed Central

Romão-Dumaresq, Aline S.; de Araújo, Welington Luiz; Talbot, Nicholas J.; Thornton, Christopher R.

2012-01-01

The sugarcane root endophyte Trichoderma virens 223 holds enormous potential as a sustainable alternative to chemical pesticides in the control of sugarcane diseases. Its efficacy as a biocontrol agent is thought to be associated with its production of chitinase enzymes, including N-acetyl-ß-D-glucosaminidases, chitobiosidases and endochitinases. We used targeted gene deletion and RNA-dependent gene silencing strategies to disrupt N-acetyl-ß-D-glucosaminidase and endochitinase activities of the fungus, and to determine their roles in the biocontrol of soil-borne plant pathogens. The loss of N-acetyl-ß-D-glucosaminidase activities was dispensable for biocontrol of the plurivorous damping-off pathogens Rhizoctonia solani and Sclerotinia sclerotiorum, and of the sugarcane pathogen Ceratocystis paradoxa, the causal agent of pineapple disease. Similarly, suppression of endochitinase activities had no effect on R. solani and S. sclerotiorum disease control, but had a pronounced effect on the ability of T. virens 223 to control pineapple disease. Our work demonstrates a critical requirement for T. virens 223 endochitinase activity in the biocontrol of C. paradoxa sugarcane disease, but not for general antagonism of other soil pathogens. This may reflect its lifestyle as a sugarcane root endophyte. PMID:23110120

The Preventive Control of Zoonotic Visceral Leishmaniasis: Efficacy and Economic Evaluation

PubMed Central

Wu, Jianhong; Massad, Eduardo

2017-01-01

Zoonotic Visceral Leishmaniasis (ZVL) is one of the world's deadliest and neglected infectious diseases, according to World Health Organization. This disease is one of major human and veterinary medical significance. The sandfly and the reservoir in urban areas remain among the major challenges for the control activities. In this paper, we evaluated five control strategies (positive dog elimination, insecticide impregnated dog collar, dog vaccination, dog treatment, and sandfly population control), considering disease control results and cost-effectiveness. We elaborated a mathematical model based on a set of differential equations in which three populations were represented (human, dog, and sandfly). Humans and dogs were divided into susceptible, latent, clinically ill, and recovery categories. Sandflies were divided into noninfected, infected, and infective. As the main conclusions, the insecticide impregnated dog collar was the strategy that presented the best combination between disease control and cost-effectiveness. But, depending on the population target, the control results and cost-effectiveness of each strategy may differ. More and detailed studies are needed, specially one which optimizes the control considering more than one strategy in activity. PMID:28588642

The Preventive Control of Zoonotic Visceral Leishmaniasis: Efficacy and Economic Evaluation.

PubMed

Shimozako, Helio Junji; Wu, Jianhong; Massad, Eduardo

2017-01-01

Zoonotic Visceral Leishmaniasis (ZVL) is one of the world's deadliest and neglected infectious diseases, according to World Health Organization. This disease is one of major human and veterinary medical significance. The sandfly and the reservoir in urban areas remain among the major challenges for the control activities. In this paper, we evaluated five control strategies (positive dog elimination, insecticide impregnated dog collar, dog vaccination, dog treatment, and sandfly population control), considering disease control results and cost-effectiveness. We elaborated a mathematical model based on a set of differential equations in which three populations were represented (human, dog, and sandfly). Humans and dogs were divided into susceptible, latent, clinically ill, and recovery categories. Sandflies were divided into noninfected, infected, and infective. As the main conclusions, the insecticide impregnated dog collar was the strategy that presented the best combination between disease control and cost-effectiveness. But, depending on the population target, the control results and cost-effectiveness of each strategy may differ. More and detailed studies are needed, specially one which optimizes the control considering more than one strategy in activity.

PCT Databank: A Tool for Planning, Implementation and Monitoring of Integrated Preventive Chemotherapy for Control of Neglected Tropical Diseases (NTD)

PubMed Central

Mikhailov, Alexei; Yajima, Aya; Mbabazi, PS; Gabrielli, Albis F.; Montresor, Antonio; Engels, Dirk

2017-01-01

The integration of vertical control programmes of neglected tropical diseases (NTDs) aims at containing operational cost, simplifies the application of the control measures and extends the intervention coverage. The Preventive Chemotherapy and Transmission Control (PCT) Databank was established by the World Health Organization to facilitate the sharing of data among the different partners involved in control activities and collects and compiles historical and current information on disease-specific epidemiological situation, the geographical overlapping of NTDs and the progress of control activities in all the NTD-endemic countries. The summary of country-specific epidemiological maps and the progress of control activities is available online as the online PCT Databank and Country Profiles. The annual progress of preventive chemotherapy (PC) interventions targeting at specific NTDs is also annually reported in the Weekly Epidemiological Record (WER). In this paper, we elucidated the methodology of data collection, compilation and mapping to establish the PCT Databank and presented the key features of the associated three online outputs, i.e. the online PCT Databank, the Country Profile and the WER. PMID:22357399

Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease.

PubMed Central

Hvatum, M; Scott, H; Brandtzaeg, P

1992-01-01

Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha-lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy. PMID:1612478

A customizable model for chronic disease coordination: Lessons learned from the coordinated chronic disease program

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

Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managedmore » resources, and 6) relationship building. Furthermore, these elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs.« less

A customizable model for chronic disease coordination: Lessons learned from the coordinated chronic disease program

DOE PAGES

Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

2016-03-31

In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managedmore » resources, and 6) relationship building. Furthermore, these elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs.« less

College adjustment in University of Michigan students with Crohn's and colitis.

PubMed

Adler, Jeremy; Raju, Sheela; Beveridge, Allison S; Wang, Sijian; Zhu, Ji; Zimmermann, Ellen M

2008-09-01

Adjustment to college is critical for academic success. Poor college adjustment correlates with poor academic performance, low graduation rates, and poor success later in life. Limited data are available on the effects of inflammatory bowel disease (IBD) on college adjustment. We hypothesize that disease activity negatively impacts on QOL, and adversely affects college adjustment. Undergraduate students (6 Crohn's disease [CD], 12 ulcerative colitis [UC], 19 healthy controls) completed a standardized college adjustment survey (SACQ) and QOL instrument (SF-12). Where appropriate, disease specific activity and QOL indices were obtained (HBI, SCCAI, SIBDQ). There was an inverse correlation between disease activity and college adjustment in CD and UC (R = -0.6554, p = 0.0032). IBD students had lower physical QOL (SF-12) than controls (p = 0.0009). Emotional domain of college adjustment correlated best with SIBDQ (R = 0.8228, p < 0.0001), and correlated better in CD (R = 0.8619) than UC (R = 0.7946). Mental QOL (SF-12) was worse in CD than UC (p = 0.0211), but neither differed from controls (p = 0.4, p = 0.6). Students with active Crohn's and colitis adjust less well to college life. Physical and emotional factors likely contribute. More aggressive medical therapy and better emotional support before and during college may result in happier and healthier college students, leading to higher graduation rates and future success. Interventions resulting in better disease control and support systems may improve college performance and provide long-term benefits to young adults with IBD.

Secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis.

PubMed

Hanaoka, Beatriz Y; Ormseth, Michelle J; Michael Stein, C; Banerjee, Daipayan; Nikolova-Karakashian, Mariana; Crofford, Leslie J

2018-05-01

The goals of this study were to determine if secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis (RA) compared to control subjects and to examine the relationships of S-SMase activity with functional status, quality of life, and RA disease activity measurements. We collected data on 33 patients who were diagnosed with RA and 17 non-RA controls who were comparable in terms of age, sex, and race. Demographic, clinical data and self-reported measures of fatigue, pain, and physical function were obtained directly from patients and controls. RA patients also completed quantitative joint assessment using a 28-joint count and functional status and quality of life assessment using the Modified Health Assessment Questionnaire (MHAQ). Archived serum samples were used to analyze retrospectively serum S-SMase activity in patients and controls. The mean serum S-SMase activity was 1.4-fold higher in patients with RA (RA 2.8 ± 1.0 nmol/ml/h vs. controls 2.0 ± 0.8 nmol/ml/h; p = 0.014). Spearman's rho correlations between S-SMase activity and oxidant activity, markers of inflammation and endothelial activation with the exception of P-selectin (rho = 0.40, p = 0.034), measures of disease activity, functional status, and quality of life were not statistically significant in patients with RA. We confirmed that S-SMase activity is higher among RA patients compared to controls, as in other acute and chronic inflammatory diseases. Future studies can build on the present findings to understand more fully the biologic role(s) of S-SMase activity in RA.

A randomized controlled trial of an activity specific exercise program for individuals with Alzheimer disease in long-term care settings.

PubMed

Roach, Kathryn E; Tappen, Ruth M; Kirk-Sanchez, Neva; Williams, Christine L; Loewenstein, David

2011-01-01

To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Randomized, controlled, single-blinded clinical trial. Residents of 7 long-term care facilities. Eighty-two long-term care residents with mild to severe AD. An activity specific exercise program was compared to a walking program and to an attention control. Ability to perform bed mobility and transfers was assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined.

[Pregnancy in systemic autoimmune diseases: Myths, certainties and doubts].

PubMed

Danza, Álvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

2016-10-07

Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk. Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

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.

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.

Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

PubMed Central

Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

2017-01-01

Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

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

Effects of levodopa on corticostriatal circuits supporting working memory in Parkinson's disease.

PubMed

Simioni, Alison C; Dagher, Alain; Fellows, Lesley K

2017-08-01

Working memory dysfunction is common in Parkinson's disease, even in its early stages, but its neural basis is debated. Working memory performance likely reflects a balance between corticostriatal dysfunction and compensatory mechanisms. We tested this hypothesis by examining working memory performance with a letter n-back task in 19 patients with mild-moderate Parkinson's disease and 20 demographically matched healthy controls. Parkinson's disease patients were tested after an overnight washout of their usual dopamine replacement therapy, and again after a standard dose of levodopa. FMRI was used to assess task-related activation and resting state functional connectivity; changes in BOLD signal were related to performance to disentangle pathological and compensatory processes. Parkinson's disease patients off dopamine replacement therapy displayed significantly reduced spatial extent of task-related activation in left prefrontal and bilateral parietal cortex, and poorer working memory performance, compared to controls. Amongst the Parkinson's disease patients off dopamine replacement therapy, relatively better performance was associated with greater activation of right dorsolateral prefrontal cortex compared to controls, consistent with compensatory right hemisphere recruitment. Administration of levodopa remediated the working memory deficit in the Parkinson's disease group, and resulted in a different pattern of performance-correlated activity, with a shift to greater left ventrolateral prefrontal cortex activation in patients on, compared to off dopamine replacement therapy. Levodopa also significantly increased resting-state functional connectivity between caudate and right parietal cortex (within the right fronto-parietal attentional network). The strength of this connectivity contributed to better performance in patients and controls, suggesting a general compensatory mechanism. These findings argue that Parkinson's disease patients can recruit additional neural resources, here, the right fronto-parietal network, to optimize working memory performance despite impaired corticostriatal function. Levodopa seems to both boost engagement of a task-specific prefrontal region, and strengthen a putative compensatory caudate-cortical network to support this executive function. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

PubMed Central

Weygandt, Martin; Meyer-Arndt, Lil; Behrens, Janina Ruth; Wakonig, Katharina; Bellmann-Strobl, Judith; Ritter, Kerstin; Scheel, Michael; Brandt, Alexander U.; Labadie, Christian; Hetzer, Stefan; Gold, Stefan M.; Paul, Friedemann; Haynes, John-Dylan

2016-01-01

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone. PMID:27821732

Clinical utility of sympathetic blockade in cardiovascular disease management.

PubMed

Park, Chan Soon; Lee, Hae-Young

2017-04-01

A dysregulated sympathetic nervous system is a major factor in the development and progression of cardiovascular disease; thus, understanding the mechanism and function of the sympathetic nervous system and appropriately regulating sympathetic activity to treat various cardiovascular diseases are crucial. Areas covered: This review focused on previous studies in managing hypertension, atrial fibrillation, coronary artery disease, heart failure, and perioperative management with sympathetic blockade. We reviewed both pharmacological and non-pharmacological management. Expert commentary: Chronic sympathetic nervous system activation is related to several cardiovascular diseases mediated by various pathways. Advancement in measuring sympathetic activity makes visualizing noninvasively and evaluating the activation level even in single fibers possible. Evidence suggests that sympathetic blockade still has a role in managing hypertension and controlling the heart rate in atrial fibrillation. For ischemic heart disease, beta-adrenergic receptor antagonists have been considered a milestone drug to control symptoms and prevent long-term adverse effects, although its clinical implication has become less potent in the era of successful revascularization. Owing to pathologic involvement of sympathetic nervous system activation in heart failure progression, sympathetic blockade has proved its value in improving the clinical course of patients with heart failure.

Enhancing biological control of basal stem rot disease (Ganoderma boninense) in oil palm plantations.

PubMed

Susanto, A; Sudharto, P S; Purba, R Y

2005-01-01

Basal Stem Rot (BSR) disease caused by Ganoderma boninense is the most destructive disease in oil palm, especially in Indonesia and Malaysia. The available control measures for BSR disease such as cultural practices and mechanical and chemical treatment have not proved satisfactory due to the fact that Ganoderma has various resting stages such as melanised mycelium, basidiospores and pseudosclerotia. Alternative control measures to overcome the Ganoderma problem are focused on the use of biological control agents and planting resistant material. Present studies conducted at Indonesian Oil Palm Research Institute (IOPRI) are focused on enhancing the use of biological control agents for Ganoderma. These activities include screening biological agents from the oil palm rhizosphere in order to evaluate their effectiveness as biological agents in glasshouse and field trials, testing their antagonistic activities in large scale experiments and eradicating potential disease inoculum with biological agents. Several promising biological agents have been isolated, mainly Trichoderma harzianum, T. viride, Gliocladium viride, Pseudomonas fluorescens, and Bacillus sp. A glasshouse and field trial for Ganoderma control indicated that treatment with T. harzianum and G. viride was superior to Bacillus sp. A large scale trial showed that the disease incidence was lower in a field treated with biological agents than in untreated fields. In a short term programme, research activities at IOPRI are currently focusing on selecting fungi that can completely degrade plant material in order to eradicate inoculum. Digging holes around the palm bole and adding empty fruit bunches have been investigated as ways to stimulate biological agents.

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

Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly.

PubMed

Mendoza-Núñez, Víctor Manuel; Martínez-Maldonado, María de la Luz; Correa-Muñoz, Elsa

2009-08-26

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. 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. 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.

78 FR 20319 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-04

... GH13-004; Monitoring and Evaluation of Malaria Control and Elimination Activities, FOA GH13-005; and...; Monitoring and Evaluation of Malaria Control and Elimination Activities, FOA GH13-005; and Research and...

Inflammatory bowel disease in children of middle eastern descent.

PubMed

Naidoo, Christina Mai Ying; Leach, Steven T; Day, Andrew S; Lemberg, Daniel A

2014-01-01

Increasing rates of inflammatory bowel disease (IBD) are now seen in populations where it was once uncommon. The pattern of IBD in children of Middle Eastern descent in Australia has never been reported. This study aimed to investigate the burden of IBD in children of Middle Eastern descent at the Sydney Children's Hospital, Randwick (SCHR). The SCHR IBD database was used to identify patients of self-reported Middle Eastern ethnicity diagnosed between 1987 and 2011. Demographic, diagnosis, and management data was collected for all Middle Eastern children and an age and gender matched non-Middle Eastern IBD control group. Twenty-four patients of Middle Eastern descent were identified. Middle Eastern Crohn's disease patients had higher disease activity at diagnosis, higher use of thiopurines, and less restricted colonic disease than controls. Although there were limitations with this dataset, we estimated a higher prevalence of IBD in Middle Eastern children and they had a different disease phenotype and behavior compared to the control group, with less disease restricted to the colon and likely a more active disease course.

Inflammatory Bowel Disease in Children of Middle Eastern Descent

PubMed Central

Naidoo, Christina Mai Ying; Leach, Steven T.; Day, Andrew S.; Lemberg, Daniel A.

2014-01-01

Increasing rates of inflammatory bowel disease (IBD) are now seen in populations where it was once uncommon. The pattern of IBD in children of Middle Eastern descent in Australia has never been reported. This study aimed to investigate the burden of IBD in children of Middle Eastern descent at the Sydney Children's Hospital, Randwick (SCHR). The SCHR IBD database was used to identify patients of self-reported Middle Eastern ethnicity diagnosed between 1987 and 2011. Demographic, diagnosis, and management data was collected for all Middle Eastern children and an age and gender matched non-Middle Eastern IBD control group. Twenty-four patients of Middle Eastern descent were identified. Middle Eastern Crohn's disease patients had higher disease activity at diagnosis, higher use of thiopurines, and less restricted colonic disease than controls. Although there were limitations with this dataset, we estimated a higher prevalence of IBD in Middle Eastern children and they had a different disease phenotype and behavior compared to the control group, with less disease restricted to the colon and likely a more active disease course. PMID:24987422

U.K. Foot and Mouth Disease: A Systemic Risk Assessment of Existing Controls.

PubMed

Delgado, João; Pollard, Simon; Pearn, Kerry; Snary, Emma L; Black, Edgar; Prpich, George; Longhurst, Phil

2017-09-01

This article details a systemic analysis of the controls in place and possible interventions available to further reduce the risk of a foot and mouth disease (FMD) outbreak in the United Kingdom. Using a research-based network analysis tool, we identify vulnerabilities within the multibarrier control system and their corresponding critical control points (CCPs). CCPs represent opportunities for active intervention that produce the greatest improvement to United Kingdom's resilience to future FMD outbreaks. Using an adapted 'features, events, and processes' (FEPs) methodology and network analysis, our results suggest that movements of animals and goods associated with legal activities significantly influence the system's behavior due to their higher frequency and ability to combine and create scenarios of exposure similar in origin to the U.K. FMD outbreaks of 1967/8 and 2001. The systemic risk assessment highlights areas outside of disease control that are relevant to disease spread. Further, it proves to be a powerful tool for demonstrating the need for implementing disease controls that have not previously been part of the system. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

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

Fractalkine (CX3CL1) levels in patients with Behçet's disease and neuro-Behçet's disease.

PubMed

Ceyla, Irkec; Tuba, Teksut Kuz; Adisen, Esra; Esra, Adisen; Banu, Ozturk; Isil, Fidan; Ali, Gurer M; Turgut, Imir; Banu, Bozkurt

2012-04-15

The aim of the present study was to assess the role of CX3CL1 in patients with active and inactive Behçet's Disease (BD), Neuro-Behçet's Disease (NBD) and control subjects. Fifty-six patients admitted to the BD and NBD Outpatient Clinics, and 30 healthy controls were enrolled in the study. Serum CX3CL1 levels were measured by an enzyme linked immunosorbent assay (ELISA). No significant difference was found between the serum CX3CL1 levels of control subjects, and patients with active and inactive BD or NBD, regardless of treatment. To our knowledge, this is the first study analyzing CX3CL1 levels in patients with BD and NBD. Our results demonstrated that serum CX3CL1 levels were not changed in active and inactive BD and NBD. However, further large-scale studies are needed to confirm our results. Copyright © 2011 Elsevier B.V. All rights reserved.

A framework for supervising lifestyle diseases using long-term activity monitoring.

PubMed

Han, Yongkoo; Han, Manhyung; Lee, Sungyoung; Sarkar, A M Jehad; Lee, Young-Koo

2012-01-01

Activity monitoring of a person for a long-term would be helpful for controlling lifestyle associated diseases. Such diseases are often linked with the way a person lives. An unhealthy and irregular standard of living influences the risk of such diseases in the later part of one's life. The symptoms and the initial signs of these diseases are common to the people with irregular lifestyle. In this paper, we propose a novel healthcare framework to manage lifestyle diseases using long-term activity monitoring. The framework recognizes the user's activities with the help of the sensed data in runtime and reports the irregular and unhealthy activity patterns to a doctor and a caregiver. The proposed framework is a hierarchical structure that consists of three modules: activity recognition, activity pattern generation and lifestyle disease prediction. We show that it is possible to assess the possibility of lifestyle diseases from the sensor data. We also show the viability of the proposed framework.

New pharmacological strategies in rheumatic diseases.

PubMed

Schiotis, R E; Buzoianu, A D; Mureșanu, D F; Suciu, S

2016-01-01

Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania. This review presents the clinical efficacy of abatacept in several rheumatic diseases and highlights the safety profile of this biological agent. Abbreviations : ACR = American College of Rheumatology, ADR = Adverse drug reaction, APC = antigen presenting cell, ApS = psoriatic arthritis, CRP = C reactive protein, CTLA-4 = Cytotoxic T-Cell Lymphocyte Antigen-4, DAS = Disease activity score, DMARDs = Disease modifying antirheumatic drugs, EMA = European Medicine Agency, EULAR = European League Against Rheumatism, FDA = Food and Drugs Administration, HBV = Hepatitis B virus, JIA = Juvenile Idiopathic Arthritis, LDA = low disease activity (LDA), MRI = magnetic resonance imaging (MRI), MTX = methotrexate, RA = rheumatoid arthritis, RCT = randomized controlled trial, SS = Sjogren's syndrome, TCR = T cell receptor.

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.

Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical prognosis in inflammatory bowel disease.

PubMed

Tran, Diana Hoang-Ngoc; Wang, Jiani; Ha, Christina; Ho, Wendy; Mattai, S Anjani; Oikonomopoulos, Angelos; Weiss, Guy; Lacey, Precious; Cheng, Michelle; Shieh, Christine; Mussatto, Caroline C; Ho, Samantha; Hommes, Daniel; Koon, Hon Wai

2017-05-12

Cathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients. Serum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development. Serum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6-18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients. Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

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

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

PubMed

Sveaas, Silje Halvorsen; Berg, Inger Jorid; Provan, Sella Aarrestad; Semb, Anne Grete; Hagen, Kåre Birger; Vøllestad, Nina; Fongen, Camilla; Olsen, Inge C; Michelsen, Annika; Ueland, Thor; Aukrust, Pål; Kvien, Tore K; Dagfinrud, Hanne

2014-01-01

Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA. In a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals. Twenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of -0.7 (95%CI: -1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: -2.0 (-3.6, -0.4), BASFI: -1.4 (-2.6, -0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): -5.3 (-11.0, -0.5), and for PVW (m/s): -0.3 (-0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): -1.8 (-3.0, -0.6). No adverse events occurred. High intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial. ClinicalTrials.gov NCT01436942.

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

Suicidal ideation among patients with Behçet's syndrome.

PubMed

Saygin, Caner; Uzunaslan, Didem; Hatemi, Gulen; Hamuryudan, Vedat

2015-01-01

To evaluate the frequency of suicidal ideation among Behçet's syndrome (BS) patients compared to healthy and diseased controls and to delineate possible factors predicting an increase in suicidal ideation. We included consecutive BS patients attending our outpatient clinic, patients with ankylosing spondylitis (AS) and healthy hospital staff as controls. Suicidal ideation was assessed by a standard questionnaire. Linear regression was used to identify the factors associated with suicidal ideation, such as demographic and clinical features, drugs, disease activity assessed using the Behçet's disease current activity form (BDCAF) for BS patients and BASDAI for AS patients, Behçet's disease quality of life (BDQoL) and Beck depression inventory (BDI) score. We surveyed 303 BS patients, 52 AS patients and 106 healthy controls. Suicidal thoughts, as reflected by a positive response to the first three items of the questionnaire, were higher among BS patients with major organ involvement (42%) than those with mucocutaneous involvement (35%) and the control groups. There were significantly more BS patients with active major organ involvement who had thought to terminate their lives without plans within the last year (25.5%) compared to those with active mucocutaneous involvement (8.7%) and active AS patients (10%) (p=0.012). Patient-reported joint pain (β=-0.155, p=0.046), BDQoL (β=0.176, p=0.032), and BDI (β=0.017, p<0.0001) scores, suicidal thoughts before the onset of BS (β=-0.124, p=0.043), neurologic involvement (β=0.119, p=0.047) and past prednisone use (β=0.212, p=0.005) were independent predictors of suicidal thoughts. BS patients with major organ involvement have increased thoughts of suicide during the active stages of their disease. A number of risk factors could help physicians to identify patients with increased suicidal thoughts.

Ultrasound discloses entheseal involvement in inactive and low active inflammatory bowel disease without clinical signs and symptoms of spondyloarthropathy.

PubMed

Bandinelli, Francesca; Milla, Monica; Genise, Stefania; Giovannini, Leonardo; Bagnoli, Siro; Candelieri, Antonio; Collaku, Ledio; Biagini, Silvia; Cerinic, Marco Matucci

2011-07-01

To investigate the presence of lower limb entheseal abnormalities in IBD patients without clinical signs and symptoms of SpA and their correlation with IBD clinical variables. A total of 81 IBD patients [55 Crohn's disease (CD) and 26 ulcerative colitis (UC), 43 females and 38 males, mean age 41.3 (12.4) years, BMI 24 (2)] with low active (12) and inactive (67) disease were consecutively studied with US (LOGIQ5 General Electric 10-MHz linear array transducer) of lower limb entheses and compared with 40 healthy controls matched for sex, age and BMI. Quadriceps, patellar, Achilleon and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. The intra- and inter-reader agreements for US were estimated in all images detected in patients and controls. Of the 81 patients, 71 (92.6%) presented almost one tendon alteration with mean GUESS 5.1 (3.5): 81.5% thickness (higher than controls P < 0.05), 67.9% enthesophytosis, 27.1% bursitis and 16.1% erosions. PD was positive in 13/81 (16%) patients. In controls, US showed only enthesophytes (5%) and no PD. GUESS and PD were independent of duration, activity or type (CD/UC) of IBD. The intra- and inter-reader agreements were high (>0.9 intra-class correlation variability). US entheseal abnormalities are present in IBD patients without clinical signs and symptoms of SpA. US enthesopathy is independent of activity, duration and type of gut disease.

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.

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

PubMed

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

2006-05-01

Quality of life (QoL) and life satisfaction (LS) are important outcome factors in chronic inflammatory conditions such as Behçet's disease (BD). The aim of this study was to investigate QoL and LS in patients with BD and determine the relationship with disease activity. Forty-one patients with BD and 40 control subjects were involved in the study. Demographic properties were obtained. Disease activity was assessed by Turkish version of BD Current Activity Form (BDCAF) in BD patients. QoL and psychological well-being were assessed by Nottingham Health Profile (NHP) and Life Satisfaction Index (LSI), respectively, in both patients and control groups. The related disease activity measures of QoL and LS were determined. Twenty-two male and 19 female BD patients with a mean age of 33.3+/-9.3 years and 20 male and 20 female control subjects with a mean age of 33.3+/-4.1 years were involved. According to BDCAF, no patient had central nervous system involvement. Thirty-four patients had headache, 33 patients had fatigue, 30 patients had articular involvement, 29 had mucocutaneous lesions, 27 had gastrointestinal involvement, 21 patients had ocular involvement, and 7 patients had vascular involvement. The scores of all dimensions of NHP were significantly higher and the mean score of LSI was significantly lower in BD patients than in control subjects (p<0.001). Correlation analysis indicated that the scores of fatigue, joint involvement, and oral ulcers were the most related factors for physical domains of NHP, whereas joint involvement and genital ulcers were the most related activity measures for psychosocial subscales of NHP. LS was found to be most related with the scores of patient's and physician's impression of disease activity and joint involvement. In conclusion, patients with BD have impaired QoL and disturbed psychological well-being. Current management strategies focusing on fatigue, arthralgia, mucocutaneous lesions, and efforts to measure psychosocial aspects and symptoms of the patients by their point of view will help to improve QoL and raise the LS in patients suffering from BD.

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

PubMed

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; Dávalos, Ingrid P

2017-11-01

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). 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. 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. 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.

Development and Validation of an Inflammatory Bowel Diseases Monitoring Index for Use With Mobile Health Technologies.

PubMed

Van Deen, Welmoed K; van der Meulen-de Jong, Andrea E; Parekh, Nimisha K; Kane, Ellen; Zand, Aria; DiNicola, Courtney A; Hall, Laurin; Inserra, Elizabeth K; Choi, Jennifer M; Ha, Christina Y; Esrailian, Eric; van Oijen, Martijn G H; Hommes, Daniel W

2016-12-01

Mobile health technologies are advancing rapidly as smartphone use increases. Patients with inflammatory bowel disease (IBD) might be managed remotely through smartphone applications, but no tools are yet available. We tested the ability of an IBD monitoring tool, which can be used with mobile technologies, to assess disease activity in patients with Crohn's disease (CD) or ulcerative colitis (UC). We performed a prospective observational study to develop and validate a mobile health index for CD and UC, which monitors IBD disease activity using patient-reported outcomes. We collected data from disease-specific questionnaires completed by 110 patients with CD and 109 with UC who visited the University of California, Los Angeles, Center for IBD from May 2013 through January 2014. Patient-reported outcomes were compared with clinical disease activity index scores to identify factors associated with disease activity. Index scores were validated in 301 patients with CD and 265 with UC who visited 3 tertiary IBD referral centers (in California or Europe) from April 2014 through March 2015. We assessed activity of CD based on liquid stool frequency, abdominal pain, patient well-being, and patient-assessed disease control, and activity of UC based on stool frequency, abdominal pain, rectal bleeding, and patient-assessed disease control. The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.90 in patients with CD and 0.91 in patients with UC. They identified endoscopic activity with area under the receiver operating characteristic values of 0.63 in patients with CD and 0.82 in patients with UC. Both scoring systems responded to changes in disease activity (P < .003). The intraclass correlation coefficient for test-retest reliability was 0.94 for CD and for UC. We developed and validated a scoring system to monitor disease activity in patients with CD and UC that can be used with mobile technologies. The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.9 or higher in patients with CD or UC, and endoscopic activity in patients with UC but not CD. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Indoleamine 2,3-dioxygenase and regulatory t cells in intestinal mucosa in children with inflammatory bowel disease.

PubMed

Sznurkowska, K; Żawrocki, A; Sznurkowski, J; Iżycka-Świeszewska, E; Landowski, P; Szlagatys-Sidorkiewicz, A; Plata-Nazar, K; Kamińska, B

2017-01-01

Impaired immune regulation has been suggested as an underlying mechanism of inflammatory bowel disease. Indoleamine 2,3-dioxygenase (IDO) and regulatory T cells expressing FOXP3 are crucial elements of immune regulation. Conversion of FOXP3- lymphocytes to Tregs is one of the functions of IDO. The aim of this study was to evaluate the number of cells expressing FOXP3 and IDO in the lamina propria of intestinal mucosa and to evaluate correlations between these parameters and disease activity. Sixty-six children newly diagnosed with inflammatory bowel disease (41 patients with ulcerative colitis and 25 patients with Crohn’s disease) were included in the study. Clinical activity of the disease was assessed by the Pediatric Ulcerative Colitis Activity Index and the Pediatric Crohn’s Disease Activity Index. Histopathological activity was scored according to the system described by Geboes. The infiltration of FOXP3+ and IDO+ cells was evaluated by immunohistochemistry. Sixteen patients with a diagnosis of irritable bowel syndrome (IBS) served as a control group. Lamina propria demonstrated a significantly higher infiltration of FOXP3+ and IDO+ cells in inflammatory bowel disease compared to the control group (p=0.001, p=0.004, respectively). The number of IDO+ and FOXP3+ cells correlated with clinical and histopathologic activity of Crohn’s disease. A positive correlation between the number of IDO+ and FOXP3+ cells was found in both types of inflammatory disease but not in patients with IBS. We conclude that indoleamine dioxygenase and FOXP3+ cells are upregulated in the intestinal mucosa of children with inflammatory bowel disease. IDO mediated conversion of FOXP3 -T cells to Tregs predominantly occurs in inflammation.

Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

PubMed

Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

2016-10-01

Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Increased brain lysosomal pepstatin-insensitive proteinase activity in patients with neurodegenerative diseases.

PubMed

Junaid, M A; Pullarkat, R K

1999-04-02

A recent study has shown mutations in CLN2 gene, that encodes a novel lysosomal pepstatin-insensitive proteinase (LPIP), in the pathophysiology of late-infantile neuronal ceroid lipofuscinosis (LINCL). We have measured the LPIP activities in brains from various forms of human neuronal ceroid lipofuscinoses (NCL), canine ceroid lipofuscinosis and other neurodegenerative disorders with a highly sensitive assay using a tetrapeptide Gly-Phe-Phe-Leu-amino-trifluoromethyl coumarin (AFC) as substrate. Brain LPIP has a pH optimum of 3.5 and an apparent km of 100 microM for the crude enzyme. The enzyme activity is totally absent in LINCL patients. Pronounced increase in the LPIP activity was seen in patients suffering from infantile (INCL), juvenile (JNCL) and adult (ANCL) forms of neuronal ceroid lipofuscinoses. LPIP activity was also found to be increased about two-fold in Alzheimer's disease when compared with normal or age-matched controls, while in globoidal-cell leukodystrophy (Krabbe's disease) it was similar to the normal controls. Although mannose-6-phosphorylated LPIP is increased 13-fold in brains of patients with JNCL, this form of LPIP did not have any enzyme activity. The mechanism by which LPIP activities are increased in a wide range of neurodegenerative diseases is unknown, although neuronal loss, followed by gliosis are common characteristics of these diseases.

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

Daily Physical Activity Patterns During the Early Stage of Alzheimer's Disease.

PubMed

Varma, Vijay R; Watts, Amber

2017-01-01

Alzheimer's disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when components of physical function and mobility may be preserved. Our study explored differences in daily physical activity profiles, independent of the effects of non-cognitive factors including physical function and age, among individuals with mild AD compared to controls. Patients with mild AD and controls (n = 92) recruited from the University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility. We found that mild AD was associated with less moderate-intensity physical activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity complexity (p < 0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates. These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function.

Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study

PubMed Central

Trejo-Vazquez, Fabiola; Garza-Veloz, Idalia; Villela-Ramirez, Gabriela Alejandra; Ortiz-Castro, Yolanda; Mauricio-Saucedo, Panfilo; Cardenas-Vargas, Edith; Diaz-Baez, Mariana; Cid-Baez, Miguel A.; Castañeda-Miranda, Rodrigo; Ortiz-Rodriguez, Jose Manuel; Solis-Sanchez, Luis Octavio; Martinez-Fierro, Margarita L.

2018-01-01

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10−4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04–53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52–22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity. PMID:29545852

Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR).

PubMed Central

Niessner, M; Volk, B A

1995-01-01

Cytokines serve a central function as key factors in the regulation of the intestinal immune response and mediation of tissue damage in inflammatory bowel disease (IBD). Abnormalities in the expression of immunoregulatory cytokines such as IL-2, IL-4, IL-10 and interferon-gamma (IFN-gamma) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. Therefore, cytokine mRNA concentrations were determined in the mucosa of patients with IBD at sites of active (n = 13) and inactive (n = 12) ulcerative colitis (UC), active (n = 11) and inactive (n = 11) Crohn's disease (CD) and in control patients (n = 14) using quantitative RT-PCR. IL-10 mRNA concentrations were significantly increased in patients with both active UC (P < 0.001) and active CD (P < 0.005) compared with control patients. IFN-gamma mRNA concentrations were also significantly increased both in patients with active UC (P < 0.02) and active CD (P < 0.05) compared with control patients, whereas IL-2 mRNA levels were significantly (P < 0.02) increased only in active CD. IL-4 mRNA expression in the intestinal mucosa was frequently below the detection limit. Our results demonstrate that chronic intestinal inflammation in patients with CD is characterized by an increase of Th1-like cytokines. Furthermore, the increased IL-10 mRNA expression at sites of active IBD suggests that IL-10 is an important regulatory component involved in the control of the inflammatory response in inflammatory bowel disease. Images Fig. 1 Fig. 4 PMID:7664489

The effect of Ramadan fasting on quiescent systemic lupus erythematosus (SLE) patients' disease activity, health quality of life and lipid profile: a pilot study.

PubMed

Goharifar, Hamid; Faezi, Seyedeh Tahereh; Paragomi, Pedram; Montazeri, Ali; Banihashemi, Arash Tehrani; Akhlaghkhah, Maryam; Abdollahi, Bahar Sadeghi; Kamazani, Zahra; Akbarian, Mahmood

2015-08-01

SLE is a common autoimmune disease with considerable morbidity. Ramadan fasting is a religious custom Muslims regularly practice. We aimed to evaluate the effect of Ramadan fasting on SLE patients' disease activity, health quality of life and lipid profile. We conducted this case control study as a pilot study in 40 quiescent SLE patients, 21 cases who decided to fast and 19 controls who decided not to have Ramadan fasting between August and November 2009 in lupus unit of Rheumatology Research Center in Tehran University of Medical Sciences, Iran. They were assessed for SLE Disease Activity Index, lipid profile and quality of life with Short-Form 36 (SF-36) Health Survey, 1 day before Ramadan, the day after and 3 months after Ramadan fasting. After 24.1 ± 5.4 (mean ± SD) days of fasting, anti-ds DNA increased for 0.34 ± 0.41 mmol/dL in cases versus 0.07 ± 0.31 in controls (P = 0.026). Likewise C3 increased more dramatically in cases (16.8 ± 17.5 vs. 2.3 ± 13.2 mg/dL, P = 0.006). Three months after fasting, anti-ds DNA was still increased 0.28 ± 0.46 mmol/dL in cases while a 0.02 ± 0.43 mmol/dL drop in controls was detected (P = 0.04). On the contrary, C3 returned to baseline. These changes were not accompanied with significant changes in disease activity and health quality of life. Ramadan fasting had no effect on lipid profile except for delayed total cholesterol decrease in cases in comparison with controls (16.4 ± 29.4 decrease vs. 4.6 ± 23.9 mg/dL decrease, P = 0.018). Ramadan fasting probably has no detrimental effect on SLE patients' disease activity and their quality of life in the quiescent phase of disease.

Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease.

PubMed

Goel, N; Ulrich, D T; St Clair, E W; Fleming, J A; Lynch, D H; Seldin, M F

1995-12-01

To determine whether elevated soluble Fas/APO-1 (sFas/APO-1) levels are associated with either autoimmune disease or evidence of flares in autoimmune disease. Thirty-seven serum samples were retrospectively obtained from normal controls and patients with laboratory evidence of autoimmune disease activity. These samples were assayed for sFas/APO-1 levels by an enzyme-linked immunosorbent assay, and hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. Soluble Fas/APO-1 levels did not correlate with clinical diagnoses or laboratory abnormalities. The mean and range of sFas/APO-1 levels were similar in systemic lupus erythematosus patients (including those with active disease), patients with other autoimmune diseases, and normal controls. These data strongly suggest that measurement of sFas/APO-1 levels is unlikely to hold clinical value or play a role in the pathogenesis of autoimmune disease.

Personality profile and affective state of patients with inflammatory bowel disease.

PubMed Central

Robertson, D A; Ray, J; Diamond, I; Edwards, J G

1989-01-01

The Eysenck Personality Inventory and Hospital Anxiety and Depression scale were administered to 80 patients undergoing medical treatment for long standing inflammatory bowel disease: 22 patients were studied before the diagnosis was established and 40 patients with diabetes mellitus served as controls. High neuroticism and introversion scores were more prevalent in the patients with inflammatory bowel disease than controls (p less than 0.05) and these characteristics were as prominent in patients before diagnosis as in established cases. Introversion scores increased with the duration of disease (r = 0.51). Depression was uncommon, occurring only in patients with active chronic disease. Patients believed there was a close link between personality, stress and disease activity. Fifty six of the patients recognised factors that initiated the disease and in 42 this was thought to be a stressful life event or a 'nervous personality'. PMID:2731754

Breathlessness during daily activity: The psychometric properties of the London Chest Activity of Daily Living Scale in patients with advanced disease and refractory breathlessness.

PubMed

Reilly, Charles C; Bausewein, Claudia; Garrod, Rachel; Jolley, Caroline J; Moxham, John; Higginson, Irene J

2017-10-01

The London Chest Activities of Daily Living Scale measures the impact of breathlessness on both activity and social functioning. However, the London Chest Activities of Daily Living Scale is not routinely used in patients with advanced disease. To assess the psychometric properties of the London Chest Activities of Daily Living Scale in patients with refractory breathlessness due to advanced disease. A cross-sectional secondary analysis of data from a randomised controlled parallel-group, pragmatic, single-blind fast-track trial (randomised controlled trial) investigating the effectiveness of an integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness, known as the Breathlessness Support Service (NCT01165034). All patients completed the following questionnaires: the London Chest Activities of Daily Living Scale, Chronic Respiratory Questionnaire, the Palliative care Outcome Scale, Palliative care Outcome Scale-symptoms, the Hospital Anxiety and Depression Scale and breathlessness measured on a numerical rating scale. Data quality, scaling assumptions, acceptability, internal consistency and construct validity of the London Chest Activities of Daily Living Scale were determined using standard psychometric approaches. Breathless patients with advanced malignant and non-malignant disease. A total of 88 patients were studied, primary diagnosis included; chronic obstructive pulmonary disease = 53, interstitial lung disease = 17, cancer = 18. Median (range) London Chest Activities of Daily Living Scale total score was 46.5 (14-67). No floor or ceiling effect was observed for the London Chest Activities of Daily Living Scale total score. Internal consistency was good, and Cronbach's alpha for the London Chest Activities of Daily Living Scale total score was 0.90. Construct validity was good with 13 out of 15 a priori hypotheses met. Psychometric analyses suggest that the London Chest Activities of Daily Living Scale is acceptable, reliable and valid in patients with advanced disease and refractory breathlessness.

Breathlessness during daily activity: The psychometric properties of the London Chest Activity of Daily Living Scale in patients with advanced disease and refractory breathlessness

PubMed Central

Reilly, Charles C; Bausewein, Claudia; Garrod, Rachel; Jolley, Caroline J; Moxham, John; Higginson, Irene J

2016-01-01

Background: The London Chest Activities of Daily Living Scale measures the impact of breathlessness on both activity and social functioning. However, the London Chest Activities of Daily Living Scale is not routinely used in patients with advanced disease. Aim: To assess the psychometric properties of the London Chest Activities of Daily Living Scale in patients with refractory breathlessness due to advanced disease. Design: A cross-sectional secondary analysis of data from a randomised controlled parallel-group, pragmatic, single-blind fast-track trial (randomised controlled trial) investigating the effectiveness of an integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness, known as the Breathlessness Support Service (NCT01165034). All patients completed the following questionnaires: the London Chest Activities of Daily Living Scale, Chronic Respiratory Questionnaire, the Palliative care Outcome Scale, Palliative care Outcome Scale–symptoms, the Hospital Anxiety and Depression Scale and breathlessness measured on a numerical rating scale. Data quality, scaling assumptions, acceptability, internal consistency and construct validity of the London Chest Activities of Daily Living Scale were determined using standard psychometric approaches. Setting/participants: Breathless patients with advanced malignant and non-malignant disease. Results: A total of 88 patients were studied, primary diagnosis included; chronic obstructive pulmonary disease = 53, interstitial lung disease = 17, cancer = 18. Median (range) London Chest Activities of Daily Living Scale total score was 46.5 (14–67). No floor or ceiling effect was observed for the London Chest Activities of Daily Living Scale total score. Internal consistency was good, and Cronbach’s alpha for the London Chest Activities of Daily Living Scale total score was 0.90. Construct validity was good with 13 out of 15 a priori hypotheses met. Conclusion: Psychometric analyses suggest that the London Chest Activities of Daily Living Scale is acceptable, reliable and valid in patients with advanced disease and refractory breathlessness. PMID:27932629

Increased resting-state brain entropy in Alzheimer's disease.

PubMed

Xue, Shao-Wei; Guo, Yonghu

2018-03-07

Entropy analysis of resting-state functional MRI (R-fMRI) is a novel approach to characterize brain temporal dynamics and facilitates the identification of abnormal brain activity caused by several disease conditions. However, Alzheimer's disease (AD)-related brain entropy mapping based on R-fMRI has not been assessed. Here, we measured the sample entropy and voxel-wise connectivity of the network degree centrality (DC) of the intrinsic brain activity acquired by R-fMRI in 26 patients with AD and 26 healthy controls. Compared with the controls, AD patients showed increased entropy in the middle temporal gyrus and the precentral gyrus and also showed decreased DC in the precuneus. Moreover, the magnitude of the negative correlation between local brain activity (entropy) and network connectivity (DC) was increased in AD patients in comparison with healthy controls. These findings provide new evidence on AD-related brain entropy alterations.

Behavioural intervention to increase physical activity among patients with coronary heart disease: protocol for a randomised controlled trial.

PubMed

Alsaleh, Eman; Blake, Holly; Windle, Richard

2012-12-01

Although physical activity has significant health benefits in the treatment of patients with coronary heart disease, patients often do not follow prescribed physical activity recommendations. Behavioural strategies have been shown to be efficacious in increasing physical activity among those patients with coronary heart disease who are attending structured cardiac rehabilitation programmes. Research has also shown that tailoring consultation according to patients' needs and sending motivational reminders are successful ways of motivating patients to be physically active. However, there is a lack of evidence for the efficacy of behavioural interventions based on individualised consultation in promoting physical activity among those patients with coronary heart disease who are not attending structured physical activity programmes. This paper outlines the study protocol for a trial which is currently underway, to examine the effect of a behavioural change intervention delivered through individualised consultation calls and motivational reminder text messages on the level of physical activity among patients with coronary heart disease. Two large hospitals in Jordan. Eligible patients aged between 18 and 70 years, who are clinically stable, are able to perform physical activity and who have access to a mobile telephone have been randomly allocated to control or intervention group. Two-group randomised controlled trial. Behavioural intervention will be compared with usual care in increasing physical activity levels among patients with coronary heart disease. The control group (n=85) will receive advice from their doctors about physical activity as they would in usual practice. The intervention group (n=71) will receive the same advice, but will also receive behavioural change intervention (goal-setting, feed-back, self-monitoring) that will be delivered over a period of six months. Intervention will be delivered through individually tailored face-to-face and telephone consultations, supported by motivational SMS text messages to encourage and remind patients to attain these goals. The participants and the researcher delivering the intervention are not blinded to group assignment. Recruitment started in February 2012 and preliminary findings are expected in November 2012. It is hypothesised that behavioural intervention delivered through tailored individualised consultation supported by motivational SMS text message reminders will help CHD patients to increase their level of PA. The study is registered as a clinical trial at ISRCTN register (ISRCTN48570595). Copyright © 2012 Elsevier Ltd. All rights reserved.

Serum prolactin in coeliac disease: a marker for disease activity

PubMed Central

Reifen, R.; Buskila, D.; Maislos, M.; Press, J.; Lerner, A.

1997-01-01

Accepted 21 April 1997
 Prolactin, a polypeptide hormone of anterior pituitary origin, has pronounced physiological effects on growth, reproduction, and osmoregulation. Increasing evidence indicates that prolactin also has an immunomodulatory influence on the immune system. The status of prolactin in patients with coeliac disease was investigated by obtaining serum samples from 48 patients with active and non-active coeliac disease. These were compared with samples from 20 children with familial Mediterranean fever and 65 normal controls. Serum prolactin in patients with active coeliac disease was significantly higher than in the other groups studied and reference values. Serum prolactin correlated well with the degree of mucosal atrophy and with the serum concentration of antiendomysial antibodies. Prolactin may play a part in immune modulation in the intestinal damage of coeliac disease and serve as a potential marker for disease activity.

 PMID:9301358

The impact of high intensity interval training on disease activity and patient disease perception in patients with psoriatic arthritis: A randomized controlled trial.

PubMed

Thomsen, Ruth S; Nilsen, Tom I L; Haugeberg, Glenn; Bye, Anja; Kavanaugh, Arthur; Hoff, Mari

2018-06-08

The aim of this study was to evaluate the impact of high intensity interval training (HIIT) on disease activity and patient disease perception in patients with psoriatic arthritis (PsA), and evaluating if a potential effect could be sustained for a longer period. We randomly assigned 67 PsA patients (43 women and 24 men) to an intervention group performing HIIT for 11 weeks or a control group who were instructed to not change their physical exercise habits. Outcomes were assessed at three and nine months with the patient global assessment (PGA), fatigue, and pain measured on a 100 mm visual analog scale and the composite disease activity score of 44 joints (DAS44) was calculated. We used linear mixed models to calculate mean difference with 95% confidence interval (CI) between the groups according to the intention-to-treat principle. At three months there was no clear difference in PGA (-0.49; 95% CI -10.91 to 9.94), DAS44 (-0.08; 95% CI -0.36 to 0.20) or pain intensity (5.45; 95% CI -4.36 to 15.26) between the groups. However, the HIIT group reported less fatigue (-12.83; 95% CI -25.88 to 0.23) than the control group. There was no evidence of long-term effects of HIIT on outcomes measured at nine months. HIIT showed no clear effects on disease activity markers in patients with PsA, but the exercise group reported meaningfully less fatigue after the intervention period. This study suggests that PsA patients tolerate HIIT without deterioration of disease activity and with improvement in fatigue. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Physical Activity and the Risk of Gallstone Disease: A Systematic Review and Meta-analysis.

PubMed

Zhang, Yan-Peng; Zhao, Ya-Lei; Sun, Yu-Ling; Zhu, Rong-Tao; Wang, Wei-Jie; Li, Jian

2017-10-01

The role of physical activity in preventing gallstone disease independent of its effect on the body weight has not been well established. We performed a systematic review and meta-analysis of cohort and case-control studies to analyze this potential association. We searched PubMed and EMBASE to identify all published studies in English through April 2016. We pooled the relative risks (RRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) from individual studies using a random-effects model to investigate associations between physical activity and the risk of gallstone disease. A total of 16 studies comprising 19 independent reports of approximately 260,000 participants met the inclusion criteria, including 6 case-control studies and 13 cohort studies. In a pooled analysis of cohort studies, physical activity (in a comparison of the highest-level and the lowest-level groups) was associated with a reduced risk of gallstone disease (RR=0.85; 95% CI, 0.78-0.92; I=79.5%). For men, the RR was 0.76 (95% CI, 0.60-0.97), and for women, the RR was similar (RR=0.77; 95% CI, 0.66-0.91). In a dose-response analysis, the RR of gallstone disease was 0.87 (95% CI, 0.83-0.92; I=1.0%) per 20 metabolic equivalent-hours of recreational physical per week. In comparison, case-control studies yielded a stronger significant risk reduction for gallstone disease (OR=0.64; 95% CI, 0.46-0.90; I=76.6%). This study suggests an inverse association between physical activity and gallstone disease in both men and women; however, these findings should be interpreted cautiously because of study heterogeneity.

A Randomized Controlled Trial of an Activity Specific Exercise Program for Individuals With Alzheimer Disease in Long-term Care Settings

PubMed Central

Roach, Kathryn E.; Tappen, Ruth M.; Kirk-Sanchez, Neva; Williams, Christine L.; Loewenstein, David

2011-01-01

Objective To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Design Randomized, controlled, single-blinded clinical trial. Setting Residents of 7 long-term care facilities. Participants Eighty-two long-term care residents with mild to severe AD. Intervention An activity specific exercise program was compared to a walking program and to an attention control. Measurements Ability to perform bed mobility and transfers were assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Results Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined. PMID:21937893

Sexual functioning of people with rheumatoid arthritis: a multicenter study.

PubMed

van Berlo, Willy T M; van de Wiel, Harry B M; Taal, Erik; Rasker, Johannes J; Weijmar Schultz, Willibrord C M; van Rijswijk, Martin H

2007-01-01

The objective of this study is to compare men and women with rheumatoid arthritis (RA) to controls regarding sexual motivation, activity, satisfaction, and specific sexual problems, and to determine the correlation of physical aspects of the disease with sexual functioning. Questionnaire for screening sexual dysfunctions (QSD), self-constructed questionnaire on experienced distress with joints during sexual activities, arthritis impact measurements scales 2 (AIMS2), and the modified disease activity score 28 (DAS 28) were the methods used. RA patients were recruited from a registration base in three Dutch hospitals. Controls were age and sex matched healthy volunteers. A completed questionnaire was sent back by 271 patients (response 23%). Forty-seven men and 93 women were clinically examined to obtain the DAS 28. Male patients felt less sexual desire, and female patients masturbated and fantasized less than controls. Differences in satisfaction were not found. Male and female patients did not experience more sexual problems than controls. Among the women, correlations were predominantly found between age and sexual motivation and activities, among the men between physical health and sexual problems. Up to 41% of the men (4-41 depending on the joints), and up to 51% of the women (10-51 depending on the joints) have troubles with several joints during sexual activities. Medications influencing ejaculation in men correlated with distress with orgasm. Conclusions are that patients are less sexually active than controls and a considerable number of both male and female patients have trouble with their joints during sexual activities. However, patients do not differ from controls regarding sexual satisfaction. Physiological changes due to RA are apparently independent from those on psychological level. It is argued that sexual satisfaction also depends on personal and social factors. In men, physical health and disease activity are more related with sexual problems than in women.

A prospective functional MRI study for executive function in patients with systemic lupus erythematosus without neuropsychiatric symptoms.

PubMed

Mak, Anselm; Ren, Tao; Fu, Erin Hui-yun; Cheak, Alicia Ai-cia; Ho, Roger Chun-man

2012-06-01

To study the functional brain activation signals before and after sufficient disease control in patients with systemic lupus erythematosus (SLE) without clinical neuropsychiatric symptoms. Blood-oxygen-level-dependent signals during event-related functional magnetic resonance imaging brain were recorded, while 14 new-onset SLE patients and 14 demographically and intelligence quotient matched healthy controls performed the computer-based Wisconsin card sorting test for assessing executive function, which probes strategic planning and goal-directed task performance during feedback evaluation (FE) and response selection (RS), respectively. Composite beta maps were constructed by a general linear model to identify regions of cortical activation. Blood-oxygen-level-dependent functional magnetic resonance imaging signals were compared between (1) new-onset SLE patients and healthy controls and (2) SLE patients before and after sufficient control of their disease activity. During RS, SLE patients demonstrated significantly higher activation than healthy controls in both caudate bodies and Brodmann area (BA) 9 to enhance event anticipation, attention, and working memory, respectively, to compensate for the reduced activation during FE in BA6, 13, 24, and 32, which serve complex motor planning and decision-making, sensory integration, error detection, and conflict processing, respectively. Despite significant reduction of SLE activity, BA32 was activated during RS to compensate for reduced activation during FE in BA6, 9, 37, and 23/32, which serve motor planning, response inhibition and attention, color processing and word recognition, error detection, and conflict evaluation, respectively. Even without clinically overt neuropsychiatric symptoms, SLE patients recruited additional pathways to execute goal-directed tasks to compensate for their reduced strategic planning skill despite clinically sufficient disease control. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of the international organisation for animal health (Office International des Epizooties: OIE) in the control of foot and mouth disease.

PubMed

Vallat, B

2002-10-01

The author describes activities conducted by the International Organisation for Animal Health (OIE: Office International des Epizooties) to control foot and mouth disease (FMD) world-wide. These activities fall within the framework of the principal missions of the OIE. The first of these missions is the collection and dissemination of epidemiological information and of scientific knowledge on animal diseases, the socio-economic or disease implications of which can be particularly serious. The implementation of the measures required to control the disease and to protect countries threatened by FMD depends on the quality and rapidity of the transmission of this information. The co-ordination of studies, research and control programmes against FMD is equally important for the OIE. This work is based, in particular, on work conducted by the OlE foot and mouth disease and other epizootics Commission. OIE Member Countries not only have access to the most recent data on the diagnosis, surveillance and control of FMD but also have recourse to the official recognition procedure for disease-free status provided by this Commission. Finally, through the standardisation of health recommendations, diagnostic tests, manufacture protocols and the control of biological products, made available by the OIE International Animal Health Code Commission in regard to the former and by the OIE Standards Commission in regard to the latter, the OIE provides the reference for international trade in animals and animal products, and is recognised in this role by the World Trade Organization.

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

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles.

PubMed

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

2015-12-01

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. 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. 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 subjects 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. This is the first time that multiple cytokines and chemokines have been examined simultaneously in LS. In general, a TH1 (IFN-γ) and TH17 (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. Copyright © 2015 Elsevier Inc. All rights reserved.

Integration and disease control: notes from the Prince Leopold Institute of Tropical Medicine Colloquium 2002.

PubMed

Mahendradhata, Yodi; Moerman, Filip

2004-06-01

The discussion on the desirability or not to integrate disease control activities with general health services is a longstanding one. The recent creations of global health initiatives for poverty-related disease control have refueled the debate. The Prince Leopold Institute of Tropical Medicine (ITM) convened a colloquium in Antwerp to clarify concepts involved in integrated disease control and contribute to the creation of a common scientific language and a better understanding of the issues at stake. We present an overview of highlights from the colloquium sessions. Some of the contributions reported here are presented in more detail elsewhere in this special issue.

Inflammatory markers in relation to body composition, physical activity and assessment of nutritional status of the adolescents.

PubMed

Neves Miranda, Valter Paulo; Gouveia Peluzio, Maria do Carmo; Rodrigues de Faria, Eliana; Castro Franceschini, Sylvia do Carmo; Eloiza Priore, Silvia

2015-05-01

The evaluation of inflammatory markers during adolescence can monitor different stages and manifestation of chronic diseases in adulthood. The control of the subclinical inflammation process through changes in lifestyle, especially in the practice of physical activity and dietary education can mitigate the effects of risk factors that trigger the process of atherosclerosis. To do a critical review regarding inflammatory markers as a risk factor of cardiovascular disease in relation to body composition, physical activity and assessment of nutritional status of adolescents. A literature review was performed in the following electronic databases: PUBMED, SCIELO and CONCHRANE COLLECTION. The following associated terms were used "inflammation AND cardiovascular diseases AND nutritional status OR body composition OR physical activity". There were topics created for the discussion of subjects: obesity and risk factors for cardiovascular disease during adolescence; expression of inflammatory markers in adolescence; development of cardiovascular disease with inflammatory markers, and finally, inflammatory markers, physical activity and nutritional evaluation. It was observed that the inflammatory markers may manifest in adolescence and be related to risk factors for cardiovascular diseases. Physical activity and nutritional evaluation featured as non-pharmacological measures to control the incidence of inflammatory markers and cardiovascular risk factor. Intervention studies may clarify how the adoption of a more proper lifestyle can influence the inflammatory process. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

PubMed

Lomer, Miranda C E; Grainger, Stephen L; Ede, Roland; Catterall, Adrian P; Greenfield, Simon M; Cowan, Russell E; Vicary, F Robin; Jenkins, Anthony P; Fidler, Helen; Harvey, Rory S; Ellis, Richard; McNair, Alistair; Ainley, Colin C; Thompson, Richard P H; Powell, Jonathan J

2005-03-01

Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.

Assessing dietary and lifestyle risk factors and their associations with disease comorbidities among patients with schizophrenia: A case-control study from Bahrain.

PubMed

Jahrami, Haitham Ali; Faris, Mo'ez Al-Islam Ezzat; Saif, Zahraa Qassim; Hammad, Laila Habib

2017-08-01

Acquired dietary habits and lifestyle behaviors of patients with schizophrenia may affect their life expectancy, disease complications and prognosis. The objectives of the current study were to assess the dietary habits and other lifestyle behaviors for Bahraini patients with schizophrenia, and to determine their associations with different medical comorbidities. A case-control study was conducted during the period of March to December 2016. A sample of 120 cases were recruited from the Psychiatric Hospital, Bahrain and age-sex-matched with 120 controls. Controls were recruited from primary health centres, and were free from serious mental illness. Dietary habits and lifestyle behaviors including smoking, alcohol intake and physical activity were assessed using a questionnaire. All medical records were reviewed retrospectively. Logistic regression analysis was used to identify dietary and lifestyle risk factors that are associated with one or more disease comorbidities. Cases had higher prevalence of smoking and alcohol intake, excessive dietary intake, and decreased physical activity (all P<0.05) compared with controls. Cases appeared to be at higher risk for developing chronic medical conditions such as obesity, type 2 diabetes, hypertension, cardiovascular disease, and musculoskeletal disorders. Cases were three times more likely to have up to three or more medical comorbidities compared with controls. Excessive dietary intake and decreased physical activity were identified as the main risk factors. Excessive caloric intake and decreased physical activity represent the main dietary and lifestyle risk factors associated with comorbidities among patients with schizophrenia in Bahrain. Copyright © 2017 Elsevier B.V. All rights reserved.

ELECTROMYOGRAPHIC ACTIVITY OF STERNOCLEIDOMASTOID AND MASTICATORY MUSCLES IN PATIENTS WITH VESTIBULAR LESIONS

PubMed Central

Tartaglia, Gianluca M.; Barozzi, Stefania; Marin, Federico; Cesarani, Antonio; Ferrario, Virgilio F.

2008-01-01

This study evaluated the electromyographic characteristics of masticatory and neck muscles in subjects with vestibular lesions. Surface electromyography of the masseter, temporalis and sternocleidomastoid muscles was performed in 19 patients with Ménière's disease, 12 patients with an acute peripheral vestibular lesion, and 19 control subjects matched for sex and age. During maximum voluntary clenching, patients with peripheral vestibular lesions had the highest co-contraction of the sternocleidomastoid muscle (analysis of covariance, p=0.02), the control subjects had the smallest values, and the patients with Ménière's disease had intermediate values. The control subjects had larger standardized muscle activities than the other patient groups (p=0.001). In conclusion, during maximum voluntary tooth clenching, patients with vestibular alterations have both more active neck muscles, and less active masticatory muscles than normal controls. Results underline the importance of a more inclusive craniocervical assessment of patients with vestibular lesions. PMID:19082397

Optimal treatment interruptions control of TB transmission model

NASA Astrophysics Data System (ADS)

Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

2018-03-01

A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

Comparison between exercise performance in asthmatic children and healthy controls--Physical Activity Questionnaire application.

PubMed

Santos-Silva, Rita; Melo, Cláudia; Gonçalves, Daniel; Coelho, Janine; Carvalho, Fernanda

2014-01-01

The PAQ questionnaire (Physical Activity Questionnaire - Kowalski, Crocker, Donen) is a self-administered 7-day recall validated questionnaire that measures physical activity levels in young people. A final activity score is obtained (1 indicates low and 5 indicates high physical activity level). Our aim was to determine whether there was any difference between the level of physical activity of children with controlled allergic disease and healthy children. We used the PAQ questionnaire with a group of asthmatic children attending hospital outpatient clinic and a group of healthy children matched for age. 155 children with allergic disease (median age of 11 years; 63% males) and 158 healthy controls (median age of 10 years; 46% males) answered the questionnaire. There were no differences in the overall level of physical activity, estimated by PAQ score, between allergic and healthy children (2,40±0,7 vs 2,48±0,62; p=0,32). Performance in physical education classes and after school sports activity was found to be different between the study groups; healthy children were more active (p=0,011) and did more sports between 6 and 10 pm (p=0,036). No other statistically significant differences were found between the study groups. Despite the fact that a majority of the parents of allergic children stated that their child's disease was a barrier to physical activity, in our study there seems to be no difference between the level of physical activity of controlled asthmatic children and their healthy peers. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

The Importance of Intestinal Eotaxin-1 in Inflammatory Bowel Disease: New Insights and Possible Therapeutic Implications.

PubMed

Adar, Tomer; Shteingart, Shimon; Ben-Ya'acov, Ami; Shitrit, Ariella Bar-Gill; Livovsky, Dan M; Shmorak, Shimrit; Mahamid, Mahmud; Melamud, Bernardo; Vernea, Fiona; Goldin, Eran

2016-07-01

Involvement of eotaxin-1 in inflammatory bowel disease has been previously suggested and increased levels of eotaxin-1 have been described in both ulcerative colitis and in Crohn's disease. The association between serum levels of eotaxin-1 and that within the colonic mucosa has not been well defined, as is the potential therapeutic value of targeting eotaxin-1. To characterize serum and intestinal wall eotaxin-1 levels in various inflammatory bowel disease patients and to explore the effect of targeting eotaxin-1 by specific antibodies in dextran sodium sulfate-induced colitis model. Eotaxin-1 levels were measured in colonic biopsies and in the sera of 60 ulcerative colitis patients, Crohn's disease patients and healthy controls. We also followed in experimental colitis the effect of targeting eotaxin-1 by a monoclonal antibody. Colon eotaxin-1 levels were significantly increased in active but not in quiescent ulcerative colitis and Crohn's disease patients compared to healthy controls. Levels of eotaxin-1 in the colon were correlated with eosinophilia only in tissues from active Crohn's disease patients. Our results did not show any statistically significant change in serum eotaxin-1 levels among ulcerative colitis, Crohn's disease and healthy controls. Moreover, we demonstrate that in dextran sodium sulfate-induced colitis, targeting of eotaxin-1 with 2 injections of anti eotaxin-1 monoclonal antibody ameliorates disease activity along with decreasing colon weight and improving histologic inflammation. Eotaxin-1 is increasingly recognized as a major mediator of intestinal inflammation. Our preliminary human and animal results further emphasize the value of targeting eotaxin-1 in inflammatory bowel disease.

Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators

PubMed Central

Uversky, Vladimir N.

2014-01-01

Biologically active proteins without stable tertiary structure are common in all known proteomes. Functions of these intrinsically disordered proteins (IDPs) are typically related to regulation, signaling, and control. Cellular levels of these important regulators are tightly regulated by a variety mechanisms ranging from firmly controlled expression to precisely targeted degradation. Functions of IDPs are controlled by binding to specific partners, alternative splicing, and posttranslational modifications among other means. In the norm, right amounts of precisely activated IDPs have to be present in right time at right places. Wrecked regulation brings havoc to the ordered world of disordered proteins, leading to protein misfolding, misidentification, and missignaling that give rise to numerous human diseases, such as cancer, cardiovascular disease, neurodegenerative diseases, and diabetes. Among factors inducing pathogenic transformations of IDPs are various cellular mechanisms, such as chromosomal translocations, damaged splicing, altered expression, frustrated posttranslational modifications, aberrant proteolytic degradation, and defective trafficking. This review presents some of the aspects of deregulated regulation of IDPs leading to human diseases. PMID:25988147

Serum gamma-glutamyltransferase activity is increased in patients with calcific aortic valve stenosis.

PubMed

Bozbas, Huseyin; Yildirir, Aylin; Demir, Ozlem; Cakmak, Abdulkadir; Karacaglar, Emir; Yilmaz, Mustafa; Eroglu, Serpil; Pirat, Bahar; Ozin, Bulent; Muderrisoglu, Haldun

2008-07-01

A growing body of data indicates an independent association between serum gamma-glutamyltransferase (GGT) activity, a marker of increased oxidative stress, and cardiovascular diseases. The process of calcific aortic valve disease has been shown to present characteristics of atherosclerosis. The study aim was to evaluate the possible role of serum GGT in patients with calcific aortic valve disease. The results of patients' echocardiography studies from 2005 for the presence of calcific aortic valve disease in the forms of aortic stenosis (AS) and aortic valve calcification (AVC) without significant valve stenosis, were retrospectively evaluated. Age-and gender-matched patients with normal aortic valve morphology were selected at random as a control group. A total of 383 patients was enrolled into the study (126 with AS, 133 with AVC, 124 controls). Serum GGT activity, along with other liver enzyme analyses and laboratory results, were determined and compared among the groups. Age, gender and clinical and laboratory results were similar among the three groups. Median serum GGT levels in the AS, AVC and control groups were 23.0 U/1 (mean 31.5 +/- 24.9 U/1), 22.0 U/1 (mean 27.6 +/- 18.6 U/) and 18.0 U/l (mean 22.4 +/- 16.4 U/l), respectively. Compared to controls, AS patients had significantly higher serum GGT and C-reactive protein levels, while the differences between AVC patients and controls for these parameters were not significant. The study results suggest that serum GGT activity is increased in patients with calcific AS. These increases seem to occur in advanced rather than milder forms of calcific aortic valve disease.

Design of optimal nonlinear network controllers for Alzheimer's disease.

PubMed

Sanchez-Rodriguez, Lazaro M; Iturria-Medina, Yasser; Baines, Erica A; Mallo, Sabela C; Dousty, Mehdy; Sotero, Roberto C

2018-05-01

Brain stimulation can modulate the activity of neural circuits impaired by Alzheimer's disease (AD), having promising clinical benefit. However, all individuals with the same condition currently receive identical brain stimulation, with limited theoretical basis for this generic approach. In this study, we introduce a control theory framework for obtaining exogenous signals that revert pathological electroencephalographic activity in AD at a minimal energetic cost, while reflecting patients' biological variability. We used anatomical networks obtained from diffusion magnetic resonance images acquired by the Alzheimer's Disease Neuroimaging Initiative (ADNI) as mediators for the interaction between Duffing oscillators. The nonlinear nature of the brain dynamics is preserved, given that we extend the so-called state-dependent Riccati equation control to reflect the stimulation objective in the high-dimensional neural system. By considering nonlinearities in our model, we identified regions for which control inputs fail to correct abnormal activity. There are changes to the way stimulated regions are ranked in terms of the energetic cost of controlling the entire network, from a linear to a nonlinear approach. We also found that limbic system and basal ganglia structures constitute the top target locations for stimulation in AD. Patients with highly integrated anatomical networks-namely, networks having low average shortest path length, high global efficiency-are the most suitable candidates for the propagation of stimuli and consequent success on the control task. Other diseases associated with alterations in brain dynamics and the self-control mechanisms of the brain can be addressed through our framework.

Outcome of an education and home-based exercise programme for patients with ankylosing spondylitis: a nationwide randomized study.

PubMed

Rodríguez-Lozano, Carlos; Juanola, Xavier; Cruz-Martínez, Juan; Peña-Arrébola, Andrés; Mulero, Juan; Gratacós, Jordi; Collantes, Eduardo

2013-01-01

This study aims to assess the impact of a structured education and home exercise programme in daily practice patients with ankylosing spondylitis. A total of 756 patients with ankylosing spondylitis (72% males, mean age 45 years) participated in a 6-month prospective multicentre controlled study, 381 of whom were randomised to an education intervention (a 2-hour informative session about the disease and the implementation of a non-supervised physical activity programme at home) and 375 to standard care (controls). Main outcome measures included Bath Ankylosing Spondylitis Disease Activity and Functional Index (BASDAI, BASFI). Secondary outcome measures were 0-10 cm visual analog scale (VAS) for total pain, nocturnal pain and global disease activity and quality of life (ASQoL), knowledge of disease (self-evaluation ordinal scale) and daily exercise (diary card). At 6 months, the adjusted mean difference between control and educational groups for BASDAI was 0.32, 95% confidence interval (CI) 0.10-0.54, p=0.005, and for BASFI 0.31, 95%CI 0.12-0.51, p=0.002. Significant differences were found also in VAS for total pain, patient´s global assessment and in ASQoL. Patients in the education group increased their knowledge about the disease and its treatments significantly (p<0.001) and practised more regular exercise than controls (p<0.001). A structured education and home exercise programme for patients with ankylosing spondylitis in daily practice was feasible and helped to increase knowledge and exercise. Although statistically significant, the magnitudes of the clinical benefits in terms of disease activity and physical function were poor.

Novel, Objective, Multivariate Biomarkers Composed of Plasma Amino Acid Profiles for the Diagnosis and Assessment of Inflammatory Bowel Disease

PubMed Central

Hisamatsu, Tadakazu; Okamoto, Susumu; Hashimoto, Masaki; Muramatsu, Takahiko; Andou, Ayatoshi; Uo, Michihide; Kitazume, Mina T.; Matsuoka, Katsuyoshi; Yajima, Tomoharu; Inoue, Nagamu; Kanai, Takanori; Ogata, Haruhiko; Iwao, Yasushi; Yamakado, Minoru; Sakai, Ryosei; Ono, Nobukazu; Ando, Toshihiko; Suzuki, Manabu; Hibi, Toshifumi

2012-01-01

Background Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). Methodology and Principal Findings We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898–0.983) and 0.894 (95%CI: 0.853–0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853–0.935) and 0.849 (95%CI: 0.770–0.928), and correlated with clinical disease activity indexes for CD (rs = 0.592, 95%CI: 0.385–0.742, p<0.001) or UC (rs = 0.598, 95%CI: 0.452–0.713, p<0.001), respectively. Conclusions and Significance In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease. PMID:22303484

PLA2G7 genotype, Lp-PLA2 activity and coronary heart disease risk in 10,494 cases and 15,624 controls of European ancestry

PubMed Central

Casas, Juan P.; Ninio, Ewa; Panayiotou, Andrie; Palmen, Jutta; Cooper, Jackie A; Ricketts, Sally L; Sofat, Reecha; Nicolaides, Andrew N; Corsetti, James P; Fowkes, F Gerry R; Tzoulaki, Ioanna; Kumari, Meena; Brunner, Eric J; Kivimaki, Mika; Marmot, Michael G; Hoffmann, Michael M; Winkler, Karl; März, Winfred; Ye, Shu; Stirnadel, Heide A; MBBChir, Kay-Tee Khaw; Humphries, Steve E; Sandhu, Manjinder S; Hingorani, Aroon D; Talmud, Philippa J

2012-01-01

Background Higher Lp-PLA2 activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. Methods and Results A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only and 2 cross-sectional, n=26,118) was undertaken to examine the association of: (i) LpPLA2 activity vs. cardiovascular biomarkers and risk factors and CHD events (two prospective studies; n=4884); ii) PLA2G7 SNPs and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and iii) PLA2G7 SNPs and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratio for CHD events top vs. bottom quartile of Lp-PLA2 activity was 1.61 (95%CI: 1.31, 1.99) and 1.17 (95%CI: 0.91, 1.51) after adjustment for baseline traits. Of seven SNPs, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (OR 1.03 (95%CI 0.80, 1.32), or CHD events (OR 0.98 (95%CI 0.82, 1.17). Conclusions Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma or CHD. Larger association studies, identification of SNPs with larger effects, or randomised trials of specific Lp-PLA2 inhibitors are needed to confirm/refute a contributory role for Lp-PLA2 in CHD. PMID:20479152

Increased expression of low density granulocytes in juvenile-onset systemic lupus erythematosus patients correlates with disease activity.

PubMed

Midgley, A; Beresford, M W

2016-04-01

Neutrophils are implicated in a wide range of non-infectious inflammatory conditions. A subset of neutrophils in the peripheral circulation of systemic lupus erythematosus (SLE) patients has been described and termed low density granulocytes (LDGs). This study investigates the expression of LDG in juvenile-onset SLE (JSLE) patients compared to controls, and any correlations with disease activity.Neutrophils and LDGs were isolated from JSLE (n = 13) and paediatric non-inflammatory control patients (n = 12). Cell populations were assessed and compared using flow cytometry and morphological analysis. Standard clinical data, which included disease activity markers/scores, were collected for each patient.Significantly increased LDG expression (%mean ± SEM, range) was observed in JSLE patients (10.4 ± 3.26, 3.41-36.3) compared to controls (2.4 ± 0.44, 0.36-5.27; p = 0.005). A statistically significant positive correlation was observed between LDG expression and the British Isles Lupus Activity Group (correlation coefficient 0.685; p = 0.010) and SLE Disease Activity Index (correlation coefficient 0.567; p = 0.043) and the biomarker of dsDNA-antibodies (correlation coefficient 0.590; p = 0.043).Here we observe increased expression in LDGs in JSLE patients, which correlate with dsDNA antibody concentration and scores of disease activity. These correlations indicate that the increased LDG expression observed in this study may have a potential role in the pathogenesis of JSLE, and may be a useful biomarker. © The Author(s) 2015.

Role of Peroxisome Proliferator-Activated Receptor γ in Ocular Diseases

PubMed Central

Gu, Hongwei

2015-01-01

Peroxisome proliferator-activated receptor γ (PPAR γ), a member of the nuclear receptor superfamily, is a ligand-activated transcription factor that plays an important role in the control of a variety of physiological processes. The last decade has witnessed an increasing interest for the role played by the agonists of PPAR γ in antiangiogenesis, antifibrosis, anti-inflammation effects and in controlling oxidative stress response in various organs. As the pathologic mechanisms of major blinding diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), keratitis, and optic neuropathy, often involve neoangiogenesis and inflammation- and oxidative stress-mediated cell death, evidences are accumulating on the potential benefits of PPAR γ to improve or prevent these vision threatening eye diseases. In this paper we describe what is known about the role of PPAR γ in the ocular pathophysiological processes and PPAR γ agonists as novel adjuvants in the treatment of eye diseases. PMID:26146566

Call for action for setting up an infectious disease control action plan for disaster area activities: learning from the experience of checking suffering volunteers in the field after the Great East Japan Earthquake.

PubMed

Takahashi, Kenzo; Kodama, Mitsuya; Kanda, Hideyuki

2013-12-01

After the Great East Japan Earthquake on March 11th, 2011, a journalist visited the disaster area with febrile symptoms and was diagnosed with measles of the D genotype, which is not indigenous to Japan. After continuing activities in disaster areas and Tokyo, 11 measles cases were reported, some of which were identified as genotype D. Meanwhile non-profit activities directed towards volunteers were offered including interviews to screen for subjective symptoms, check body temperature and advise volunteers to refrain from working in shelter areas during the period of sickness. As a consequence, disease transmission was controlled among volunteers. In disaster areas, anyone can be an infection vector. In order to prevent transmission of infectious diseases, a field action plan, which includes body temperature checks and standard precautions should be formulated and put into place. If the action plans are shared among local governments and non-governmental organizations (NGOs), they can become a norm and be expected to control infectious disease transmission.

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

Investigating relationships between ancestry, lifestyle behaviors and perceptions of heart disease and breast cancer among Canadian women with British and with South Asian ancestry.

PubMed

Curtin, Kimberley D; Berry, Tanya R; Courneya, Kerry S; McGannon, Kerry R; Norris, Colleen M; Rodgers, Wendy M; Spence, John C

2018-04-01

Ethnic minority groups including Asians in Canada have different knowledge and perceptions of heart disease and breast cancer compared with the ethnic majority group. Examine relationships between perceptions of heart disease and breast cancer, and lifestyle behaviors for Canadian women with British and with South Asian ancestry. Women with South Asian ( n = 170) and with British ( n = 373) ancestry ( M age = 33.01, SD = 12.86) reported leisure time physical activity, intended fruit and vegetable consumption, disease perceptions (ability to reduce risk, control over getting the diseases, and influence of family history), and demographic information. Mann-Whitney tests and multiple hierarchical linear regressions were used to examine the relationships between lifestyle behaviors and disease perceptions, with ancestry explored as a possible moderator. Participants with South Asian ancestry believed they had greater ability to reduce their risk and have control over getting breast cancer than participants with British ancestry. Family history influences on getting either disease was perceived as higher for women with British ancestry. Age was positively related to all three perceptions in both diseases. Intended fruit and vegetable consumption was positively related to perceptions of ability to reduce risk and control of both diseases, but was stronger for women with South Asian ancestry regarding perceptions of breast cancer. Leisure time physical activity was positively related to perceptions of control over getting heart disease for women with British ancestry. Women's disease perceptions can vary by ancestry and lifestyle behaviors. Accurate representation of diseases is essential in promoting effective preventative behaviors.

Arterial properties in acromegaly: relation to disease activity and associated cardiovascular risk factors.

PubMed

Yaron, Marianna; Izkhakov, Elena; Sack, Jessica; Azzam, Ibrahim; Osher, Etty; Tordjman, Karen; Stern, Naftali; Greenman, Yona

2016-06-01

Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function. Twenty-nine subjects with acromegaly (11 males, 52 ± 14 year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD). IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2 ± 1.1 in patients with active disease versus 0.7 ± 0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4 ± 2.7 % in active acromegaly, 4.4 ± 3.3 % in controlled acromegaly and 7.5 ± 3.8 % in controls; p = 0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1× ULN and IMT (r = 0.4; P = 0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r = 0.46; p = 0.017) and negatively with small vessel compliance (r = -0.44, p = 0.02). Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.

Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection.

PubMed

Gul, Kiran Aftab; Sonerud, Tonje; Fjærli, Hans O; Nakstad, Britt; Abrahamsen, Tore Gunnar; Inchley, Christopher S

2017-01-05

Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in previously healthy infants. Immunological mechanisms predisposing infants to severe disease are poorly understood. Early biomarkers for disease severity may assist clinical decisions. We investigated T-cell receptor excision circles (TREC), episomal DNA made during thymic T-cell receptor rearrangement, and a marker for thymus activity, both during disease and in neonatal screening cards as a risk factor for RSV disease severity. One hundred thirteen patients hospitalized with RSV infection <12 months of age, grouped by disease severity, were available for this investigation, in which we conducted both a prospective and a case-control study. The prospective study included 47 RSV positive infants (mild n = 13, moderate n = 10, severe n = 24). TREC counts were determined by PCR of DNA extracted from EDTA-blood collected on hospitalization, and corrected for lymphocytes using ANCOVA. The case-control study included 85 newborns who later in infancy became RSV positive (mild n = 32, moderate n = 24, severe n = 29) and 47 newborns who never developed RSV disease as healthy controls included from health centres in the same catchment area. TRECs were measured using DNA extracted from dry blood spots from stored neonatal screening cards, followed by PCR. Student's T-test compared patients with controls, ANOVA compared disease severity groups. During RSV infection patients in the severe disease group had significantly lower (p = 0.017) TREC/200 μL blood compared to the other two disease groups, after correction for lymphocyte count. Newborn TREC levels, were significantly higher in RSV patients compared to controls (p < 0.0001). No significant differences in TREC copies at birth were found between disease severities. During acute RSV infection a lower number of TREC is found in the severe disease group. TREC has potential as an immunological marker for severe RSV infection. Higher neonatal TREC counts indicate that infants later presenting with severe RSV do not have reduced thymic activity at birth and probably no congenital T-cell defect.

On lupus, vitamin D and leukopenia.

PubMed

Simioni, Juliana A; Heimovski, Flavia; Skare, Thelma L

2016-01-01

Immune regulation is among the noncalcemic effects of vitamin D. So, this vitamin may play a role in autoimmune diseases such as systemic lupus erythematosus (SLE). To study the prevalence of vitamin D deficiency in SLE and its association with clinical, serological and treatment profile as well as with disease activity. Serum OH vitamin D3 levels were measured in 153 SLE patients and 85 controls. Data on clinical, serological and treatment profile of lupus patients were obtained through chart review. Blood cell count and SLEDAI (SLE disease activity index) were measured simultaneously with vitamin D determination. SLE patients have lower levels of vitamin D than controls (p=0.03). In univariate analysis serum vitamin D was associated with leukopenia (p=0.02), use of cyclophosphamide (p=0.007) and methotrexate (p=0.03). A negative correlation was verified with prednisone dose (p=0.003). No association was found with disease activity measured by SLEDAI (p=0.88). In a multiple regression study only leukopenia remained as an independent association (B=4.04; p=0.02). A negative correlation of serum vitamin level with granulocyte (p=0.01) was also found, but not with lymphocyte count (p=0.33). SLE patients have more deficiency of vitamin D than controls. This deficiency is not associated with disease activity but with leucopenia (granulocytopenia). Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

[The importance of oxidative stress in pathogenesis of type 1 diabetes--determination of catalase activity in lymphocytes of diabetic patients].

PubMed

Zivić, Sasa; Vlaski, Jovan; Kocić, Gordana; Pesić, Milica; Cirić, Vesna; Durić, Zlatko

2008-01-01

Type 1 diabetes is a protoype of disease with an intensive oxidative stress. The oxidative stress means disturbing dynamic balance between prooxidants and antioxidants, either due to the increased production of the oxygen free radicals or the decreased antioxidant activity. The antioxidative enzyme catalase diminishes free radical hydrogen-peroxyde, which can be very toxic to pancreatic cells. Our study included 40 children with type 1 diabetes. We analysed the activity of enzyme catalase in lymphocytes in different phases of disease: at the beginning of diabetes, in remission period and in the later chronic course. There is a significant increase in the catalase activity during all phases of disease (p<0.00001) compared with the control group. The highest catalase activity occurs in the early course of disease (p<0.05) followed by a linear decrease and the lowest activity in chronic course. If metabolic control gets worse, the catalase activity gets higher with statistic significance at p<0.05. A higher residual beta cells secretion is associated with a lower catalase activity. Therefore, the catalase activity is in direct corelation with GHbA1 (r=0.895), and inverse correlation with C-peptide (r=-0.945). A significant increase in the catalase activity in all phases of type 1 diabetes indirectly confirms the importance of the oxidative stress in pathogenesis of disease. The activation of catalase is probably the secundary phenomenon. The fact that the catalase activity reaches its highest values at the beginning of diabetes could implicate the predictive value of catalase determination.

Situation of Sri Lanka, where autochthonous malaria is no longer a problem, and other infections dominate, such as dengue, leptospirosis and rickettsioses.

PubMed

Agampodi, Suneth; Wijerathne, Buddhika; Weerakoon, Kosala

2016-10-01

Sri Lanka achieved a major milestone in communicable disease control in 2012 by reporting zero incidence of autochthonous malaria. However, reduction of malaria was associated with concurrent increase of several tropical diseases. This review looks into the time trends and epidemiology of these communicable diseases in Sri Lanka. Reduction of malaria cases coincides with an increase of dengue, leptospirosis and rickettsioses in Sri Lanka. Although the case fatality rate of dengue has reduced and maintained below 1%, leptospirosis in clinical management is questionable. Despite having national focal points for control and prevention, these emerging diseases are completely out of control. Whether the holding back of vector control activities of malaria after a successful control programme is having an effect on emergence of other vector-borne diseases should be studied. The communicable disease control programme in Sri Lanka should be further strengthened with availability of proper and rapid diagnostic facilities. Malaria control could not be considered as a great achievement due to the fact that other emerging infectious diseases are replacing malaria.

Remission is the goal for cardiovascular risk management in patients with rheumatoid arthritis: a cross-sectional comparative study.

PubMed

Provan, Sella A; Semb, Anne Grete; Hisdal, Jonny; Stranden, Einar; Agewall, Stefan; Dagfinrud, Hanne; Angel, Kristin; Atar, Dan; Kvien, Tore K

2011-05-01

To compare markers of cardiovascular disease (CVD) risk between patients with rheumatoid arthritis (RA) in an active disease state and those with RA in remission, and to compare both groups with community controls. 113 patients with RA and 86 community controls were assessed across a panel of biomarkers for CVD. RA in remission was defined as Clinical Disease Activity Index ≤2.8. Community controls were selected at random by Statistics Norway, and controls were matched with patients in the cohorts in strata using details of age, sex and residential area. A panel of biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), total cholesterol, reactive hyperaemia index (RHI), pressure measurements, measures of arterial stiffness and intima-media thickness) were compared between patients with active RA and those with RA in remission. Both groups were compared with controls. In addition, biomarker levels were compared across subgroups based on anticyclic citrullinated peptide status, level of joint destruction and presence of extra-articular manifestations. Patients with active RA had significantly higher levels of NT-proBNP, brachial systolic pressure, augmentation index and central systolic pressure but lower cholesterol than patients in remission and controls. In addition, patients with active RA had significantly higher levels of pulse wave velocity and worse RHI than patients in remission. Comparison across other subgroups gave less consistent differentiations in levels of CVD risk markers. Patients with active RA, but not those in remission, had significantly increased levels of CVD risk markers. These results link inflammatory activity to markers of CVD risk in patients with RA and may indirectly support the notion that remission in RA confers diminished cardiovascular morbidity.

Relationship between chronic disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes and Alzheimer disease.

PubMed

Kosenko, Elena A; Aliev, Gjumrakch; Kaminsky, Yury G

2016-01-01

Alzheimer disease (AD) is one of the most common neurodegenerative disorders widely occurring among the elderly. The pathogenic mechanisms involved in the development of this disease are still unknown. In AD, in addition to brain, a number of peripheral tissues and cells are affected, including erythrocytes. In this study, we analyzed glycolytic energy metabolism, antioxidant status, glutathione, adenylate and proteolytic systems in erythrocytes from patients with AD and compared with those from age-matched controls and young adult controls. Glycolytic enzymes hexokinase, phosphofructokinase, bisphosphoglycerate mutase and bisphosphoglycerate phosphatase displayed lower activities in agematched controls, and higher activities in AD patients, as compared to those in young adult control subjects. In both aging and AD, oxidative stress is increased in erythrocytes whereas elevated concentrations of hydrogen peroxide and organic hydroperoxides as well as decreased glutathione/glutathione disulfide ratio and glutathione transferase activity can be detected. These oxidative disturbances are also accompanied by reductions in ATP levels, adenine nucleotide pool size and adenylate energy charge. Caspase-3 and calpain activities in age-matched controls and AD patients were about three times those of young adult controls. 2,3-diphosphoglycerate levels were significantly decreased in AD patients. Taken together these data suggest that AD patients are associated with chronic disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes. These defects may play a central role in pathophysiological processes predisposing elderly subjects to dementia.

Serum Epstein-Barr virus DNA, detected by droplet digital PCR, correlates with disease activity in patients with rheumatoid arthritis.

PubMed

Kuusela, Elina; Kouri, Vesa-Petteri; Olkkonen, Juri; Koivuniemi, Riitta; Äyräväinen, Leena; Rajamäki, Kristiina; Valleala, Heikki; Nordström, Dan; Leirisalo-Repo, Marjatta; Ainola, Mari; Eklund, Kari K

2018-03-20

To study the prevalence of asymptomatic activation of Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to analyse the correlation of serum EBV DNA with the disease activity. The level of EBV DNA was determined by droplet digital PCR assay from the serum of 46 DMARD naive early RA (ERA) and 22 chronic RA (CRA)-patients at study onset. Follow-up samples from 31 ERA and 16 CRA patients were obtained after starting or modifying the anti-rheumatic treatment. EBV DNA was also measured from 33 healthy controls and 9 patients with adult onset Still's disease (AOSD). Disease activity was assessed by the disease activity score (DAS28). At baseline, EBV DNA was detected in the serum of 7 of the 46 ERA patients all of whom had moderate or high disease activity. In the follow-up samples, 11 of 31 patients were EBV DNA positive. At baseline EBV positive patients had significantly higher disease activity (p=0.036) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.333, p=0.024). EBV DNA was detected in 3 of 22 CRA patients at study onset and in 8 of 16 in the follow-up samples. At follow-up EBV positive patients had significantly higher DAS28 (p=0.027) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.724, p=0.002). Only one of the healthy controls and none of the AOSD patients were positive for EBV DNA. Active RA is associated with a lytic EBV infection which may have a role in the pathogenesis of RA.

Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis.

PubMed

Barbosa-Cobos, Rosa Elda; Lugo-Zamudio, Gustavo; Flores-Estrada, Javier; Becerril-Mendoza, Lizbeth Teresa; Rodríguez-Henríquez, Pedro; Torres-González, Rubén; Moreno-Eutimio, Mario Adán; Ramirez-Bello, Julian; Moreno, José

2018-04-01

The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student's t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p < 0.0001). SP levels correlated with DAS28-CRP (r = 0.5050, p < 0.0001), number of tender joints (NTJ, r = 0.4668, p < 0.0001), number of swollen joints (NSJ, r = 0.4439, p < 0.0001), visual analogue scale (VAS, r = 0.5131, p < 0.0001). However, SP did not correlate with CRP levels (r = 0.0468, p = 0.6613), nor with the USPD (r = 0.1740, p = 0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.

Impact of Bacillus amyloliquefaciens S13-3 on control of bacterial wilt and powdery mildew in tomato.

PubMed

Yamamoto, Shoko; Shiraishi, Soma; Kawagoe, Yumi; Mochizuki, Mai; Suzuki, Shunji

2015-05-01

Biological control is a non-hazardous technique to control plant diseases. Researchers have explored microorganisms that show high plant-disease control efficiency for use as biological control agents. A single soil application of Bacillus amyloliquefaciens strain S13-3 suppressed tomato bacterial wilt caused by Ralstonia solanacearum, a soilborne bacterial pathogen, through production of antibiotics augmented possibly by induction of systemic acquired resistance. Soil application also controlled tomato powdery mildew disease through induction of systemic acquired resistance. S13-3 showing bifunctional activity with a single application to soil may be an innovative biological control agent against bacterial wilt and powdery mildew in tomato. © 2014 Society of Chemical Industry.

The impact of a ten-week physical exercise program on health-related quality of life in patients with inflammatory bowel disease: a prospective randomized controlled trial.

PubMed

Klare, Peter; Nigg, Johanna; Nold, Johannes; Haller, Bernhard; Krug, Anne B; Mair, Sebastian; Thoeringer, Christoph K; Christle, Jeffrey W; Schmid, Roland M; Halle, Martin; Huber, Wolfgang

2015-01-01

Improving health-related quality of life is a primary target of therapy for patients with inflammatory bowel disease. Physical activity has been demonstrated to improve health-related quality of life in several patient populations with chronic disease. There are very few studies investigating the effects of physical activity on health-related quality of life in inflammatory bowel disease. The primary purpose of this study is to investigate the effects of 10 weeks of moderate physical activity on health-related quality of life in patients with inflammatory bowel disease. Thirty patients with mild to moderate IBD (Crohn's Disease Activity Index (CDAI) <220 or Rachmilewitz Index (RI) <11) were randomized 1:1 to either supervised moderate-intensity running thrice a week for 10 weeks or a control group who were not prescribed any exercise. Health-related quality of life, symptoms, and inflammation were assessed at baseline and after 10 weeks. Participants were 41 ± 14 years (73% female), had a body mass index of 22.8 ± 4.1 kg/m(2), and an average CDAI or RI of 66.8 ± 42.4 and 3.6 ± 3.1. No adverse events occurred during the 10-week training period. Health-related quality of life, reported as IBDQ total score, improved 19% in the intervention group and 8% in the control group. Scores for the IBDQ social sub-scale were significantly improved in the intervention group compared with controls (ΔIBDQsocial = 6.27 ± 5.46 vs. 1.87 ± 4.76, p = 0.023). Patients suffering from moderately active IBD are capable of performing symptom-free regular endurance exercise. Our data support the assumption that PA is feasible in IBD patients. PA may furthermore improve quality of life through improvements in social well-being, and may, therefore, be a useful adjunct to IBD therapy. © 2015 S. Karger AG, Basel.

Venereal Disease Control Demonstrations among Rural Blacks in the American South.

ERIC Educational Resources Information Center

Stanfield, John H.

1981-01-01

Compares the 1929-32 Venereal Disease Control Demonstration Project conducted among Southern Blacks with the 1932 Tuskegee Syphilis Experiment. Asserts that while the latter involved unethical research activities, the former fell outside the realm of research ethics, because it exploited human subjects for political gain. (Author/MJL)

IFN-γ, CXCL16, uPAR: potential biomarkers for systemic lupus erythematosus.

PubMed

Wen, Si; He, Fang; Zhu, Xuejing; Yuan, Shuguang; Liu, Hong; Sun, Lin

2018-01-01

IFN-γ, CXCL16 and uPAR have recently been regarded as potential biomarkers in systemic lupus erythematosus (SLE). However, few researches have focused on the comparison of these three markers in SLE. We conducted this study to evaluate their role as biomarkers of disease activity and renal damage. We enrolled 50 SLE patients with or without lupus nephritis (LN) and 15 healthy control subjects. The levels of IFN-γ, CXCL16, uPAR in serum, urine and renal tissues were detected by ELISA or immunohistochemistry. Relevant clinical and laboratory features were recorded. Serum and urine IFN-γ, CXCL16 and suPAR levels in SLE patients were significantly higher than that in healthy controls. Moreover, LN patients had higher levels than non-LN patients. A positive correlation was observed between these markers, and disease activity and suPAR had a stronger association with disease activity. The expression of these biomarkers in renal tissues was significantly higher in LN patients and was also associated with the activity of pathological lesions. IFN-γ, CXCL16 and uPAR are promising as effective biomarkers of disease activity, renal damage, and the activity of pathological lesions in SLE.

Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.

PubMed

Mok, Chi Chiu; Soliman, Samar; Ho, Ling Yin; Mohamed, Fatma A; Mohamed, Faten Ismail; Mohan, Chandra

2018-01-11

The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE). Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine. Receiver operating characteristic analysis was performed to obtain the best cutoff values to calculate the performance of these markers in differentiating the different groups of patients as compared to anti-double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these urinary biomarkers and various renal parameters was also tested. Patients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal disease and 80 with active renal disease; 94% women; age 39.2 ± 13.8 years) and 53 controls (96% women) were studied. All were ethnic Chinese. Urinary angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly higher in patients with active renal disease than in patients with active non-renal disease, patients with inactive SLE and controls. These markers correlated significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin exhibited higher specificity and sensitivity in differentiating active renal from active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3. Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed similarly to anti-dsDNA/C3. All three markers performed comparably to anti-dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients with paired renal biopsy, the urinary levels of these proteins did not differ significantly between the proliferative and non-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup. Urinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.

Induction of plant defense gene expression by plant activators and Pseudomonas syringae pv. tomato in greenhouse-grown tomatoes.

PubMed

Herman, M A B; Davidson, J K; Smart, C D

2008-11-01

Plant activators provide an appealing management option for bacterial diseases of greenhouse-grown tomatoes. Two types of plant activators, one that induces systemic acquired resistance (SAR) and a second that activates induced systemic resistance (ISR), were evaluated for control of Pseudomonas syringae pv. tomato and effect on plant defense gene activation. Benzothiadiazole (BTH, SAR-inducing compound) effectively reduced bacterial speck incidence and severity, both alone and in combination with the ISR-inducing product. Application of BTH also led to elevated activation of salicylic acid and ethylene-mediated responses, based on real-time polymerase chain reaction analysis of marker gene expression levels. In contrast, the ISR-inducing product (made up of plant growth-promoting rhizobacteria) inconsistently modified defense gene expression and did not provide disease control to the same level as did BTH. No antagonism was observed by combining the two activators as control of bacterial speck was similar to or better than BTH alone.

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

PubMed

Alemao, Evo; Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J; Allison, Paul D; Rutten-van Mölken, Maureen P M H; Frits, Michelle L; Iannaccone, Christine K; Shadick, Nancy A; Weinblatt, Michael E

2016-03-01

To evaluate associations between achieving guideline-recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M-HAQ), the EuroQol 5-domain (EQ-5D; a quality-of-life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM-HAQ -0.047; P = 0.0100) and CDAI ≤2.8 (-0.073; P = 0.0003) but not DAS28-CRP <2.6 (-0.022; P = 0.1735). Target attainment was associated with significantly improved EQ-5D (0.022-0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline-recommended disease targets were 36-45% less likely to be hospitalized (P < 0.0500) and 23-45% less likely to utilize DME (P < 0.0100). Attaining recommended target disease-activity measures was associated with enhanced physical functioning and health-related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial.

PubMed

Hawkey, Christopher J; Allez, Matthieu; Clark, Miranda M; Labopin, Myriam; Lindsay, James O; Ricart, Elena; Rogler, Gerhard; Rovira, Montserrat; Satsangi, Jack; Danese, Silvio; Russell, Nigel; Gribben, John; Johnson, Peter; Larghero, Jerome; Thieblemont, Catherine; Ardizzone, Sandro; Dierickx, Daan; Ibatici, Adalberto; Littlewood, Timothy; Onida, Francesco; Schanz, Urs; Vermeire, Severine; Colombel, Jean-Frederic; Jouet, Jean-Paul; Clark, Elizabeth; Saccardi, Riccardo; Tyndall, Alan; Travis, Simon; Farge, Dominique

2015-12-15

Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .052). Eight (34.8%) vs 2 (9.1%) patients were adjudicated free of active disease on endoscopy and radiology at final assessment (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .054). There were 76 serious adverse events in patients undergoing HSCT vs 38 in controls. One patient undergoing HSCT died. Among adult patients with refractory Crohn disease not amenable to surgery who had impaired quality of life, HSCT, compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year and was associated with significant toxicity. These findings do not support the widespread use of HSCT for patients with refractory Crohn disease. clinicaltrials.gov Identifier: NCT00297193.

Patterns of brain activity during a semantic task differentiate normal aging from early Alzheimer's disease.

PubMed

McGeown, William Jonathan; Shanks, Michael Fraser; Forbes-McKay, Katrina Elaine; Venneri, Annalena

2009-09-30

In a study of the effects of normal and pathological aging on semantic-related brain activity, 29 patients with Alzheimer's disease (AD) and 19 controls subjects (10 young and 9 older controls) performed a version of the Pyramids and Palm Trees Test that had been adapted for use during functional magnetic resonance imaging (fMRI). Young and older controls activated the left inferior and middle frontal gyri, precuneus and superior parietal lobule. Right frontal and left temporal cortices were activated only in the young. The AD group activated only the left prefrontal and cingulate cortex. Separate analyses of high- and low-performing AD subgroups showed a similar pattern of activation in the left frontal lobe, although activiation was more widespread in low performers. High performers significantly deactivated anterior midline frontal structures, however, while low performers did not. When the older adult and AD groups were combined, there was a significant positive correlation between left frontal and parietal activation and Mini-Mental State Examination (MMSE) score (covarying for age), suggesting a disease effect. A significant negative correlation between activation in the left temporal cortex and age (covarying for MMSE score) reflected a possible age effect. These differential effects suggest that semantic activation paradigms might aid diagnosis in those cases for whom conventional assessments lack the necessary sensitivity to detect subtle changes.

29 CFR 1630.16 - Specific activities permitted.

Code of Federal Regulations, 2012 CFR

2012-07-01

... infectious and communicable diseases which are transmitted through the handling of food. (Copies may be obtained from Center for Infectious Diseases, Centers for Disease Control, 1600 Clifton Road, NE., Mailstop... and communicable diseases; food handling jobs—(1) In general. Under title I of the ADA, section 103(d...

29 CFR 1630.16 - Specific activities permitted.

Code of Federal Regulations, 2013 CFR

2013-07-01

... infectious and communicable diseases which are transmitted through the handling of food. (Copies may be obtained from Center for Infectious Diseases, Centers for Disease Control, 1600 Clifton Road, NE., Mailstop... and communicable diseases; food handling jobs—(1) In general. Under title I of the ADA, section 103(d...

Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey.

PubMed

Arima, Kazuhiko; Gupta, Shaloo; Gadkari, Abhijit; Hiragun, Takaaki; Kono, Takeshi; Katayama, Ichiro; Demiya, Sven; Eckert, Laurent

2018-04-01

Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general population. Japanese adults (≥18 years) with a self-reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity-score matched with non-atopic dermatitis controls (1:2 ratio) on demographic variables. Patient-reported outcome data on comorbidities, mood and sleep disorders, health-related quality of life, work productivity and activity impairment, and health-care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as "moderate/severe" and 348 (54.5%) as "mild". The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health-related quality of life, higher overall work and activity impairment, and higher health-care resource utilization (all P < 0.001). Self-rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management. © 2018 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

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.

Metabolism as a Target for Modulation in Autoimmune Diseases.

PubMed

Huang, Nick; Perl, Andras

2018-05-05

Metabolic pathways are now well recognized as important regulators of immune differentiation and activation, and thus influence the development of autoimmune diseases such as systemic lupus erythematosus (SLE). The mechanistic target of rapamycin (mTOR) has emerged as a key sensor of metabolic stress and an important mediator of proinflammatory lineage specification. Metabolic pathways control the production of mitochondrial reactive oxygen species (ROS), which promote mTOR activation and also modulate the antigenicity of proteins, lipids, and DNA, thus placing ROS at the heart of metabolic disturbances during pathogenesis of SLE. Therefore, we review here the pathways that control ROS production and mTOR activation and identify targets for safe therapeutic modulation of the signaling network that underlies autoimmune diseases, focusing on SLE. Copyright © 2018. Published by Elsevier Ltd.

Beta-glucuronidase and Beta-glucosidase activity in stool specimens of children with inflammatory bowel disease.

PubMed

Mroczyńska, Marta; Galecka, Miroslawa; Szachta, Patrycja; Kamoda, Dorota; Libudzisz, Zdzislawa; Roszak, Dorota

2013-01-01

The aim of the study was to analyze the differences in the activity of beta-glucuronidase and beta-glucosidase in stool specimens of children with Inflammatory Bowel Diseases (IBD) and healthy subjects. The disease activity was determined according to the PCDAI scale (Crohn disease) and Truelove-Witts scale (Ulcerative colitis). Enzyme activity was determined by spectrophotometry. There was a correlation between the level of beta - glucosidase activity in stool and patient's age in the group of healthy controls, but not in the IBD group. beta-glucosidase activity in IBD and healthy subjects stool specimens did not differ significantly. The activity of beta-glucuronidase in children with IBD was two times lower than in the healthy group and was correlated with age in children with IBD, but not in the group of healthy ones.

Circulating anti-double-stranded DNA antibody-secreting cells in patients with systemic lupus erythematosus: a novel biomarker for disease activity.

PubMed

Hanaoka, H; Okazaki, Y; Satoh, T; Kaneko, Y; Yasuoka, H; Seta, N; Kuwana, M

2012-10-01

Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p < 0.001). Circulating anti-dsDNA antibody-secreting cells are a useful biomarker for assessing disease activity in SLE patients.

Interleukin 27 is up-regulated in patients with active inflammatory bowel disease.

PubMed

Furuzawa Carballeda, Janette; Fonseca Camarillo, Gabriela; Yamamoto-Furusho, Jesús K

2016-08-01

The aim of the study was to characterize and quantify tissue gene and protein expression of IL-27 in ulcerative colitis (UC) and Crohn's disease (CD) patients. This is an observational and cross-sectional study. Fifty-four patients with IBD were studied: 27 active UC, 12 inactive UC, 10 active CD, and 5 inactive CD. All patients belonged to the Inflammatory Bowel Disease Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición. We found that IL-27 gene expression was significantly higher in active UC versus inactive UC group (P = 0.015). The IL-27 mRNA expression was increased in patients with active CD compared with inactive CD disease (P = 0.035). The percentage of IL-27 immunoreactive cells was higher in active UC versus active CD patients and non-inflamed tissue controls. The IL-27 was significantly elevated in active UC and CD patients, and it was associated with disease severity.

Gastric myoelectrical activity in patients with inflammatory bowel disease

PubMed Central

Sharma, Purnima; Makharia, Govind; Yadav, Rajeev; Dwivedi, Sada Nand; Deepak, Kishore Kumar

2015-01-01

Aim: Inflammatory bowel disease is characterized by the presence of gastrointestinal motility disturbances; however alterations in the gastric myoelectrical activity have not been characterized. In this study we have recorded the gastric myoelectrical activity in patients with ulcerative colitis (UC) and Crohn's disease (CD) during their clinical remission. Materials and Methods: Gastric activity was assessed using electrogastrography (EGG) in patients with UC (n = 60), CD (n = 40) and healthy controls (n = 40). In each case, their response to water load test, as well as the dominant frequency (DF), dominant power (DP) and the power ratio (PR) of the electrical activity were recorded. Results: In healthy controls, the resting DF was 2.57 ± 1.05 cycles per minute (cpm), which decreased after water ingestion (2.34 ± 0.99 cpm; P = 0.001). Compared to healthy controls, patients with UC had low resting DF (bradygastria) (2.57 ± 1.05 vs. 1.86 ± 1.28 cpm; P = 0.01). The change in DF after water ingestion was insignificant in patients with UC and CD. Post-water ingestion, healthy controls exhibited an increase in the DP as compared to the resting state, (7.1 [2.93, 102.56] vs. 15.94 [3.92, 133.41] µV2; P = 0.02). Patients with UC (1.26 [0.14, 9.83] vs. 3.27 [0.61, 42.12] µV2) and CD (2.54 [0.44, 47.06] vs. 15.8 [0.1, 126.68] µV2) also showed a significant increase in the DP post-water ingestion. Conclusions: Patients with ulcerative colitis have altered resting gastric myoelectrical activity during the remission phase of the disease. PMID:26447103

Optical coherence tomography angiography indicates associations of the retinal vascular network and disease activity in multiple sclerosis.

PubMed

Feucht, Nikolaus; Maier, Mathias; Lepennetier, Gildas; Pettenkofer, Moritz; Wetzlmair, Carmen; Daltrozzo, Tanja; Scherm, Pauline; Zimmer, Claus; Hoshi, Muna-Miriam; Hemmer, Bernhard; Korn, Thomas; Knier, Benjamin

2018-01-01

Patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) may show alterations of retinal layer architecture as measured by optical coherence tomography. Little is known about changes in the retinal vascular network during MS. To characterize retinal vessel structures in patients with MS and CIS and to test for associations with MS disease activity. In all, 42 patients with MS or CIS and 50 healthy controls underwent retinal optical coherence tomography angiography (OCT-A) with analysis of the superficial and deep vascular plexuses and the choriocapillaries. We tested OCT-A parameters for associations with retinal layer volumes, history of optic neuritis (ON), and the retrospective disease activity. Inner retinal layer volumes correlated positively with the density of both the superficial and deep vascular plexuses. Eyes of MS/CIS patients with a history of ON revealed reduced vessel densities of the superficial and deep vascular plexuses as compared to healthy controls. Higher choriocapillary vessel densities were associated with ongoing inflammatory disease activity during 24 months prior to OCT-A examination in MS and CIS patients. Optic neuritis is associated with rarefaction of the superficial and deep retinal vessels. Alterations of the choriocapillaries might be linked to disease activity in MS.

Sex workers and the control of sexually transmitted disease.

PubMed

Day, S; Ward, H

1997-06-01

To describe and assess measures to control sexually transmitted diseases (STDs) among sex workers and their partners. A review of medical, historical and social literature, focusing on selected cases. Measures to control disease in sex workers today are often prompted by concerns about HIV transmission. However, the literature shows that prostitution varies from one place and time to another, together with the risk of sexually transmitted disease. A broad social definition of prostitution rather than a narrow reference to levels of sexual activity is important for effective disease control, as an understanding of the relation between social disadvantage and sexual activity enables the provision of occupational services that sex workers actually want and use. Social prejudice and legal sanctions cause some sex workers and their partners to avoid even the most appropriate and accessible specialist services. Therefore targeted programmes can only complement, and not replace, general measures to control STDs, which are developed for other social groups or the local population as a whole. Sex workers and sex work differ from one place to another and so a single model for STD control is inappropriate. None the less, occupational health risks suggest a general need for specialist services. Where these do not compound the disadvantages that sex workers already suffer, medical services are likely to offer significant benefits in prevention, early diagnosis, and treatment of STDs. As the stigma of prostitution leads many people to remain invisible to services, a general health infrastructure and anti-discriminatory measures will be equally important to effective disease control.

Sex workers and the control of sexually transmitted disease.

PubMed Central

Day, S; Ward, H

1997-01-01

OBJECTIVES: To describe and assess measures to control sexually transmitted diseases (STDs) among sex workers and their partners. METHODS: A review of medical, historical and social literature, focusing on selected cases. RESULTS: Measures to control disease in sex workers today are often prompted by concerns about HIV transmission. However, the literature shows that prostitution varies from one place and time to another, together with the risk of sexually transmitted disease. A broad social definition of prostitution rather than a narrow reference to levels of sexual activity is important for effective disease control, as an understanding of the relation between social disadvantage and sexual activity enables the provision of occupational services that sex workers actually want and use. Social prejudice and legal sanctions cause some sex workers and their partners to avoid even the most appropriate and accessible specialist services. Therefore targeted programmes can only complement, and not replace, general measures to control STDs, which are developed for other social groups or the local population as a whole. CONCLUSIONS: Sex workers and sex work differ from one place to another and so a single model for STD control is inappropriate. None the less, occupational health risks suggest a general need for specialist services. Where these do not compound the disadvantages that sex workers already suffer, medical services are likely to offer significant benefits in prevention, early diagnosis, and treatment of STDs. As the stigma of prostitution leads many people to remain invisible to services, a general health infrastructure and anti-discriminatory measures will be equally important to effective disease control. PMID:9306894

Coagulation and fibrinolysis in inflammatory bowel disease and in giant cell arteritis.

PubMed

Vrij, Anton A; Rijken, Joop; van Wersch, Jan W J; Stockbrügger, Reinhold W

2003-01-01

In inflammatory bowel disease (IBD), gut microvascular thrombosis as well as thromboembolic complications have repeatedly been observed. We examined the long-term course of markers of coagulation and fibrinolysis in relation to clinical disease activity. In a prospective study, prothrombin fragment 1 and 2 (F1.2), thrombin-antithrombin complex (TAT), antithrombin, D-dimer, plasmin-alpha(2)-antiplasmin complex (PAP) and plasminogen activator inhibitor-1 (PAI-1) were measured in 20 patients with Crohn's disease (CD), 18 with ulcerative colitis (UC), and 19 with giant cell arteritis during active and inactive disease, as well as in 51 controls without inflammation. Levels of F1.2, TAT, D-dimer, PAP and PAI-1 were significantly higher in active versus inactive CD and UC. However, even after 12 months of follow-up, in CD and UC the mean levels of F1.2, D-dimer and PAP were significantly higher than the levels of the controls. Levels of F1.2, D-dimer and PAP were markedly raised for a long time in clinically inactive IBD, underlining a chronic state of hypercoagulation and enhanced fibrinolysis. Copyright 2003 S. Karger AG, Basel

Sexual activity and prostate cancer risk in men diagnosed at a younger age.

PubMed

Dimitropoulou, Polyxeni; Lophatananon, Artitaya; Easton, Douglas; Pocock, Richard; Dearnaley, David P; Guy, Michelle; Edwards, Steven; O'Brien, Lynne; Hall, Amanda; Wilkinson, Rosemary; Eeles, Rosalind; Muir, Kenneth R

2009-01-01

To examine, in a case-control study, the association between the frequency of sexual activity (intercourse, masturbation, overall) and prostate cancer risk in younger men diagnosed at < or = 60 years old. In all, 431 prostate cancer cases and 409 controls participated and provided information on their sexual activity. In particular, the frequencies of intercourse and masturbation during the participants' different age decades (20s, 30s, 40s, 50s) were collected. Whereas frequent overall sexual activity in younger life (20s) increased the disease risk, it appeared to be protective against the disease when older (50s). Alone, frequent masturbation activity was a marker for increased risk in the 20s and 30s but appeared to be associated with a decreased risk in the 50s, while intercourse activity alone was not associated with the disease. These findings could imply different mechanisms by which sexual activity is involved in the aetiology of prostate cancer at different ages. Alternatively, there is a possibility of reverse causation in explaining part of the protective effect seen for men in their 50s.

A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease.

PubMed

Tovoli, Francesco; Napoli, Lucia; Negrini, Giulia; D'Addato, Sergio; Tozzi, Giulia; D'Amico, Jessica; Piscaglia, Fabio; Bolondi, Luigi

2017-05-25

Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

Survey of farmer knowledge and attitudes to endemic disease management in South Australia, with a focus on bovine viral diarrhoea (bovine pestivirus).

PubMed

Lanyon, S R; Anderson, M L; Reichel, M P

2015-05-01

We aimed to establish the attitudes of South Australian cattle farmers towards endemic animal disease prevention and control, with a particular focus on the awareness of and attitudes towards bovine viral diarrhoea (BVD). This cross-sectional postal survey involved mailing a questionnaire to all South Australian cattle owners with 35 or more head of cattle. Worms and lice were the most common animal disease concerns. Less than half of responding farmers were adequately vaccinating their herds against clostridial diseases, but 53.0% stated that they utilised quarantine procedures. Less than 20% of respondents had actively taken part in BVD educational opportunities, or had vaccinated or tested their herd for BVD; less than 20% of respondents were actively involved in any systematic control of Johne's disease. Overall, farmers' actual knowledge of BVD was lower than their perceived understanding, although their interest in BVD and its control was high. Disease prevention measures such as vaccination, quarantine and participation in systematic control schemes were used by a minority of respondents. The results suggest that respondents acknowledge BVD as an important and relevant disease, despite many believing it was not a problem in their herd. Interest in BVD appears to be high and it is likely that an education program would be well received. © 2015 Australian Veterinary Association.

Sugar-Coated PPE's, Novel Nanomaterial's and Sensing Modules for Disease and Bioterrorism Related Threats

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

Bunz, Uwe

2003-11-21

The detection and sensing of biological warfare agents (ricin, anthrax toxin), of disease agents (cholera, botulinum, and tetnus toxins, influenza virus, etc.) and of biologically active species important for national security and disease control.

The effect of positive family history of autoimmunity in juvenile idiopathic arthritis characteristics; a case control study.

PubMed

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

2013-10-01

To compare Juvenile Idiopathic Arthritis (JIA) patients with and without family history of autoimmune disease with respect to clinical features and laboratory data. 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. 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. 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.

Dissociation between active and observational learning from positive and negative feedback in Parkinsonism.

PubMed

Kobza, Stefan; Ferrea, Stefano; Schnitzler, Alfons; Pollok, Bettina; Südmeyer, Martin; Bellebaum, Christian

2012-01-01

Feedback to both actively performed and observed behaviour allows adaptation of future actions. Positive feedback leads to increased activity of dopamine neurons in the substantia nigra, whereas dopamine neuron activity is decreased following negative feedback. Dopamine level reduction in unmedicated Parkinson's Disease patients has been shown to lead to a negative learning bias, i.e. enhanced learning from negative feedback. Recent findings suggest that the neural mechanisms of active and observational learning from feedback might differ, with the striatum playing a less prominent role in observational learning. Therefore, it was hypothesized that unmedicated Parkinson's Disease patients would show a negative learning bias only in active but not in observational learning. In a between-group design, 19 Parkinson's Disease patients and 40 healthy controls engaged in either an active or an observational probabilistic feedback-learning task. For both tasks, transfer phases aimed to assess the bias to learn better from positive or negative feedback. As expected, actively learning patients showed a negative learning bias, whereas controls learned better from positive feedback. In contrast, no difference between patients and controls emerged for observational learning, with both groups showing better learning from positive feedback. These findings add to neural models of reinforcement-learning by suggesting that dopamine-modulated input to the striatum plays a minor role in observational learning from feedback. Future research will have to elucidate the specific neural underpinnings of observational learning.

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.

Unexpected arterial wall and cellular inflammation in patients with rheumatoid arthritis in remission using biological therapy: a cross-sectional study.

PubMed

Bernelot Moens, Sophie J; van der Valk, Fleur M; Strang, Aart C; Kroon, Jeffrey; Smits, Loek P; Kneepkens, Eva L; Verberne, Hein J; van Buul, Jaap D; Nurmohamed, Michael T; Stroes, Erik S G

2016-05-21

Increasing numbers of patients (up to 40 %) with rheumatoid arthritis (RA) achieve remission, yet it remains to be elucidated whether this also normalizes their cardiovascular risk. Short-term treatment with TNF inhibitors lowers arterial wall inflammation, but not to levels of healthy controls. We investigated whether RA patients in long-term remission are characterized by normalized inflammatory activity of the arterial wall and if this is dependent on type of medication used (TNF-inhibitor versus nonbiological disease-modifying antirheumatic drugs (DMARDs)). Arterial wall inflammation, bone marrow and splenic activity (index of progenitor cell activity) was assessed with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in RA patients in remission (disease activity score (DAS28) <2.6 for >6 months) and healthy controls. We performed ex vivo characterization of monocytes using flow cytometry and a transendothelial migration assay. Overall, arterial wall inflammation was comparable in RA patients (n = 23) in long-term remission and controls (n = 17). However, RA subjects using current anti-TNF therapy (n = 13, disease activity score 1.98[1.8-2.2]) have an almost 1.2-fold higher (18)F-FDG uptake in the arterial wall compared to those using DMARDs (but with previous anti-TNF therapy) (n = 10, disease activity score 2.24[1.3-2.5]), which seemed to be predominantly explained by longer duration of their rheumatic disease in a multivariate linear regression analysis. This coincided with increased expression of pro-adhesive (CCR2) and migratory (CD11c, CD18) surface markers on monocytes and a concomitant increased migratory capacity. Finally, we found increased activity in bone marrow and spleen in RA patients using anti-TNF therapy compared to those with DMARDs and controls. A subset of patients with RA in clinical remission have activated monocytes and increased inflammation in the arterial wall, despite the use of potent TNF blocking therapies. In these subjects, RA disease duration was the most important contributor to the level of arterial wall inflammation. This increased inflammatory state implies higher cardiovascular risk in these patients, who thus may require more stringent CV risk management.

Anti-nucleosome antibodies as a disease marker in systemic lupus erythematosus and its correlation with disease activity and other autoantibodies.

PubMed

Pradhan, Vandana D; Patwardhan, Manisha M; Ghosh, Kanjaksha

2010-01-01

Detection of anti-nucleosome antibodies (anti-nuc) in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. The aim of this study is to evaluate the incidence of anti-nuc antibodies and to correlate them with disease activity and its association with other autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), as well as autoantibodies to histone subfractions like H1, (H2A-H4) complex, H2B, and H3. This cross-sectional study included 100 SLE patients referred from the Rheumatology, Dermatology, and Nephrology Departments. SLE disease activity was evaluated by using SLE-Disease Activity Index (SLEDAI) score. A patient was defined as having active SLE when the SLEDAI score was more than 5.0. Fifty normal controls were also tested as a healthy control group. Anti-nuc antibodies, anti-dsDNA, and AHA were tested by Enzyme-Linked Immunosorbent Assay (ELISA) and ANA was detected by an indirect immunofluorescence test. All patients studied were in an active stage of disease and were untreated, of which 44 patients had renal biopsy-proven kidney involvement, which was categorized as lupus nephritis (LN) and 56 patients did not show any renal manifestations (SLE without LN). Anti-nuc antibodies were positive in 88%, anti-dsDNA in 80%, and AHA in 38% of the cases. ANA was positive in all SLE patients studied. None of the normal controls was found to be positive for these antibodies. Although a slightly higher incidence of autoantibodies were noted in LN, there was no statistical difference noted between LN and SLE without LN groups for anti-nuc and anti-dsDNA antibodies (p > 0.05). A higher incidence of autoantibodies to ANA specificities were noted in anti-nuc positive cases, but there was no statistical difference between anti-nuc positive and anti-nuc negative cases for ANA specificities among LN and SLE without nephritis groups (p > 0.05). Anti-nuc antibody detection could be a better tool for the diagnosis of SLE. Although there was no significant difference in LN and SLE without LN groups, this study suggests that anti-nuc detection can be useful as an additional disease activity marker to other laboratory tests.

Expression of autophagy related genes mTOR, Becline-1, LC3 and p62 in the peripheral blood mononuclear cells of systemic lupus erythematosus.

PubMed

Wu, Zhen-Zhen; Zhang, Jun-Jun; Gao, Cong-Cong; Zhao, Man; Liu, Sheng-Yun; Gao, Guan-Min; Zheng, Zhao-Hui

2017-01-01

To determine the expression of mTOR, Becline-1, LC3 and p62 in the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) and assess their relationship with disease activity and immunologic features. The expression of mTOR, Becline-1, LC3 and p62 was detected by RT-PCR in 81 SLE subjects and 86 age- and sex-matched healthy controls. Data regarding demographics and clinical parameters were collected. Disease activity of SLE was evaluated according to the SLE Disease Activity Index (SLEDAI) score. Independent sample t-test was used to analyze the expression of mTOR, Becline-1, LC3, and p62 in the two groups. Pearson's or Spearman's correlation was performed to analyze their relationship with disease activity and immunologic features. The mean levels of Becline-1, LC3 and p62 mRNA were significantly higher in SLE patients than the controls (9.96×10 -4 vs 7.38×10 -4 for Becline-1 with P <0.001; 4.04×10 -5 vs 2.62×10 -5 for LC3 with P <0.001; 9.51×10 -4 vs 7.59×10 -4 for p62 with P =0.008). However, the levels of mTOR mRNA in SLE patients were not significantly different from that in controls. Correlation analysis showed that Becline-1, LC3 and p62 mRNA levels correlated positively with SLEDAI, IgG and ds-DNA, negatively with C3. Our results suggested that autophagosomes formation were activated and their degradation were blocked in SLE. Moreover, the maintenance of autophagy balance can improve disease activity and immune disorders in SLE patients.

Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.

PubMed

Huffman, Kim M; Jessee, Ryan; Andonian, Brian; Davis, Brittany N; Narowski, Rachel; Huebner, Janet L; Kraus, Virginia B; McCracken, Julie; Gilmore, Brian F; Tune, K Noelle; Campbell, Milton; Koves, Timothy R; Muoio, Deborah M; Hubal, Monica J; Kraus, William E

2017-01-23

To identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA. Persons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, body mass index (BMI), and physical activity (n = 51) underwent assessment of disease activity, disability, pain, physical activity and thigh muscle biopsies. Muscle tissue was used for measurement of pro-inflammatory markers, transcriptomics, and comprehensive profiling of metabolic intermediates. Groups were compared using mixed models. Bivariate associations were assessed with Spearman correlation. Compared to controls, patients with RA had 75% greater muscle concentrations of IL-6 protein (p = 0.006). In patients with RA, muscle concentrations of inflammatory markers were positively associated (p < 0.05 for all) with disease activity (IL-1β, IL-8), disability (IL-1β, IL-6), pain (IL-1β, TNF-α, toll-like receptor (TLR)-4), and physical inactivity (IL-1β, IL-6). Muscle cytokines were not related to corresponding systemic cytokines. Prominent among the gene sets differentially expressed in muscles in RA versus controls were those involved in skeletal muscle repair processes and glycolytic metabolism. Metabolic profiling revealed 46% higher concentrations of pyruvate in muscle in RA (p < 0.05), and strong positive correlation between levels of amino acids involved in fibrosis (arginine, ornithine, proline, and glycine) and disability (p < 0.05). RA is accompanied by broad-ranging molecular alterations in skeletal muscle. Analysis of inflammatory markers, gene expression, and metabolic intermediates linked disease-related disruptions in muscle inflammatory signaling, remodeling, and metabolic programming to physical inactivity and disability. Thus, skeletal muscle dysfunction might contribute to a viscous cycle of RA disease activity, physical inactivity, and disability.

Autonomic Dysfunction Correlates with Clinical and Inflammatory Activity in Patients with Crohn's Disease.

PubMed

Engel, Tal; Ben-Horin, Shomron; Beer-Gabel, Marc

2015-10-01

Autonomic dysfunction has been implicated in Crohn's disease (CD). We aimed to investigate heart rate variability (HRV) as a marker of possible autonomic imbalance in patients with CD. Thirty patients with CD and 30 age- and gender-matched healthy controls were enrolled in a prospective cohort study and underwent HRV study. Anxiety level was scored using the STAI questionnaire and CD clinical activity was assessed by Harvey-Bradshaw index. Blood tests including inflammatory markers were obtained for all participants. CD subjects had lower mean blood pressure (85.51 ± 11.07 mm Hg, 91.51 ± 6.99, P = 0.015) and albumin and significantly higher CRP and IL-6 compared with controls (P < 0.002 for all comparisons). Mean HRV values of very low-frequency power and low-frequency power components were significantly lower among CD subjects (P = 0.038 and 0.027, respectively), implying a predominant sympathetic tone. Anxiety level scores were significantly higher among patients with CD for both state anxiety (P = 0.001) and trait anxiety (P < 0.0001). However, patients with active disease had similar anxiety scores as patients in remission, yet had a significantly lower BMI, lower albumin level, and higher CRP and IL-6 levels (P < 0.05 for all comparisons). Moreover, despite similar anxiety scores, patients with active disease had higher pulse rate (P = 0.02) and lower HRV indexes, which correlated with albumin levels(r = 0.7, P = 0.001). Although patients with CD have higher anxiety levels compared with controls, they exhibit depressed HRV independent of this anxiety state and in direct correlation with disease activity and inflammatory markers. These observations suggest an inherent imbalance of autonomic function associated with active inflammation.

Increased serum APRIL differentially correlates with distinct cytokine profiles and disease activity in systemic lupus erythematosus patients.

PubMed

Boghdadi, Ghada; Elewa, Enass A

2014-09-01

Cytokines play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Among the cytokines that regulate B cell homeostasis is a proliferation-inducing ligand (APRIL). This study aimed to determine whether serum levels of APRIL are raised in patients with SLE and correlate with disease activity or proinflammatory cytokines production, or both. Serum APRIL, interleukin-17 (IL-17), IL-4 and interferon gamma (IFN-γ) levels were measured in forty patients with SLE and 30 healthy controls. Disease activity was assessed by SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Serum APRIL levels were significantly higher in patients with SLE than in healthy controls. Positive correlation was found between serum APRIL levels and total SLEDAI score and anti-dsDNA antibody titers. Moreover, serum APRIL levels was significantly higher in patients with arthritis, mucocutaneous manifestations and proteinuria. APRIL is increased in patients with active SLE accompanying the increase of IL-17 and IFN-γ. Significant positive correlations between serum levels of APRIL and IL-17 and IFN-γ and a negative correlation between serum levels of APRIL and IL-4 were found. The results suggest that APRIL may be an important marker of disease activity in patients with SLE. We provide the analyses of APRIL levels in patients with SLE, suggesting new tools for the diagnosis, prognosis and possible therapeutic management of SLE.

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.

Elevated Expression of the NLRP3 Inflammasome and Its Correlation with Disease Activity in Adult-onset Still Disease.

PubMed

Hsieh, Chia-Wei; Chen, Yi-Ming; Lin, Chi-Chen; Tang, Kuo-Tung; Chen, Hsin-Hua; Hung, Wei-Ting; Lai, Kuo-Lung; Chen, Der-Yuan

2017-08-01

The dysregulation of the NLRP3 (NLR containing a pyrin domain) inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease (AOSD) is regarded as an autoinflammatory disease. However, the pathogenic involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in AOSD are currently unknown. The mRNA expression of NLRP3 inflammasome signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD and 14 healthy subjects was determined using quantitative-PCR (qPCR). The changes in mRNA and protein levels of NLRP3 inflammasome signaling in PBMC treated with the potential activator [imiquimod (IMQ)] or inhibitor of NLRP3 were evaluated using qPCR and immunoblotting, respectively. The supernatant levels of interleukin (IL)-1β and IL-18 were determined by ELISA. Significantly higher mRNA levels of NLRP3 inflammasome signaling were observed in patients with AOSD compared with healthy controls. NLRP3 expressions were positively correlated with disease activity in patients with AOSD. IMQ (an effective Toll-like receptor 7 ligand; 10 µ g/ml and 25 µ g/ml) stimulation of PBMC from patients with AOSD induced dose-dependent increases of mRNA expression of NLRP3 (mean ± standard error of the mean, 2.06 ± 0.46 and 6.05 ± 1.84, respectively), caspase-1 (1.81 ± 0.23 and 4.25 ± 0.48), IL-1β (5.68 ± 1.51 and 12.13 ± 3.71), and IL-18 (2.32 ± 0.37 and 4.81 ± 0.51) compared with controls (all p < 0.005). IMQ stimulation of PBMC from patients similarly induced greater increases in protein expressions of NLRP3 inflammasome compared with controls. The protein expressions of NLRP3, IL-1β, and IL-18 on PBMC significantly decreased after treatment with NLRP3 inhibitor in patients with AOSD. Increased expression of NLRP3 inflammasome and its positive correlation with disease activity in AOSD suggest its involvement in disease pathogenesis. IMQ upregulated expressions of NLRP3 inflammasome signaling, and IMQ might be an activator of NLRP3 inflammasome in AOSD.

Habitual physical activity in mitochondrial disease.

PubMed

Apabhai, Shehnaz; Gorman, Grainne S; Sutton, Laura; Elson, Joanna L; Plötz, Thomas; Turnbull, Douglass M; Trenell, Michael I

2011-01-01

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype. Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. Patients with mitochondrial disease had significantly lower levels of physical activity in comparison to matched people without mitochondrial disease (steps/day; 6883±3944 vs. 9924±4088, p = 0.001). 78% of the mitochondrial disease cohort did not achieve 10,000 steps per day and 48% were classified as overweight or obese. Mitochondrial disease was associated with less breaks in sedentary activity (Sedentary to Active Transitions, % per day; 13±0.03 vs. 14±0.03, p = 0.001) and an increase in sedentary bout duration (bout lengths/fraction of total sedentary time; 0.206±0.044 vs. 0.187±0.026, p = 0.001). After adjusting for covariates, higher physical activity was moderately associated with lower clinical disease burden (steps/day; r(s) = -0.49; 95% CI -0.33, -0.63, P<0.01). There were no systematic differences in physical activity between different genotypes mitochondrial disease. These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease.

Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases.

PubMed

Broccolo, Francesco; Drago, Francesco; Cassina, Giulia; Fava, Andrea; Fusetti, Lisa; Matteoli, Barbara; Ceccherini-Nelli, Luca; Sabbadini, Maria Grazia; Lusso, Paolo; Parodi, Aurora; Malnati, Mauro S

2013-11-01

Viral infections have been associated with autoimmune connective tissue diseases. To evaluate whether active infection by Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6, -7, -8, as well as parvovirus B19 (B19V) occur in patients with autoimmune connective tissue diseases, viral DNA loads were assessed in paired samples of serum and peripheral blood mononuclear cells (PBMCs) of 115 patients affected by different disorders, including systemic sclerosis, systemic, and discoid lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Two additional groups, patients affected by inflammatory diseases (n=51) and healthy subjects (n=58) were studied as controls. The titers of anti-HHV-6 and anti-EBV antibodies were also evaluated. Cell-free HHV-6 serum viremia was detected in a significantly higher proportion of connective tissue diseases patients compared to controls (P<0.0002); a significant association between HHV-6 reactivation and the active disease state was found only for lupus erythematosus (P=0.021). By contrast, the rate of cell-free EBV viremia was similar in patients and controls groups. Cell-free CMV, HHV-8, and B19V viremia was not detected in any subject. Anti-HHV-6 and anti-EBV early antigen IgG titers were both significantly higher in autoimmune diseases patients as compared to healthy controls, although they were not associated with the presence of viremia. EBV, HHV-6, -7 prevalence and viral load in PBMCs of patients with connective tissue diseases and controls were similar. These data suggest that HHV-6 may act as a pathogenic factor predisposing patients to the development of autoimmune connective tissue diseases or, conversely, that these disorders may predispose patients to HHV-6 reactivation. © 2013 Wiley Periodicals, Inc.

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

Regulatory T cell subsets in children with systemic lupus erythematosus.

PubMed

Eltayeb, Azza A; Sayed, Douaa M; Afifi, Noha A; Ibrahim, Maggie A; Sheref, Tahra M

2014-08-01

The aim of this work was to quantify CD4(+)CD25(+)Foxp3(+) T cells (Tregs) in Egyptian children with SLE and to correlate these findings with their disease activity scores and drug therapy. We enrolled 37 Egyptian children with active SLE. Disease activity was assessed by measuring serum levels of anti-dsDNA antibody and by the SLEDAI scores. Twenty healthy children were also enrolled as normal controls. The CD4+CD25+, CD4+CD25(bright), and CD4+CD25(dim) cells in patients were significantly increased in comparison to controls. There was no significant difference in the Foxp3 gated on CD4+CD25(bright) and CD4+CD25(dim), but there was a significant increase when gated on CD4+CD25- and whole CD4+ cells in patients than controls. There was no significant difference among patients with different degrees of activity on different lines of treatments and their outcomes as regards all studied values. There was no significant correlation between SLEDAI score and any of the studied parameters except for a significant negative correlation with gated lymphocytes. There is increased expression of Foxp3 in CD4+ T cells mostly CD25- in Egyptian children with active SLE under corticosteroid treatment regardless of disease activity.

A mineral seed coating for control of seedling diseases of alfalfa suitable for organic production systems

USDA-ARS?s Scientific Manuscript database

Most alfalfa seed is treated with the systemic fungicide mefenoxam (Apron XL) for control of soilborne seedling diseases. However, Apron XL does not have activity against Aphanomyces euteiches, the causal agent of Aphanomyces root rot (ARR), which is an important component of the alfalfa root rot co...

[Institutional insertion of Chagas' disease control].

PubMed

Silveira, Antônio Carlos; Pimenta, Fabiano

2011-01-01

After the starting of the Center for studies and prophylaxis of Chagas disease in 1943, with the help of Oswaldo Cruz Foundation, in the city of Bambuí, state of Minas Gerais, technological and methodological basis for the extensive control of the disease were conceived. A main step to achieve success was the introduction of a new insecticide (gammexane, P 530) and the demonstration of its efficacy in the vector control. A consequence of these improvements was the official inauguration of the first prophylactic campaign for Chagas disease in Brazil, held in Uberaba in May, 1950. Even with the knowledge of how to control the vectorial transmission, financial resources were not available by this time, at a necessary degree to make it both regularly and in all the affected area. The institutional allocation of these activities is useful to understand the low priority given to them at that time. Several national services were created in 1941, for diseases as malaria, pest, smallpox, among others, but Chagas was included in a group of diseases with lower importance, inside a Division of Sanitary Organization. In 1956, the National Department of Rural endemies (DNERu) allocate all the major endemic diseases in a single institution, however this was not translated in an implementation program for the control of Chagas disease. After profound changes at the Ministry of Health, in 1970, the Superintendência de Campanhas de Saúde Pública (SUCAM) was in charge of all rural endemies including Chagas disease, which now could compete with other diseases transmitted by vectors, formerly priorities, included in the National Division. With this new status, more funds were available, as well as redistribution of personnel and expenses from the malaria program to the vectorial control of Chagas disease. In 1991 the Health National foundation was created to substitute SUCAM in the control of endemic diseases and it included all the units of the Ministry of Health related to epidemiology and disease control. By this time a new tendency for decentralization of these programs was clear. In the case of diseases transmitted by vectors, this was a major difference from the campaign model so far employed. At the same time, the Initiative for the South Cone countries for the control of Chagas disease started, sharing techniques among the countries of this region, as well as establishing similar objectives and trends, what possible helped to maintain Chagas disease as a priority among all the public health issues. From 2003 on, all activities for control of the disease at a national level are under responsibility of the Secretary of Health Surveillance of the Ministry of Health.

Relationship of work disability between the disease activity, depression and quality of life in patients with ankylosing spondylitis.

PubMed

Sağ, Sinem; Nas, Kemal; Sağ, Mustafa Serdar; Tekeoğlu, İbrahim; Kamanlı, Ayhan

2018-02-02

In this study, our objective was to determine the work productivity and work disability of the patients with ankylosing spondylitis (AS) and to investigate the relation of these parameters with disease activity, anxiety, depression and quality of life. Fifty patients with the diagnosis of AS and 30 healthy control were included in the study. In patients with AS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to evaluate the disease activity; Bath Ankylosing Spondylitis Metrology Index (BASMI) was used to evaluate the spinal mobility and Bath Ankylosing Spondylitis Functional Index (BASFI) was used to determine the functional status. In addition, the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire and The Short Form (SF-36) Health Survey was used to evaluate the health status, Hospital Anxiety and Depression Scale (HADS) was used for the evaluation of depression and anxiety and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem v2.0 (WPAI:SHP) was used to evaluate the work productivity. In AS patients duration of disease at the diagnosis was 7.24 ± 6.23 years. The time lost at work due to the disease, decrease in the work productivity and impairment in the time off daily activities were worse in the patient group compared with the control group (p< 0.05). The impairment in the work productivity was correlated with BASDAI and depression; difficulty in time-off activities was correlated with BASFI and anxiety and depression was correlated with BASDAI (p< 0.05). While the impairment in work productivity was correlated with the subparameter vitality in SF-36, difficulty in time off activities was correlated with general health status, social functions, vitality and mental health (p< 0.05). In this study, we determined that AS had a significant influence on the working conditions and the factors related to the disease had a significant correlation with work productivity. Factors related to the psychology and the disease were also correlated with the working conditions.

Impact of psoriasis flare and remission on quality of life and work productivity: a real-world study in the USA.

PubMed

Korman, N J; Zhao, Y; Roberts, J; Pike, J; Sullivan, E; Tsang, Y; Karagiannis, T

2016-07-15

Although psoriasis patients often report a negative impact on health-related quality of life (HRQoL) and work productivity, less is known about how disease burden varies between periods of flare and remission. The aim of this study was tocompare HRQoL and work productivity by disease activity level. Data were extracted from Adelphi 2011/2013 Disease Specific Programmes, two real world surveys of US dermatologists and psoriasis patients. HRQoL was measured using the EuroQOL 5-Dimension Health Questionnaire (EQ-5D) and Dermatology Life Quality Index (DLQI). Work productivity was measured using the Work Productivity Activity index (WPAI). Three levels of disease activity were constructed based on physician reports: remission, active not flaring, active, and flaring. Multivariable regression analyses explored the relationship between disease activity, HRQoL and work productivity, controlling for differences in demographics and comorbidities. Out of 681 psoriasis patients 24% were in remission, 62% had active disease without flaring, and 15% experienced active disease and were currently flaring. Greater disease activity was associated with worse HRQoL. EQ-5D scores decreased with more active disease (remission vs. active not flaring vs. active and flaring: 0.93 vs. 0.90 vs. 0.82; p<0.05), while DLQI scores increased (remission vs. active not flaring vs. active and flaring: 2.0 vs. 5.00 vs. 8.7; p<0.05). WPAI scores increased with disease activity indicating increased productivity loss (remission vs. active not flaring vs. active and flaring: 5.9 vs. 14.8 vs. 26.9; p<0.05). The same trends were confirmed by multivariable regression analyses.

Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease.

PubMed

Passos, Lívia Silva Araújo; Villani, Fernanda Nobre Amaral; Magalhães, Luísa Mourão Dias; Gollob, Kenneth J; Antonelli, Lis Ribeiro do Vale; Nunes, Maria Carmo Pereira; Dutra, Walderez Ornelas

2016-09-15

The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon γ (IFN-γ) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN-γ by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Smelling the Diagnosis: The Electronic Nose as Diagnostic Tool in Inflammatory Arthritis. A Case-Reference Study.

PubMed

Brekelmans, Marjolein P; Fens, Niki; Brinkman, Paul; Bos, Lieuwe D; Sterk, Peter J; Tak, Paul P; Gerlag, Daniëlle M

2016-01-01

To investigate whether exhaled breath analysis using an electronic nose can identify differences between inflammatory joint diseases and healthy controls. In a cross-sectional study, the exhaled breath of 21 rheumatoid arthritis (RA) and 18 psoriatic arthritis (PsA) patients with active disease was compared to 21 healthy controls using an electronic nose (Cyranose 320; Smiths Detection, Pasadena, CA, USA). Breathprints were analyzed with principal component analysis, discriminant analysis, and area under curve (AUC) of receiver operating characteristics (ROC) curves. Volatile organic compounds (VOCs) were identified by gas chromatography and mass spectrometry (GC-MS), and relationships between breathprints and markers of disease activity were explored. Breathprints of RA patients could be distinguished from controls with an accuracy of 71% (AUC 0.75, 95% CI 0.60-0.90, sensitivity 76%, specificity 67%). Breathprints from PsA patients were separated from controls with 69% accuracy (AUC 0.77, 95% CI 0.61-0.92, sensitivity 72%, specificity 71%). Distinction between exhaled breath of RA and PsA patients exhibited an accuracy of 69% (AUC 0.72, 95% CI 0.55-0.89, sensitivity 71%, specificity 72%). There was a positive correlation in RA patients of exhaled breathprints with disease activity score (DAS28) and number of painful joints. GC-MS identified seven key VOCs that significantly differed between the groups. Exhaled breath analysis by an electronic nose may play a role in differential diagnosis of inflammatory joint diseases. Data from this study warrant external validation.

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

A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design.

PubMed

Khanna, Reena; Bouguen, Guillaume; Feagan, Brian G; DʼHaens, Geert; Sandborn, William J; Dubcenco, Elena; Baker, K Adam; Levesque, Barrett G

2014-10-01

Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties. Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

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; Valeyre, Dominique; 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

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. 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. 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. 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. 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.

Larvicidal and Adulticidal Activity of Chroman and Chromene Analogues against Susceptible and Permethrin-Resistant Mosquito Strains.

PubMed

Meepagala, Kumudini M; Estep, Alden S; Becnel, James J

2016-06-22

Mosquitoes play a major role as vectors that transmit parasitic and viral diseases worldwide, especially in tropical and subtropical countries. Mosquito borne diseases not only affect humans but they also affect livestock in many parts of the world. They carry diseases that are lethal to dogs and horses. Dog heartworm disease (Dirofilaria immitis) is a parasitic disease spread through mosquitoes. This disease is not limited to dogs, but it can affect other animals and humans as well. Eastern equine encephalitis (EEE) and West Nile virus (WNV) are also mosquito borne diseases that affect the central nervous system of horses and cause severe complications and death. Emergence of resistance among mosquitoes to current pesticides has increased the importance of the search for alternate compounds that are effective and environmentally benign with diverse modes of actions than those that are commercially available. Aedes aegypti mosquitoes are the primary vector for transmission of Zika viral fever, yellow fever, dengue fever, and chikungunya. Mosquito control is currently the best strategy to prevent mosquito borne diseases. There are numerous approaches for control of potentially dangerous mosquito populations. These approaches include the use of adulticides (insecticides), larvicides, and, to a limited extent, the use of repellents. Our previous studies have shown the mosquito repellent activity of chromenes. In the present study, we demonstrate larvicidal and adulticidal activity of chroman and chromene analogues against a permethrin susceptible laboratory strain as well as activity against a permethrin-resistant strain of Aedes aegypti.

Physical functioning in patients with ankylosing spondylitis: comparing approaches of experienced ability with self-reported and objectively measured physical activity.

PubMed

van Genderen, Simon; van den Borne, Carlie; Geusens, Piet; van der Linden, Sjef; Boonen, Annelies; Plasqui, Guy

2014-04-01

Physical functioning can be assessed by different approaches that are characterized by increasing levels of individual appraisal. There is insufficient insight into which approach is the most informative in patients with ankylosing spondylitis (AS) compared with control subjects. The objective of this study was to compare patients with AS and control subjects regarding 3 approaches of functioning: experienced ability to perform activities (Bath Ankylosing Spondylitis Functional Index [BASFI]), self-reported amount of physical activity (PA) (Baecke questionnaire), and the objectively measured amount of PA (triaxial accelerometer). This case-control study included 24 AS patients and 24 control subjects (matched for age, gender, and body mass index). Subjects completed the BASFI and Baecke questionnaire and wore a triaxial accelerometer. Subjects also completed other self-reported measures on disease activity (Bath AS Disease Activity Index), fatigue (Multidimensional Fatigue Inventory), and overall health (EuroQol visual analog scale). Both groups included 14 men (58%), and the mean age was 48 years. Patients scored significantly worse on the BASFI (3.9 vs 0.2) than their healthy peers, whereas PA assessed by Baecke and the accelerometer did not differ between groups. Correlations between approaches of physical functioning were low to moderate. Bath Ankylosing Spondylitis Functional Index was associated with disease activity (r = 0.49) and physical fatigue (0.73) and Baecke with physical and activity related fatigue (r = 0.54 and r = 0.54), but total PA assessed by accelerometer was not associated with any of these experience-based health outcomes. Different approaches of the concept physical functioning in patients with AS provide different information. Compared with matched control subjects, patients with AS report more difficulties but report and objectively perform the same amount of PA.

Role of interleukin-23 as a biomarker in rheumatoid arthritis patients and its correlation with disease activity.

PubMed

Zaky, Doaa S E; El-Nahrery, Eslam M A

2016-02-01

IL-23 is a pro-inflammatory cytokine belonging to the IL-12 cytokine family. IL-23 is essential for the differentiation of Th17 lymphocytes, a subtype of T lymphocyte implicated in chronic inflammatory/autoimmune mediated diseases. Experimental models of arthritis and clinical indications have highlighted an important role for Th17 lymphocytes in the pathogenesis of RA. However the role and mechanism of action of IL-23 in the pathogenesis of RA are still not fully understood. This study was conducted to assess the level of IL-23 in patients with RA as well as the relationship between the IL-23 level and disease activity. The study includes 77 patients with RA fulfilling the American College of Rheumatology (ACR) revised criteria for diagnosis of RA as well as 25 age and sex matched healthy subjects as controls. Patients were divided according to disease activity into four groups: DAS 28 score (˂ 2.6), 10 patients in remission, DAS 28 score between 2.6-3.2, 10 patients with low disease activity, DAS 28 score ranges between (3.2-5.1), 30 patients with moderate disease activity and DAS 28 score (˂ 5.1), 27 patients with High disease activity. Disease activity were determined by the 28-joint disease activity score (DAS 28). Anti-citrullinated protein antibodies (ACPA) was done. The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA). Serum level of IL-23 was significantly elevated in RA patients (78.92±52.47) compared to control group (33.34±3.99) (P<0.001). However, no correlations were found between IL-23 and DAS 28 score, and other patients characteristics. Our results imply that IL-23 may potentially play a role in the pathogenesis of RA and may be a useful biomarker for the diagnosis of this disease. Targeting the IL-23 cytokine may provide a new therapeutic approach in the treatment of RA. Copyright © 2015 Elsevier B.V. All rights reserved.

Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities

PubMed Central

Rahmani, Arshad H; shabrmi, Fahad M Al; Aly, Salah M

2014-01-01

The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities. PMID:25057339

The Tie2 receptor antagonist angiopoietin-2 in systemic lupus erythematosus: its correlation with various disease activity parameters.

PubMed

Salama, Maysa K; Taha, Fatma M; Safwat, Miriam; Darweesh, Hanan E A; Basel, Mohamed El

2012-01-01

Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage. to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity. The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins. The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p < 0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE. Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.

Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson's disease.

PubMed

Zhu, Dan; Liu, Gui-you; Lv, Zheng; Wen, Shi-rong; Bi, Sheng; Wang, Wei-zhi

2014-10-01

Early studies had suggested that vitamin D intake was inversely associated with neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis. However, the associations of vitamin D intake and outdoor activities with Parkinson's disease (PD) are still unclear, so this study is to evaluate these relationships from a case-control study in elderly Chinese. The study population involved 209 cases with new onsets of PD and 210 controls without neurodegenerative diseases. The data on dietary vitamin D and outdoor activities were collected using a food-frequency questionnaire and self-report questionnaire. Multivariable logistic regressions were used to examine the associations between dietary outdoor activities, vitamin D intake and PD. Adjustment was made for sex, age, smoking, alcohol use, education, and body mass index (BMI). Adjusted odds ratios (ORs) for PD in quartiles for outdoor physical activity were 1 (reference), 0.739 (0.413, 1.321), 0.501 (0.282, 0.891), and 0.437 (0.241, 0.795), respectively (P=0.002 for trend). Adjusted ORs for PD in quartiles for total vitamin D intake were 1 (reference), 0.647 (0.357, 1.170), 0.571 (0.318, 1.022), and 0.538 (0.301, 0.960), respectively (P=0.011 for trend). Our study suggested that outdoor activity and total vitamin D intake were inversely associated with PD, and outdoor activity seems to be more significantly associated with decreased risk for PD.

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

PubMed

Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

2018-01-01

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Rivastigmine is Associated with Restoration of Left Frontal Brain Activity in Parkinson’s Disease

PubMed Central

Possin, Katherine L.; Kang, Gail A.; Guo, Christine; Fine, Eric M.; Trujillo, Andrew J.; Racine, Caroline A.; Wilheim, Reva; Johnson, Erica T.; Witt, Jennifer L.; Seeley, William W.; Miller, Bruce L.; Kramer, Joel H.

2013-01-01

Objective To investigate how acetylcholinesterase inhibitor (ChEI) treatment impacts brain function in Parkinson’s disease (PD). Methods Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after three months of ChEI treatment and were compared to 15 age and sex matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low frequency fluctuations. Results At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (e.g., caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (e.g., lateral prefrontal cortex), and episodic memory (e.g., precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased post-treatment compared to baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. Conclusions PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared to controls, and rivastigmine is associated with performance-related normalization in left frontal cortex function. PMID:23847120

A Statewide Management Information System for the Control of Sexually Transmitted Diseases

PubMed Central

Fichtner, Ronald R.; Blount, Joseph H.; Spencer, Jack N.

1983-01-01

The persistent endemicity in the U.S. of infectious syphilis and gonorrhea, together with increasing diagnoses of gonococcal-related pelvic inflammatory disease in women and genital herpes infections, have intensified pressures on state and local VD control programs to measure, analyze, and interpret the distribution and transmission of these and other sexually transmitted diseases. In response, the Division of Venereal Disease Control (DVDC) of the Centers for Disease Control (CDC) is participating in the development of three state-wide, prototype sexually transmitted disease (STD) management information systems. A systems analysis of a typical state-wide STD control program indicated that timely, comprehensive, informational support to public health managers and policy makers should be combined with rapid, direct support of program activities using an on-line, integrated data base, computer system with telecommunications capability. This methodology uses a data base management system, query facility for ad hoc inquiries, custom design philosophies, but utilizes distinct hardware and software implementations.

Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity.

PubMed

Slobodin, Gleb; Ahmad, Mohammad Sheikh; Rosner, Itzhak; Peri, Regina; Rozenbaum, Michael; Kessel, Aharon; Toubi, Elias; Odeh, Majed

2010-01-01

The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc). Ten patients with SSc donated 20ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4(+) cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-beta and IL-10 by activated CD4(+) cells was measured by ELISA in culture supernatants. The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r=0.71, p=0.034 and r=0.67, p=0.044, respectively). ELISA-measured production of TGF-beta and IL-10 by CD4(+) cells was similar in patients and controls. Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-beta or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed. 2010 Elsevier Inc. All rights reserved.

Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative Treatment▿

PubMed Central

Sahiratmadja, Edhyana; Alisjahbana, Bachti; de Boer, Tjitske; Adnan, Iskandar; Maya, Anugrah; Danusantoso, Halim; Nelwan, Ronald H. H.; Marzuki, Sangkot; van der Meer, Jos W. M.; van Crevel, Reinout; van de Vosse, Esther; Ottenhoff, Tom H. M.

2007-01-01

Pro- and anti-inflammatory cytokines and their signaling pathways play key roles in protection from and pathogenesis of mycobacterial infection, and their balance and dynamic changes may control or predict clinical outcome. Peripheral blood cells' capacity to produce proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin-12/23p40 [IL-12/23p40], and gamma interferon [IFN-γ]) and anti-inflammatory (IL-10) cytokines in response to Mycobacterium tuberculosis or unrelated stimuli (lipopolysaccharide, phytohemagglutinin) was studied in 93 pulmonary tuberculosis (TB) patients and 127 healthy controls from Indonesia. Their cells' ability to respond to IFN-γ was examined to investigate whether M. tuberculosis infection can also inhibit IFN-γ receptor (IFN-γR) signaling. Although there was interindividual variability in the observed responses, the overall results revealed that M. tuberculosis-induced TNF-α and IFN-γ levels showed opposite trends. Whereas TNF-α production was higher in active-TB patients than in controls, IFN-γ production was strongly depressed during active TB, correlated inversely with TB disease severity, and increased during therapy. By contrast, mitogen-induced IFN-γ production, although lower in patients than in controls, did not change during treatment, suggesting an M. tuberculosis-specific and reversible component in the depression of IFN-γ. Depressed IFN-γ production was not due to decreased IL-12/IL-23 production. Importantly, IFN-γ-inducible responses were also significantly depressed during active TB and normalized during treatment, revealing disease activity-related and reversible impairment in IFN-γR signaling in TB. Finally, IFN-γ/IL-10 ratios significantly correlated with TB cure. Taken together, these results show that M. tuberculosis-specific stimulation of IFN-γ (but not TNF-α) production and IFN-γR signaling are significantly depressed in active TB, correlate with TB disease severity and activity, and normalize during microbiological TB cure. The depression of both IFN-γ production and IFN-γR signaling may synergize in contributing to defective host control in active TB. PMID:17145950

[Strategies and development of quality assurance and control in the ELSA-Brasil].

PubMed

Schmidt, Maria Inês; Griep, Rosane Härter; Passos, Valéria Maria; Luft, Vivian Cristine; Goulart, Alessandra Carvalho; Menezes, Greice Maria de Souza; Molina, Maria del Carmen Bisi; Vigo, Alvaro; Nunes, Maria Angélica

2013-06-01

The ELSA-Brasil (Estudo Longitudinal de Saúde do Adulto - Brazilian Longitudinal Study for Adult Health) is a cohort study composed of 15,105 adults followed up in order to assess the development of chronic diseases, especially diabetes and cardiovascular disease. Its size, multicenter nature and the diversity of measurements required effective and efficient mechanisms of quality assurance and control. The main quality assurance activities (those developed before data collection) were: careful selection of research instruments, centralized training and certification, pretesting and pilot studies, and preparation of operation manuals for the procedures. Quality control activities (developed during data collection and processing) were performed more intensively at the beginning, when routines had not been established yet. The main quality control activities were: periodic observation of technicians, test-retest studies, data monitoring, network of supervisors, and cross visits. Data that estimate the reliability of the obtained information attest that the quality goals have been achieved.

Does the perception that God controls health outcomes matter for health behaviors?

PubMed

Karvinen, Kristina H; Carr, Lucas J

2014-04-01

The purpose of this study was to examine the associations between God Locus of Health Control, health behaviors, and beliefs utilizing a cross-sectional online survey (N = 549). Results indicated that God Locus of Health Control was correlated with alcohol use, physical activity, perceived risk of chronic disease, and beliefs that poor health behaviors contribute to chronic disease (all p values < .05). Multiple regression analyses including covariates and other locus of control variables revealed that God Locus of Health Control was only an independent correlate of the belief that physical inactivity contributed to chronic disease. Insights from this study may be important for future faith-based health behavior change interventions.

Charting a Path to Location Intelligence for STD Control.

PubMed

Gerber, Todd M; Du, Ping; Armstrong-Brown, Janelle; McNutt, Louise-Anne; Coles, F Bruce

2009-01-01

This article describes the New York State Department of Health's GeoDatabase project, which developed new methods and techniques for designing and building a geocoding and mapping data repository for sexually transmitted disease (STD) control. The GeoDatabase development was supported through the Centers for Disease Control and Prevention's Outcome Assessment through Systems of Integrated Surveillance workgroup. The design and operation of the GeoDatabase relied upon commercial-off-the-shelf tools that other public health programs may also use for disease-control systems. This article provides a blueprint of the structure and software used to build the GeoDatabase and integrate location data from multiple data sources into the everyday activities of STD control programs.

Towards effective prevention and control of helminth neglected tropical diseases in the Western Pacific Region through multi-disease and multi-sectoral interventions.

PubMed

Nakagawa, Jun; Ehrenberg, John P; Nealon, Joshua; Fürst, Thomas; Aratchige, Padmasiri; Gonzales, Glenda; Chanthavisouk, Chitsavang; Hernandez, Leda M; Fengthong, Tayphasavanh; Utzinger, Jürg; Steinmann, Peter

2015-01-01

Neglected tropical diseases (NTDs) cause serious health, social and economic burdens in the countries of the World Health Organization Western Pacific Region. Among the NTDs, helminth infections are particularly prominent with regard to the number of infected individuals and health impact. Co-endemicity is common among impoverished and marginalized populations. To achieve effective and sustainable control of helminth NTDs, a deeper understanding of the social-ecological systems governing their endemicity and strategies beyond preventive chemotherapy are required to tackle the multiple causes of infection and re-infection. We discuss the feasibility of implementing multi-disease, multi-sectoral intervention packages for helminth NTDs in the Western Pacific Region. After reviewing the main determinants for helminth NTD endemicity and current control strategies, key control activities that involve or concern other programmes within and beyond the health sector are discussed. A considerable number of activities that have an impact on more than one helminth NTD are identified in a variety of sectors, suggesting an untapped potential for synergies. We also highlight the challenges of multi-sectoral collaboration, particularly of involving non-health sectors. We conclude that multi-sectoral collaboration for helminth NTD control is feasible if the target diseases and sectors are carefully selected. To do so, an incentive analysis covering key stakeholders in the sectors is crucial, and the disease-control strategies need to be well understood. The benefits of multi-disease, multi-sectoral approaches could go beyond immediate health impacts by contributing to sustainable development, raising educational attainment, increasing productivity and reducing health inequities. Copyright © 2013 Elsevier B.V. All rights reserved.

Managing pregnancy in inflammatory rheumatological diseases

PubMed Central

2011-01-01

Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsible for most complications. Disease flares, pre-eclampsia, and thrombosis are the main maternal complications, whereas fetal loss and intrauterine growth restriction are the main fetal complications. Antirheumatic drugs used during pregnancy and lactation to control disease activity are corticosteroids, hydroxychloroquine, sulphasalzine, and azathioprine. Vaginal delivery is possible in most circumstances, with cesarean section being reserved for complications. PMID:21371350

Age- or stage-appropriate? Recreation and the relevance of Piaget's theory in dementia care.

PubMed

Mahoney, Alison E J

2003-01-01

In this study, the immediate effects (within 10 minutes) of age- and stage-appropriate activities and two control activities were observed in 56 dementia sufferers. Compared with the control activities, the two experimental treatment conditions elicited greater reductions in agitation and negative emotion and increases in positive emotion and duration of activity. Stage-appropriate activity was superior to age-appropriate activity in increasing positive emotion and had about the same effect in reducing negative emotion and agitation. The study also addressed the idea that people with Alzheimer's disease may regress through Piaget's stages of cognitive development and thus display the play interests associated with each stage. There was a significant relationship between cognitive level and type of Piagetian play observed; however, Piaget's descriptions of play were not entirely appropriate for persons with with Alzheimer's disease.

Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial.

PubMed

van Herwaarden, Noortje; van der Maas, Aatke; Minten, Michiel J M; van den Hoogen, Frank H J; Kievit, Wietske; van Vollenhoven, Ronald F; Bijlsma, Johannes W J; van den Bemt, Bart J F; den Broeder, Alfons A

2015-04-09

To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or etanercept, is non-inferior in maintaining disease control in patients with rheumatoid arthritis compared with usual care. Randomised controlled, open label, non-inferiority strategy trial. Two rheumatology outpatient clinics in the Netherlands, from December 2011 to May 2014. 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care. Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was restarted or escalated. Difference in proportions of patients with major flare (DAS28-CRP based flare longer than three months) between the two groups at 18 months, compared against a non-inferiority margin of 20%. Secondary outcomes included TNF inhibitor use at study end, functioning, quality of life, radiographic progression, and adverse events. Dose reduction of adalimumab or etanercept was non-inferior to usual care (proportion of patients with major flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval -12% to 12%). In the dose reduction group, TNF inhibitor use could successfully be stopped in 20% (95% confidence interval 13% to 28%), the injection interval successfully increased in 43% (34% to 53%), but no dose reduction was possible in 37% (28% to 46%). Functional status, quality of life, relevant radiographic progression, and adverse events did not differ between the groups, although short lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were more frequent in dose reduction than usual care. A disease activity guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid arthritis is non-inferior to usual care with regard to major flaring, while resulting in the successful dose reduction or stopping in two thirds of patients.Trial registration Dutch trial register (www.trialregister.nl), NTR 3216. © van Herwaarden et al 2015.

Improving response inhibition in Parkinson's disease with atomoxetine.

PubMed

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

2015-04-15

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. 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. 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. 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. Crown Copyright © 2015. Published by Elsevier Inc. 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

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.

[Study on the effectiveness of implementation: the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

PubMed

Zhang, J; Jin, R R; Li, J J; Li, J L; Su, X W; Deng, G J; Ma, S; Zhao, J; Wang, Y P; Bian, F; Qu, Y M; Shen, Z Z; Jiang, Y; Liu, Y L

2018-04-10

Objective: To assess the implementation and impact of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: Both sociological and epidemiological methods were used to collect qualitative and quantitative data in November and December, 2016 in order to conduct on process and outcome evaluation of the above mentioned objective. In the meantime, case study was also conducted. Results: All the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were found well implemented across the country, with health education and health promotion, surveillance and safeguard measures in particular. A government-led and inter-sector coordination and communication mechanism had been well established, with more than 16 non-health departments actively involved. 28.7% of the residents living in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were aware of the key messages related to chronic diseases. Among the residents, 72.1% of them consumed vegetables and 53.6% consumed fruits daily, with another 86.9% walked at least 10 minutes per day. Over 70% of the patients with hypertension or diabetes reported that they were taken care of by the Community Health Centers, and above 50% of them were under standardized management. Residents, living in the National Demonstration Areas under higher ranking of implementation scores, were more likely to be aware of relevant knowledge on chronic disease control and prevention ( OR =6.591, 95% CI : 5.188-8.373), salt reduction ( OR =1.352, 95% CI : 1.151-1.589), oil reduction ( OR =1.477, 95% CI : 1.249-1.746) and recommendation on physical activities ( OR =1.975, 95% CI : 1.623- 2.403). Conclusion: The implementation of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases had served a local platform for the control and prevention of non-communicable diseases, and thus become an important 'carrier' for chronic disease prevention and control programs in China.

Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

NASA Astrophysics Data System (ADS)

Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

1980-12-01

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

Fengycin produced by Bacillus subtilis 9407 plays a major role in the biocontrol of apple ring rot disease.

PubMed

Fan, Haiyan; Ru, Jinjiang; Zhang, Yuanyuan; Wang, Qi; Li, Yan

2017-06-01

Apple ring rot, caused by Botryosphaeria dothidea, is a serious apple disease in China. Bacillus subtilis 9407 was isolated from healthy apples and showed strong antifungal activity against B. dothidea. To identify the primary antifungal compound of B. subtilis 9407 and determine its role in controlling apple ring rot, a transposon mutant library was constructed using TnYLB-1, and a mutant completely defective in antifungal activity was obtained. The gene inactivated in the antifungal activity mutant had 98.5% similarity to ppsB in B. subtilis subsp. subtilis str. 168, which encodes one of the five synthetases responsible for synthesizing fengycin. A markerless ppsB deletion mutant was constructed. Compared with the wild-type strain, lipopeptide crude extracts from ΔppsB showed almost no inhibition of B. dothidea mycelial growth. Furthermore, fengycin-like lipopeptides (retention factor 0.1-0.2) that exhibited antifungal activity against B. dothidea were observed in the wild-type strain by thin-layer chromatography (TLC)-bioautography analysis, but not in ΔppsB. Semipreparative reverse-phase high performance liquid chromatography (RP-HPLC) detection revealed that ΔppsB lost the ability to synthesize fengycin. These results suggest that ppsB is responsible for synthesizing fengycin and that fengycin is the major antifungal compound produced by B. subtilis 9407 against B. dothidea. Moreover, a biocontrol assay showed that the control efficacy of ΔppsB was reduced by half compared with the wild-type strain, indicating that fengycin plays a major role in controlling apple ring rot disease. This is the first report on the use of a B. subtilis strain as a potential biological control agent to control apple ring rot disease by the production of fengycin. Copyright © 2017 Elsevier GmbH. All rights reserved.

Fibrinolytic activity in cerebrospinal fluid of dogs with different neurological disorders.

PubMed

de la Fuente, C; Monreal, L; Cerón, J; Pastor, J; Viu, J; Añor, S

2012-01-01

Fibrinolytic activity in cerebrospinal fluid (CSF) is activated in humans by different pathologic processes. To investigate fibrinolytic activity in the CSF of dogs with neurological disorders by measuring CSF D-dimer concentrations. One hundred and sixty-nine dogs with neurological disorders, 7 dogs with systemic inflammatory diseases without central nervous system involvement (SID), and 7 healthy Beagles were included in the study. Dogs with neurological disorders included 11 with steroid-responsive meningitis-arteritis (SRMA), 37 with other inflammatory neurological diseases (INF), 38 with neoplasia affecting the central nervous system (NEO), 28 with spinal compressive disorders (SCC), 15 with idiopathic epilepsy (IE), and 40 with noninflammatory neurological disorders (NON-INF). Prospective observational study. D-dimers and C-reactive protein (CRP) were simultaneously measured in paired CSF and blood samples. D-dimers and CRP were detected in 79/183 (43%) and in 182/183 (99.5%) CSF samples, respectively. All dogs with IE, SID, and controls had undetectable concentrations of D-dimers in the CSF. CSF D-dimer concentrations were significantly (P < .001) higher in dogs with SRMA than in dogs with other diseases and controls. CSF CRP concentration in dogs with SRMA was significantly (P < .001) higher than in dogs of other groups and controls, except for the SID group. No correlation was found between blood and CSF D-dimer concentrations. Intrathecal fibrinolytic activity seems to be activated in some canine neurological disorders, and it is high in severe meningeal inflammatory diseases. CSF D-dimer concentrations may be considered a diagnostic marker for SRMA. Copyright © 2012 by the American College of Veterinary Internal Medicine.

[The control of vectorial transmission].

PubMed

Silveira, Antônio Carlos; Dias, João Carlos Pinto

2011-01-01

Between 1950 and 1951, the first Prophylactic campaign against Chagas Diseases was carried on in Brazil by the so existing Serviço Nacional de Malária. The actions involving chemical vector control comprehended 74 municipalities along the Rio Grande Valley, between the States of São Paulo and Minas Gerais. Ever since, until 1975, the activities were performed according the availability of resources, being executed with more or less regularity and coverage. At that time, Chagas disease did no represent priority, in comparison with other endemic diseases prevalent in the Country. Even so, taking into account the accumulated data along those 25 years, the volume of work realized cannot be considered despicable. Nevertheless, it was few consistent, in terms of its impact on disease transmission. In 1975, with an additional injection of resources surpassed from the malaria program, plus the methodological systematization of the activities, and with the results of two extensive national inquiries (entomologic and serologic), the activities for vector control could be performed regularly, following two basic principles: interventions in always contiguous areas, progressively enlarged, and sustainability (continuity) of the activities, until being attained determined requirements and purpose previously established. Such actions and strategies lead into the exhaustion of the populations of the principal vector species, Triatoma infestans, no autochthonous and exclusively domiciliary, as well as the control of the domiciliary colonization of autochthonous species important to disease transmission. Vector transmission today is being considered residual, by means of some few native and peridomestic species, such as Triatoma brasiliensis and Triatoma pseudomaculata. There is, also, the risk of progressive domiciliation of some species before considered sylvatic, such as Panstrongylus lutzi and Triatoma rubrovaria. Finally, there is the possibility of the occurrence of cases of human infection directly related to the enzootic cycle of the parasite. By all these reasons, it is still indispensable the maintenance of a strict epidemiological surveillance against Chagas Disease in Brazil.

Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease

PubMed Central

Westerlund, Marie; Behbahani, Homira; Gellhaar, Sandra; Forsell, Charlotte; Belin, Andrea Carmine; Anvret, Anna; Zettergren, Anna; Nissbrandt, Hans; Lind, Charlotta; Sydow, Olof; Graff, Caroline; Olson, Lars; Ankarcrona, Maria; Galter, Dagmar

2011-01-01

The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n=10) and control subjects (n=10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n=10) compared to matched control subjects (n=10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n=10) and matched control subjects (n=10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration.—Westerlund, M., Behbahani, H., Gellhaar, S., Forsell, C., Carmine Belin, A., Anvret, A., Zettergren, A., Nissbrandt, H., Lind, C., Sydow, O., Graff, C., Olson, L., Ankarcrona, M., Galter, D. Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease. PMID:21163861

Self-efficacy and physical activity in children with congenital heart disease: is there a relationship?

PubMed

Ray, Trenda D; Henry, Karen

2011-04-01

This study examined the relationship between self-efficacy and physical activity in 10- to 14-year-old children with congenital heart disease. Cross-sectional study using self-report instruments. In 84 participants, self-efficacy scores were similar to those published for healthy adolescents, 30.8 as compared with 29.4. Physical activity participation as prescribed by the Centers for Disease Control and Prevention was low (38%). Self-efficacy scores were moderately correlated with physical activity participation (r = .47; p < .001). Interventions are needed to increase physical activity in this high-risk group. Interventions that focus on self-efficacy may be particularly helpful given the link between self-efficacy and physical activity. © 2011, Wiley Periodicals, Inc.

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

Maintenance Therapy in IBD

MedlinePlus

... for cures; participate in a clinical trial of experimental treatments. Interactive Disease Tracker Use GI Buddy to ... colitis, new medications will be developed—both to control active disease and to maintain ... Related Resources Order Patient Brochures ...

Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life.

PubMed

El-Rabbat M, Sarah; Mahmoud, Nermeen K; Gheita, Tamer A

2017-04-11

To describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL). 160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding healthy controls were included. Disease activity was assessed using disease activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI), modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL was also recorded. Severity in FMS cases was estimated using the revised Fibromyalgia Impact Questionnaire score. In the RA, SLE, SSc and BD patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to 2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was significantly higher in those with FMS (p=0.009) and significantly correlated with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale (p=0.012). The QoL scale in those with FMS was significantly worse (62.3±7.9) compared to those without (71.7±14.4) (p=0.023). In SLE patients, The WPI and SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049 and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated (p=0.03). Fibromyalgia syndrome is more frequent in rheumatic diseases, could be related to the disease activity in RA and BD patients and to thrombosis in SLE and affected the QoL in RA. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Interconnected network motifs control podocyte morphology and kidney function.

PubMed

Azeloglu, Evren U; Hardy, Simon V; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y; Fang, Wei; Xiong, Huabao; Neves, Susana R; Jain, Mohit R; Li, Hong; Ma'ayan, Avi; Gordon, Ronald E; He, John Cijiang; Iyengar, Ravi

2014-02-04

Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3',5'-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element-binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor-driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease.

Interconnected Network Motifs Control Podocyte Morphology and Kidney Function

PubMed Central

Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi

2014-01-01

Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609

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

PubMed

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

2017-08-01

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. 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. 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). 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.

Labor characteristics and program costs of a successful diabetes disease management program.

PubMed

Rothman, Russell L; So, Stephanie A; Shin, John; Malone, Robert M; Bryant, Betsy; Dewalt, Darren A; Pignone, Michael P; Dittus, Robert S

2006-05-01

Organizations have invested in disease management programs to improve quality and to reduce costs, but little is known about the labor characteristics and the program costs necessary to implement a program. To examine the labor characteristics and the program costs of a successful diabetes disease management program. We performed a labor and cost analysis within a randomized controlled trial of a primary care-based diabetes disease management intervention. Participants included 217 patients with type 2 diabetes mellitus and poor glycemic control (glycosylated hemoglobin levels, > or = 8.0%). The intervention group received 12 months of intensive management from clinical pharmacists and a diabetes care coordinator who provided education, applied algorithms for medication management, and addressed barriers to care. The control group attended a single session led by pharmacists, followed by usual care from their primary providers. The process outcomes included the number of patient care-related activities, time spent per patient, and number of drug titrations or additions. The program costs were calculated based on Bureau of Labor Statistics wage data using a sensitivity analysis. The disease management team performed a mean of 4.0 care-related activities for a mean of 38.6 minutes per patient per month for intervention patients and performed a mean of 1.1 care-related activities for a mean of 10.7 minutes per patient per month for control patients (P < .001). Intervention patients had a median of 7 drug titrations or additions during the study. The incremental program cost for the intervention was 36.97 dollars (sensitivity analysis, 6.22 dollars-88.56 dollars) per patient per month. A successful diabetes disease management program can be integrated into an academic clinic for modest labor and cost.

Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease.

PubMed

Bjerrum, Jacob Tveiten; Steenholdt, Casper; Ainsworth, Mark; Nielsen, Ole Haagen; Reed, Michelle Ac; Atkins, Karen; Günther, Ulrich Leonhard; Hao, Fuhua; Wang, Yulan

2017-10-16

One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential biomarkers of treatment response and (3) to characterise the metabolic changes during management of patients with tumour necrosis factor-α inhibitors. Successive serum samples collected during IFX induction treatment (weeks 0, 2, 6 and 14) from 87 IBD patients and 37 controls were analysed by 1 H nuclear magnetic resonance (NMR) spectroscopy. Data were analysed with principal components analysis and orthogonal projection to latent structures discriminant analysis using SIMCA-P+ v12 and MATLAB. Metabolic profiles were significantly different between active ulcerative colitis and controls, active Crohn's disease and controls, and quiescent Crohn's disease and controls. Metabolites holding differential power belonged primarily to lipids and phospholipids with proatherogenic characteristics and metabolites in the pyruvate metabolism, suggestive of an intense inflammation-driven energy demand. IBD patients not responding to IFX were identified as a potentially distinct group based on their metabolic profile, although no applicable response biomarkers could be singled out in the current setting. 1 H NMR spectroscopy of serum samples is a powerful semi-invasive diagnostic tool in flaring IBD. With its use, we provide unique insights into the metabolic changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially explains the increased risk of cardiovascular disease associated with IBD.

Increased Rho kinase activity in congestive heart failure

PubMed Central

Dong, Ming; Liao, James K.; Fang, Fang; Lee, Alex Pui-Wai; Yan, Bryan Ping-Yen; Liu, Ming; Yu, Cheuk-Man

2012-01-01

Aims Rho kinases (ROCKs) are the best characterized effectors of the small G-protein RhoA, and play a role in enhanced vasoconstriction in animal models of congestive heart failure (CHF). This study examined if ROCK activity is increased in CHF and how it is associated with the outcome in CHF. Methods and results Patients admitted with CHF (n =178), disease controls (n =31), and normal subjects (n =30) were studied. Baseline ROCK activity was measured by phosphorylation of themyosin-binding subunit in peripheral leucocytes. The patients were followed up for 14.4 ± 7.2 months (range 0.5–26 months) or until the occurrence of cardiac death. The ROCK activity in CHF patients (2.93 ± 0.87) was significantly higher than that of the disease control (2.06 ± 0.38, P < 0.001) and normal control (1.57 ± 0.43, P < 0.001) groups. Similarly, protein levels of ROCK1 and ROCK2 as well as the activity of RhoA in CHF were significantly higher than in disease controls and normal controls (all P < 0.05). Dyspnoea at rest (β =0.338, P < 0.001), low left ventricular ejection fraction (β = –0.277, P < 0.001), and high creatinine (β =0.202, P =0.006) were independent predictors of the baseline ROCK activity in CHF. Forty-five patients died within 2 years follow-up (25.3%). Combining ROCK activity and N-terminal pro brain natriuretic peptide (NT-proBNP) had an incremental value (log rank χ2 =11.62) in predicting long-term mortality when compared with only NT-proBNP (log rank χ2 =5.16, P < 0.05). Conclusion ROCK activity is increased in CHF and it might be associated with the mortality in CHF. ROCK activity might be a complementary biomarker to CHF risk stratification. PMID:22588320

Report of the Bluetongue and Bovine Retroviruses Committee.

USDA-ARS?s Scientific Manuscript database

New strategies for preventing bluetongue in sheep, W.K. Reeves. Bluetongue disease is a sporadic and unpredictable disease in the northern Rocky Mountains. Epizootics can be separated by decades of little to no disease activity. Woolgrowers need access to control technologies that can be used after ...

Physiological Responses to Arm Activity in Individuals With Chronic Obstructive Pulmonary Disease Compared With Healthy Controls: A SYSTEMATIC REVIEW.

PubMed

Lima, Vanessa Pereira; Iamonti, Vinicius C; Velloso, Marcelo; Janaudis-Ferreira, Tania

The mechanisms underlying physiological limitations during arm activity in individuals with chronic obstructive pulmonary disease (COPD) are unknown. The objective of this systematic review was to describe cardiorespiratory responses, symptoms, chest wall kinematics, muscle activity, and lung volumes during arm activity in individuals with COPD relative to the responses of healthy controls. Original research articles that compared cardiorespiratory responses, symptoms, muscle activity, chest wall kinematics, and lung function during arm activity between individuals with COPD and healthy controls were identified after searches of 5 electronic databases and reference lists of pertinent articles. Two reviewers performed the electronic and manual searches with 1 screening title and abstracts. Two investigators screened the full texts to determine eligibility for inclusion. One reviewer performed the data extraction and tabulation using a standardized form with a second reviewer double-checking the data extracted. Of the 54 full-text articles assessed for eligibility, 6 met the inclusion criteria. Reduced cardiorespiratory responses during peak arm exercise in individuals with COPD compared with healthy controls were evident. Compared with healthy controls, individuals with COPD had increased dyspnea and hyperinflation during peak arm exercise. Increased effort of the trapezius muscle during arm activities was also found in persons with COPD compared with healthy controls. There is limited evidence describing physiological responses during arm activity in individuals with COPD. Findings of this systematic review suggest that individuals with COPD have decreased cardiorespiratory responses during peak arm exercise compared with controls but increased dyspnea, hyperinflation, and arm muscle effort.

Dissociation between Active and Observational Learning from Positive and Negative Feedback in Parkinsonism

PubMed Central

Kobza, Stefan; Ferrea, Stefano; Schnitzler, Alfons; Pollok, Bettina

2012-01-01

Feedback to both actively performed and observed behaviour allows adaptation of future actions. Positive feedback leads to increased activity of dopamine neurons in the substantia nigra, whereas dopamine neuron activity is decreased following negative feedback. Dopamine level reduction in unmedicated Parkinson’s Disease patients has been shown to lead to a negative learning bias, i.e. enhanced learning from negative feedback. Recent findings suggest that the neural mechanisms of active and observational learning from feedback might differ, with the striatum playing a less prominent role in observational learning. Therefore, it was hypothesized that unmedicated Parkinson’s Disease patients would show a negative learning bias only in active but not in observational learning. In a between-group design, 19 Parkinson’s Disease patients and 40 healthy controls engaged in either an active or an observational probabilistic feedback-learning task. For both tasks, transfer phases aimed to assess the bias to learn better from positive or negative feedback. As expected, actively learning patients showed a negative learning bias, whereas controls learned better from positive feedback. In contrast, no difference between patients and controls emerged for observational learning, with both groups showing better learning from positive feedback. These findings add to neural models of reinforcement-learning by suggesting that dopamine-modulated input to the striatum plays a minor role in observational learning from feedback. Future research will have to elucidate the specific neural underpinnings of observational learning. PMID:23185586

Costs of Dengue Control Activities and Hospitalizations in the Public Health Sector during an Epidemic Year in Urban Sri Lanka.

PubMed

Thalagala, Neil; Tissera, Hasitha; Palihawadana, Paba; Amarasinghe, Ananda; Ambagahawita, Anuradha; Wilder-Smith, Annelies; Shepard, Donald S; Tozan, Yeşim

2016-02-01

Reported as a public health problem since the 1960s in Sri Lanka, dengue has become a high priority disease for public health authorities. The Ministry of Health is responsible for controlling dengue and other disease outbreaks and associated health care. The involvement of large numbers of public health staff in dengue control activities year-round and the provision of free medical care to dengue patients at secondary care hospitals place a formidable financial burden on the public health sector. We estimated the public sector costs of dengue control activities and the direct costs of hospitalizations in Colombo, the most heavily urbanized district in Sri Lanka, during the epidemic year of 2012 from the Ministry of Health's perspective. The financial costs borne by public health agencies and hospitals are collected using cost extraction tools designed specifically for the study and analysed retrospectively using a combination of activity-based and gross costing approaches. The total cost of dengue control and reported hospitalizations was estimated at US$3.45 million (US$1.50 per capita) in Colombo district in 2012. Personnel costs accounted for the largest shares of the total costs of dengue control activities (79%) and hospitalizations (46%). The results indicated a per capita cost of US$0.42 for dengue control activities. The average costs per hospitalization ranged between US$216-609 for pediatric cases and between US$196-866 for adult cases according to disease severity and treatment setting. This analysis is a first attempt to assess the economic burden of dengue response in the public health sector in Sri Lanka. Country-specific evidence is needed for setting public health priorities and deciding about the deployment of existing or new technologies. Our results suggest that dengue poses a major economic burden on the public health sector in Sri Lanka.

Costs of Dengue Control Activities and Hospitalizations in the Public Health Sector during an Epidemic Year in Urban Sri Lanka

PubMed Central

Thalagala, Neil; Tissera, Hasitha; Palihawadana, Paba; Amarasinghe, Ananda; Ambagahawita, Anuradha; Wilder-Smith, Annelies; Shepard, Donald S.; Tozan, Yeşim

2016-01-01

Background Reported as a public health problem since the 1960s in Sri Lanka, dengue has become a high priority disease for public health authorities. The Ministry of Health is responsible for controlling dengue and other disease outbreaks and associated health care. The involvement of large numbers of public health staff in dengue control activities year-round and the provision of free medical care to dengue patients at secondary care hospitals place a formidable financial burden on the public health sector. Methods We estimated the public sector costs of dengue control activities and the direct costs of hospitalizations in Colombo, the most heavily urbanized district in Sri Lanka, during the epidemic year of 2012 from the Ministry of Health’s perspective. The financial costs borne by public health agencies and hospitals are collected using cost extraction tools designed specifically for the study and analysed retrospectively using a combination of activity-based and gross costing approaches. Results The total cost of dengue control and reported hospitalizations was estimated at US$3.45 million (US$1.50 per capita) in Colombo district in 2012. Personnel costs accounted for the largest shares of the total costs of dengue control activities (79%) and hospitalizations (46%). The results indicated a per capita cost of US$0.42 for dengue control activities. The average costs per hospitalization ranged between US$216–609 for pediatric cases and between US$196–866 for adult cases according to disease severity and treatment setting. Conclusions This analysis is a first attempt to assess the economic burden of dengue response in the public health sector in Sri Lanka. Country-specific evidence is needed for setting public health priorities and deciding about the deployment of existing or new technologies. Our results suggest that dengue poses a major economic burden on the public health sector in Sri Lanka. PMID:26910907

Detection of Active Epstein-Barr Virus Infection in Duodenal Mucosa of Patients With Refractory Celiac Disease.

PubMed

Perfetti, Vittorio; Baldanti, Fausto; Lenti, Marco Vincenzo; Vanoli, Alessandro; Biagi, Federico; Gatti, Marta; Riboni, Roberta; Dallera, Elena; Paulli, Marco; Pedrazzoli, Paolo; Corazza, Gino Roberto

2016-08-01

Refractory celiac disease is characterized by mucosal damage in patients with celiac disease despite a gluten-free diet. Little is known about the mechanisms that cause persistent intestinal inflammation in these patients. We performed a case-control study of 17 consecutive patients diagnosed with refractory celiac disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with uncomplicated celiac disease (controls) to determine whether refractory disease is associated with infection by lymphotropic oncogenic viruses. We performed real-time PCR analyses of duodenal biopsy samples from all patients to detect Epstein-Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, -II, or -III. We used in situ hybridization and immunohistochemical analyses to identify infected cells and viral proteins. We did not detect human herpesvirus-8 or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12 of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls (P < .001). EBV was detected in inflammatory cells and enterocytes. An analysis of latency- and replication-associated proteins confirmed active infection. Further studies are needed to determine whether EBV infection contributes to the pathogenesis of refractory celiac disease and enteropathy-associated T-cell lymphoma. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Angiotensin-converting enzyme-inhibitory activity in protein hydrolysates from normal and anthracnose disease-damaged Phaseolus vulgaris seeds.

PubMed

Hernández-Álvarez, Alan Javier; Carrasco-Castilla, Janet; Dávila-Ortiz, Gloria; Alaiz, Manuel; Girón-Calle, Julio; Vioque-Peña, Javier; Jacinto-Hernández, Carmen; Jiménez-Martínez, Cristian

2013-03-15

Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity. Protein concentrates from beans spoiled by anthracnose disease and from regular beans as controls were prepared by alkaline extraction and precipitation at isolelectric pH and hydrolysed using Alcalase 2.4 L. The hydrolysates from spoiled beans had ACE-I-inhibitory activity (IC(50) 0.0191 mg protein mL(-1)) and were very similar to those from control beans in terms of ACE-I inhibition, peptide electrophoretic profile and kinetics of hydrolysis. Thus preparation of hydrolysates using beans affected by anthracnose disease would allow for revalorisation of this otherwise wasted product. The present results suggest the use of spoiled bean seeds, e.g. anthracnose-damaged beans, as an alternative for the isolation of ACE-I-inhibitory peptides to be further introduced as active ingredients in functional foods. © 2012 Society of Chemical Industry.

High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study.

PubMed

Arts, Elke; Fransen, Jaap; Lemmers, Heidi; Stalenhoef, Anton; Joosten, Leo; van Riel, Piet; Popa, Calin D

2012-05-14

Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity. Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol. HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186). Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.

ACE phenotyping in Gaucher disease.

PubMed

Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

2018-04-01

Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Postural set for balance control is normal in Alzheimer's but not in Parkinson's disease.

PubMed

Chong, R K; Jones, C L; Horak, F B

1999-03-01

It has been suggested that patients with dementia of the Alzheimer type have abnormalities in the basal ganglia, and thus, may have similar sensorimotor problems as patients with basal ganglia degeneration from Parkinson's disease. Whether the similarity extends to balance control is unknown. One distinguishing feature of balance disorder in Parkinson's disease is difficulty with changing postural set in terms of adapting the amplitude of leg muscle activity as a function of support condition. We, therefore, tested whether patients with Alzheimer's disease without extrapyramidal signs would show a similar problem in changing postural set as patients with Parkinson's disease. The ability to quickly change postural set was measured by comparing leg muscle activity under two conditions of support (free stance, versus grasping a frame, or sitting) during backward surface translations, during toes up surface rotations, and during voluntary rise to toes. Results were compared among 12 healthy adults, 8 nondemented Parkinson's patients on their usual dose of medication, and 11 Alzheimer patients without extrapyramidal signs. Subjects with Alzheimer's, but not Parkinson's, disease performed similarly to the healthy control subjects. They changed postural set immediately, by suppressing leg muscle activity to low levels when supported. Parkinson subjects did not change postural set immediately. They did not suppress the tibialis anterior in voluntary rise to toes when holding, nor the soleus in perturbed sitting as much as the healthy control and Alzheimer subjects in the first trial. Instead, the Parkinson subjects changed set more slowly, over repeated and consecutive trials in both protocols. The onset latencies of soleus responses to backward surface translations and perturbed sitting, as well as tibialis anterior responses to toes up rotations, were the same for all three groups. Alzheimer patients without extrapyramidal signs, unlike nondemented Parkinson's disease patients, have no difficulty in quickly changing postural set in response to altered support conditions. Our results, therefore, do not support the hypothesis that Parkinson's and uncomplicated Alzheimer's diseases share common postural set problems that may contribute to disordered balance control.

[Insight into the training of patients with idiopathic inflammatory myopathy].

PubMed

Váncsa, Andrea

2016-09-01

Using current recommended treatment, a majority of patients with idiopathic inflammatory myopathy develop muscle impairment and poor health. Beneficial effects of exercise have been reported on muscle performance, aerobic capacity and health in chronic polymyositis and dermatomyositis, as well as in active disease and inclusion body myositis to some extent. Importantly, randomized controlled trials indicate that improved health and decreased clinical disease activity could be mediated through increased aerobic capacity. Recently, reports seeking pathomechanisms of the underlying effects of exercise on skeletal muscle indicate increased aerobic capacity (i.e. increased mitochondrial capacity and capillary density, reduced lactate levels), activation of genes of aerobic phenotype and muscle growth programs and down regulation of genes related to inflammation. Exercise contributes to both systemic and within-muscle adaptations demonstrating that it is fundamental for improving muscle performance and health in patients with idiopathic inflammatory myopathy. There is a need for randomized controlled trials to study the effects of exercise in patients with active disease and inclusion body myositis. Orv. Hetil., 2016, 157(39), 1557-1562.

Prefrontal involvement related to cognitive impairment in progressive muscular atrophy.

PubMed

Raaphorst, Joost; van Tol, Marie-José; Groot, Paul F C; Altena, Ellemarije; van der Werf, Ysbrand D; Majoie, Charles B; van der Kooi, Anneke J; van den Berg, Leonard H; Schmand, Ben; de Visser, Marianne; Veltman, Dick J

2014-08-26

To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p<0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation. Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALS

Serum and tissue angiotensin-converting enzyme in patients with alopecia areata.

PubMed

Fahim, Shabnam; Montazer, Fatemeh; Tohidinik, Hamid Reza; Naraghi, Zahra Safaei; Abedini, Robabeh; Nasimi, Maryam; Ghandi, Narges

2018-03-27

Alopecia areata is an immune-dependent disorder characterized by the interaction of T-lymphocytes with follicular antigens. Recent studies have shown the existence of a local renin-angiotensin system in the skin, where angiotensin-converting enzyme (ACE) plays a role in autoimmunity and inflammation. The objective of this study was to evaluate serum and tissue ACE activity in patients with alopecia areata. This case-control study was conducted on patients with alopecia areata and healthy controls. Serum and tissue ACE activity were assessed and compared between the two groups. Twenty-five alopecia areata patients (60% male, mean age 32.1 ± 9.9 years) and 24 controls (50% male, mean age 37.4 ± 8.8 years) were included. Mean serum ACE activity was 52.1 ± 9 U/L in cases and 55.3 ± 14.7 U/L in controls (P = 0.37). Tissue ACE activity was significantly lower in cases in all parts of the skin i.e. epidermis (P = 0.016), follicular epithelium (P = 0.004), and endothelium (P = 0.037). Among cases, serum ACE activity was significantly higher in patients with more severe disease (P = 0.030), nonpatchy alopecia areata (alopecia universalis; ophiasis, patchy and ophiasis, diffuse) (P = 0.029), and with nail involvement (P = 0.027). The sample size was too small to draw definite conclusions. Further, most of the patients had only mild or moderate alopecia areata. Unlike in some other inflammatory diseases, the tissue level of ACE seems to be significantly lower in alopecia areata compared to normal controls. Serum ACE was significantly higher in patients with more severe disease.

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

Control of Avian Coccidiosis: Future and Present Natural Alternatives

PubMed Central

Quiroz-Castañeda, Rosa Estela; Dantán-González, Edgar

2015-01-01

Numerous efforts to date have been implemented in the control of avian coccidiosis caused by the Eimeria parasite. Since the appearance of anticoccidial chemical compounds, the search for new alternatives continues. Today, no product is available to cope with the disease; however, the number of products commercially available is constantly increasing. In this review, we focus on natural products and their anticoccidial activity. This group comprises fatty acids, antioxidants, fungal and herbal extracts, and immune response modulators with proven anticoccidial activity, many of which exist as dietary supplements. Additionally, we offer an overview of the poultry industry and the economic cost of coccidiosis as well as the classical strategies used to control the disease. PMID:25785269

HDL Function in Rheumatoid Arthritis

PubMed Central

Ormseth, Michelle J; Stein, C. Michael

2015-01-01

Purpose of review Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis despite the appearance of having a less atherogenic lipid profile; however, lipoprotein function rather than concentration may be a better indicator of atherosclerotic risk. The purpose of this review is to summarize recent findings concerning HDL function in patients with RA. Recent findings Two major activities of HDL, its antioxidant and cholesterol efflux functions have been examined in RA. HDL antioxidant capacity is inversely associated with inflammation and RA disease activity; however, there is no clear consensus if antioxidant capacity is altered significantly in RA compared to control subjects. Moreover, despite numerous studies there is no consensus whether HDL cholesterol efflux capacity is significantly altered in RA compared to control subjects or influenced by inflammation or disease activity. Summary Additional studies will be valuable to consolidate existing data and find consensus. Moreover, studies evaluating the impact of various HDL functions on cardiovascular disease in RA are needed. PMID:26709471

[Physiotherapy for juvenile idiopathic arthritis].

PubMed

Spamer, M; Georgi, M; Häfner, R; Händel, H; König, M; Haas, J-P

2012-07-01

Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today.

PubMed

Caslin, Heather L; Kiwanuka, Kasalina N; Haque, Tamara T; Taruselli, Marcela T; MacKnight, H Patrick; Paranjape, Anuya; Ryan, John J

2018-01-01

Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with FcεRI and FγR signaling, IL-4, IL-10, and TGF-β1 treatment, and Stat5. We conclude with potential therapeutics for allergic disease. Much of these efforts have been influenced by the work of Bill Paul. With many mechanistic targets for mast cell activation and different classes of therapeutics being studied, there is reason to be hopeful for continued clinical progress in this area.

[Globalization, inequity and Chagas disease].

PubMed

Dias, João Carlos Pinto

2007-01-01

Chagas disease (American trypanosomiasis) bears a close relationship to multiple social and political aspects involving issues of globalization and inequity. Such relations concern the process of disease production and control in parallel with medical management. Despite the poverty in Latin America and various problems related to inequities and globalization, Chagas disease has been controlled in several areas, a fact that reinforces the countries' self-reliance. Several problems and challenges related to the disease can be expected in the future, mainly concerning medical care for already infected individuals and the sustainability of effective epidemiological surveillance. Both points depend heavily on improved performance by the national health systems, principally in terms of their efficiency and their capacity to overcome inequity. A particularly important role has been attributed to the Latin American scientific and academic community in the implementation and sustainability of efficient control policies. Control activities have now evolved towards internationally shared initiatives, a major new stride forward in the region's political context.

Impacts of abstinence education on teen sexual activity, risk of pregnancy, and risk of sexually transmitted diseases.

PubMed

Trenholm, Christopher; Devaney, Barbara; Fortson, Kenneth; Clark, Melissa; Bridgespan, Lisa Quay; Wheeler, Justin

2008-01-01

This paper examines the impacts of four abstinence-only education programs on adolescent sexual activity and risks of pregnancy and sexually transmitted diseases (STDs). Based on an experimental design, the impact analysis uses survey data collected in 2005 and early 2006 from more than 2,000 teens who had been randomly assigned to either a program group that was eligible to participate in one of the four programs or a control group that was not. The findings show no significant impact on teen sexual activity, no differences in rates of unprotected sex, and some impacts on knowledge of STDs and perceived effectiveness of condoms and birth control pills

Evidence for adaptive cortical changes in swallowing in Parkinson's disease.

PubMed

Suntrup, Sonja; Teismann, Inga; Bejer, Joke; Suttrup, Inga; Winkels, Martin; Mehler, David; Pantev, Christo; Dziewas, Rainer; Warnecke, Tobias

2013-03-01

Dysphagia is a relevant symptom in Parkinson's disease, whose pathophysiology is poorly understood. It is mainly attributed to degeneration of brainstem nuclei. However, alterations in the cortical contribution to deglutition control in the course of Parkinson's disease have not been investigated. Here, we sought to determine the patterns of cortical swallowing processing in patients with Parkinson's disease with and without dysphagia. Swallowing function in patients was objectively assessed with fiberoptic endoscopic evaluation. Swallow-related cortical activation was measured using whole-head magnetoencephalography in 10 dysphagic and 10 non-dysphagic patients with Parkinson's disease and a healthy control group during self-paced swallowing. Data were analysed applying synthetic aperture magnetometry, and group analyses were done using a permutation test. Compared with healthy subjects, a strong decrease of cortical swallowing activation was found in all patients. It was most prominent in participants with manifest dysphagia. Non-dysphagic patients with Parkinson's disease showed a pronounced shift of peak activation towards lateral parts of the premotor, motor and inferolateral parietal cortex with reduced activation of the supplementary motor area. This pattern was not found in dysphagic patients with Parkinson's disease. We conclude that in Parkinson's disease, not only brainstem and basal ganglia circuits, but also cortical areas modulate swallowing function in a clinically relevant way. Our results point towards adaptive cerebral changes in swallowing to compensate for deficient motor pathways. Recruitment of better preserved parallel motor loops driven by sensory afferent input seems to maintain swallowing function until progressing neurodegeneration exceeds beyond the means of this adaptive strategy, resulting in manifestation of dysphagia.

Disease activity in and quality of life of patients with psoriatic arthritis mutilans: the Nordic PAM Study.

PubMed

Lindqvist, U; Gudbjornsson, B; Iversen, L; Laasonen, L; Ejstrup, L; Ternowitz, T; Ståhle, M

2017-11-01

To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries. Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM. Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group. PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.

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

Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients.

PubMed

Adu-Gyamfi, Clement G; Snyman, Tracy; Hoffmann, Christopher J; Martinson, Neil A; Chaisson, Richard E; George, Jaya A; Suchard, Melinda S

2017-10-15

There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P < .001). Six months before tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P < .001) than controls. After 6 months of tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Physical activity, opportunity for reinfection, and sibling history of heart disease as risk factors for Chagas' cardiopathy.

PubMed

Zicker, F; Smith, P G; Netto, J C; Oliveira, R M; Zicker, E M

1990-11-01

A case-control study was conducted to examine whether physical activity, sibling history of heart disease (HHD), and length of residence in an area endemic for Chagas' disease were associated with the risk of developing Chagas' cardiopathy. Two hundred forty-seven cases of Chagas' heart disease and 345 seropositive subjects with normal ECG (controls) were selected in a population survey in Goiânia, Brazil. Prevalence ratios for exposure variables were estimated for cases in relation to controls and for subgroups of seropositives with selected ECG abnormalities in relation to controls. Increasing age and male sex were consistently and significantly related to an increased risk of ECG abnormalities. HHD was significantly associated with ECG alterations in 3 of the 5 comparison subgroups (any ECG alteration, right bundle branch block, and left anterior hemiblock). No association was found between length of residence in an area endemic, physical activity, and ECG abnormalities. A sample of 529 seronegative subjects were also examined and the interaction between exposure variables and seropositivity was tested to assess whether the associations found were specific for seropositives. Males were at greater risk of any ECG alteration and left anterior hemiblock in relation to females if they were seropositive. An increasing risk of ventricular premature beats with age was clearer for seropositive than for seronegative subjects. Subjects with HHD were at an increased risk of ECG abnormalities and this was greater in those with a positive serological test (P less than 0.05). The findings suggest a possible geographical clustering or a familial aggregation of cases of Chagas' heart disease.

Arm Activity During Daily Life in Individuals With Chronic Obstructive Pulmonary Disease.

PubMed

Janaudis-Ferreira, Tania; Mathur, Sunita; Romano, Julia Marie; Goldstein, Roger Samuel; Brooks, Dina

2016-01-01

To determine whether individuals with chronic obstructive pulmonary disease (COPD) have decreased arm activity during daily life compared with healthy controls and explore the relationships between arm activity during daily life and arm functional measures in individuals with COPD. This was a prospective cross-sectional study that included 30 people with COPD and 14 healthy controls. Subjects attended a single assessment session in which measurements of arm exercise capacity, arm functional performance, self-perception of performance during activities of daily living (ADL), shoulder and elbow flexion force and biceps and triceps thickness were performed. On completion of this session, participants were issued a wrist actigraph and asked to wear the device on the dominant arm for 24 hours for 7 consecutive days. Compared with healthy controls, patients with COPD presented decreased total activity level in daily life (P = .001). When corrected for walking, the level of arm activity did not differ between individuals with COPD and healthy controls (P = .62). No correlations were found between arm activity and arm exercise capacity, arm functional performance, upper limb muscle strength, and self-perception of performance during ADL (r =-0.20 to 0.14; all P ≥ .10). Arm activity intensity in individuals with COPD did not differ from that of healthy controls when measured by a wrist actigraph. Moreover, arm activity was not associated with other clinical outcomes of arm function. Disability during ADL is multifactorial, and only limited inferences of function can be made from accelerometer data.

Family history of chronic disease and meeting public health guidelines for physical activity: the cooper center longitudinal study.

PubMed

Shuval, Kerem; Chiu, Chung-Yi; Barlow, Carolyn E; Gabriel, Kelley Pettee; Kendzor, Darla E; Businelle, Michael S; Skinner, Celette Sugg; Balasubramanian, Bijal A

2013-06-01

We aimed to assess whether a family history of coronary heart disease, diabetes, or cancer is linked to meeting public health guidelines for health-promoting physical activity. To achieve this objective, we analyzed data on 29,513 adults who came to the Cooper Clinic (Dallas, Texas) between January 1, 1990, and December 31, 2010, for a preventive medicine visit. Patients completed a comprehensive medical survey including information on family medical history, physical activity, and other lifestyle behaviors. Bivariate and multivariate logistic regression were used to examine the relationship between having a family history of chronic disease and meeting physical activity guidelines. The results indicated that individuals with a family history of disease had reduced odds for meeting or exceeding physical activity guidelines. For example, participants with a family history of 3 diseases were 36% less likely to meet or exceed physical activity guidelines than their counterparts without a family history of disease (odds ratio, 0.64; 95% CI, 0.58-0.72), while controlling for covariates. Among this large sample of adults, those with a family history of chronic disease were less inclined to regularly engage in physical activity. Thus, targeted programs encouraging adoption and maintenance of health-promoting physical activity might be warranted, specifically targeting individuals with familial history of disease. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

No direct association among respiratory function, disease control and family functioning in a sample of Mexican children with intermittent asthma.

PubMed

Rodriguez-Orozco, Alain Raimundo; Núñez-Tapia, Rosa María; Ramírez-Silva, Armando; Gómez-Alonso, Carlos

2013-05-15

Asthma has been linked to family disfunctioning and poor control of the disease.This study was conducted to analyze the interactions between the level of intermittent asthma control, family functioning and respiratory function and between quality of life of asthmatic patients and their caregivers.7 to 15 years old children with intermittent asthma were included. Asthma Control Test Questionnaire, Pediatric Asthma Quality of Life Questionnaire (PAQLQ) test, and flowmetry were applied to children and Pediatric Asthma Caregiver´s Quatily of Life Questionnaire (PAQCLQ) and the Family Functioning Perception Test (FF-SIL) were applied to their parents.The most affected areas of family functioning in dysfunctional families were adaptability and permeability. A medium to high strength of association was founded between the emotional function of parents and the emotional function of children, R2=0.552. The most remarkable associations were among parents' limitation of activities and parents' emotional function (r=0.837), parents' limitation of activities and child's emotional function (r=0.722), parents' emotional role and limitation of activities (r=0.837), parents' emotional role and emotional functioning of children with asthma (r=0.743) and the limitation of activities of children with asthma and the emotional function of children with asthma (r=0.870).No direct associations were founded among respiratory function, disease control and family functioning in Mexican children with intermittent asthma and emotional function of parents and children were associated in both groups.

Erythrocyte deformability and oxidative stress in inflammatory bowel disease.

PubMed

Akman, Tulay; Akarsu, Mesut; Akpinar, Hale; Resmi, Halil; Taylan, Ebru; Sezer, Ebru

2012-02-01

Oxidative stress and reduced microvascular flow are important factors in the pathogenesis of inflammatory bowel disease (IBD). The increased oxidative stress reduces the erythrocyte deformability. However, in IBD, there are no studies in the literature which evaluate erythrocyte deformability. In our study, we investigated the effect of oxidative stress and erythrocyte deformability in IBD. Forty-three patients with active IBD, 48 patients with inactive IBD and 45 healthy controls were included. The erytrocyte deformability, malonyldialdehyde levels, glutation peroxidase and sulfhydryl levels were measured in peripheral venous blood samples. Erytrocyte malonyldialdehyde levels in both active and inactive IBD were significantly increased compared with control groups. Plasma glutation peroxidase levels did not show statistically significant difference between all groups. The decreased plasma sulfhydryl levels in active IBD were statistically significant compared with both the inactive IBD and the control group, but plasma sulfhydryl levels in inactive IBD group did not show statistically significant differences when compared with the control group. Elongation index values in both active and inactive IBD increased significantly compared with the control group. Statistically significant correlations were not found between the elongation index and glutation peroxidase, malonyldialdehyde, sulfhydryl levels in all groups. Our study is the first to evaluate the erythrocyte deformability in IBD. In our study, increased erytrocyte malonyldialdehyde levels and decreased plasma sulfhydryl levels manifested the role of oxidative stress in the pathogenesis of the disease. It is thought that the increased erythrocyte malonyldialdehyde values cause the reduction in erythrocyte deformability.

Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.

PubMed

De Greef, Elisabeth; Hoffman, Ilse; Smets, Francoise; Van Biervliet, Stephanie; Bontems, Patrick; Hauser, Bruno; Paquot, Isabelle; Alliet, Philippe; Arts, Wim; Dewit, Olivier; De Vos, Martine; Baert, Filip; Bossuyt, Peter; Rahier, Jean-Francois; Franchimont, Denis; Vermeire, Severine; Fontaine, Fernand; Louis, Edouard; Coche, J C; Veereman, Gigi

2016-08-01

The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.

Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

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

B McCray; E Skordalakes; J Taylor

2011-12-31

Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Throughmore » extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.« less

Effect of chitosan solution on the inhibition of Acidovorax citrulli causing bacterial fruit blotch of watermelon.

PubMed

Li, Bin; Shi, Yu; Shan, Changlin; Zhou, Qing; Ibrahim, Muhammad; Wang, Yanli; Wu, Guoxing; Li, Hongye; Xie, Guanlin; Sun, Guochang

2013-03-30

The production of watermelon in China has been seriously hampered by fruit blotch disease and limited control measures are now applied. Chitosan has been employed to control a variety of plant diseases and is considered to be the most promising biochemical to control this disease. The in vitro antibacterial effect of chitosan and its ability in protection of watermelon seedlings from bacterial fruit blotch were evaluated. Results showed that three types of chitosan, in particular, chitosan A at 0.40 mg mL⁻¹ significantly inhibited the growth of Acidovorax citrulli. The antibacterial activity of chitosan A was affected by chitosan concentration and incubation time. The direct antibacterial activity of chitosan may be attributed to membrane lysis evidenced by transmission electron microscopic observation. The disease index of watermelon seedlings planted in soil and the death rate of seedlings planted in perlite were significantly reduced by chitosan A at 0.40 mg mL⁻¹ compared to the pathogen control. Fresh and dry weight of watermelon seedlings planted in soil was increased by chitosan seed treatment, but not by chitosan leaf spraying. The results indicated that chitosan solution may have a potential in controlling bacterial fruit blotch of watermelon. © 2013 Society of Chemical Industry.

Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment.

PubMed

Taylor, Peter C; Alten, Rieke; Gomez-Reino, Juan J; Caporali, Roberto; Bertin, Philippe; Sullivan, Emma; Wood, Robert; Piercy, James; Vasilescu, Radu; Spurden, Dean; Alvir, Jose; Tarallo, Miriam

2018-01-01

Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy ≥3 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 ≤3.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients.

Antifungal and antibacterial activities of Petroselinum crispum essential oil.

PubMed

Linde, G A; Gazim, Z C; Cardoso, B K; Jorge, L F; Tešević, V; Glamoćlija, J; Soković, M; Colauto, N B

2016-07-29

Parsley [Petroselinum crispum (Mill.) Fuss] is regarded as an aromatic, culinary, and medicinal plant and is used in the cosmetic, food, and pharmaceutical industries. However, few studies with conflicting results have been conducted on the antimicrobial activity of parsley essential oil. In addition, there have been no reports of essential oil obtained from parsley aerial parts, except seeds, as an alternative natural antimicrobial agent. Also, microorganism resistance is still a challenge for health and food production. Based on the demand for natural products to control microorganisms, and the re-evaluation of potential medicinal plants for controlling diseases, the objective of this study was to determine the chemical composition and antibacterial and antifungal activities of parsley essential oil against foodborne diseases and opportunistic pathogens. Seven bacteria and eight fungi were tested. The essential oil major compounds were apiol, myristicin, and b-phellandrene. Parsley essential oil had bacteriostatic activity against all tested bacteria, mainly Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica, at similar or lower concentrations than at least one of the controls, and bactericidal activity against all tested bacteria, mainly S. aureus, at similar or lower concentrations than at least one of the controls. This essential oil also had fungistatic activity against all tested fungi, mainly, Penicillium ochrochloron and Trichoderma viride, at lower concentrations than the ketoconazole control and fungicidal activity against all tested fungi at higher concentrations than the controls. Parsley is used in cooking and medicine, and its essential oil is an effective antimicrobial agent.

Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease.

PubMed

Wang, Liqun; Xia, Jing; Li, Jonathan; Hagemann, Tracy L; Jones, Jeffrey R; Fraenkel, Ernest; Weitz, David A; Zhang, Su-Chun; Messing, Albee; Feany, Mel B

2018-05-15

Glial cells have increasingly been implicated as active participants in the pathogenesis of neurological diseases, but critical pathways and mechanisms controlling glial function and secondary non-cell autonomous neuronal injury remain incompletely defined. Here we use models of Alexander disease, a severe brain disorder caused by gain-of-function mutations in GFAP, to demonstrate that misregulation of GFAP leads to activation of a mechanosensitive signaling cascade characterized by activation of the Hippo pathway and consequent increased expression of A-type lamin. Importantly, we use genetics to verify a functional role for dysregulated mechanotransduction signaling in promoting behavioral abnormalities and non-cell autonomous neurodegeneration. Further, we take cell biological and biophysical approaches to suggest that brain tissue stiffness is increased in Alexander disease. Our findings implicate altered mechanotransduction signaling as a key pathological cascade driving neuronal dysfunction and neurodegeneration in Alexander disease, and possibly also in other brain disorders characterized by gliosis.

3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims

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

Schwarcz, R.; Okuno, E.; White, R.J.

1988-06-01

An excess of the tryptophan metabolite quinolinic acid in the brain has been hypothetically related to the pathogenesis of Huntington disease. Quinolinate's immediate biosynthetic enzyme, 3-hydroxyanthranilate oxygenase, has now been detected in human brain tissue. The activity of 3-hydroxyanthranilate oxygenase is increased in Huntington disease brains as compared to control brains. The increment is particularly pronounced in the striatum, which is known to exhibit the most prominent nerve-cell loss in Huntington disease. Thus, the Huntington disease brain has a disproportionately high capability to produce the endogenous excitotoxin quinolinic acid. This finding may be of relevance for clinical, neuropathologic, and biochemicalmore » features associated with Huntington disease.« less

Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications.

PubMed

McConnell, Ryan A; Mahadevan, Uma

2016-06-01

For many women with inflammatory bowel disease (IBD), the illness coincides with their childbearing years. IBD increases the risk of pregnancy complications and adverse pregnancy outcomes. The multidisciplinary care team should emphasize the importance of medication adherence to achieve preconception disease control and maintain corticosteroid-free remission throughout pregnancy. Medication adjustments to reduce fetal exposure may be considered on an individualized basis in quiescent disease; however, any benefits of such adjustments remain theoretic and there is risk of worsening disease activity. Mode of delivery is determined by obstetric indications, except for women with active perianal disease who should consider cesarean delivery. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of a partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease: a pragmatic randomized controlled trial.

PubMed

Jonsdottir, Helga; Amundadottir, Olof R; Gudmundsson, Gunnar; Halldorsdottir, Bryndis S; Hrafnkelsson, Birgir; Ingadottir, Thorbjorg Soley; Jonsdottir, Rosa; Jonsson, Jon Steinar; Sigurjonsdottir, Ellen D; Stefansdottir, Ingibjorg K

2015-11-01

To evaluate the effectiveness of a 6-month, partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease. Self-management is a widely valued concept used to address contemporary issues of chronic health problems. Findings of self-management programmes for people with chronic obstructive pulmonary disease are inconclusive. Pragmatic randomized control trial. Patients, 45-65 years old, with mild and moderate chronic obstructive pulmonary disease were invited with a family member. Experimental group (n = 48) participated in a 6-month, partnership-based self-management programme consisting of: (a) three to four conversations between nurse and patient-family member; (b) 6 months of smoking cessation; and (c) interdisciplinary team-patient-family member group meeting. Control group (n = 52) received usual care. Data were collected at months zero, six and 12. The trial lasted from June 2009-March 2013. Patients with mild and moderate chronic obstructive pulmonary disease who participated in the partnership-based self-management programme perceived less intrusiveness of the disease and its treatment than patients in the control group. Patients in the experimental group did not have better health-related quality of life, less anxiety or depression, increased physical activity, fewer exacerbations or better smoking status than patients in the control group. Patients in both groups found participation in the research useful and important. The partnership-based self-management programme had benefits concerning perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles, activities and interests for young patients with the disease in its early stages. High satisfaction in control group, low family attendance and the relatively short treatment period may explain the less than expected benefits of the programme. © 2015 John Wiley & Sons Ltd.

Up regulation of serum tumor necrosis factor-related apoptosis inducing ligand in juvenile-onset systemic lupus erythematosus: relations with disease activity, antibodies to double -stranded DNA, nephritis and neutropenia.

PubMed

Ezzat, Mohamed H M; El-Gammasy, Tarek M A; Shaheen, Kareem Y A; El-Mezdawi, Ramzi A M; Youssef, Mervat S M

2013-06-01

Apoptosis is induced by binding of death receptor ligands, members of the tumor necrosis factor (TNF) superfamily, to their cognate receptors. It is suggested that TNF-related apoptosis inducing ligand (TRAIL) is involved in pathogenesis of juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to assess TRAIL concentrations in sera of JSLE children and to determine their potential relationship with disease activity, anti-double-stranded DNA (anti-dsDNA) levels, neutropenia and renal involvement. Circulating levels of TRAIL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 40 JSLE patients (20 with active and 20 with inactive disease) and 20 controls. The mean (SEM) serum TRAIL concentration in JSLE was 1750.7 (440.2) pg/mL. Serum TRAIL concentrations in patients were higher than those in controls (P < 0.01). Serum TRAIL concentrations for children with inactive disease (1854.8 [485.4] pg/mL) and those with activity (1646.6 [390.6] pg/mL) were statistically comparable. JSLE children with positive anti-dsDNA antibodies had significantly higher TRAIL levels (mean = 1846 [456] vs. 1455 [325] pg/mL; P < 0.05). Serum TRAIL concentrations were significantly higher in classes III and IV nephritis compared to classes I and II nephritis (1970 [512] vs. 1330 [331] pg/mL; P < 0.01). Serum TRAIL concentrations in patients with neutropenia were higher than those without neutropenia (1805 [505] vs. 1516 [400] pg/mL; P = 0.042) and in controls (P = 0.024). Our data indicate that an increased level of TRAIL is a feature of JSLE that correlates with disease activity, anti-dsDNA titers neutropenia and lupus nephritis. © 2013 The Authors International Journal of Rheumatic Diseases © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Norrie disease gene is distinct from the monoamine oxidase genes.

PubMed

Sims, K B; Ozelius, L; Corey, T; Rinehart, W B; Liberfarb, R; Haines, J; Chen, W J; Norio, R; Sankila, E; de la Chapelle, A

1989-09-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and/or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in "classic" Norrie disease patients. Genomic DNA from these "nondeletion" Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease.

Effects of postharvest salicylic acid dipping on Alternaria rot and disease resistance of jujube fruit during storage.

PubMed

Cao, Jiankang; Yan, Jiaqi; Zhao, Yumei; Jiang, Weibo

2013-10-01

Considerable postharvest losses caused by Alternaria alternata often occur in Chinese jujube fruit, and synthetic fungicides have been widely used to protect the fruit from Alternaria rot. However, the potential harmfulness of fungicide residues to human health and the environment cannot be ignored. This study was conducted to develop an alternative approach for controlling postharvest disease by inducing fruit resistance with salicylic acid (SA) dipping. Disease incidence and lesion area in the jujube fruit inoculated with A. alternata were significantly inhibited by 2 and 2.5 mmol L(-1) SA dipping. Naturally infected decay rate and index in jujubes were also significantly reduced by SA dipping during long-term storage at 0°C. SA enhanced activities of the main defense-related enzymes including phenylalanine ammonia-lyase, peroxidase, chitinase and β-1,3-glucanase in the fruit during storage. SA strongly decreased catalase activity but increased superoxide dismutase activity and ascorbic acid content in jujubes. The beneficial effects of SA on fruit protection may be due to its ability to activate several highly coordinated defence-related systems in jujubes, instead of its fungicidal activity. The findings indicated that application of SA would offer an alternative approach that helps to control postharvest disease and maintain storage quality in fruits. © 2013 Society of Chemical Industry.

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

Mitogen-activated protein kinase phosphatase (MKP)-1 in immunology, physiology, and disease.

PubMed

Wancket, Lyn M; Frazier, W Joshua; Liu, Yusen

2012-02-13

Mitogen-activated protein kinases (MAPKs) are key regulators of cellular physiology and immune responses, and abnormalities in MAPKs are implicated in many diseases. MAPKs are activated by MAPK kinases through phosphorylation of the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr domain, where Xaa represents amino acid residues characteristic of distinct MAPK subfamilies. Since MAPKs play a crucial role in a variety of cellular processes, a delicate regulatory network has evolved to control their activities. Over the past two decades, a group of dual specificity MAPK phosphatases (MKPs) has been identified that deactivates MAPKs. Since MAPKs can enhance MKP activities, MKPs are considered as an important feedback control mechanism that limits the MAPK cascades. This review outlines the role of MKP-1, a prototypical MKP family member, in physiology and disease. We will first discuss the basic biochemistry and regulation of MKP-1. Next, we will present the current consensus on the immunological and physiological functions of MKP-1 in infectious, inflammatory, metabolic, and nervous system diseases as revealed by studies using animal models. We will also discuss the emerging evidence implicating MKP-1 in human disorders. Finally, we will conclude with a discussion of the potential for pharmacomodulation of MKP-1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer's disease.

PubMed

Hamelin, Lorraine; Lagarde, Julien; Dorothée, Guillaume; Potier, Marie Claude; Corlier, Fabian; Kuhnast, Bertrand; Caillé, Fabien; Dubois, Bruno; Fillon, Ludovic; Chupin, Marie; Bottlaender, Michel; Sarazin, Marie

2018-06-01

Although brain neuroinflammation may play an instrumental role in the pathophysiology of Alzheimer's disease, its actual impact on disease progression remains controversial, being reported as either detrimental or protective. This work aimed at investigating the temporal relationship between microglial activation and clinical progression of Alzheimer's disease. First, in a large cohort of patients with Alzheimer's disease we analysed the predictive value of microglial activation assessed by 18F-DPA-714 PET imaging on functional, cognitive and MRI biomarkers outcomes after a 2-year follow-up. Second, we analysed the longitudinal progression of 18F-DPA-714 binding in patients with Alzheimer's disease by comparison with controls, and assessed its influence on clinical progression. At baseline, all participants underwent a clinical assessment, brain MRI, 11C-PiB, 18F-DPA-714 PET imaging and TSPO genotyping. Participants were followed-up annually for 2 years. At the end of the study, subjects were asked to repeat a second 18F-DPA-714-PET imaging. Initial 18F-DPA-714 binding was higher in prodromal (n = 33) and in demented patients with Alzheimer's disease (n = 19) compared to controls (n = 17). After classifying patients into slow and fast decliners according to functional (Clinical Dementia Rating change) or cognitive (Mini-Mental State Examination score decline) outcomes, we found a higher initial 18F-DPA-714 binding in slow than fast decliners. Negative correlations were observed between initial 18F-DPA-714 binding and the Clinical Dementia Rating Sum of Boxes score increase, the MMSE score loss and the progression of hippocampal atrophy. This suggests that higher initial 18F-DPA-714 binding is associated with better clinical prognosis. Twenty-four patients with Alzheimer's disease and 15 control subjects performed a second DPA-PET. We observed an increase of 18F-DPA-714 in patients with Alzheimer's disease as compared with controls (mean 13.2% per year versus 4.2%) both at the prodromal (15.8%) and at the demented stages (8.3%). The positive correlations between change in 18F-DPA-714 binding over time and the three clinical outcome measures (Clinical Dementia Rating, Mini-Mental State Examination, hippocampal atrophy) suggested a detrimental effect on clinical Alzheimer's disease progression of increased neuroinflammation after the initial PET examination, without correlation with PiB-PET uptake at baseline. High initial 18F-DPA-714 binding was correlated with a low subsequent increase of microglial activation and favourable clinical evolution, whereas the opposite profile was observed when initial 18F-DPA-714 binding was low, independently of disease severity at baseline. Taken together, our results support a pathophysiological model involving two distinct profiles of microglial activation signatures with different dynamics, which differentially impact on disease progression and may vary depending on patients rather than disease stages.

Phosphatidylinositol 3-kinase activity in murine motoneuron disease: the progressive motor neuropathy mouse.

PubMed

Wagey, R; Lurot, S; Perrelet, D; Pelech, S L; Sagot, Y; Krieger, C

2001-01-01

A murine model of motoneuron disease, the pmn/pmn mouse, shows a reduction in the retrograde transport of fluorescent probes applied directly onto the cut end of sciatic nerve. Brain-derived neurotrophic factor (BDNF), when co-applied with fluorescent tracers, increases the number of retrograde labelled motoneurons. We demonstrate here that spinal cord tissue from pmn/pmn mice had significantly reduced phosphatidylinositol 3-kinase activity and expression in the particulate fraction compared to controls, without changes in the activities or expression of the downstream kinases, protein kinase B/Akt or Erk1. Systemic administration of BDNF augmented phosphatidylinositol 3-kinase specific activity in spinal cord tissue from pmn/pmn and control mice, with a greater elevation in the particulate fractions of pmn/pmn mice than in controls. We examined the effect of inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase on the retrograde labelling of motoneurons, 24h following the direct application of inhibitors and Fluorogold to the cut end of sciatic nerve in control and pmn/pmn mice (labelling index). The mitogen-activated protein kinase kinase inhibitor PD 98059 had no effect on the labelling index in control or pmn/pmn mice. In the absence of exogenous BDNF, phosphatidylinositol 3-kinase inhibitors reduced the number of labelled motoneurons in control mice, without changing the labelling index in pmn/pmn. Co-application of phosphatidylinositol 3-kinase inhibitors with BDNF to the cut end of sciatic nerve blocked the action of BDNF on retrograde labelling in pmn/pmn mice. These results indicate that the retrograde labelling of motoneurons is mediated by phosphatidylinositol 3-kinase-dependent and -independent pathways. In pmn/pmn mice, phosphatidylinositol 3-kinase activity in spinal neurons is below the level required for optimal retrograde labelling of motoneurons and labelling can be augmented by the administration of growth factors stimulating phosphatidylinositol 3-kinase activity. The data indicate that phosphatidylinositol 3-kinase activity is important in the uptake and/or retrograde transport of substances by motoneurons and is altered in this model of motoneuron diseases.

Pathological histone acetylation in Parkinson's disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition.

PubMed

Harrison, Ian F; Smith, Andrew D; Dexter, David T

2018-02-14

Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD. Here we quantify histone acetylation in the Substantia Nigra pars compacta (SNpc) in the brains of control, early and late stage PD cases to determine if histone acetylation is a function of disease progression. PD development is associated with Braak-dependent increases in histone acetylation. Concurrently, we show that as expected disease progression is associated with reduced markers of dopaminergic neurons and increased markers of activated microglia. We go on to demonstrate that in vitro, degenerating dopaminergic neurons exhibit histone hypoacetylation whereas activated microglia exhibit histone hyperacetylation. This suggests that the disease-dependent increase in histone acetylation observed in human PD cases is likely a combination of the contributions of both degenerating dopaminergic neurons and infiltrating activated microglia. The HDAC SIRT 2 has become increasingly implicated as a novel target for mediation of neuroprotection in PD: the neuronal and microglial specific effects of its inhibition however remain unclear. We demonstrate that SIRT 2 expression in the SNpc of PD brains remains relatively unchanged from controls and that SIRT 2 inhibition, via AGK2 treatment of neuronal and microglial cultures, results in neuroprotection of dopaminergic neurons and reduced activation of microglial cells. Taken together, here we demonstrate that histone acetylation is disease-dependently altered in PD, likely due the effects of dopaminergic neurodegeneration and microglial infiltration; yet SIRT 2 remains relatively unaltered with disease. Given the stable nature of SIRT 2 expression with disease and the effects of SIRT 2 inhibitor treatment on degenerating dopaminergic neurons and activated microglia detected in vitro, SIRT 2 inhibitors warrant further investigation as potential therapeutics for the treatment of the PD. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Cerebral perfusion imaging in Alzheimer's disease. Use of single photon emission computed tomography and iofetamine hydrochloride I 123

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

Johnson, K.A.; Mueller, S.T.; Walshe, T.M.

1987-02-01

We used single photon emission computed tomography (SPECT) to study 15 patients with Alzheimer's disease and nine controls. Iofetamine hydrochloride I 123 uptake data were recorded from the entire brain using a rotating gamma camera. Activity ratios were measured for the frontal, posterior parietal, posterior, medial, and lateral cortical temporal regions and striate cortex and were normalized by the activity in the cerebellum. Abnormalities in iofetamine hydrochloride I 123 activity were similar to the abnormalities in glucose metabolism observed with positron emission tomography. Cortical tracer activity was globally depressed in patients with Alzheimer's disease, with the greatest reduction in themore » posterior parietal cortex.« less

Effect of probiotics enriched diet on Paralichthys olivaceus infected with lymphocystis disease virus (LCDV).

PubMed

Harikrishnan, Ramasamy; Balasundaram, Chellam; Heo, Moon-Soo

2010-11-01

We report the effect of two probiotics, Lactobacil and Sporolac as separate or mixed diets on innate immune mechanisms, such as phagocytosis activity, superoxide anion production of blood leukocytes, complement activity and plasma lysozyme activity, and disease resistance in lymphocystis disease virus (LCDV) infected olive flounder, Paralichthys olivaceus (523.5 +/- 18.3 g) on week 1, 2, and 4. In infected fish, administration of diet supplemented with Lactobacil individually or mixed with Sporolac significantly enhanced the immune parameters like phagocytic activity superoxide anion production, complement activity, and plasma lysozyme. However administration of supplemented diet with Sporolac alone, all the chosen immune parameters did not enhance when compared to control group; this diets resulted in lower mortality (30% and 25%) than Sporolac diet group (45%) in 30 days. We conclude that Lactobacil individually or mixed with Sporolac act as immunostimulants that enhance the innate immune response and disease resistance in lymphocystis disease virus (LCDV) infected olive flounder. Published by Elsevier Ltd.

Intravenous Immunoglobulin in the Therapeutic Armamentarium of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

PubMed Central

Sakthiswary, Rajalingham; D’Cruz, David

2014-01-01

Abstract Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants. IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221–0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1–41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels. PMID:25310743

Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis.

PubMed

Sakthiswary, Rajalingham; D'Cruz, David

2014-10-01

Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants.IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221-0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1-41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels.

Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease

PubMed Central

Kotze, Paulo Gustavo; Martinez, Carlos Augusto Real; Camargo, Michel Gardere; Guadagnini, Dioze; Calixto, Antonio Ramos; Vasques, Ana Carolina Junqueira; Ayrizono, Maria de Lourdes Setsuko; Geloneze, Bruno; Pareja, José Carlos; Saad, Mario José; Coy, Claudio Saddy Rodrigues

2017-01-01

Background/Aims Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α). Methods Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP. Results Serum levels of LPS were significantly elevated in the active CD group (P=0.003). Levels of IL-1β (P=0.002), IL-6 (P=0.003), and IL-17 (P<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (P<0.001). The CD26 levels were lower in the CD groups than in the control group (P<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=−0.53, P=0.016) in the CD groups. Conclusions Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers. PMID:28670232

Exploring the ameliorative potential of probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum on dextran sodium sulphate induced colitis in mice.

PubMed

Jadhav, Sagar R; Shandilya, Umesh Kr; Kansal, Vinod K

2013-02-01

Conventional medical therapies for ulcerative colitis (UC) are still limited due to the adverse side effects like dose-dependent diarrhoea and insufficient potency to keep in remission for long-term periods. So, new alternatives that provide more effective and safe therapies for ulcerative colitis are constantly being sought. In the present study, probiotic LaBb Dahi was selected for investigation of its therapeutic effect on DSS-induced colitis model in mice. LaBb Dahi was prepared by co-culturing Dahi culture of Lactococci along with selected strain of Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 in buffalo milk. Four groups of mice (12 each) were fed for 17 d with buffalo milk (normal control), buffalo milk plus DSS (Colitis control), Dahi plus DSS, and LaBb Dahi plus DSS, respectively, with basal diet. The disease activity scores, weight loss, organ weight, colon length, myeloperoxidase (MPO) and β-glucoronidase activity was assessed, and the histopathological picture of the colon of mice was studied. All colitis control mice evidenced significant increase in MPO, β-glucoronidase activity and showed high disease activity scores along with histological damage to colonic tissue. Feeding with LaBb Dahi offered significant reduction in MPO activity, β-glucoronidase activity and improved disease activity scores. We found significant decline in length of colon, organ weight and body weight in colitis induced controls which were improved significantly by feeding LaBb Dahi. The present study suggests that LaBb Dahi can be used as a potential nutraceutical intervention to combat UC related changes and may offer effective adjunctive treatment for management of UC.

Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease: The PReVaiL randomized clinical trial.

PubMed

Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars; Jakobsen, Janus Christian; Zoffmann, Vibeke; Dideriksen, Kasper; Kruse, Anne; Mikkelsen, Ulla Ramer; Wetterslev, Jørn

2016-10-15

To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. Randomized clinical trial. Denmark. A total of 158 adolescents aged 13-16years with no physical activity restrictions after repaired complex congenital heart disease. PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. The primary outcome was maximal oxygen uptake (VO2 peak) at 52weeks after randomization. The secondary outcome was physical activity. Exploratory outcomes were generic and disease-specific questionnaires. In the intervention group, 58 patients (72%) completed the final test, but of those, only 46 (57%) fulfilled the compliance criteria of using the eHealth application for at least 2 consecutive weeks. In the control group, 61 patients (79%) completed both exercise tests. Adjusted for baseline values, the difference between the intervention group and the control group in mean VO2 peak at 1year was -0.65ml·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. Adding a tailored eHealth intervention to health education and individual counseling did not affect outcomes among adolescents with congenital heart disease. Our results do not support the use of this eHealth intervention in adolescents with complex congenital heart disease. Clinical trials.gov identifier: NCT01189981. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

PubMed

Howe, H S; Thong, B Y H; Kong, K O; Chng, H H; Lian, T Y; Chia, F L; Tay, K S S; Lau, T C; Law, W G; Koh, E T; Leung, B P

2017-09-01

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies. © 2017 British Society for Immunology.

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.

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.

Cardiovascular involvement in systemic rheumatic diseases: An integrated view for the treating physicians.

PubMed

Lee, Kwang Seob; Kronbichler, Andreas; Eisenhut, Michael; Lee, Keum Hwa; Shin, Jae Il

2018-03-01

Systemic autoimmune diseases can affect various kinds of organs including the kidney, the skin, soft tissue and the bone. Among others, cardiovascular involvement in rheumatic diseases has been shown to affect myocardium, pericardium, cardiac vessels, conduction system and valves, eventually leading to increased mortality. In general, underlying chronic inflammation leads to premature atherosclerosis, but also other manifestations such as arrhythmia and heart failure may have a 'silent' progress. Traditional cardiovascular risk factors play a secondary role, while disease-specific factors (i.e. disease duration, severity, antibody positivity, persistent disease activity) can directly influence the cardiovascular system. Therefore, early diagnosis is critical to optimize management and to control inflammatory activity and recent data suggest that risk factors (i.e. hypercholesterolemia and hypertension) need intensive treatment as well. With the advent of immunosuppressive agents, most rheumatic diseases are well controlled on treatment, but information related to their cardioprotective efficacy is not well-defined. In this review, we focus on cardiovascular involvement in rheumatic diseases and highlight current evidence which should be of help for the treating physicians. Moreover, cardiotoxicity of immunosuppressive drugs is a rare issue and such potential adverse events will be briefly discussed. Copyright © 2018. Published by Elsevier B.V.

MCP-1 in urine as biomarker of disease activity in Systemic Lupus Erythematosus.

PubMed

Barbado, Julia; Martin, Debora; Vega, Luisa; Almansa, Raquel; Gonçalves, Lisbeth; Nocito, Mercedes; Jimeno, Antonio; Ortiz de Lejarazu, Raúl; Bermejo-Martin, Jesus F

2012-11-01

Conventional clinical parameters are not sensitive or specific enough for detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE). Measurement of cytokines in urine is an encouraging approach to detection of early flares in this disease. Here we have profiled 27 different cytokines, chemokines and celular growth factors in the urine of 48 patients previously diagnosed of SLE as potential biomarkers of disease activity. Correlation analysis with Bonferroni correction showed that MCP-1 was the only immune mediator which levels in urine correlated directly with the SLE Disease Activity Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003). MCP-1 correlated inversely with levels of C3 complement protein in serum (-0.50,0.001). MCP-1 showed significant higher levels in patients with severe disease activity in comparison with those exhibiting mild activity. Levels of this chemokine were also higher in patients with severe disease activity in comparison with patients with inactive disease and healthy controls. Areas under receiver operating characteristic curves (AUROC) for detection of severe disease (SLEDAI⩾8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65-0.96) 0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for detecting renal involvement [0.70 (0.52-0.87) 0.050]. When correlation analysis were repeated excluding those patients with active renal disease (n=14), levels of MCP-1 in urine kept on showing a significant positive association with SLEDAI-2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated the superiority of MCP-1 over a wide range of cytokines as biomarker of disease activity in SLE. Copyright © 2012 Elsevier Ltd. All rights reserved.

Linking tobacco control policies and practices to early cancer endpoints: surveillance as an agent for change.

PubMed

Hartman, Anne M; Thun, Michael J; Ballard-Barbash, Rachel

2008-09-01

State tobacco control programs provide an important laboratory for the development, implementation, and evaluation of comprehensive tobacco control interventions. Studies have shown that states and municipalities with aggressive tobacco control programs have experienced more rapid decreases in per capita cigarette sales, smoking prevalence, lung cancer, and heart disease than entities without such programs. Despite strong evidence that population-level interventions are critical in achieving large and sustained reductions in tobacco use, states do not fund tobacco control efforts at levels recommended by the Centers for Disease Control and Prevention. Research on the effectiveness and cost effectiveness of these activities is essential to inform and strengthen tobacco control at the state level. A workshop, co-organized by the American Cancer Society, the National Cancer Institute, the American Association for Cancer Research, and the Centers for Disease Control and Prevention, was held in Philadelphia in December, 2007, to discuss the topic "Linking tobacco control policies and practices to early cancer endpoints: surveillance as an agent for change." Participants represented three different disciplines. Tobacco surveillance researchers described the data currently collected on state-level tobacco control policies, protobacco countermeasures by the industry, public attitudes toward tobacco use, and measures of smoking prevalence and consumption. Cancer registry experts described the geographic coverage of high quality, population-based cancer registries. Mathematical modeling experts discussed various modeling approaches that can be used to relate upstream tobacco promotion and control activities to downstream measures such as public attitudes, changes in tobacco use, and trends in tobacco-related diseases. The most important recommendation of the Workshop was a call for national leadership to enhance the collection and integration of data from multiple sources as a resource to further study and strengthen the scientific basis for tobacco control.

Abnormal regional activity and functional connectivity in resting-state brain networks associated with etiology confirmed unilateral pulsatile tinnitus in the early stage of disease.

PubMed

Lv, Han; Zhao, Pengfei; Liu, Zhaohui; Li, Rui; Zhang, Ling; Wang, Peng; Yan, Fei; Liu, Liheng; Wang, Guopeng; Zeng, Rong; Li, Ting; Dong, Cheng; Gong, Shusheng; Wang, Zhenchang

2017-03-01

Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging (rs-fMRI) using analyses of the regional activity and functional connectivity (FC) of the networks in the brain. This study was designed to demonstrate the functional network alterations in the patients with pulsatile tinnitus (PT). In this study, we recruited 45 patients with unilateral PT in the early stage of disease (less than 48 months of disease duration) and 45 normal controls. We used regional homogeneity (ReHo) and seed-based FC computational methods to reveal resting-state brain activity features associated with pulsatile tinnitus. Compared with healthy controls, PT patients showed regional abnormalities mainly in the left middle occipital gyrus (MOG), posterior cingulate gyrus (PCC), precuneus and right anterior insula (AI). When these regions were defined as seeds, we demonstrated widespread modification of interaction between the auditory and non-auditory networks. The auditory network was positively connected with the cognitive control network (CCN), which may associate with tinnitus related distress. Both altered regional activity and changed FC were found in the visual network. The modification of interactions of higher order networks were mainly found in the DMN, CCN and limbic networks. Functional connectivity between the left MOG and left parahippocampal gyrus could also be an index to reflect the disease duration. This study helped us gain a better understanding of the characteristics of neural network modifications in patients with pulsatile tinnitus. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-cleavage of human CLCA1 protein by a novel internal metalloprotease domain controls calcium-activated chloride channel activation.

PubMed

Yurtsever, Zeynep; Sala-Rabanal, Monica; Randolph, David T; Scheaffer, Suzanne M; Roswit, William T; Alevy, Yael G; Patel, Anand C; Heier, Richard F; Romero, Arthur G; Nichols, Colin G; Holtzman, Michael J; Brett, Tom J

2012-12-07

The chloride channel calcium-activated (CLCA) family are secreted proteins that regulate both chloride transport and mucin expression, thus controlling the production of mucus in respiratory and other systems. Accordingly, human CLCA1 is a critical mediator of hypersecretory lung diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, that manifest mucus obstruction. Despite relevance to homeostasis and disease, the mechanism of CLCA1 function remains largely undefined. We address this void by showing that CLCA proteins contain a consensus proteolytic cleavage site recognized by a novel zincin metalloprotease domain located within the N terminus of CLCA itself. CLCA1 mutations that inhibit self-cleavage prevent activation of calcium-activated chloride channel (CaCC)-mediated chloride transport. CaCC activation requires cleavage to unmask the N-terminal fragment of CLCA1, which can independently gate CaCCs. Gating of CaCCs mediated by CLCA1 does not appear to involve proteolytic cleavage of the channel because a mutant N-terminal fragment deficient in proteolytic activity is able to induce currents comparable with that of the native fragment. These data provide both a mechanistic basis for CLCA1 self-cleavage and a novel mechanism for regulation of chloride channel activity specific to the mucosal interface.

Self-cleavage of Human CLCA1 Protein by a Novel Internal Metalloprotease Domain Controls Calcium-activated Chloride Channel Activation*♦

PubMed Central

Yurtsever, Zeynep; Sala-Rabanal, Monica; Randolph, David T.; Scheaffer, Suzanne M.; Roswit, William T.; Alevy, Yael G.; Patel, Anand C.; Heier, Richard F.; Romero, Arthur G.; Nichols, Colin G.; Holtzman, Michael J.; Brett, Tom J.

2012-01-01

The chloride channel calcium-activated (CLCA) family are secreted proteins that regulate both chloride transport and mucin expression, thus controlling the production of mucus in respiratory and other systems. Accordingly, human CLCA1 is a critical mediator of hypersecretory lung diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, that manifest mucus obstruction. Despite relevance to homeostasis and disease, the mechanism of CLCA1 function remains largely undefined. We address this void by showing that CLCA proteins contain a consensus proteolytic cleavage site recognized by a novel zincin metalloprotease domain located within the N terminus of CLCA itself. CLCA1 mutations that inhibit self-cleavage prevent activation of calcium-activated chloride channel (CaCC)-mediated chloride transport. CaCC activation requires cleavage to unmask the N-terminal fragment of CLCA1, which can independently gate CaCCs. Gating of CaCCs mediated by CLCA1 does not appear to involve proteolytic cleavage of the channel because a mutant N-terminal fragment deficient in proteolytic activity is able to induce currents comparable with that of the native fragment. These data provide both a mechanistic basis for CLCA1 self-cleavage and a novel mechanism for regulation of chloride channel activity specific to the mucosal interface. PMID:23112050

The effect of an active implementation of a disease management programme for chronic obstructive pulmonary disease on healthcare utilization - a cluster-randomised controlled trial

PubMed Central

2013-01-01

Background The growing population living with chronic conditions calls for efficient healthcare-planning and effective care. Implementing disease-management-programmes is one option for responding to this demand. Knowledge is scarce about the effect of implementation processes and their effect on patients; only few studies have reported the effectiveness of disease-management-programmes targeting patients with chronic obstructive pulmonary disease (COPD). The objective of this paper was to determine the effect on healthcare-utilization of an active implementation model for a disease-management-programme for patients with one of the major multimorbidity diseases, COPD. Methods The standard implementation of a new disease-management-programme for COPD was ongoing during the study-period from November 2008 to November 2010 in the Central Denmark Region. We wanted to test a strategy using Breakthrough Series, academic detailing and lists of patients with COPD. It targeted GPs and three hospitals serving approx. 60,000 inhabitants aged 35 or older and included interventions directed at professionals, organisations and patients. The study was a non-blinded block- and cluster-randomised controlled trial with GP-practices as the unit of randomisation. In Ringkoebing-Skjern Municipality, Denmark, 16 GP-practices involving 38 GPs were randomised to either the intervention-group or the control-group. A comparable neighbouring municipality acted as an external-control-group which included nine GP-practices with 25 GPs. An algorithm based on health-registry-data on lung-related contacts to the healthcare-system identified 2,736 patients who were alive at the end of the study-period. The population included in this study counted 1,372 (69.2%) patients who responded to the baseline questionnaire and confirmed their COPD diagnosis; 458 (33.4%) patients were from the intervention-group, 376 (27.4%) from the control-group and 538(39.2%) from the external-control-group. The primary outcome was adherence to the disease-management-programme measured at patient-level by use of specific services from general practice. Secondary outcomes were use of out-of-hours-services, outpatient-clinic, and emergency-department and hospital-admissions. Results The intervention practices provided more planned preventive consultations, additional preventive consultations and spirometries than non-intervention practices. A comparison of the development in the intervention practices with the development in the control-practices showed that the intervention resulted in more planned preventive-consultations, fewer conventional consultations and fewer patients admitted without a lung-related-diagnosis. Conclusions Use of the active implementation model for the disease-management-programme for COPD changed the healthcare utilization in accordance with the programme. Trial registration Clinicaltrials.gov identifier: NCT01228708. PMID:24090189

The effect of an active implementation of a disease management programme for chronic obstructive pulmonary disease on healthcare utilization--a cluster-randomised controlled trial.

PubMed

Smidth, Margrethe; Christensen, Morten Bondo; Fenger-Grøn, Morten; Olesen, Frede; Vedsted, Peter

2013-10-03

The growing population living with chronic conditions calls for efficient healthcare-planning and effective care. Implementing disease-management-programmes is one option for responding to this demand. Knowledge is scarce about the effect of implementation processes and their effect on patients; only few studies have reported the effectiveness of disease-management-programmes targeting patients with chronic obstructive pulmonary disease (COPD). The objective of this paper was to determine the effect on healthcare-utilization of an active implementation model for a disease-management-programme for patients with one of the major multimorbidity diseases, COPD. The standard implementation of a new disease-management-programme for COPD was ongoing during the study-period from November 2008 to November 2010 in the Central Denmark Region. We wanted to test a strategy using Breakthrough Series, academic detailing and lists of patients with COPD. It targeted GPs and three hospitals serving approx. 60,000 inhabitants aged 35 or older and included interventions directed at professionals, organisations and patients. The study was a non-blinded block- and cluster-randomised controlled trial with GP-practices as the unit of randomisation. In Ringkoebing-Skjern Municipality, Denmark, 16 GP-practices involving 38 GPs were randomised to either the intervention-group or the control-group. A comparable neighbouring municipality acted as an external-control-group which included nine GP-practices with 25 GPs. An algorithm based on health-registry-data on lung-related contacts to the healthcare-system identified 2,736 patients who were alive at the end of the study-period. The population included in this study counted 1,372 (69.2%) patients who responded to the baseline questionnaire and confirmed their COPD diagnosis; 458 (33.4%) patients were from the intervention-group, 376 (27.4%) from the control-group and 538(39.2%) from the external-control-group. The primary outcome was adherence to the disease-management-programme measured at patient-level by use of specific services from general practice. Secondary outcomes were use of out-of-hours-services, outpatient-clinic, and emergency-department and hospital-admissions. The intervention practices provided more planned preventive consultations, additional preventive consultations and spirometries than non-intervention practices. A comparison of the development in the intervention practices with the development in the control-practices showed that the intervention resulted in more planned preventive-consultations, fewer conventional consultations and fewer patients admitted without a lung-related-diagnosis. Use of the active implementation model for the disease-management-programme for COPD changed the healthcare utilization in accordance with the programme. Clinicaltrials.gov identifier: NCT01228708.

The Work of US Public Health Service Officers in Puerto Rico, 1898-1919.

PubMed

Rigau-Pérez, Jose G

2017-09-01

The history of the US Public Health Service (PHS) is usually presented in terms of diseases or discoveries; this article examines twenty years' activity in one location. When the United States invaded Puerto Rico in 1898, the Marine Hospital Service (now PHS) took responsibility for foreign quarantine, inspection of immigrants, and medical care for merchant seamen. Its officers evaluated the sanitary conditions of port cities, helped reorganize local disease surveillance and control, and investigated endemic diseases (e.g., hookworm-related anemia) and epidemics (e.g., bubonic plague). After World War I and pandemic influenza, and the greater self-government allowed Puerto Rico by Congress in 1917, PHS officers withdrew from routine local sanitary actions. A narrow geographic focus (Puerto Rico), to examine PHS activity over time (1898 to 1919) provides a richer picture of the agency's impact, and reveals how the sum of disease control activities affected the development of an area's health status and institutions. The duties and, importantly, the personal initiatives of PHS officers in Puerto Rico, such as WW King, produced lasting impact on scientific institutions and administrative, professional, and health care practices.

Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa.

PubMed

Holsen, Laura M; Lawson, Elizabeth A; Blum, Justine; Ko, Eunice; Makris, Nikos; Fazeli, Pouneh K; Klibanski, Anne; Goldstein, Jill M

2012-09-01

Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with interoceptive signalling of one's internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa.

CD4+CD25highFOXP3+ T regulatory cells as a biomarker of disease activity in systemic lupus erythematosus: a prospective study.

PubMed

Tselios, Konstantinos; Sarantopoulos, Alexandros; Gkougkourelas, Ioannis; Boura, Panagiota

2014-01-01

Several studies have reported low numbers of T regulatory cells (Tregs) in active systemic lupus erythematosus (SLE). However, it is not evident if these cells may be utilised as a biomarker in assessing disease activity. Tregs (CD4+CD25highFOXP3+) were prospectively assessed by flow cytometry in 285 separate blood samples from 100 white Caucasian SLE patients and 20 healthy controls. Patients were divided, according to disease activity (as measured by SLEDAI) into groups A (n=39, samples=94, SLEDAI=0), B (n=33, samples=92, SLEDAI=1-5), C (n=10, samples=53, SLEDAI=6-10) and D (n=18, samples=46, SLEDAI>10). Longitudinal measurements were performed in 131 cases (37 relapses, 44 remissions and 50 cases with stable disease activity) during three years. Statistics were performed by Student's t-test or one-way ANOVA; correlations with Pearson co-efficient, while p<0.05 was considered significant. Tregs were found significantly lower in severely active disease (group D), compared to healthy controls, inactive disease, mild and moderate disease activity (0.57±0.16% vs. 1.49±0.19%, 1.19±0.34% and 1.05±0.36%, 0.72±0.21%, p<0.05, respectively). There was a strongly inverse correlation between Tregs and SLEDAI (r=-0.644, p<0.001). Alterations in disease activity were characterised by inverse alterations in Tregs: relapse (from 1.23±0.44% to 0.64±0.19%, p<0.001, mean change 0.59±0.41%), remission (from 0.65±0.27% to 1.17±0.30%, p<0.001, mean change 0.52±0.35%). In cases with unaltered disease activity, Treg numbers remained stable (from 0.98±0.35% to 1.03±0.34%, p=0.245). Tregs were practically halved during relapse (mean reduction 42.6±22.2%), and doubled during remission (mean increment 113±120.9%). Mean change of Tregs in stable disease was significantly lower (7.3±20.6%, p<0.001). A clinically significant change in SLEDAI (sum of cases with relapse and remission, n=81) was followed by a significant (>20%) inverse change in Tregs in 71/81 cases (sensitivity 87.7%). In 50 cases of stable disease activity, Tregs were significantly changed (>20%) in 13 cases (specificity 74%). Positive predictive value (PPV) was 84.5% and negative predictive value (NPV) was 78.7%. CD4+CD25highFOXP3+ T regulatory cells displayed a strongly inverse correlation to disease activity in the long term. Treg alterations reflected changes in SLEDAI with high sensitivity. These cells may be a reliable biomarker for the assessment of disease activity in SLE by longitudinal measurements.

Quantitative nailfold video capillaroscopy in patients with idiopathic inflammatory myopathy.

PubMed

Mercer, Louise K; Moore, Tonia L; Chinoy, Hector; Murray, Andrea K; Vail, Andy; Cooper, Robert G; Herrick, Ariane L

2010-09-01

To quantify nailfold capillary density and dimensions in patients with idiopathic inflammatory myopathy (IIM) and compare them with those in healthy controls; to look for associations with microvascular disease in IIM; and to determine whether nailfold capillary density and dimensions change over time. Nailfold video microscopy (x300 magnification) was performed on 24 patients with IIM and 35 healthy controls. Capillary density and dimensions (total width and apical width) were quantified. Patients were clinically assessed and disease activity recorded using the Myositis Disease Activity Assessment Tool. Disease severity and physical function were assessed using the myositis damage index and Stanford HAQ, respectively. Findings were analysed using linear and logistic regression, adjusted for age and sex. In a subgroup of 16 patients with IIM and 27 controls, the process was repeated 6-12 months later and the results were analysed using Student's t-test. Capillary density was lower and dimensions were higher in patients with IIM compared with healthy controls (P < 0.001 for all). Anti-Jo-1 antibody was associated with reduced capillary density. In the longitudinal cohort, the mean change in capillary density was -1.4 in patients vs -0.4 in controls (P = 0.07). Mean change in capillary dimensions did not differ between patients and controls, but some patients demonstrated pronounced changes in capillary morphology over time. Reduced capillary density and increased dimensions in patients with IIM can be quantified using nailfold capillaroscopy, suggesting that nailfold capillaroscopy may be useful as an outcome measure of microvascular disease in studies of IIM.

Expression analysis in intestinal mucosa reveals complex relations among genes under the association peaks in celiac disease.

PubMed

Plaza-Izurieta, Leticia; Fernandez-Jimenez, Nora; Irastorza, Iñaki; Jauregi-Miguel, Amaia; Romero-Garmendia, Irati; Vitoria, Juan Carlos; Bilbao, Jose Ramon

2015-08-01

Celiac disease is a chronic immune-mediated disorder with an important genetic component. To date, there are 57 independent association signals from 39 non-HLA loci, and a total of 66 candidate genes have been proposed. We aimed to scrutinize the functional implication of 45 of those genes by analyzing their expression in the disease tissue of celiac patients (at diagnosis/treatment) compared with non-celiac controls. Moreover, we investigated the SNP genotype effect in gene expression and performed coexpression analyses. Several genes showed differential expression among disease groups, most of them related to immune response. Multiple trans-eQTLs but only four cis-eQTLs were found, and surprisingly the genotype effect seems to be stimulus dependent as it differs among groups. Coexpression levels vary from higher to lower levels in active patients at diagnosis, treated patients and non-celiac controls respectively. A subset of 18 genes tightly correlated in both groups of patients but not in controls was identified. Interestingly, this subset of genes was influenced by the genotype of three SNPs. One of the SNPs, rs1018326 on chromosome two is on top of a known lincRNA whose function is not yet described, and whose expression seems to be upregulated in active disease when comparing biopsy pairs from the same individuals. Our results strongly suggest that the effects of disease-associated SNPs go far beyond the oversimplistic idea of transcriptional control at a nearby locus. Further investigations are needed to determine how each variant disrupts fine-tuning mechanisms in the genome that eventually lead to disease.

Public Health Research at the CDC: Implications for Communication Sciences and Disorders

ERIC Educational Resources Information Center

Boyle, C.; Alexander, M.

2005-01-01

The following paper provides an overview of public health research at the Centers for Disease Control and Prevention (CDC), with emphasis on research involving speech, language and hearing disorders. Public health research involves a sequence of activities from disease tracking to disease prevention. Public health focuses on populations and works…

Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

PubMed

Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

2014-09-01

Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

Rheumatic disease among Oklahoma tribal populations: a cross-sectional study.

PubMed

Gaddy, Jasmine R; Vista, Evan S; Robertson, Julie M; Dedeke, Amy B; Roberts, Virginia C; Klein, Wendy S; Levin, Jeremy H; Mota, Fabio H; Cooper, Tina M; Grim, Gloria A; Khan, Sohail; James, Judith A

2012-10-01

Rheumatic diseases cause significant morbidity within American Indian populations. Clinical disease presentations, as well as historically associated autoantibodies, are not always useful in making a rapid diagnosis or assessing prognosis. The purpose of our study was to identify autoantibody associations among Oklahoma tribal populations with rheumatic disease. Oklahoma tribal members (110 patients with rheumatic disease and 110 controls) were enrolled at tribal-based clinics. Patients with rheumatic disease (suspected or confirmed diagnosis) were assessed by a rheumatologist for clinical features, disease criteria, and activity measures. Blood samples were collected and tested for common rheumatic disease autoantibodies [antinuclear antibody (ANA), anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), anti-Ro, anti-La, anti-Sm, anti-nRNP, anti-ribosomal P, anti-dsDNA, and anticardiolipins]. In patients with suspected systemic rheumatic diseases, 72% satisfied American College of Rheumatology classification criteria: 40 (36%) had rheumatoid arthritis (RA), 16 (15%) systemic lupus erythematosus, 8 (7%) scleroderma, 8 (7%) osteoarthritis, 4 (4%) fibromyalgia, 2 (2%) seronegative spondyloarthropathy, 1 Sjögren's syndrome, and 1 sarcoidosis. Compared to controls, RA patient sera were more likely to contain anti-CCP (55% vs 2%; p < 0.001) or RF IgM antibodies (57% vs 10%; p < 0.001); however, the difference was greater for anti-CCP. Anti-CCP positivity conferred higher disease activity scores (DAS28 5.6 vs 4.45; p = 0.021) while RF positivity did not (DAS28 5.36 vs 4.64; p = 0.15). Anticardiolipin antibodies (25% of rheumatic disease patients vs 10% of controls; p = 0.0022) and ANA (63% vs 21%; p < 0.0001) were more common in rheumatic disease patients. Anti-CCP may serve as a more specific RA biomarker in American Indian patients, while the clinical significance of increased frequency of anticardiolipin antibodies needs further evaluation.

Estradiol targets T cell signaling pathways in human systemic lupus.

PubMed

Walters, Emily; Rider, Virginia; Abdou, Nabih I; Greenwell, Cindy; Svojanovsky, Stan; Smith, Peter; Kimler, Bruce F

2009-12-01

The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.

Sleep quality in fibromyalgia and rheumatoid arthritis: associations with pain, fatigue, depression, and disease activity.

PubMed

Ulus, Y; Akyol, Y; Tander, B; Durmus, D; Bilgici, A; Kuru, O

2011-01-01

The aim of this study was to compare the sleep quality in patients with rheumatoid arthritis (RA) and fibromyalgia syndrome (FMS); and to evaluate the relationship between sleep quality and pain, fatigue, depression, and disease activity in patients with RA and FMS. Forty RA, 40 FMS and 40 healthy controls were enrolled in the study. Disease activity and disease duration were reported in patients. Pain by visual analogue scale (VAS), fatigue by Multidimensional Assesment of Fatigue (MAF), depression by Beck Depression Index (BDI), and sleep quality by Pittsburgh Sleep Quality Index (PSQI) were gathered in all participants. All participants were aged between 20 and 65 years, with a mean age of 42.97±10.75 years. There was no significant difference with respect to demographic characteristics among the three study groups. Patients reported more depression than controls, but BDI scores were similar in FMS and RA patients. VAS pain scores and MAF scores were significantly different in the three groups (p<0.001). FMS and RA patients had poor sleep quality (p<0.001). FMS patients had daytime dysfunction due to sleep disorder and had worse habitual sleep efficiency than RA patients (p<0.05). In patients, positive correlations were found between PSQI and clinic assessment variables except disease duration. FMS and RA may have poor sleep quality when compared to subjects without rheumatologic disorders. The quality of sleep can be impaired by pain, fatigue, depression, and disease activity in such patients.

Cognitive-Behavioural Therapy for Inflammatory Bowel Disease: 24-Month Data from a Randomised Controlled Trial.

PubMed

Mikocka-Walus, Antonina; Bampton, Peter; Hetzel, David; Hughes, Patrick; Esterman, Adrian; Andrews, Jane M

2017-02-01

There is ongoing controversy on the effectiveness of psychotherapy in inflammatory bowel disease (IBD). In the few small studies, cognitive-behavioural therapy (CBT) has been shown to alleviate symptoms of anxiety or depression. However, there is little research on the impact of CBT on physical outcomes in IBD and no studies on long-term effectiveness of CBT. The present two-arm pragmatic randomised controlled trial aimed to establish the impact of CBT on disease course after 24 months of observation. The study compared standard care plus CBT (+CBT) with standard care alone (SC). CBT was delivered over 10 weeks, face-to-face (F2F) or online (cCBT). The data were analysed using linear mixed-effects models. CBT did not significantly influence disease activity as measured by disease activity indices at 24 months (Crohn's Disease Activity Index (CDAI), p = 0.92; Simple Clinical Colitis Activity Index (SCCAI), p = 0.88) or blood parameters (C-reactive protein (CRP), p < 0.62; haemoglobin (Hb), p = 0.77; platelet, p = 0.64; white cell count (WCC), p = 0.59) nor did CBT significantly affect mental health, coping or quality of life (all p > 0.05). Therefore, we conclude that CBT does not influence the course of IBD over 24 months. Given the high rate of attrition, particularly in the CBT group, future trials should consider a personalised approach to psychotherapy, perhaps combining online and one-to-one therapist time.

Prevalence of Sexually Transmitted Diseases in Asymptomatic Renal Transplant Recipients.

PubMed

Sarier, Mehmet; Sepin Ozen, Nevgun; Guler, Hicran; Duman, Ibrahim; Yüksel, Yücel; Tekin, Sabri; Yavuz, Asuman Havva; Yucetin, Levent; Erdogan Yilmaz, Mine

2018-04-04

Sexually transmitted diseases, which may be asymptomatic, have the potential to cause serious health problems in renal transplant recipients. The aim of this study was to determine the prevalence of sexually transmitted diseases in sexually active asymptomatic renal transplant patients by using real-time multiplex polymerase chain reaction assays. This prospective controlled study was conducted between November 2016 and January 2017 in our hospital. Our study group included 80 consecutive, sexually active asymptomatic patients (40 men and 40 women) who had undergone renal transplant in our hospital and who presented to our outpatient clinic for routine follow-up. We also included a control group of 80 consecutive, sexually active nontransplant patients (40 men and 40 women). All patient samples were tested for Gardnerella vaginalis and obligate anaerobes (Prevotella bivia, Porphyromonas species), Candida species, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma species, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2, and Cytomegalovirus by real-time multiplex polymerase chain reaction. The prevalences of infection with Gardnerella vaginalis and obligate anaerobes (P = .043), Ureaplasma species (P = .02), and Cytomegalovirus (P = .016) were found to be significantly higher in the study group versus the control group. However, there was no difference between the 2 groups regarding the prevalence of Mycoplasma infection (P = .70). Sexually transmitted diseases may occur more frequently in sexually active asymptomatic renal transplant recipients than in nontransplanted individuals. Real-time multiplex polymerase chain reaction analysis may be a suitable method for determining these pathogens.

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

PubMed Central

Newton, Julia L; Frith, James; Powell, Danielle; Hackett, Kate; Wilton, Katharine; Bowman, Simon; Price, Elizabeth; Pease, Colin; Andrews, Jacqueline; Emery, Paul; Hunter, John; Gupta, Monica; Vadivelu, Saravanan; Giles, Ian; Isenberg, David; Lanyon, Peter; Jones, Adrian; Regan, Marian; Cooper, Annie; Moots, Robert; Sutcliffe, Nurhan; Bombardieri, Michele; Pitzalis, Costantino; McLaren, John; Young-Min, Steven; Dasgupta, Bhaskar; Griffiths, Bridget; Lendrem, Dennis; Mitchell, Sheryl; Ng, Wan-Fai

2012-01-01

Objectives To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS. Methods Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis. Results COMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009). Conclusions Autonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity. PMID:22562982

Altered peripheral amino acid profile indicate a systemic impact of active celiac disease and a possible role of amino acids in disease pathogenesis.

PubMed

Torinsson Naluai, Åsa; Saadat Vafa, Ladan; Gudjonsdottir, Audur H; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel

2018-01-01

We have previously performed a Genome Wide Association and linkage study that indicated a new disease triggering mechanism involving amino acid metabolism and nutrient sensing signaling pathways. The aim of this study was to investigate if plasma amino acid levels differed among children with celiac disease compared with disease controls. Fasting plasma samples from 141 children with celiac disease and 129 non-celiac disease controls, were analyzed for amino acid levels by liquid chromatography-tandem mass spectrometry (LC/MS). A general linear model using age and experimental effects as covariates was used to compare amino acid levels between children with a diagnosis of celiac disease and controls. Seven out of twenty-three analyzed amino acids were elevated in children with celiac disease compared with controls (tryptophan, taurine, glutamic acid, proline, ornithine, alanine and methionine). The significance of the individual amino acids do not survive multiple correction, however, multivariate analyses of the amino acid profile showed significantly altered amino acid levels in children with celiac disease overall and after correction for age, sex and experimental effects (p = 8.4 × 10-8). These findings support the idea that amino acids could influence systemic inflammation and play a possible role in disease pathogenesis.

Functional magnetic resonance imaging exploration of combined hand and speech movements in Parkinson's disease.

PubMed

Pinto, Serge; Mancini, Laura; Jahanshahi, Marjan; Thornton, John S; Tripoliti, Elina; Yousry, Tarek A; Limousin, Patricia

2011-10-01

Among the repertoire of motor functions, although hand movement and speech production tasks have been investigated widely by functional neuroimaging, paradigms combining both movements have been studied less so. Such paradigms are of particular interest in Parkinson's disease, in which patients have specific difficulties performing two movements simultaneously. In 9 unmedicated patients with Parkinson's disease and 15 healthy control subjects, externally cued tasks (i.e., hand movement, speech production, and combined hand movement and speech production) were performed twice in a random order and functional magnetic resonance imaging detected cerebral activations, compared to the rest. F-statistics tested within-group (significant activations at P values < 0.05, familywise error corrected), between-group, and between-task comparisons (regional activations significant at P values < 0.001, uncorrected, with cluster size > 10 voxels). For control subjects, the combined task activations comprised the sum of those obtained during hand movement and speech production performed separately, reflecting the neural correlates of performing movements sharing similar programming modalities. In patients with Parkinson's disease, only activations underlying hand movement were observed during the combined task. We interpreted this phenomenon as patients' potential inability to recruit facilitatory activations while performing two movements simultaneously. This lost capacity could be related to a functional prioritization of one movement (i.e., hand movement), in comparison with the other (i.e., speech production). Our observation could also reflect the inability of patients with Parkinson's disease to intrinsically engage the motor coordination necessary to perform a combined task. Copyright © 2011 Movement Disorder Society.

Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

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

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency ofmore » abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.« less

Impact of an active patient education program on gastrointestinal symptoms in women with celiac disease following a gluten-free diet: a randomized controlled trial.

PubMed

Jacobsson, Lisa Ring; Friedrichsen, Maria; Göransson, Anne; Hallert, Claes

2012-01-01

Despite living with a gluten-free diet, Swedish women with celiac disease report a higher rate of gastrointestinal symptoms than women without the disease. This study was designed to assess the impact of active patient education on gastrointestinal symptoms in women with a gluten-free diet. A total of 106 Swedish women, aged 20 years or older, with celiac disease on a gluten-free diet for a minimum of 5 years took part in a randomized controlled trial. The intervention group (n = 54) underwent a 10-session educational program, "Celiac School," based on problem-based learning. Controls (n = 52) were sent information regarding celiac disease at home. The outcome measure was gastrointestinal symptoms at 10 weeks and 6 months after intervention, assessed with the Gastrointestinal Symptom Rating Scale. After 10 weeks of "Celiac School," the participating women reported significant improvements that remained 6 months later (p = .029). The controls did not improve significantly. A comparison of the development of scores, from baseline to 10 weeks, could not demonstrate a significant difference in the overall index between the 2 groups but showed a significant improvement concerning 1 of its components, namely the index reflecting Abdominal Pain (p = .007). Intervention methods should be refined to reach an even more pronounced effect.

Tofacitinib suppresses disease activity and febrile attacks in a patient with coexisting rheumatoid arthritis and familial Mediterranean fever.

PubMed

Gök, Kevser; Cengiz, Gizem; Erol, Kemal; Ozgocmen, Salih

2017-01-01

Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA). Herein we report a female patient with coexisting RA and colchicine resistant FMF whose FMF attacks and disease activity were completely controlled after treatment with tofacitinib, a small-molecule JAK3 inhibitor.

The role of alectinib in the treatment of advanced ALK-rearranged non-small-cell lung cancer.

PubMed

Srinivasamaharaj, Srividya; Salame, Bilal Khameze; Rios-Perez, Jorge; Kloecker, Goetz; Perez, Cesar A

2016-12-01

The identification of anaplastic lymphoma kinase (ALK) gene rearrangements in subsets of non-small cell lung cancer patients has provided with unparalleled opportunities to hinder the progression of this disease through targeting the activity of these specific molecules. Unfortunately most patients develop disease progression in less than a year of treatment with crizotinib, the first-generation ALK-inhibitor. Areas covered: We review the resistance mechanisms to ALK inhibitors as well as an overview of the clinical activity of the alectinib, a second generation ALK inhibitor. Expert commentary: Second generation ALK inhibitors as alectinib and ceritinib can overcome crizotinib-resistant mutations and improve central nervous system control. Novel third-generation inhibitors and combination of agents give hope of achieving an even longer disease control in the next decade.

COPD control: Can a consensus be found?

PubMed

Guimarães, M; Bugalho, A; Oliveira, A S; Moita, J; Marques, A

2016-01-01

There are currently no reliable instruments for assessing the onset and progression of chronic obstructive pulmonary disease (COPD) or predicting its prognosis. Currently, a comprehensive assessment of COPD including several objective and subjective parameters is recommended. However, the lack of biomarkers precludes a correct assessment of COPD severity, which consequently hampers adequate therapeutic approaches and COPD control. In the absence of a definition of "well-controlled disease", a consensus regarding COPD control will be difficult to reach. However, COPD patient assessment should be multidimensional, and anchored in five points: control of symptoms, decline of pulmonary function, levels of physical activity, exacerbations, and Quality of Life. Several non-pharmacological and pharmacological measures are currently available to achieve disease control. Smoking cessation, vaccination, exercise training programs and pulmonary rehabilitation are recognized as important non-pharmacological measures but bronchodilators are the pivotal therapy in the control of COPD. This paper discusses several objective and subjective parameters that may bridge the gap between disease assessment and disease control. The authors conclude that, at present, it is not possible to reach a consensus regarding COPD control, essentially due to the lack of objective instruments to measure it. Some recommendations are set forth, but true COPD control awaits further objective assessments. Copyright © 2016. Published by Elsevier España, S.L.U.

Phenotypic regional fMRI activation patterns during memory encoding in MCI and AD

PubMed Central

Browndyke, Jeffrey N.; Giovanello, Kelly; Petrella, Jeffrey; Hayden, Kathleen; Chiba-Falek, Ornit; Tucker, Karen A.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2014-01-01

Background Reliable blood-oxygen-level-dependent (BOLD) fMRI phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. Methods A series of random-effects, activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based upon a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. Results ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal controls across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe (MTL), specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal controls. Conclusions ALE consistencies broadly support the presence of frontal compensatory activity, MTL activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective pre-disease condition. Taken together these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD. PMID:22841497

The farnesoid-X-receptor in myeloid cells controls CNS autoimmunity in an IL-10-dependent fashion.

PubMed

Hucke, Stephanie; Herold, Martin; Liebmann, Marie; Freise, Nicole; Lindner, Maren; Fleck, Ann-Katrin; Zenker, Stefanie; Thiebes, Stephanie; Fernandez-Orth, Juncal; Buck, Dorothea; Luessi, Felix; Meuth, Sven G; Zipp, Frauke; Hemmer, Bernhard; Engel, Daniel Robert; Roth, Johannes; Kuhlmann, Tanja; Wiendl, Heinz; Klotz, Luisa

2016-09-01

Innate immune responses by myeloid cells decisively contribute to perpetuation of central nervous system (CNS) autoimmunity and their pharmacologic modulation represents a promising strategy to prevent disease progression in Multiple Sclerosis (MS). Based on our observation that peripheral immune cells from relapsing-remitting and primary progressive MS patients exhibited strongly decreased levels of the bile acid receptor FXR (farnesoid-X-receptor, NR1H4), we evaluated its potential relevance as therapeutic target for control of established CNS autoimmunity. Pharmacological FXR activation promoted generation of anti-inflammatory macrophages characterized by arginase-1, increased IL-10 production, and suppression of T cell responses. In mice, FXR activation ameliorated CNS autoimmunity in an IL-10-dependent fashion and even suppressed advanced clinical disease upon therapeutic administration. In analogy to rodents, pharmacological FXR activation in human monocytes from healthy controls and MS patients induced an anti-inflammatory phenotype with suppressive properties including control of effector T cell proliferation. We therefore, propose an important role of FXR in control of T cell-mediated autoimmunity by promoting anti-inflammatory macrophage responses.

Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

PubMed

Walters, Tomos E; Kalman, Jonathan M; Patel, Sheila K; Mearns, Megan; Velkoska, Elena; Burrell, Louise M

2017-08-01

Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

High-Throughput Multi-Analyte Luminex Profiling Implicates Eotaxin-1 in Ulcerative Colitis

PubMed Central

Coburn, Lori A.; Horst, Sara N.; Chaturvedi, Rupesh; Brown, Caroline T.; Allaman, Margaret M.; Scull, Brooks P.; Singh, Kshipra; Piazuelo, M. Blanca; Chitnavis, Maithili V.; Hodges, Mallary E.; Rosen, Michael J.; Williams, Christopher S.; Slaughter, James C.; Beaulieu, Dawn B.; Schwartz, David A.; Wilson, Keith T.

2013-01-01

Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies. PMID:24367513

NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation

PubMed Central

Nivon, Mathieu; Fort, Loïc; Muller, Pascale; Richet, Emma; Simon, Stéphanie; Guey, Baptiste; Fournier, Maëlenn; Arrigo, André-Patrick; Hetz, Claudio; Atkin, Julie D.; Kretz-Remy, Carole

2016-01-01

During cell life, proteins often misfold, depending on particular mutations or environmental changes, which may lead to protein aggregates that are toxic for the cell. Such protein aggregates are the root cause of numerous diseases called “protein conformational diseases,” such as myofibrillar myopathy and familial amyotrophic lateral sclerosis. To fight against aggregates, cells are equipped with protein quality control mechanisms. Here we report that NFκB transcription factor is activated by misincorporation of amino acid analogues into proteins, inhibition of proteasomal activity, expression of the R120G mutated form of HspB5 (associated with myofibrillar myopathy), or expression of the G985R and G93A mutated forms of superoxide dismutase 1 (linked to familial amyotrophic lateral sclerosis). This noncanonical stimulation of NFκB triggers the up-regulation of BAG3 and HspB8 expression, two activators of selective autophagy, which relocalize to protein aggregates. Then NFκB-dependent autophagy allows the clearance of protein aggregates. Thus NFκB appears as a central and major regulator of protein aggregate clearance by modulating autophagic activity. In this context, the pharmacological stimulation of this quality control pathway might represent a valuable strategy for therapies against protein conformational diseases. PMID:27075172

Neural response to visual sexual cues in dopamine treatment-linked hypersexuality in Parkinson's disease.

PubMed

Politis, Marios; Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Woodhead, Zoe; Kiferle, Lorenzo; Lawrence, Andrew D; Lees, Andrew J; Piccini, Paola

2013-02-01

Hypersexuality with compulsive sexual behaviour is a significant source of morbidity for patients with Parkinson's disease receiving dopamine replacement therapies. We know relatively little about the pathophysiology of hypersexuality in Parkinson's disease, and it is unknown how visual sexual stimuli, similar to the portrayals of sexuality in the mainstream mass media may affect the brain and behaviour in such susceptible individuals. Here, we have studied a group of 12 patients with Parkinson's disease with hypersexuality using a functional magnetic resonance imaging block design exposing participants to both sexual, other reward-related and neutral visual cues. We hypothesized that exposure to visual sexual cues would trigger increased sexual desire in patients with Parkinson's disease with hypersexuality that would correspond to changes in brain activity in regions linked to dopaminergically stimulated sexual motivation. Patients with Parkinson's disease with hypersexuality were scanned ON and OFF dopamine drugs, and their results were compared with a group of 12 Parkinson's disease control patients without hypersexuality or other impulse control disorders. Exposure to sexual cues significantly increased sexual desire and hedonic responses in the Parkinson's disease hypersexuality group compared with the Parkinson's disease control patients. These behavioural changes corresponded to significant blood oxygen level-dependent signal changes in regions within limbic, paralimbic, temporal, occipital, somatosensory and prefrontal cortices that correspond to emotional, cognitive, autonomic, visual and motivational processes. The functional imaging data showed that the hypersexuality patients' increased sexual desire correlated with enhanced activations in the ventral striatum, and cingulate and orbitofrontal cortices. When the patients with Parkinson's disease with hypersexuality were OFF medication, the functional imaging data showed decreases in activation during the presentation of sexual cues relative to rest. These deactivations were not observed when the patients were ON medication, suggesting that dopamine drugs may release inhibition within local neuronal circuits in the cerebral cortex that may contribute to compulsive sexual behaviour. The findings of this study have implications with respect to the potential influence of cue exposure via exposure to mass media in enhancing libido, which in this group of vulnerable patients can lead to devastating social consequences and occasionally, custodial sentences. Stimulation through exposure to sexual visual cues in patients with Parkinson's disease with hypersexuality provides a motivational impetus for seeking this reward behaviour through activations and deactivations of cerebral cortex.

CASP-19 special section: how does chronic disease status affect CASP quality of life at older ages? Examining the WHO ICF disability domains as mediators of this relationship.

PubMed

Sexton, E; King-Kallimanis, B L; Layte, R; Hickey, A

2015-07-01

The effect of chronic disease status on quality of life (QoL) has been well established. However, less is known about how chronic diseases affect QoL. This article examines impairment in three domains of the WHO International Classification of Functioning, Health and Disability (ICF) - body function, activity and participation, as well as affective well-being, - as potential mediators of the relationship between chronic disease and QoL. A cross-sectional sample (n = 4961) of the general Irish community-dwelling population aged 50+ years was obtained from the Irish Longitudinal Study of Ageing (TILDA). The CASP measure of QoL was examined as two dimensions - control/autonomy and self-realisation/pleasure. Structural equation modelling was used to test the direct and indirect effects of chronic disease on QoL, via variables capturing body function, activity, participation and positive affect. A factor analysis showed that indicators of body function and activity loaded onto a single overall physical impairment factor. This physical impairment factor fully mediated the effect of chronic disease on positive affect and QoL. The total effect of chronic disease on control/autonomy (-0.160) was primarily composed of an indirect effect via physical impairment (-0.86), and via physical impairment and positive affect (-0.45). The decomposition of effects on self-realisation/pleasure was similar, although the direct effect of physical impairment was weaker. The model fitted the data well (RMSEA = 0.02, TLI = 0.96, CFI = 0.96). Chronic disease affects QoL through increased deficits in physical body function and activity. This overall physical impairment affects QoL both directly and indirectly via reduced positive affect.

24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial.

PubMed

Soininen, Hilkka; Solomon, Alina; Visser, Pieter Jelle; Hendrix, Suzanne B; Blennow, Kaj; Kivipelto, Miia; Hartmann, Tobias

2017-12-01

Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial. LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1:1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705. Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0·028 (SD 0·453) in the active group and -0·108 (0·528) in the control group; estimated mean treatment difference was 0·098 (95% CI -0·041 to 0·237; p=0·166). The decline in the control group was less than the prestudy estimate of -0·4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0·487), none of which were regarded as related to the study intervention. The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed. European Commission 7th Framework Programme. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

The impact of lymphatic filariasis on labour inputs in southern India: results of a multi-site study.

PubMed

Ramaiah, K D; Radhamani, M P; John, K R; Evans, D B; Guyatt, H; Joseph, A; Datta, M; Vanamail, P

2000-06-01

A multi-site study was undertaken, in the rural areas of three districts in Tamil Nadu state, in southern India, to examine the impact of acute and chronic forms of lymphatic filariasis, caused by infection with Wuchereria bancrofti, on labour inputs. More than half of the acute episodes of adenolymphangitis (ADL) observed in the study communities caused total disability. The mean (S.D.) time that each ADL case was able to allocate to economic activity each day during these acute episodes was much less than seen in the controls matched for sex, age and occupation [0.97 (2.36) v. 4.48 (3.82) h; P < 0.01]. The acute disease also severely affected domestic activities, with female ADL cases spending only 1.54 (2.12) h/day on domestic activity, compared with 4.18 (2.61) h by controls. The subjects with chronic filariasis also spent significantly less time in economic activity than their matched controls [4.40 (3.79) v. 5.13 (3.83) h/day; P < 0.01). Although the acute episodes have a dramatic effect on the productivity of the affected individual, the labour loss caused by chronic disease is more serious, as the manifestations of chronic disease mostly affect the most productive age-groups, persist for life and are mostly irreversible. The adverse impact of acute and chronic filariasis was observed in males and females, farmers and non-farmers and during the rainy, winter and summer seasons. It is estimated that about 3.8% of the potential labour inputs of the men and 0.77% of those of the women were lost because of lymphatic filariasis. In addition to this loss, the total economic burden of the disease must include the costs of treatment and other health care and of the resources spent on control programmes. Estimates of the disease burden are likely to be useful in determining the costs and benefits of the recently launched campaign to eliminate lymphatic filariasis.

Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled trials.

PubMed

Shen, Jun; Zuo, Zhi-Xiang; Mao, Ai-Ping

2014-01-01

Whether probiotics are beneficial at all stages of treatment in inflammatory bowel disease or superior to placebo remains controversial. Two reviewers independently selected randomized controlled trials comparing probiotics with controls in inflammatory bowel disease and extracted data related to remission/response rates, relapse rates, and adverse events. Subanalyses were also performed. Twenty-three randomized controlled trials with a total of 1763 participants met the inclusion criteria. From the meta-analysis, probiotics significantly increase the remission rates in patients with active ulcerative colitis (UC) (P = 0.01, risk ratio [RR] = 1.51). The remission rates were significantly higher in patients with active UC treated with probiotics than placebo (P < 0.0001, RR = 1.80). Unfortunately, subgroup analysis found that only VSL#3 significantly increased the remission rates compared with controls in patients with active UC (P = 0.004, RR = 1.74). Interestingly, VSL#3 (P < 0.00001, RR = 0.18) also significantly reduced the clinical relapse rates for maintaining remission in patients with pouchitis. No significantly different adverse events were detected between probiotics and controls in the treatment of UC (P = 0.94, RR = 0.99) or CD (P = 0.33, RR = 0.87). Administration of probiotics results in additional benefit in inducing remission of patients with UC. VSL#3 are beneficial for maintaining remission in patients with pouchitis. And, probiotics can provide the similar effect as 5-aminosalicylic acid on maintaining remission of UC, although no additional adverse events presented.

Anti-DNase I antibodies in systemic lupus erythematosus: diagnostic value and share in the enzyme inhibition.

PubMed

Trofimenko, A S; Gontar, I P; Zborovsky, A B; Paramonova, O V

2016-04-01

Diagnostic accuracy of anti-DNase I antibodies measurement in a differentiation between SLE and other autoimmune rheumatic diseases was evaluated. The share of anti-DNase I and actin in the DNase I activity decrease in SLE was established. Serum samples were obtained from 54 patients with verified SLE, 52 control patients with other autoimmune rheumatic diseases, and 44 healthy persons. Anti-DNase I concentrations were measured by ELISA. Free and actin inhibited DNase I activities were evaluated in the fresh serum samples. The appraisal of antibodies and actin effects on DNase I activity was made using multiple regression. Anti-DNase I antibodies were positive in 35 SLE and 8 control patients, without significant difference between the mean antibody concentrations. Sensitivity of this test was 64.81 %, and specificity-84.62 %. Mean free DNase I activity in SLE was somewhat lower than in the control group as a result of augmented frequency of extremely low enzyme activities. On the contrary, after the exclusion of the latter cases we have revealed elevated mean free DNase I activity in the other SLE patients comparing to the similar control subgroup. Unlike the controls, low serum DNase I activity in SLE arose not only from actin and antibody action, but also, in half of the cases, from unidentified factor, related to active SLE. The accuracy of the anti-DNase I antibodies measurement is approximate to the present reference standard of SLE diagnostics. We first demonstrated that neither antibodies nor actin caused DNase I activity decrease in SLE.

Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population.

PubMed

Fattah, Shaimaa A; Ghattas, Maivel H; Saleh, Samy M; Abo-Elmatty, Dina M

2018-01-01

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction-restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects ( P  = 0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients.

PubMed

Farouk, H M; Mansour, H E; Rahman, S A; Mostafa, A A; Shamy, H A; Zarouk, W A

2009-09-01

Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

Levels of physical activity in patients with severe psoriasis: a cross-sectional questionnaire study.

PubMed

Torres, Tiago; Alexandre, José Manuel; Mendonça, Denisa; Vasconcelos, Carlos; Silva, Berta Martins; Selores, Manuela

2014-04-01

Psoriasis is a chronic inflammatory disease associated with increased cardiovascular mortality, secondary to the increased prevalence of cardiovascular risk factors and premature atherosclerosis. Physical activity is a vital component in prevention and management of cardiovascular disease. Few studies have examined the level of physical activity in psoriasis patients, using validated questionnaires or other objective assessment tools. The aim of this study was to analyze and compare physical activity undertaken by patients with severe psoriasis and healthy controls, using the International Physical Activity Questionnaire-Short Form (IPAQ-S), a validated instrument for assessing physical activity. Ninety patients with severe plaque-type psoriasis and 160 healthy subjects were enrolled in the present study. Physical activity was evaluated using IPAQ-S. Psoriasis patients had reduced levels of physical activity compared with non-psoriasis patients, regardless of sex or whether the variable was continuous or categorical. The odds ratio for low-level physical activity for psoriasis patients, compared with controls, was 3.42 (95% CI 1.47-7.91), indicating that this severe psoriasis population did not undertake recommended levels of physical activity. Psoriasis patients exhibit decreased levels of physical activity, possibly for both psychological and physiological reasons. The lack of physical activity may contribute to the increased risk of cardiovascular disease in psoriasis patients, in addition to the intrinsic risks related to systemic inflammation and psoriasis-linked comorbidities. Regular physical activity should be encouraged in all psoriasis patients because of its beneficial effects on systemic inflammation and cardiometabolic comorbidities associated with psoriasis.

Frontoparietal cognitive control of verbal memory recall in Alzheimer's disease.

PubMed

Dhanjal, Novraj S; Wise, Richard J S

2014-08-01

Episodic memory retrieval is reliant upon cognitive control systems, of which 2 have been identified with functional neuroimaging: a cingulo-opercular salience network (SN) and a frontoparietal executive network (EN). In Alzheimer's disease (AD), pathology is distributed throughout higher-order cortices. The hypotheses were that this frontoparietal pathology would impair activity associated with verbal memory recall; and that central cholinesterase inhibition (ChI) would modulate this, improving memory recall. Functional magnetic resonance imaging was used to study normal participants and 2 patient groups: mild cognitive impairment (MCI) and AD. Activity within the EN and SN was observed during free recall of previously heard sentences, and related to measures of recall accuracy. In normal subjects, trials with reduced recall were associated with greater activity in both the SN and EN. Better recall was associated with greater activity in medial regions of the default mode network. By comparison, AD patients showed attenuated responses in both the SN and EN compared with either controls or MCI patients, even after recall performance was matched between groups. Following ChI, AD patients showed no modulation of activity within the SN, but increased activity within the EN. There was also enhanced activity within regions associated with episodic and semantic memory during less successful recall, requiring greater cognitive control. The results indicate that in AD, impaired responses of cognitive control networks during verbal memory recall are partly responsible for reduced recall performance. One action of symptom-modifying treatment is partially to reverse the abnormal function of frontoparietal cognitive control and temporal lobe memory networks. © 2014 American Neurological Association.

Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development

PubMed Central

Mueller, Kristina M.; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P.; Moriggl, Richard

2012-01-01

Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5–GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development. PMID:22564914

Propolis--based chitosan varnish: drug delivery, controlled release and antimicrobial activity against oral pathogen bacteria.

PubMed

Franca, Juçara R; De Luca, Mariana P; Ribeiro, Tatiana G; Castilho, Rachel O; Moreira, Allyson N; Santos, Vagner R; Faraco, André A G

2014-12-12

Dental caries is the most prevalent oral disease in several Asian and Latin American countries. It is an infectious disease and different types of bacteria are involved in the process. Synthetic antimicrobials are used against this disease; however, many of these substances cause unwarranted undesirable effects like vomiting, diarrhea and tooth staining. Propolis, a resinous substance collected by honeybees, has been used to control the oral microbiota. So, the objective of this study was to develop and characterize sustained-release propolis-based chitosan varnish useful on dental cariogenic biofilm prevention, besides the in vitro antimicrobial activity. Three formulations of propolis - based chitosan varnish (PCV) containing different concentrations (5%, 10% and 15%) were produced by dissolution of propolis with chitosan on hydro-alcoholic vehicle. Bovine teeth were used for testing adhesion of coatings and to observe the controlled release of propolis associated with varnish. It was characterized by infrared spectroscopy, scanning electron microscopy, casting time, diffusion test in vitro antimicrobial activity and controlled release. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were tested for the main microorganisms involved in the cariogenic biofilm through the microdilution test in 96-well plates. The formulations presented a tooth surface adherence and were able to form films very fast on bovine tooth surface. Also, propolis-based chitosan varnishes have shown antimicrobial activity similar to or better than chlorhexidine varnish against all oral pathogen bacteria. All microorganisms were sensitive to propolis varnish and chitosan. MIC and MBC for microorganisms of cariogenic biofilme showed better results than chlorhexidine. Propolis active components were released for more than one week. All developed formulations turn them, 5%, 10% and 15% propolis content varnish, into products suitable for clinical application on dental caries prevention field, deserving clinical studies to confirm its in vivo activity.

Serum interleukin measurement may help identify thyroid cancer patients with active disease.

PubMed

Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Peres, Karina Colombera; Meneghetti, Murilo; Ward, Mirela Andrea Latham; Etchebehere, Elba Cristina Sá de Camargo; da Assumpção, Ligia Vera Montali; Ward, Laura Sterian

2018-02-01

Investigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease. We evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA. All ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p=0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p<0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p=0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p<0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness. We suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Mechanisms controlling nucleic acid-sensing Toll-like receptors.

PubMed

Miyake, Kensuke; Shibata, Takuma; Ohto, Umeharu; Shimizu, Toshiyuki; Saitoh, Shin-Ichiroh; Fukui, Ryutaro; Murakami, Yusuke

2018-03-08

Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and TLR8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization. Trafficking of ligand-activated TLRs in endosomal and lysosomal compartments is requisite for production of type I interferons. Activation of NA-sensing TLRs is required for the control of viruses such as herpes simplex virus and endogenous retroviruses. On the other hand, excessive activation of NA-sensing TLRs drives disease progression in a variety of inflammatory diseases including systemic lupus erythematosus, heart failure, arthritis and non-alcoholic steatohepatitis. NA-sensing TLRs are targets for therapeutic intervention in these diseases. We here focus on our recent progresses in our understanding of NA-sensing TLRs.

Chronic Active Epstein–Barr Virus Disease

PubMed Central

Kimura, Hiroshi; Cohen, Jeffrey I.

2017-01-01

Chronic active Epstein–Barr virus (CAEBV) disease is a rare disorder in which persons are unable to control infection with the virus. The disease is progressive with markedly elevated levels of EBV DNA in the blood and infiltration of organs by EBV-positive lymphocytes. Patients often present with fever, lymphadenopathy, splenomegaly, EBV hepatitis, or pancytopenia. Over time, these patients develop progressive immunodeficiency and if not treated, succumb to opportunistic infections, hemophagocytosis, multiorgan failure, or EBV-positive lymphomas. Patients with CAEBV in the United States most often present with disease involving B or T cells, while in Asia, the disease usually involves T or NK cells. The only proven effective treatment for the disease is hematopoietic stem cell transplantation. Current studies to find a cause of this disease focus on immune defects and genetic abnormalities associated with the disease. PMID:29375552

Chronic Active Epstein-Barr Virus Disease.

PubMed

Kimura, Hiroshi; Cohen, Jeffrey I

2017-01-01

Chronic active Epstein-Barr virus (CAEBV) disease is a rare disorder in which persons are unable to control infection with the virus. The disease is progressive with markedly elevated levels of EBV DNA in the blood and infiltration of organs by EBV-positive lymphocytes. Patients often present with fever, lymphadenopathy, splenomegaly, EBV hepatitis, or pancytopenia. Over time, these patients develop progressive immunodeficiency and if not treated, succumb to opportunistic infections, hemophagocytosis, multiorgan failure, or EBV-positive lymphomas. Patients with CAEBV in the United States most often present with disease involving B or T cells, while in Asia, the disease usually involves T or NK cells. The only proven effective treatment for the disease is hematopoietic stem cell transplantation. Current studies to find a cause of this disease focus on immune defects and genetic abnormalities associated with the disease.

Potential Challenges of Controlling Leishmaniasis in Sri Lanka at a Disease Outbreak

PubMed Central

Gunawardana, Kithsiri; Rodrigo, Wasana

2017-01-01

The present works reviewed the existing information on leishmaniasis in Sri Lanka and in other countries, focusing on challenges of controlling leishmaniasis in the country, in an outbreak. Evidence from recent studies suggests that there is a possibility of a leishmaniasis outbreak in Sri Lanka in the near future. Difficulty of early diagnosis due to lack of awareness and unavailability or inadequacy of sensitive tests are two of the main challenges for effective case management. Furthermore, the absence of a proper drug for treatment and lack of knowledge about vector biology, distribution, taxonomy and bionomics, and reservoir hosts make the problem serious. The evident potential for visceralization in the cutaneous variant of L. donovani in Sri Lanka may also complicate the issue. Lack of knowledge among local communities also reduces the effectiveness of vector and reservoir host control programs. Immediate actions need to be taken in order to increase scientific knowledge about the disease and a higher effectiveness of the patient management and control programs must be achieved through increased awareness about the disease among general public and active participation of local community in control activities. PMID:28630867

Killer (FASL regulatory) B cells are present during latent TB and are induced by BCG stimulation in participants with and without latent tuberculosis.

PubMed

van Rensburg, Ilana C; Loxton, Andre G

2018-01-01

Regulatory B cells (Bregs) have been shown to be present during several disease states. The phenotype of the cells is not completely defined and the function of these cells differ between disease. The presence of FASL expressing (killer) B cells during latent and successfully treated TB disease have been shown but whether these cells are similar to regulatory B cells remain unclear. We assessed the receptor expression of FASL/IL5 (killer B cells), CD24/CD38 (regulatory B cells) on whole peripheral blood of participants with untreated active TB and healthy controls. We then isolated B cells from a second cohort of M.tb exposed (Quantiferon (QFN) positive) and unexposed (Quantiferon negative) HIV negative participants, and evaluated the frequency of killer B cells induced following stimulation with BCG and/or CD40 and IL5. Our data reveal no difference in the expression on CD24 and CD38 between participants with active TB and the controls. There was also no difference in the frequency of regulatory B cells measured in the peripheral blood mononuclear cells (PBMC) fraction between latent TB and uninfected controls. We did however notice that regulatory B cells (CD24hiCD38hi) population express the FASL receptor. The expression of killer B cell phenotype (CD178+IL5RA+) was significantly higher in controls compared to those with active TB disease (1,06% vs 0,455%). Furthermore, we found that BCG restimulation significantly induced the FASL/IL5RA B cells but this was only evident in the QFN positive group. Our data suggest that both regulatory and killer B cells are present during latent and active TB disease but that the frequency of these populations are increased during latent disease. We also show that the FASL+IL5RA+ B killer B cells are induced in latent TB infection following BCG restimulation but whether these cells are indicative of protection remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

Correlation of cell-free DNA plasma concentration with severity of non-alcoholic fatty liver disease.

PubMed

Karlas, Thomas; Weise, Lara; Kuhn, Stephanie; Krenzien, Felix; Mehdorn, Matthias; Petroff, David; Linder, Nicolas; Schaudinn, Alexander; Busse, Harald; Keim, Volker; Pratschke, Johann; Wiegand, Johannes; Splith, Katrin; Schmelzle, Moritz

2017-05-19

The assessment of fibrosis and inflammatory activity is essential to identify patients with non-alcoholic fatty liver disease (NAFLD) at risk for progressive disease. Serum markers and ultrasound-based methods can replace liver biopsy for fibrosis staging, whereas non-invasive characterization of inflammatory activity remains a clinical challenge. Cell-free DNA (cfDNA) is a novel non-invasive biomarker for assessing cellular inflammation and cell death, which has not been evaluated in NAFLD. Patients and healthy controls from two previous studies were included. NAFLD disease activity and severity were non-invasively characterized by liver stiffness measurement (transient elastography, TE) including steatosis assessment with controlled attenuation parameter (CAP), single-proton magnetic resonance spectroscopy ( 1 H-MRS) for determination of hepatic fat fraction, aminotransferases and serum ferritin. cfDNA levels (90 and 222 bp fragments) were analyzed using quantitative real-time PCR. Fifty-eight NAFLD patients (age 62 ± 11 years, BMI 28.2 ± 3.5 kg/m 2 ) and 13 healthy controls (age 38 ± 12 years, BMI 22.4 ± 2.1 kg/m 2 ) were included. 90 bp cfDNA levels were significantly higher in NAFLD patients compared to healthy controls: 3.7 (1.3-23.1) vs. 2.9 (1.4-4.1) ng/mL (p = 0.014). In the NAFLD cohort, circulating cfDNA correlated significantly with disease activity and severity, especially in patients with elevated liver stiffness (n = 13, 22%) compared to cases with TE values ≤7 kPa: cf90 bp 6.05 (2.41-23.13) vs. 3.16 (1.29-7.31) ng/mL (p < 0.001), and cf222 bp 14.41 (9.27-22.90) vs. 11.32 (6.05-18.28) ng/mL (p = 0.0041). Cell-free DNA plasma concentration correlates with established non-invasive markers of NAFLD activity and severity. Therefore, cfDNA should be further evaluated as biomarker for identifying patients at risk for progressive NAFLD.

Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis.

PubMed

Habets, Kim L L; Trouw, Leendert A; Levarht, E W Nivine; Korporaal, Suzanne J A; Habets, Petra A M; de Groot, Philip; Huizinga, Tom W J; Toes, René E M

2015-08-24

Although the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis. We set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of anti-citrullinated protein antibodies (ACPA). Platelets from healthy controls were incubated in the presence of plasma of patients with RA or age- and sex-matched healthy controls and plasma from ACPA(neg) or ACPA(pos) patients or in the presence of plate-bound ACPA. Characteristics of platelets isolated from patients with RA were correlated to disease activity. Platelets isolated from healthy controls displayed markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of soluble CD40 ligand (sCD40L). Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titres. In accordance with these findings, enhanced platelet activation was observed after incubation with ACPA(pos) plasma versus ACPA(neg) plasma. Pre-incubation of platelets with blocking antibodies directed against low-affinity immunoglobulin G receptor (FcγRIIa) completely inhibited the ACPA-mediated activation. In addition, expression of P-selectin measured as number of platelets correlated with Disease Activity Score in 44 joints, C-reactive protein level, ACPA status and ACPA level. We show for the first time that ACPA can mediate an FcγRIIa-dependent activation of platelets. As ACPA can be detected several years before RA disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis onset.

The ethyl acetate extract of alfalfa sprout ameliorates disease severity of autoimmune-prone MRL-lpr/lpr mice.

PubMed

Hong, Y H; Huang, C J; Wang, S C; Lin, B F

2009-03-01

Previous study showed that soy isoflavone supplement alleviates disease severity in autoimmune-prone mice. As the ethyl acetate extract of alfalfa sprout (AS) has selective oestrogenic and anti-inflammatory activity, this study evaluated the effects of alfalfa sprout ethyl acetate extract (ASEA) on disease severity of systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. In Experiment 1, five groups of 12-week-old female mice were per oral treated with vehicle (control), lyophilized AS (550 mg wt/kg BW), ASEA (ASEA, 25 mg/kg BW), coumestrol (CUM, 0.075 mg/kg BW) and tamoxifen (TAM, 0.375 mg/kg BW) as the positive control. The onset of proteinuria was delayed, and the life span was significantly longer in the ASEA and TAM groups but neither in the AS nor in the CUM groups, compared to the control. To examine the changes in the immunological parameters related to disease process, three more groups of MRL-lpr/lpr female mice (control, ASEA and TAM) were fed in a similar manner for 6 weeks in the Experiment 2. Flow cytometric analysis of splenocytes showed a significantly lower percentage of activated T cells in the ASEA and TAM groups. The ex-vivo interferon-gamma and interleukin (IL)-4 production from splenocytes and tumour necrosis factor-alpha and IL-1beta production from peritoneal exudate cells were also significantly lower in the ASEA group compared with the control. The ASEA group also had less severe glomerulonephritis. Thus, ASEA attenuated cytokine and inflammatory responses of self-reactive lymphocytes, decreased the disease severity, increased survival and life span of the autoimmune-prone MRL-lpr/lpr mice, suggesting a potential of ASEA in the treatment of autoimmune diseases.

U.S. Army Public Health Command (Provisional ) - Organization Overview and Environmental Health Engineering Services

DTIC Science & Technology

2010-06-15

Veterinary Medical care for Government-Owned Animals Zoonotic disease surveillance and control Food safety and food defense quality assurance...surveillance and epidemiology • Laboratory services • Health risk assessment • Zoonotic disease surveillance and control • Food safety and food...Command vs Technical – Lack of flexibility in resource cross leveling • 1994: VETCOM activated with HQ at Ft. Sam Houston Texas VETCOM Mission Food

Norrie disease gene is distinct from the monoamine oxidase genes

PubMed Central

Sims, Katherine B.; Ozelius, Laurie; Corey, Timothy; Rinehart, William B.; Liberfarb, Ruth; Haines, Jonathan; Chen, Wei Jane; Norio, Reijo; Sankila, Eeva; de la Chapelle, Albert; Murphy, Dennis L.; Gusella, James; Breakefield, Xandra O.

1989-01-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and /or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in “classic” Norrie disease patients. Genomic DNA from these “nondeletion” Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease. ImagesFigure 2Figure 3 PMID:2773935

Gonzalez Regimen (PDQ)

MedlinePlus

... were more active than the rats in the control group , which did not receive the enzyme. Have any ... was how well patients in the Gonzalez regimen group actually followed the ... or control or cure disease. Unlike conventional treatments for cancer, ...

77 FR 58847 - Board of Scientific Counselors, National Center for Injury Prevention and Control (BSC, NCIPC)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-24

... the causes, diagnosis, treatment, control, and prevention of physical and mental diseases, and other..., reorganization and partnerships; Science Update; health communication; global activities; Research to Practice...

Voice Tremor in Parkinson's Disease: An Acoustic Study.

PubMed

Gillivan-Murphy, Patricia; Miller, Nick; Carding, Paul

2018-01-30

Voice tremor associated with Parkinson disease (PD) has not been characterized. Its relationship with voice disability and disease variables is unknown. This study aimed to evaluate voice tremor in people with PD (pwPD) and a matched control group using acoustic analysis, and to examine correlations with voice disability and disease variables. Acoustic voice tremor analysis was completed on 30 pwPD and 28 age-gender matched controls. Voice disability (Voice Handicap Index), and disease variables of disease duration, Activities of Daily Living (Unified Parkinson's Disease Rating Scale [UPDRS II]), and motor symptoms related to PD (UPDRS III) were examined for relationship with voice tremor measures. Voice tremor was detected acoustically in pwPD and controls with similar frequency. PwPD had a statistically significantly higher rate of amplitude tremor (Hz) than controls (P = 0.001). Rate of amplitude tremor was negatively and significantly correlated with UPDRS III total score (rho -0.509). For pwPD, the magnitude and periodicity of acoustic tremor was higher than for controls without statistical significance. The magnitude of frequency tremor (Mftr%) was positively and significantly correlated with disease duration (rho 0.463). PwPD had higher Voice Handicap Index total, functional, emotional, and physical subscale scores than matched controls (P < 0.001). Voice disability did not correlate significantly with acoustic voice tremor measures. Acoustic analysis enhances understanding of PD voice tremor characteristics, its pathophysiology, and its relationship with voice disability and disease symptomatology. Copyright © 2018 The Voice Foundation. All rights reserved.

Efficacy and safety of down-titration versus continuation strategies of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis with low disease activity or in remission: a systematic review and meta-analysis.

PubMed

Jiang, Mei; Ren, Feifeng; Zheng, Yaning; Yan, Ruyu; Huang, Wenhan; Xia, Ning; Luo, Lei; Zhou, Jun; Tang, Lin

2017-01-01

To evaluate the efficacy and safety of down-titration (dose reduction/tapering) strategies compared with continuation of biological disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who achieved and maintained low disease activity or remission. We searched the following electronic database up to March 2016: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and conference proceedings of the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR). Our meta-analysis included randomized controlled trials (RCTs) of RA patients with low disease activity or in remission that compared down-titration treatment with continuation treatment. Data on flare, defined as a 28-joint Disease Activity Score of ≥3.2, had to have been reported. Outcomes on efficacy or safety were collected. Of 1136 references identified, five RCTs (total, 771 participants) were included. The incidence of disease relapse in the down-titration and continuation groups was similar (risk ratio (RR)=1.14, 95% CI=0.88-1.49). There was no statistical difference in the number of serious adverse events (RR=1.15, 95% CI=0.53-2.49). Withdrawals due to inefficacy or toxicity were similar between groups and no clinically meaningful difference in efficacy outcomes was observed by continuation treatment. Our findings indicated that continuing a standard dose of biological DMARDs in patients with low disease activity conveyed no significant benefit as compared with down-titration therapy, suggesting that a down-titration strategy is as effective as a continuation strategy. Since the number of trials meeting the criteria for this meta-analysis was relatively low, future analyses with additional prospective RCTs are required to compare other biological agents and evaluate the long-term efficacy of these two strategies.

Serum angiotensin-converting enzyme (SACE) in sarcoidosis and other granulomatous disorders.

PubMed

Studdy, P; Bird, R; James, D G

Serum angiotensin-converting enzyme (SACE) activity was significantly higher in 90 patients with sarcoidosis (55 +/- [S.D.] 23 nmol min-1 ml-1) than in 80 healthy controls (34 +/- 9 nmol min-1 ml-1). Steroid therapy modified SACE activity; 60 sarcoidosis patients who were not being treated with steroids had significantly higher enzyme activities (58 +/- 24 nmol min-1 ml-1) than 30 steroid-treated sarcoidosis patients (40 +/- 19 nmol min-1 ml-1). In 50% of the non-steroid treated sarcoidosis patients SACE activity was more than 2 S.D. above the mean value for the controls. SACE activity was measured in 22 tuberculous patients (38 +/- 14 nmol min-1 ml-1), 20 leprosy patients (34 +/- 9 nmol min-1 ml-1), 31 with primary biliary cirrhosis (44 +/- 20 nmol min-1 ml-1), 26 with inflammatory bowel disease (31 +/- 9 nmol min-1 ml-1), 8 with hepatic granulomatous disease, 5 with Hodgkin's disease, and 2 with schistosomiasis. The combined false-positive rate for these non-sarcoidosis patients was 10%. Serial SACE assays provide useful information on the course of sarcoidosis and response to steroid treatment.

Serum angiotensin--converting enzyme (SACE) in sarcoidosis and other granulomatous disorders.

PubMed

Studdy, P; Bird; James, D G; Sherlock, S

Serum angiotensin-converting enzyme (SACE) activity was significantly higher in 90 patients with sarcoidosis (55 +/- [S.D.] 23 nmol min-1 ml-1) than in 80 healthy controls (34 +/- 9 nmol min-1 ml-1). Steroid therapy modified SACE activity; 60 sarcoidosis patients who were not being treated with steroids had significantly higher enzyme activities (58 +/- 24 nmol min-1 ml-1) than 30 steroid-treated sarcoidosis patients (40 +/- 19 nmol min-1 ml-1). In 50% of the non-steroid treated sarcoidosis patients SACE activity was more than than 2 S.D. above the mean value for the controls. SACE activity was measured in 22 tuberculous patients (38 +/- 14 nmol min-1 ml-1), 20 leprosy patients (34 +/- 9 nmol min-1 ml-1), 31 with primary biliary cirrhosis (44 +/- 20 nmol min-1 ml-1), 26 with inflammatory bowel disease (31 +/- 9 nmol min-1 ml-1), eight with hepatic granulomatous disease, five with Hodgkin's disease, and two with schistosomiasis. The combined false-positive rate for these non-sarcoidosis patients was 10%. Serial SACE assays provide useful information on the course of sarcoidosis and response to steroid treatment.

Behavioral, normative and control beliefs underlying low-fat dietary and regular physical activity behaviors for adults diagnosed with type 2 diabetes and/or cardiovascular disease.

PubMed

White, Katherine M; Terry, Deborah J; Troup, Carolyn; Rempel, Lynn A

2007-08-01

Promoting healthy lifestyle behaviors is an important aspect of interventions designed to improve the management of chronic diseases such as Type 2 diabetes and cardiovascular disease. The present study used Ajzen's (1991) theory of planned behavior as a framework to examine beliefs amongst adults diagnosed with these conditions who do and do not engage in low-fat dietary and regular physical activity behaviors. Participants (N = 192) completed a questionnaire assessing their behavioral, normative and control beliefs in relation to regular, moderate physical activity and eating foods low in saturated fats. Measures of self-reported behavior were also examined. The findings revealed that, in general, it is the underlying behavioral beliefs that are important determinants for both physical activity and low-fat food consumption with some evidence to suggest that pressure from significant others is an important consideration for low-fat food consumption. Laziness, as a barrier to engaging in physical activity, also emerged as an important factor. To encourage a healthy lifestyle amongst this population, interventions should address the perceived costs associated with behavioral performance and encourage people to maintain healthy behaviors in light of these costs.

Thyroid function and obesity.

PubMed

Laurberg, Peter; Knudsen, Nils; Andersen, Stig; Carlé, Allan; Pedersen, Inge Bülow; Karmisholt, Jesper

2012-10-01

Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail.

Paratransgenic Control of Vector Borne Diseases

PubMed Central

Hurwitz, Ivy; Fieck, Annabeth; Read, Amber; Hillesland, Heidi; Klein, Nichole; Kang, Angray; Durvasula, Ravi

2011-01-01

Conventional methodologies to control vector borne diseases with chemical pesticides are often associated with environmental toxicity, adverse effects on human health and the emergence of insect resistance. In the paratransgenic strategy, symbiotic or commensal microbes of host insects are transformed to express gene products that interfere with pathogen transmission. These genetically altered microbes are re-introduced back to the insect where expression of the engineered molecules decreases the host's ability to transmit the pathogen. We have successfully utilized this strategy to reduce carriage rates of Trypanosoma cruzi, the causative agent of Chagas disease, in the triatomine bug, Rhodnius prolixus, and are currently developing this methodology to control the transmission of Leishmania donovani by the sand fly Phlebotomus argentipes. Several effector molecules, including antimicrobial peptides and highly specific single chain antibodies, are currently being explored for their anti-parasite activities in these two systems. In preparation for eventual field use, we are actively engaged in risk assessment studies addressing the issue of horizontal gene transfer from the modified bacteria to environmental microbes. PMID:22110385

Applying Science: Opportunities to Inform Disease Management Policy with Cooperative Research within a One Health Framework.

PubMed

Blackburn, Jason K; Kracalik, Ian T; Fair, Jeanne Marie

2015-01-01

The ongoing Ebola outbreak in West Africa and the current saiga antelope die off in Kazakhstan each represent very real and difficult to manage public or veterinary health crises. They also illustrate the importance of stable and funded surveillance and sound policy for intervention or disease control. While these two events highlight extreme cases of infectious disease (Ebola) or (possible) environmental exposure (saiga), diseases such as anthrax, brucellosis, tularemia, and plague are all zoonoses that pose risks and present surveillance challenges at the wildlife-livestock-human interfaces. These four diseases are also considered important actors in the threat of biological terror activities and have a long history as legacy biowarfare pathogens. This paper reviews recent studies done cooperatively between American and institutions within nations of the Former Soviet Union (FSU) focused on spatiotemporal, epidemiological, and ecological patterns of these four zoonoses. We examine recent studies and discuss the possible ways in which techniques, including ecological niche modeling, disease risk modeling, and spatiotemporal cluster analysis, can inform disease surveillance, control efforts, and impact policy. Our focus is to posit ways to apply science to disease management policy and actual management or mitigation practices. Across these examples, we illustrate the value of cooperative studies that bring together modern geospatial and epidemiological analyses to improve our understanding of the distribution of pathogens and diseases in livestock, wildlife, and humans. For example, ecological niche modeling can provide national level maps of pathogen distributions for surveillance planning, while space-time models can identify the timing and location of significant outbreak events for defining active control strategies. We advocate for the need to bring the results and the researchers from cooperative studies into the meeting rooms where policy is negotiated and use these results to inform future disease surveillance and control or eradication campaigns.

Semantic memory activation in individuals at risk for developing Alzheimer disease.

PubMed

Seidenberg, M; Guidotti, L; Nielson, K A; Woodard, J L; Durgerian, S; Antuono, P; Zhang, Q; Rao, S M

2009-08-25

To determine whether whole-brain, event-related fMRI can distinguish healthy older adults with known Alzheimer disease (AD) risk factors (family history, APOE epsilon4) from controls using a semantic memory task involving discrimination of famous from unfamiliar names. Sixty-nine cognitively asymptomatic adults were divided into 3 groups (n = 23 each) based on AD risk: 1) no family history, no epsilon4 allele (control [CON]); 2) family history, no epsilon4 allele (FH); and 3) family history and epsilon4 allele (FH+epsilon4). Separate hemodynamic response functions were extracted for famous and unfamiliar names using deconvolution analysis (correct trials only). Cognitively intact older adults with AD risk factors (FH and FH+epsilon4) exhibited greater activation in recognizing famous relative to unfamiliar names than a group without risk factors (CON), especially in the bilateral posterior cingulate/precuneus, bilateral temporoparietal junction, and bilateral prefrontal cortex. The increased activation was more apparent in the FH+epsilon4 than in the FH group. Unlike the 2 at-risk groups, the control group demonstrated greater activation for unfamiliar than familiar names, predominately in the supplementary motor area, bilateral precentral, left inferior frontal, right insula, precuneus, and angular gyrus. These results could not be attributed to differences in demographic variables, cerebral atrophy, episodic memory performance, global cognitive functioning, activities of daily living, or depression. Results demonstrate that a low-effort, high-accuracy semantic memory activation task is sensitive to Alzheimer disease risk factors in a dose-related manner. This increased activation in at-risk individuals may reflect a compensatory brain response to support task performance in otherwise asymptomatic older adults.

Pediatric inflammatory bowel disease and bone health.

PubMed

Mascarenhas, Maria R; Thayu, Meena

2010-08-01

Childhood and adolescence are important periods for bone development. Any disease that affects bone health has the potential to affect the bones not only in the short term but also later in life. Bone health abnormalities in patients with inflammatory bowel disease are being increasingly recognized. Screening the at-risk patient is important so that appropriate treatments can be instituted. Treatment options are limited to vitamin D and calcium supplementation, control of underlying disease activity, and appropriate physical activity. The role of bisphosphonates in these patients needs to be better studied, and treatment with bisphosphonates may be considered for some patients in consultation with a bone health expert.

Veterinary public health activities at FAO: echinococcosis/hydatid disease.

PubMed

Eddi, C; de Balogh, K; Lubroth, J; Amanfu, W; Speedy, A; Battaglia, D

2004-12-01

Cystic hydatidosis is a zoonotic disease that remain as a significant cause of human morbidity and mortality in many parts of the world. The disease has veterinary public health implications. FAO is involved with some activities in the control of echinococcosis/hydatid disease: within the Animal Production and Health Division the Veterinary Public Health (VHP) Programme is constituted by members of the different Services (Animal Health, Animal Production, and Livestock Policy) within the Division. FAO regular programme has also established a global network of professionals directly involved in VPH. Furthermore FAO's Technical Cooperation Projects (TCP) is a tool to assist member countries in responding to urgent and unforeseen demands.

Motor Control Abnormalities in Parkinson’s Disease

PubMed Central

Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

2012-01-01

The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

Effect of a multimodal exercise program on sleep disturbances and instrumental activities of daily living performance on Parkinson's and Alzheimer's disease patients.

PubMed

Nascimento, Carla Manuela Crispim; Ayan, Carlos; Cancela, Jose Maria; Gobbi, Lilian Teresa Bucken; Gobbi, Sebastião; Stella, Florindo

2014-04-01

To assess the contribution of a multimodal exercise program on the sleep disturbances (SD) and on the performance of instrumental activities daily living (IADL) in patients with clinical diagnosis of Alzheimer's disease (AD) and Parkinson's disease patients (PD). A total of 42 consecutive patients (23 training group, 19 control group) with PD and 35 demented patients with AD (19 trained group, 16 control group) were recruited. Participants in both training groups carried out three 1-h sessions per week of a multimodal exercise program for 6 months. The Pfeffer Questionnaire for Instrumental Activities and the Mini-Sleep Questionnaire were used to assess the effects of the program on IADL and SD respectively. Two-way ancova showed interactions in IADL and SD. Significant improvements were observed for these variables in both intervention groups, and maintenance or worsening was observed in control groups. The analysis of effect size showed these improvements. The present study results show that a mild to moderate intensity of multimodal physical exercises carried out on a regular basis over 6 months can contribute to reducing IADL deficits and attenuating SD. © 2013 Japan Geriatrics Society.

A partially supervised physical activity program for adult and adolescent survivors of childhood cancer (SURfit): study design of a randomized controlled trial [NCT02730767].

PubMed

Rueegg, Corina S; Kriemler, Susi; Zuercher, Simeon J; Schindera, Christina; Renner, Andrea; Hebestreit, Helge; Meier, Christian; Eser, Prisca; von der Weid, Nicolas X

2017-12-05

Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today's survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). Primary outcome of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. Secondary outcomes are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety). A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant. The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients. Prospectively registered in clinicaltrials.gov [ NCT02730767 ], registration date: 10.12.2015.

Neural correlates of impaired emotion processing in manifest Huntington's disease.

PubMed

Dogan, Imis; Saß, Christian; Mirzazade, Shahram; Kleiman, Alexandra; Werner, Cornelius J; Pohl, Anna; Schiefer, Johannes; Binkofski, Ferdinand; Schulz, Jörg B; Shah, N Jon; Reetz, Kathrin

2014-05-01

The complex phenotype of Huntington's disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.

Is Vector Control Sufficient to Limit Pathogen Spread in Vineyards?

PubMed

Daugherty, M P; O'Neill, S; Byrne, F; Zeilinger, A

2015-06-01

Vector control is widely viewed as an integral part of disease management. Yet epidemiological theory suggests that the effectiveness of control programs at limiting pathogen spread depends on a variety of intrinsic and extrinsic aspects of a pathosystem. Moreover, control programs rarely evaluate whether reductions in vector density or activity translate into reduced disease prevalence. In areas of California invaded by the glassy-winged sharpshooter (Homalodisca vitripennis Germar), Pierce's disease management relies heavily on chemical control of this vector, primarily via systemic conventional insecticides (i.e., imidacloprid). But, data are lacking that attribute reduced vector pressure and pathogen spread to sharpshooter control. We surveyed 34 vineyards over successive years to assess the epidemiological value of within-vineyard chemical control. The results showed that imidacloprid reduced vector pressure without clear nontarget effects or secondary pest outbreaks. Effects on disease prevalence were more nuanced. Treatment history over the preceding 5 yr affected disease prevalence, with significantly more diseased vines in untreated compared with regularly or intermittently treated vineyards. Yet, the change in disease prevalence between years was low, with no significant effects of insecticide treatment or vector abundance. Collectively, the results suggest that within-vineyard applications of imidacloprid can reduce pathogen spread, but with benefits that may take multiple seasons to become apparent. The relatively modest effect of vector control on disease prevalence in this system may be attributable in part to the currently low regional sharpshooter population densities stemming from area-wide control, without which the need for within-vineyard vector control would be more pronounced. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Patient-experienced effect of an active implementation of a disease management programme for COPD – a randomised trial

PubMed Central

2013-01-01

Background People living with chronic disease currently account for the majority of the total healthcare costs. The Central Denmark Region implemented a disease management programme (DMP) for chronic obstructive pulmonary disease (COPD) in 2008. This presented an opportunity to examine the effect of an evidence-based, planned and proactive implementation of a DMP compared to the usual implementation strategy. Methods We performed a block- and cluster-randomised controlled trial with two groups and an extra external control group. The primary outcome was patients’ assessment of their care after using an active implementation model for a DMP for COPD measured with the Patient-Assessment-of-Chronic-Illness-Care (PACIC) instrument. At baseline, questionnaires were sent to 2,895 patients identified by an algorithm based on health registry data on lung-related contacts to the healthcare system. Patients were asked to confirm or refute their diagnosis of COPD. Of those who responded, 1,445 (72.8%) confirmed their diagnosis. PACIC data were collected at baseline and at a 12-month follow-up for 744 (51.1%) patients. Results Comparing the three groups after the implementation of the DMP, we found a statistically significantly higher change in the PACIC score in the intervention group than in the control groups. No statistically significant differences were found between the control and the external control groups in any of the dimensions. Conclusions Reinforcing the role of general practice as coordinator for care-and self-management-support with an active implementation of a DMP for COPD made patients score higher on the PACIC instrument, which indicates a better experience of the received healthcare. Trial registration NCT01228708. PMID:24088417

[Vitamin D levels in ankylosing spondylitis: does deficiency correspond to disease activity?].

PubMed

Pokhai, Gabriel G; Bandagi, Sabiha; Abrudescu, Adriana

2014-01-01

Ankylosing spondylitis (AS) is an inflammatory disorder that presents with arthritis of the axial skeleton, including sacroiliac joints. Vitamin D is a secosteroid hormone with a long-established role in calcium and phosphate homeostasis, and in the regulation of bone formation and resorption. It is now known that vitamin D plays an immunosuppressive role in the body, and there is interest of late in the role of vitamin D in autoimmune diseases. Inflammation may be responsible for some of the loss of bone mineral density seen in AS. We reviewed the literature for studies assessing vitamin D level as a marker of AS disease activity and those examining vitamin D levels in AS in comparison to healthy controls. Four of 7 studies found a significant negative correlation between vitamin D levels and Bath Ankylosing Spondylitis Index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In a review of 8 case-control studies, the mean level of 25-hydroxyvitamin D3 was 22.8 ± 14.1 ng/mL in 555 AS patients versus 26.6 ± 12.5 ng/mL in 557 healthy controls. When compared with a 2-sample t test, vitamin D levels were significantly higher in healthy controls (p < 0.01). We conclude that patients with AS appear to have lower vitamin D levels versus healthy controls; however, the cause is unclear. Existing studies do not demonstrate a consistent link between vitamin D levels and disease activity in AS. Further studies are in need to determine if a causative link exists between vitamin D deficiency and AS. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Patient-experienced effect of an active implementation of a disease management programme for COPD - a randomised trial.

PubMed

Smidth, Margrethe; Olesen, Frede; Fenger-Grøn, Morten; Vedsted, Peter

2013-10-03

People living with chronic disease currently account for the majority of the total healthcare costs. The Central Denmark Region implemented a disease management programme (DMP) for chronic obstructive pulmonary disease (COPD) in 2008. This presented an opportunity to examine the effect of an evidence-based, planned and proactive implementation of a DMP compared to the usual implementation strategy. We performed a block- and cluster-randomised controlled trial with two groups and an extra external control group. The primary outcome was patients' assessment of their care after using an active implementation model for a DMP for COPD measured with the Patient-Assessment-of-Chronic-Illness-Care (PACIC) instrument. At baseline, questionnaires were sent to 2,895 patients identified by an algorithm based on health registry data on lung-related contacts to the healthcare system. Patients were asked to confirm or refute their diagnosis of COPD. Of those who responded, 1,445 (72.8%) confirmed their diagnosis. PACIC data were collected at baseline and at a 12-month follow-up for 744 (51.1%) patients. Comparing the three groups after the implementation of the DMP, we found a statistically significantly higher change in the PACIC score in the intervention group than in the control groups. No statistically significant differences were found between the control and the external control groups in any of the dimensions. Reinforcing the role of general practice as coordinator for care-and self-management-support with an active implementation of a DMP for COPD made patients score higher on the PACIC instrument, which indicates a better experience of the received healthcare. NCT01228708.

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease

PubMed Central

Yüksel, Harun; Türkcü, Fatih M.; Hamidi, Cihat; Cingü, Abdullah K.; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

ABSTRACT In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group (p < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients PMID:27928286

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease.

PubMed

Yüksel, Harun; Türkcü, Fatih M; Hamidi, Cihat; Cingü, Abdullah K; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group ( p  < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients.

Physical Activity during the School Day

ERIC Educational Resources Information Center

Castelli, Darla M.; Ward, Kimberly

2012-01-01

In response to concerns that children are physically inactive, a Centers for Disease Control and Prevention committee developed school-based implementation strategies centered on the components of a Comprehensive School Physical Activity Program (CSPAP), composed of the physical education program, physical activity during the school day, staff…

SARCOSPA - Sarcopenia in spondyloarthritis patients.

PubMed

Aguiar, R; Sequeira, J; Meirinhos, T; Ambrósio, C; Barcelos, A

2014-01-01

The loss of muscle mass (MM) is a serious problem which has been demonstrated in patients with rheumatoid arthritis. There are few studies about the loss of MM in patients with spondyloarthritis (Spa). To assess muscle mass index (MMI) in a cohort of patients with Spa and compare it with a control group of healthy individuals; to verify if a higher risk of sarcopenia is related with disease activity, functional impairment, duration of the illness and radiological damage. Case control study. Muscle mass index (MMI) was determined, from the value of MM, using Lee's equation, in a cohort of patients with spondyloarthritis and in a control group. Bath Ankylosing Spondylitis Disease Activity and Function Indexes (BASDAI and BASFI), Ankylosing Spondylitis Quality of Life (ASQoL) and Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were assessed in a cohort of patients with axial Spa, as well as Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 (DAS28) in patients with peripheral disease. Data were treated using SPSS version 17.0. Values of p<0,05 were considered with statistical significance. 60 patients were enrolled; 48.2% were males, mean age 45.5±13.4 years, mean disease duration 10.9±11.6 years; 36 had ankylosing spondylitis and 24 had psoriatic arthritis. 62% of patients had sarcopenia and there was a significant difference in mean MMI between patients and controls (7.65±0.98 vs 8.25±0.92; p=0.001, OR =5.23. In male patients, there was a statistically significant moderate negative correlation between MMI and BASDAI and BASFI (p=-0.536 and p=-0.445). No other significant correlations were identified. Our study supports the hypothesis of a greater prevalence of sarcopenia in patients with Spa compared to healthy controls. Some limitations included the sample size, potential confounding factor such the bias of measurement and the use of a non-validated equation to Portuguese population to calculate MM.

Efficacy of microorganisms selected from compost to control soil-borne pathogens.

PubMed

Pugliese, M; Gullino, M L; Garibaldi, A

2010-01-01

Suppression of soil-borne plant pathogens with compost has been widely studied. Compost has been found to be suppressive against several soil-borne pathogens in various cropping systems. However, an increase of some diseases due to compost usage has also been observed, since compost is a product that varies considerably in chemical, physical and biotic composition, and, consequently, also in ability to suppress soil borne diseases. New opportunities in disease management can be obtained by the selection of antagonists from suppressive composts. The objective of the present work was to isolate microorganisms from a suppressive compost and to test them for their activity against soil-borne pathogens. A compost from green wastes, organic domestic wastes and urban sludge's that showed a good suppressive activity in previous trials was used as source of microorganisms. Serial diluted suspensions of compost samples were plated on five different media: selective for Fusarium sp., selective for Trichoderma sp., selective for oomycetes, potato dextrose agar (PDA) for isolation of fungi, lysogeny broth (LB) for isolation of bacteria. In total, 101 colonies were isolated from plates and tested under laboratory conditions on tomato seedlings growing on perlite medium in Petri plates infected with Fusarium oxysporum f.sp. radicis-lycopersici and compared to a commercial antagonist (Streptomyces griserovidis, Mycostop, Bioplanet). Among them, 28 showed a significant disease reduction and were assessed under greenhouse condition on three pathosystems: Fusarium oxysporum f.sp. basilica/basil, Phytophthora nicotianae/tomato and Rhizoctonia solani/bean. Fusarium spp. selected from compost generally showed a good disease control against Fusarium wilts, while only bacteria significantly controlled P. nicotianae on tomato under greenhouse conditions. None of the microorganisms was able to control the three soil-borne pathogens together, in particular Rhizoctonia solani. Results confirmed the good suppressive activity of the compost under study against soil-borne pathogens. The selection of antagonists from compost is a promising strategy for the development of new biological control agents against soil-borne pathogens.

78 FR 1826 - International Sanitary and Phytosanitary Standard-Setting Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... Health (OIE, formerly known as the Office International des Epizooties) regarding animal health and... international significance, publishes bulletins on global disease status, and provides animal disease control guidelines to Members. Various OIE commissions and working groups undertake the development and preparation...

Deep-brain stimulator and control of Parkinson's disease

NASA Astrophysics Data System (ADS)

Varadan, Vijay K.; Harbaugh, Robert; Abraham, Jose K.

2004-07-01

The design of a novel feedback sensor system with wireless implantable polymer MEMS sensors for detecting and wirelessly transmitting physiological data that can be used for the diagnosis and treatment of various neurological disorders, such as Parkinson's disease, epilepsy, head injury, stroke, hydrocephalus, changes in pressure, patient movements, and tremors is presented in this paper. The sensor system includes MEMS gyroscopes, accelerometers, and pressure sensors. This feedback sensor system focuses on the development and integration of implantable systems with various wireless sensors for medical applications, particularly for the Parkinson's disease. It is easy to integrate and modify the sensor network feed back system for other neurological disorders mentioned above. The monitoring and control of tremor in Parkinson's disease can be simulated on a skeleton via wireless telemetry system communicating with electroactive polymer actuator, and microsensors attached to the skeleton hand and legs. Upon sensing any abnormal motor activity which represent the characteristic rhythmic motion of a typical Parkinson's (PD) patient, these sensors will generate necessary control pulses which will be transmitted to a hat sensor system on the skeleton head. Tiny inductively coupled antennas attached to the hat sensor system can receive these control pulses, demodulate and deliver it to actuate the parts of the skeleton to control the abnormal motor activity. This feedback sensor system can further monitor and control depending on the amplitude of the abnormal motor activity. This microsystem offers cost effective means of monitoring and controlling of neurological disorders in real PD patients. Also, this network system offers a remote monitoring of the patients conditions without visiting doctors office or hospitals. The data can be monitored using PDA and can be accessed using internet (or cell phone). Cellular phone technology will allow a health care worker to be automatically notified if monitoring indicates an emergency situation. The main advantage of such system is that it can effectively monitor large number of patients at the same time, which helps to compensate the present shortage of health care workers.

Oxidative stress and fatigue in systemic lupus erythematosus.

PubMed

Segal, B M; Thomas, W; Zhu, X; Diebes, A; McElvain, G; Baechler, E; Gross, M

2012-08-01

The objective of this study is to investigate the relationship of oxidative stress to fatigue in systemic lupus erythematosus (SLE). Patients with a confirmed diagnosis of SLE by ACR criteria and healthy controls completed validated questionnaires to assess depression and fatigue. Fatigue was measured with the Fatigue Severity Scale (FSS) and the Profile of Fatigue (Prof-F). Visual analogue scales (VAS) were also used to assess fatigue and pain. Depression was measured with the Center for Epidemiologic Studies Depression Scale (CES-D). Plasma F(2)-isoprostane was measured with gas chromatography/mass spectroscopy to assess oxidative stress. Evaluation included medical record review, physical exam and calculation of body mass index (BMI), disease activity (SLEDAI) and damage (SLICC) in the SLE patients. Seventy-one SLE patients with low disease activity (mean SLEDAI = 1.62 standard error (SE) 0.37, range 0-8) were compared to 51 controls. Fatigue-limiting physical activity (defined as FSS ≥ 4) was present in 56% of patients and 12% of controls. F(2)-isoprostane was higher in SLE patients with fatigue compared to not-fatigued SLE subjects (p = .0076) who were otherwise similar in ethnicity, disease activity and cardiovascular risk factors. Plasma F(2)-isoprostane was strongly correlated with FSS and Profile of Somatic Fatigue (Prof-S) (p < .0001), VAS fatigue (p = .005), CES-D (p = .008) and with BMI (p = .0001.) In a multivariate model, F(2)-isoprostane was a significant predictor of FSS after adjustment for age, BMI, pain and depression (p = .0002). Fatigue in SLE patients with low disease activity is associated with increased F(2)-isoprostane. F2-isoprostane could provide a useful biomarker to explore mitochondrial function and the regulation of oxidative pathways in patients with SLE in whom fatigue is a debilitating symptom.

Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

PubMed

Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

2015-07-01

Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

PubMed

Yang, J; Li, Q; Yang, X; Li, M

2016-04-01

Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

Impact of early diagnosis and control of chronic respiratory diseases on active and healthy ageing. A debate at the European Union Parliament.

PubMed

Bousquet, J; Tanasescu, C C; Camuzat, T; Anto, J M; Blasi, F; Neou, A; Palkonen, S; Papadopoulos, N G; Antunes, J P; Samolinski, B; Yiallouros, P; Zuberbier, T

2013-01-01

A debate at the European Union Parliament was held on 13 November 2012 on the Impact of early diagnosis and control of chronic respiratory diseases on Active and Healthy Ageing (AHA). The debate was held under the auspices of the Cyprus Presidency of the European Union (2012) and represents a follow-up of the priorities of the Polish Presidency of the European Union (2011). It highlighted the importance of early life events on the occurrence of chronic respiratory diseases later in life and their impact on active and healthy ageing. Epidemiologic evidence was followed by actions that should be taken to prevent and manage chronic respiratory diseases in children. The debate ended by practical, feasible and achievable projects, demonstrating the strength of the political action in the field. Three projects will be initiated from this debate: The first will be a meeting sponsored by the Région Languedoc-Roussillon on the developmental origins of chronic diseases and ageing: from research to policies and value creation. The second project is being led by the WHO Collaborating Centre for Asthma and Rhinitis: Prevention of Asthma, Prevention of Allergy (PAPA). The third project is the GA(2)LEN sentinel network. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Prospective validation study of the International Classification of Functioning, Disability and Health score in Crohn's disease and ulcerative colitis.

PubMed

Leong, Rupert W L; Huang, Tony; Ko, Yanna; Jeon, Ari; Chang, Jeff; Kohler, Friedbert; Kariyawasam, Viraj

2014-10-01

Inflammatory bowel diseases (IBD) may result in disability. We aim to validate a novel scoring system for the IBD disability index (IBD-DI), and identify predictors of disability and its correlation with work absenteeism. This prospective IBD ambulatory clinic cohort study measured IBD-DI, Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) or partial Mayo score (pMayo) for ulcerative colitis (UC), IBDQ quality-of-life, and Work Productivity and Activity Impairment. Negative IBD-DI represented greater disability. Validation tests were performed and predictors and extent of work absenteeism were determined. 166 consecutive subjects were recruited (75 CD, 41 UC, 50 controls). IBD-DI correlated with CDAI (r=-0.77, P<0.001), pMayo (r=-0.82, P<0.001) and IBDQ (r=0.86, P<0.001). IBD-DI differentiated CD, and UC from controls (medians -7, -4, +10; P<0.001) with a score of >3.5 identifying controls with 94% sensitivity and 83% specificity (area-under-curve 0.92). Stable patients had unchanged IBD-DI (P=ns) but not in those who relapsed (P<0.001). Intraclass correlation was 0.89 and Cronbach's alpha of internal consistency was 0.94. Diagnosis age, sex, phenotype, perianal disease, prior surgery, steroid-use and disease duration did not influence the IBD-DI but active use of biological agents significantly reduced disability (P=0.03). 21.6% of IBD patients had moderate-severe disability equating to missing >25% of work hours in the previous week. Multivariate analysis identified that only IBD-DI to be predictive of unemployment status (OR: 0.94; 95% CI: 0.89-0.99). The IBD-DI is a valid tool measuring disability in both CD and UC and correlates with workforce participation. It is a potential useful tool in the assessment of participation restriction and activity limitation. ACTRN12613000903785. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

An examination of appetite and disordered eating in active Crohn's disease.

PubMed

Wardle, Richard Anthony; Thapaliya, Gita; Nowak, Adam; Radford, Shellie; Dalton, Michelle; Finlayson, Graham; Moran, Gordon W

2018-04-03

Crohn's disease (CD) patients suffer from nutritional deficiencies when in active disease. We aim to examine calorific intake, macronutrient choice and disordered eating behaviour in patients with active CD. CD patients with matched healthy volunteers (HV) were recruited. Active disease was defined by faecal calprotectin >250ug/g, C-reactive protein >5mg/dl, or active disease seen on endoscopy or imaging. Symptoms were quantified by Harvey-Bradshaw Index (HBI). Calorific intake was assessed by 24-h dietary recall. Disordered eating was assessed using validated questionnaires [Binge Eating Scale (BES); Power of Food Scale (PFS); Control of Eating Questionnaire (CoEQ); Dutch Eating Behaviour Questionnaire (DEBQ); Three Factor Eating Questionnaire (TFEQ)]. 30 CD (18M:12F, Age:32.3±2.19, BMI:24.9±0.8) and 31 matched HV (19M:12F, Age:32.8±2.0, BMI:24.7±0.5) were recruited. Mean faecal calprotectin was 1032.5±176µg/g,C-reactive protein 83.8±47.1mg/L and HBI 4.8±1. There were no significant differences in calorific intake between groups. Protein intake was lower in the CD cohort (p=0.03). Hospital Anxiety and Depression score was higher (p=0.01) and CoEQ-Positive Mood (p=0.001) lower in CD. CD were characterised by higher BES (p=0.01) and lower CoEQ Craving Control (p=0.027) with greater craving for Sweet (p=0.043), Savoury (p=0.021) foods. PFS food present (p=0.005), DEBQ Emotional (p=<0.001) and External Eating (p=0.022) were significantly higher than HV. Reduced protein consumption and more prevalent disordered eating behaviour traits were present in CD. Greater binge eating and decreased control of cravings may be attributed to lower mood and higher anxiety observed. Patients may benefit from stronger psychological support with firm dietetic advice for healthy eating.

Pruritus in Autoimmune Connective Tissue Diseases.

PubMed

Smith, Gideon P; Argobi, Yahya

2018-07-01

Pruritus in autoimmune connective tissue diseases is a common symptom that can be severe and affect the quality of life of patients. It can be related to disease activity and severity or occur independent of the disease. Appropriate therapy to control the itch depends on the etiology, and it is therefore essential to first work-up these patients for the underlying trigger. Copyright © 2018 Elsevier Inc. All rights reserved.

Active Vaccines for Alzheimer Disease Treatment.

PubMed

Sterner, Rosalie M; Takahashi, Paul Y; Yu Ballard, Aimee C

2016-09-01

Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression. PubMed and Scopus were searched for clinical trial articles, review articles, and preclinical studies relevant to the field of active Alzheimer disease vaccines and raw searches yielded articles ranging from 2016 to 1973. ClinicalTrials.gov was searched for active Alzheimer disease vaccine trials. Manual research and cross-referencing from reviews and original articles was performed. First generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis in 6% of patients, so next generation vaccines are working to target more specific epitopes to induce a more controlled immune response. Difficulty in developing these vaccines resides in striking a balance between providing a vaccine that induces enough of an immune response to actually clear protein sustainably but not so much of a response that results in excess immune activation and possibly adverse effects such as meningoencephalitis. Although much work still needs to be done in the field to make this a practical possibility, the enticing allure of being able to treat or even prevent the extraordinarily impactful disease that is Alzheimer disease makes the idea of active vaccination for Alzheimer disease very appealing and something worth striving toward. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

PGC-1α, A Potential Therapeutic Target for Early Intervention in Parkinson’s Disease

PubMed Central

Zheng, Bin; Liao, Zhixiang; Locascio, Joseph J.; Lesniak, Kristen A.; Roderick, Sarah S.; Watt, Marla L.; Eklund, Aron C.; Zhang-James, Yanli; Kim, Peter D.; Hauser, Michael A.; Grünblatt, Edna; Moran, Linda B.; Mandel, Silvia A.; Riederer, Peter; Miller, Renee M.; Federoff, Howard J.; Wüllner, Ullrich; Papapetropoulos, Spyridon; Youdim, Moussa B.; Cantuti-Castelvetri, Ippolita; Young, Anne B.; Vance, Jeffery M.; Davis, Richard L.; Hedreen, John C.; Adler, Charles H.; Beach, Thomas G.; Graeber, Manuel B.; Middleton, Frank A.; Rochet, Jean-Christophe; Scherzer, Clemens R.

2011-01-01

Parkinson’s disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson’s and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene sets with previously unknown associations with Parkinson’s disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed in response to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) are underexpressed in Parkinson’s disease patients. Activation of PGC-1α results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced by mutant α-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson’s disease identifies PGC-1α as a potential therapeutic target for early intervention. PMID:20926834

Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD.

PubMed

Cosnes, Jacques

2010-01-01

Current smoking increases the risk of developing Crohn's disease and worsens its course, increasing the need for steroids, immunosuppressants, and re-operations. On the contrary, smoking protects against ulcerative colitis and after disease onset improves its course, decreasing the need for colectomy. Smoking cessation improves Crohn's disease and worsens ulcerative colitis. Achieving smoking cessation in Crohn's disease is thus an important goal of therapy, whereas patients with ulcerative colitis should not be discouraged to quit, because the beneficial effect of smoking for their disease is counterbalanced by the deleterious respiratory and cardiovascular effects of tobacco. Physical activity improves quality of life without detrimental effect on disease activity, and may contribute to increase muscle mass and to prevent osteoporosis. Regarding nutrition, a Western diet may be associated with an increased risk of IBD, and a case-control study revealed an increased consumption of linoleic acid before diagnosis of ulcerative colitis. Liquid diets may improve Crohn's disease flares and decrease the need for steroids; however, there are no defined diets able to improve the disease course, and in Crohn's disease, supplementation with omega-3 fatty acids did not show a significant benefit. Obesity is becoming more prevalent in IBD and may be associated with higher disease activity. In total, adhering to four simple lifestyle factors - never smoking, physical activity, prudent diet and body mass index <25 - may have a strong impact both on the prevention of major chronic diseases and on the course of IBD. Copyright © 2010 S. Karger AG, Basel.

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

Physical activity in the prevention of the most frequent chronic diseases: an analysis of the recent evidence.

PubMed

Kruk, Joanna

2007-01-01

Physical activity is widely recognized as a means for the primary prevention of chronic diseases as well as in patients' treatment and rehabilitation. Moreover, activity has beneficial effects on an individual's health and well-being. Despite the benefits of regular physical activity, the percentage of physically inactive adults in the world is high. Environmental and policy approaches aimed to increase physical activity require continual stress of the epidemiological evidence from studies investigating disease mechanisms as well as controlled clinical trials. To update the evidence that physical activity/exercise is important for reducing the chronic diseases (cardiovascular and heart, diabetes, cancer, obesity, osteoporosis, and fall-related injuries, depression and emotional stress) and for mechanisms that may operate in the relation between physical activity and a disease risk. Research studies published from 2004 through to March 2007 were identified through a review of the literature available on the NLM PubMed, Medline, Current Contents, and Elsevier-Science Direct databases. Recent evidence on physical activity/exercise and reduction of chronic major diseases incidence and rehabilitation of patients replicates previous findings. The strongest evidence exists for colon cancer, breast cancer, and cardiovascular diseases. The maximal magnitudes of the risk reduction reported were: 75% for breast cancer, 49% for cardiovascular and heart diseases, 35% for diabetes, 22% for colorectal cancer. Increased physical activity also prevented the weight gain associated with aging at least 2-times greater in individuals who were more active compared with those who were inactive. Limited new findings has been reported for the beneficial role of physical activity in fall-related injures, depression and emotional distress. Recent evidence confirms previous findings that engaging in moderate physical activity is very important for the primary prevention of chronic diseases, decreasing all causes of mortality and that exercise is one of the determinants for physical and psychological well-being. The current evidence provides further support that physical activity can suppress concentrations of 17 alpha-estradiol in women.

Clinical Trials of Aspirin Treatment After Desensitization in Aspirin-Exacerbated Respiratory Disease.

PubMed

Kowalski, Marek L; Wardzyńska, Aleksandra; Makowska, Joanna S

2016-11-01

The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Should the patient with coronary artery disease use sildenafil?

PubMed

Cheitlin, Melvin D

2003-01-01

Since the etiology of erectile dysfunction is frequently related to endothelial dysfunction, a problem in common with much vascular disease, erectile dysfunction disproportionately affects patients with cardiovascular disease. With the development of phosphodiesterase 5 inhibitors, the first of which was sildenafil (Viagra), an effective oral medication became available. The question of safety of these drugs, especially in patients with latent or overt coronary artery disease, is of concern. Sildenafil relaxes smooth muscle and therefore lowers systolic and diastolic blood pressure slightly. With organic nitrates, the drop in blood pressure is potentiated, at times dangerously, thereby making it contraindicated to take nitrates within 24 hours of using sildenafil. In double-blind, placebo-controlled trials, there was no difference between sildenafil subjects and control patients in the incidence of myocardial infarction, cardiovascular, and total deaths. Coronary disease patients with stable angina, controlled on medications, were included in the trials. Therefore, sildenafil, as a drug, is safe in such patients. With a patient with coronary artery disease suddenly engaging in the physical exercise associated with sexual intercourse, there is the danger of increased risk of precipitating myocardial infarction or death. The cardiovascular metabolic cost of sexual activity is reviewed and appears to be approximately at the level of 3-5 metabolic equivalents of exercise. Sexual activity occurs within 2 hours of the onset of an acute myocardial infarction in <1.0% of patients. Although sexual intercourse is estimated to increase the risk of myocardial infarction by a factor of 2x, there is still only a very small increase in risk, a risk acceptable to patients who feel their quality of life will be markedly improved by their ability to engage in sexual activity.

Caribbean yellow band disease compromises the activity of catalase and glutathione S-transferase in the reef-building coral Orbicella faveolata exposed to anthracene.

PubMed

Montilla, Luis Miguel; Ramos, Ruth; García, Elia; Cróquer, Aldo

2016-05-03

Healthy and diseased corals are threatened by different anthropogenic sources, such as pollution, a problem expected to become more severe in the near future. Despite the fact that coastal pollution and coral diseases might represent a serious threat to coral reef health, there is a paucity of controlled experiments showing whether the response of diseased and healthy corals to xenobiotics differs. In this study, we exposed healthy and Caribbean yellow band disease (CYBD)-affected Orbicella faveolata colonies to 3 sublethal concentrations of anthracene to test if enzymatic responses to this hydrocarbon were compromised in CYBD-affected tissues. For this, a 2-factorial fully orthogonal design was used in a controlled laboratory bioassay, using tissue condition (2 levels: apparently healthy and diseased) and pollutant concentration (4 levels: experimental control, 10, 30 and 100 ppb concentration) as fixed factors. A permutation-based ANOVA (PERMANOVA) was used to test the effects of condition and concentration on the specific activity of 3 enzymatic biomarkers: catalase, glutathione S-transferase, and glutathione peroxidase. We found a significant interaction between the concentration of anthracene and the colony condition for catalase (Pseudo-F = 3.84, df = 3, p < 0.05) and glutathione S-transferase (Pseudo-F = 3.29, df = 3, p < 0.05). Moreover, our results indicated that the enzymatic response to anthracene in CYBD-affected tissues was compromised, as the activity of these enzymes decreased 3- to 4-fold compared to healthy tissues. These results suggest that under a potential scenario of increasing hydrocarbon coastal pollution, colonies of O. faveolata affected with CYBD might become more vulnerable to the deleterious effects of chemical pollution.

Identification of GLI Mutations in Patients With Hirschsprung Disease That Disrupt Enteric Nervous System Development in Mice.

PubMed

Liu, Jessica Ai-Jia; Lai, Frank Pui-Ling; Gui, Hong-Sheng; Sham, Mai-Har; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercedes; Hui, Chi-Chung; Ngan, Elly Sau-Wai

2015-12-01

Hirschsprung disease is characterized by a deficit in enteric neurons, which are derived from neural crest cells (NCCs). Aberrant hedgehog signaling disrupts NCC differentiation and might cause Hirschsprung disease. We performed genetic analyses to determine whether hedgehog signaling is involved in pathogenesis. We performed deep-target sequencing of DNA from 20 patients with Hirschsprung disease (16 men, 4 women), and 20 individuals without (controls), and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10. Biological effects of GLI mutations were tested in luciferase reporter assays using HeLa or neuroblastoma cell lines. Development of the enteric nervous system was studied in Sufu(f/f), Gli3(Δ699), Wnt1-Cre, and Sox10(NGFP) mice using immunohistochemical and whole-mount staining procedures to quantify enteric neurons and glia and analyze axon fasciculation, respectively. NCC migration was studied using time-lapse imaging. We identified 3 mutations in GLI in 5 patients with Hirschsprung disease but no controls; all lead to increased transcription of SOX10 in cell lines. SUFU, GLI, and SOX10 form a regulatory loop that controls the neuronal vs glial lineages and migration of NCCs. Sufu mutants mice had high Gli activity, due to loss of Sufu, disrupting the regulatory loop and migration of enteric NCCs, leading to defective axonal fasciculation, delayed gut colonization, or intestinal hypoganglionosis. The ratio of enteric neurons to glia correlated inversely with Gli activity. We identified mutations that increase GLI activity in patients with Hirschsprung disease. Disruption of the SUFU-GLI-SOX10 regulatory loop disrupts migration of NCCs and development of the enteric nervous system in mice. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Effects of applying behavior modification to improve HbA1C levels in a diabetic patient].

PubMed

Chen, Wen-Chun; Huang, You-Rong; Lin, Chiu-Chu

2010-04-01

Diabetes is a chronic disease. To prevent and delay complications, diabetic patients must adjust their lifestyle as part of a comprehensive approach to disease control. Diabetic patients must be able to self-manage their disease and establish healthy habits in their daily routine. In this study, prior to intervention, the subject was unable to control her diet, do exercise, check sugars properly or integrate disease management effectively into her daily routine. By applying self-regulation theory through the keeping of a diary for sugar and daily activity self-monitoring, she became able to self-assess the causes of poor disease control. Such further facilitated her setting goals and developing strategies to link her habits with disease management. When failing to achieve goals even after execution, she could consider the factors contributing to the failure and modify her behaviors, goals and/or strategies accordingly. We helped this patient learn behavior modification methods in order to achieve her goal of better HbA(1)C control. This case example may help clinical nursing educators move beyond the confines of the traditional one-way educational model to guide diabetic patients to achieve good sugar control. We hope our findings help many chronic disease sufferers achieve self-management objectives in order to assume greater self-care responsibilities.

Elevated levels of serum-soluble triggering receptor expressed on myeloid cells-1 in patients with IBD do not correlate with intestinal TREM-1 mRNA expression and endoscopic disease activity.

PubMed

Saurer, Leslie; Rihs, Silvia; Birrer, Michèle; Saxer-Seculic, Nikolina; Radsak, Markus; Mueller, Christoph

2012-10-01

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory responses. We have previously demonstrated a substantial increase in TREM-1-expressing macrophages in the inflamed intestinal mucosa of patients with inflammatory bowel diseases (IBD). TREM-1 is also produced as a soluble receptor (sTREM-1). Here, we aimed to determine whether serum sTREM-1 could be used as a surrogate marker of disease activity in patients with IBD. Intestinal biopsies and concurrently collected sera from patients with Crohn's disease (CD) and Ulcerative colitis (UC) enrolled in the Swiss IBD cohort study were analyzed for intestinal TREM-1 mRNA and serum sTREM-1 expression. TREM-1 mRNA and sTREM-1 were correlated with the endoscopically determined disease activity. Serum sTREM-1 and TREM-1 mRNA expression levels were further determined in sera and colonic tissues collected at various time-points post disease induction in an experimental mouse model of colitis and correlated with disease activity. Expression of TREM-1 mRNA was upregulated in intestinal biopsies from patients with active disease but not in patients with quiescent disease. Serum sTREM-1 was elevated in IBD patients compared to normal controls. No substantial differences in sTREM-1 expression levels were found in patients with active versus quiescent disease. In colitic mice, colonic TREM-1 mRNA and serum sTREM-1 were also upregulated. While colonic TREM-1 mRNA expression levels correlated with disease activity, augmented serum sTREM-1 in fact associated with a milder course of disease. Analysis of sTREM-1 as a surrogate marker of disease activity in patients with IBD warrants caution. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Systemic lupus erythematosus: an update.

PubMed

Golder, Vera; Hoi, Alberta

2017-03-20

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease predominantly affecting women of childbearing age. New classification criteria for SLE have greater sensitivity and therefore improve the diagnostic certainty for some patients, especially those who may previously have been labelled as having undifferentiated symptoms. Uncontrolled disease activity leads to irreversible end-organ damage, which in turn increases the risk of premature death; early and sustained control of disease activity can usually be achieved by conventional immunosuppressant therapy. The development of biological therapy lags behind that for other rheumatic diseases, with belimumab being the only targeted therapy approved by the Therapeutic Goods Administration. "Treat-to-target" concepts are changing trial design and clinical practice, with evidence-based definition of response criteria in the form of remission and low disease activity now on the horizon. While new therapies are awaited, research should also focus on optimising the use of current therapy and improving the quality of care of patients with SLE.

Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases.

PubMed

Croft, Michael; Siegel, Richard M

2017-04-01

TNF blockers are highly efficacious at dampening inflammation and reducing symptoms in rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and also in nonrheumatic syndromes such as inflammatory bowel disease. As TNF belongs to a superfamily of 19 structurally related proteins that have both proinflammatory and anti-inflammatory activity, reagents that disrupt the interaction between proinflammatory TNF family cytokines and their receptors, or agonize the anti-inflammatory receptors, are being considered for the treatment of rheumatic diseases. Biologic agents that block B cell activating factor (BAFF) and receptor activator of nuclear factor-κB ligand (RANKL) have been approved for the treatment of systemic lupus erythematosus and osteoporosis, respectively. In this Review, we focus on additional members of the TNF superfamily that could be relevant for the pathogenesis of rheumatic disease, including those that can strongly promote activity of immune cells or increase activity of tissue cells, as well as those that promote death pathways and might limit inflammation. We examine preclinical mouse and human data linking these molecules to the control of damage in the joints, muscle, bone or other tissues, and discuss their potential as targets for future therapy of rheumatic diseases.

The diabetes type 1 locus Idd6 modulates activity of CD4+CD25+ regulatory T-cells.

PubMed

Rogner, Ute Christine; Lepault, Françoise; Gagnerault, Marie-Claude; Vallois, David; Morin, Joëlle; Avner, Philip; Boitard, Christian

2006-01-01

The genetic locus Idd6 confers susceptibility to the spontaneous development of type 1 diabetes in the NOD mouse. Our studies on disease resistance of the congenic mouse strain NOD.C3H 6.VIII showed that Idd6 influences T-cell activities in the peripheral immune system and suggest that a major mechanism by which the Idd6 locus modifies diabetes development is via modulation of regulatory T-cell activities. Our transfer experiments using total splenocytes and purified T-cells demonstrated that the locus specifically controls the efficiency of disease protection mediated by the regulatory CD4(+)CD25(+) T-cell subset. Our data also implicate the Idd6 locus in controlling the balance between infiltrating lymphocytes and antigen-presenting cells within the pancreatic islet.

Telomerase activity in solid transitional cell carcinoma, bladder washings, and voided urine.

PubMed

Lance, R S; Aldous, W K; Blaser, J; Thrasher, J B

1998-03-04

Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in patients with benign urologic diseases, especially those with symptomatic benign prostatic hyperplasia. An additional study of a larger number of both bladder cancer patients and those at risk is necessary to determine if telomerase activity could play a role as a diagnostic and/or surveillance marker of TCC. Published by Elsevier Science Inc.

Inhibition of Phytophthora species, agents of cocoa black pod disease, by secondary metabolites of Trichoderma species.

PubMed

Pakora, Gilles-Alex; Mpika, Joseph; Kone, Daouda; Ducamp, Michel; Kebe, Ismael; Nay, Bastien; Buisson, Didier

2017-09-30

Cocoa production is affected by the black pod disease caused by several Phytophthora species that bring, about each year, an estimated loss of 44% of world production. Chemical control remains expensive and poses an enormous risk of poisoning for the users and the environment. Biocontrol by using antagonistic microorganisms has become an alternative to the integrated control strategy against this disease. Trichoderma viride T7, T. harzanium T40, and T. asperellum T54, which showed in vivo and in vitro antagonistic activity against P. palmivora, were cultured and mycelia extracted. Inhibition activity of crude extracts was determined, and then organic compounds were isolated and characterized. The in vitro effect of each compound on the conidia germination and mycelia growth of four P. palmivora, two P. megakaria, and one P. capsici was evaluated. T. viride that displayed best activities produced two active metabolites, viridin and gliovirin, against P. palmivora and P. megakaria strains. However, no activity against P. capsici was observed. Besides being active separately, these two compounds have a synergistic effect for both inhibitions, mycelia growth and conidia germination. These results provide the basis for the development of a low-impact pesticide based on a mixture of viridin and gliovirine.

Decreased expression of the aryl hydrocarbon receptor in ocular Behcet's disease.

PubMed

Wang, Chaokui; Ye, Zi; Kijlstra, Aize; Zhou, Yan; Yang, Peizeng

2014-01-01

Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in immune responses. AhR is activated following interaction with its ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's disease (BD). The expression of AhR was significantly decreased in active BD patients as compared to inactive BD patients and normal controls. Both FICZ and ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by PBMCs and by CD4(+)T cells in active BD patients and normal controls. Stimulation of purified CD4(+)T cells with FICZ or ITE caused a decreased expression of RORC, IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The present study suggests that a decreased AhR expression is associated with disease activity in BD patients. The activation of AhR by either FICZ or ITE was able to inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate whether modulation of AhR might be used in the treatment of BD.

Physical Activity Outcomes of Nurse-Delivered Lifestyle Interventions.

PubMed

Richards, Elizabeth A; Cai, Yun

2016-02-01

Promotion of physical activity has been a public health priority for decades. Over two million home healthcare nurses are at the front line to deliver effective health education and health promotion interventions in the United States. The purpose of this systematic review is to examine the effectiveness of nurse-delivered lifestyle physical interventions on physical activity outcomes conducted in home settings. Computerized database and ancestry search strategies located distinct intervention trials between 1990 and 2015. A total of eight quantitative studies were reviewed. Four of the eight studies were randomized control trials and four studies used an uncontrolled pretest-posttest design. The eight studies represented a total of 1,221 participants with mean ages from 43 to 81. Study sample sizes ranged from 16 to 504. Seven of the eight studies demonstrated modest effect of nurse-delivered home-based interventions on physical activity behaviors. Home-based physical activity promotion was most often incorporated into secondary prevention of postacute diseases, chronic disease management, or disease prevention/health promotion. Findings indicate that nurse-delivered home-based physical activity promotion show overall effectiveness in general adult populations. Possible effective intervention domains were also discussed in this review to guide future home-based health promotion. More large randomized controlled trials with longer study/follow-up periods and studies with cost-effectiveness data are warranted in future research.

NO-Synthase Activity in Patients with Coronary Heart Disease Associated with Hypertension of Different Age Groups.

PubMed

Besedina, Anna

2016-01-01

Coronary heart disease is the leading cause of death and disability worldwide. Hypertension is a major independent risk factor for the development of CHD. Abnormalities in NO generation or activity have been proposed as a major mechanism of CHD. The purpose of this article is to determine the activity of eNOS and iNOS in patients with isolated CHD and CHD associated with HT of different age groups. Fifty patients with isolated CHD and 42 patients with CHD associated with HT were enrolled in this study. NOS activity was determined by nitrite anion formed in the reaction. A statistically significant increase in iNOS activity is observed in elderly donors. In patients with isolated coronary heart disease cNOS activity is statistically significantly reduced with respect to the control group. The reduction of enzymatic activity of cNOS is more expressed in elderly patients than in middle-aged patients with coronary heart disease. Alterations in eNOS activity are more expressed in patients with coronary heart disease associated with hypertension than in patients with isolated coronary heart disease. Against the background of cNOS inhibition in the patients, a sharp increase in iNOS activity is observed. It has been shown that disturbance of endothelial function in patients with coronary heart disease associated with hypertension is characterized by reduced endothelial NO synthesis by cNOS and increased systemic NO synthesis due to increased iNOS activity. It has been found that the lack of endothelial NO and hyperproduction of »harmful« NO by iNOS are more expressed in elderly patients.

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

78 FR 17411 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... announced below concerns Monitoring and Evaluation of Malaria Control and Elimination Activities, FOA GH13..., discussion, and evaluation of applications received in response to ``Monitoring and Evaluation of Malaria...

FTO genotype, physical activity, and coronary heart disease risk in Swedish men and women.

PubMed

Gustavsson, Jaana; Mehlig, Kirsten; Leander, Karin; Lissner, Lauren; Björck, Lena; Rosengren, Annika; Nyberg, Fredrik

2014-04-01

Variants in the fat mass- and obesity-associated gene (FTO) predisposing to obesity and diabetes mellitus have also been associated with cardiovascular disease. Physical activity has been suggested to attenuate the FTO effect on obesity, but it is unknown whether this is also true for cardiovascular disease. Therefore, we explored whether physical activity modifies the FTO association with coronary heart disease (CHD). FTO rs9939609 (T>A) polymorphism was genotyped in 2 Swedish population-based case-control studies with 1743 CHD cases and 4402 population controls (25-74 years of age; 41% women). Leisure time physical activity was assessed by questionnaires, and 3 levels were defined: low, medium, and high. Overall, carriers of the FTO A allele had an increased risk of CHD (odds ratio, 1.20; 95% confidence interval, 1.06-1.37) adjusted for age, sex, study, and body mass index. Although A-allele carriers with low physical activity had the highest CHD risk (odds ratio, 3.30; 95% confidence interval, 2.44-4.46) compared with those with TT genotype and high activity, the effects of FTO genotype and physical activity on CHD risk were approximately additive, indicating the absence of additive interaction. The stratum-specific relative risks of CHD from the A allele in subjects with low, medium, and high physical activity were odds ratio 1.11 (95% confidence interval, 0.77-1.60), 1.22 (1.04-1.44), and 1.38 (1.06-1.80), respectively, but the suggested multiplicative interaction was not significant. FTO rs9939609 A-allele carriers have an increased CHD risk, and the association is not counteracted by increased physical activity.

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus.

PubMed

Liu, Chau-Ching; Manzi, Susan; Kao, Amy H; Navratil, Jeannine S; Ruffing, Margie J; Ahearn, Joseph M

2005-10-01

There is an urgent need for biomarkers with which to monitor disease activity in patients with systemic lupus erythematosus (SLE). We recently showed that abnormal levels of C4d, an activation-derived fragment of complement component C4, are deposited on the surface of erythrocytes from patients with SLE. This study focused on reticulocytes, the youngest and shortest-lived erythrocytes (lifespan 24-48 hours), with the objective of testing our hypothesis that when reticulocytes emerge from the bone marrow, they are immediately exposed to and acquire C4d at levels proportionate to the extent of complement activation at that time, thereby reflecting disease activity in SLE. We conducted a cross-sectional study of 156 patients with SLE, 140 patients with other diseases, and 159 healthy controls. Levels of C4d on the surface of reticulocytes were examined using a 2-color flow cytometric assay. The results were analyzed for correlations with SLE disease activity. A wide range of increased levels of reticulocyte C4d was specifically detected in SLE patients. These levels fluctuated in SLE patients and correlated with clinical disease activity, as determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM). Specifically, in cross-sectional analyses, patients with reticulocyte C4d levels in the highest quartile compared with those in the lowest quartile had significantly higher SELENA-SLEDAI (P = 0.00002) and SLAM (P = 0.02) scores. Longitudinal observation demonstrated that the reticulocyte C4d levels changed in relation to the clinical course in individual patients. These findings support our hypothesis that C4d-bearing reticulocytes may serve as biomarkers of disease activity in patients with SLE.

Misclassification of Physical Activity Level Due to Exclusion of Workplace Activity

ERIC Educational Resources Information Center

Boslaugh, Sarah E.; Kreuter, Matthew W.; Weaver, Nancy L.; Naleid, Kimberly S.; Brownson, Ross C.

2005-01-01

This study examined the effect of including workplace physical activity in calculating the proportion of adults meeting Centers for Disease Control (CDC) guidelines for physical activity. Data on leisure-time and workplace activity were collected from 1,090 Black and White adults in St. Louis, MO. A series of assumptions were used to equate…

Antimicrobial Activity of Plant Extracts from Aloe Vera, Citrus Hystrix, Sabah Snake Grass and Zingiber Officinale against Pyricularia Oryzae that causes Rice Blast Disease in Paddy Plants

NASA Astrophysics Data System (ADS)

Uda, M. N. A.; Harzana Shaari, N.; Shamiera. Said, N.; Hulwani Ibrahim, Nur; Akhir, Maisara A. M.; Khairul Rabani Hashim, Mohd; Salimi, M. N.; Nuradibah, M. A.; Hashim, Uda; Gopinath, Subash C. B.

2018-03-01

Rice blast disease, caused by the fungus known as Pyricularia oryzae, has become an important and serious disease of rice worldwide. Around 50% of production may be lost in a field moderately affected by infection and each year the fungus destroys rice, which is enough to feed an estimated 60 million people. Therefore, use of herbal plants offer an alternative for the management of plant diseases. Herbal plant like Aloe vera, Citrus hystrix, Sabah snake grass and Zingiber officinale extracts can be used for controlling disease of rice blast. In this study, these four herbal plants were used for evaluating antimicrobial activity against rice plant fungus Pyricularia oryzae, which causes rice blast disease.

TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis.

PubMed

Facco, M; Cabrelle, A; Calabrese, F; Teramo, A; Cinetto, F; Carraro, S; Martini, V; Calzetti, F; Tamassia, N; Cassatella, M A; Semenzato, G; Agostini, C

2015-01-01

TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place. In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects. Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1. These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.

Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases.

PubMed

Lucas, Márcio L; Carraro, Cristina C; Belló-Klein, Adriane; Kalil, Antônio N; Aerts, Newton R; Carvalho, Fabiano B; Fernandes, Marilda C; Zettler, Claudio G

2018-06-06

Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA. Copyright © 2018 Elsevier Inc. All rights reserved.

Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM.

PubMed

Goetz, Lindsey; Laskowski, Jennifer; Renner, Brandon; Pickering, Matthew C; Kulik, Liudmila; Klawitter, Jelena; Stites, Erik; Christians, Uwe; van der Vlag, Johan; Ravichandran, Kameswaran; Holers, V Michael; Thurman, Joshua M

2018-05-01

Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chromosome and oxidative damage biomarkers in lymphocytes of Parkinson's disease patients.

PubMed

Migliore, L; Scarpato, R; Coppede, F; Petrozzi, L; Bonuccelli, U; Rodilla, V

2001-10-01

As cancer development usually results from exposure to several environmental risk factors in interaction with the genetic susceptibility of the host, it could be of interest to investigate if neurodegeneration, as occurs in Parkinson's disease (PD) patients can be attributed at least partially, to environmental risk factors. There is growing evidence that oxidative stress could play a significant role as a risk factor in the aetiology and pathogenesis of neurodegenerative diseases, emphasising the need for new individual and human-based approaches. The aim of our research is to explore the relation between chromosome instability and oxidative stress biomarkers in Parkinson's disease using a variety of strategies. We determined peripheral markers for oxidative damage in PD by testing for spontaneous and induced chromosomal damage, DNA strand breaks, oxidised pyrimidines and altered purines both in peripheral blood and cultured lymphocytes. We also measured glutathione S-transferase activity in the plasma of patients and controls. Compared to healthy controls, PD patients show higher frequencies of micronuclei (17.2 +/- 4.8 vs. 9.0 +/- 3.4, p < 0.001) and a significant increase in the levels of single strand breaks (SSB). Significant differences were also obtained in the distribution of oxidised purine bases between the two groups. Preliminary data obtained by fluorescence in situ hybridization analysis showed that the percentage of centromere negative micronuclei is higher than that of centromere positive micronuclei. Glutathione S-transferase activity in plasma from PD patients and controls was also measured and the enzymatic activity in PD patients was lower than in healthy controls.

Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis.

PubMed

Tzelepis, Fanny; Blagih, Julianna; Khan, Nargis; Gillard, Joshua; Mendonca, Laura; Roy, Dominic G; Ma, Eric H; Joubert, Philippe; Jones, Russell G; Divangahi, Maziar

2018-05-11

Mycobacterium tuberculosis ( Mtb ) is one of the most ancient human pathogens, yet the exact mechanism(s) of host defense against Mtb remains unclear. Although one-third of the world's population is chronically infected with Mtb , only 5 to 10% develop active disease. This indicates that, in addition to resistance mechanisms that control bacterial burden, the host has also evolved strategies to tolerate the presence of Mtb to limit disease severity. We identify mitochondrial cyclophilin D (CypD) as a critical checkpoint of T cell metabolism that controls the expansion of activated T cells. Although loss of CypD function in T cells led to enhanced Mtb antigen-specific T cell responses, this increased T cell response had no impact on bacterial burden. Rather, mice containing CypD-deficient T cells exhibited substantially compromised disease tolerance and succumbed to Mtb infection. This study establishes a mechanistic link between T cell-mediated immunity and disease tolerance during Mtb infection. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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.

A survey of core and support activities of communicable disease surveillance systems at operating-level CDCs in China.

PubMed

Xiong, Weiyi; Lv, Jun; Li, Liming

2010-11-17

In recent years, problems like insufficient coordination, low efficiency, and heavy working load in national communicable disease surveillance systems in China have been pointed out by many researchers. To strengthen the national communicable disease surveillance systems becomes an immediate concern. Since the World Health Organization has recommended that a structured approach to strengthen national communicable disease surveillance must include an evaluation to existing systems which usually begins with a systematic description, we conducted the first survey for communicable disease surveillance systems in China, in order to understand the situation of core and support surveillance activities at province-level and county-level centers for disease control and prevention (CDCs). A nationwide survey was conducted by mail between May and October 2006 to investigate the implementation of core and support activities of the Notifiable Disease Reporting System (NDRS) and disease-specific surveillance systems in all of the 31 province-level and selected 14 county-level CDCs in Mainland China The comments on the performance of communicable disease surveillance systems were also collected from the directors of CDCs in this survey. The core activities of NDRS such as confirmation, reporting and analysis and some support activities such as supervision and staff training were found sufficient in both province-level and county-level surveyed CDCs, but other support activities including information feedback, equipment and financial support need to be strengthened in most of the investigated CDCs. A total of 47 communicable diseases or syndromes were under surveillance at province level, and 20 diseases or syndromes at county level. The activities among different disease-specific surveillance systems varied widely. Acute flaccid paralysis (AFP), measles and tuberculosis (TB) surveillance systems got relatively high recognition both at province level and county level. China has already established a national communicable disease surveillance framework that combines NDRS and disease-specific surveillance systems. The core and support activities of NDRS were found sufficient, while the implementation of those activities varied among different disease-specific surveillance systems.

Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.

PubMed

Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Ţieranu, Eugen Nicolae; Popa, Caterina; Mănuc, Mircea; Preda, Carmen Monica; Ţieranu, Ioana; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

2017-01-01

A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.

Physical and cognitive stimulation in Alzheimer Disease. the GAIA Project: a pilot study.

PubMed

Maci, Tiziana; Pira, Francesco Le; Quattrocchi, Graziella; Nuovo, Santo Di; Perciavalle, Vincenzo; Zappia, Mario

2012-03-01

Several data suggest that physical activity and cognitive stimulation have a positive effect on the quality of life (QoL) of people with Alzheimer's disease (AD), slowing the decline due to the disease. A pilot project was undertaken to assess the effect of cognitive stimulation, physical activity, and socialization on patients with AD and their informal caregiver's QoL and mood. Fourteen patients with AD were randomly divided into active treatment group and control group. At the end of treatment, a significant improvement in apathy, anxiety, depression, and QoL in the active treatment group was found. Considering caregivers, those of the active treatment group exhibited a significant improvement in their mood and in their perception of patients' QoL. This study provides evidence that a combined approach based on cognitive stimulation, physical activity, and socialization is a feasible tool to improve mood and QoL in patients with AD and their caregivers.

MicroRNAs-Dependent Regulation of PPARs in Metabolic Diseases and Cancers

PubMed Central

Portius, Dorothea; Sobolewski, Cyril

2017-01-01

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-dependent nuclear receptors, which control the transcription of genes involved in energy homeostasis and inflammation and cell proliferation/differentiation. Alterations of PPARs' expression and/or activity are commonly associated with metabolic disorders occurring with obesity, type 2 diabetes, and fatty liver disease, as well as with inflammation and cancer. Emerging evidence now indicates that microRNAs (miRNAs), a family of small noncoding RNAs, which fine-tune gene expression, play a significant role in the pathophysiological mechanisms regulating the expression and activity of PPARs. Herein, the regulation of PPARs by miRNAs is reviewed in the context of metabolic disorders, inflammation, and cancer. The reciprocal control of miRNAs expression by PPARs, as well as the therapeutic potential of modulating PPAR expression/activity by pharmacological compounds targeting miRNA, is also discussed. PMID:28167956

Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

PubMed

Ehinger, Johannes K; Morota, Saori; Hansson, Magnus J; Paul, Gesine; Elmér, Eskil

2015-06-01

Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease.

Progress Made in Lupus Diagnosis and Treatment | NIH MedlinePlus the Magazine

MedlinePlus

... what ways can lupus accelerate the challenges of cardiovascular disease in many patients? Lupus patients have significant increases ... for improving vascular health and proper control of disease activity. We need ... best cardiovascular preventive strategies are for these patients and we ...

Dysregulation of neural calcium signaling in Alzheimer disease, bipolar disorder and schizophrenia

PubMed Central

Berridge, Michael J.

2013-01-01

Neurons have highly developed Ca2+ signaling systems responsible for regulating a large number of neural functions such as the control of brain rhythms, information processing and the changes in synaptic plasticity that underpin learning and memory. The tonic excitatory drive, which is activated by the ascending arousal system, is particularly important for processes such as sensory perception, cognition and consciousness. The Ca2+ signaling pathway is a key component of this arousal system that regulates the neuronal excitability responsible for controlling the neural brain rhythms required for information processing and cognition. Dysregulation of the Ca2+ signaling pathway responsible for many of these neuronal processes has been implicated in the development of some of the major neural diseases in man such as Alzheimer disease, bipolar disorder and schizophrenia. Various treatments, which are known to act by reducing the activity of Ca2+ signaling, have proved successful in alleviating the symptoms of some of these neural diseases. PMID:22895098

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.

Immunohistochemical expression of AQP-3 in vitiligo: a new potential guide for disease activity.

PubMed

Hodeib, Abeer; Hegab, Doaa; Rizk, Omnia; Mohammed, Shahdan

2017-08-01

Vitiligo is a depigmenting skin disorder, with disappearance of functioning epidermal melanocytes. Aquaporin-3 (AQP-3) is an aquaglyceroporin expressed in epidermal keratinocytes, where it shares in regulating their proliferation and differentiation, and so it might affect melanocytes indirectly. So far, little is known regarding its possible role in vitiligo. This work aimed to study the changes in immunohistochemical expression of AQP-3 protein in vitiligo to detect its possible role in disease pathogenesis. Skin biopsies were taken from lesional skin of 30 vitiligo patients in addition to 20 normal controls. Epidermal immunohistochemical expression of AQP-3 was assessed as: +3 = strong expression, +2 = moderate, +1= weak and 0= negative expression. AQP-3 was significantly less expressed in vitiligo epidermis than control (P<0.001) with an inverse correlation with Vitiligo Index of Disease Activity (r =-0.505, P=0.004). Reduced epidermal AQP-3 may have a role in impaired melanocyte survival in vitiligo, and might be a potential negative biological marker for vitiligo activity. Larger trials should further elucidate the effect of changes in epidermal AQP-3 expression in development of vitiligo, and that might pave the road for discovering new therapeutic modalities for the disease.

Evaluation of a Pomegranate Peel Extract as an Alternative Means to Control Olive Anthracnose.

PubMed

Pangallo, Sonia; Nicosia, Maria G Li Destri; Agosteo, Giovanni E; Abdelfattah, Ahmed; Romeo, Flora V; Cacciola, Santa O; Rapisarda, Paolo; Schena, Leonardo

2017-12-01

Olive anthracnose is caused by different species of Colletotrichum spp. and may be regarded as the most damaging disease of olive fruit worldwide, greatly affecting quality and quantity of the productions. A pomegranate peel extract (PGE) proved very effective in controlling the disease. The extract had a strong in vitro fungicidal activity against Colletotrichum acutatum sensu stricto, was very effective in both preventive and curative trials with artificially inoculated fruit, and induced resistance in treated olive tissues. In field trials, PGE was significantly more effective than copper, which is traditionally used to control the disease. The highest level of protection was achieved by applying the extract in the early ascending phase of the disease outbreaks because natural rots were completely inhibited with PGE at 12 g/liter and were reduced by 98.6 and by 93.0% on plants treated with PGE at 6 and 3 g/liter, respectively. Two treatments carried out 30 and 15 days before the expected epidemic outbreak reduced the incidence of the disease by 77.6, 57.0, and 51.8%, depending on the PGE concentration. The analysis of epiphytic populations showed a strong antimicrobial activity of PGE, which sharply reduced both fungal and bacterial populations. Because PGE was obtained from a natural matrix using safe chemicals and did not have any apparent phytotoxic effect on treated olive fruit, it may be regarded as a safe and effective natural antifungal preparation to control olive anthracnose and improve olive productions.

Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study.

PubMed

2008-12-01

To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an omega-3 fatty acid, improves the motor features of Huntington disease. Six-month multicenter, randomized, double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Forty-one research sites in the United States and Canada. Three hundred sixteen adults with Huntington disease, enriched for a population with shorter trinucleotide (cytosine-adenine-guanine) repeat length expansions. Random assignment to placebo or ethyl-EPA, 1 g twice a day, followed by open-label treatment with ethyl-EPA. Six-month change in the Total Motor Score 4 component of the Unified Huntington's Disease Rating Scale analyzed for all research participants and those with shorter cytosine-adenine-guanine repeat length expansions (<45). At 6 months, the Total Motor Score 4 point change for patients receiving ethyl-EPA did not differ from that for those receiving placebo. No differences were found in measures of function, cognition, or global impression. Before public disclosure of the 6-month placebo-controlled results, 192 individuals completed the open-label phase. The Total Motor Score 4 change did not worsen for those who received active treatment for 12 continuous months compared with those who received active treatment for only 6 months (2.0-point worsening; P=.02). Ethyl-EPA was not beneficial in patients with Huntington disease during 6 months of placebo-controlled evaluation. Clinical Trial Registry clinicaltrials.gov Identifier: NCT00146211.

Changes of Serum Angiotensin-Converting Enzyme Activity During Treatment of Patients with Graves’ Disease*

PubMed Central

Lee, Dong Soo; Chung, June-Key; Cho, Bo Youn; Koh, Chang-Soon; Lee, Munho

1986-01-01

Serum angiotensin-converting enzyme activity was measured spectrophotometrically, and serum thyrotropin-binding-inhibitory immunoglobulin (TBII) activity was measured by radioreceptor assay in normal subjects and in patients with Graves’ disease serially before and during treatment, and these activities were compared with each other and with thyroid hormone levels in various thyroid functional status. Correlation between serum angiotensin-converting enzyme activity and serum thyroid hormone level was pursued with relation to the changes of thyroid functional status in patients with Graves’ disease during treatment. Serum angiotensin-converting enzyme activity was significantly elevated in patients with hyperthyroid Graves’ disease before the start of treatment (35 ± 13 nmol/min/ml, n=50), and not in patients with Graves’ disease, euthyroid state during treatment with antithyroid drugs or radioactive iodine (23 ± 9 nmol/min/ml, n=12), but decreased significantly in patients with Graves’ disease, hypothyroid state transiently during treatment (15 ± 4 nmol/min/ml, n=12), respectively in comparison with normal control subjects. Serum angiotensin-converting enzyme activity was positively correlated with the log value of serum T3 concentration (r=0.62, p<0.001, n=95), and with the log value of free thyroxine index (r=0.66, p<0.001, n=91) but not statistically significantly with serum TBII activity. Serum angiotensin-converting enzyme activity was followed in 11 patients with initially increased activity and the activity decreased in proportion to serum thyroid hormone level during treatment, irrespective of treatment modality. It is suggested that thyroid hormones play a role in the increase and decrease of serum angiotensin-converting enzyme activity directly or indirectly influencing the peripheral tissues (probably reticuloendothelial cells or peripheral endothelial cells) in patients with Graves’ disease. PMID:15759385

Fat-soluble vitamins as disease modulators in multiple sclerosis.

PubMed

Torkildsen, Ø; Løken-Amsrud, K I; Wergeland, S; Myhr, K-M; Holmøy, T

2013-01-01

Fat-soluble vitamins (A, D, E and K) have properties that could be relevant as modulators of disease activity in multiple sclerosis (MS). We performed a systematic search on PubMed and Medline up to May 2012, using the search strings 'vitamin A', 'retinol', 'retinal', 'carotenoids', 'vitamin D', 'vitamin E', 'alpha-tocopherol', 'vitamin K' in conjunction with 'multiple sclerosis', 'animal model' and 'experimental autoimmune encephalitis (EAE)'. In addition, the reference lists of the publications identified were examined for further citations of relevance. There is comprehensive evidence from epidemiological, observational, and experimental studies that vitamin D may be beneficial in MS. Results from small-scale clinical studies are inconclusive, and large-scale, adequately powered, randomized, controlled trials are still lacking. For vitamin D, Oxford Centre for Evidence-Based Medicine level 2c evidence exists for a positive therapeutic effect. Evidence from animal models indicates that all the examined fat-soluble vitamins could have potential as modulators of disease activity in MS. For vitamin A and E, level 4 and 5 evidence exists for a modulatory effect in MS; for vitamin K, too few studies have been conducted to indicate an effect in humans. Vitamin D is a promising candidate as modulator of disease activity in MS, and controlled studies are currently being conducted. All the fat-soluble vitamins have, however, been demonstrated to be effective in different animal models for the disease, and vitamin A and E have biological properties that could be relevant for MS pathogenesis. Thus, vitamin A and E seem to be promising candidates for future case-control and cohort studies. © 2012 John Wiley & Sons A/S.

Modification of insulin sensitivity and glycemic control by activity and exercise.

PubMed

Roberts, Christian K; Little, Jonathan P; Thyfault, John P

2013-10-01

Type 2 diabetes has progressed into a major contributor to preventable death, and developing optimal therapeutic strategies to prevent future type 2 diabetes and its primary clinical manifestation of cardiovascular disease is a major public health challenge. This article will provide a brief overview of the role of activity and exercise in modulating insulin sensitivity and will outline the effect of physical activity, high-intensity interval training, and resistance training on insulin sensitivity and glycemic control.

Thinning southern bottomland hardwoods stands: Insect and disease consideratons

Treesearch

T. Evan Nebeker; Theodor D. Leininger; James S. Meadows; Michael D. Warriner

2005-01-01

The effects of thinning on insects and diseases have not been thoroughly examined in southern bottomland hardwood forests. To adress this issue, a study was initiated at sites in Mississippi and Alabama. These study sites allowed us to make observations concerning insect and disease activity 1-5 years following thinning. On all sites there was an unthinned control and...

Xanthine oxidase activity is associated with risk factors for cardiovascular disease and inflammatory and oxidative status markers in metabolic syndrome: effects of a single exercise session.

PubMed

Feoli, Ana Maria Pandolfo; Macagnan, Fabrício Edler; Piovesan, Carla Haas; Bodanese, Luiz Carlos; Siqueira, Ionara Rodrigues

2014-01-01

The main goal of the present study was to investigate the xanthine oxidase (XO) activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. A case-control study (9 healthy and 8 MS volunteers) was performed to measure XO, superoxide dismutase (SOD), glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP) content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome.

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.

/sup 67/Ga citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

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

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

/sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n . 30) and in 71% of patients with inactive disease (n . 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r..436; p less than .005). The frequency of abnormalmore » /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical indentification of inactive sacoidosis.« less

Health promotion for mid- and later-life women.

PubMed

Zurakowski, Tamara L

2004-01-01

Health outcomes in later life are dependent in part on activities started in midlife. Primary and secondary prevention strategies include seeking healthier life choices, early detection of disease, and specific disease avoidance through immunization and other activities. The recommendations for various screenings and health care for postmenopausal women have changed rapidly over the past 2 years but still include the basics of nutrition, exercise, testing for common illnesses, and control of existing health problems.

Activation of the Cannabinoid Type 2 Receptor by a Novel Indazole Derivative Normalizes the Survival Pattern of Lymphoblasts from Patients with Late-Onset Alzheimer's Disease.

PubMed

Del Cerro, Patricia; Alquézar, Carolina; Bartolomé, Fernando; González-Naranjo, Pedro; Pérez, Concepción; Carro, Eva; Páez, Juan A; Campillo, Nuria E; Martín-Requero, Ángeles

2018-05-07

Alzheimer's disease is a multifactorial disorder for which there is no disease-modifying treatment yet. CB2 receptors have emerged as a promising therapeutic target for Alzheimer's disease because they are expressed in neuronal and glial cells and their activation has no psychoactive effects. The aim of this study was to investigate whether activation of the CB2 receptor would restore the aberrant enhanced proliferative activity characteristic of immortalized lymphocytes from patients with late-onset Alzheimer's disease. It is assumed that cell-cycle dysfunction occurs in both peripheral cells and neurons in patients with Alzheimer's disease, contributing to the instigation of the disease. Lymphoblastoid cell lines from patients with Alzheimer's disease and age-matched control individuals were treated with a new, in-house-designed dual drug PGN33, which behaves as a CB2 agonist and butyrylcholinesterase inhibitor. We analyzed the effects of this compound on the rate of cell proliferation and levels of key regulatory proteins. In addition, we investigated the potential neuroprotective action of PGN33 in β-amyloid-treated neuronal cells. We report here that PGN33 normalized the increased proliferative activity of Alzheimer's disease lymphoblasts. The compound blunted the calmodulin-dependent overactivation of the PI3K/Akt pathway, by restoring the cyclin-dependent kinase inhibitor p27 levels, which in turn reduced the activity of the cyclin-dependent kinase/pRb cascade. Moreover, this CB2 agonist prevented β-amyloid-induced cell death in neuronal cells. Our results suggest that the activation of CB2 receptors could be considered a useful therapeutic approach for Alzheimer's disease.

Switched Memory B Cells Are Increased in Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis and Their Change Over Time Is Related to Response to Tumor Necrosis Factor Inhibitors.

PubMed

Marasco, Emiliano; Aquilani, Angela; Cascioli, Simona; Moneta, Gian Marco; Caiello, Ivan; Farroni, Chiara; Giorda, Ezio; D'Oria, Valentina; Marafon, Denise Pires; Magni-Manzoni, Silvia; Carsetti, Rita; De Benedetti, Fabrizio

2018-04-01

To investigate whether abnormalities in B cell subsets in patients with juvenile idiopathic arthritis (JIA) correlate with clinical features and response to treatment. A total of 109 patients diagnosed as having oligoarticular JIA or polyarticular JIA were enrolled in the study. B cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry. Switched memory B cells were significantly increased in patients compared to age-matched healthy controls (P < 0.0001). When patients were divided according to age at onset of JIA, in patients with early-onset disease (presenting before age 6 years) the expansion in switched memory B cells was more pronounced than that in patients with late-onset disease and persisted throughout the disease course. In longitudinal studies, during methotrexate (MTX) treatment, regardless of the presence or absence of active disease, the number of switched memory B cells increased significantly (median change from baseline 36% [interquartile range {IQR} 15, 66]). During treatment with MTX plus tumor necrosis factor inhibitors (TNFi), in patients maintaining disease remission, the increase in switched memory B cells was significantly lower than that in patients who experienced active disease (median change from baseline 4% [IQR -6, 32] versus 41% [IQR 11, 73]; P = 0.004). The yearly rate of increases in switched memory B cells was 1.5% in healthy controls, 1.2% in patients who maintained remission during treatment with MTX plus TNFi, 4.7% in patients who experienced active disease during treatment with MTX plus TNFi, and ~4% in patients treated with MTX alone. Switched memory B cells expand during the disease course at a faster rate in JIA patients than in healthy children. This increase is more evident in patients with early-onset JIA. TNFi treatment inhibits this increase in patients who achieve and maintain remission, but not in those with active disease. © 2018, American College of Rheumatology.

Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

PubMed

Niv, Y; Ilani, S; Levi, Z; Hershkowitz, M; Niv, E; Fireman, Z; O'Donnel, S; O'Morain, C; Eliakim, R; Scapa, E; Kalantzis, N; Kalantzis, C; Apostolopoulos, P; Gal, E

2012-01-01

The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated. © Georg Thieme Verlag KG Stuttgart · New York.

Neuromuscular Impairments Are Associated With Impaired Head and Trunk Stability During Gait in Parkinson Fallers.

PubMed

Cole, Michael H; Naughton, Geraldine A; Silburn, Peter A

2017-01-01

Background The trunk plays a critical role in attenuating movement-related forces that threaten to challenge the body's postural control system. For people with Parkinson's disease (PD), disease progression often leads to dopamine-resistant axial symptoms, which impair trunk control and increase falls risk. Objective This prospective study aimed to evaluate the relationship between impaired trunk muscle function, segmental coordination, and future falls in people with PD. Methods Seventy-nine PD patients and 82 age-matched controls completed clinical assessments and questionnaires to establish their medical history, symptom severity, balance confidence, and falls history. Gait characteristics and trunk muscle activity were assessed using 3-dimensional motion analysis and surface electromyography. The incidence, cause, and consequence of any falls experienced over the next 12 months were recorded and indicated that 48 PD and 29 control participants fell at least once during this time. Results PD fallers had greater peak and baseline lumbar multifidus (LMF) and thoracic erector spinae (TES) activations than control fallers and nonfallers. Analysis of covariance indicated that the higher LMF activity was attributable to the stooped posture adopted by PD fallers, but TES activity was independent of medication use, symptom severity, and trunk orientation. Furthermore, greater LMF and TES baseline activity contributed to increasing lateral head, trunk, and pelvis movements in PD fallers but not nonfallers or controls. Conclusions The results provide evidence of neuromuscular deficits for PD fallers that are independent of medications, symptom severity, and posture and contribute to impaired head, trunk, and pelvis control associated with falls in this population. © The Author(s) 2016.

Low serum vitamin D concentrations in patients with schizophrenia.

PubMed

Itzhaky, Dganit; Amital, Daniela; Gorden, Katya; Bogomolni, Alisa; Arnson, Yoav; Amital, Howard

2012-02-01

Vitamin D is increasingly associated with the pathology of cognition and mental illness. Vitamin D receptors have been detected on neurons that regulate behavior. To assess vitamin D serum concentrations in patients with major depression and schizophrenia as compared to healthy controls and to determine if a correlation exists between serum levels of vitamin D and disease activity. We recruited 50 patients with schizophrenia and compared them to 33 patients with major depression and 50 controls with no major psychopathology. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia and the Hamilton Depression scale for depression were administered on the same day the blood samples were drawn. We used LIAISON 25-OH vitamin D (DiaSorin) immunoassay to measure serum concentrations of 25-OH vitamin D. Lower serum vitamin D concentrations were detected among patients with schizophrenia (15.0 +/- 7.3 ng/ml) compared to patients with depression (19.6 +/- 8.3 ng/ml) and to controls (20.2 +/- 7.8 ng/ml, P < 0.05). We found no correlation between disease activity, measured by the PANSS score, and vitamin D levels. Serum vitamin D levels were lower in patients with schizophrenia as compared to patients with depression and to healthy controls. No correlation was found between serum concentration and disease activity. Additional studies are needed to elucidate the role of vitamin D in the autoimmune mechanism and in the pathogenesis of schizophrenia.

2, 3-Butanediol activated disease-resistance of creeping bentgrass by inducing phytohormone and antioxidant responses.

PubMed

Shi, Yi; Liu, Xinju; Fang, Yuanyuan; Tian, Qing; Jiang, Hanyu; Ma, Huiling

2018-06-12

Brown patch, caused by Rhizoctonia solani, is a serious disease in Agrostis stolonifera. 2, 3-butanediol (2, 3-BD) is the major component of volatile organic compounds and was found to initiate induced systemic resistance (ISR). To investigate the induced resistance mechanism of 2, 3-BD, we examined the effects of resistance by area affected, along with changes in the content of phytohormones (Zeatin (ZT), Abscisic Acid (ABA) and Indole-3-Acetic Acid (IAA)), the activities of three phenylpropanoid metabolic enzymes (Phenylalaninammo-Nialyase (PAL), Chalcone Isomerase (CHI) and 4-Coumarate:Coenzyme A Ligase (4CL)) and the level of secondary metabolites (total phenols, flavonoid and lignin). The result showed that 2, 3-BD treatment at 250 μmoL/L had the best induction effect with the area affected decreased from 95% of the control to 55%. Compared to the controls, treatment with 250 μmoL/L 2, 3-BD induced higher levels of PAL, CHI and 4CL activity and increased total phenols, flavonoid and lignin levels. While 2, 3-BD treatment decreased the content of ZT and ABA but increased the content of IAA compared to controls. This study provides a basis for elucidating the mechanism of 2, 3-BD as a new plant disease control agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effects of enteral nutritional support on malnourished patients with inflammatory bowel disease by subjective global assessment.

PubMed

Sökülmez, Pınar; Demirbağ, Ali Eba; Arslan, Perihan; Dişibeyaz, Selçuk

2014-10-01

To investigate the prevalence of malnutrition in patients with inflammatory bowel disease (IBD) by subjective global assessment (SGA) and the effects of oral nutritional support on the clinical parameters, consumption of energy, macronutrients and fiber intake in the Study and Control groups, prospectively. A total of 38 (28 Male; 10 Female) hospitalized patients with moderate or severe IBD (13 with Crohn's disease (CD); 25 with Ulcerative colitis (UC)) were included. At stage 1, the disease severity, clinical symptoms and, signs, food consumption and nutritional status by using subjective global assessment (SGA) were recorded. At stage 2, the patients were blindly randomized into a Study Group and Controls. In the Study Group, a standard enteral product was added into the regulated hospital diets, but for the Controls, deficits were regulated by only hospital diets for 3 weeks. the independent variables were the group, the disease and its activity, age, Body body mass index (BMI), weight loss history, the hospitalization period; the dependent variables were SGA, bowel movements, change in nutritional status, disease severity, clinical findings, and also consumption of macronutrients. Prevalance of malnutrition (SGA-B or SGA-C) for all the patients was 92.1% at the beginning and 71.1% at the end of study. Improvements in disease activity score for the patients with UC were statistically significant in both the Study Group and the Controls (p=0.006 for the Study Group and p=0.001 for the Controls, respectively). Macronutrients, total and water soluble fiber consumption levels improved, with statistically significant differences for all the groups. The prevalence of malnutrition is a major problem in patients with IBD. Not only the regulation of hospital food, but also enteral nutritional support, improved their levels of malnutrition, as well as their energy, macronutrients, and fiber consumption, and SGA is an easy method for nutritional monitoring.

A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease.

PubMed

Nascimento, Carla M C; Teixeira, Camila V L; Gobbi, Lilian T B; Gobbi, Sebastião; Stella, Florindo

2012-06-01

To analyze the influence of a six-month exercise program on neuropsychiatric disorders and on the performance of instrumental activities in elderly patients with Alzheimer's disease (AD). The study included 20 patients with AD in the mild to moderate stages of the Clinical Dementia Rating (CDR) divided into two groups: the experimental group, composed of 10 women who participated in the six-month exercise program, and the control group, composed of the 10 remaining AD patients who did not take part in an exercise program during the same period. All participants were evaluated using the Mini-Mental State Exam for global cognitive function, the Neuropsychiatric Inventory Questionnaire for neuropsychiatric disorders, and the Pfeffer Functional Activities Questionnaire for the degree of functional impairment. The control group showed functional and neuropsychiatric deterioration in the comparisons between pre- and post-intervention times and between groups. The experimental group showed a propensity for less deterioration in neuropsychiatric disorders and performance of instrumental activities compared to the sedentary group.

Modeling the role of information and limited optimal treatment on disease prevalence.

PubMed

Kumar, Anuj; Srivastava, Prashant K; Takeuchi, Yasuhiro

2017-02-07

Disease outbreaks induce behavioural changes in healthy individuals to avoid contracting infection. We first propose a compartmental model which accounts for the effect of individual's behavioural response due to information of the disease prevalence. It is assumed that the information is growing as a function of infective population density that saturates at higher density of infective population and depends on active educational and social programmes. Model analysis has been performed and the global stability of equilibrium points is established. Further, choosing the treatment (a pharmaceutical intervention) and the effect of information (a non-pharmaceutical intervention) as controls, an optimal control problem is formulated to minimize the cost and disease fatality. In the cost functional, the nonlinear effect of controls is accounted. Analytical characterization of optimal control paths is done with the help of Pontryagin's Maximum Principle. Numerical findings suggest that if only control via information is used, it is effective and economical for early phase of disease spread whereas treatment works well for long term control except for initial phase. Furthermore, we observe that the effect of information induced behavioural response plays a crucial role in the absence of pharmaceutical control. Moreover, comprehensive use of both the control interventions is more effective than any single applied control policy and it reduces the number of infective individuals and minimizes the economic cost generated from disease burden and applied controls. Thus, the combined effect of both the control policies is found more economical during the entire epidemic period whereas the implementation of a single policy is not found economically viable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Expression of neutrophil gelatinase-associated lipocalin (NGAL) in the gut in Crohn's disease.

PubMed

Thorsvik, Silje; Bakke, Ingunn; van Beelen Granlund, Atle; Røyset, Elin Synnøve; Damås, Jan Kristian; Østvik, Ann Elisabet; Sandvik, Arne Kristian

2018-06-05

The antimicrobial glycoprotein neutrophil gelatinase-associated lipocalin (NGAL) is strongly expressed in several infectious, inflammatory and malignant disorders, among these inflammatory bowel disease (IBD). Fecal and serum NGAL is elevated during active IBD and we have recently shown that fecal NGAL is a novel biomarker for IBD with a test performance comparable to the established fecal biomarker calprotectin. This study examines expression of NGAL in the healthy gut and in Crohn's disease (CD), with emphasis on the previously unexplored small intestine. Pinch biopsies were taken from active and inactive CD in jejunum, ileum and colon and from the same sites in healthy controls. Microarray gene expression showed that the NGAL gene, LCN2, was the second most upregulated among 1820 differentially expressed genes in terminal ileum comparing active CD and controls (FC 5.86, p = 0.027). Based on immunohistochemistry and in situ hybridization findings, this upregulation most likely represented increased expression in epithelial cells. Double immunofluorescence showed NGAL expression in 49% (range 19-70) of Paneth cells (PCs) in control ileum with no change during inflammation. In healthy jejunum, the NGAL expression in PCs was weak to none but markedly increased during active CD. We further found NGAL also in metaplastic PCs in colon. Finally, we show for the first time that NGAL is expressed in enteroendocrine cells in small intestine as well as in colon.

Review: Evaluation of Foot-and-Mouth Disease Control Using Fault Tree Analysis.

PubMed

Isoda, N; Kadohira, M; Sekiguchi, S; Schuppers, M; Stärk, K D C

2015-06-01

An outbreak of foot-and-mouth disease (FMD) causes huge economic losses and animal welfare problems. Although much can be learnt from past FMD outbreaks, several countries are not satisfied with their degree of contingency planning and aiming at more assurance that their control measures will be effective. The purpose of the present article was to develop a generic fault tree framework for the control of an FMD outbreak as a basis for systematic improvement and refinement of control activities and general preparedness. Fault trees are typically used in engineering to document pathways that can lead to an undesired event, that is, ineffective FMD control. The fault tree method allows risk managers to identify immature parts of the control system and to analyse the events or steps that will most probably delay rapid and effective disease control during a real outbreak. The present developed fault tree is generic and can be tailored to fit the specific needs of countries. For instance, the specific fault tree for the 2001 FMD outbreak in the UK was refined based on control weaknesses discussed in peer-reviewed articles. Furthermore, the specific fault tree based on the 2001 outbreak was applied to the subsequent FMD outbreak in 2007 to assess the refinement of control measures following the earlier, major outbreak. The FMD fault tree can assist risk managers to develop more refined and adequate control activities against FMD outbreaks and to find optimum strategies for rapid control. Further application using the current tree will be one of the basic measures for FMD control worldwide. © 2013 Blackwell Verlag GmbH.

Submaximal Exercise Capacity in Juvenile Dermatomyositis after Longterm Disease: The Contribution of Muscle, Lung, and Heart Involvement.

PubMed

Berntsen, Kristin Schjander; Tollisen, Anita; Schwartz, Thomas; Kirkhus, Eva; Aaløkken, Trond Mogens; Lund, May Brit; Flatø, Berit; Sjaastad, Ivar; Sanner, Helga

2017-06-01

To compare submaximal exercise capacity in patients with juvenile dermatomyositis (JDM) with controls, and analyze contributions of muscle, heart, and lung impairment in patients. Fifty-nine patients with JDM, with a mean 16.9 years after symptom onset, and 59 sex- and age-matched controls completed a 6-min walk test (6MWT) and a timed up and go (TUG) test. Muscle function, disease activity/damage, and health-related quality of life (HRQOL) were assessed by validated tools; heart function by echocardiography and electrocardiography; and lung function by spirometry, DLCO, and body plethysmography. A thoracic high-resolution computed tomography (HRCT) scan and magnetic resonance imaging of the thighs were completed in patients. The 6MWT distance (6MWD) was 592 ± 81 m in patients versus 649 ± 79 m in controls (p < 0.001), and 563 ± 75 m in active versus 622 ± 76 m in inactive JDM (p = 0.004). The TUG time was 13.1 ± 2.1 s in patients versus 12.3 ± 2.0 s in controls (p = 0.034), and 13.7 ± 2.2 s in active versus 12.5 ± 1.8 s in inactive JDM (p = 0.028). No statistically significant difference was found between inactive JDM and controls in either test. In patients, the Childhood Myositis Assessment Score influenced the 6MWD and TUG time the most, followed by a low DLCO and HRCT pathology in the 6MWT and forced vital capacity in the TUG test. Medical Outcomes Study Short Form-36 physical component summary correlated strongly with both tests. Submaximal exercise capacity was reduced in patients with JDM, particularly those with active disease. This reduction was associated with muscle and lung dysfunction and poorer HRQOL.

Functional magnetic resonance imaging of working memory in Huntington's disease: cross-sectional data from the IMAGE-HD study.

PubMed

Georgiou-Karistianis, Nellie; Stout, Julie C; Domínguez D, Juan F; Carron, Sarah P; Ando, Ayaka; Churchyard, Andrew; Chua, Phyllis; Bohanna, India; Dymowski, Alicia R; Poudel, Govinda; Egan, Gary F

2014-05-01

We used functional magnetic resonance imaging (fMRI) to investigate spatial working memory (WM) in an N-BACK task (0, 1, and 2-BACK) in premanifest Huntington's disease (pre-HD, n = 35), early symptomatic Huntington's disease (symp-HD, n = 23), and control (n = 32) individuals. Overall, both WM conditions (1-BACK and 2-BACK) activated a large network of regions throughout the brain, common to all groups. However, voxel-wise and time-course analyses revealed significant functional group differences, despite no significant behavioral performance differences. During 1-BACK, voxel-wise blood-oxygen-level-dependent (BOLD) signal activity was significantly reduced in a number of regions from the WM network (inferior frontal gyrus, anterior insula, caudate, putamen, and cerebellum) in pre-HD and symp-HD groups, compared with controls; however, time-course analysis of the BOLD response in the dorsolateral prefrontal cortex (DLPFC) showed increased activation in symp-HD, compared with pre-HD and controls. The pattern of reduced voxel-wise BOLD activity in pre-HD and symp-HD, relative to controls, became more pervasive during 2-BACK affecting the same structures as in 1-BACK, but also incorporated further WM regions (anterior cingulate gyrus, parietal lobe and thalamus). The DLPFC BOLD time-course for 2-BACK showed a reversed pattern to that observed in 1-BACK, with a significantly diminished signal in symp-HD, relative to pre-HD and controls. Our findings provide support for functional brain reorganisation in cortical and subcortical regions in both pre-HD and symp-HD, which are modulated by task difficulty. Moreover, the lack of a robust striatal BOLD signal in pre-HD may represent a very early signature of change observed up to 15 years prior to clinical diagnosis. Copyright © 2013 Wiley Periodicals, Inc.

Exercise and physical activity in systemic lupus erythematosus: A systematic review with meta-analyses.

PubMed

O'Dwyer, Tom; Durcan, Laura; Wilson, Fiona

2017-10-01

Systemic lupus erythematosus (SLE) associates with enhanced cardiovascular (CV) risk frequently unexplained by traditional risk factors. Physical inactivity, common in SLE, likely contributes to the burden of CV risk and may also be a factor in co-morbid chronic fatigue. This systematic review evaluates whether exercise has a deleterious effect on disease activity in SLE, and explores effects on CV function and risk factors, physical fitness and function and health-related measures. A systematic review, with meta-analyses, was conducted; quasi-randomised and randomised controlled trials in SLE comparing at least one exercise group to controls were included. MEDLINE/PubMed, EMBASE, PEDro, AMED, CINAHL, The Cochrane Central Register of Controlled Trials, and relevant conference abstracts were searched. Random-effects meta-analyses were used to pool extracted data as mean differences. Heterogeneity was evaluated with χ 2 test and I 2 , with p < 0.05 considered significant. The search identified 3068 records, and 31 full-texts were assessed for eligibility. Eleven studies, including 469 participants, were included. Overall risk of bias of these studies was unclear. Exercise interventions were reported to be safe, while adverse effects were rare. Meta-analyses suggest that exercise does not adversely affect disease activity, positively influences depression, improves cardiorespiratory capacity and reduces fatigue, compared to controls. Exercise programmes had no significant effects on CV risk factors compared to controls. Therapeutic exercise programmes appear safe, and do not adversely affect disease activity. Fatigue, depression and physical fitness were improved following exercise-based interventions. A multimodal approach may be suggested, however the optimal exercise protocol remains unclear. Copyright © 2017 Elsevier Inc. All rights reserved.

Aortic, carotid intima-media thickness and flow- mediated dilation as markers of early atherosclerosis in a cohort of pediatric patients with rheumatic diseases.

PubMed

Del Giudice, Emanuela; Dilillo, Anna; Tromba, Luciana; La Torre, Giuseppe; Blasi, Sara; Conti, Fabrizio; Viola, Franca; Cucchiara, Salvatore; Duse, Marzia

2018-06-01

The aims of this study were to identify the presence of endothelial dysfunction as a marker of early atherosclerosis by measuring aortic and carotid intimal-medial thickness (aIMT and cIMT) and flow-mediated dilation (FMD) and their correlation with traditional and no traditional risk factors for atherosclerosis in children with rheumatic diseases. Thirty-nine patients (mean age 15.3 ± 5.7 years), 23 juvenile idiopathic arthritis, 9 juvenile spondyloarthropathies, 7 connective tissue diseases (mean disease duration and onset respectively 5 ± 3.6 and 10 ± 5 years), and 52 healthy children matched for sex and age were enrolled. Demographic data (age, sex, familiarity for cardiovascular disease), traditional risk factors for atherosclerosis (BMI, active and passive smoking, dyslipidemia), activity disease indexes (reactive count protein, erythrocyte sedimentation rate) autoantibodies, and complement tests were collected. aIMT, cIMT, and FMD were assessed following a standardized protocol by high-resolution ultrasonography. Patients resulted significantly more exposed to passive smoking and had a lower BMI and higher homocysteine level than controls. cIMT and aIMT were significantly higher in patients than controls (p < 0.001) and correlated with age at diagnosis (p < 0.001 r 0.516 and 0.706, respectively) but not with mean disease duration. FMD % was significantly reduced in patients compared to controls (p < 0.001). Subclinical atherosclerosis occurs in pediatric rheumatic diseases, mainly in early onset forms, and aIMT is an earlier marker of preclinical atherosclerosis. Premature endothelial dysfunction could be included in the follow-up of children with rheumatic disorders to plan prevention strategies of cardiovascular disease already in pediatrics.

Sustainability of vector control strategies in the Gran Chaco Region: current challenges and possible approaches

PubMed Central

Gürtler, Ricardo E

2011-01-01

Sustainability has become a focal point of the international agenda. At the heart of its range of distribution in the Gran Chaco Region, the elimination of Triatoma infestans has failed, even in areas subject to intensive professional vector control efforts. Chagas disease control programs traditionally have been composed of two divorced entities: a vector control program in charge of routine field operations (bug detection and insecticide spraying) and a disease control program in charge of screening blood donors, diagnosis, etiologic treatment and providing medical care to chronic patients. The challenge of sustainable suppression of bug infestation and Trypanosoma cruzi transmission can be met through integrated disease management, in which vector control is combined with active case detection and treatment to increase impact, cost-effectiveness and public acceptance in resource-limited settings. Multi-stakeholder involvement may add sustainability and resilience to the surveillance system. Chagas vector control and disease management must remain a regional effort within the frame of sustainable development rather than being viewed exclusively as a matter of health pertinent to the health sector. Sustained and continuous coordination between governments, agencies, control programs, academia and the affected communities is critical. PMID:19753458

Occurrence of serum antibodies against wheat alpha-amylase inhibitor 0.19 in celiac disease.

PubMed

Sánchez, D; Štěpánová-Honzová, S; Hospodková, M; Hoffmanová, I; Hábová, V; Halada, P; Tlaskalová-Hogenová, H; Tučková, L

2018-05-10

The alcohol-soluble fraction of wheat gluten (gliadins) induces in genetically susceptible individuals immunologically mediated celiac disease (CLD). However, gliadins and related cereal proteins are not unique foodstuff targets of CLD patients´ immune system. Non-gluten wheat alpha-amylase inhibitor 0.19 (AAI 0.19) has been found to be capable of activating human monocyte-derived dendritic cells and inducing pro-inflammatory status in intestinal mucosa of patients with celiac disease (CLD). The possible contribution of this reactivity in incomplete remission of CLD patients on a gluten-free diet (GFD) is matter of contention. In an attempt to characterize the antigenicity of AAI 0.19 in patients with active CLD, patients on a GFD and healthy controls we developed ELISA employing wheat recombinant AAI 0.19. Using this test we revealed a significant (P<0.001) elevation of IgA anti-AAI 0.19 antibodies (Ab) in patients with active CLD (12 out of 30 patients were seropositive) but also in CLD patients on a GFD (15/46), in contrast to healthy controls (2/59). Anti-AAI 0.19 IgG Ab levels were increased (P<0.001) only in patients with active CLD (14/30) in contrast to the controls. Interestingly, the levels of anti-AAI 0.19 IgG Ab were decreased in CLD patients on a GFD (P<0.001, 1/46) compared to the controls (1/59). Notably, 20 out of 30 of patients with active CLD were positive either for IgA or for IgG anti-AAI 0.19 Ab. Thus, the majority of CLD patients developed a robust IgA and IgG Ab response against AAI 0.19. These findings may contribute to the broadening of the knowledge about CLD pathogenesis.

Physical therapy and occupational therapy in Parkinson's disease.

PubMed

Radder, Danique L M; Sturkenboom, Ingrid H; van Nimwegen, Marlies; Keus, Samyra H; Bloem, Bastiaan R; de Vries, Nienke M

2017-10-01

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in daily activities. In this narrative review, we address the limitations that people with Parkinson's disease may encounter despite optimal medical management, and we clarify both the unique and shared approaches that physical therapists and occupational therapists can apply in treating these limitations.

Gastric secretory function in coeliac disease.

PubMed

Marcello, U; Deganello, A; Consolaro, G; Zoppi, G

1979-01-18

Volume, total titrable acidity, total proteolytic activity and pepsin activity have been determined in 14 coeliac patients and in 8 controls of comparable ages and body weights. Basal secretion (B.O.), total outputs (T. O.) and peak outputs (P.O.) after pentagastrin injection have been determined. Peak outputs (values 60 min/kg) of these parameters are as follows: volume 5.0+/-1.7 ml in coeliacs, 4.3+/-1.2 ml in controls; total titrable acidity 406.1+/-155.0 mEq in patients, 296.1+/-182.4 in conttrols; total proteolytic activity 962.1+/-501.1 micronEq in coeliacs, 569.6+/-272.2 in controls; pepsin activity 789.1+/-521.8 micronEq in patients, 447.6+/-150.4 in controls.

CRYAB modulates the activation of CD4+ T cells from relapsing-remitting multiple sclerosis patients.

PubMed

Quach, Que Lan; Metz, Luanne M; Thomas, Jenna C; Rothbard, Jonathan B; Steinman, Lawrence; Ousman, Shalina S

2013-12-01

Suppression of activation of pathogenic CD4(+) T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. CD4(+) T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73-92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. The secretion of pro-inflammatory cytokines by CD4(+) T cells was decreased in the presence of CRYAB in a subset of relapsing-remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8(+) T cells, in CD4(+) T cells of MS patients that displayed suppressed cytokine production (responders). CRYAB may be capable of suppressing the activation of CD4(+) T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis.

PubMed

Tito, Raul Y; Cypers, Heleen; Joossens, Marie; Varkas, Gaëlle; Van Praet, Liesbet; Glorieus, Elien; Van den Bosch, Filip; De Vos, Martine; Raes, Jeroen; Elewaut, Dirk

2017-01-01

Dysbiosis of the intestinal microbiota has been widely established in inflammatory bowel disease (IBD). There is significant clinical and genetic overlap between spondyloarthritis (SpA) and IBD, and up to 50% of all patients with SpA exhibit microscopic signs of bowel inflammation, often bearing particular resemblance to early Crohn's disease, a subtype of IBD. This study was undertaken to assess the relationship between intestinal microbial composition, gut histology, and disease activity markers in SpA. Gene analysis by 16S ribosomal RNA amplicon sequencing was used to compare the microbial composition in ileal and colonic biopsy specimens from 27 patients with SpA (14 with microscopic bowel inflammation, 13 without) and 15 healthy control subjects (ileal samples from all 15 subjects and colonic samples from 6). Spearman's rank correlation tests were used to assess correlations of the microbial composition with disease activity measures. The intestinal inflammation status (histologically normal versus acute or chronic inflammation) was strongly associated with the mucosal microbiota profile of patients with SpA. In inflamed biopsy tissue, the detected bacterial community composition clustered separately from that in noninflamed biopsy tissue (P < 0.05 by permutational multivariate analysis of variance, using hierarchical clustering on Bray-Curtis distances). Interestingly, abundance of the genus Dialister was found to be positively correlated with the Ankylosing Spondylitis Disease Activity Score (Spearman's rho = 0.62, false discovery rate-corrected q < 0.01). This finding was further supported by the low frequency of Dialister observed in noninflamed ileal and colonic biopsy tissue from patients with SpA and healthy controls. These findings demonstrate a significant difference in the intestinal microbial composition in patients with SpA who have microscopic gut inflammation compared to those without microscopic gut inflammation. Moreover, Dialister may represent a potential microbial marker of disease activity in SpA. © 2016, American College of Rheumatology.

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

From hemobiology to vascular disease: a review of the potential of gliclazide to influence the pathogenesis of diabetic vascular disease.

PubMed

Jennings, P E

1994-01-01

Patients with type II diabetes commonly die from thrombotic vascular disease. Large vessel occlusion due to thrombosis or atherosclerotic stenosis is a process accelerated by diabetes and results in premature death. Diabetic small vessel disease, with its unique microangiopathic process, underlies many of the large vessel changes as well as causing retinopathy and nephropathy. The microangiopathic changes produce a prothrombotic tendency that has been widely reported in type II diabetes. There is reduced endothelial cell production of prostacyclin and the activators of fibrinolysis, together with increased platelet reactivity. In addition, there is increased lipid peroxidation and oxidative stress due to excess free-radical activity and impaired antioxidant defenses particularly in the presence of microvascular disease. The development of many of these abnormalities is associated with poor long-term glycemic control. However, the changes are also seen in atherosclerosis in nondiabetic patients where the progression of the disease can be modified by antiplatelet agents and antioxidants. The process of vascular damage is accelerated by diabetes, often due to co-existing disease and aging, although it is not clear that improvement in long-term glycemic control by lowering blood glucose levels to near to the nondiabetic state reduces the development of small and large vessel disease. Although the biochemical mechanism underlying this observation remains uncertain, protein glycosylation and increased platelet reactivity are implicated and interrelated. Increased oxidative stress due to excess free-radical activity may be central to diabetic vascular disease as endothelial cell damage, lipoprotein oxidation, modification of both platelet reactivity and arachidonic acid cascade are all properties of free radicals and their reaction products lipid peroxides.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical Activity in Patients Treated With Peritoneal Dialysis: A Protocol for a Systematic Review.

PubMed

Thangarasa, Tharshika; Imtiaz, Rameez; Hiremath, Swapnil; Zimmerman, Deborah

2017-01-01

Patients with chronic diseases are known to benefit from exercise. Despite a lack of compelling evidence, patients with end-stage kidney disease treated with peritoneal dialysis are often discouraged from participating in exercise programs that include resistance training due to concerns about the development of hernias and leaks. The actual effects of physical activity with or without structured exercise programs for these patients remain unclear. The purpose of this study is to more completely define the risks and benefits of physical activity in the end-stage kidney disease population treated with peritoneal dialysis. We will conduct a systematic review examining the effects of physical activity on end-stage kidney disease patients treated with peritoneal dialysis. For the purposes of this review, exercise will be considered a purposive subcategory of physical activity. The primary objective is to determine if physical activity in this patient population is associated with improvements in mental health, physical functioning, fatigue and quality of life and if there is an increase in adverse outcomes. With the help of a skilled librarian, we will search MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials for randomized trials and observational studies. We will include adult end-stage kidney disease patients treated with peritoneal dialysis that have participated in an exercise training program or had their level of physical activity assessed directly or by self-report. The study must include an assessment of the association between physical activity and one of our primary or secondary outcomes measures. We will report study quality using the Cochrane Risk of Bias Assessment Tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. Quality across studies will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The results of this review may help to inform guideline development for exercise recommendations specific to this patient population. PROSPERO:CRD42016041695.

Promoting Physical Activity in Adapted Physical Education

ERIC Educational Resources Information Center

Yun, Joonkoo; Beamer, Jennifer

2018-01-01

The importance of physical activity has received considerable attention during the past decade. Physical education has been viewed as a cost-effective way to promote physical activity as a public health initiative. In fact, the Centers for Disease Control and Prevention recommends that a "substantial percentage" of students' overall…

β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly

PubMed Central

Steffener, Jason; Razlighi, Qolamreza R.; Habeck, Christian; Stern, Yaakov

2016-01-01

The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Aβ deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Aβ deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans. Forty-three young and 62 cognitively normal older adults underwent an fMRI session during an executive contextual task in which task difficulty varied: single (either letter case or vowel/consonant judgment task) vs dual (switching between letter case and vowel/consonant decisions) task. Older subjects additionally completed 18F-florbetaben positron emission tomography scans and were classified as either amyloid positive (Aβ+) or negative (Aβ−). Consistent with previous reports, age-related increases in brain activity were found in FPC regions commonly identified across groups. For both task conditions, Aβ-related increases in brain activity were found compared with baseline activity. For higher cognitive control load, however, Aβ+ elderly showed reduced task-switching activation in the right inferior frontal cortex. Our findings suggest that with Aβ deposition, brain activation in the cognitive control region reaches a maximum with lower control demand and decreases with higher control demand, which may underlie early impairment in cognitive control with AD progression. SIGNIFICANCE STATEMENT The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Aβ deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Aβ-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Aβ-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Aβ deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Aβ pathology. PMID:26865619

Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa

PubMed Central

Holsen, Laura M.; Lawson, Elizabeth A.; Blum, Justine; Ko, Eunice; Makris, Nikos; Fazeli, Pouneh K.; Klibanski, Anne; Goldstein, Jill M.

2012-01-01

Background Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. Methods We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. Results We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Limitations Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Conclusion Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food’s reward value and integration of these with interoceptive signalling of one’s internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa. PMID:22498079

76 FR 65166 - International Sanitary and Phytosanitary Standard-Setting Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

..., formerly known as the Office International des Epizooties) regarding animal health and welfare, and... bulletins on global disease status, and provides animal disease control guidelines to Members. Various OIE commissions and working groups undertake the development and preparation of draft standards, which are then...

Early response to therapy predicts 6-month and 1-year disease activity outcomes in psoriatic arthritis patients.

PubMed

Schoels, Monika M; Landesmann, Uriel; Alasti, Farideh; Baker, Daniel; Smolen, Josef S; Aletaha, Daniel

2018-06-01

In PsA management, remission and low disease activity represent preferential treatment targets. We aimed at evaluating the predictive value and clinical use of initial therapeutic response for subsequent achievement of these targets. Based on data of 216 patients enrolled in a randomized controlled trial of golimumab (GO-REVEAL), we performed diagnostic testing analyses using 3- and 6-month disease activity as tests for treatment outcomes to understand the implications of early response. In regression analyses, we estimated the probabilities for achieving at least LDA. Disease activity was measured by the disease activity index for PsA (DAPSA). Three-month DAPSA levels were excellent tests for disease activity at 6 months (and at 1 year), with areas under the receiver operating characteristic curves of 0.92 (and 0.88, respectively). The estimated probability for 6-month LDA could be quantified as <22% if patients did not reach at least moderate disease activity after 3 months on golimumab. Similar data were seen for early DAPSA response: patients achieving a DAPSA 85% at 3 months had an 84% probability for 6-month LDA or REM. All results were validated in an independent trial cohort of patients treated with infliximab (IMPACT 2). Three months after implementation of therapy in PsA, it is already possible to evaluate the potential for accomplishing therapeutic goals. This substantiates the choice of the 3-month assessment as essential for treatment adaptations.

Systematic Review of the Effectiveness of Occupational Therapy–Related Interventions for People With Parkinson’s Disease

PubMed Central

Foster, Erin R.; Bedekar, Mayuri

2014-01-01

We describe the results of a systematic review of the literature on occupational therapy–related interventions for people with Parkinson’s disease (PD). Three broad categories of intervention emerged: (1) exercise or physical activity; (2) environmental cues, stimuli, and objects; and (3) self-management and cognitive–behavioral strategies. Moderate to strong evidence exists for task-specific benefits of targeted physical activity training on motor performance, postural stability, and balance. Low to moderate evidence indicates that more complex, multimodal activity training supports improvement in functional movement activities. The evidence is moderate that the use of external supports during functional mobility or other movement activities has positive effects on motor control. In addition, moderate evidence is available that individualized interventions focused on promoting participant wellness initiatives and personal control by means of cognitive–behavioral strategies can improve targeted areas of quality of life. The implications for practice, education, and research are discussed. PMID:24367954